Search

Lifelong premature ejaculation (LPE) may have heritable components. Selective serotonin reuptake inhibitors have been proven effective in prolonging intravaginal ejaculation latency time (IELT). Given that serotonergic pathways are involved in the ejaculation mechanism, we aimed to investigate whether His452Tyr, also known as the C1354T (RS6314) polymorphism of the 5-HT2A receptor, contributes to LPE pathogenesis and IELT differences among patients with LPE. Dutch Caucasian men with LPE (n = 65) attending the Outpatient Department of Neurosexology, HagaZiekenhuis for drug treatment for LPE in 2009 were selected and included in this case-control study. IELT during coitus was measured using a stopwatch, and all men were genotyped for the His452Tyr polymorphism. Analysis of variance (ANOVA) was performed to determine the association between the genotypes and IELTs. Mean IELTs with standard deviations were 29.7 (+/- 20.9), 31.5 (+/- 14.7), and 26.0 s, and the frequencies were 83.1%, 15.4%, and 1.5% for the CC, CT, and TT groups, respectively, with an average IELT of 29.9 s. No difference in mean IELT was observed between these groups. In the affected group, the frequencies of alleles C and T were 90.8% and 9.2%, respectively; whereas those among randomly selected European Caucasian male controls (n = 503) from the CEPH database were of 92.0% and 8.0%, respectively. No significant difference was observed between the groups. Therefore, no correlation was found between the His452Tyr polymorphism and IELT distribution in patients with LPE.

18 pages, 6 figures, 1 table.-- Data availability statement: No new data were generated or analysed in support of this research, Cuttlefish are an important global fisheries resource, and their demand is placing increasing pressure on populations in many areas, necessitating conservation measures. We reviewed evidence from case studies spanning Europe, Africa, Asia, and Australia encompassing diverse intervention methods (fisheries closures, protected areas, habitat restoration, fishing-gear modifications, promoting egg survival, and restocking), and we also discuss the effects of pollution on cuttlefish. We conclude: (1) spatio-temporal closures need to encompass substantial portions of a species’ range and protect at least one major part of their life cycle; (2) fishing-gear modifications have the potential to reduce unwanted cuttlefish capture, but more comprehensive trials are needed; (3) egg survival can be improved by diverting and salvaging from traps; (4) existing lab rearing and restocking may not produce financially viable results; and (5) fisheries management policies should be regularly reviewed in light of rapid changes in cuttlefish stock status. Further, citizen science can provide data to reduce uncertainty in empirical assessments. The information synthesized in this review will guide managers and stakeholders to implement regulations and conservation initiatives that increase the productivity and sustainability of fisheries interacting with cuttlefish, and highlights gaps in knowledge that need to be addressed, This work was supported by the Irish Research Council-Government of Ireland Post-doctoral Fellowship Award (Ref. GOIPD/2019/460) and a Juan de la Cierva Incorporación fellowship (code TBC) granted by MCIN/AEI/10.13039/501100011033 and the European Union NextGenerationEU/PRTR. JHU was supported by a Juan de la Cierva Incorporación fellowship (IJC2020-043701-I) granted by MCIN/AEI. GS and SKK are grantful to the Director, ICAR-CMFRI, India; KS and PR for the facilities and encouragement. Support to RV, FÁFÁ, OE, and JGR was provided by the Direcció General de Política Marítima i Pesca Sostenible, Catalan government; the research project MITICEPH (Ref. TED2021-130193B-I00) granted by MCIN/AEI/10.13039/501100011033 and the European Union NextGenerationEU/PRTR; and by the Spanish government through the “Severo Ochoa Center of Excellence” accreditation (CEX2019-000928-S)

What is this summary about? People with multiple sclerosis (shortened to MS) who are taking cladribine tablets may have concerns about whether they can be vaccinated against COVID-19. This summary details the findings from a previously published article, in which an international committee of 10 MS experts developed recommendations to answer some important questions about COVID-19 vaccines in people with MS (including relapsing–remitting or active secondary progressive disease) taking cladribine tablets. What were the results? The committee identified 13 recommendations, which were all agreed upon by at least three-quarters (75%) of the 38 voting MS experts. Generally, they recommended that people with MS taking cladribine tablets should be vaccinated for COVID-19 as soon as possible, because the vaccine is thought to be both safe and effective, and vaccine responses were not likely to be affected by cladribine tablets. What do the results mean? Overall, people with MS taking cladribine tablets should receive the COVID-19 vaccine to protect themselves, unless advised differently by their healthcare provider.

