Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmental Tightening of Cerebellar Cortical Synaptic Influx-Release Coupling

Tight coupling between Ca2+ channels and the sensor for vesicular transmitter release at the presynaptic active zone (AZ) is crucial for high-fidelity synaptic transmission. It has been hypothesized that a switch from a loosely coupled to a tightly coupled transmission mode is a common step in the maturation of CNS synapses. However, this hypothesis has never been tested at cortical synapses. We addressed this hypothesis at a representative small cortical synapse: the synapse connecting mouse cerebellar cortical parallel fibers to Purkinje neurons. We found that the slow Ca2+ chelator EGTA affected release significantly stronger at immature than at mature synapses, while the fast chelator BAPTA was similarly effective in both groups. Analysis of paired-pulse ratios and quantification of release probability (pr) with multiple-probability fluctuation analysis revealed increased facilitation at immature synapses accompanied by reduced pr. Cav2.1 Ca2+ channel immunoreactivity, assessed by quantitative high-resolution immuno-electron microscopy, was scattered over immature boutons but confined to putative AZs at mature boutons. Presynaptic Ca2+ signals were quantified with two-photon microscopy and found to be similar between maturation stages. Models adjusted to fit EGTA dose–response curves as well as differential effects of the Ca2+ channel blocker Cd2+ indicate looser and less homogenous coupling at immature terminals compared with mature ones. These results demonstrate functionally relevant developmental tightening of influx-release coupling at a single AZ cortical synapse and corroborate developmental tightening of coupling as a prevalent phenomenon in the mammalian brain.
Pain and health related quality of life after heart, kidney, and liver transplantation

No study has focused particularly on the sensory and affective experience of bodily pain among transplanted patients. The aim of this study was to explore pain and other factors that influence health related quality of life (HRQOL) in heart, kidney, and liver transplant recipients during the first 2 yr after transplantation, and to define similarities and/or differences in the three groups.A total of 76 patients, 18–60 yr old, undergoing heart, kidney, or liver transplantation between 1995 and 1997 with a follow‐up of 6–24 months were included. HRQOL and pain were investigated by using the Short‐Form‐36 items (SF‐36), the Hospital Anxiety and Depression Scale (HAD), and the Pain‐O‐Meter (POM). Overall, the patients show satisfactory HRQOL. There were no differences in experienced HRQOL 6–24 months after transplantation between kidney, liver, and heart transplant recipients except in the area of Role‐Physical (RP). Fifty‐three percent of all patients reported bodily pain. The most common locations were the hands, feet, and back, and sensory experiences were burning, stabbing, or dull pain. There was a correlation between number of rejections and total score for POM‐VAS (p<0.05) (rho=0.47). There was also a correlation between the number of rejection episodes and the total pain intensity score for POM‐WDS (p<0.05) (rho=0.48). Patients with pain scored higher in the area of depression (p<0.05). Bodily pain is an important problem after organ transplantation, affecting daily living even in patients with good allograft function and it limits physical function, vitality, and general health.
An electrically small transverse bilateral helical antenna for portable personal wireless applications

Simulations comparing the TBH and normal mode helical antennas were conducted and shown to be in close agreement with measured data. Based on this comparison, the TBH antenna provides greater efficiency and an omni directional pattern that is maintained when placed next to the human hand. The TBH further exhibits reduced sensitivity to detuning. Agreement between measured and simulated data also indicates that the three layer hand model is a practical approximation for simulation of the human hand.
Acquiring and transferring intellectual skills with modifiable software advisors in a virtual inquiry support environment

