Miracle-dz/UniFAR-FTUs huggingface dataset:
Brugada Syndrome Caused by a Large Deletion in SCN5A Only Detected by Multiplex Ligation‐Dependent Probe Amplification

SCN5A deletion only detected by MLPA. A 14‐year‐old boy presented with atrial flutter. His ECG showed Brugada changes, first‐degree AV block and major sinus pauses. Polymorphic VT was inducible at electrophysiology study. A pacemaker defibrillator was placed. Classic sequencing for SCN5A was normal. Multiplex ligation‐dependent probe amplification, however, detected a major deletion in SCN5A. It is predicted that this deletion would result in haploinsufficiency. The report is the first description of a large‐scale rearrangement of the SCN5A gene and supports the association between the molecular pathology and the phenotypic expression. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1073‐1076, September 2011)
Compensation Benchmarking, Leapfrogs, and the Surge in Executive Pay1

Scholars frequently argue whether the sharp rise in chief executive officer (CEO) pay in recent years is “efficient” or is a consequence of “rent extraction” because of the failure of corporate governance in individual firms. This article argues that governance failure must be conceptualized at the market rather than the firm level because excessive pay increases for even relatively few CEOs a year spread to other firms through the cognitively and rhetorically constructed compensation networks of “peer groups,” which are used in the benchmarking process to negotiate the compensation of CEOs. Counterfactual simulation based on Standard and Poor’s ExecuComp data demonstrates that the effects of CEO “leapfrogging” potentially explain a considerable fraction of the overall upward movement of executive compensation since the early 1990s.
Index Cache Consistency in Client-Server Database Systems

In this paper, we present an enhanced cacheconsistency (concurrency-control and replicamanagement) protocol and B±tree algorithms for clientserver database management systems in which the physical database is organized as a sparse (B±tree) index. We improve the concurrency-control and the callback-locking (for replica-management) protocols by augmenting these protocols with the U-locking protocol. In our cache-consistency protocol, concurrency control and replica management are performed at the page level. Our cache consistency protocol and B±tree algorithms improve concurrency in client-server database system.
Collective Irrationality and Positive Feedback

Recent experiments on ants and slime moulds have assessed the degree to which they make rational decisions when presented with a number of alternative food sources or shelter. Ants and slime moulds are just two examples of a wide range of species and biological processes that use positive feedback mechanisms to reach decisions. Here we use a generic, experimentally validated model of positive feedback between group members to show that the probability of taking the best of options depends crucially on the strength of feedback. We show how the probability of choosing the best option can be maximized by applying an optimal feedback strength. Importantly, this optimal value depends on the number of options, so that when we change the number of options the preference of the group changes, producing apparent “irrationalities”. We thus reinterpret the idea that collectives show "rational" or "irrational" preferences as being a necessary consequence of the use of positive feedback. We argue that positive feedback is a heuristic which often produces fast and accurate group decision-making, but is always susceptible to apparent irrationality when studied under particular experimental conditions.
Mucosal immunity to influenza without IgA: an IgA knockout mouse model.

IgA knockout mice (IgA-/-) were generated by gene targeting and were used to determine the role of IgA in protection against mucosal infection by influenza and the value of immunization for preferential induction of secretory IgA. Aerosol challenge of naive IgA-/- mice and their wild-type IgA+/+ littermates with sublethal and lethal doses of influenza virus resulted in similar levels of pulmonary virus infection and mortality. Intranasal and i.p. immunization with influenza vaccine plus cholera toxin/cholera toxin B induced significant mucosal and serum influenza hemagglutinin-specific IgA Abs in IgA+/+ (but not IgA-/-) mice as well as IgG and IgM Abs in both IgA-/- and IgA+/+ mice; both exhibited similar levels of pulmonary and nasal virus replication and mortality following a lethal influenza virus challenge. Monoclonal anti-hemagglutinin IgG1, IgG2a, IgM, and polymeric IgA Abs were equally effective in preventing influenza virus infection in IgA-/- mice. These results indicate that IgA is not required for prevention of influenza virus infection and disease. Indeed, while mucosal immunization for selective induction of IgA against influenza may constitute a useful approach for control of influenza and other respiratory viral infections, strategies that stimulate other Igs in addition may be more desirable.
Inverter Device Nonlinearity Characterization Technique for Use in a Motor Drive System