The concept of instructional competence, which refers to the ability to show that one has the readiness and effectiveness of necessary skills within the teaching framework in public schools, has hardly ever been investigated. This qualitative descriptive phenomenological study aimed to discover the instructional competence of newly hired public school teachers. Through the lens of Albert Bandura's (1997) Self-Efficacy Theory, it investigated what instructional competencies a newly hired teacher possessed that demonstrated readiness and efficacy of the required skills. The focus group discussions highlighted the crucial characteristics for improving the competencies. The results revealed six (6) emergent themes: the acquisition of baseline instructional standards, coping with the shift of instructional quality, planning for quality instruction, an initiative for instructional improvement, dealing with uncertainties, and health and well-being stability. The results highlighted that instructional competency might become self-efficient with increased experience and practice. Their prior teaching experience influenced the quality of a new teacher's instruction. In addition, teachers' competencies are gradually enhanced and strengthened as they gain experience in the field. As students discover new concepts, teachers begin to hone the skills that will allow them to manage classroom instruction effectively. This study deepens the understanding of instructional competence and may enable teachers and policymakers to design and implement initiatives. Since there is strong evidence that newly hired teachers may be self-sufficient, instructional managers must assure support by creating policies and programs that bridge instructional competencies to practice. These professional development programs allow newly hired teachers eventually gain instructional competency and well-motivated public-school teaching., {"references":["Bartell, T., Floden, R., & Richmond, G. (2018). What Data and Measures Should Inform Teacher Preparation? Reclaiming Accountability. Journal of Teacher Education, 69(5), 426-428. https://doi.org/10.1177/0022487118797326","Broomhead, K.E. (2018). Perceived Responsibility for Developing and Maintaining Home-School Partnerships: The Experiences of Parents and Practitioners. British Journal of Special Education, 45(4), 435-453. https://doi.org/10.1111/1467-8578.12242","Buehl, M. & Beck, J. (2015). The Relationship Between Teachers' Beliefs and Teachers' Practices: International Handbook of Research on Teachers' Beliefs. Taylor & Francis. https://www.taylorfrancis.com/books/e/9780203108437/chapters/10.4324/9780","Corbo, J.C., Reinholz, D.L., Dancy, M.H., Deetz, S., & Finkelstein, N. (2016). Framework for transforming departmental culture to support educational innovation. Physical Review, Physics Education Research, 12(1). https://doi.org/10.1103/physrevphyseducres.12.010113","Cox, A., Solomon, B., & Parris, D. (2018). Teacher Well-Being is A Critical and Often Overlooked Part of School Health. Child Trends. https://www.childtrends.org/teacher-well-being-is-a-critical-and-often-overlooked-part-of-school-health.","Creswell, J.W. & Poth, C.N. (2018). Phenomenological Study. In Qualitative Inquiry & Research Design: Choosing Among Five Approaches (4th ed., pp. 64-76). SAGE.","Czerniawski, G., Guberman, A., & Macphail, A. (2016). The Professional Developmental Needs of Higher Education-Based Teacher Educators: An International Comparative Needs Analysis. European Journal of Teacher Education, 40(1), 127–140. https://doi.org/10.1080/02619768.2016.1246528","Cull, E. (2019). Teachers Observing Teachers: A Professional Development Tool for Every School: Education World. Teachers Observing Teachers: A Professional Development Tool for Every School | Education World. https://www.educationworld.com/a_admin/admin/admin297.shtml","Davis, L. (2019). Teacher Collaboration: How to Approach It In 2020. Schoology. https://www.schoology.com/blog/teacher-collaboration","Davis, A. & Mcdonald, D. (2019). Teachers' Reflections of Instructional Effectiveness: Self-assessment Through a Standards-based Appraisal Process. Reflective Practice, 20(1), 125-141. https://doi.org/10.1080/14623943.2019.1569508","Dela Fuente, J.A. (2021). Implementing inclusive education in the Philippines: College teacher experiences with deaf students. Issues in Educational Research, 31(1), 94-110. http://www.iier.org.au/iier31/dela-fuente.pdf","Dela Fuente, J.A. (2019). Driving Forces of Students' Choice in Specializing Science: A Science Education Context in the Philippines Perspective. The Normal Lights, 13(2), 225 - 250. https://po.pnuresearchportal.org/ejournal/index.php/normallights/article/view/1393","Ginsburg, M. (2017). Teachers as Human Capital or Human Beings? USAID's Perspective on Teachers. Maryland; ERIC.","Goldhaber, D. (2015). Exploring the Potential of Value-Added Performance Measures to Affect the Quality of the Teacher Workforce. Educational Researcher, 44(2), 87-95. https://doi.org/10.3102/0013189x15574905","Hökkä, P., Vähäsantanen, K., & Mahlakaarto, S. (2017). Teacher Educators' Collective Professional Agency and Identity – Transforming Marginality to Strength. Teaching and Teacher Education, 63, 36-46. https://doi.org/10.1016/j.tate.2016.12.001","Jun, P. (2019). Never Stop Learning: How Self-Education Creates a Bullet-Proof Career. Adobe 99U. https://99u.adobe.com/articles/29995/never-stop-learning-how-self-education-creates-a-bullet-proof-career.","Kearney, S. (2016). What happens when induction goes wrong: Case studies from the field. Cogent Education, 3(1). https://doi.org/10.1080/2331186x.2016.1160525","Lewis, C. (2016). How Does Lesson Study Improve Mathematics Instruction? ERIC, 48(4), 571-580. https://doi.org/10.1007/11858.1863-9704","Lynch, D.E., Provost, S., Turner, D., Smith, R., & Yeigh, T. (2017). The Correlation between 'Teacher Readiness' and Student Learning Improvement. International Journal of Innovation, Creativity and Change, 3(1).","Lynch, D., Smith, R., Provost, S., & Madden, J. (2016). Improving teaching capacity to increase student achievement. Journal of Educational Administration, 54(5), 575-592. https://doi.org/10.1108/jea-10-2015-0092","Martin, K.L., Buelow, S.M., & Hoffman, J.T. (2015). New teacher induction: Support that impacts beginning middle-level educators. Middle School Journal, 47(1), 4–12. https://doi.org/10.1080/00940771.2016.1059725","Matsko, K.K., Ronfeldt, M., Nolan, H.G., Klugman, J., Reininger, M., & Brockman, S.L. (2018). Cooperating Teacher as Model and Coach: What Leads to Student Teachers' Perceptions of Preparedness? Journal of Teacher Education, 71(1), 41-62. https://doi.org/10.1177/0022487118791992","Montebon, D.R. (2015). Student Teaching Enhancement Program (Step) And Preservice Teachers' Teaching Efficacy In Science. Journal of Computer and Education Research, 3(5), 1. https://doi.org/10.18009/jcer.49008","Punongbayan, E.J. & Simeon M. Bauyon. (2015). Instructional Performance of Teacher Education Faculty Members in One State University in the Philippines. Asia Pacific Journal of Multidisciplinary Research, 3(5), 135-143.","Ronfeldt, M., Matsko, K.K., Nolan, H.G., & Reininger, M. (2018). Who Knows if our Teachers are Prepared? Three Different Perspectives on Graduates' Instructional Readiness and the Features of Preservice Preparation that Predict them. Center for Education Policy Analysis, 18.","Schumacher, G., Grigsby, B., & Vesey, W. (2015). Determining effective teaching behaviors through the hiring process. International Journal of Educational Management, 29(1), 139–155. https://doi.org/10.1108/ijem-04-2013-0071","Smith, C.A.S., Martin, J., Macdonald, G.T., & Wao, H. (2015). Designing a Survey for Engineering Undergraduates using Free Listing -An Anthropological Structured Technique. American Society for Engineering Education, 12.","Snead, L.O., & Freiberg, H.J. (2017). Rethinking Student-Teacher Feedback: Using a Self-Assessment Resource With Student Teachers. Journal of Teacher Education, 70(2), 155-168. https://doi.org/10.1177/0022487117734535","Teacher Induction: Providing Comprehensive Training for New Special Educators. IRIS Center. (2013). https://iris.peabody.vanderbilt.edu/module/induction/","Truesdale, V. (2018). Investing in Healthy Teachers. http://www.ascd.org/publications/newsletters/education-update/oct08/vol50/num10/Investing-in-Healthy-Teachers.aspx","Tugsbaatar, U. (2020). Albert Bandura: Self-Efficacy for Agentic Positive Psychology. https://positivepsychology.com/bandura-self-efficacy/","Umugiraneza, O., Bansilal, S., & North, D. (2016). Teachers' Confidence And Beliefs In Teaching Mathematics And Statistics Concepts. PONTE International Scientific Research's Journal, 72(9). https://doi.org/10.21506/j.ponte.2016.9.34","Manen, M.V. (2016). Phenomenology of Practice. https://doi.org/10.4324/9781315422657","Wan, S.Y. (2016). Differentiated instruction: are Hong Kong in-service teachers ready? Teachers and Teaching, 1–28. https://doi.org/10.1080/13540602.2016.1204289","Welch, A., & Napoleon, L. (2015). Professional Teaching Dispositions of Online Instructors: Why they Matter. Procedia - Social and Behavioral Sciences, 171, 584-589. https://doi.org/10.1016/j.sbspro.2015.01.164"]}