Our previous work with the ThinkerTools Inquiry Curriculum found that students who were prompted to reflect on their work performed better on inquiry projects, and attained a better understanding of the inquiry process. These prompts, however, were in a pencil-and-paper form, which did not allow for individual, on-line needs. We hypothesize that improvement will be further enhanced by introducing an adaptive, user-controlled system of software agents that can advise students on completing specific inquiry tasks and their application of general intellectual and collaborative skills. In addition, students can modify the system to help students meet their own knowledge-building goals. Factors such as an advisor's goals, the type of help an advisor can offer, when the advisor gives advice, and an advisor's personality can be modified. For example, an inquiry task advisor, the Hypothesizer, helps students come up with alternative hypotheses that are testable. The students and the advisors work in a virtual inquiry support environment of typical artifacts such as a journal, progress report, meeting rooms and a dialogue box for communication.
An adaptive sliding-mode observer incorporating core loss

A novel adaptive sliding-mode observer has been developed for a three-phase squirrel-cage induction motor. With the new scheme taking core loss into account, the observer can accurately estimate rotor flux and speed, resistances of stator, rotor and core loss by using measured stator voltages and currents. Essences of switching conditions and adaptive manners are based on Lyapunov stability.
Nitrate in vegetables: toxicity, content, intake and EC regulation

Nitrate content is an important quality characteristic of vegetables. Vegetable nitrate content is of interest to governments and regulators owing to the possible implications for health and to check that controls on the content are effective. Nitrate itself is relatively non-toxic but its metabolites may produce a number of health effects. Until recently nitrate was perceived as a purely harmful dietary component which causes infantile methaemoglobinaemia, carcinogenesis and possibly even teratogenesis. Recent research studies suggest that nitrate is actually a key part of our bodies' defences against gastroenteritis. In this review are reported: (1) vegetable classification as a function of nitrate accumulation; (2) vegetable contribution to the total dietary exposure of nitrate; (3) European Commission Regulation No. 563/2002 which sets limits for nitrate in lettuce and spinach; (4) the maximum levels set in some countries for beetroot, cabbage, carrot, celery, endive, Lamb's lettuce, potato, radish and rocket; (5) the results of surveys on the nitrate content of vegetables in Italy and other European countries.  2005 Society of Chemical Industry
Revision Cochlear Implantation Surgery in Adults: Indications and Results

Objective: To assess the efficacy, risks, and indications of revision cochlear implantation (RCI) and to identify the clinical, audiologic, and device-related characteristics that predict outcome. Study Design: Retrospective case series. Setting: Academic tertiary referral center. Patients: Adults (≥18 yr) who underwent RCI at Johns Hopkins University. Intervention: Revision cochlear implant surgery. Main Outcome Measures: Speech perception by open-set testing and patient report and patient report of symptom resolution. Results: During the 16-year period of this study, 4.8% of all adults implanted at our center have required 1 or more RCI surgeries. A total of 48 RCIs have been performed. The indications for RCI included infection (12%), electrode extrusion (15%), hard failure (23%), suspected device failure (42%), and isolated facial nerve stimulation (8%). Overall, successful resolution of the implant-related or medical condition was achieved with RCI in 83% of cases. Speech perception was lower in only 1 (2.1%) of 48 cases. Satisfactory preoperative speech recognition was preserved or surpassed in 5 of 6 infection cases and 8 cases with progressive symptoms of tinnitus and facial nerve stimulation. All cases of hard failure regained or surpassed previous peak performance. Improved speech recognition was experienced by 75% of cases with suspected device failure. Of cases in which RCI failed to restore previous functional benefit, there was a significant association with advanced age (>70 yr). Whereas an abnormal integrity test was predictive of favorable outcome after RCI, a negative test was not predictive of outcome. A similar pattern of results was observed with respect to ex vivo device analysis. Conclusion: Revision cochlear implantation can be safely performed to restore lost benefit in appropriately selected cases. When properly performed after medical and audiologic options have been exhausted, RCI rarely compromises previous function and, in most cases, can resolve functional complaints and distracting symptoms. When positive, integrity testing is a useful screen for the presence of a device defect. In cases in which device integrity is uncertain, clinical judgment guided by longitudinal assessment can help determine whether RCI is likely to be beneficial.
The Human I-mfa Domain-Containing Protein, HIC, Interacts with Cyclin T1 and Modulates P-TEFb-Dependent Transcription

