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The well-demonstrated biological functions of DNA G-quadruplex inside cells call for small molecules that can modulate these activities by interacting with G-quadruplexes. However, the paucity of the understanding of the G-quadruplex stability contributed from submolecular elements, such as loops and tetraguanine (G) planes (or G-quartets), has hindered the development of small-molecule binders. Assisted by click chemistry, herein, we attached pulling handles via two modified guanines in each of the three G-quartets in human telomeric G-quadruplex. Mechanical unfolding using these handles revealed that the loop interaction contributed more to the G-quadruplex stability than the stacking of G-quartets. This result was further confirmed by the binding of stacking ligands, such as telomestatin derivatives, which led to similar mechanical stability for all three G-quartets by significant reduction of loop interactions for the top and bottom G-quartets. The direct comparison of loop interaction and G-quartet stacking in G-quadruplex provides unprecedented insights for the design of more efficient G-quadruplex-interacting molecules. Compared to traditional experiments, in which mutations are employed to elucidate the roles of specific residues in a biological molecule, our submolecular dissection offers a complementary approach to evaluate individual domains inside a molecule with fewer disturbances to the native structure.

Nitrones (III) generated in situ from dihydropyran (I) and hydroxylamines (II) undergo further cycloaddition with alkynes (III) or methacrolein (VI) to give title compounds (V) or (VII).

The repair of atrioventricular valves requires optimal valve exposure through even unconventional surgical approaches. This is especially true in the situation of multiple re-do valve surgeries, where extensive adhesions may prevent adequate valve exposure. When multiple valve surgeries are contemplated, an extensive incisional approach is required without causing damage to any surrounding crucial structures. Re-do surgeries are described in patients with prosthetic valve endocarditis where the correction of all valves involved is necessary, as is the correction of underlying ventricular pathologies such as sinuses and atrioventricular tunnels. As several surgical approaches have been attempted in these situations, a technique is described which involves a superior biatrial approach after transecting the aorta, which addresses the mitral, tricuspid and aortic valves and allows the correction of associated ventricular pathologies.

As an intracellular organelle, phospholipid-coated lipid droplets have shown increasing importance due to their expanding biological functions other than the lipid storage. The growing biological significance necessitates a close scrutiny on lipid droplets, which have been proposed to mature in a cell through processes such as fusion. Unlike phospholipid vesicles that are well-known to fuse through docking and hemifusion steps, little is known on the fusion of lipid droplets. Herein, we used laser tweezers to capture two micrometer-sized 1,2,3-trioleoylglycerol (triolein) droplets coated with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) that closely resemble intracellular lipid droplets. We started the fusion processes by a well-controlled collision between the two lipid droplets in phosphate buffer at pH 7.4. By monitoring the change in the pathway of a trapping laser that captures the collided lipid droplets, docking and physical fusion events were clearly distinguished for the first time and their lifetimes were determined with a resolution of 10 μs after postsynchronization analysis. Our method revealed that the rate-limiting docking process is affected by anions according to a Hofmeister series, which sheds light on the important role of interfacial water shedding during the process. During the physical fusion, the kinetics between bare triolein droplets is faster than lipid droplets, suggesting that breaking of phospholipid coating is involved in the process. This scenario was further supported by direct observation of a short-lived hemifusion state with ∼46 ms lifetime in POPC-coated lipid droplets, but not in bare triolein droplets.

Starting from the known dihydropyran-derived nitrone (I), a series of isoxazolines are prepared via regioselective cycloaddition reaction with electron-deficient alkynes.

This study presents effects of intravenous laser blood irradiation (ILBI) in a transient immunodeficiency patient with juvenile idiopathic arthritis (JIA) treated with an interleukin-6 receptor inhibitor (Tocilizumab). Biological agents induce JIA remission, but some patients do not respond favorably to this final therapeutic line of defense. ILBI was performed in a 16-year-old male patient, with JIA and transient immunodeficiency. When ILBI was introduced, the patient was receiving disease-modifying drugs, steroids, tocilizumab, and physical therapy. Because the disease was not well controlled, ILBI was applied in addition to other ongoing therapies. The patient underwent 1 session daily, and 10 successive sessions per month, repeated every 3 months, for 7 months. Patient evaluation was performed before ILBI was started and at 3, 6, 9, and 12 months after ILBI initiation, using the ACR Pediatric response. The outcome was evaluated using Pediatric 50, 70, and 90 responses and compared to initial status, after 3, 6, 9, and 12 months. At the end of study, the titre of IgA and IgG levels returned to normal. Synergistic anti-inflammatory effect of ILBI was evident, if applied additionally in combination with tocilizumab, in a patient with a therapy-resistant severe form of JIA and related subacute transient immunodeficiency.