Eight drimane sesquiterpenoids including (-)-drimenol and (+)-albicanol were synthesized from (+)-sclareolide and evaluated for their antifungal activities. Three compounds, (-)-drimenol, (+)-albicanol, and (1R,2R,4aS,8aS)-2-hydroxy-2,5,5,8a-tetramethyl-decahydronaphthalene-1-carbaldehyde (4) showed strong activity against C. albicans. (-)-Drimenol, the strongest inhibitor of the three, (at concentrations of 8 – 64 μg/ml, causing 100% death of fungi), acts not only against C. albicans as a fungicidal manner, but also inhibits other fungi such as Aspergillus, Cryptococcus, Pneumocystis, Blastomyces, Fusarium, Rhizopus, Saksenaea and FLU resistant strains of C. albicans, C. glabrata, C. krusei, C. parapsilosis and C. auris. These observations suggest drimenol is a broad-spectrum antifungal agent. At high concentration (100 μg/ml), drimenol caused a rupture of the fungal cell wall/membrane. In a nematode model of C. albicans infection, drimenol rescued the worms from C. albicans-mediated death, indicating drimenol is tolerable and bioactive in a metazoan. Genome-wide fitness profiling assays of both S. cerevisiae (nonessential homozygous and essential heterozygous) and C. albicans (Tn-insertion mutants) collections revealed putative genes and pathways affected by drimenol. Using a C. albicans mutants spot assay, the Crk1 kinase associated gene products, Ret2, Cdc37, and novel putative targets orf19.759, orf19.1672, and orf19.4382 were revealed to be the potential targets of drimenol. Further, computational modeling results suggest possible modification of the structure of drimenol including the A ring for improving antifungal activity.

Two nearly degenerate positive-parity bands with the πg9/22⊗νg9/2−1 configuration and three nearly degenerate negative-parity bands with the πg9/2(p3/2,f5/2)⊗νg9/2−1 configuration have been identified in $^{81}$Kr. They are interpreted as chiral doublet bands and pseudospin-chiral triplet bands, which is supported by the constrained covariant density functional theory and the multiparticle plus rotor model calculations. The present work reports two new chiral configurations πg9/22⊗νg9/2−1 and πg9/2(p3/2,f5/2)⊗νg9/2−1, and the first example of pseudospin-chiral triplet bands involving the π(p3/2,f5/2) pseudospin doublet.

This paper mainly investigates the iterative structures whose decryption is similar to the encryption. Firstly, we unify many well-known structures which share similar procedures between the decryption and the encryption, and give a sufficient and necessary condition for this structure to be bijective, which reveals many new insights into the Feistel structure as well as the Lai-Massey structure. Secondly, we analyze the security of the unified structure against the known cryptanalysis. By extending the dual structure from a Feistel structure to the unified structure, we prove that a differential of the unified structure is impossible if and only if it is a zero-correlation linear hull of its dual structure, which presents a generalized link between the impossible differential and zero-correlation linear cryptanalysis shown in CRYPTO 2015. Significantly, several constraints on the linear components of the cipher and the permutation on the branches of the cipher are specified to make the structure resilient to differential and linear cryptanalysis. Furthermore, in the case that the order of the permutation equals the number of the branches n, we prove that there always exist a (3n−1) -round impossible differential and a (3n−1) -round zero-correlation linear hull of the structure, and also present an algorithm to construct these distinguishers. Finally, we propose some novel structures which might be used in future block cipher designs.

