Miracle-dz/UniFAR-FTUs huggingface dataset:
Systematic Identification of Genes that Regulate Neuronal Wiring in the Drosophila Visual System

Forward genetic screens in model organisms are an attractive means to identify those genes involved in any complex biological process, including neural circuit assembly. Although mutagenesis screens are readily performed to saturation, gene identification rarely is, being limited by the considerable effort generally required for positional cloning. Here, we apply a systematic positional cloning strategy to identify many of the genes required for neuronal wiring in the Drosophila visual system. From a large-scale forward genetic screen selecting for visual system wiring defects with a normal retinal pattern, we recovered 122 mutations in 42 genetic loci. For 6 of these loci, the underlying genetic lesions were previously identified using traditional methods. Using SNP-based mapping approaches, we have now identified 30 additional genes. Neuronal phenotypes have not previously been reported for 20 of these genes, and no mutant phenotype has been previously described for 5 genes. The genes encode a variety of proteins implicated in cellular processes such as gene regulation, cytoskeletal dynamics, axonal transport, and cell signalling. We conducted a comprehensive phenotypic analysis of 35 genes, scoring wiring defects according to 33 criteria. This work demonstrates the feasibility of combining large-scale gene identification with large-scale mutagenesis in Drosophila, and provides a comprehensive overview of the molecular mechanisms that regulate visual system wiring.
Transgenic expression of the human A20 gene in cloned pigs provides protection against apoptotic and inflammatory stimuli

Oropeza M, Petersen B, Carnwath JW, Lucas‐Hahn A, Lemme E, Hassel P, Herrmann D, Barg‐Kues B, Holler S, Queisser A‐L, Schwinzer R, Hinkel R, Kupatt C, Niemann H. Transgenic expression of the human A20 gene in cloned pigs provides protection against apoptotic and inflammatory stimuli. Xenotransplantation 2009; 16: 522–534. © 2009 John Wiley & Sons A/S.
A Role for Syndecan-1 in Coupling Fascin Spike Formation by Thrombospondin-1

An important role of cell matrix adhesion receptors is to mediate transmembrane coupling between extracellular matrix attachment, actin reorganization, and cell spreading. Thrombospondin (TSP)-1 is a modulatory component of matrix expressed during development, immune response, or wound repair. Cell adhesion to TSP-1 involves formation of biochemically distinct matrix contacts based on stable fascin spikes. The cell surface adhesion receptors required have not been identified. We report here that antibody clustering of syndecan-1 proteoglycan specifically transduces organization of cortical actin and fascin bundles in several cell types. Transfection of COS-7 cells with syndecan-1 is sufficient to stimulate cell spreading, fascin spike assembly, and extensive protrusive lateral ruffling on TSP-1 or on syndecan-1 antibody. The underlying molecular mechanism depends on glycosaminoglycan (GAG) modification of the syndecan-1 core protein at residues S45 or S47 for cell membrane spreading and on the VC2 region of the cytoplasmic domain for spreading and fascin spike formation. Expression of the VC2 deletion mutant or GAG-negative syndecan-1 showed that syndecan-1 is necessary in spreading and fascin spike formation by C2C12 cells on TSP-1. These results establish a novel role for syndecan-1 protein in coupling a physiological matrix ligand to formation of a specific matrix contact structure.
Cross-Layer Rate Control in Wireless Networks with Lossy Links: Leaky-Pipe Flow, Effective Network Utility Maximization and Hop-by-Hop Algorithms

