Miracle-dz/UniFAR-FTUs huggingface dataset:
Conditionally oncogenic forms of the A-Raf and B-Raf protein kinases display different biological and biochemical properties in NIH 3T3 cells

The protein kinase domains of mouse A-Raf and B-Raf were expressed as fusion proteins with the hormone binding domain of the human estrogen receptor in mammalian cells. In the absence of estradiol, 3T3 and rat1a cells expressing delta A-Raf:ER and delta B-Raf:ER were nontransformed, but upon the addition of estradiol the cells became oncogenically transformed. Morphological oncogenic transformation was more rapid and distinctive in cells expressing delta B-Raf:ER compared with cells expressing delta A-Raf:ER. Biochemical analysis of cells transformed by delta A-Raf:ER and delta B-Raf:ER revealed several interesting differences. The activation of delta B-Raf:ER consistently led to the rapid and robust activation of both MEK and p42/p44 MAP kinases. By contrast, the activation of delta A-Raf:ER led to a weak activation of MEK and the p42/p44 MAP kinases. The extent of activation of MEK in cells correlated with the ability of the different Raf kinases to phosphorylate and activate MEK1 in vitro. delta B-Raf:ER phosphorylated MEK1 approximately 10 times more efficiently than delta Raf-1:ER and at least 500 times more efficiently than delta A-Raf:ER under the conditions of the immune-complex kinase assays. These results were confirmed with epitope-tagged versions of the Raf kinase domains expressed in insect cells. The activation of all three delta Raf:ER proteins in 3T3 cells led to the hyperphosphorylation of the resident p74raf-1 and mSOS1 proteins, suggesting the possibility of "cross-talk" between the different Raf kinases and feedback regulation of intracellular signaling pathways. The activation of either delta B-Raf:ER or delta Raf-1:ER in quiescent 3T3 cells was insufficient to promote the entry of the cells into DNA synthesis. By contrast, the activation of delta A-Raf:ER in quiescent 3T3 cells was sufficient to promote the entry of the cells into S phase after prolonged exposure to beta-estradiol. The delta Raf:ER system has allowed us to reveal significant differences between the biological and biochemical properties of oncogenic forms of the Raf family of protein kinases. We anticipate that cells expressing these proteins and other estradiol-regulated protein kinases will be useful tools in future attempts to unravel the complex web of interactions involved in intracellular signal transduction pathways.
Coupling In Silico and In Vitro Analysis of Peptide-MHC Binding: A Bioinformatic Approach Enabling Prediction of Superbinding Peptides and Anchorless Epitopes

The ability to define and manipulate the interaction of peptides with MHC molecules has immense immunological utility, with applications in epitope identification, vaccine design, and immunomodulation. However, the methods currently available for prediction of peptide-MHC binding are far from ideal. We recently described the application of a bioinformatic prediction method based on quantitative structure-affinity relationship methods to peptide-MHC binding. In this study we demonstrate the predictivity and utility of this approach. We determined the binding affinities of a set of 90 nonamer peptides for the MHC class I allele HLA-A*0201 using an in-house, FACS-based, MHC stabilization assay, and from these data we derived an additive quantitative structure-affinity relationship model for peptide interaction with the HLA-A*0201 molecule. Using this model we then designed a series of high affinity HLA-A2-binding peptides. Experimental analysis revealed that all these peptides showed high binding affinities to the HLA-A*0201 molecule, significantly higher than the highest previously recorded. In addition, by the use of systematic substitution at principal anchor positions 2 and 9, we showed that high binding peptides are tolerant to a wide range of nonpreferred amino acids. Our results support a model in which the affinity of peptide binding to MHC is determined by the interactions of amino acids at multiple positions with the MHC molecule and may be enhanced by enthalpic cooperativity between these component interactions.
Antigenic Differences between Clinical and Environmental Isolates of Burkholderia pseudomallei