This study presents effects of intravenous laser blood irradiation (ILBI) in a transient immunodeficiency patient with juvenile idiopathic arthritis (JIA) treated with an interleukin-6 receptor inhibitor (Tocilizumab). Biological agents induce JIA remission, but some patients do not respond favorably to this final therapeutic line of defense. ILBI was performed in a 16-year-old male patient, with JIA and transient immunodeficiency. When ILBI was introduced, the patient was receiving disease-modifying drugs, steroids, tocilizumab, and physical therapy. Because the disease was not well controlled, ILBI was applied in addition to other ongoing therapies. The patient underwent 1 session daily, and 10 successive sessions per month, repeated every 3 months, for 7 months. Patient evaluation was performed before ILBI was started and at 3, 6, 9, and 12 months after ILBI initiation, using the ACR Pediatric response. The outcome was evaluated using Pediatric 50, 70, and 90 responses and compared to initial status, after 3, 6, 9, and 12 months. At the end of study, the titre of IgA and IgG levels returned to normal. Synergistic anti-inflammatory effect of ILBI was evident, if applied additionally in combination with tocilizumab, in a patient with a therapy-resistant severe form of JIA and related subacute transient immunodeficiency.

Sublingual laser blood irradiation (SLBI) was applied into a randomized, single-blind, placebo-controlled study in juvenile idiopathic arthritis (JIA), aimed at inducing disease remission. 105 children with JIA, without an adequate response to classical treatment, were administrated a disease modifying drug (Methotrexate) and were randomly assigned to three groups. Group I (36 patients) received SLBI with the Weberneedle Lasershower Mouth Applicator with three wavelengths (635 nm, 536 nm, and 405 nm), 5 mW maximum output power each, in continuous mode, simultaneously, for 20 minutes daily, 7 successive sessions per month, repeated every 7 weeks, for three times. Group II (36 patients) received placebo SLBI. Group III (33 patients) received only treatment with Methotrexate. Evaluation was performed using American College of Rheumatology Pediatric criteria (ACR Pedi) at study enrollment and at 8, 16, 24, and 48 weeks. At the end of study, there was an improvement of the ACR Pedi 30 by 86.11% in SLBI group compared to only 61.11% in Group II, respectively, and 60.6% in Group III (P=0.001), with significant statistical differences. SLBI has reduced the pain, lowered the number of articulations with movement limitation, increased the quality of life, and made it possible to avoid the administration of biological agents.

A patient who had a small bowel mesentery perforation following insertion of a suprapubic catheter (SPC) is described. He had no bowel complaints immediately following the procedure, but presented 10 weeks later with insidious onset bowel obstruction due to the kink caused by the catheter. This complication occurred despite cystoscopy control and adequate bladder distension prior to the procedure. This isolated case illustrates the fact that regardless of the ease and frequency of SPC insertion, complications do occur.