Due to multi-path fading and co-channel interference, wireless links are lossy in nature. As a result, the data rate of a given flow becomes "thinner and thinner" along its routing path, and the data rate received successfully at the destination node (the effective rate) is typically lower than the transmission rate at the source node (the injection rate). In light of this observation, each flow is treated as a "leaky-pipe" model in this study. Moreover, we introduce the notion of "effective utility" associated with the effective rate (not the injection rate) for each flow, and explore rate control mechanisms through effective network utility maximization (ENUM). We focus on two network models: (1) ENUM with link outage constraints with a maximum error rate at each link; (2) ENUM with path outage constraints where there exists an end-to-end outage requirement for each flow. For both problems, we explicitly take into account the "thinning" feature of data flows and devise distributed hop-by-hop rate control algorithms accordingly. Our numerical examples corroborate that higher effective network utility and better fairness among effective flow rates can be achieved by the ENUM algorithms than the standard NUM.
Collagen VI related muscle disorders

Mutations in the genes encoding collagen VI (COL6A1, COL6A2, and COL6A3) cause Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), two conditions which were previously believed to be completely separate entities. BM is a relatively mild dominantly inherited disorder characterised by proximal weakness and distal joint contractures. UCMD was originally described as an autosomal recessive condition causing severe muscle weakness with proximal joint contractures and distal hyperlaxity. Here we review the clinical phenotypes of BM and UCMD and their diagnosis and management, and provide an overview of the current knowledge of the pathogenesis of collagen VI related disorders.
Could recent decreases in breast cancer incidence really be due to lower HRT use? Trends in attributable risk for modifiable breast cancer risk factors in Canadian women.

OBJECTIVES Recent downward trends in breast cancer incidence have been attributed to declining use of hormone replacement therapy (HRT). To determine whether this is a credible conclusion, this study calculated population attributable risk (PAR) for HRT and other modifiable breast cancer risk factors. METHODS PAR calculation needs both the prevalence of a risk factor, and the relative risk (RR) for breast cancer incidence for that risk factor. Prevalences were calculated for Canadian women, aged 50-69, participating in the National Population Health Survey, 1994-2006. RR were derived from published research: 1.4 for HRT use, 1.4 for excessive alcohol use, 1.15 for physical inactivity, 1.25 for smoking, 1.4 for BMI over 30 kg/m2. Trends for PAR were calculated for the risk factors separately, as well as combined. Age-adjusted breast cancer incidence rates were calculated for Canadian women aged 50-69 for the years 1994-2004. RESULTS Between 1998 and 2004, PAR for HRT decreased by 50%. PAR for other risk factors showed only small changes, and the combined PAR decreased by 18.6%. Age-adjusted breast cancer incidence for women aged 50-69 peaked in 2000 at 330.0/100,000, then dropped by 17.2% by 2004. CONCLUSION Patterns of PAR for HRT use in Canada are consistent with the noticeable decrease in breast cancer incidence observed for women of the same age group. Combining PAR for all risk factors indicated that changes in HRT use overpowered any trends of other risk factors. The combined PAR suggest that alterations in lifestyle could have considerable impact on breast cancer incidence.
Why coelacanths are not ‘living fossils’

A series of recent studies on extant coelacanths has emphasised the slow rate of molecular and morphological evolution in these species. These studies were based on the assumption that a coelacanth is a ‘living fossil’ that has shown little morphological change since the Devonian, and they proposed a causal link between low molecular evolutionary rate and morphological stasis. Here, we have examined the available molecular and morphological data and show that: (i) low intra‐specific molecular diversity does not imply low mutation rate, (ii) studies not showing low substitution rates in coelacanth are often neglected, (iii) the morphological stability of coelacanths is not supported by paleontological evidence. We recall that intra‐species levels of molecular diversity, inter‐species genome divergence rates and morphological divergence rates are under different constraints and they are not necessarily correlated. Finally, we emphasise that concepts such as ‘living fossil’, ‘basal lineage’, or ‘primitive extant species’ do not make sense from a tree‐thinking perspective.
Randomized controlled trial to evaluate the impact of aerobic exercise on visceral fat in overweight chronic kidney disease patients.