Background: Cognitive impairment is common sequelae of multiple sclerosis (MS); however, relatively little is known about cognitive impairment in late-onset multiple sclerosis (LOMS). Objective: To investigate differences in disease characteristics and cognition in LOMS and adult-onset multiple sclerosis (AOMS) patients. Methods: Archival medical records and neuropsychological evaluations from an MS specialty center were reviewed. Differences in disease characteristics between 53 LOMS and 124 AOMS were compared using chi-square or analysis of variance (ANOVA). To investigate differences in cognitive functioning, age-adjusted standardized scores were compared via analysis of covariance (ANCOVA), using cardiac risk factors and disease duration as covariates. Results: Compared to AOMS, LOMS patients had significantly more cardiac risk factors, shorter disease duration, and shorter time to diagnosis. LOMS patients had similar Expanded Disability Status Scale scores as AOMS patients. LOMS patients demonstrated significantly more impairment on tasks of visual learning and memory, and working memory than AOMS patients. Conclusion: Despite a shorter disease duration, LOMS and AOMS patients had similar levels of physical impairment. However, even after accounting for differences in disease duration and cardiac risk, LOMS patients showed a greater burden of cognitive impairment than AOMS patients, suggesting MS diagnosed later in life may progress faster due to the interaction between MS neuropathology and aging.

Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.

Journal of Instrumentation 17(05), P05022 (2022). doi:10.1088/1748-0221/17/05/P05022, The Compact Muon Solenoid collaboration is designing a new high-granularity endcap calorimeter, HGCAL, to be installed later this decade. As part of this development work, a prototype system was built, with an electromagnetic section consisting of 14 double-sided structures, providing 28 sampling layers. Each sampling layer has an hexagonal module, where a multipad large-area silicon sensor is glued between an electronics circuit board and a metal baseplate. The sensor pads of approximately 1.1 cm$^{2}$ are wire-bonded to the circuit board and are readout by custom integrated circuits. The prototype was extensively tested with beams at CERN's Super Proton Synchrotron in 2018. Based on the data collected with beams of positrons, with energies ranging from 20 to 300 GeV, measurements of the energy resolution and linearity, the position and angular resolutions, and the shower shapes are presented and compared to a detailed Geant4 simulation., Published by Inst. of Physics, London

An inelastic excitation and cluster-decay experiment $\rm {^2H}(^{16}C,~{^{4}He}+{^{12}Be}~or~{^{6}He}+{^{10}Be}){^2H}$ was carried out to investigate the linear-chain clustering structure in neutron-rich $\rm {^{16}C}$. For the first time, decay-paths from the $\rm {^{16}C}$ resonances to various states of the final nuclei were determined, thanks to the well-resolved $Q$-value spectra obtained from the three-fold coincident measurement. The close-threshold resonance at 16.5 MeV is assigned as the ${J^\pi}={0^+}$ band head of the predicted positive-parity linear-chain molecular band with ${(3/2_\pi^-)^2}{(1/2_\sigma^-)^2}$ configuration, according to the associated angular correlation and decay analysis. Other members of this band were found at 17.3, 19.4, and 21.6 MeV based on their selective decay properties, being consistent with the theoretical predictions. Another intriguing high-lying state was observed at 27.2 MeV which decays almost exclusively to $\rm {^{6}He}+{^{10}Be{(\sim6~ MeV)}}$ final channel, corresponding well to another predicted linear-chain structure with the pure $\sigma$-bond configuration., Comment: 6 pages, 4 figures

There is an urgent unmet need for new therapeutics for Alzheimer's disease (AD), the most common cause of dementia in the elderly. Therapeutic approaches targeting amyloid-β (Aβ) and its downstream toxicities have become major strategies in AD drug development. We have taken a rational design approach and synthesized a class of tricyclic pyrone (TP) compounds that show anti-Aβ and other neuroprotective actions. The in vivo efficacy of a lead TP named CP2 to ameliorate AD-like pathologies has been shown in mouse models. Here we report the selection and initial characterization of a new lead TP70, which exhibited an anti-Aβ therapeutic index even higher than CP2. Moreover, TP70 was able to reduce oxidative stress, inhibit acyl-coenzyme A:cholesterol acyltransferase (ACAT), and upregulate the expression of ATP-binding cassette subfamily A, member 1 (ABCA1), actions considered neuroprotective in AD. TP70 further showed excellent pharmacokinetic properties, including brain penetration and oral availability. When administered to 5xFAD mice via intraperitoneal or oral route, TP70 enhanced the overall solubility and decreased the level of cerebral Aβ, including both fibrillary and soluble Aβ species. Interestingly, TP70 enhanced N-methyl-D-aspartate (NMDA) receptor-mediated excitatory post-synaptic potential (EPSP) in the hippocampal CA1 area, increased the magnitude of NMDA-dependent hippocampal long-term potentiation (LTP), a cellular model of learning and memory, and prevented the Aβ oligomer-impaired LTP. Significantly, a single dose of TP70 administered to aged 5xFAD mice was effective in mitigating the impaired LTP induction, recorded at 24 h after administration. Our results support a potential of TP70 in clinical development for AD in view of its synergistic neuroprotective actions, ability to positively modulate NMDA receptor-mediated hippocampal plasticity, and favorable pharmacokinetic properties in rodents.

There is a strong demand for bioanalytical techniques to rapidly detect protease activities with high sensitivity and high specificity. This study reports an activity-based electrochemical method toward this goal. Nanoelectrode arrays (NEAs) fabricated with embedded vertically aligned carbon nanofibers (VACNFs) are functionalized with specific peptide substrates containing a ferrocene (Fc) tag. The kinetic proteolysis curves are measured with continuously repeated ac voltammetry, from which the catalytic activity is derived as the inverse of the exponential decay time constant based on a heterogeneous Michaelis–Menten model. Comparison of three peptide substrates with different lengths reveals that the hexapeptide H(2)N─(CH(2))(4)─CO─Pro-Leu-Arg-Phe-Gly-Ala─NH─CH(2)─Fc is the optimal probe for cathepsin B. The activity strongly depends on temperature and is the highest around the body temperature. With the optimized peptide substrate and measuring conditions, the limit of detection of cathepsin B activity and concentration can reach 2.49 × 10(−4) s(−1) and 0.32 nM, respectively. The peptide substrates show high specificity to the cognate proteases, with negligible cross-reactions among three cancer-related proteases cathepsin B, ADAM10, and ADAM17. This electrochemical method can be developed into multiplex chips for rapid profiling of protease activities in cancer diagnosis and treatment monitoring.

