Miracle-dz/UniFAR-FTUs huggingface dataset:
The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP

Lung cancers caused by activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to small molecule tyrosine kinase inhibitors (TKIs), but the efficacy of these agents is often limited because of the emergence of drug resistance conferred by a second mutation, T790M. Threonine 790 is the “gatekeeper” residue, an important determinant of inhibitor specificity in the ATP binding pocket. The T790M mutation has been thought to cause resistance by sterically blocking binding of TKIs such as gefitinib and erlotinib, but this explanation is difficult to reconcile with the fact that it remains sensitive to structurally similar irreversible inhibitors. Here, we show by using a direct binding assay that T790M mutants retain low-nanomolar affinity for gefitinib. Furthermore, we show that the T790M mutation activates WT EGFR and that introduction of the T790M mutation increases the ATP affinity of the oncogenic L858R mutant by more than an order of magnitude. The increased ATP affinity is the primary mechanism by which the T790M mutation confers drug resistance. Crystallographic analysis of the T790M mutant shows how it can adapt to accommodate tight binding of diverse inhibitors, including the irreversible inhibitor HKI-272, and also suggests a structural mechanism for catalytic activation. We conclude that the T790M mutation is a “generic” resistance mutation that will reduce the potency of any ATP-competitive kinase inhibitor and that irreversible inhibitors overcome this resistance simply through covalent binding, not as a result of an alternative binding mode.
Language skills and school achievement in talented

Resumen El estudio del talento es un area que ha venido desarrollandose con fuerza en los ultimos anos. Se presenta una mirada contrastiva del comportamiento linguistico con el rendimiento cognitivo de alumnos considerados talentosos provenientes de sectores vulnerables y que han participado del programa Talentos UdeC (Universidad de Concepcion), con el objeto de determinar si existe relacion entre el alto potencial intelectual, el lenguaje y el rendimiento escolar de estos jovenes. Se consideraron datos tanto de inteligencia (Raven) como de las notas de los cuatro ultimos anos escolares y las pruebas de seleccion universitarias. Para medir el rendimiento linguistico de los alumnos se aplico pruebas de comprension lectora y de vocabulario. Por una parte, los resultados muestran que un nivel de inteligencia alto se relaciona con un rendimiento alto o medianamente alto en todas las pruebas aplicadas, asi como tambien con las pruebas de matematicas. Por otra parte, un estudio de regresiones multiples demuestra la importancia del lenguaje para explicar los resultados en las pruebas de seleccion universitaria. Las habilidades linguisticas bien desarrolladas cumplen una funcion destacada dentro de todas las areas del desarrollo cognitivo y debieran potenciarse tanto como las matematicas en la escuela.
Structural research on surface layers: a focus on stability, surface layer homology domains, and surface layer-cell wall interactions.

Surface layers (S-layers) from Bacteria and Archaea are built from protein molecules arrayed in a two-dimensional lattice, forming the outermost cell wall layer in many prokaryotes. In almost half a century of S-layer research a wealth of structural, biochemical, and genetic data have accumulated, but it has not been possible to correlate sequence data with the tertiary structure of S-layer proteins to date. In this paper, some highlights of structural aspects of archaeal and bacterial S-layers that allow us to draw some conclusions on molecular properties are reviewed. We focus on the structural requirements for the extraordinary stability of many S-layer proteins, the structural and functional aspects of the S-layer homology domain found in S-layers, extracellular enzymes and related functional proteins, and outer membrane proteins, and the molecular interactions of S-layer proteins with other cell wall components. Finally, the perspectives and requirements for structural research on S-layers, which indicate that the investigation of isolated protein domains will be a prerequisite for solving S-layer structures at atomic resolution, are discussed.
Practical Improvements to the Minimizing Delta Debugging Algorithm