BACKGROUND The prevalence of obesity has markedly increased in patients with chronic kidney disease (CKD). Studies on the impact of exercise focusing on obese CKD patients are scarce. Therefore, we aimed to investigate the effect of aerobic exercise performed either in an exercise centre or at home on visceral fat in overweight non-dialysed CKD patients. METHODS Twenty-seven sedentary men (52.1 ± 9.5 years, body mass index 30.4 ± 3.8 kg/m(2), estimated glomerular filtration rate (eGFR) 27.5 ± 11.6 mL/min) were randomly assigned to a centre-based exercise group (n = 10), home-based exercise group (n = 8) or control group (n = 9). The aerobic training was prescribed according to ventilatory threshold and performed three times per week during 12 weeks. Body composition was assessed by dual energy X-ray absorptiometry (DEXA) and the distribution of abdominal fat by computed tomography. RESULTS In the centre-based group, visceral fat and waist circumference decreased 6.4 ± 6.4 mm (P < 0.01) and 2.0 ± 2.3 cm (P = 0.03) and leg lean mass increased 0.5 ± 0.4 kg (P < 0.01). No significant changes were observed in the home-based group. Visceral fat increased 5.0 ± 4.4 mm in the control group (P = 0.01). In relation to the control, a group-by-time interaction was significant for visceral fat and waist circumference for both exercise groups and for leg lean mass for the centre-based group. Mean blood pressure decreased in both exercise groups (centre-based 13%, P < 0.01 and home-based 10%, P = 0.03) and eGFR increased 3.6 ± 4.6 mL/min (P = 0.03) in the centre-based group. These parameters remained unchanged in the control group. CONCLUSIONS Centre-based aerobic exercise is an effective approach to reduce visceral fat besides promoting relevant clinical benefits in male overweight CKD patients.
Molecular Tectonic Model of Virus Structural Transitions: the Putative Cell Entry States of Poliovirus

ABSTRACT Upon interacting with its receptor, poliovirus undergoes conformational changes that are implicated in cell entry, including the externalization of the viral protein VP4 and the N terminus of VP1. We have determined the structures of native virions and of two putative cell entry intermediates, the 135S and 80S particles, at ∼22-Å resolution by cryo-electron microscopy. The 135S and 80S particles are both ∼4% larger than the virion. Pseudoatomic models were constructed by adjusting the beta-barrel domains of the three capsid proteins VP1, VP2, and VP3 from their known positions in the virion to fit the 135S and 80S reconstructions. Domain movements of up to 9 Å were detected, analogous to the shifting of tectonic plates. These movements create gaps between adjacent subunits. The gaps at the sites where VP1, VP2, and VP3 subunits meet are plausible candidates for the emergence of VP4 and the N terminus of VP1. The implications of these observations are discussed for models in which the externalized components form a transmembrane pore through which viral RNA enters the infected cell.
New Approaches to the Treatment of Hepatic Malignancies Radiofrequency Ablation of Malignant Liver Tumors

Background: Radiofrequency ablation (RFA) is being used to treat primary and metastatic liver tumors. The indications, treatment planning, and limitations of hepatic RFA must be defined and refined by surgeons treating hepatic malignancies. Methods: A review of the experience using RFA to treat unresectable primary and secondary hepatic malignancies at the University of Texas M. D. Anderson Cancer Center in Houston, Texas, and the G. Pascale National Cancer Institute in Naples, Italy, is provided. Patient selection, treatment approach, local recurrence rates, and overall cancer recurrence rates following RFA are described. The current literature on RFA of hepatic malignancies is reviewed. Results: RFA of hepatic tumors can be performed percutaneously, laparoscopically, or during an open surgical procedure. Incomplete treatment manifest as local recurrence is more common with a percutaneous approach. The morbidity and mortality rates associated with hepatic RFA are low. Local recurrence rates are low if meticulous treatment planning is performed. RFA can be combined safely with partial hepatic resection of large lesions. The long-term survival rates following RFA of primary and metastatic liver tumors have not yet been established. Conclusions: RFA of hepatic malignancies is a safe and promising technique to produce coagulative necrosis of unresectable hepatic malignancies. Experience with this treatment modality is not yet mature enough to establish long-term outcomes.
Cardiovascular outcomes associated with use of clarithromycin: population based study

