Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of the complete genome sequence information of Haemophilus influenzae strain Rd to investigate lipopolysaccharide biosynthesis

The availability of the complete 1.83‐megabase‐pair sequence of the Haemophilus influenzae strain Rd genome has facilitated significant progress in investigating the biology of H. influenzae lipopolysaccharide (LPS), a major virulence determinant of this human pathogen. By searching the H. influenzae genomic database, with sequences of known LPS biosynthetic genes from other organisms, we identified and then cloned 25 candidate LPS genes. Construction of mutant strains and characterization of the LPS by reactivity with monoclonal antibodies, PAGE fractionation patterns and electrospray mass spectrometry comparative analysis have confirmed a potential role in LPS biosynthesis for the majority of these candidate genes. Virulence studies in the infant rat have allowed us to estimate the minimal LPS structure required for intravascular dissemination. This study is one of the first to demonstrate the rapidity, economy and completeness with which novel biological information can be accessed once the complete genome sequence of an organism is available.
Cloning of Human Junctional Adhesion Molecule 3 (JAM3) and Its Identification as the JAM2 Counter-receptor*

We have identified a third member of the junctional adhesion molecule (JAM) family. At the protein level JAM3 displays 36 and 32% identity to JAM2 and JAM1, respectively. The coding region is distributed over 9 exons and maps to chromosome 11q25. The gene shows widespread tissue expression with higher levels apparent in the kidney, brain, and placenta. At the cellular level we show expression of JAM3 transcript within endothelial cells. Our major finding is that JAM3 and JAM2 are binding partners. Thus, JAM3 ectodomain binds firmly to JAM2-Fc. This heterotypic interaction is maintained when JAM3-Fc is used to capture Chinese hamster ovary cells expressing full-length JAM2. In static adhesion assays we show that JAM3 is unable to bind to leukocyte cell lines. This is consistent with the lack of JAM2 expression. However, using JAM2-Fc pull-down experiments in combination with polyclonal anti-JAM3 serum, we demonstrate that JAM3 is the previously uncharacterized 43-kDa counter-receptor that mediates JAM2 adhesion to T cells. Most significantly we demonstrate up-regulation of JAM3 protein on peripheral blood lymphocytes following activation. Finally we show the utility of JAM3 ectodomain as an inhibitor of JAM2 adhesion.
High-Grade Neuroendocrine Carcinoma of the Ampulla of Vater: A Clinicopathologic and Immunohistochemical Analysis of 14 Cases

We describe the clinical and pathologic features of 14 cases of high-grade neuroendocrine carcinoma (HGNEC) of the ampulla of Vater classified according to WHO classification of lung tumors into small cell carcinoma (SCC, 6 cases) and large cell neuroendocrine carcinoma (LCNEC, 8 cases) types. The immunohistochemical findings were compared with those of 13 cases of primary poorly differentiated ampullary adenocarcinomas (PDACA) lacking neuroendocrine morphology. The mean age of 10 males and 4 females was 70 years. The mean tumor size was 2.5 cm. Ten of 13 patients had lymph node metastases (mean, 2.3 nodes involved). Documented sites of distant metastases included brain and liver. Overall, 64% of patients with ampullary HGNEC died of disease (mean follow-up, 14.5 months). Four patients had no evidence of disease after resection (mean, 20 months). Half of the tumors were associated with adenomas of the adjacent mucosa, 2 with high-grade dysplasia. Two HGNECs were combined with a conventional adenocarcinoma and another with a squamous cell carcinoma component. By immunohistochemistry, the HGNECs were positive for cytokeratins (AE1/AE3, 100%; Cam5.2, 67%; CK7, 87%; CK20, 38%), similar to the pattern found in PDACAs. p27 expression was lost in 1 case of HGNEC and in all PDACAs. Retinoblastoma (Rb) protein expression was lost in 60% of HGNECs and in none of the PDACA cases. In conclusion, HGNECs of the ampulla are rare (2%-3% of ampullary tumors in our material). The clinical course parallels that of their pulmonary counterparts and appears to be worse than that of locally advanced ampullary adenocarcinomas. The association with adenoma and or conventional adenocarcinoma components may suggest a common pathway in the initial carcinogenesis of these two types of tumors. Loss of Rb expression, a characteristic finding in pulmonary SCCs, is present in almost half of ampullary HGNECs. In contrast, p27 expression is lost in PDACAs and retained in most HGNECs. Thus, there are differences in the molecular phenotypes of these two types of ampullary carcinoma, supporting the distinction of poorly differentiated carcinomas with a neuroendocrine phenotype from those without.
Multiple roles of the Rho GEF ephexin1 in synapse remodeling

