72 results on '"Y. Porat"'
Search Results
2. Enhancing Cancer Cell Membrane Permeability by Application of Tumor Treating Fields (TTFields)
- Author
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B. Koltun, T. Voloshin, T. Kan, C. David, L. Koren, Y. Porat, A. Volodin, N. Kaynan, A. Klein-Goldberg, R. Paz, B. Brant, Y. Barsheshet, E. Zemer-Tov, A. Haber, M. Giladi, U. Weinberg, and Y. Palti
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Cancer Research ,Radiation ,Oncology ,Radiology, Nuclear Medicine and imaging - Published
- 2022
3. P-121 Effects of tumor treating fields (TTFields) on gastric cancer cells and their potential concomitant application with FOLFOX
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N. Flint-Brodsly, E. Zeevi, E. Dor-On, R. Schneiderman, M. Munster, Y. Porat, T. Voloshin, S. Davidi, J. León, A. Haber, M. Giladi, U. Weinberg, and Y. Palti
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Oncology ,Hematology - Published
- 2022
4. A promising blood-derived novel treatment for critical limb ischemia and beyond
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Y. Porat
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Cancer Research ,Transplantation ,business.industry ,Vascular disease ,medicine.medical_treatment ,Immunology ,Therapeutic effect ,Cell Biology ,Critical limb ischemia ,medicine.disease ,Revascularization ,Oncology ,Anesthesia ,Diabetes mellitus ,Immunology and Allergy ,Medicine ,Progenitor cell ,medicine.symptom ,business ,Adverse effect ,Wound healing ,Genetics (clinical) - Abstract
Background & Aim Peripheral vascular disease in people with diabetes and the elderly affects principally medium and small caliber vessels which are less amenable to surgical intervention. Stem/progenitor cell (SPCs) treatments with bone-marrow-derived cells show promising outcomes in treating vascular diseases, albeit not without adverse events related to cell mobilization and collection. A unique patented treatment product of enriched endothelial progenitor cells (EnEPCs) generated from peripheral blood was developed, that utilizes a novel one-day technology employing dendritic cells (DCs) to specifically direct potentially therapeutic stem/progenitor cell (SPC) activity in-vitro. Previous animal studies have shown promising results in reversing induced limb ischemia. We describe a" first in human "pilot study of the product for treating patients with severe peripheral vascular disease with no available surgical option. Methods, Results & Conclusion We performed a pilot open-label study of treatment with the product in patients with critical limb ischemia (CLI) characterized by rest pain and/or ulceration, and with no surgical option for revascularization. The product was prepared from 250—350 ml of a standard blood draw. Co-culture of activated DCs with SPCs from the same patient sample yielded 97% viability. Treatment consisted of a single treatment session with intramuscular injections into the gastrocnemius muscle of the diseased leg. Acute safety follow-up was conducted during the initial 48±6 hours in the hospital and long-term follow-up at 1 week and at 1, 3, 6 and 12 months. Results revealed that the treatment is well tolerated and safe. The therapy showed promising therapeutic effects in objective outcomes including limb salvage, increased leg blood flow and wound healing, as well as, subjective outcomes including walking ability, reduction of pain, decreased usage of narcotic medications and improved quality of life (QoL). Conclusion These observations indicate that the cell product, derived from a standard peripheral blood draw of EPC-enriched SPCs, generated by a novel culture process taking less than one day, shows promising preliminary results in the treatment of CLI and may also be therapeutic in other vascular conditions.
- Published
- 2019
5. Acyl-Substituted Dermaseptin S4 Derivatives with Improved Bactericidal Properties, Including on Oral Microflora
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Amram Mor, K. Marynka, Doron Steinberg, A. Tam, and Y. Porat
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Acylation ,Antimicrobial peptides ,Colony Count, Microbial ,Peptide ,Microbial Sensitivity Tests ,Biology ,Amphibian Proteins ,Protein Structure, Secondary ,Microbiology ,Structure-Activity Relationship ,chemistry.chemical_compound ,Potency ,Pharmacology (medical) ,Amino Acid Sequence ,Peptide sequence ,Pharmacology ,chemistry.chemical_classification ,Mouth ,Microscopy, Confocal ,Dermaseptin ,Dipeptide ,Circular Dichroism ,Fatty Acids ,Anti-Bacterial Agents ,Amino acid ,Kinetics ,Infectious Diseases ,Amino Acid Substitution ,chemistry ,Biochemistry ,Susceptibility ,Biofilms ,Peptides ,Hydrophobic and Hydrophilic Interactions ,Antimicrobial Cationic Peptides - Abstract
The 15-mer dermaseptin S4 derivative S4(1-15) was recently shown to exhibit potent activity against oral pathogens associated with caries and periodontitis. Here, we investigated possible modes for improving the peptide's properties through systematic replacement of an N-terminal amino acid(s) with various fatty acids that modulate the peptide's hydrophobicity and/or charge. Deletion of 1 to 3 residues led to progressive loss of potency as assessed by MIC experiments performed on four test bacteria. Replacing the deleted amino acids with fatty acids most often resulted in potency recovery or improvement, as evidenced by lower MICs and faster bactericidal kinetics in culture media. Best results were obtained after replacement of the N-terminal dipeptide alanine-leucine with heptanoic (C 7 ) or aminododecanoic (NC 12 ) acid. Circular dichroism analysis correlated antibacterial properties to the peptide's secondary structure. MIC experiments and confocal laser scanning microscopy results indicated that C 7 -S4(3-15) and NC 12 -S4(3-15) were bactericidal to various oral pathogens, including those which are immobilized in a biofilm. C 7 -S4(3-15) performed similarly to or better than (depending on growth medium) IB-367, a peptide assessed in clinical trials for treatment of oral mucositis, reducing CFU counts by >3 log units within 2 min of incubation. Collectively, the data indicate that substitution of fatty acids for amino acids may be a useful strategy in revealing improved derivatives of known antimicrobial peptides and suggest the suitability of such compounds for controlling pathogens associated with oral diseases.
- Published
- 2006
6. Tumor Treating Fields (TTFields) Sensitize Glioma Tumor Cells to Radiation Therapy by Delaying DNA Damage Repair Through Homologous Recombination
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Y. Porat, Eilon D. Kirson, R.S. Schneiderman, Uri Weinberg, R. Blat, Zeev Bomzon, Moshe Giladi, T. Voloshin, M. Munster, Yoram Palti, and S. Sherbo
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Cancer Research ,Radiation ,business.industry ,medicine.medical_treatment ,Tumor cells ,medicine.disease ,DNA Damage Repair ,Virology ,Radiation therapy ,Oncology ,Glioma ,Cancer research ,Medicine ,Radiology, Nuclear Medicine and imaging ,business ,Homologous recombination - Published
- 2015
7. Tumor Treating Fields (TTFields) Delay DNA Damage Repair Following Radiation Treatment of Glioma Cells: Implications for Irradiation Through TTFields Transducer Arrays
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Moshe Giladi, Yoram Palti, M. Munster, Eilon D. Kirson, Zeev Bomzon, Y. Porat, Uri Weinberg, R.S. Schneiderman, and T. Voloshin
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Cancer Research ,Radiation ,business.industry ,medicine.disease ,DNA Damage Repair ,Transducer ,Oncology ,Glioma ,Cancer research ,Medicine ,Radiology, Nuclear Medicine and imaging ,Irradiation ,business ,Nuclear medicine - Published
- 2017
8. Dynamic Collapse of the Common Pharynx in a Cat
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A.S. Mosenco, Y. Porat-Mosenco, and M.S. Zaid
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Male ,General Veterinary ,business.industry ,Pharynx ,Pharyngeal Diseases ,Anatomy ,Cat Diseases ,medicine.anatomical_structure ,Cats ,Animals ,Medicine ,Nasal Obstruction ,medicine.symptom ,business ,Collapse (medical) - Published
- 2011
9. EXPERIMENTAL THERAPEUTICS AND PHARMACOLOGY