Study question What is the association between clarithromycin use and cardiovascular outcomes? Methods In this population based study the authors compared cardiovascular outcomes in adults aged 18 or more receiving oral clarithromycin or amoxicillin during 2005-09 in Hong Kong. Based on age within five years, sex, and calendar year at use, each clarithromycin user was matched to one or two amoxicillin users. The cohort analysis included patients who received clarithromycin (n=108 988) or amoxicillin (n=217 793). The self controlled case series and case crossover analysis included those who received Helicobacter pylori eradication treatment containing clarithromycin. The primary outcome was myocardial infarction. Secondary outcomes were all cause, cardiac, or non-cardiac mortality, arrhythmia, and stroke. Study answer and limitations The propensity score adjusted rate ratio of myocardial infarction 14 days after the start of antibiotic treatment was 3.66 (95% confidence interval 2.82 to 4.76) comparing clarithromycin use (132 events, rate 44.4 per 1000 person years) with amoxicillin use (149 events, 19.2 per 1000 person years), but no long term increased risk was observed. Similarly, rate ratios of secondary outcomes increased significantly only with current use of clarithromycin versus amoxicillin, except for stroke. In the self controlled case analysis, there was an association between current use of H pylori eradication treatment containing clarithromycin and cardiovascular events. The risk returned to baseline after treatment had ended. The case crossover analysis also showed an increased risk of cardiovascular events during current use of H pylori eradication treatment containing clarithromycin. The adjusted absolute risk difference for current use of clarithromycin versus amoxicillin was 1.90 excess myocardial infarction events (95% confidence interval 1.30 to 2.68) per 1000 patients. What this study adds Current use of clarithromycin was associated with an increased risk of myocardial infarction, arrhythmia, and cardiac mortality short term but no association with long term cardiovascular risks among the Hong Kong population. Funding, competing interests, data sharing ID was funded by grants from the Medical Research Council for this project. LS was funded by a grant from the Wellcome Trust. The authors have no competing interests. No additional data are available.
Channel Vector Quantization for Multiuser MIMO Systems Aiming at Maximum Sum Rate

For downlink transmission in a multiuser Multiple-Input Multiple-Output (MIMO) communication system, quantized Channel State Information (CSI) is fed back to the base station in an uplink channel of finite rate. The quantized CSI is obtained via Channel Vector Quantization (CVQ) of the so-called composite channel vector, i.e., the product of the channel matrix and an estimation of the receive filter, which cannot be computed exactly at the stage of quantization because of its dependency on the finally chosen precoder. Here, the state-of-the-art approach estimates the receive filter and quantize the composite channel vector such that its Euclidean distance to the estimated composite channel vector is minimized. In this paper, we propose an alternative CVQ method which determines the estimated receive filter vector and the quantized composite channel vector such that the resulting Signal-to-Interference-and-Noise Ratio (SINR), or an approximation thereof, is maximized. Since the SINR is related to the individual user rates, and therefore related to the sum rate of the system, the presented solution aims at maximizing the system sum rate. Simulation results of a multiuser MIMO system with linear zero-forcing precoding show that the proposed schemes achieve significant performance improvements compared to the state-of-the-art method, especially in the low signal-to-noise ratio region.
An investigation of antimalarial potential against Plasmodium berghei in infected mice

Antimalarial activity of the crude aqueous leaf extract of Pyrenacantha staudtii was evaluated using chloroquine-sensitive Plasmodium berghei infection in mice with an objective to finding scientific evidence for the use of the plant as traditional antimalarial remedy in Ido/Osi LGA of Ekiti state, Nigeria. The crude aqueous extract of P. staudtii Engl. (Icacinaceae) (100, 200 and 500 mg/kg) was administered orally to mice infected with P. berghei in 4 days suppressive test. The antiplasmodial effect during the test of the plant in blood was determined and the extract at these doses induced 58.0 to 63.4% activity in comparison with untreated (negative) control group. Chloroquine produced 100% activity. The antimalarial activity showed by P. staudtii during the test justifies its use in traditional medicine for treating of malaria in the area.
Application of Physicochemical Properties and Process Parameters in the Development of a Neural Network Model for Prediction of Tablet Characteristics