ABSTRACT Positive transcription elongation factor b (P-TEFb) hyperphosphorylates the carboxy-terminal domain of RNA polymerase II, permitting productive transcriptional elongation. The cyclin T1 subunit of P-TEFb engages cellular transcription factors as well as the human immunodeficiency virus type 1 (HIV-1) transactivator Tat. To identify potential P-TEFb regulators, we conducted a yeast two-hybrid screen with cyclin T1 as bait. Among the proteins isolated was the human I-mfa domain-containing protein (HIC). HIC has been reported to modulate expression from both cellular and viral promoters via its C-terminal cysteine-rich domain, which is similar to the inhibitor of MyoD family a (I-mfa) protein. We show that HIC binds cyclin T1 in yeast and mammalian cells and that it interacts with intact P-TEFb in mammalian cell extracts. The interaction involves the I-mfa domain of HIC and the regulatory histidine-rich region of cyclin T1. HIC also binds Tat via its I-mfa domain, although the sequence requirements are different. HIC colocalizes with cyclin T1 in nuclear speckle regions and with Tat in the nucleolus. Expression of the HIC cDNA modulates Tat transactivation of the HIV-1 long terminal repeat (LTR) in a cell type-specific fashion. It is mildly inhibitory in CEM cells but stimulates gene expression in HeLa, COS, and NIH 3T3 cells. The isolated I-mfa domain acts as a dominant negative inhibitor. Activation of the HIV-1 LTR by HIC in NIH 3T3 cells occurs at the RNA level and is mediated by direct interactions with P-TEFb.
Is Your Parallel Algorithm Correct?

Verifying the correctness of parallel algorithms is not trivial, and it is usually omitted in the works from the parallel computation field. In this paper, we discuss in detail how to show that a certain parallel algorithm is correct. This process involves proving its safety and liveness. We perform the in-depth analysis of our parallel guided ejection search (P–GES) for the pickup and delivery problem with time windows, which serves as an excellent case study. P–GES was implemented as a distributed algorithm using the Message Passing Interface library with asynchronous communications, and was validated using the well-known Li and Lim’s benchmark containing demanding test instances. We already proved the efficacy of this algorithm and showed that it can retrieve very high-quality (quite often better than the world’s best at that time) routing schedules.
Gene expression of tumor necrosis factor α and TNF‐receptors, p55 and p75, in nonalcoholic steatohepatitis patients

The main objective of this study was to analyze the pathogenic role of the tumor necrosis factor α (TNF‐α) system in the development of nonalcoholic steatohepatitis (NASH). Fifty‐two obese patients were studied. We investigated: (1) the expression of mRNA of TNF‐α and their p55 and p75‐receptors by quantitative reverse‐transcriptase polymerase chain reaction (RT‐PCR) in hepatic and adipose tissues; and (2) the relationship between TNF‐α, p55, and p75 and the severity of NASH. Obese patients without NASH were the control group. A remarkable increase in the expression of mRNA of TNF‐α was found in patients with NASH in hepatic tissue (0.65 ± 0.54) and in peripheral fat (0.43 ± 0.45); in the control samples, the mRNA expression was 0.28 ± 0.32, P < . 007, and 0.26 ± 0.22, P < . 018, respectively. Furthermore, we found a significant increase in the mRNA levels of p55 receptor (2.42 ± 1.81 vs. 1.56 ± 1.17; P < .05); however, the mRNA expression of the p75 receptor was similar in both patients. Those patients with NASH with significant fibrosis presented an increase in the expression of mRNA TNF‐α in comparison with those with a slight or nonexistent fibrosis. An overexpression of TNF‐α mRNA is found in the liver and in the adipose tissue of NASH patients. The levels of mRNA‐p55 are increased in the liver tissue of NASH patients. This overexpression is more elevated in patients with more advanced NASH. These findings suggest that the TNF‐α system may be involved in the pathogenesis of NASH.
Stratus OCT in Dominant Optic Atrophy: Features Differentiating it From Glaucoma