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C. Aaberg-Jessen, L. Fogh, B. Halle, V. Jensen, N. Brunner, B. W. Kristensen, T. Abe, Y. Momii, J. Watanabe, I. Morisaki, A. Natsume, T. Wakabayashi, M. Fujiki, B. Aldaz, A. W. M. Fabius, J. Silber, G. Harinath, T. A. Chan, J. T. Huse, S. Anai, T. Hide, H. Nakamura, K. Makino, S. Yano, J.-i. Kuratsu, I. V. Balyasnikova, M. S. Prasol, D. K. Kanoija, K. S. Aboody, M. S. Lesniak, T. Barone, C. Burkhart, A. Purmal, A. Gudkov, K. Gurova, R. Plunkett, K. Barton, K. Misuraca, F. Cordero, E. Dobrikova, H. Min, M. Gromeier, D. Kirsch, O. Becher, L. B. Pont, J. Kloezeman, M. van den Bent, R. Kanaar, A. Kremer, S. Swagemakers, P. French, C. Dirven, M. Lamfers, S. Leenstra, R. Balvers, A. Kleijn, S. Lawler, X. Gong, A. Andres, J. Hanson, J. Delashaw, D. Bota, C.-C. Chen, N.-W. Yao, W.-J. Chuang, C. Chang, P.-Y. Chen, C.-Y. Huang, K.-C. Wei, Y. Cheng, Q. Dai, R. Morshed, Y. Han, B. Auffinger, D. Wainwright, L. Zhang, A. Tobias, E. Rincon, B. Thaci, A. Ahmed, C. He, M. Lesniak, Y. A. Choi, H. Pandya, D. M. Gibo, I. Fokt, W. Priebe, W. Debinski, Y. Chornenkyy, S. Agnihotri, P. Buczkowicz, P. Rakopoulos, A. Morrison, M. Barszczyk, C. Hawkins, S. Chung, S. Decollogne, P. Luk, H. Shen, W. Ha, B. Day, B. Stringer, P. Hogg, P. Dilda, K. McDonald, S. Moore, M. Hayden-Gephart, J. Bergen, Y. Su, H. Rayburn, M. Edwards, M. Scott, J. Cochran, A. Das, A. K. Varma, G. C. Wallace, Y. N. Dixon-Mah, W. A. Vandergrift, P. Giglio, S. K. Ray, S. J. Patel, N. L. Banik, T. Dasgupta, A. Olow, X. Yang, S. Mueller, M. Prados, C. D. James, D. Haas-Kogan, N. D. Dave, P. B. Desai, G. A. Gudelsky, L. M. L. Chow, K. LaSance, X. Qi, J. Driscoll, K. Ebsworth, M. J. Walters, L. S. Ertl, Y. Wang, R. D. Berahovic, J. McMahon, J. P. Powers, J. C. Jaen, T. J. Schall, Z. Eroglu, J. Portnow, A. Sacramento, E. Garcia, A. Raubitschek, T. Synold, S. Esaki, S. Rabkin, R. Martuza, H. Wakimoto, S. Ferluga, C. L. Tome, H. E. Forde, I. A. Netland, L. Sleire, B. Skeie, P. O. Enger, D. Goplen, M. Giladi, A. Tichon, R. Schneiderman, Y. Porat, M. Munster, M. Dishon, U. Weinberg, E. Kirson, Y. Wasserman, Y. Palti, D. Gramatzki, M. Staudinger, K. Frei, M. Peipp, M. Weller, C. Grasso, L. Liu, N. Berlow, L. Davis, M. Fouladi, A. Gajjar, E. Huang, E. Hulleman, M. Hutt, C. Keller, X.-N. Li, P. Meltzer, M. Quezado, M. Quist, E. Raabe, P. Spellman, N. Truffaux, D. van Vurden, N. Wang, K. Warren, R. Pal, J. Grill, M. Monje, A. L. Green, S. Ramkissoon, D. McCauley, K. Jones, J. A. Perry, L. Ramkissoon, C. Maire, S. Shacham, K. L. Ligon, A. L. Kung, K. Zielinska-Chomej, V. Grozman, J. Tu, K. Viktorsson, R. Lewensohn, S. Gupta, A. Mladek, K. Bakken, B. Carlson, F. Boakye-Agyeman, S. Kizilbash, M. Schroeder, J. Reid, J. Sarkaria, P. Hadaczek, T. Ozawa, L. Soroceanu, Y. Yoshida, L. Matlaf, E. Singer, E. Fiallos, C. S. Cobbs, R. Hashizume, M. Tom, Y. Ihara, R. Santos, J. D. L. Torre, E. Lepe, T. Waldman, D. James, X. Huang, L. Yu-Jen, N. Gupta, D. Solomon, Z. Zhang, T. Hayashi, K. Adachi, S. Nagahisa, M. Hasegawa, Y. Hirose, M. H. Gephart, Y. S. Su, S. Hingtgen, R. Kasmieh, I. Nesterenko, J.-L. Figueiredo, R. Dash, D. Sarkar, P. Fisher, K. Shah, E. Horne, P. Diaz, N. Stella, C. Huang, H. Yang, K. Wei, T. Huang, J. Hlavaty, D. Ostertag, F. L. Espinoza, B. Martin, H. Petznek, M. Rodriguez-Aguirre, C. Ibanez, N. Kasahara, W. Gunzburg, H. Gruber, D. Pertschuk, D. Jolly, J. Robbins, B. Hurwitz, J. Y. Yoo, C. Bolyard, J.-G. Yu, J. Wojton, J. Zhang, Z. Bailey, D. Eaves, T. Cripe, M. Old, B. Kaur, L. Serwer, N. Le Moan, S. Ng, N. Butowski, A. Krtolica, S. P. L. Cary, T. Johns, S. Greenall, J. Donoghue, T. Adams, G. Karpel-Massler, M.-A. Westhoff, R. E. Kast, A. Dwucet, C. R. Wirtz, K.-M. Debatin, M.-E. Halatsch, N. Merkur, F. Kievit, Z. Stephen, K. Wang, D. Kolstoe, R. Ellenbogen, M. Zhang, G. Kitange, E. Haefner, K. Knubel, B. M. Pernu, A. Sufit, A. M. Pierce, S. K. Nelson, A. K. Keating, S. S. Jensen, J. Lachowicz, M. Demeule, A. Regina, S. Tripathy, J.-C. Curry, T. Nguyen, J.-P. Castaigne, T. Davis, A. Davis, K. Tanaka, T. Keating, J. Getz, G. T. Kapp, J. M. Romero, S. Lee, S. Ramisetti, B. Slagle-Webb, A. Sharma, J. Connor, W.-S. Lee, M. Kluk, J. C. Aster, K. Ligon, S. Sun, D. Lee, A. S. W. Ho, J. K. S. Pu, Z.-q. Zhang, N. P. Lee, P. J. R. Day, G. K. K. Leung, Z. Liu, X. Liu, A. B. Madhankumar, P. Miller, B. Webb, J. R. Connor, Q. X. Yang, M. Lobo, S. Green, M. Schabel, Y. Gillespie, R. Woltjer, M. Pike, Y.-J. Lu, H. A. Luchman, O. Stechishin, S. Nguyen, J. G. Cairncross, S. Weiss, X. Lun, J. C. Wells, X. Hao, N. Grinshtein, D. Kaplan, A. Luchman, D. Senger, S. Robbins, A. Madhankumar, E. Rizk, R. Payne, A. Park, M. Pang, K. Harbaugh, A. Wilisch-Neumann, D. Pachow, E. Kirches, C. Mawrin, S. McDonell, J. Liang, Y. Piao, N. Nguyen, A. Yung, R. Verhaak, E. Sulman, C. Stephan, F. Lang, J. de Groot, Y. Mizobuchi, T. Okazaki, T. Kageji, K. Kuwayama, K. T. Kitazato, H. Mure, K. Hara, R. Morigaki, K. Matsuzaki, K. Nakajima, S. Nagahiro, S. Kumala, M. Heravi, S. Devic, T. Muanza, K. H. Knubel, A. Neuwelt, Y. J. Wu, A. Donson, R. Vibhakar, S. Venkatamaran, V. Amani, E. Neuwelt, L. Rapkin, N. Foreman, F. Ibrahim, P. New, K. Cui, H. Zhao, D. Chow, W. Stephen, K. Nozue-Okada, M. Nagane, K. L. McDonald, D. Ogawa, E. Chiocca, J. Godlewski, A. Patel, N. Pasupuleti, F. Gorin, A. Valenzuela, L. Leon, K. Carraway, C. Ramachandran, S. Nair, K.-W. Quirrin, Z. Khatib, E. Escalon, S. Melnick, A. Phillips, E. Boghaert, K. Vaidya, P. Ansell, D. Shalinsky, Y. Zhang, M. Voorbach, S. Mudd, K. Holen, R. Humerickhouse, E. Reilly, S. Parab, O. Diago, T. Ryken, S. Agarwal, M. Al-Keilani, M. Alqudah, Z. Sibenaller, M. Assemolt, K. Sai, W.-y. Li, W.-p. Li, Z.-p. Chen, R. Saito, Y. Sonoda, M. Kanamori, Y. Yamashita, T. Kumabe, T. Tominaga, G. Sarkar, G. Curran, R. Jenkins, R. Scharnweber, Y. Kato, J. Lin, R. Everson, H. Soto, C. Kruse, L. Liau, R. Prins, S. Semenkow, Q. Chu, C. Eberhart, R. Sengupta, J. Marassa, D. Piwnica-Worms, J. Rubin, R. Shai, T. Pismenyuk, I. Moshe, T. Fisher, S. Freedman, A. Simon, N. Amariglio, G. Rechavi, A. Toren, M. Yalon, Y. Shimazu, K. Kurozumi, T. Ichikawa, K. Fujii, M. Onishi, J. Ishida, T. Oka, M. Watanabe, Y. Nasu, H. Kumon, I. Date, R. W. Sirianni, R. L. McCall, J. Spoor, M. van der Kaaij, M. Geurtjens, O. Veiseh, C. Fang, M. Leung, G. Strohbehn, K.-K. Atsina, T. Patel, J. Piepmeier, J. Zhou, W. M. Saltzman, M. Takahashi, G. Valdes, A. Inagaki, S. Kamijima, K. Hiraoka, E. Micewicz, W. H. McBride, K. S. Iwamoto, H. E. Gruber, J. M. Robbins, D. J. Jolly, C. McCully, J. Bacher, T. Thomas, R. Murphy, E. Steffen-Smith, R. McAllister, D. Pastakia, B. Widemann, P. Chen, M. Hua, H. Liu, E. C. Woolf, M. G. Abdelwahab, K. E. Fenton, Q. Liu, G. Turner, M. C. Preul, A. C. Scheck, W. Shen, D. Brown, H. Pedersen, S. Hariono, T.-W. Yao, A. Sidhu, W. A. Weiss, T. P. Nicolaides, and T. Olusanya
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Cancer Research ,Abstracts ,Oncology ,business.industry ,Medicine ,Neurology (clinical) ,Pharmacology ,business - Published
- 2013
10. METABOLIC PATHWAYS
- Author
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S. Adams, C. Teo, K. McDonald, A. Zinger, S. Bustamante, C. K. Lim, N. Braidy, B. J. Brew, G. J. Guillemin, S. Agnihotri, K. Burrell, S. Singh, A. Vartanian, A. Wolf, F. Lang, R. Verhaak, C. Hawkins, K. Aldape, G. Zadeh, C. Chesnelong, M. Chaumeil, M. D. Blough, M. Al-Najjar, O. D. Stechishin, S. Ronen, S. Weiss, H. A. Luchman, J. G. Cairncross, E. Fonkem, R. Tobin, J. Griffin, A. Zuzek, M. Rogers, M. Giladi, Y. Wasserman, N. Urman, Y. Porat, R. Schneiderman, M. Munster, U. Weinberg, E. Kirson, Y. Palti, J. Godlewski, A. Bronisz, K. Ansari, D. Ogawa, M. O. Nowicki, E. A. Chiocca, A. Kathagen, A. Schulte, G. Balcke, H. Phillips, H. Gunther, M. Westphal, K. Lamszus, K. Makino, H. Nakamura, T.-i. Hide, S. Yano, J.-i. Kuroda, J.-i. Kuratsu, F. Fack, D. Bonnel, G. Hochart, A. C. Navis, P. Wesseling, W. P. J. Leenders, J. Stauber, S. P. Niclou, F. Sahm, I. Oezen, C. Opitz, B. Radlwimmer, A. von Deimling, H. B. Bode, T. Ahrendt, G. Guillemin, W. Wick, M. Platten, D. Schonberg, D. Lubelski, J. Rich, S. K. Singh, and N. Sabha
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Cancer Research ,Abstracts ,Oncology ,Neurology (clinical) - Published
- 2013
11. In vitro assessment of antimicrobial peptides as potential agents against several oral bacteria
- Author
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Amram Mor, D. Fridman, Gilad Bachrach, Hamutal Altman, Y. Porat, Doron Steinberg, and Michael Friedman
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Pharmacology ,Microbiology (medical) ,Mouth ,biology ,Bacteria ,Antimicrobial peptides ,Biofilm ,biology.organism_classification ,Antimicrobial ,Streptococcus mutans ,Streptococcus sobrinus ,Microbiology ,Anti-Bacterial Agents ,Infectious Diseases ,Humans ,Pharmacology (medical) ,Porphyromonas gingivalis ,Actinomyces ,Antimicrobial Cationic Peptides - Abstract
Background: Antimicrobial peptides are components of the innate immunity that play an important role in systemic and oral health. Objectives: The antibacterial activity of the amphibian-derived K 4 -S4(1-15)a antimicrobial peptide was tested against oral pathogens associated with caries and periodontitis and compared with the activities of the human-derived antimicrobial peptides LL-37 and dhvar4a. Methods: Growth inhibition of planktonic bacteria was tested using standard microdilution assays. Live/ Dead staining followed by confocal scanning laser microscopy (CSLM) was used to determine the bactericidal effect of K 4 -S4(1-15)a on Streptococcus mutans attached to a glass surface or grown as biofilm. Results: The cariogenic species S. mutans, Streptococcus sobrinus, Lactobaclllus paracasel and Actinomyces viscosuswere resistant to LL-37 found in the oral cavity. Porphyromonas gingivalis was the species most resistant to the three tested peptides. K4-S4(1-15)a demonstrated the highest activity against the tested planktonic bacteria. In addition, K 4 -S4(1-15)a was bactericidal to surface-attached S. mutans as well as to S. mutans biofilms grown in vitro. However, surface attachment increased S. mutans resistance to the antimicrobial peptide. Conclusions: Our results support growing evidence suggesting the use of antimicrobial peptides for prevention and treatment of oral disease.