Zn and ZnFe coated 22MnB5 and 34MnB5 steels were subjected to the direct press hardening process in order to investigate the influence of steel composition on the resulting phase structures. Microstructures were characterized using advanced methods of microscopy. In addition, X-ray diffraction, glow discharge optical emission spectroscopy and thermodynamic calculations with Thermo-Calc® were carried out to support the analysis. The results indicate that the steel composition has a clear effect on the phase development within coating and interface regions. Whereas the behavior of the 22MnB5 was comparable to earlier investigations, a clearly non-conventional behavior of the 34MnB5 was observed: the formation of martensitic micro constituents, designated here as α′-Fe(Zn), were identified after die-quenching. The regions of the α′-Fe(Zn) formed mainly in vicinity of steel/coating interface and were emerged into the steel by sharing martensitic morphology with the base steel. The thermodynamic calculations suggest that carbon is effective in stabilizing the γ-Fe(Zn) phase, which enables the formation of the α′-Fe(Zn) in fast cooling. Therefore, the higher initial C content of the 34MnB5 may result in the kinetic stabilization of the γ-Fe(Zn) as the inter-diffusion between Zn and Fe occurs during annealing. Simultaneously occurring carbon partitioning from α-Fe(Zn) to γ-Fe(Zn) could explain a clearly increased C content of the coating/steel interface as well as higher Zn contents in the α′-Fe(Zn) phase compared to 22MnB5. Actually, the present study shows that the same phenomenon occurs also in 22MnB5 steels, but in a much smaller scale. In Zn and ZnFe coated 34MnB5, the thickness of the α′-Fe(Zn) layer was increased with longer annealing times and at higher temperatures. The morphology of the α′-Fe(Zn) layer resembled plate-like martensite and can be assumed to be brittle. Regarding this, the formation of α′-Fe(Zn) interface layer needs to be taken into account in press hardening of 34MnB5 steels.

Sulfur deactivation and regeneration behavior of the Pd/Al₂O₃ catalyst has been investigated via experimental characterization and density functional theory (DFT) simulations. During the sulfur exposure, PdO crystallites grow slightly while bulk Al₂(SO₄)₃ forms on the support. DFT calculations indicate that SOₓ species interact strongly with the catalyst surface making it chemically inactive in agreement with the experimental results. During the regeneration treatment (CH₄ conditions), PdO particles reduce, Al₂(SO₄)₃ is partially removed, and the activity for CH₄ conversion is increased. No full recovery can be observed due to remaining Al₂(SO₄)₃, the formation of encapsulating sulfur species, and the partial reduction of PdO particles. To reoxidize Pd, the catalyst is further regenerated (O₂ conditions). The resulting CH₄ conversion is at the same level than with the regenerated catalyst. Thus, a small amount of Al₂(SO₄)₃ appears to have a stronger effect on the performance than the state of Pd.

An advanced model is proposed, describing the capacity losses of C6/LiFePO4 batteries under storage and cycling conditions. These capacity losses are attributed to the growth of a Solid Electrolyte Interface (SEI) at the surface of graphite particles in the negative electrode. The model assumes the existence of an inner and outer SEI layer. The rate determining step is considered to be electron tunneling through the inner SEI layer. The inner SEI layer grows much slower than the outer SEI layer. Another contribution to the degradation process is the exfoliation of SEI near the edges of graphite particles during discharging and the formation of new SEI induced by the volumetric changes during the subsequent charging. The model has been validated by storage and cycling experiments. The simulation results show that the capacity losses are dependent on the State-of-Charge (SoC), the storage time, cycle number and graphite particle size. The model can be used to predict both the calendar and cycling life of the Li-ion batteries.

β -decay studies of neutron-rich nuclei in and around the “island of inversion” have been performed. With a systematic investigation of half-lives for the isotonic chains from N = 19 to 22, conspicuous kinks observed at Z = 13 provide a clear signature of a boundary on the northern (high- Z ) side of the island. Based on the comparison with shell model calculations using Gogny D1S and SDPF-M interactions, a newly determined 2 2 + state in 34 Si at 4519 keV presents an experimental evidence of triaxiality in this region and sheds more light on the structure of the transition across the northern boundary of the island.

A new class of poly-N-vinylpyrrolidinones containing an asymmetric center at C5 of the pyrrolidinone ring were synthesized from L-amino acids. The polymers, particularly 17, were used to stabilize nanoclusters such as Pd/Au for the catalytic asymmetric oxidations of 1,3- and 1,2-cycloalkanediols and alkenes, and Cu/Au for C-H oxidation of cycloalkanes. It was found that the bulkier the C5 substituent in the pyrrolidinone ring, the greater the optical yields produced. Both oxidative kinetic resolution of (±)-1,3- and 1,2-trans-cycloalkanediols and desymmetrization of meso cis-diols took place with 0.15 mol% of Pd/Au (3:1)-17 under oxygen atmosphere in water to give excellent chemical and optical yields of (S)-hydroxy ketones. Various alkenes were oxidized with 0.5 mol% of Pd/Au (3:1)-17 under 30 psi. of oxygen in water to give the dihydroxylated products in >93% ee. Oxidation of (R)-limonene at 25(o)C occurred at the C-1,2-cyclic alkene function yielding (1S,2R,4R)-dihydroxylimonene 49 in 92% yield. Importantly, cycloalkanes were oxidized with 1 mol% of Cu/Au (3:1)-17 and 30% H(2)O(2) in acetonitrile to afford chiral ketones in very good to excellent chemical and optical yields. Alkene function was not oxidized under the reaction conditions. Mechanisms were proposed for the oxidation reactions and observed stereo- and regio-chemistry were summarized.