The first step in dealing with an input that triggers a fault in a software is simplifying it as much and as automatically as possible, since a minimal test case can ensure the efficient use of human developer resources. The well-known minimizing Delta Debugging algorithm is widely used for automated test case simplification but even its last published revision is more than a decade old. Thus, in this paper, we investigate how it performs nowadays, especially (but not exclusively) focusing on its parallelization potential. We present new improvement ideas, give algorithm variants formally and in pseudo-code, and evaluate them in a large-scale experiment of more than 1000 test minimization sessions featuring real test cases. Our results show that with the help of the proposed improvements, Delta Debugging needs only one-fourth to one-fifth of the original execution time to reach 1-minimal results.
CORRELATION BETWEEN MORPHOLOGICAL AND BIOCHEMICAL CHANGES AND THE APPEARANCE OF INFECTIVITY IN FL CELL CULTURES INFECTED WITH TRACHOMA AGENT *

After the cultivation of strains of the trachoma agent in fertilized eggs had been accomplished,’s2 it seemed an obvious next step to use cell cultures for the same purpose. The first successful cultivation in vitro was reported by Gordon et aL.,3 who grew a strain isolated in Taiwan in explants of yolk sac cells. In these cultures a study of certain morphological stages in the development of the agent could be carried out. Infection was, however, confined to a minority of cells, and it was difficult to obtain more than a single cycle of multiplication. Pollard et aZ.4 reported observations made with the fluorescence microscope on the growth of a trachoma strain, isolated in Arabia, in the Fernandes line of human amnion and the McCoy line of human synovial cells. Five successive passages could be carried out in the latter cells. The present work has been carried out with one of the strains isolated in China by T’ang et aL.’ This strain, obtained through the kindness of Dr. Collier, was grown in the FL line of human amnion cells.6 The same strain has been grown in HeLa cells by Furness et aL6 In FL cell cultures the T’ang strain has so far undergone more than 60 passages. The medium used contained Earle’s salt solution, lactalbumin hydrolyzate, yeast extract, and 20 per cent human serum, to which streptomycin and mycostatin were added. The same cell line and medium proved to be unsuitable for the growth of another trachoma strain which was isolated more recently in IsraeL7 In a subline of the FL strain, on the other hand, which is cultivated in bovine instead of human serum, the T’ang strain did not reach full maturation, even when the bovine was replaced by human serum a t the time of infection. Multiplication of the T’ang strain in FL cells cultivated continuously in human serum is accompanied by a characteristic cytopathic effect. Large vacuoles full of elementary bodies develop in the infected cells. Their enumeration in infected monolayers gives a good quantitative estimate of the infectivity of a preparation. The method has been described in detail by Furness et al? and has also been used in the present work.
An Autocrine Loop Involving Ret and Glial Cell–Derived Neurotrophic Factor Mediates Retinoic Acid–Induced Neuroblastoma Cell Differentiation

In several neuroblastoma cell lines, retinoic acid (RA)–induced differentiation is coupled to increased expression of functional neurotrophic factor receptors, including Trk family receptors and the glial cell–derived neurotrophic factor receptor, Ret. In several cases, increased expression is dependent on signaling through TrkB. Unlike TrkA and TrkB, Ret has never been implicated as a prognostic marker for neuroblastomas. SK-N-BE(2) cells do not express any of Trk family receptors; therefore, they are a choice system to study the specific role of Ret in RA-induced differentiation. Using a 2′-fluoro-RNA aptamer and a truncated Ret protein as specific inhibitors of Ret, we show that RA-induced differentiation is mediated by a positive autocrine loop that sustains Ret downstream signaling and depends on glial cell–derived neurotrophic factor expression and release. This report shows that in SK-N-BE(2) cells, stimulation of Ret is a major upstream mechanism needed to mediate RA-induced differentiation. These results provide important insights on the molecular mechanism of RA action, which might be relevant for the development of biologically based therapeutic strategies. (Mol Cancer Res 2006;4(7):481–8)
Anti-PD-1 antibodies for the treatment of B-cell lymphoma