The study aimed to identify the logical structure of data and particularities of developing and testing a website designed for selling farm products through online auctions. The research is based on a short literature review in the field and exploratory trials of some successful models from other industries, in order to identify the advantages of using such tool, as well as the optimal structure and functionality of an auction portal. In the last part, the study focuses on the results of testing the website by the potential beneficiaries. Conclusions of the study underlines that the particularities of some agricultural products could raise difficulties in the process of selling them through online auctions, but the use of such system it is perceived to bring significant improvements in the supply chain. The results of scientific investigations require a more detailed study regarding the importance of using quality standards for agricultural products sold via online auction, the impact that implementation of an online payment system could have on trade with agricultural products and problems which could arise in using the website in different countries., {"references":["Aida Opoku Mensah, et al, 2005 E-commerce challenges in Africa:\nissues , constraints, opportunities, World Summit on the Information\nSociety, Tunis 2005 http://www.uneca.org/aisi/docs/ PolicyBriefs/Ecommerce%\n20challenges%20in%20Africa.pdf (accessed June 15,\n2012), p1-2","Bejjani, G., 2000. Venture Capital Perspectives on the Ag.com Industry.\nPresentation at Forum entitled :E-commerce: The Net Effect on\nAgribusiness, Iowa, February 28, 2000\nwww.agforum.org/2000/home.html (accessed June 12, 2012).","Diane H. Parente, Ray Venkataraman, John Fizel and Ido Millet, 2001.\nB2B Online Reverse Auctions: What-s New? School of Business,\nPennsylvania State University - Erie, Decision Line, July 2001, Vol 32,\np.13","Ecommerce Europe, 2012. PRESS RELEASE: European E-commerce to\nreach over Ôé¼ 300 billion in 2012, http://www.ecommerceeurope.\neu/press/2012/12/european-e-commerce-to-reach-over-300-\nbillion-in-2012 (accessed June 12, 2012).","Fu-Shan Liu, 2002 E-Commerce in Taiwan-s Agricultural Marketing,\nFarmers' Service Department 37, Taipei, Taiwan ROC, 2002-11-01,\nhttp://www.agnet.org/htmlarea_file/library/20110725174056/ eb525.pdf\n, p. 6 (accessed June 12, 2012).","GfK Romania, 2011. FMDS 2011, habits of using paying online services\nby Romanian citizens in comparison with the other countries of Central\nand Eastern Europe., Bucharest, 9 June 2011 http://www.gfk-ro.com/\npublic_ relations/press/multiple_pg/ 008143/ index.ro.html (accessed\nJune 12, 2012).","Kym Anderson, 2010. Globalization's effects on world agricultural\ntrade, 1960-2050, published online August 16, 2010 doi:\n10.1098/rstb.2010.0131 vol. 365 no. 1554 p. 3007,3019","Myungsin Chae et al 2007. An Empirical Analysis of Fraud Detection in\nOnline Auctions: Credit Card Phantom Transaction, in proceeding of\n40th Annual Hawaii International Conference on System Sciences\nDOI:10. 1109/HICSS.2007.61, http://originwww.\ncomputer.org/csdl/proceedings/hicss/2007/2755/00/ 27 55 0\n155a.pdf (accessed June 14, 2012)","Paul Wilson (EUROPEAN COMMISSION), 2000. An overview of\ndevelopments and prospects for e-commerce in the agricultural sector, p.\n3, 9\n[10] Rolf A. E. Mueller, 2001. E-Commerce and Entrepreneurship in\nAgricultural Markets, American Journal of Agricultural Economics Vol.\n83, No. 5, Proceedings Issue (No 5, December 2001), p. 1243\n[11] United Nations, 2010, The Development Impact of Information\nTechnology in Trade Facilitation, A Study by the Asia-Pacific Research\nand Training Network on Trade, United Nations, ISBN: 978-92-1-\n120617-3, p.4\n[12] Yan Zhuang, 2011. Analysis on E-Commerce Transaction Chain of\nAgricultural Product, International Symposium on Information\nEngineering and Electronic Commerce, 3rd (IEEC 2011), ISBN:\n9780791859759, p.380"]}

Single-stranded guanine (G)-rich sequences at the 3' end of human telomeres provide ample opportunities for physiologically relevant structures, such as G-quadruplexes, to form and interconvert. Population equilibrium in this long sequence is expected to be intricate and beyond the resolution of ensemble-average techniques, such as circular dichroism, NMR, or X-ray crystallography. By combining a force-jump method at the single-molecular level and a statistical population deconvolution at the sub-nanometer resolution, we reveal a complex population network with unprecedented transition dynamics in human telomeric sequences that contain four to eight TTAGGG repeats. Our kinetic data firmly establish that G-triplexes are intermediates to G-quadruplexes while long-loop G-quadruplexes are misfolded population minorities whose formation and disassembly are faster than G-triplexes or regular G-quadruplexes. The existence of misfolded DNA supports the emerging view that structural and kinetic complexities of DNA can rival those of RNA or proteins. While G-quadruplexes are the most prevalent species in all the sequences studied, the abundance of a misfolded G-quadruplex in a particular telomeric sequence decreases with an increase in the loop length or the number of long-loops in the structure. These population patterns support the prediction that in the full-length 3' overhang of human telomeres, G-quadruplexes with shortest TTA loops would be the most dominant species, which justifies the modeling role of regular G-quadruplexes in the investigation of telomeric structures.