This paper has completed the theoretical modeling of the cured surface reflection RIM-FOS under the typical optical fiber bundle structure. Firstly, the modeling of the fiber’s axial symmetry distribution structure is made by analytical method to get the intensity modulation function M. Then the modeling of the fiber’s coaxial distribution structure is made by analytical method to get its intensity modulation function M. Finally, the simulation experiment about the mathematical model of the two typical optical fiber beam structure is conducted to get the corresponding P- M curve when the variables d, r, ???change. The simulation results show that the relationships between the variable d, r, ???and the received light intensity under different fiber bundle structures indicate that the calculation results of the mathematical model are in conformity with the actual situation. Finally, it is concluded that detection range is similar to the detection sensitivity under the two typical optical fiber bundle structures, which provides a good theoretical basis for practical design of RIM-FOS.

Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro) with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for further development for important coronaviruses in animals and humans.

Polyhydroxyalkanoates (PHAs) are carbon and energy storage polymers produced by a variety of microbial organisms under nutrient-limited conditions. They have been considered as an environmentally friendly alternative to oil-based plastics due to their renewability, versatility, and biodegradability. PHA synthase (PhaC) plays a central role in PHA biosynthesis, in which its activity and substrate specificity are major factors in determining the productivity and properties of the produced polymers. However, the effects of modifying the substrate side chain are not well understood because of the difficulty to accessing the desired analogues. In this report, a series of 3-(R)-hydroxyacyl coenzyme A (HACoA) analogues were synthesized and tested with class I synthases from Chromobacterium sp. USM2 (PhaCCs and A479S-PhaCCs) and Caulobacter crescentus (PhaCCc) as well as class III synthase from Allochromatium vinosum (PhaECAv). It was found that, while different PHA synthases displayed distinct preference with regard to the length of the alkyl side chains, they could withstand moderate side chain modifications such as terminal unsaturated bonds and the azide group. Specifically, the specific activity of PhaCCs toward propynyl analogue (HHxyCoA) was only 5-fold less than that toward the classical substrate HBCoA. The catalytic efficiency (kcat/Km) of PhaECAv toward azide analogue (HABCoA) was determined to be 2.86 × 10(5) M(-1) s(-1), which was 6.2% of the value of HBCoA (4.62 × 10(6) M(-1) s(-1)) measured in the presence of bovine serum albumin (BSA). These side chain modifications may be employed to introduce new material functions to PHAs as well as to study PHA biogenesis via click-chemistry, in which the latter remains unknown and is important for metabolic engineering to produce PHAs economically.

Silica cocoons are synthesized via a cooperation of hexagonal P123 micelles and O/W emulsions. These silica cocoons are closed on one side but open on another side. The wall of these silica cocoons is hierarchically constructed by hexagonally ordered channels, which is produced by the aggregation of P123 micelles onto the emulsion droplets while the alternating protuberant and hollow wall of these silica cocoons result from a preferential silica condensation around the emulsion droplets. This paper provides a tunable route to synthesis hierarchically constructed nano-sized silica material with 200–500 nm long hexagonally ordered channels, which is determined by the size of the emulsion droplets.

A. Vogt et al. ; 12 págs.; 9 figs.; 1 tab., Detailed spectroscopic information on the N∼82 nuclei is necessary to benchmark shell-model calculations in the region. The nuclear structure above long-lived isomers in Xe134 is investigated after multinucleon transfer (MNT) and actinide fission. Xenon-134 was populated as (i) a transfer product in Xe136+U238 and Xe136+Pb208 MNT reactions and (ii) as a fission product in the Xe136+U238 reaction employing the high-resolution Advanced Gamma Tracking Array (AGATA). Trajectory reconstruction has been applied for the complete identification of beamlike transfer products with the magnetic spectrometer PRISMA. The Xe136+Pt198 MNT reaction was studied with the γ-ray spectrometer GAMMASPHERE in combination with the gas detector array Compact Heavy Ion Counter (CHICO). Several high-spin states in Xe134 on top of the two long-lived isomers are discovered based on γγ-coincidence relationships and information on the γ-ray angular distributions as well as excitation energies from the total kinetic energy loss and fission fragments. The revised level scheme of Xe134 is extended up to an excitation energy of 5.832 MeV with tentative spin-parity assignments up to 16+. Previous assignments of states above the 7- isomer are revised. Latest shell-model calculations employing two different effective interactions reproduce the experimental findings and support the new spin and parity assignments., The research leading to these results has received funding from the German BMBF under Contract No. 05P12PKFNE TP4, from the European Union Seventh Framework Programme FP7/2007–2013 under Grant Agreement No. 262010 - ENSAR, from the Spanish Ministerio de Ciencia e Innovación under Contract No. FPA2011-29854-C04, from the Spanish Ministerio de Economía y Competitividad under Contract No. FPA2014-57196-C5, from the Bonn-Cologne Graduate School of Physics and Astronomy (BCGS), from the UK Science and Technology Facilities Council (STFC), and from the US National Science Foundation (NSF). One of the authors (A. Gadea) has been supported by the Generalitat Valenciana, Spain, under Grant No. PROMETEOII/2014/019 and EU under the FEDER program.

The proteolytic activity of a cancer-related enzyme cathepsin B is measured with alternating current voltammetry (ACV) using ferrocene (Fc) labeled tetrapeptides attached to nanoelectrode arrays (NEAs) fabricated with vertically aligned carbon nanofibers (VACNFs). This combination enables the use of high AC frequencies (~1kHz) with enhanced electrochemical signals. The specific proteolysis of the Fc-peptide by cathepsin B produces decay in the ACV peak current versus the reaction time. The exponential component of the raw data can be extracted and defined as the "extracted proteolytic signal" which allows consistent quantitative analyses using a heterogeneous Michaelis-Menten model. A "specificity constant" kcat/KM = (3.68 ± 0.50) × 10(4)M(-1)s(-1) for purified cathepsin B was obtained. The detections of cathepsin B activity in different concentrations of whole lysate of human breast tissue, tissue lysate spiked with varied concentrations of cathepsin B, and the tissue lysate after immunoprecipitation showed that there is ~13.4 nM higher cathepsin B concentration in 29.1 µg mL(-1) of whole tissue lysate than the immunoprecipitated sample. The well-defined regular VACNF NEAs by e-beam lithography show a much faster kinetics for cathepsin B proteolysis with kcat/KM = 9.2 × 10(4)M(-1)s(-1). These results illustrate the potential of this technique as a portable multiplex electronic system for cancer diagnosis by rapid protease profiling of serum or blood samples.