The importance of in silico modeling in the pharmaceutical industry is continuously increasing. The aim of the present study was the development of a neural network model for prediction of the postcompressional properties of scored tablets based on the application of existing data sets from our previous studies. Some important process parameters and physicochemical characteristics of the powder mixtures were used as training factors to achieve the best applicability in a wide range of possible compositions. The results demonstrated that, after some pre-processing of the factors, an appropriate prediction performance could be achieved. However, because of the poor extrapolation capacity, broadening of the training data range appears necessary.
Incremental Estimation of Project Failure Risk with Naive Bayes Classifier

Background: Estimation and prediction techniques using quantitative models are considered to be major contributors to early risk control of software projects. Since software projects tend to involve instability and uncertainty, "dynamic" approaches, which perform early estimations and predictions with limited data and then update them incrementally with newly acquired data during project execution, are highly effective. Aim: showing the effectiveness of the incremental estimation of project failure risk using Naïve Bayes classifier. Method: We conducted experiments with data of 104 projects from an organization in which the prediction results obtained using Naïve Bayes classifier were compared with those obtained using the Poisson regression model in each development phase: low-level design (LD), coding (CD), and unit testing (UT). The experiments were carried out with 10-fold cross-validation and the results were evaluated with the area under ROC curve (AUC). Results: Whereas the AUCs obtained using Poisson regression were 0.708, 0.709, and 0.663, those obtained using Naïve Bayes classifier were 0.702, 0.748, and 0.764, respectively, in LD, CD, and UT. Conclusions: The results of the experiments in which Naïve Bayes classifier achieved overall higher accuracy and robustness than Poisson regression support the effectiveness of applying Naïve Bayes classifier to the incremental estimation of project failure risk.
Immune Responses Induced by the Leishmania (Leishmania) donovani A2 Antigen, but Not by the LACK Antigen, Are Protective against Experimental Leishmania (Leishmania) amazonensis Infection

ABSTRACT Leishmania amazonensis is one of the major etiologic agents of a broad spectrum of clinical forms of leishmaniasis and has a wide geographical distribution in the Americas, which overlaps with the areas of transmission of many other Leishmania species. The LACK and A2 antigens are shared by various Leishmania species. A2 was previously shown to induce a potent Th1 immune response and protection against L. donovani infection in BALB/c mice. LACK is effective against L. major infection, but no significant protection against L. donovani infection was observed, in spite of the induction of a potent Th1 immune response. In an attempt to select candidate antigens for an American leishmaniasis vaccine, we investigated the protective effect of these recombinant antigens (rLACK and rA2) and recombinant interleukin-12 (rIL-12) against L. amazonensis infection in BALB/c mice. As expected, immunization with either rA2-rIL-12 or rLACK-rIL-12 induced a robust Th1 response prior to infection. However, only the BALB/c mice immunized with rA2-rIL-12 were protected against infection. Sustained gamma interferon (IFN-γ) production, high levels of anti-A2 antibodies, and low levels of parasite-specific antibodies were detected in these mice after infection. In contrast, mice immunized with rLACK-rIL-12 displayed decreased levels of IFN-γ and high levels of both anti-LACK and parasite-specific antibodies. Curiously, the association between rA2 and rLACK antigens in the same vaccine completely inhibited the rA2-specific IFN-γ and humoral responses and, consequently, the protective effect of the rA2 antigen against L. amazonensis infection. We concluded that A2, but not LACK, fits the requirements for a safe vaccine against American leishmaniasis.