- Published
- 2006
12. Burst error characteristics of Viterbi decoding of convolutional codes
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Y. Porat and A. Reichman
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Iterative Viterbi decoding ,Computer science ,business.industry ,List decoding ,Pattern recognition ,Sequential decoding ,Viterbi algorithm ,Burst error ,symbols.namesake ,Viterbi decoder ,Convolutional code ,symbols ,Artificial intelligence ,business ,Algorithm ,Soft output Viterbi algorithm - Abstract
This article introduces an upper bound on the probability of error bursts of a specific length at the Viterbi maximum likelihood decoder output. It shows a recursive method for calculation of the generating function coefficients necessary for evaluating this bound. Among the many applications of these results, the calculation of an upper bound on the message error probability is presented. >
- Published
- 2002
13. [Eosinophilia as an unfavorable prognostic factor for clozapine-induced severe adverse side-effects]
- Author
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R, Shiloh, D Y, Porat, A, Weizman, and H, Munitz
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Eosinophilia ,Humans ,Prognosis ,Clozapine ,Antipsychotic Agents - Published
- 2002
14. Induction of responsiveness in lymphocytes of immunodeficient patients' cells implanted with foreign plasma membranes
- Author
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D, Levy, Y, Porat, I, Pick, Z T, Handzel, M, Schlesinger, A, Tanay, and I, Zan-Bar
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B-Lymphocytes ,T-Lymphocytes ,Cell Membrane ,Immunologic Deficiency Syndromes ,Immunoglobulins ,In Vitro Techniques ,Lymphocyte Activation ,Mice ,Common Variable Immunodeficiency ,Agammaglobulinemia ,Animals ,Humans ,Lymphocytes ,Mitogens ,Receptors, Immunologic ,Signal Transduction - Published
- 1993
15. Huntingtin oligomeric structures and their potential neurotoxic role in Huntington's disease
- Author
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Zhipeng Hou, Michelle A. Poirier, Christopher A. Ross, and Y. Porat
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Huntingtin ,Huntington's disease ,Biomedical Engineering ,medicine ,Pharmaceutical Science ,Molecular Medicine ,Medicine (miscellaneous) ,General Materials Science ,Bioengineering ,Biology ,medicine.disease ,Neuroscience - Published
- 2006
16. Evaluation of human monoclonal antibodies to HCV in the HCV-trimera model: a mouse model for HCV infection
- Author
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Ofer Nussbaum, Steven K. H. Foung, G. Livneh, Y. Porat, Y. Arazi, Rachel Eren, Lewis Neville, Ehud Ilan, S. Shavit, Arie Zauberman, Kenneth G. Hadlock, and Shlomo Dagan
- Subjects
Hepatology ,medicine.drug_class ,business.industry ,medicine ,Monoclonal antibody ,business ,Virology - Published
- 2001
17. In vitro assessment of antimicrobial peptides as potential agents against several oral bacteria.
- Author
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H. Altman, D. Steinberg, Y. Porat, A. Mor, D. Fridman, M. Friedman, and G. Bachrach
- Subjects
ANTIMICROBIAL peptides ,FUNGUS-bacterium relationships ,STREPTOCOCCUS ,STREPTOCOCCACEAE - Abstract
Background: Antimicrobial peptides are components of the innate immunity that play an important role in systemic and oral health.Objectives: The antibacterial activity of the amphibian-derived K4-S4(1-15)a antimicrobial peptide was tested against oral pathogens associated with caries and periodontitis and compared with the activities of the human-derived antimicrobial peptides LL-37 and dhvar4a.Methods: Growth inhibition of planktonic bacteria was tested using standard microdilution assays. Live/Dead staining followed by confocal scanning laser microscopy (CSLM) was used to determine the bactericidal effect of K4-S4(1-15)a on Streptococcus mutans attached to a glass surface or grown as biofilm.Results: The cariogenic species S. mutans, Streptococcus sobrinus, Lactobacillus paracasei and Actinomyces viscosus were resistant to LL-37 found in the oral cavity. Porphyromonas gingivalis was the species most resistant to the three tested peptides. K4-S4(1-15)a demonstrated the highest activity against the tested planktonic bacteria. In addition, K4-S4(1-15)a was bactericidal to surface-attached S. mutans as well as to S. mutans biofilms grown in vitro. However, surface attachment increased S. mutans resistance to the antimicrobial peptide.Conclusions: Our results support growing evidence suggesting the use of antimicrobial peptides for prevention and treatment of oral disease. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
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18. Investigation of the reaction 3H(n, 2n)2H at En = 13.95 MeV and the neutron-neutron scattering length
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Y. Porat, G. Adam, R. Fox, and E.Bar Avraham
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Nuclear physics ,Physics ,Nuclear reaction ,Nuclear and High Energy Physics ,Neutron ,Scattering length ,Neutron scattering ,Atomic physics ,Neutron radiation ,Wave function ,Small-angle neutron scattering ,Neutron time-of-flight scattering - Abstract
The reaction 3H(n, 2n)2H has been investigated theoretically and experimentally, with particular emphasis on its relation to the n-n scattering length. It was found that the deduced n-n scattering length depends sensitively on the choice of the triton wave function and its size.
- Published
- 1971
19. The performance of a short-barrelled gas gun
- Author
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Y Porat and M Gvishi
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Impact studies ,Materials science ,law ,Projectile ,Nuclear engineering ,Light-gas gun ,General Engineering ,Physics::Accelerator Physics ,General Physics and Astronomy ,General Materials Science ,Instrumentation ,law.invention - Abstract
A short-barrelled gas gun for impact studies with a length-to-diameter ratio of 69 has been designed and installed. The design considerations and parameters of gun performance are discussed. The measured projectile velocities (up to 550 m s-1), are compared with the curves calculated by the dynamic gas theory.
- Published
- 1980
20. Lifetime of a fast, high-voltage vacuum spark gap
- Author
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Y. Porat and E. Bar Avraham
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Materials science ,business.industry ,ComputingMilieux_PERSONALCOMPUTING ,ComputerApplications_COMPUTERSINOTHERSYSTEMS ,High voltage ,Hardware_PERFORMANCEANDRELIABILITY ,Spark gap ,Condensed Matter::Mesoscopic Systems and Quantum Hall Effect ,Shot (pellet) ,Hardware_INTEGRATEDCIRCUITS ,Optoelectronics ,ComputerSystemsOrganization_SPECIAL-PURPOSEANDAPPLICATION-BASEDSYSTEMS ,business ,Instrumentation - Abstract
The operation of a fast, high‐voltage vacuum spark gap is affected by the pumping speed after each shot. A simple means to prolong the gap lifetime is proposed.
- Published
- 1976
21. Tumor Treating Fields (TTFields) demonstrate antiviral functions in vitro , and safety for application to COVID-19 patients in a pilot clinical study.
- Author
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Abutbul A, Mumblat H, Porat Y, Friedman N, Atari N, Sharabi S, Nama A, Mugahed W, Kessler A, Kolben Y, Shamir RR, Manzur D, Farber O, Bosch L, Lavy-Shahaf G, Dor-On E, Haber A, Giladi M, Weinberg U, Palti Y, Mardor Y, and Mandelboim M
- Abstract
Coronaviruses are the causative agents of several recent outbreaks, including the COVID-19 pandemic. One therapeutic approach is blocking viral binding to the host receptor. As binding largely depends on electrostatic interactions, we hypothesized possible inhibition of viral infection through application of electric fields, and tested the effectiveness of Tumor Treating Fields (TTFields), a clinically approved cancer treatment based on delivery of electric fields. In preclinical models, TTFields were found to inhibit coronavirus infection and replication, leading to lower viral secretion and higher cell survival, and to formation of progeny virions with lower infectivity, overall demonstrating antiviral activity. In a pilot clinical study (NCT04953234), TTFields therapy was safe for patients with severe COVID-19, also demonstrating preliminary effectiveness data, that correlated with higher device usage., Competing Interests: HM, YaP, DM, OF, LB, GL-S, ED-O, AH, MG, and UW were employed by Novocure and hold stocks in Novocure Ltd. YoP holds stocks in Novocure Ltd. MG, UW and YoP hold several patents related to TTFields. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abutbul, Mumblat, Porat, Friedman, Atari, Sharabi, Nama, Mugahed, Kessler, Kolben, Shamir, Manzur, Farber, Bosch, Lavy-Shahaf, Dor-On, Haber, Giladi, Weinberg, Palti, Mardor and Mandelboim.)
- Published
- 2023
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22. Domestic cat nose functions as a highly efficient coiled parallel gas chromatograph.