OBJECTIVE: To report the 5-year risk and to identify risk factors for the development of a seminal acute or progressive clinical event in a multi-national cohort of asymptomatic subjects meeting 2009 RIS Criteria. METHODS: Retrospectively identified RIS subjects from 22 databases within 5 countries were evaluated. Time to the first clinical event related to demyelination (acute or 12-month progression of neurological deficits) was compared across different groups by univariate and multivariate analyses utilizing a Cox regression model. RESULTS: Data were available in 451 RIS subjects (F: 354 (78.5%)). The mean age at from the time of the first brain MRI revealing anomalies suggestive of MS was 37.2 years (y) (median: 37.1 y, range: 11-74 y) with mean clinical follow-up time of 4.4 y (median: 2.8 y, range: 0.01-21.1 y). Clinical events were identified in 34% (standard error=3%) of individuals within a 5-year period from the first brain MRI study. Of those who developed symptoms, 9.6% fulfilled criteria for primary progressive MS. In the multivariate model, age [hazard ratio (HR): 0.98 (95% CI: 0.96-0.99); p=0.03], sex (male) [HR: 1.93 (1.24-2.99); p=0.004], and lesions within the cervical or thoracic spinal cord [HR: 3.08 (2.06-4.62); p=

Aims Serelaxin is effective in relieving dyspnoea and improving multiple outcomes in acute heart failure (AHF). Many AHF patients have preserved ejection fraction (HFpEF). Given the lack of evidence-based therapies in this population, we evaluated the effects of serelaxin according to EF in RELAX-AHF trial. Methods and results RELAX-AHF randomized 1161 AHF patients to 48-h serelaxin (30 mu g/kg/day) or placebo within 16 h from presentation. We compared the effects of serelaxin on efficacy endpoints, safety endpoints, and biomarkers of organ damage between preserved (a parts per thousand yen50%) and reduced (< 50%, HFrEF) EF. HFpEF was present in 26% of patients. Serelaxin induced a similar dyspnoea relief in HFpEF vs. HFrEF patients by visual analogue scale-area under the curve (VAS-AUC) through Day 5 [mean change, 461 (-195, 1117) vs. 397 (10, 783) mm h, P = 0.87], but had possibly different effects on the proportion of patients with moderately or markedly dyspnoea improvement by Likert scale at 6, 12, and 24 h [odds ratio for favourable response, 1.70 (0.98, 2.95) vs. 0.85 (0.62, 1.15), interaction P = 0.030]. No differences were encountered in the effect of serelaxin on short- or long-term outcome between HFpEF and HFrEF patients including cardiovascular death or hospitalization for heart/renal failure through Day 60, cardiovascular death through Day 180, and all-cause death through Day 180. Similar safety and changes in biomarkers (high-sensitivity troponin T, cystatin-C, and alanine/aspartate aminotransferases) were found in both groups. Conclusions In AHF patients with HFpEF compared with those with HFrEF, serelaxin was well tolerated and effective in relieving dyspnoea and had a similar effect on short- and long-term outcome, including survival improvement.

Gap junctions are intercellular channels connecting adjacent cells, allowing cells to transport small molecules. The loss of gap junctional intercellular communication (GJIC) is one of the important hallmarks of cancer. Restoration of GJIC is related to the reduction of tumorigenesis and increase in drug sensitivity. Previous reports have shown that PQ1, a quinoline derivative, increases GJIC in T47D breast cancer cells, and subsequently attenuates xenograft breast tumor growth. Combinational treatment of PQ1 and tamoxifen can lower the effective dose of tamoxifen in cancer cells. In this study, the effects of PQ1 were examined in normal C57BL/6J mice, evaluating the distribution, toxicity, and adverse effects. The distribution of PQ1 was quantified by high-performance liquid chromatography and mass spectrometry. The expressions of survivin, caspase-8, cleaved caspase-3, aryl hydrocarbon receptor (AhR), and gap junction protein, connexin 43 (Cx43), were assessed using western blot analysis. Our results showed that PQ1 was absorbed and distributed to vital organs within 1 h and the level of PQ1 decreased after 24 h. Furthermore, PQ1 increased the expression of survivin, but decreased the expression of caspase-8 and caspase-3 activity. Interestingly, the expression of AhR increased in the presence of PQ1, suggesting that PQ1 may be involved in the AhR-mediated response. Previously, PQ1 caused an increase in Cx43 expression in breast cancer cells; however, PQ1 induced a decrease in Cx43 in normal tissues. Hemotoxylin and eosin staining of the tissues showed no histological change between the treated and the untreated organs. Our studies indicate that the administration of PQ1 by an oral gavage can be achieved with low toxicity to normal vital organs.

Moyamoya disease is a stenoocclusive disease involving the intracranial carotid and proximal middle cerebral arteries. There are rarely any additional extracranial stenoses occurring concurrently with moyamoya. The pathophysiology of moyamoya remains obscure, but hematologic disorders, notably sickle-cell anemia, have been associated in some cases. We describe the novel case of polycythemia vera associated with severe steno-occlusive disease of both intracranial and extracranial large arteries. A 47-year-old woman with polycythemia vera had multiple transient ischemic attacks, and noninvasive vessel imaging revealed steno-occlusive disease of bilateral supraclinoid internal carotid arteries with moyamoya-type collaterals, proximal left subclavian artery, right vertebral artery origin, bilateral renal arteries, superior mesenteric artery, and right common iliac artery. Laboratory workup for systemic vasculitis was negative. She required bilateral direct external carotid to internal carotid bypass procedures and percutaneous balloon angioplasty of her right VA origin stenosis. This case suggests that hematologic disorders can lead to vessel stenoses and occlusion. The pathophysiology may be due to a prothrombotic state leading to repeated endothelial injury, resultant intimal hyperplasia, and progressive steno-occlusion.