This paper introduces a detailed nonlinearity characterization technique for insulated-gate bipolar transistor inverters in a drive system which is able to measure device nonlinearities. Methods are derived from measurements of the voltage on the inverter phases. These measurements are obtained while applying a set of direct currents to an electrical machine. These methods are then applied to tests using alternating current. The study of inverter nonlinearities is useful in order to conduct condition monitoring. These methods fulfill the need to characterize each device in an inverter. In addition to characterizing every device using either ac or dc current, the method is resistant to noise; for these reasons, the method is applicable in the field. Simulations and experimental work demonstrate the benefits and applicability of the methods.
Molecular reorganization of Cx43, Zo-1 and Src complexes during the endocytosis of gap junction plaques in response to a non-genomic carcinogen

The gap junction protein connexin 43 (Cx43) exhibits dynamic trafficking that is altered in most tumor cells and in response to carcinogen exposure. A number of connexin (Cx)-binding proteins are known to be involved in endocytic internalization of gap junctions. Here, we analyzed the discrete molecular interactions that occur between Src, ZO-1 and Cx43 during Cx43 internalization in response to the non-genomic carcinogen γ-hexachlorocyclohexane (HCH). Internalization of the Cx43 gap junction plaque was significantly accelerated in Cx43-GFP transfected 42GPA9 Sertoli cells that were exposed to the carcinogen. HCH induced the rapid recruitment of Src to the plasma membrane, activation of Src within 3 minutes and the efficient inhibition of gap junctional coupling, but had no effect in the presence of the Src inhibitor PP2. Immunoprecipitation experiments demonstrated that HCH increased Cx43-Src interaction and concomitantly decreased Cx43–ZO-1 association. ZO-1 was detected on both sides of the gap junction plaques in untreated cells, but appeared to be mainly localized on one side during HCH-induced internalization. The dissociation of ZO-1 from Cx43 appears to occur specifically on the side of the plaque to which Src was recruited. These findings provide mechanistic evidence by which internalization of the Cx43 gap junction plaque might be initiated, suggesting that Src-mediated dissociation of ZO-1 from one side of the plaque initiates endocytic internalization of gap junctions and that this process is amplified in response to exposure to HCH.
An Evaluation of Alternative Measures of Corporate Tax Rates

This paper examines the ability of financial statement measures of average and marginal tax rates to capture tax attributes utilizing a matched sample of firm-level tax return and Compustat data. The results suggest that commonly used measures of average tax rates provide little insight about annual corporate tax burdens, and may introduce substantial bias into statistical models. Marginal tax rates proxies perform better, but there appears to be little, if any, empirical value added by methods that go beyond easily constructed measures traditionally used in the literature.
Assessment of current technologies for communition of forest residues

Recent legislation and energy prices have led to an increased need for alternative energy sources. Biomass, including forest residues, is expected to replace a part of the nation's reliance on petroleum consumption. This paper provides an overview of existing literature related to the harvest, communition and transport of forest residues. Past studies have investigated the systems associated with biomass harvesting. Researchers have explored whether to incorporate the biomass component with other forest product removals, or to harvest it in a separate entry. Land managers do not have the tools to adequately assess the cost of biomass processing prior to treatments. Handling residue can be awkward due to the size and arrangement of the material. Dirt and rocks can contaminate residues and cause equipment repair problems or reduced utilization of the resource. These issues coupled with the problems of comparing existing production studies lead to some of the reasons why land managers have difficulty in assessing communition processing costs. Logging residue and unmerchantable stems are expensive to transport without some sort of communition prior to transport. There are few studies available today that investigate some of the newer technology, such as horizontal grinders and slash bundling machines. Forest professionals could benefit from further research in this area to provide a means of more adequately determining production and costs of biomass harvesting.
Comparison of Influenza Epidemiological and Virological Characteristics between Outpatients and Inpatients in Zhejiang Province, China, March 2011–June 2015