Monoclonal antibodies specific for programmed cell death 1 (PDCD1, best known as PD-1) have been shown to mediate antineoplastic effects in follicular lymphoma patients. However, the relative proportion of intratumoral PD-1+ T-cell subsets, in particular follicular helper T cells (which exert pro-tumor functions) and effector T cells (which have anticancer activity), may impact clinical outcome, and should therefore be carefully considered for patient selection in this setting.
Retrieving high-resolution surface solar radiation with cloud parameters derived by combining MODIS and MTSAT data

Abstract. Cloud parameters (cloud mask, effective particle radius, and liquid/ice water path) are the important inputs in estimating surface solar radiation (SSR). These parameters can be derived from MODIS with high accuracy, but their temporal resolution is too low to obtain high-temporal-resolution SSR retrievals. In order to obtain hourly cloud parameters, an artificial neural network (ANN) is applied in this study to directly construct a functional relationship between MODIS cloud products and Multifunctional Transport Satellite (MTSAT) geostationary satellite signals. In addition, an efficient parameterization model for SSR retrieval is introduced and, when driven with MODIS atmospheric and land products, its root mean square error (RMSE) is about 100 W m−2 for 44 Baseline Surface Radiation Network (BSRN) stations. Once the estimated cloud parameters and other information (such as aerosol, precipitable water, ozone) are input to the model, we can derive SSR at high spatiotemporal resolution. The retrieved SSR is first evaluated against hourly radiation data at three experimental stations in the Haihe River basin of China. The mean bias error (MBE) and RMSE in hourly SSR estimate are 12.0 W m−2 (or 3.5 %) and 98.5 W m−2 (or 28.9 %), respectively. The retrieved SSR is also evaluated against daily radiation data at 90 China Meteorological Administration (CMA) stations. The MBEs are 9.8 W m−2 (or 5.4 %); the RMSEs in daily and monthly mean SSR estimates are 34.2 W m−2 (or 19.1 %) and 22.1 W m−2 (or 12.3 %), respectively. The accuracy is comparable to or even higher than two other radiation products (GLASS and ISCCP-FD), and the present method is more computationally efficient and can produce hourly SSR data at a spatial resolution of 5 km.
Null infinity waveforms from extreme-mass-ratio inspirals in Kerr spacetime

We describe the hyperboloidal compactification for Teukolsky equations in Kerr spacetime. We include null infinity on the numerical grid by attaching a hyperboloidal layer to a compact domain surrounding the rotating black hole and the orbit of an inspiralling point particle. This technique allows us to study, for the first time, gravitational waveforms from large- and extreme-mass-ratio inspirals in Kerr spacetime extracted at null infinity. Tests and comparisons of our results with previous calculations establish the accuracy and efficiency of the hyperboloidal layer method.
Suppression and stabilisation of noise

In this article, we investigate the stochastic suppression and stabilisation of nonlinear systems. Given an unstable differential equation , in which f satisfies the one-sided polynomial growth condition, we introduce two Brownian noise feedbacks and therefore stochastically perturb this system into the nonlinear stochastic differential equation . This article shows that appropriate β may guarantee that this stochastic system exists as a unique global solution although the corresponding deterministic may explode in a finite time. Then sufficiently large q may ensure that this stochastic system is almost surely exponentially stable.
Bioverse: functional, structural and contextual annotation of proteins and proteomes

Functional annotation is routinely performed for large-scale genomics projects and databases. Researchers working on more specific problems, for instance on an individual pathway or complex, also need to be able to quickly, completely and accurately annotate sequences. The Bioverse sequence annotation server (http://bioverse.compbio.washington.edu) provides a web-based interface to allow users to submit protein sequences to the Bioverse framework. Sequences are functionally and structurally annotated and potential contextual annotations are provided. Researchers can also submit candidate genomes for annotation of all proteins encoded by the genome (proteome).
Factors associated with late antiretroviral therapy initiation in Cameroon: a representative multilevel analysis.