Synapse remodeling, which involves changes in the synaptic structure and their molecular composition, is required for the maturation and refinement of neural circuits. Although synapse remodeling is known to be tightly dependent on the assembly of local actin cytoskeleton, how actin directs the structural changes of synapse and targeting of synaptic proteins are not fully understood. Recently, we identified ephexin1, a Rho guanine nucleotide exchange factor (GEF) that regulates actin dynamics, plays an essential role in the maturation and functioning of the mammalian neuromuscular junction (NMJ). We showed that ephexin1 regulates the synaptic organization of the neurotransmitter receptor acetylcholine receptor (AChR) clusters through RhoA-dependent actin reorganization. Interestingly, ephexin1 has been implicated in the regulation of postsynaptic structure as well as the presynaptic vesicle release at various types of synapses. Our findings thus establish a novel function of ephexin1 in synapse remodeling through regulating the synaptic targeting of neurotransmitter receptors, revealing a versatile role of ephexin1 at synapses.
Reactivity and transient dynamics of discrete-time ecological systems

Most studies of ecological models focus exclusively on the asymptotic stability properties of equilibria. However, short-term transient effects can be important, and can in some cases dominate the dynamics seen in experimental or field studies. The reactivity of a stable equilibrium point measures the potential for short-term amplification of perturbations. The reactivity of a fixed point in a discrete-time system is given by the natural logarithm of the largest singular value of the Jacobian matrix of the linear approximation near the fixed point. If the reactivity is positive, the fixed point is said to be reactive. Here we examine the reactivity of discrete-time predator–prey models and density-dependent matrix population models. We find reactivity to be common (but not universal) and sometimes extremely high. Predator–prey or food web models that include a predator whose per-capita growth rate depends on the density of its prey, but not on its own density, are a special case. Any positive equilibrium of such a model must be reactive. Reactivity of discrete-time models depends on the timing of the census relative to the timing of reproduction. Perturbation analysis of singular values can be used to calculate the sensitivity and elasticity of reactivity to changes in model parameters. We conclude that transient amplification of perturbations should be a common ecological phenomenon. The interaction of these transient effects with the asymptotic nonlinear dynamics warrants further study.
Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: further support that PTPN22 is an autoimmunity gene.

OBJECTIVE The protein tyrosine phosphatase N22 (PTPN22) gene exhibits regulatory activities for both T cells and B cells. A missense single-nucleotide polymorphism (SNP) within this gene (rs2476601) has recently been associated with 4 autoimmune diseases: rheumatoid arthritis (RA), systemic lupus erythematosus, autoimmune thyroid disease, and type 1 diabetes mellitus, all of which are T cell-mediated and associated with the elaboration of autoantibody. The aim of this study was to investigate associations of the missense SNP of PTPN22 in a number of autoimmune diseases in the UK population, including RA, juvenile idiopathic arthritis (JIA), psoriasis, psoriatic arthritis (PsA), and multiple sclerosis (MS), some of which have not been examined previously. METHODS The PTPN22 missense SNP was genotyped in 886 RA, 661 JIA, 279 psoriasis, 455 PsA, and 379 MS patients and in 595 healthy controls. Association with the PTPN22 SNP was analyzed by chi-square test as implemented in Stata software. RESULTS There was a significant association between the PTPN22 SNP and RA (P = 1.8 x 10(-8)) and JIA (P = 0.0005). In contrast, no association with psoriasis, PsA, or MS was detected. CONCLUSION We replicated the findings of a previous association with RA and identified a novel association with JIA. Together with previous data showing associations with other autoimmune diseases, our findings provide further evidence that the PTPN22 gene plays a role in the pathogenesis of a subgroup of autoimmune diseases.
Study of the SH3‐domain GRB2‐like 2 gene expression in laryngeal carcinoma