PurposeTo describe the Stratus optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness profile of dominant optic atrophy (DOA), to differentiate it from that of glaucoma. MethodsRNFL thickness was measured using Stratus OCT in 32 eyes of 16 DOA patients. ResultsThe temporal-most clock hour measurement was outside the 95% normal limit in 29 of the 32 DOA eyes (90.6%). The pattern of RNFL damage was bilaterally symmetrical in location and severity in all subjects. ConclusionStratus OCT shows characteristic findings differentiating DOA from glaucoma.
Protein Synthesis and Ageing

Protein synthesis is an essential cellular process affecting growth, reproduction and survival in response to both intrinsic and extrinsic cues such as nutrient availability and energy levels. Studies in many organisms, including humans, have revealed that during ageing, the rate of global protein synthesis declines, indicating a link between the regulation of protein synthesis and the ageing process. Recent studies in C. elegans demonstrate that depletion of specific translation initiation factors, such as eIF4G, eIF2B and eIF4E increases lifespan. Similarly, depletion of specific ribosomal proteins increases lifespan both in yeast and worms. In all cases, these manipulations reduce the rate of general protein synthesis. Why does attenuation of protein synthesis promote longevity? The process of mRNA translation is one of the most energy consuming cellular processes, requiring, depending on growth conditions, up to 50% of the total energy generated by the cell. A reduction of protein synthesis would moderate this energy load, generating an energy surplus, which can be channeled to mechanisms of damage repair and cellular maintenance, thus, extending lifespan. In addition, lowering protein synthesis may be beneficial during ageing by reducing the accumulation of altered, misfolded, aggregated or damaged proteins, as it occurs in many age-related pathologies, such as Alzheimer’s and Parkinson’s disease. The recent experimental findings reveal a key role for protein synthesis in ageing and suggest that perturbation of mRNA translation provides an effective approach for interventions aiming to modulate ageing and senescent decline.
Activation of human monocytic cells by Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides proceeds via a pathway distinct from that of lipopolysaccharide but involves the transcriptional activator NF-kappa B

There is increasing evidence that lipoproteins of Treponema pallidum and Borrelia burgdorferi are key inflammatory mediators during syphilis and Lyme disease. A principal objective of the present study was to identify more precisely similarities and divergences among lipopolysaccharide (LPS)- and lipoprotein-lipopeptide-induced immune cell signaling events. Like LPS, purified native B. burgdorferi OspA and synthetic analogs of OspA, OspB, and two T. pallidum lipoproteins (Tpp47 and Tpp17) all induced NF-kappa B translocation in THP-1 human monocytoid cells. Acylation of OspA and the synthetic peptides was requisite for cell activation. Polymyxin B abrogated only the response to LPS. By using 70Z/3-derived pre-B-cell lines either lacking or expressing human CD14 (the LPS receptor), it was observed that expression of human CD14 imparted responsiveness to LPS but not to OspA or spirochetal lipopeptides (assessed by induction of NF-kappa B and expression of surface immunoglobulin M). Finally, the biological relevance of the observation that T. pallidum lipoproteins-lipopeptides induce both NF-kappa B and cytokine production in monocytes was supported by the ability of the synthetic analogs to promote human immunodeficiency virus replication in chronically infected U1 monocytoid cells; these observations also suggest a potential mechanism whereby a syphilitic chancre can serve as a cofactor for human immunodeficiency virus transmission. The combined data lend additional support to the proposal that spirochetal lipoproteins and LPS initiate monocyte activation via different cell surface events but that the signaling pathways ultimately converge to produce qualitatively similar cellular responses.
PAIN RELIEF AND PALLIATIVE CARE IN LEBANON PRESSURE ULCERS Prevention and Management