OBJECTIVES Many people living with HIV/AIDS in resource-limited settings begin antiretroviral therapy (ART) at low CD4 counts. Here, we investigated the simultaneous effect of individual-, facility- and regional-level factors on late ART initiation. METHODS We conducted a survey in a nationally representative sample of 55 HIV treatment facilities in Cameroon. Medical records of 4935 patients >15 years of age who initiated ART in the month of October during the period 2007-10 were reviewed to gather individual characteristics. Late ART initiation was defined as CD4 count ≤ 100 cells/mm(3). Facility- and regional-level characteristics were also collected. Two-level regression logistic models were used to identify factors associated with late ART initiation. RESULTS Late ART initiation was associated with being a male younger than 45 years versus female younger than 45 years [adjusted OR (AOR) = 1.5, 95% CI: 1.3-1.7] and initiating ART in the period 2007-09 versus 2010 (AOR = 1.2, 95% CI: 1.0-1.4). Late initiation was more likely in central than in district hospitals (AOR = 1.3, 95% CI: 1.1-1.6) and in hospitals without a mother-to-child transmission programme (AOR = 1.9, 95% CI: 1.3-2.8). Living in a region with a higher comprehensive knowledge of HIV/AIDS was associated with not initiating ART late (AOR = 0.8, 95% CI: 0.6-1.0). CONCLUSIONS This study shows that risk factors associated with late ART initiation operate at multiple levels and that multilevel interventions are therefore necessary to promote earlier HIV testing and treatment.
Identify Avoided Childhood Obesity Cases Obesity Cases Averted Based on El Paso CATCH Intervention From the CATCH Trial Predict 25 − 29 year old Predict 40 − 64 year old Include Intervention Cost Include Medical Costs Averted

Background: This study assesses the net benefit and the cost-effectiveness of the Coordinated Approach to Child Health (CATCH) intervention program, using parameter estimates from the El Paso trial. There were two standard economic measures used. First, from a societal perspective on costs, cost-effectiveness ratios (CER) were estimated, revealing the intervention costs per qualityadjusted life years (QALYs) saved. QALY weights were estimated using National Health Interview Survey (NHIS) data. Second, the net benefit (NB) of CATCH was estimated, which compared the present value of averted future costs with the cost of the CATCH intervention. Using National Health and Nutrition Examination Survey I (NHANES) and NHANES follow-up data, we predicted the number of adult obesity cases avoided for ages 40–64 with a lifetime obesity progression model. Results: The results show that CATCH is cost-effective and net beneficial. The CER was US$900 (US$903 using Hispanic parameters) and the NB was US$68,125 (US$43,239 using Hispanic parameters), all in 2004 dollars. This is much lower than the benchmark for CER of US$30,000 and higher than the NB of US$0. Both were robust to sensitivity analyses. Conclusion: Childhood school-based programs such as CATCH are beneficial investments. Both NB and CER declined when Hispanic parameters were included, primarily due to the lower wages earned by Hispanics. However, both NB and CER for Hispanics were well within standard costeffectiveness and net benefit thresholds. Background Childhood overweight is a major threat to child health in the US [1]. Unfortunately, overweight children are not likely to return to normal weight later in life [2-4]. Aside from the correlation of lifetime behaviors [5], treatment strategies for obese adults remain largely ineffective [611]. Obesity in adulthood is closely associated with chronic diseases including cardiovascular disease (CVD), Published: 1 October 2007 International Journal of Behavioral Nutrition and Physical Activity 2007, 4:47 doi:10.1186/14795868-4-47 Received: 26 January 2007 Accepted: 1 October 2007 This article is available from: http://www.ijbnpa. org/content/4/1/47 © 2007 Brown et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Achieving low-latency communication in future wireless networks : the 5 G NORMA approach

The end-to-end network latency is generally considered by the 5G community a key requirement for future wireless networks, enabling new applications by means of end-toend figures up to a few ms, which is a target that cannot be achieved by the current 4G technology. 5G Novel Radio Multiservice adaptive network Architecture (5G NORMA) project aims at providing a new network architecture design able to cope with the diverse and stringent 5G KPIs, including network latency. This paper describes the low latency issue from a network architecture perspective, starting from the 3GPP stateof-the-art and then describing the 5G NORMA novelties Keywords—latency; 5G technology; networking functions; flexible allocation
Ultraviolet light induced linking of deoxyribonucleic acid strands and its reversal by photoreactivating enzyme.