Laccase-2 is a highly conserved multicopper oxidase that functions in insect cuticle pigmentation and tanning. In many species, alternative splicing gives rise to two laccase-2 isoforms. A comparison of laccase-2 sequences from three orders of insects revealed eleven positions at which there are conserved differences between the A and B isoforms. Homology modeling suggested that these eleven residues are not part of the substrate binding pocket. To determine whether the isoforms have different kinetic properties, we compared the activity of laccase-2 isoforms from Tribolium castaneum and Anopheles gambiae . We partially purified the four laccases as recombinant enzymes and analyzed their ability to oxidize a range of laccase substrates. The predicted endogenous substrates tested were dopamine, N -acetyldopamine (NADA), N -β-alanyldopamine (NBAD) and dopa, which were detected in T. castaneum previously and in A. gambiae as part of this study. Two additional diphenols (catechol and hydroquinone) and one non-phenolic substrate (2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)) were also tested. We observed no major differences in substrate specificity between the A and B isoforms. Dopamine, NADA and NBAD were oxidized with catalytic efficiencies ranging from 51 to 550 min −1 mM −1 . These results support the hypothesis that dopamine, NADA and NBAD are endogenous substrates for both isoforms of laccase-2. Catalytic efficiencies associated with dopa oxidation were low, ranging from 8 to 30 min −1 mM −1 ; in comparison, insect tyrosinase oxidized dopa with a catalytic efficiency of 201 min −1 mM −1 . We found that dopa had the highest redox potential of the four endogenous substrates, and this property of dopa may explain its poor oxidation by laccase-2. We conclude that laccase-2 splice isoforms are likely to oxidize the same substrates in vivo , and additional experiments will be required to discover any isoform-specific functions.

Influenza viruses are important pathogens that cause respiratory infections in humans and animals. In addition to vaccination, antiviral drugs against influenza virus play a significant role in controlling viral infections by reducing disease progression and virus transmission. Plant derived polyphenols are associated with antioxidant activity, anti-carcinogenic, and cardio- and neuro-protective actions. Some polyphenols, such as resveratrol and epigallocatechin gallate (EGCG), showed significant anti-influenza activity in vitro and/or in vivo. Recently we showed that quercetin and isoquercetin (quercetin-3-β-d-glucoside), a glucoside form of quercetin, significantly reduced the replication of influenza viruses in vitro and in vivo (isoquercetin). The antiviral effects of isoquercetin were greater than that of quercetin with lower IC(50) values and higher in vitro therapeutic index. Thus, we investigated the synthesis and antiviral activities of various quercetin derivatives with substitution of C3, C3', and C5 hydroxyl functions with various phenolic ester, alkoxy, and aminoalkoxy moieties. Among newly synthesized compounds, quercetin-3-gallate which is structurally related to EGCG showed comparable antiviral activity against influenza virus (porcine H1N1 strain) to that of EGCG with improved in vitro therapeutic index.

New insecticides are urgently needed because resistance to current insecticides allows resurgence of disease-transmitting mosquitoes while concerns for human toxicity from current compounds are growing. We previously reported the finding of a free cysteine (Cys) residue at the entrance of the active site of acetylcholinesterase (AChE) in some insects but not in mammals, birds, and fish. These insects have two AChE genes (AP and AO), and only AP-AChE carries the Cys residue. Most of these insects are disease vectors such as the African malaria mosquito (Anopheles gambiae sensu stricto) or crop pests such as aphids. Recently we reported a Cys-targeting small molecule that irreversibly inhibited all AChE activity extracted from aphids while an identical exposure caused no effect on the human AChE. Full inhibition of AChE in aphids indicates that AP-AChE contributes most of the enzymatic activity and suggests that the Cys residue might serve as a target for developing better aphicides. It is therefore worth investigating whether the Cys-targeting strategy is applicable to mosquitocides. Herein, we report that, under conditions that spare the human AChE, a methanethiosulfonate-containing molecule at 6 microM irreversibly inhibited 95% of the AChE activity extracted from An. gambiae s. str. and >80% of the activity from the yellow fever mosquito (Aedes aegypti L.) or the northern house mosquito (Culex pipiens L.) that is a vector of St. Louis encephalitis. This type of inhibition is fast ( approximately 30 min) and due to conjugation of the inhibitor to the active-site Cys of mosquito AP-AChE, according to our observed reactivation of the methanethiosulfonate-inhibited AChE by 2-mercaptoethanol. We also note that our sulfhydryl agents partially and irreversibly inhibited the human AChE after prolonged exposure (>4 hr). This slow inhibition is due to partial enzyme denaturation by the inhibitor and/or micelles of the inhibitor, according to our studies using atomic force microscopy, circular dichroism spectroscopy, X-ray crystallography, time-resolved fluorescence spectroscopy, and liquid chromatography triple quadrupole mass spectrometry. These results support our view that the mosquito-specific Cys is a viable target for developing new mosquitocides to control disease vectors and to alleviate resistance problems with reduced toxicity toward non-target species.

A MMIC predistortion circuit that operates at up to 10 GHz and improves the spurious free dynamic range of a broadband analog fiber-optic link from 108 dB/Hz2/3 to 111 dB/Hz2/3 is developed. The experimental results agree with the performed theoretical analysis, indicating that the link dynamic range improvement through the predistortion technique is limited by the high driving voltage of a standard LiNbO3 Mach-Zehnder modulator, that is, by the third-order intercept point of commercial microwave broadband power amplifiers. To overcome this limitation a low-voltage modulator should be employed. © 1996 John Wiley & Sons, Inc.

For detection and estimation of 2-D frequencies from a 2-D array of data using a subspace decomposition method, one needs to construct a block Hankel matrix. For reliable detection and estimation, the rank of the block Hankel matrix should be made equal to the number of 2-D frequencies inherent in the data in the absence of noise. In this work, we provide the conditions for achieving the desired rank.