Burkholderia pseudomallei is a free‐living organism that causes the potentially lethal tropical infection melioidosis. The disease is endemic in many parts of eastern Asia and northern Australia. The presence of two distinct biotypes in soil can be reliably distinguished by their ability to assimilate l‐arabinose. Whereas some soil isolates could utilize this substrate (Ara+), the remaining soil isolates and all clinical isolates tested so far could not (Ara−). Only the Ara− isolates were virulent in animal models. We have raised a murine monoclonal antibody (MAb) that can readily distinguish Ara− from Ara+ biotypes. The MAb reacted with a high molecular weight component present only on the Ara− biotype. With this MAb, clinical and soil Ara−isolates gave identical positive reactions in agglutination, immunofluorescence, ELISA and immunoblot assays. Using these same assay systems, the soil Ara+ biotype did not react with the MAb. Similar but distinct immunoblot patterns were also noted when these two Ara biotypes were probed with sera from patients with melioidosis or with polyclonal immune rabbit sera. These data showed that the Ara− biotype from both clinical and environmental isolates is antigenically different from its Ara+ environmental counterpart. The SDS‐PAGE protein and lectin‐binding profiles of both groups of Ara− isolates were also found to be different from those of the Ara+ biotype.
Implication of MicroRNAs in the Pathophysiology of Cardiac and Vascular Smooth Muscle Cells

© 2012 Metzinger-Le Meuth et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Implication of MicroRNAs in the Pathophysiology of Cardiac and Vascular Smooth Muscle Cells
The presence of glomerular sclerosis at time zero has a significant impact on function after cadaveric renal transplantation

Introduction. The aim was to determine the impact of donor glomerulosclerosis on allograft outcome. Methods. The percentage of glomerular sclerosis (%GS) was calculated in protocol biopsies taken at engraftment. Clinical variables were obtained from the Welsh Transplantation Research Group (WTRG) database. Results. Of 210 allografts, 129 showed %GS=0, but 81 kidneys showed %GS between 1 and 60. Patients with %GS=0 had the highest glomerular filtration rate (GFR) at 1 year (62.0 mL/min) and the slowest deterioration of function (−3.8 mL/min per year). Patients with %GS greater than 20 had the lowest GFR at 1 year (36.0 mL/min) and the steepest rate of deterioration (−9.0 mL/min per year). The %GS of 10 alone can reduce GFR at 4 years by 8 mL/min, a similar reduction to a single rejection episode or an increase in donor age of 30 years. Actuarial 5-year graft survival for %GS=0 was 80%, and for %GS greater than 20 was 35% (P =0.04). Conclusion. The findings indicate that a biopsy taken at procurement will provide information for the most appropriate allocation of a kidney.
Incidence and Mortality of Nasopharynx Cancer and Its Relationship With Human Development Index in the World in 2012

Background One of the most common cancers in head and neck is nasopharynx. Knowledge about the incidence and mortality of this disease and its distribution in terms of geographical areas is necessary for further study, better planning and prevention. Therefore, this study aimed to determine the incidence and mortality of nasopharynx cancer and its relationship with human development index (HDI) in the world in 2012. Methods This study was an ecological study conducted based on GLOBOCAN project of World Health Organization (WHO) for the countries in world. The correlation between standardized incidence rates (SIRs) and standardized mortality rates (SMRs) of nasopharynx cancer with HDI and its components was assessed with correlation coefficient by using SPSS 15. Results In 2012, 86,691 nasopharynx cancer cases occurred in the world, so that 60,896 new cases were seen in men and 25,795 new cases in women (sex ratio = 2.36). SIR of the cancer was 1.2 per 100,000 (1.7 in men and 0.7 in women per 100,000) in the world. In 2012, 50,831 nasopharynx death cases occurred in the world, so that 35,756 death cases were seen in men and 15,075 death cases in women (sex ratio = 2.37). SIR of mortality from the cancer was 0.7 per 100,000 (0.7 in women and 1 in men per 100,000) in the world. The results of correlation analysis showed a negative correlation between the SIR and HDI (r = -0.037, P = 0.629), and also the results of correlation analysis showed a negative correlation between the SMR and HDI (r = -0.237, P = 0.002). Conclusion Nasopharyngeal cancer is native to Southeast Asia and the highest incidence and mortality were seen in countries with moderate and low HDI. It is suggested that studies are conducted on determining the causes of the cancer incidence and mortality in the world and the differences between various regions.
Postnatal ethanol exposure simplifies the dendritic morphology of medium spiny neurons independently of adenylyl cyclase 1 and 8 activity in mice.