Given the rapid rate of global spread and consequently healthcare costs related to influenza, surveillance plays an important role in monitoring the emerging pandemics in China. However, the characteristics of influenza in Southeast of China haven’t been fully studied. Our study use the surveillance data collected from 16 sentinel hospitals across Zhejiang Province during March 2011 through June 2015, including the demographic information and respiratory specimens from influenza-like illness (ILI) patients and severe acute respiratory illness (SARI) patients. As analysis results, most SARI and ILI patients were in the age group of 0–4 years old (62.38% of ILI and 71.54% of SARI). The respiratory specimens have statistically significantly higher positive rate for influenza among ILI patients than that among SARI patients (p < 0.001). The comparison between ILI patients and SARI patients shows no statistically significantly difference in detecting influenza virus type and influenza A virus subtype. The SARI and ILI patients were found to be positively correlated for overall positive rate (r = 0.63, p < 0.001), the weekly percentage of A(H1N1)pdm09 (r = 0.51, p < 0.001), influenza B virus (r = 0.17, p = 0.013), and A/H3N2 (r = 0.43, p < 0.001) among all the positive numbers. Our study demonstrated that the activities of influenza virus, including its subtypes, had a similar temporal pattern between ILI and SARI cases.
Complete remission through icotinib treatment in Non-small cell lung cancer epidermal growth factor receptor mutation patient with brain metastasis: A case report

Abstract Brain metastasis (BM) has been universally recognized as a poor prognostic factor in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown efficacy in treating BM with an EGFR mutation. This paper reports a case of BM patient with EGFR-mutated NSCLC. According to the findings, a complete remission (CR) of the BM was achieved by icotinib treatment without conducting a radiotherapy, which was followed by a resection of the primary lung cancer lesion and lymph nodes. After one-year follow-up, the disease progressed to liver metastasis and liver lesion biopsy showed a T790M mutation. The patient responded well to the combination treatment of AZD9291 and icotinib after the failure of transcatheter arterial chemoembolization (TACE). This case report suggests that icotinib has a sustainable anticancer response to BM and the combination with icotinib and AZD9291 is effective for liver metastasis with T790M.
Natural Transformation of Gallibacterium anatis

ABSTRACT Gallibacterium anatis is a pathogen of poultry. Very little is known about its genetics and pathogenesis. To enable the study of gene function in G. anatis, we have established methods for transformation and targeted mutagenesis. The genus Gallibacterium belongs to the Pasteurellaceae, a group with several naturally transformable members, including Haemophilus influenzae. Bioinformatics analysis identified G. anatis homologs of the H. influenzae competence genes, and natural competence was induced in G. anatis by the procedure established for H. influenzae: transfer from rich medium to the starvation medium M-IV. This procedure gave reproducibly high transformation frequencies with G. anatis chromosomal DNA and with linearized plasmid DNA carrying G. anatis sequences. Both DNA types integrated into the G. anatis chromosome by homologous recombination. Targeted mutagenesis gave transformation frequencies of >2 × 10−4 transformants CFU−1. Transformation was also efficient with circular plasmid containing no G. anatis DNA; this resulted in the establishment of a self-replicating plasmid. Nine diverse G. anatis strains were found to be naturally transformable by this procedure, suggesting that natural competence is common and the M-IV transformation procedure widely applicable for this species. The G. anatis genome is only slightly enriched for the uptake signal sequences identified in other pasteurellaceaen genomes, but G. anatis did preferentially take up its own DNA over that of Escherichia coli. Transformation by electroporation was not effective for chromosomal integration but could be used to introduce self-replicating plasmids. The findings described here provide important tools for the genetic manipulation of G. anatis.
Haem oxygenase‐1 inhibits phosphorylation of the Helicobacter pylori oncoprotein CagA in gastric epithelial cells