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Wu Z, Jiang J, Lischka FW, McGrane SJ, Porat-Mesenco Y, and Zhao K
- Subjects
- Cats, Animals, Head, Acclimatization, Mammals, Smell, Ear, Inner
- Abstract
The peripheral structures of mammalian sensory organs often serve to support their functionality, such as alignment of hair cells to the mechanical properties of the inner ear. Here, we examined the structure-function relationship for mammalian olfaction by creating an anatomically accurate computational nasal model for the domestic cat (Felis catus) based on high resolution microCT and sequential histological sections. Our results showed a distinct separation of respiratory and olfactory flow regimes, featuring a high-speed dorsal medial stream that increases odor delivery speed and efficiency to the ethmoid olfactory region without compromising the filtration and conditioning purpose of the nose. These results corroborated previous findings in other mammalian species, which implicates a common theme to deal with the physical size limitation of the head that confines the nasal airway from increasing in length infinitely as a straight tube. We thus hypothesized that these ethmoid olfactory channels function as parallel coiled chromatograph channels, and further showed that the theoretical plate number, a widely-used indicator of gas chromatograph efficiency, is more than 100 times higher in the cat nose than an "amphibian-like" straight channel fitting the similar skull space, at restful breathing state. The parallel feature also reduces airflow speed within each coil, which is critical to achieve the high plate number, while feeding collectively from the high-speed dorsal medial stream so that total odor sampling speed is not sacrificed. The occurrence of ethmoid turbinates is an important step in the evolution of mammalian species that correlates to their expansive olfactory function and brain development. Our findings reveal novel mechanisms on how such structure may facilitate better olfactory performance, furthering our understanding of the successful adaptation of mammalian species, including F. catus, a popular pet, to diverse environments., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: S.J.M. is an employee of Mars Petcare UK, a manufacturer of petfood and a provider of veterinary services. Mars Petcare UK is a corporate sponsor of the Monell Chemical Senses Center. K.Z. is paid consultant to Diceros Therapeutics, Inc., which is unrelated to the project., (Copyright: © 2023 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
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23. When Patient Expectations Are Not Met: A Case Report.
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Sadowsky A, Porat Y, Faruki AA, and Vitter JS
- Subjects
- Female, Humans, Middle Aged, Motivation, Treatment Outcome, Anesthesia, General, Parkinson Disease surgery, Deep Brain Stimulation
- Abstract
Successful anesthetics occur when safe, effective perioperative care is coupled with patient satisfaction. We present the case of a 63-year-old woman with advanced Parkinson's disease who presented for a deep brain stimulation (DBS) device battery change under monitored anesthesia care (MAC). While MAC is commonly utilized for a DBS battery change, our patient reported previously experiencing intraoperative pain, anxiety, and the inability to communicate discomfort under MAC, leading to posttraumatic stress disorder. This case report highlights the importance of preoperative informed consent, discussion of patient expectations, and proactive planning for intraoperative communication strategies when MAC is the chosen method., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)
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- 2023
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24. Aurora B Kinase Inhibition by AZD1152 Concomitant with Tumor Treating Fields Is Effective in the Treatment of Cultures from Primary and Recurrent Glioblastomas.
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Krex D, Bartmann P, Lachmann D, Hagstotz A, Jugel W, Schneiderman RS, Gotlib K, Porat Y, Robel K, Temme A, Giladi M, and Michen S
- Subjects
- Humans, Aurora Kinase B metabolism, Neoplasm Recurrence, Local, Glioblastoma, Antineoplastic Agents pharmacology
- Abstract
Tumor Treating Fields (TTFields) were incorporated into the treatment of glioblastoma, the most malignant brain tumor, after showing an effect on progression-free and overall survival in a phase III clinical trial. The combination of TTFields and an antimitotic drug might further improve this approach. Here, we tested the combination of TTFields with AZD1152, an Aurora B kinase inhibitor, in primary cultures of newly diagnosed (ndGBM) and recurrent glioblastoma (rGBM). AZD1152 concentration was titrated for each cell line and 5-30 nM were used alone or in addition to TTFields (1.6 V/cm RMS; 200 kHz) applied for 72 h using the inovitro™ system. Cell morphological changes were visualized by conventional and confocal laser microscopy. The cytotoxic effects were determined by cell viability assays. Primary cultures of ndGBM and rGBM varied in p53 mutational status; ploidy; EGFR expression and MGMT-promoter methylation status. Nevertheless; in all primary cultures; a significant cytotoxic effect was found following TTFields treatment alone and in all but one, a significant effect after treatment with AZD1152 alone was also observed. Moreover, in all primary cultures the combined treatment had the most pronounced cytotoxic effect in parallel with morphological changes. The combined treatment of TTFields and AZD1152 led to a significant reduction in the number of ndGBM and rGBM cells compared to each treatment alone. Further evaluation of this approach, which has to be considered as a proof of concept, is warranted, before entering into early clinical trials.
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- 2023
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25. Gaze following requires early visual experience.
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Zohary E, Harari D, Ullman S, Ben-Zion I, Doron R, Attias S, Porat Y, Sklar AY, and Mckyton A
- Subjects
- Attention, Blindness, Child, Humans, Visual Acuity, Fixation, Ocular, Vision, Ocular
- Abstract
Gaze understanding—a suggested precursor for understanding others’ intentions—requires recovery of gaze direction from the observed person's head and eye position. This challenging computation is naturally acquired at infancy without explicit external guidance, but can it be learned later if vision is extremely poor throughout early childhood? We addressed this question by studying gaze following in Ethiopian patients with early bilateral congenital cataracts diagnosed and treated by us only at late childhood. This sight restoration provided a unique opportunity to directly address basic issues on the roles of “nature” and “nurture” in development, as it caused a selective perturbation to the natural process, eliminating some gaze-direction cues while leaving others still available. Following surgery, the patients’ visual acuity typically improved substantially, allowing discrimination of pupil position in the eye. Yet, the patients failed to show eye gaze-following effects and fixated less than controls on the eyes—two spontaneous behaviors typically seen in controls. Our model for unsupervised learning of gaze direction explains how head-based gaze following can develop under severe image blur, resembling preoperative conditions. It also suggests why, despite acquiring sufficient resolution to extract eye position, automatic eye gaze following is not established after surgery due to lack of detailed early visual experience. We suggest that visual skills acquired in infancy in an unsupervised manner will be difficult or impossible to acquire when internal guidance is no longer available, even when sufficient image resolution for the task is restored. This creates fundamental barriers to spontaneous vision recovery following prolonged deprivation in early age.
- Published
- 2022
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26. Protocol for live-cell imaging during Tumor Treating Fields treatment with Inovitro Live.
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Slangen PLG, Porat Y, Mertz M, van den Broek B, Jalink K, de Gooijer MC, van Tellingen O, and Borst GR
- Subjects
- Combined Modality Therapy, Humans, Electric Stimulation Therapy methods, Neoplasms diagnostic imaging
- Abstract
Tumor Treating Fields (TTFields) are an FDA-approved anticancer treatment using alternating electric fields. Here, we present a protocol to perform live-cell imaging (LCI) of cells during TTFields treatment with the Inovitro Live
TM system. The setup we describe dissipates TTFields-related heat production and can be used in conjunction with any LCI-compatible microscope setup. This approach will enable further elucidation of TTFields' mechanism of action at the molecular level and facilitate the development of promising combination strategies., Competing Interests: Y.P. is an employee and shareholder of Novocure, which has applied for a patent for the use of a 'System for Viewing Cell Cultures under a Microscope Whilst Applying TTFields' (US20180202991A1)., (© 2022 The Authors.)- Published
- 2022
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27. Tumor Treating Fields (TTFields) downregulate the Fanconi Anemia-BRCA pathway and increase the efficacy of chemotherapy in malignant pleural mesothelioma preclinical models.
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Mumblat H, Martinez-Conde A, Braten O, Munster M, Dor-On E, Schneiderman RS, Porat Y, Voloshin T, Davidi S, Blatt R, Shteingauz A, Tempel-Brami C, Zeevi E, Lajterer C, Shmueli Y, Danilov S, Haber A, Giladi M, Weinberg U, Kinzel A, and Palti Y
- Subjects
- Animals, Cisplatin, Humans, Mice, Pemetrexed, Fanconi Anemia, Lung Neoplasms drug therapy, Mesothelioma, Malignant
- Abstract
Objectives: Tumor Treating Fields (TTFields) are low intensity, intermediate frequency, alternating electric fields with antimitotic effects on cancerous cells. TTFields concomitant with pemetrexed and a platinum agent are approved in the US and EU as first line therapy for unresectable, locally advanced or metastatic malignant pleural mesothelioma (MPM). The goal of the current study was to characterize the mechanism of action of TTFields in MPM cell lines and animal models., Methods: Human MPM cell lines MSTO-211H and NCI-H2052 were treated with TTFields to determine the frequency that elicits maximal cytotoxicity. The effect of TTFields on DNA damage and repair, and the cytotoxic effect of TTFields in combination with cisplatin and/or pemetrexed were examined. Efficacy of TTFields concomitant with cisplatin and pemetrexed was evaluated in orthotopic IL-45 and subcutaneous RN5 murine models., Results: TTFields at a frequency of 150 kHz demonstrated the highest cytotoxicity to MPM cells. Application of 150 kHz TTFields resulted in increased formation of DNA double strand breaks, elevated expression of DNA damage induced cell cycle arrest proteins, and reduced expression of Fanconi Anemia (FA)-BRCA DNA repair pathway proteins. Co-treatment of TTFields with cisplatin or pemetrexed significantly increased treatment efficacy versus each modality alone, with additivity and synergy exhibited by the TTFields-pemetrexed and TTFields-cisplatin combinations, respectively. In animal models, tumor volume was significantly lower for the TTFields-cisplatin-pemetrexed combination compared to control, accompanied by increased DNA damage within the tumor., Conclusion: This research demonstrated that the efficacy of TTFields for the treatment of MPM is associated with reduced expression of FA-BRCA pathway proteins and increased DNA damage. This mechanism of action is consistent with the observed synergism for TTFields-cisplatin vs additivity for TTFields-pemetrexed, as cisplatin-induced DNA damage is repaired via the FA-BRCA pathway., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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28. Predictors of Readmission Following Discharge of Patients With Gram-Negative Bacteremia: A Retrospective Cohort Study.