The irradiation of DNA in solution with ultraviolet light with doses approximating those used for the inactivation of transforming activity causes the irreversible hydrogenbond breakage, most likely in internal regions of the DNA molecule and the formation of formamide- and heat-stable linkages between the two complementary DNA strands. Repair of the latter damage is catalyzed by the photoreactivating enzyme from bakers' yeast. The cross-links are in keeping with the observations of others on the irradiation of thymine in the frozen state and may be due to the formation of dimers of thymine. (auth)
EUS–FNA of Brunner’s gland hamartoma: a case report

A 50-year-old woman was evaluated at an outside institution for iron deficiency anaemia. Esophagogastroduodenoscopy demonstrated a polypoid tumour in the distal duodenum. Punch biopsy was unremarkable. Multi-sliced computed tomography revealed a mass inseparable from the pancreatic head. Apart from anaemia (Hb 108 g ⁄ l), other laboratory findings were unremarkable. The patient was referred to our institution for EUS, which revealed a 40 · 63-mm mostly hypoechogenic mass with small cystic spaces, not in contact with the pancreatic head. The lesion was sited within the duodenal wall and probably originated in the fourth echolayer (Figure 1), so suspicion of gastrointestinal stromal tumour (GIST) was raised.
Enciphering using Elegant Pairing Functions and Logical Operators

technology started growing verbal exchange became a principal method of exchanging data. With the introduction of web and pay out programs protection problems are more difficult and elaborate. Secure correspondence is a remarkable worry by which individuals can communicate data to changing degrees of assurance that outsiders can't catch the data that is transmitted over system. Consequently data security is an essential thought in nowadays. Cryptography and data security is growing more to deal with authorized security for systems. In this work the proposed algorithm makes use of basic encryption methods like substitution, transposition, bitwise logical operations together with pairing operate to encrypt the information. The algorithm itself generates the important key from simple text and hides inside plaintext.
The Performance Impact of Context in TQM Implementation: The Nursing Facility Industry

This study develops a model and empirically assesses how# organizational context mediates the impact of total quality management (TQM) implementation on perceived performance in the nursing facility industry. Outcomes are analysed for financial, human resources and resident-care performance. Contextual factors related to TQM implementation include managerial control, reward systems, organizational structure and the extent of implementation. Duration of TQM implementation is included as a control variable. Benchmarking has a positive impact on financial outcomes, and the extent of TQM implementation and required reporting of quality improvement activity results have a positive impact on both financial and human resources performance. The presence of a Quality Steering Council has a positive impact on financial performance, but only among larger facilities.
Edinburgh Research Explorer Bacterial Growth Rate and Host Factors as Determinants of Intracellular Bacterial Distributions in Systemic Salmonella enterica Infections

Bacteria of the species Salmonella enterica cause a range of life-threatening diseases in humans and animals worldwide. The within-host quantitative, spatial, and temporal dynamics of S. enterica interactions are key to understanding how immunity acts on these infections and how bacteria evade immune surveillance. In this study, we test hypotheses generated from mathematical models of in vivo dynamics of Salmonella infections with experimental observation of bacteria at the single-cell level in infected mouse organs to improve our understanding of the dynamic interactions between host and bacterial mechanisms that determine net growth rates of S. enterica within the host. We show that both bacterial and host factors determine the numerical distributions of bacteria within host cells and thus the level of dispersiveness of the infection. Bacteria of the species Salmonella enterica are a threat to public health, causing enteric systemic diseases (typhoid and paratyphoid fever), gastroenteritis and nontyphoidal septicemia in humans and similar diseases in many other animal species worldwide. The emergence of multidrug-resistant Salmonella strains and the insufﬁcient efﬁcacy of some of the currently available