The cytotoxin‐associated gene A protein (CagA) plays a pivotal role in the aetiology of Helicobacter pylori‐associated gastric diseases. CagA is injected into the cytoplasm of host cells by a type IV secretion system, and is phosphorylated on tyrosine residues by the host enzyme c‐Src. We previously reported that the enzyme haem oxygenase‐1 (HO‐1) inhibits IL‐8 secretion by H. pylori‐infected cells. However, the cellular mechanism by which HO‐1 regulates the innate immune function of infected cells remains unknown. We now show that nitric oxide and haemin, two inducers of HO‐1, decrease the level of phosphorylated CagA (p‐CagA) in H. pylori‐infected gastric epithelial cells and this is blocked by either pharmacological inhibition of HO‐1 or siRNA knockdown of hmox‐1. Moreover, forced expression of HO‐1 by transfection of a plasmid expressing hmox‐1 also results in a strong attenuation of CagA phosphorylation. This occurs through the inhibition of H. pylori‐induced c‐Src phosphorylation/activation by HO‐1.Consequently, H. pylori‐induced cytoskeletal rearrangements and activation of the pro‐inflammatory response mediated by p‐CagA are inhibited in HO‐1‐expressing cells. These data highlight a mechanism by which the innate immune response of the host can restrict the pathogenicity of H. pylori by attenuating CagA phosphorylation in gastric epithelial cells.
Proliferation in African Breast Cancer: Biology and Prognostication in Nigerian Breast Cancer Material

Three hundred cases of invasive breast carcinoma from the University of Calabar Teaching Hospital, Nigeria were subjected to evaluation of proliferative activity by mitotic counts. The prognostic significance and association with other prognostic factors were evaluated. The mitotic activity was expressed as mitotic activity index (MAI), and standardized mitotic index (SMI). Pearson's correlation and univariate and multivariate Cox's regression were used. The mean follow-up time was 25.9 months. The mean values of SMI and MAI were 42.6 mitotic figures per square millimeter and 30.5 mitotic figures per 10 high-power fields, respectively, and these were much higher than values reported for Europe or other Western countries. The SMI had a positive correlation with tumor size (r = 0.31, P < .0001), histologic grade (r = 0.68, P < .0001), nuclear area (r = 0.45, P < .0001), and negative correlation with fraction of fields with tubular differentiation (FTD; r = −0.56, P = <0.0001). There was no statistically significant difference in the mitotic activity between the postmenopausal and the premenopausal patients. Also, lymph node-positive patients had higher counts than did lymph node-negative patients. Earlier determined grading associated decision thresholds divided the patients into groups of favorable and unfavorable prognosis. However, the statistically optimal thresholds for Nigerian material were different (32 and 92 mitotic figures per square millimeter for SMI). Tumor size of 5 cm, SMI, and MAI were independent prognostic factors. Nigerian breast cancers are high-grade, high-stage, and high-proliferating cancers occurring in a younger population than those of the Western countries. Proliferation is also more active. Evaluation of SMI or MAI can improve the distinction between aggressive and less aggressive variants of breast cancer.
Motor cortex rTMS restores defective intracortical inhibition in chronic neuropathic pain

Objective: To assess cortical excitability changes in patients with chronic neuropathic pain at baseline and after repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. Methods: In 22 patients with unilateral hand pain of various neurologic origins and 22 age-matched healthy controls, we studied the following parameters of cortical excitability: motor threshold at rest, motor evoked potential amplitude ratio at two intensities, cortical silent period (CSP), and intracortical inhibition (ICI) and intracortical facilitation. We compared these parameters between healthy subjects and patients at baseline. We also studied excitability changes in the motor cortex corresponding to the painful hand of patients after active or sham rTMS of this cortical region at 1 or 10 Hz. Results: At baseline, CSP was shortened for the both hemispheres of patients vs healthy subjects, in correlation with pain score, while ICI was reduced only for the motor cortex corresponding to the painful hand. Regarding rTMS effects, the single significant change was ICI increase in the motor cortex corresponding to the painful hand, after active 10-Hz rTMS, in correlation with pain relief. Conclusion: Chronic neuropathic pain was associated with motor cortex disinhibition, suggesting impaired GABAergic neurotransmission related to some aspects of pain or to underlying sensory or motor disturbances. The analgesic effects produced by motor cortex stimulation could result, at least partly, from the restoration of defective intracortical inhibitory processes.
Distributed Supervised Learning using Neural Networks