This single-blind, placebo-controlled study assesses the efficacy of synergic administration of intravenous laser blood irradiation (ILBI) and etanercept in selected subtypes of juvenile idiopathic arthritis (JIA). Etanercept is a tumor necrosis factor alpha blocking agent with recognized importance in JIA. Laser radiation has immunomodulatory effects in animal and human studies. Fourteen patients (Group I) received ILBI and 9 patients (Group II) received placebo laser. ILBI was performed in addition to ongoing JIA medication, including etanercept. ILBI was administrated in 3 sets of 5 consecutive daily sessions, with a 7-week interval between every set of sessions. Evaluation was performed using ACR (American College of Rheumatology) Pediatric Criteria (ACR Pedi) at study enrollment and at 10 and 20 weeks, respectively. After 10 weeks, 85.7% of the patients in Group I fulfilled Pedi 30 criteria, compared to only 55.6% of the patients in Group II. After 20 weeks, all patients in both groups had a Pedi 30 response. In Group I, 92.8% of the subjects met the Pedi 50 response, compared to only 55.6% in the placebo group. One patient in Group I responded best, fulfilling Pedi 70 criteria. If applied synergistically, ILBI and etanercept would have an increased efficacy in promoting JIA remission.

Polytetrafluoroethylene or Gore-Tex sutures are used for chordal replacement, and are durable but extremely slippery, a property which causes knot slippage and ineffective neochordal length. We report a modification that is simple and reproducible in preventing knot slippage and maintaining optimal neochordal length, without the use of devices or additional sutures.

Microwave-induced 1,3-dipolar cycloaddition reactions of nitrone (III) with activated alkenes such as (IV) and (VIII) provides access to new isoxazolidine derivatives.

The concept of surgically restoring the ventricle to a near-normal physiologic geometry has been the goal of successful treatment of advanced heart failure due to left ventricular aneurysms following transmural myocardial infarctions [1]. The resulting geometry after surgical restoration has concerned a number of surgeons since the first successful repair in 1958, but little attention was placed on the altered geometry until attempts were made to effect a more physiologic aneurysmorrhaphy in 1973. Substantial attention was focused on a concept of geometric reconstruction from within the left ventricle in 1985 [2]. A prosthetic patch was employed with the concept to redirect normal muscle bundles to their original orientation and position. Further refinements include use of improved materials for the repair, preservation, and bypass of the left anterior descending coronary artery, ablation of ventricular arrhythmias when indicated, and the absence of prosthetic material used in contact with the pericardial surface. The previous chapters have dealt with the innovations in surgical technique which has led to an evolution toward greater normalcy in the restored ventricular geometry.

On analyse les spectres electroniques d'absorption (EAS) et les spectrese electroniques de diffusion (EDS) de quelques pyridazinuium ylures. En solution, le caractere dipolaires des molecules fait apparaitre des interactions d'orientation induction. Dans les solvents protiques des interactions specifiques accentuent le deplacement hypsochrome de la bande d'absorption a caractere de transfert de charge situee dans la visible