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Porat Y, Nashashibi J, Poran I, and Paul M
- Abstract
Background: Short-term readmission is an important outcome reflecting the poor trajectory of sepsis survivors. The aim of this study was to identify the major risk factors for 30-day readmission among patients with gram-negative bacteremia., Methods: This was a retrospective cohort study including all consecutive adults hospitalized in the medical departments in a referral hospital in Israel with gram-negative bacteremia between 2011 and 2020, who were discharged alive. Predictors for 30-day readmission were investigated, considering death after discharge as a competing event. Cephalosporin resistance was our predictor of interest. Subdistribution hazard ratios (HRs) of the cumulative incidence function were investigated using the Fine and Gray multivariable competing-risk regression model. The prediction models were cross-validated using the k-fold method., Results: Among 2196 patients surviving hospitalization with gram-negative bacteremia, the mean age was 70 ± 16 years and 432 (19.6%) were readmitted within 30 days. Variables associated with readmission hazards were Arab ethnicity, active malignancy, conditions requiring immunosuppression, anxiolytics or hypnotics, anticoagulant or antiplatelet therapy, discharge with a nasogastric tube, higher predischarge heart rate, duration of antibiotic therapy during hospitalization, and bacteremia caused by cephalosporin-resistant bacteria (HR, 1.23 [95% confidence interval {CI}, .99-1.52]). The area under the receiver operating characteristic curve for this model was 75.5% (95% CI, 71.3%-79.1%). In secondary models, cephalosporin resistance, inappropriate empirical antibiotic treatment, and lower predischarge albumin were significantly associated with readmission., Conclusions: Thirty-day readmissions among patients with gram-negative bacteremia surviving the index admission were high. Readmission was related to comorbidities and infections caused by multidrug-resistant infections.Main point: Among 2196 adults surviving hospitalization with gram-negative bacteremia, 432 (19.6%) were rehospitalized within 30 days. Comorbidities, inappropriate empirical antibiotic treatment, bacteremia caused by cephalosporin-resistant bacteria, predischarge heart rate, and albumin were associated with readmissions., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2021
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29. Performance comparison: exome sequencing as a single test replacing Sanger sequencing.
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Fridman H, Bormans C, Einhorn M, Au D, Bormans A, Porat Y, Sanchez LF, Manning B, Levy-Lahad E, and Behar DM
- Subjects
- DNA genetics, Exons genetics, Genetic Variation genetics, Humans, Sequence Analysis, DNA methods, Exome genetics, High-Throughput Nucleotide Sequencing methods, Exome Sequencing methods
- Abstract
Next generation sequencing tests are used routinely as first-choice tests in the clinic. However, systematic performance comparing the results of exome sequencing as a single test replacing Sanger sequencing of targeted gene(s) is still lacking. Performance comparison data are critically important for clinical case management. In this study, we compared Sanger-sequencing results of 258 genes to those obtained from next generation sequencing (NGS) using two exome-sequencing enrichment kits: Agilent-SureSelectQXT and Illumina-Nextera. Sequencing was performed on leukocytes and buccal-derived DNA from a single individual, and all 258 genes were sequenced a total of 11 times (using different sequencing methods and DNA sources). Sanger sequencing was completed for all exons, including flanking ± 8 bp regions. For the 258 genes, NGS mean coverage was > 20 × for > 98 and > 91% of the regions targeted by SureSelect and Nextera, respectively. Overall, 449 variants were identified in at least one experiment, and 407/449 (90.6%) were detected by all. Of the 42 discordant variants, 23 were determined as true calls, summing-up to a truth set of 430 variants. Sensitivity of true-variant detection was 99% for Sanger sequencing and 97-100% for the NGS experiments. Mean false-positive rates were 3.7E-6 for Sanger sequencing, 2.5E-6 for SureSelect-NGS and 5.2E-6 for Nextera-NGS. Our findings suggest a high overall concordance between Sanger sequencing and NGS performances. Both methods demonstrated false-positive and false-negative calls. High clinical suspicion for a specific diagnosis should, therefore, override negative results of either Sanger sequencing or NGS.
- Published
- 2021
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30. Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy.
- Author
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Voloshin T, Kaynan N, Davidi S, Porat Y, Shteingauz A, Schneiderman RS, Zeevi E, Munster M, Blat R, Tempel Brami C, Cahal S, Itzhaki A, Giladi M, Kirson ED, Weinberg U, Kinzel A, and Palti Y
- Subjects
- Animals, Apoptosis, Carcinoma, Hepatocellular immunology, Carcinoma, Hepatocellular pathology, Carcinoma, Lewis Lung immunology, Carcinoma, Lewis Lung pathology, Cell Proliferation, Combined Modality Therapy, Female, Humans, Liver Neoplasms immunology, Liver Neoplasms pathology, Liver Neoplasms therapy, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Antineoplastic Agents, Immunological pharmacology, Carcinoma, Hepatocellular therapy, Carcinoma, Lewis Lung therapy, Electric Stimulation Therapy methods, Immunogenic Cell Death, Lymphocytes, Tumor-Infiltrating immunology, Programmed Cell Death 1 Receptor antagonists & inhibitors
- Abstract
Tumor-treating fields (TTFields) are alternating electric fields in a specific frequency range (100-300 kHz) delivered to the human body through transducer arrays. In this study, we evaluated whether TTFields-mediated cell death can elicit antitumoral immunity and hence would be effectively combined with anti-PD-1 therapy. We demonstrate that in TTFields-treated cancer cells, damage-associated molecular patterns including high-mobility group B1 and adenosine triphosphate are released and calreticulin is exposed on the cell surface. Moreover, we show that TTFields treatment promotes the engulfment of cancer cells by dendritic cells (DCs) and DCs maturation in vitro, as well as recruitment of immune cells in vivo. Additionally, our study demonstrates that the combination of TTFields with anti-PD-1 therapy results in a significant decline of tumor volume and increase in the percentage of tumor-infiltrating leukocytes in two tumor models. In orthotopic lung tumors, these infiltrating leukocytes, specifically macrophages and DCs, showed elevated expression of PD-L1. Compatibly, cytotoxic T-cells isolated from these tumors demonstrated increased production of IFN-γ. In colon cancer tumors, T-cells infiltration was significantly increased following long treatment duration with TTFields plus anti-PD-1. Collectively, our results suggest that TTFields therapy can induce anticancer immune response. Furthermore, we demonstrate robust efficacy of concomitant application of TTFields and anti-PD-1 therapy. These data suggest that integrating TTFields with anti-PD-1 therapy may further enhance antitumor immunity, hence achieve better tumor control.
- Published
- 2020
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31. Identification of the Identical Human Mutation in ACVR1 in 2 Cats With Fibrodysplasia Ossificans Progressiva.
- Author
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Casal ML, Engiles JB, Zakošek Pipan M, Berkowitz A, Porat-Mosenco Y, Mai W, Wurzburg K, Xu MQ, Allen R, ODonnell PA, Henthorn PS, Thompson K, and Shore EM
- Subjects
- Animals, Bone Diseases diagnostic imaging, Bone Diseases genetics, Bone Diseases pathology, Bone and Bones diagnostic imaging, Bone and Bones pathology, Cat Diseases diagnostic imaging, Cat Diseases pathology, Cats, Female, Heterozygote, Male, Mutation, Myositis Ossificans diagnostic imaging, Myositis Ossificans pathology, Ossification, Heterotopic diagnostic imaging, Ossification, Heterotopic genetics, Ossification, Heterotopic pathology, Activin Receptors, Type I genetics, Bone Diseases veterinary, Cat Diseases genetics, Myositis Ossificans genetics, Ossification, Heterotopic veterinary
- Abstract
Two domestic shorthair cats, 1 intact female and 1 intact male, presented with progressive limb lameness and digital deformities at 4 and 6 months of age. Stiffness and swelling of the distal thoracic and pelvic limb joints progressed to involve hip and shoulder joints, resulting in reduced mobility. Radiographs in both cats and computed tomography of the male cat revealed ankylosing, polyarticular deposits of extracortical heterotopic bone spanning multiple axial and appendicular joints, extending into adjacent musculotendinous tissues. All findings supported fibrodysplasia ossificans progressiva (FOP), a disorder characterized by toe malformations and progressive heterotopic ossification in humans. In both cats, molecular analyses revealed the same heterozygous mutation in the activin A receptor type I ( ACVR1 ) gene that occurs in humans with FOP. Several reports of heterotopic ossification in cats exist, but this is the first one to identify clinical FOP in 2 cats with the identical mutation that occurs in >95% of humans with FOP.
- Published
- 2019
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32. Loss of Protocadherin-12 Leads to Diencephalic-Mesencephalic Junction Dysplasia Syndrome.
- Author
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Guemez-Gamboa A, Çağlayan AO, Stanley V, Gregor A, Zaki MS, Saleem SN, Musaev D, McEvoy-Venneri J, Belandres D, Akizu N, Silhavy JL, Schroth J, Rosti RO, Copeland B, Lewis SM, Fang R, Issa MY, Per H, Gumus H, Bayram AK, Kumandas S, Akgumus GT, Erson-Omay EZ, Yasuno K, Bilguvar K, Heimer G, Pillar N, Shomron N, Weissglas-Volkov D, Porat Y, Einhorn Y, Gabriel S, Ben-Zeev B, Gunel M, and Gleeson JG
- Subjects
- Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Mutation, Protocadherins, Brain Stem abnormalities, Cadherins genetics, Nervous System Malformations genetics, Nervous System Malformations pathology
- Abstract
Objective: To identify causes of the autosomal-recessive malformation, diencephalic-mesencephalic junction dysplasia (DMJD) syndrome., Methods: Eight families with DMJD were studied by whole-exome or targeted sequencing, with detailed clinical and radiological characterization. Patient-derived induced pluripotent stem cells were derived into neural precursor and endothelial cells to study gene expression., Results: All patients showed biallelic mutations in the nonclustered protocadherin-12 (PCDH12) gene. The characteristic clinical presentation included progressive microcephaly, craniofacial dysmorphism, psychomotor disability, epilepsy, and axial hypotonia with variable appendicular spasticity. Brain imaging showed brainstem malformations and with frequent thinned corpus callosum with punctate brain calcifications, reflecting expression of PCDH12 in neural and endothelial cells. These cells showed lack of PCDH12 expression and impaired neurite outgrowth., Interpretation: DMJD patients have biallelic mutations in PCDH12 and lack of protein expression. These patients present with characteristic microcephaly and abnormalities of white matter tracts. Such pathogenic variants predict a poor outcome as a result of brainstem malformation and evidence of white matter tract defects, and should be added to the phenotypic spectrum associated with PCDH12-related conditions. Ann Neurol 2018;84:646-655., (© 2018 American Neurological Association.)
- Published
- 2018
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33. AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields).