BACKGROUND Fetal exposure to alcohol can have multiple deleterious effects, including learning disorders and behavioral and executive functioning abnormalities, collectively termed fetal alcohol spectrum disorders. Neonatal mice lacking both calcium-/calmodulin-stimulated adenylyl cyclases (ACs) 1 and 8 demonstrate increased vulnerability to ethanol (EtOH)-induced neurotoxicity in the striatum compared with wild-type (WT) controls. However, the developmental impact on surviving neurons is still unclear. METHODS WT and AC1/8 double knockout (DKO) mice were administered 1 dose of EtOH (2.5 g/kg) between postnatal days 5 to 7 (P5-7). At P30, brains were removed and processed for Golgi-Cox staining. Medium spiny neurons (MSNs) from the caudate putamen were analyzed for changes in dendritic complexity; number of branches, branch points and terminals, total and average dendritic length; spine density and soma size. RESULTS EtOH significantly reduced the dendritic complexity and soma size in surviving MSNs regardless of genotype without affecting spine density. In the absence of EtOH, genetic deletion of AC1/8 reduced the dendritic complexity, number of branch points, spine density, and soma size of MSNs compared with WT controls. CONCLUSIONS These data indicate that neonatal exposure to a single dose of EtOH is sufficient to cause long-term alterations in the dendritic complexity of MSNs and that this outcome is not altered by the functional status of AC1 and AC8. Therefore, although deletion of AC1/8 demonstrates a role for the ACs in normal morphologic development and EtOH-induced neurodegeneration, loss of AC1/8 activity does not exacerbate the effects of EtOH on dendritic morphology or spine density.
Proteolytic regulation of alginate overproduction in Pseudomonas aeruginosa

Pseudomonas aeruginosa, a Gram‐negative bacterium, is a significant opportunistic pathogen associated with skin and soft tissue infections, nosocomial pneumonia and sepsis. In addition, it can chronically colonize the lungs of cystic fibrosis (CF) patients. Overproduction of the exopolysaccharide called alginate provides P. aeruginosa with a selective advantage and facilitates survival in the CF lung. The in vitro phenotype of alginate overproduction observed on solid culture media is referred to as mucoid. Expression of the alginate machinery and biosynthetic enzymes are controlled by the extracytoplasmic sigma factor, σ22 (AlgU/T). The key negative regulator of both σ22 activity and the mucoid phenotype is the cognate anti‐sigma factor MucA. MucA sequesters σ22 to the inner membrane inhibiting the sigma factor's transcriptional activity. The well‐studied mechanism for transition to the mucoid phenotype is mutation of mucA, leading to loss of MucA function and therefore activation of σ22. Recently, regulated intramembrane proteolysis (RIP) has been recognized as a mechanism whereby proteolysis of the anti‐sigma factor MucA leads to active σ22 allowing P. aeruginosa to respond to environmental stress conditions by overproduction of alginate. The goal of this review is to illuminate the pathways leading to RIP that have been identified and proposed.
High‐density marker loss of heterozygosity analysis of rat chromosome 10 in endometrial adenocarcinoma