P796 – Figure 1 LP31 EEG and MEG source localization of the epileptogenic foci in tuberous sclerosis complex: a pediatric case report A. Hunold1, J. Haueisen1, B. Ahtam2,3, C. Doshi2,4, C. Harini4, S. Camposano4, S.K. Warfield5,6, P.E. Grant2,3,6, Y. Okada2,4, C. Papadelis2,4 1Technische Universitaet Ilmenau, Institute of Biomedical Engineering and Informatics, Ilmenau, Germany; 2Boston Children’s Hospital, Harvard Medical School, Fetal-Neonatal Neuroimaging & Developmental Science Center, Boston, MA, United States; 3Boston Children’s Hospital, Harvard Medical School, Department of Newborn Medicine, Boston, MA, United States; 4Boston Children’s Hospital, Harvard Medical School, Department of Neurology, Boston, MA, United States; 5Boston Children’s Hospital, Harvard Medical School, Department of Radiology, Boston, MA, United States; 6Boston Children’s Hospital, Harvard Medical School, Computational Radiology Laboratory, Boston, MA, United States Question: Tuberous sclerosis complex (TSC) is a disorder of tissue growth and differentiation, characterized by benign hamartomas in the brain triggering epilepsy in up to 90% of TSC patients. There is an ongoing debate on whether or not the epileptogenic zone is within the tuber itself or in abnormally developed surrounding tissue. Methods: We examined a four-year old patient with TSC-related refractory epilepsy undergoing magnetoencephalography (MEG) and electroencephalography (EEG) recordings. For MEG, we used a prototype system that offers higher spatial resolution and sensitivity compared to the conventional adult systems. EEG was simultaneously recorded from 32-leads according to the 10-20 international system. The source analysis of interictal activity was performed using both EEG and MEG data. Equivalent current dipoles (ECD) were fitted to the peak of individual interictal spikes. For averaged interictal spike signals, we performed ECD localizations to the spike upslope. Further, we estimated the minimum norm estimates (MNEs) to averaged interictal spike signals. Results: Multiple cortical tubers were identified in patient’s MRI including one prominent calcified tuber in the right parietal-occipital lobe. The simultaneously recorded spikes in EEG and MEG data provided a time shift of 20 ms between peak latencies. ECDs localized to individual and averaged interictal activity in EEG and MEG consistently clustered in the millimeter Abstracts of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339 S175s of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339 S175 vicinity of the large calcified cortical tuber. The ECD trace localized to the averaged EEG data located on the posterior side ∼5 mm superior to the tuber. The ECD trace localized to the averaged MEG spike located ∼4 mm anterior to the tuber. MNE and ECDs indicated epileptiform activity in the same areas. Conclusion: Our source analysis indicated generators of epileptiform activity in the millimeter vicinity of the tuber margin outside the tuber volume. Separate EEG and MEG source analysis provided distinct source characteristics. LP32 Scalp EEG in malformations of cortical development (MDC). Analysis by localization S. Cieza, A. Gomez, F. Escobar, N. Pereira, C. Viteri, J. Artieda, E. Urrestarazu Clinica Universidad de Navarra, Neurophysiology, Pamplona, Spain Objectives: The aim of our study was to describe the EEG findings of the MDC according to the localisation in the MRI. Patients and methods: We analyze the scalpEEGs of the patients diagnosed of MDC by RM in the Clinica Universidad de Navarra, and we considerate: the background activity, the presence and regional localisation of focal slow waves, interictal epileptiform discharges and focal fast frequencies. Results: We identified 51 patients with MDC (31 women and 20 men). In 21 patients the MDC was located in the temporal lobe, 12 showed focal slow waves and 13 showed epileptiform discharges. These EEG abnormalities had a high topographic correlation with MRI findings (>80% for slow waves and>90% for epileptiform discharges). In 19 patients the lesion was located in the frontal lobe, and the EEG showed focal slow waves in 12 of these patients, and epileptiform discharges in 9; however, these abnormalities coincide with the location in the MRI in less than 50% of the cases. In 8 patients the lesion was located in the parietal lobe, and just in only one case the EEG abnormalities correctly identified the location showed by MRI. Finally in 3 patients the lesion was located in the occipital lobe, and EEG showed slow waves in one case and epileptiform discharges in 2 cases. Only 2 patients had theta-alpha rhythm and were well correlated with the MRI findings (frontal and temporal MDC). One patient with temporal lobe MDC had a no localising continuos beta rhythm. Conclusions: Most of the MDC were located in the