- Author
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Shteingauz A, Porat Y, Voloshin T, Schneiderman RS, Munster M, Zeevi E, Kaynan N, Gotlib K, Giladi M, Kirson ED, Weinberg U, Kinzel A, and Palti Y
- Subjects
- Adenosine Triphosphate metabolism, Aneuploidy, Animals, Autophagosomes metabolism, Autophagy-Related Protein 7 antagonists & inhibitors, Brain Neoplasms therapy, Cell Line, Tumor, Cell Survival, Electric Stimulation Therapy, Endoplasmic Reticulum Chaperone BiP, Endoplasmic Reticulum Stress, Glioblastoma therapy, Heat-Shock Proteins metabolism, Humans, Lysosomes metabolism, Mice, Microtubule-Associated Proteins metabolism, Mitosis, Rats, Vascular Endothelial Growth Factor A, AMP-Activated Protein Kinases metabolism, Autophagy, Brain Neoplasms pathology, Electric Stimulation methods, Glioblastoma pathology, Up-Regulation
- Abstract
Tumor Treating Fields (TTFields), an approved treatment modality for glioblastoma, are delivered via non-invasive application of low-intensity, intermediate-frequency, alternating electric fields. TTFields application leads to abnormal mitosis, aneuploidy, and increased cell granularity, which are often associated with enhancement of autophagy. In this work, we evaluated whether TTFields effected the regulation of autophagy in glioma cells. We found that autophagy is upregulated in glioma cells treated with TTFields as demonstrated by immunoblot analysis of the lipidated microtubule-associated protein light chain 3 (LC3-II). Fluorescence and transmission electron microscopy demonstrated the presence of LC3 puncta and typical autophagosome-like structures in TTFields-treated cells. Utilizing time-lapse microscopy, we found that the significant increase in the formation of LC3 puncta was specific to cells that divided during TTFields application. Evaluation of selected cell stress parameters revealed an increase in the expression of the endoplasmic reticulum (ER) stress marker GRP78 and decreased intracellular ATP levels, both of which are indicative of increased proteotoxic stress. Pathway analysis demonstrated that TTFields-induced upregulation of autophagy is dependent on AMP-activated protein kinase (AMPK) activation. Depletion of AMPK or autophagy-related protein 7 (ATG7) inhibited the upregulation of autophagy in response to TTFields, as well as sensitized cells to the treatment, suggesting that cancer cells utilize autophagy as a resistance mechanism to TTFields. Combining TTFields with the autophagy inhibitor chloroquine (CQ) resulted in a significant dose-dependent reduction in cell growth compared with either TTFields or CQ alone. These results suggest that dividing cells upregulate autophagy in response to aneuploidy and ER stress induced by TTFields, and that AMPK serves as a key regulator of this process.
- Published
- 2018
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34. Oxytocin as a Neurobiological Marker of Ruptures in the Working Alliance.
- Author
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Zilcha-Mano S, Porat Y, Dolev T, and Shamay-Tsoory S
- Subjects
- Adult, Biomarkers metabolism, Depressive Disorder, Major psychology, Female, Humans, Male, Interpersonal Relations, Oxytocin metabolism, Professional-Patient Relations, Psychotherapy methods
- Published
- 2018
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35. Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells.
- Author
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Giladi M, Munster M, Schneiderman RS, Voloshin T, Porat Y, Blat R, Zielinska-Chomej K, Hååg P, Bomzon Z, Kirson ED, Weinberg U, Viktorsson K, Lewensohn R, and Palti Y
- Subjects
- Animals, Glioma genetics, Glioma pathology, Humans, Rats, Rats, Sprague-Dawley, Tumor Cells, Cultured, DNA Breaks, Double-Stranded radiation effects, DNA Repair radiation effects, Electric Stimulation Therapy, Glioma radiotherapy, Phantoms, Imaging, Skin Diseases prevention & control
- Abstract
Background: Tumor Treating Fields (TTFields) are an anti-neoplastic treatment modality delivered via application of alternating electric fields using insulated transducer arrays placed directly on the skin in the region surrounding the tumor. A Phase 3 clinical trial has demonstrated the effectiveness of continuous TTFields application in patients with glioblastoma during maintenance treatment with Temozolomide. The goal of this study was to evaluate the efficacy of combining TTFields with radiation treatment (RT) in glioma cells. We also examined the effect of TTFields transducer arrays on RT distribution in a phantom model and the impact on rat skin toxicity., Methods: The efficacy of TTFields application after induction of DNA damage by RT or bleomycin was tested in U-118 MG and LN-18 glioma cells. The alkaline comet assay was used to measure repair of DNA lesions. Repair of DNA double strand breaks (DSBs) were assessed by analyzing γH2AX or Rad51 foci. DNA damage and repair signaled by the activation pattern of phospho-ATM (pS1981) and phospho-DNA-PKcs (pS2056) was evaluated by immunoblotting. The absorption of the RT energy by transducer arrays was measured by applying RT through arrays placed on a solid-state phantom. Skin toxicities were tested in rats irradiated daily through the arrays with 2Gy (total dose of 20Gy)., Results: TTFields synergistically enhanced the efficacy of RT in glioma cells. Application of TTFields to irradiated cells impaired repair of irradiation- or chemically-induced DNA damage, possibly by blocking homologous recombination repair. Transducer arrays presence caused a minor reduction in RT intensity at 20 mm and 60 mm below the arrays, but led to a significant increase in RT dosage at the phantom surface jeopardizing the "skin sparing effect". Nevertheless, transducer arrays placed on the rat skin during RT did not lead to additional skin reactions., Conclusions: Administration of TTFields after RT increases glioma cells treatment efficacy possibly by inhibition of DNA damage repair. These preclinical results support the application of TTFields therapy immediately after RT as a viable regimen to enhance RT outcome. Phantom measurements and animal models imply that it may be possible to leave the transducer arrays in place during RT without increasing skin toxicities.
- Published
- 2017
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36. Determining the Optimal Inhibitory Frequency for Cancerous Cells Using Tumor Treating Fields (TTFields).
- Author
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Porat Y, Giladi M, Schneiderman RS, Blat R, Shteingauz A, Zeevi E, Munster M, Voloshin T, Kaynan N, Tal O, Kirson ED, Weinberg U, and Palti Y
- Subjects
- Antineoplastic Protocols, Cell Line, Tumor, Female, Humans, Treatment Outcome, Colony-Forming Units Assay methods, Electric Stimulation Therapy, Electricity, Glioma therapy, Ovarian Neoplasms therapy
- Abstract
Tumor Treating Fields (TTFields) are an effective treatment modality delivered via the continuous, noninvasive application of low-intensity (1-3 V/cm), alternating electric fields in the frequency range of several hundred kHz. The study of TTFields in tissue culture is carried out using the TTFields in vitro application system, which allows for the application of electric fields of varying frequencies and intensities to ceramic Petri dishes with a high dielectric constant (Ɛ > 5,000). Cancerous cell lines plated on coverslips at the bottom of the ceramic Petri dishes are subjected to TTFields delivered in two orthogonal directions at various frequencies to facilitate treatment outcome tests, such as cell counts and clonogenic assays. The results presented in this report demonstrate that the optimal frequency of the TTFields with respect to both cell counts and clonogenic assays is 200 kHz for both ovarian and glioma cells.
- Published
- 2017
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37. Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo.
- Author
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Voloshin T, Munster M, Blatt R, Shteingauz A, Roberts PC, Schmelz EM, Giladi M, Schneiderman RS, Zeevi E, Porat Y, Bomzon Z, Urman N, Itzhaki A, Cahal S, Kirson ED, Weinberg U, and Palti Y
- Subjects
- Animals, Cell Line, Tumor, Cell Survival drug effects, Cell Survival radiation effects, Combined Modality Therapy, Disease Models, Animal, Female, Humans, Mice, Ovarian Neoplasms diagnostic imaging, Ovarian Neoplasms therapy, Treatment Outcome, Xenograft Model Antitumor Assays, Antineoplastic Agents pharmacology, Ovarian Neoplasms pathology, Paclitaxel pharmacology
- Abstract
Long-term survival rates for advanced ovarian cancer patients have not changed appreciably over the past four decades; therefore, development of new, effective treatment modalities remains a high priority. Tumor Treating Fields (TTFields), a clinically active anticancer modality utilize low-intensity, intermediate frequency, alternating electric fields. The goal of this study was to evaluate the efficacy of combining TTFields with paclitaxel against ovarian cancer cells in vitro and in vivo. In vitro application of TTFields on human ovarian cancer cell lines led to a significant reduction in cell counts as compared to untreated cells. The effect was found to be frequency and intensity dependent. Further reduction in the number of viable cells was achieved when TTFields treatment was combined with paclitaxel. The in vivo effect of the combined treatment was tested in mice orthotopically implanted with MOSE-L
TICv cells. In this model, combined treatment led to a significant reduction in tumor luminescence and in tumor weight as compared to untreated mice. The feasibility of effective local delivery of TTFields to the human abdomen was examined using finite element mesh simulations performed using the Sim4life software. These simulations demonstrated that electric fields intensities inside and in the vicinity of the ovaries of a realistic human computational phantom are about 1 and 2 V/cm pk-pk, respectively, which is within the range of intensities required for TTFields effect. These results suggest that prospective clinical investigation of the combination of TTFields and paclitaxel is warranted., (© 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)- Published
- 2016
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38. Practice improves peri-saccadic shape judgment but does not diminish target mislocalization.
- Author
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Porat Y and Zohary E
- Subjects
- Adult, Discrimination, Psychological, Female, Humans, Male, Young Adult, Form Perception physiology, Learning physiology, Saccades physiology, Visual Perception physiology
- Abstract
Visual sensitivity is markedly reduced during an eye movement. Peri-saccadic vision is also characterized by a mislocalization of the briefly presented stimulus closer to the saccadic target. These features are commonly viewed as obligatory elements of peri-saccadic vision. However, practice improves performance in many perceptual tasks performed at threshold conditions. We wondered if this could also be the case with peri-saccadic perception. To test this, we used a paradigm in which subjects reported the orientation (or location) of an ellipse briefly presented during a saccade. Practice on peri-saccadic orientation discrimination led to long-lasting gains in that task but did not alter the classical mislocalization of the visual stimulus. Shape discrimination gains were largely generalized to other untrained conditions when the same stimuli were used (discrimination during a saccade in the opposite direction or at a different stimulus location than previously trained). However, performance dropped to baseline level when participants shifted to a novel Vernier discrimination task under identical saccade conditions. Furthermore, practice on the location task did not induce better stimulus localization or discrimination. These results suggest that the limited visual information available during a saccade may be better used with practice, possibly by focusing attention on the specific target features or a better readout of the available information. Saccadic mislocalization, by contrast, is robust and resistant to top-down modulations, suggesting that it involves an automatic process triggered by the upcoming execution of a saccade (e.g., an efference copy signal)., Competing Interests: The authors declare no conflict of interest.
- Published
- 2016
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- View/download PDF
39. Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells.