Endometrial cancer is a disease with serious impact on the human population, but not much is known about genetic factors involved in this complex disease. Female BDII rats are genetically predisposed to spontaneous endometrial carcinoma, and the BDII inbred strain provides an experimental animal model for endometrial carcinoma development. In the present study, BDII females were crossed with males from two nonsusceptible inbred rat strains. Endometrial adenocarcinomas (EACs) developed in a proportion of the F1 and F2 progeny. We screened 18 EAC solid tumors and 9 EAC cell cultures for loss of heterozygosity (LOH) using fluorescent‐PCR‐based marker allelotyping methodology with 47 microsatellite markers covering the proximal part of rat chromosome 10 (RNO10). Conclusive evidence was obtained for LOH/deletion involving about 56 cM in the proximal part of RNO10 in DNA from six out of seven informative tumor cell cultures. Analysis of the solid tumors confirmed the presence of LOH in this part of RNO10 in 14 of 17 informative tumors. However, from the studies in the solid tumors it appeared that in fact three separate segments in the proximal part of RNO10 were affected. These three LOH/deletion regions were located approximately in cytogenetic bands 10q11‐12, 10q22, and 10q24. © 2001 Wiley‐Liss, Inc.
Searching a pattern in token scene image via multi-variant symmetric pattern matching technique

One of the fundamental tasks of pattern recognition is pattern matching. It is the act of checking for presence of a pattern's constituents within token image to have exact match. For that, most distinctive fiducial features of pattern have to be assessed and searched in the sliding windows of same pattern size formed by logically dividing the token scene image. As huge numbers of sliding windows are to be checked with pattern, pattern matching process should be time efficient and to increase pattern matching accuracy impacts due to illumination, resolution, occlusion and pose variation must be reduced. For pattern matching, this paper presents a novel local feature descriptor, multi variant symmetric local graph structure (MVSLGS) taking into account symmetric local graph structure (SLGS) as precedent approach. The computational adequacy of the proposed approach is tested on two publicly available databases with high matching accuracy, showing its proficiency over the process of pattern matching.
Comparación y combinación de los sistemas de traducción automática basados en n-gramas y en sintaxis

En este articulo se comparan dos sistemas basados en dos aproximaciones diferentes de traduccion automatica: El denominado sistema de la Traduccion Automatica Aumentado con Sintaxis (SAMT / TAAS), basado en una sintaxis subyacente al modelo basado en frases, y el sistema de traduccion automatica estadistica (TAE) basado en n-gramas en el cual el proceso de traduccion esta basado en el modelado estocastico del contexto bilingue. Se realiza una comparacion de la arquitectura de los dos sistemas paso a paso y se comparan tambien los resultados en base a las medidas automaticas de evaluacion de la calidad de traduccion y los recursos computacionales para una pequena tarea arabe-ingles que pertenece al dominio de noticias. Finalmente, se combinan las salidas de ambos sistemas para obtener una mejora significativa de la calidad de la traduccion.
Cetuximab in the treatment of metastatic colorectal cancer

Cetuximab is a chimeric monoclonal antibody that binds to the epidermal growth factor receptor and thereby inhibits cell proliferation, metastasis and angiogenesis. Preclinical studies indicate that cetuximab induces synergistic antitumor activity when combined with chemotherapy or radiation. This observation is supported by clinical trials demonstrating that cetuximab improves tumor response when used in conjunction with modern chemotherapy in patients with metastatic colorectal cancer. Improved treatment efficacy may help to increase the rate of hepatic metastasis resection after downsizing of initially unresectable lesions. In pretreated patients, cetuximab may restore the sensitivity to irinotecan and, therefore, has been registered in this setting. Ongoing studies are investigating the integration of anti-epidermal growth factor receptor and anti-vascular endothelial growth factor strategies into new treatment regimens. Promising results have already been obtained in a trial combining irinotecan, bevacizumab and cetuximab.
Development of synaptic currents in immobilized muscle of Xenopus laevis.