Background Laryngeal carcinoma is a common malignant tumor of the upper respiratory tract, and in 95% of cases the tumor is laryngeal squamous cell carcinoma (LSCC). The abnormity of SH3‐domain GRB2‐like 2 (SH3GL2) gene was found in LSCC. In order to clarify the relationship between SH3GL2 gene and LSCC, we evaluated the expression of the SH3GL2 gene in LSCC. Method Real‐time PCR, immunohistochemistry and Western blotting were used to detect the mRNA and protein expression and find the various rules of SH3GL2 gene in LSCC. Results The result of real‐time PCR showed that the expression level of SH3GL2 mRNA in LSCC tissue was apparently down‐regulated; immunohistochemical analysis showed that SH3GL2 protein was mainly located in cytoplasm, the rate of positive cells and SH3GL2 protein expression level were fluctuated with the pathological classification of LSCC; the result of Western blotting showed that SH3GL2 protein was down‐regulated significantly in LSCC samples, especially in metastatic lymph nodes. Conclusions These results suggest that SH3GL2 is a LSCC related gene and its expression level is fluctuated with the pathological classification which indicate that SH3GL2 participates in the development and progression of LSCC. And it may be considered as a novel tumor marker to find both a new anti‐oncogene and relative factors of invasion and metastasis of laryngeal carcinoma.
Organization of the tectofugal visual pathway in the pigeon: A retrograde transport study

In birds, superficial laminae of the optic tectum receive a massive retinal input; the tectum in turn projects upon the nucleus rotundus thalami, which then sends its efferents to the ectostriatal core of the telencephalon. To examine the detailed organization of this principal ascending visual pathway, small injections of the marker horseradish peroxidase (HRP) were placed in various sites throughout the ectostriatum (E) or nucleus rotundus (Rt) in pigeons. Analysis of the resulting patterns of retrograde labeling indicates the tectofugal pathway to be comprised of at least five different channels. Cells which lie at various depths in the stratum griseum centrale (SGC) of the tectum project upon distinct subdivisions of nucleus rotundus. Anterior portions of Rt receive input from superficial most cells in the SGC, while medial and more caudal portions of Rt are projected upon by deeper SGC neurons. A ventral subdivision of Rt was found to receive its primary input from two pretectal nuclei. Additional inputs to all portions of Rt arise from nucleus reticularis superior thalami.
Exploring capabilities within ForTrilinos by solving the 3D Burgers equation

We present the first three-dimensional, partial differential equation solver to be built atop the recently released, open-source ForTrilinos package http://trilinos.sandia. gov/packages/fortrilinos. ForTrilinos currently provides portable, object-oriented Fortran 2003 interfaces to the C++ packages Epetra, AztecOO and Pliris in the Trilinos library and framework [ACM Trans. Math. Softw. 313 2005, 397--423]. Epetra provides distributed matrix and vector storage and basic linear algebra calculations. Pliris provides direct solvers for dense linear systems. AztecOO provides iterative sparse linear solvers. We demonstrate how to build a parallel application that encapsulates the Message Passing Interface MPI without requiring the user to make direct calls to MPI except for startup and shutdown. The presented example demonstrates the level of effort required to set up a high-order, finite-difference solution on a Cartesian grid. The example employs an abstract data type ADT calculus [Sci. Program. 164 2008, 329--339] that empowers programmers to write serial code that lower-level abstractions resolve into distributed-memory, parallel implementations. The ADT calculus uses compilable Fortran constructs that resemble the mathematical formulation of the partial differential equation of interest.
Phase II trial of arsenic trioxide and ascorbic acid with temozolomide in patients with metastatic melanoma with or without central nervous system metastases