- Author
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Giladi M, Schneiderman RS, Voloshin T, Porat Y, Munster M, Blat R, Sherbo S, Bomzon Z, Urman N, Itzhaki A, Cahal S, Shteingauz A, Chaudhry A, Kirson ED, Weinberg U, and Palti Y
- Subjects
- Animals, Apoptosis physiology, Cell Line, Tumor, Cell Survival physiology, Electricity, Humans, MCF-7 Cells, Microtubules metabolism, Microtubules pathology, Neoplasms metabolism, Rats, Rats, Inbred F344, Tubulin metabolism, Chromosome Segregation physiology, Mitosis physiology, Neoplasms pathology, Spindle Apparatus pathology
- Abstract
Tumor Treating Fields (TTFields) are low intensity, intermediate frequency, alternating electric fields. TTFields are a unique anti-mitotic treatment modality delivered in a continuous, noninvasive manner to the region of a tumor. It was previously postulated that by exerting directional forces on highly polar intracellular elements during mitosis, TTFields could disrupt the normal assembly of spindle microtubules. However there is limited evidence directly linking TTFields to an effect on microtubules. Here we report that TTFields decrease the ratio between polymerized and total tubulin, and prevent proper mitotic spindle assembly. The aberrant mitotic events induced by TTFields lead to abnormal chromosome segregation, cellular multinucleation, and caspase dependent apoptosis of daughter cells. The effect of TTFields on cell viability and clonogenic survival substantially depends upon the cell division rate. We show that by extending the duration of exposure to TTFields, slowly dividing cells can be affected to a similar extent as rapidly dividing cells.
- Published
- 2015
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40. Critical elements in the development of cell therapy potency assays for ischemic conditions.
- Author
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Porat Y, Abraham E, Karnieli O, Nahum S, Woda J, and Zylberberg C
- Subjects
- Humans, Ischemia diagnosis, Neovascularization, Physiologic physiology, Biological Assay methods, Cell- and Tissue-Based Therapy methods, Ischemia therapy
- Abstract
A successful potency assay for a cell therapy product (CTP) used in the treatment of ischemic conditions should quantitatively measure relevant biological properties that predict therapeutic activity. This is especially challenging because of numerous degrees of complexity stemming from factors that include a multifactorial complex mechanism of action, cell source, inherent cell characteristics, culture method, administration mode and the in vivo conditions to which the cells are exposed. The expected biological function of a CTP encompasses complex interactions that range from a biochemical, metabolic or immunological activity to structural replacement of damaged tissue or organ. Therefore, the requirements for full characterization of the active substance with respect to biological function could be taxing. Moreover, the specific mechanism of action is often difficult to pinpoint to a specific molecular entity; rather, it is more dependent on the functionality of the cellular components acting in a in a multifactorial fashion. In the case of ischemic conditions, the cell therapy mechanism of action can vary from angiogenesis, vasculogenesis and arteriogenesis that may activate different pathways and clinical outcomes. The CTP cellular attributes with relation to the suggested mechanism of action can be used for the development of quantitative and reproducible analytical potency assays. CTPs selected and released on the basis of such potency assays should have the highest probability of providing meaningful clinical benefit for patients. This White Paper will discuss and give examples for key elements in the development of a potency assay for treatment of ischemic disorders treated by the use of CTPs., (Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
41. Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo.
- Author
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Giladi M, Weinberg U, Schneiderman RS, Porat Y, Munster M, Voloshin T, Blatt R, Cahal S, Itzhaki A, Onn A, Kirson ED, and Palti Y
- Subjects
- Adenocarcinoma mortality, Adenocarcinoma pathology, Animals, Apoptosis, Carcinoma, Lewis Lung mortality, Carcinoma, Lewis Lung pathology, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell pathology, Cell Proliferation, Cisplatin administration & dosage, Combined Modality Therapy, Glutamates administration & dosage, Guanine administration & dosage, Guanine analogs & derivatives, Humans, In Vitro Techniques, Lung Neoplasms mortality, Lung Neoplasms pathology, Mice, Mice, Inbred C57BL, Paclitaxel administration & dosage, Pemetrexed, Survival Rate, Treatment Outcome, Tumor Cells, Cultured, Adenocarcinoma therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Lewis Lung therapy, Carcinoma, Non-Small-Cell Lung therapy, Carcinoma, Squamous Cell therapy, Electric Stimulation Therapy, Lung Neoplasms therapy
- Abstract
Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide. Common treatment modalities for NSCLC include surgery, radiotherapy, chemotherapy, and, in recent years, the clinical management paradigm has evolved with the advent of targeted therapies. Despite such advances, the impact of systemic therapies for advanced disease remains modest, and as such, the prognosis for patients with NSCLC remains poor. Standard modalities are not without their respective toxicities and there is a clear need to improve both efficacy and safety for current management approaches. Tumor-treating fields (TTFields) are low-intensity, intermediate-frequency alternating electric fields that disrupt proper spindle microtubule arrangement, thereby leading to mitotic arrest and ultimately to cell death. We evaluated the effects of combining TTFields with standard chemotherapeutic agents on several NSCLC cell lines, both in vitro and in vivo. Frequency titration curves demonstrated that the inhibitory effects of TTFields were maximal at 150 kHz for all NSCLC cell lines tested, and that the addition of TTFields to chemotherapy resulted in enhanced treatment efficacy across all cell lines. We investigated the response of Lewis lung carcinoma and KLN205 squamous cell carcinoma in mice treated with TTFields in combination with pemetrexed, cisplatin, or paclitaxel and compared these to the efficacy observed in mice exposed only to the single agents. Combining TTFields with these therapeutic agents enhanced treatment efficacy in comparison with the respective single agents and control groups in all animal models. Together, these findings suggest that combining TTFields therapy with chemotherapy may provide an additive efficacy benefit in the management of NSCLC., (Copyright © 2014. Published by Elsevier Inc.)
- Published
- 2014
- Full Text
- View/download PDF
42. A novel potential therapy for vascular diseases: blood-derived stem/progenitor cells specifically activated by dendritic cells.
- Author
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Porat Y, Assa-Kunik E, Belkin M, Krakovsky M, Lamensdorf I, Duvdevani R, Sivak G, Niven MJ, and Bulvik S
- Subjects
- Adolescent, Adult, Aged, Animals, Blood Donors, Cells, Cultured, Coculture Techniques, Dendritic Cells physiology, Diabetes Mellitus blood, Disease Models, Animal, Endothelial Progenitor Cells physiology, Female, Hindlimb blood supply, Humans, In Vitro Techniques, Ischemia therapy, Male, Mice, Mice, Nude, Middle Aged, Signal Transduction physiology, Treatment Outcome, Young Adult, Cell Communication physiology, Cell- and Tissue-Based Therapy methods, Dendritic Cells cytology, Dendritic Cells transplantation, Diabetic Angiopathies therapy, Endothelial Progenitor Cells cytology, Endothelial Progenitor Cells transplantation
- Abstract
Background: Vascular diseases are a major cause of morbidity and mortality, particularly in diabetic patients. Stem/progenitor cell treatments with bone marrow-derived cells show safety and promising outcomes, albeit not without some preprocedural adverse events related to cell collection and mobilization. We describe a novel technology for generating a therapeutic population (BGC101) of enriched endothelial progenitor cells (EPCs) from non-mobilized blood, using dendritic cells to specifically direct stem/progenitor cell activity in vitro., Methods and Results: Selected immature plasmacytoid and myeloid dendritic cells from 24 healthy and two diabetic donors were activated with anti-inflammatory and pro-angiogenic molecules to induce specific activation signals. Co-culturing of activated dendritic cells with stem/progenitor cells for 12-66 h generated 83.7 ± 7.4 × 10(6) BGC101 cells with 97% viability from 250 mL of blood. BGC101, comprising 52.4 ± 2.5% EPCs (expressing Ulex-lectin, AcLDL uptake, Tie2, vascular endothelial growth factor receptor 1 and 2, and CD31), 16.1 ± 1.9% stem/progenitor cells (expressing CD34 and CD184) and residual B and T helper cells, demonstrated angiogenic and stemness potential and secretion of interleukin-8, interleukin-10, vascular endothelial growth factor and osteopontin. When administered to immunodeficient mice with limb ischemia (n = 40), BGC101 yielded a high safety profile and significantly increased blood perfusion, capillary density and leg function after 21 days. Cell tracking and biodistribution showed that engraftment was restricted to the ischemic leg., Conclusions: These observations provide preliminary evidence that alternatively activated dendritic cells can promote the generation of EPC-enriched stem/progenitor cells within a 1-day culture. The resulting product BGC101 has the potential for treatment of various vascular conditions such as coronary heart disease, stroke and peripheral ischemia., (Copyright © 2014 John Wiley & Sons, Ltd.)
- Published
- 2014
- Full Text
- View/download PDF
43. Hands in motion: an upper-limb-selective area in the occipitotemporal cortex shows sensitivity to viewed hand kinematics.
- Author
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Orlov T, Porat Y, Makin TR, and Zohary E
- Subjects
- Adult, Biomechanical Phenomena, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Occipital Lobe blood supply, Oxygen blood, Photic Stimulation, Psychomotor Performance physiology, Temporal Lobe blood supply, Young Adult, Brain Mapping, Hand, Movement, Occipital Lobe physiology, Temporal Lobe physiology, Upper Extremity innervation
- Abstract
Regions in the occipitotemporal cortex (OTC) show clear selectivity to static images of human body parts, and upper limbs in particular, with respect to other object categories. Such selectivity was previously attributed to shape aspects, which presumably vary across categories. Alternatively, it has been proposed that functional selectivity for upper limbs is driven by processing of their distinctive motion features. In the present study we show that selectivity to static upper-limb images and motion processing go hand in hand. Using resting-state and task-based functional MRI, we demonstrate that OTC voxels showing greater preference to static images of arms and hands also show stronger functional connectivity with motion coding regions within the human middle temporal complex (hMT+), but not with shape-selective midtier areas, such as hV4 or LO-1, suggesting a tight link between upper-limb selectivity and motion processing. To test this directly, we created a set of natural arm-movement videos where kinematic patterns were parametrically manipulated, while keeping shape information constant. Using multivariate pattern analysis, we show that the degree of (dis)similarity in arm-velocity profiles across the video set predicts, to a significant extent, the degree of (dis)similarity in multivoxel activation patterns in both upper-limb-selective OTC regions and the hMT+. Together, these results suggest that the functional specificity of upper-limb-selective regions may be partially determined by their involvement in the processing of upper-limb dynamics. We propose that the selectivity to static upper-limb images in the OTC may be a result of experience-dependent association between shape elements, which characterize upper limbs, and upper-limb-specific motion patterns.
- Published
- 2014
- Full Text
- View/download PDF
44. Mitotic disruption and reduced clonogenicity of pancreatic cancer cells in vitro and in vivo by tumor treating fields.