Distributed learning is the problem of inferring a function in the case where training data is distributed among multiple geographically separated sources. Particularly, the focus is on designing learning strategies with low computational requirements, in which communication is restricted only to neighboring agents, with no reliance on a centralized authority. In this thesis, we analyze multiple distributed protocols for a large number of neural network architectures. The first part of the thesis is devoted to a definition of the problem, followed by an extensive overview of the state-of-the-art. Next, we introduce different strategies for a relatively simple class of single layer neural networks, where a linear output layer is preceded by a nonlinear layer, whose weights are stochastically assigned in the beginning of the learning process. We consider both batch and sequential learning, with horizontally and vertically partitioned data. In the third part, we consider instead the more complex problem of semi-supervised distributed learning, where each agent is provided with an additional set of unlabeled training samples. We propose two different algorithms based on diffusion processes for linear support vector machines and kernel ridge regression. Subsequently, the fourth part extends the discussion to learning with time-varying data (e.g. time-series) using recurrent neural networks. We consider two different families of networks, namely echo state networks (extending the algorithms introduced in the second part), and spline adaptive filters. Overall, the algorithms presented throughout the thesis cover a wide range of possible practical applications, and lead the way to numerous future extensions, which are briefly summarized in the conclusive chapter.
Platelet-rich Plasma for Muscle Injury and Tendinopathy

Platelet-rich plasma (PRP) is increasingly used in Regenerative Medicine. The concept of PRP as a natural source of signaling molecules with paracrine effects in different cells is the basis for the increased PRP application as treatment for sports injuries. PRP recapitulates the principal functions of the natural healing response in orchestrating cell proliferation, differentiation, migration, and angiogenesis. After systematically searching the literature, we identified 21 trials for PRP injections in tendinopathy: 57% were uncontrolled trials and 1 cohort study in muscle. Leukocyte-PRP was used in 91.7% of tendons, of which 65.5% received 1 single injection. Given the lack of large controlled trials, it is clear that the effectiveness of conservative L-PRP treatments is not proven. The clinical evaluation of alternative formulations can be extremely informative. Other unexplored issues include activation, redosing, and concomitant longitudinal tenotomies. Limiting factors for the acceptance of PRP are the lack of evidence of obvious clinical improvement and reimbursement.
Therapeutic potential of targeting IL-1 and IL-18 in inflammation

Interleukin (IL)-1 and IL-18 are cytokines that play a major role in autoimmune and inflammatory human disease. Both cytokines drive a wide range of pro-inflammatory effector networks in many cell types and use common signal transduction cascades. IL-1, IL-18 and other members of the IL-1 superfamily are expressed at elevated levels in tissue and fluid samples isolated from patients with many chronic inflammatory diseases. These cytokines are primary drivers in acute and chronic animal models of inflammation and their blockade has been shown to ameliorate disease in preclinical studies. Biological agents that target IL-1 have demonstrated efficacy in patients with rheumatoid arthritis, and further agents targeting IL-1 or IL-18 neutralisation are in clinical development. The potential for such agents spans human disease where tissue destruction is a primary end point of cytokine action.
Crime and punishment in Islamic law: theory and practice from the sixteenth to the twenty-first century

In recent years some of the more fundamentalist regimes in the developing world (such as those of Iran, Pakistan, Sudan and the northern states of Nigeria) have reintroduced Islamic law in place of western criminal codes. Rudolph Peters presents a detailed account of the classical doctrine and traces the enforcement of criminal law from the Ottoman period to the present day. Accounts of actual cases, ranging from theft and banditry to murder, fornication and apostasy, shed light on the complexities of the law, and the sensitivity and intelligence of the qadis who implemented it.