We conducted a single institution phase II trial to evaluate the tolerability and effectiveness of therapy with arsenic trioxide (ATO) and ascorbic acid (AA) with temozolomide (TMZ) in patients with advanced melanoma. Planned enrollment was for 40 patients. Eligible patients were required to have metastatic melanoma with or without brain metastases, an ECOG performance status of 0–2, and adequate organ function. The primary endpoints were overall response rate and degree of grade 4 toxicity. ATO was administered as a loading dose at 0.25 mg/kg/day for 5 days during week 0, and then twice weekly at 0.35 mg/kg during an 8-week cycle. Each infusion of ATO was followed by an infusion of 1000 mg of AA. TMZ was given at the standard dose of 200 mg/m2 for 5 days during weeks 1 and 5 of each cycle. Eleven patients were enrolled with 10 evaluable for response, five with central nervous system disease. No responses were seen among the first 10 patients and on the basis of a predetermined stopping rule, the trial was terminated. Common grade 1 and 2 side effects included nausea and vomiting (10), fatigue (six), edema (six), rash (six), and elevated AST or ALT (six). Grade 3 and 4 side effects included nausea and vomiting (three), elevated AST or ALT (two), seizure (one), and renal failure (one). This is the first trial combining ATO with chemotherapy in a solid tumor. ATO and AA were administered in the outpatient setting with TMZ in 11 patients with an acceptable side effect profile. No responses were seen in the first 10 evaluable patients leading to early closure of the study. Further studies using ATO and AA with TMZ with this dosing schedule in advanced melanoma are not warranted.
Anorexic behaviour and attitudes among female medical and nursing students at a private university hospital.

OBJECTIVE To study the anorexic behaviour and attitude among female medical and nursing students in a tertiary care hospital. SUBJECTS AND METHODS A cross-sectional survey to determine the proportion of anorexic behaviour among female medical and nursing students at The Aga Khan University Hospital Karachi was conducted. A multistaged sampling technique was utilized in which our study population was first divided according to field of enrollment (medical or nursing school) and then stratified by class. Within each stratum, we used convenience sampling due to time and availability constraints. We utilized a modified Eating Attitudes Test (EAT-26) to collect data. The Eating Attitude Test is probably the most widely used standardized measure of symptoms characteristic of eating disorders, including anorexia nervosa. RESULTS A total of 180 female students were interviewed. Ninety-four (52.2%) were medical students and 86 (47.8%) were nursing students. Among the 94 medical students, 26 (27.7%) were from first year, 14 (14.9%) from second year, 15 (16.0%) from third year, 20 (21.3%) from fourth year and 19 (20.2%) from the final year of medical college. Among the 86 nursing students 34 (39.5%) were from first year, 23 (26.7%) from second year, 27 (31.4%) from third year and 2 (2.4%) from fourth year. The proportion of anorexic behaviour among medical students was 8.0%, 7.1% and 20.0% in first, third and fourth years respectively. No individuals with anorexic behaviour were found in second and fifth years. The total proportion of anorexic behaviour among female health care students was 21.7%. CONCLUSION Results showed a 21.7% prevalence of anorexic behaviour, a figure much higher than that reported in similar studies conducted in Asia. We also found that the proportion was much higher among female nursing students as compared to female medical students. A previous visit to a psychiatrist for reasons other than eating disorders was found to be associated with anorexic behaviour.
Differential diagnosis of focal pancreatitis and pancreatic cancer.