- Author
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Giladi M, Schneiderman RS, Porat Y, Munster M, Itzhaki A, Mordechovich D, Cahal S, Kirson ED, Weinberg U, and Palti Y
- Subjects
- Animals, Cell Line, Tumor, Cell Size drug effects, Combined Modality Therapy, Cricetinae, Deoxycytidine analogs & derivatives, Deoxycytidine therapeutic use, Electricity, Humans, Male, Mesocricetus, Pancreatic Neoplasms drug therapy, Treatment Outcome, Tumor Stem Cell Assay, Gemcitabine, Mitosis drug effects, Pancreatic Neoplasms pathology
- Abstract
Objectives: Tumor Treating Fields (TTFields) are a non-invasive cancer treatment modality approved for the treatment of patients with recurrent glioblastoma. The present study determined the efficacy and mechanism of action of TTFields in preclinical models of pancreatic cancer., Methods: The effect of TTFields in vitro was assessed using cell counts, clonogenic assays, cell cycle analysis and analysis of mitotic figures. The effect in vivo effect was studied in the PC1-0 hamster pancreatic cancer model., Results: Application of TTFields in vitro showed a significant decrease in cell count, an increase in cell volume and reduced clonogenicity. Further analysis demonstrated significant increase in the number of abnormal mitotic figures, as well as a decrease in G2-M cell population. In hamsters with orthotopic pancreatic tumors, TTFields significantly reduced tumor volume accompanied by an increase in the frequency of abnormal mitotic events. TTFields efficacy was enhanced both in vitro and in vivo when combined with chemotherapy., Conclusions: These results provide the first evidence that TTFields serve as an effective antimitotic treatment in preclinical pancreatic cancer models and have a long term negative effect on cancer cell survival. These results make TTFields an attractive candidate for testing in the treatment of patients with pancreatic cancer., (Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
45. Dynamic collapse of the common pharynx in a cat.
- Author
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Zaid MS, Porat-Mosenco Y, and Mosenco AS
- Subjects
- Animals, Cats, Male, Nasal Obstruction pathology, Nasal Obstruction veterinary, Pharyngeal Diseases pathology, Cat Diseases pathology, Pharyngeal Diseases veterinary, Pharynx pathology
- Published
- 2011
- Full Text
- View/download PDF
46. Viewed actions are mapped in retinotopic coordinates in the human visual pathways.
- Author
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Porat Y, Pertzov Y, and Zohary E
- Subjects
- Adult, Female, Fixation, Ocular, Humans, Male, Photic Stimulation methods, Visual Fields physiology, Pattern Recognition, Visual physiology, Retina physiology, Space Perception physiology, Visual Cortex physiology, Visual Pathways physiology
- Abstract
Viewed object-oriented actions elicit widespread fMRI activation in the dorsal and ventral visual pathways. This activation is typically stronger in the hemisphere contralateral to the visual field in which action is seen. However, since in previous studies participants kept fixation at the same screen position throughout the scan, it was impossible to infer if the viewed actions are represented in retina-based coordinates or in a more elaborated coordinate system. Here, participants changed their gaze between experimental conditions, such that some conditions shared the same retinotopic coordinates (but differed in their screen position), while other pairs of conditions shared the opposite trait. The degree of similarity between the patterns of activation elicited by the various conditions was assessed using multivoxel pattern analysis methods. Regions of interest, showing robust overall activation, included the intraparietal sulcus (IPS) and the occipitotemporal cortex. In these areas, the correlation between activation patterns for conditions sharing the same retinotopic coordinates was significantly higher than that of those having different retinotopic coordinates. In contrast, the correlations between activation patterns for conditions with the same spatiotopic coordinates were not significantly greater than for non-spatiotopic conditions. These results suggest that viewed object-oriented actions are likely to be maintained in retinotopic-framed coordinates.
- Published
- 2011
- Full Text
- View/download PDF
47. Transient extremity ischemia augments CD34+ progenitor cell availability.
- Author
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Czeiger D, Dukhno O, Douvdevani A, Porat Y, Shimoni D, Fulga V, Ament JD, and Shaked G
- Subjects
- Biomarkers metabolism, Humans, Interleukin-8 blood, Neovascularization, Physiologic physiology, Nitric Oxide blood, Stem Cells cytology, Vascular Endothelial Growth Factor A blood, Antigens, CD34 metabolism, Extremities blood supply, Ischemia metabolism, Ischemic Preconditioning, Stem Cells physiology
- Abstract
Peripheral blood is an easily accessed source for stem cell production; however, the number of cells produced is relatively low. We hypothesized that ischemic preconditioning may serve as a safe method to increase the number of CD34+ cells that can be harvested and cultured in a short period. This study was conducted to test this hypothesis by examining the safety and efficacy of brief, transient ischemia of the lower limbs to augment the number of cells that can be produced from blood of healthy volunteers. Following induction of ischemia, blood samples were withdrawn at baseline, 30 min, 12 h and 24 h. The number of progenitor cells was determined by flow cytometry after the harvested cells were cultured for 5 days. We also analyzed the blood samples to determine IL-8 and VEGF concentrations. No serious adverse events were observed. The total number of cells increased from 0.46 ± 0.1 × 10(6) cells/ml in the pretreatment blood samples to 0.7 ± 0.1 × 10(6) cells/ml in blood taken 12 h after the conclusion of transient ischemia, p = 0.0029. The number of CD34+ cells increased from 4.23 ± 0.8 × 10(4) cells/ml in the pretreatment samples to 7.17 ± 1.34 × 10(4) cells/ml in blood taken 12 h after ischemia, p = 0.0001. The harvested stem cells maintained their ability to construct tubular structures. The augmentation in the number of CD34+ cells was positively correlated with the increase of IL-8, but not with VEGF concentrations. Ischemic preconditioning is a safe and effective technique to increase the availability of stem cells for therapeutic purposes.
- Published
- 2011
- Full Text
- View/download PDF
48. Modality-specific and modality-independent components of the human imagery system.
- Author
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Daselaar SM, Porat Y, Huijbers W, and Pennartz CM
- Subjects
- Auditory Cortex physiology, Auditory Perception physiology, Brain Mapping, Cues, Female, Humans, Linear Models, Magnetic Resonance Imaging, Male, Neural Pathways physiology, Neuropsychological Tests, Visual Cortex physiology, Visual Perception physiology, Young Adult, Brain physiology, Imagination physiology
- Abstract
Imagery research typically deals with the commonalities and differences between imagery and perception. As such, it is usually confined to one specific modality. Yet, it is likely that some of the underlying processes are shared between different sensory modalities while others are modality-specific. In this fMRI study, we used a balanced design that allowed for a direct comparison between imagery and perception in visual and auditory modalities, and also for a link between subjective imagery experience and brain activation. Results indicated a selective role for the "default mode network" as a modality-independent "core" imagery network. In addition, results identified areas in the visual and auditory association cortices that contributed to mental imagery in a modality-specific fashion. Interestingly during mental imagery, primary visual and auditory cortices showed modality-specific suppression of activity. This is the first fMRI study to characterize both modality-specific and modality-independent components of the human imagery system., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
49. Microbial growth inhibition by alternating electric fields in mice with Pseudomonas aeruginosa lung infection.
- Author
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Giladi M, Porat Y, Blatt A, Shmueli E, Wasserman Y, Kirson ED, and Palti Y
- Subjects
- Animals, Anti-Bacterial Agents therapeutic use, Ceftazidime therapeutic use, Colony Count, Microbial, Disease Models, Animal, Electrodes, Female, Hot Temperature, Humans, Lung microbiology, Lung pathology, Lung Diseases drug therapy, Lung Diseases microbiology, Lung Diseases pathology, Mice, Mice, Inbred ICR, Pseudomonas Infections drug therapy, Pseudomonas Infections microbiology, Pseudomonas Infections pathology, Treatment Outcome, Electricity, Lung Diseases therapy, Pseudomonas Infections therapy, Pseudomonas aeruginosa growth & development, Pseudomonas aeruginosa radiation effects
- Abstract
High-frequency, low-intensity electric fields generated by insulated electrodes have previously been shown to inhibit bacterial growth in vitro. In the present study, we tested the effect of these antimicrobial fields (AMFields) on the development of lung infection caused by Pseudomonas aeruginosa in mice. We demonstrate that AMFields (10 MHz) significantly inhibit bacterial growth in vivo, both as a stand-alone treatment and in combination with ceftazidime. In addition, we show that peripheral (skin) heating of about 2 degrees C can contribute to bacterial growth inhibition in the lungs of mice. We suggest that the combination of alternating electric fields, together with the heat produced during their application, may serve as a novel antibacterial treatment modality.
- Published
- 2010
- Full Text
- View/download PDF
50. Baicalein reduces E46K alpha-synuclein aggregation in vitro and protects cells against E46K alpha-synuclein toxicity in cell models of familiar Parkinsonism.
- Author
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Jiang M, Porat-Shliom Y, Pei Z, Cheng Y, Xiang L, Sommers K, Li Q, Gillardon F, Hengerer B, Berlinicke C, Smith WW, Zack DJ, Poirier MA, Ross CA, and Duan W
- Subjects
- Animals, Cell Death, Cell Differentiation, Membrane Potential, Mitochondrial drug effects, Mutation, Neurons metabolism, Neurons ultrastructure, PC12 Cells, Parkinsonian Disorders genetics, Proteasome Inhibitors, Rats, alpha-Synuclein biosynthesis, Flavanones pharmacology, Parkinsonian Disorders metabolism, alpha-Synuclein genetics
- Abstract
The E46K is a point mutation in alpha-synuclein (alpha-syn) that causes familial Parkinsonism with Lewy body dementia. We have now generated a cell model of Parkinsonism/Parkinson's disease (PD) and demonstrated cell toxicity after expression of E46K in the differentiated PC12 cells. E46K alpha-syn inhibited proteasome activity and induced mitochondrial depolarization in the cell model. Baicalein has been reported to inhibit fibrillation of wild type alpha-syn in vitro, and to protect neurons against several chemical-induced models of PD. We now report that baicalein significantly attenuated E46K-induced mitochondrial depolarization and proteasome inhibition, and protected cells against E46K-induced toxicity in a cell model of PD. Baicalein also reduced E46K fibrilization in vitro, with a concentration-dependent decrease in beta sheet conformation, though it increased some oligomeric species, and decreased formation of E46K alpha-syn-induced aggregates and rescued toxicity in N2A cells. Taken together, these data indicate that mitochondrial dysfunction, proteasome inhibition and specific aspects of abnormal E46K aggregation accompany E46K alpha-syn-induced cell toxicity, and baicalein can protect as well as altering aggregation properties. Baicalein has potential as a tool to understand the relation between different aggregation species and toxicity, and might be a candidate compound for further validation by using in vivo alpha-syn genetic PD models.
- Published
- 2010
- Full Text
- View/download PDF
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