A B S T R A C T : Pre s s u re ulcers are a significant medical p roblem that greatly affects the geriatric population. We reviewed pertinent published data in the literature concerning the prevention and treatment of pr e s s u re ulcers. The development of pre s s u re ulcers is associated with well known risk factors including unrelieved pre ss u re, skin maceration, shear f o rces, malnutrition and i m m o b i l i t y. Risk factor modification is an import a n t aspect in prevention and treatment. When a pre s s u re u l c e r develops, various specialized support surfaces and wound care products exist to accelerate wound healing. Alternative therapeutic modalities such as ultrasonic mist and wound vacuum therapy are inc reasingly being used with success for such ulcers. P re s s u re ulcers are typically the consequence of underlying medical conditions that should be tr e a t e d a p p ropriately in order f o r the wound to heal.
UVB Radiation Induces Persistent Activation of Ribosome and Oxidative Phosphorylation Pathways

Abstract Tsai, M-L. , Chang, K-Y. , Chiang, C-S. , Shu, W-Y. , Weng, T-C. , Chen, C. R. , Huang, C-L. , Lin, H-K. and Hsu, I. C. UVB Radiation Induces Persistent Activation of Ribosome and Oxidative Phosphorylation Pathways. Radiat. Res. 171, 716–724 (2009). Ultraviolet B (UVB) radiation has strong biological effects and modulates the expression of many genes. The major biological pathways affected by UVB radiation remain controversial. In this work, we used a loop-design microarray approach and applied rigorous statistical analyses to identify differentially regulated genes at 4, 8, 16 or 24 h after UVB irradiation. The most prominent biological categories in lists of differentially regulated gene sets were extracted by functional enrichment analysis. With this approach, we determined that genes participating in two prime cellular processes, the ribosome pathway and the oxidative phosphorylation pathway, were persistently activated after UVB irradiation. Mitochondrial activity assays confirmed increased activity for up to 24 h after UVB irradiation. These results suggest that the persistent activation of ribosome and oxidative phosphorylation pathways may have a key role in UVB-radiation-induced cellular responses. For the first time, the specific cellular pathways that respond to UVB radiation consistently and persistently can be delineated with confidence using a loop-design microarray approach and functional bioinformatics analysis. The results of this study offer further insight into UVB-radiation-induced stress responses.
Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study.

PURPOSE Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged overall survival (OS) compared with tamoxifen monotherapy. PATIENTS AND METHODS Of 8,010 postmenopausal women with hormone receptor-positive, early breast cancer enrolled on the Breast International Group (BIG) 1-98 study, 4,922 were randomly assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen. Of 2,459 patients enrolled in the tamoxifen treatment arm, 619 (25.2%) selectively crossed over to either adjuvant or extended letrozole after initial trial results were presented in January 2005. To gain better estimates of relative treatment effects in the presence of selective crossover, we used inverse probability of censoring weighted (IPCW) modeling. RESULTS Weighted Cox models, by using IPCW, estimated a statistically significant, 18% reduction in the hazard of an OS event with letrozole treatment (hazard ratio [HR], 0.82; 95% CI, 0.70 to 0.95). Estimates of 5-year OS on the basis of IPCW were 91.8% and 90.4% for letrozole and tamoxifen, respectively. The HRs of DFS and TDR events by using IPCW modeling were 0.83 (95% CI, 0.74 to 0.94) and 0.80 (95% CI, 0.67 to 0.94), respectively (P < .05 for DFS, OS, and TDR). Median follow-up was 74 months. CONCLUSION Adjuvant treatment with letrozole, compared with tamoxifen, significantly reduces the risk of death, the risk of recurrent disease, and the risk of recurrence at distant sites in postmenopausal women with hormone receptor-positive breast cancer.