UNLABELLED The differentiation of focal, chronic pancreatitis (CP) and pancreatic cancer (PAC) poses a diagnostic dilemma. Both conditions may present with the same symptoms and signs. The complexity of differential diagnosis is enhanced because PAC is frequently associated with secondary inflammatory changes and CP may develop into PAC. The aim of this study was tot analyze two sets of patients (group A and B) who were misdiagnosed to have either CP or PAC. The clinical and radiographical features of these patients were reviewed. Group A consisted of 22 patients (median age 54.5 years) who were referred with PAC after a previous diagnosis of PC. Eleven patients had a history of CP of > 12 mths (mean 40.2 mths) whereas in 11 patients, PAC became apparent within 12 mths (mean 4.9 mths) after the diagnosis of CP was made. The etiology of CP was alcohol abuse in 9 patients, pancreas divisum in 3 patients and was undefined in the remaining 10 patients. Imaging studies showed features of CP (parenchymal calcifications, irregularities and stenoses of the pancreatic duct wall). Pseudocysts were present in 13 patients. A mass lesion was detected in 13 patients. At the time of diagnosis, 20 patients had unresectable tumors and 2 patients underwent a Whipple resection which proved non-radical. Group B consisted of 14 patients (median age 53 years) who underwent a Whipple resection for a presumed PAC that on histopathology of the lesion proved to be CP. These patients accounted for 6% of all 220 patients who had undergone resection for PAC in the same period. Reassessment of clinical presentation and all imaging studies confirmed a high index of suspicion on PAC in these patients. CONCLUSION In patients known with CP, misdiagnosis of PAC is a potential pitfall leading to delay of treatment. For any lesion suspicious of PAC an aggressive surgical approach is justified lest a potentially curable lesion is missed. As a consequence, there is at least a 5% chance of resecting a lesion based on CP, mimicking PAC.
Nonlinear aerodynamic damping of sharp-edged flexible beams oscillating at low Keulegan–Carpenter numbers

Slender sharp-edged flexible beams such as flapping wings of micro air vehicles (MAVs), piezoelectric fans and insect wings typically oscillate at moderate-to-high values of non-dimensional frequency parameter β with amplitudes as large as their widths resulting in Keulegan–Carpenter (KC) numbers of order one. Their oscillations give rise to aerodynamic damping forces which vary nonlinearly with the oscillation amplitude and frequency; in contrast, at infinitesimal KC numbers the fluid damping coefficient is independent of the oscillation amplitude. In this article, we present experimental results to demonstrate the phenomenon of nonlinear aerodynamic damping in slender sharp-edged beams oscillating in surrounding fluid with amplitudes comparable to their widths. Furthermore, we develop a general theory to predict the amplitude and frequency dependence of aerodynamic damping of these beams by coupling the structural motions to an inviscid incompressible fluid. The fluid–structure interaction model developed here accounts for separation of flow and vortex shedding at sharp edges of the beam, and studies vortex-shedding-induced aerodynamic damping in slender sharp-edged beams for different values of the KC number and the frequency parameter β. The predictions of the theoretical model agree well with the experimental results obtained after performing experiments with piezoelectric fans under vacuum and ambient conditions.
Brivaracetam for the treatment of epilepsy in adults

Brivaracetam (BRV) is a new antiepileptic drug structurally related to levetiracetam but with a 15 to 30-fold increased affinity for the same molecular target, namely the SV2A ligand. BRV is currently under Phase III development as adjunctive treatment for partial onset seizures but data from some Phase III suggest also potential efficacy for primary generalized seizures. Although two studies are negative for the primary efficacy endpoint, global results seem to suggest a wide spectrum of efficacy for both partial onset and primary generalized seizures and a favourable safety and pharmacokinetic profile. This article is aimed at providing a comprehensive overview of current evidence about BRV in the treatment of epilepsy taking into account emerging concerns regarding clinical trials in epilepsy.
Geodesics and horizontal-path spaces in Carnot groups

We study properties of the space of horizontal paths joining the origin with a vertical point on a generic two-step Carnot group. The energy is a Morse-Bott functional on paths and its critical points (sub-Riemannian geodesics) appear in families (compact critical manifolds) with controlled topology. We study the asymptotic of the number of critical manifolds as the energy grows. The topology of the horizontal-path space is also investigated, and we find asymptotic results for the total Betti number of the sublevels of the energy as it goes to infinity. We interpret these results as local invariants of the sub-Riemannian structure. 53C17; 37J60, 58E05