temporal and frontal lobes. The slow waves and the epileptiform discharges were highly well localising when the lesion was located in the temporal lobe, but failed in more than 50% of the cases when it was extra temporal. Focal rhythms were rare but have a good correlation with dysplasia. Therefore the presence and locator value of the EEG abnormalities are highly dependent on the location of the focus. Poster session 27. ICU monitoring P472 Epileptiform activity in patients treated with therapeutic hypothermia after cardiac arrest C. Santos-Sanchez1, M. Agundez Sarasola2, X. Mancisidor Solaberrie3, A. Martin Lopez3, P. Goiriena Seijo3, T. Perez Concha2, I. Yurrebaso Santamaria1 1Cruces University Hospital, Clinical Neurophysiology, Barakaldo, Spain; 2Cruces University Hospital, Neurology, Barakaldo, Spain; 3Cruces University Hospital, Cardiology, Barakaldo, Spain Question: Since the implementation of therapeutic hypothermia (TH) after cardiac arrest (CA), some researchers have been trying to redefine the value of the parameters traditionally used as predictors of neurologic outcome. In this context, the EEG represents an important tool to improve prognostication in postanoxic coma. Methods: We retrospectively reviewed the electronic medical records of all patients undergoing TH after CA from January 2011 until October 2013. We identified the patients with any type of epileptiform activity and reviewed their EEGs. Results: Forty patients were included. Sixteen died (40%). Epileptiform activity was found in 11 patients (27.5%), from whom only 2 (18.2%) had a favorable outcome (CPC 1 or 2). This epileptiform activity appeared in the following patterns; 2 patients had isolated interictal discharges, 2 had 2-2.5 Hz generalized periodic epileptiform discharges (GPEDs) over a continuous, diffusely slowed background, 2 had 2-2.5 Hz GPEDs over a suppressed background and 6 fulfilled non convulsive status epilepticus (NCSE) criteria. In one of the patients with NCSE, the EEG evolved into the pattern of GPEDs at 2-2.5 Hz over a suppressed background. When treating these 3 patients with benzodiazepine trials, even though they remained comatose, the epileptiform discharges stopped, and a continuous theta background appeared. Two of these patients died eventually, and the other one remains in a persistent vegetative state. Conclusions: Epileptiform activity is common in comatose patients treated with TH after CA. The presence of epileptiform discharges during the TH or shortly after was associated with a poor outcome. P473 Defining EEG reactivity in patients treated with therapeutic hypothermia after cardiac arrest C. Santos-Sanchez1, M. Agundez Sarasola2, X. Mancisidor Solaberrie3, P. Goiriena Seijo3, A. Martin Lopez3, T. Perez Concha2, I. Yurrebaso Santamaria1 1Cruces University Hospital, Clinical Neurophysiology, Barakaldo, Spain; 2Cruces University Hospital, Neurology, Barakaldo, Spain; 3Cruces University Hospital, Cardiology, Barakaldo, Spain Question: In patients treated with therapeutic hypothermia (TH) after cardiac arrest (CA), the EEG reactivity in the first 24 hours has an important prognostic value. However, it has not been reported yet whether or not there are differences between the type of stimuli required or the reactivity patterns obtained. Methods: We prospectively assessed EEG background continuity and reactivity in 16 consecutive patients undergoing TH after CA from August 2012 to October 2013. EEG background reactivity was tested to auditory, tactile and painful stimuli. We analyzed the relation between the continuity of the background, the EEG reactivity patterns, and the neurologic outcome. Results: All of our patients had the first EEG done within 24 hours after the CA. We established 4 backgrounds categories; continuous, discontinuous, burst-suppression and low voltage, and 2 reactivity patterns; increase of faster frequencies and background attenuation. All survivors (11/16) had different degrees of background reactivity in the first EEG (

This study aimed at establishing service quality determinants which may affect customer satisfaction in university libraries in Sri Lanka. Using the literature, 113 service quality determinants were identified. These were then reviewed by eight focus groups in four different universities. Forty of the determinants were perceived to be applicable to their context. The participants also added 14 quality requirements which they thought were not provided for in the list. Finally, the content and face validity of the 54 determinants were evaluated by a panel of experts who ultimately reduced them to 50. This study recommends the use of the identified quality determinants by library administrators and policymakers in the higher education sector in Sri Lanka to gauge the levels of customer satisfaction and assure quality of service.