The effect of chronic immobilization on the development of synaptic currents was studied in myotomal muscle of Xenopus laevis. Embryos and tadpoles were immobilized by rearing them in the presence of tetrodotoxin (TTX) after removal of the egg membranes. Immobilization did not affect the developmental change in duration of miniature end‐plate currents (m.e.p.c.s). Rise times decreased from about 3 to 0.6 ms in both immobilized and control muscle, and decay constants decreased from about 7 to 1 ‐ 2 ms in both conditions. M.e. p.c. s with double exponential decays were recorded in both immobilized and control muscle at intermediate and late developmental stages. The fast and slow decay constants were 0.7 ms and slightly less than 3 ms in older muscle of both groups. These values are comparable to the apparent open times of fast and slow ACh receptors present on Xenopus muscle. Application of an anticholinesterase (methanesulphonyl fluoride) lengthened the duration of m.e. p.c. s comparably in immobilized and control muscle. These data indicate that the deposition of junctional acetylcholinesterase and the reduction in open time of acetylcholine receptor channels in developing Xenopus myotomal muscle are independent of contractile activity of muscle and TTX‐blockable action potentials in muscle or motoneurones.
Assessment of suicidal behavior in the emergency department.

194 INTRODUCTION Dr. Targum: Hospital emergency departments see a lot of people who are seriously thinking about suicide or have made suicide attempts. In fact, emergency departments (ED) in the United States treat over 500,000 people annually for suicide-related issues. Within many healthcare systems, the ED has become a critical thoroughfare (the default option) for acute and chronically suicidal patients. Mills et al found that the ED had the second highest number of reported completed suicides and attempts within the Veterans Affairs (VA) healthcare system and was second only to inpatient psychiatric units. Suicide attempts leading to ED visits are not restricted to any age group, ethnicity, or socio-economic status and are not always associated with psychiatric comorbidity like depression, conduct disorder, or substance abuse. Suicide attempts leading to ED visits occur in adolescents as well as the elderly, may be impulsive or deliberate, may follow alcohol intoxication, and vary widely in the actual intent to die. The obvious high risk of a repeat suicide attempt generates an urgency to make an accurate assessment and create a safe, yet plausible treatment plan. ED physicians need to quickly assess the potential lethality of suicidal patients and determine whether to retain them (hospital admission) or discharge them. The majority of suicide attempt patients seen in the ED are discharged without hospitalization after medical stabilization and psychosocial evaluation. Yet, these patients still have a high risk for repeated attempts. Up to 25 percent of these suicide attempters return to the ED after another attempt, and 5 to 10 percent eventually die by suicide. Given this context, it is intriguing that hospitalization rates following suicide attempt-related ED visits actually decreased from 49 percent to 32 percent during the same time period (1992–2001) that ED visits for suicide attempts had increased by 47 percent. Clearly, the ED is a vital setting for suicide prevention and may be the only access to healthcare available for some patients. Of course, the busy ED has to deal with cardiac arrests, gun shot wounds, sick babies, and every other conceivable medical emergency at the same time that they assess a suicidal patient. For this column, I discuss the assessment of suicidal patients with two physicians who work at the very busy ED at Tufts Medical Center in downtown Boston, Massachusetts. Their views go beyond the theoretical and reflect the experience and wisdom of physicians who work on the front line of healthcare. Dr. Frank Friedman is an Assistant Professor of Emergency Medicine at Tufts University School of Medicine and the Director of Prehospital Care and Emergency Preparedness at Tufts Medical Center. Dr. Manuel N. Pacheco is an Assistant Professor of Psychiatry at Tufts Research to Practice
E-Quest: Ein Online-Befragunswerkzeug für Web Usability

E-Quest ist ein Werkzeug zu automatisierten Online-Befragungen. Es bietet ohne grosen Konfigurationsaufwand die Moglichkeit zur komfortablen Gestaltung der Fragebogen und vielfaltigen Auswertungsmoglichkeiten, um die Usability einer Webseite zu evaluieren.
Reducing lightning damages and outages

Thus was born the Lightning Detection Network (LDN). It was designed to gather long-term data that could be used to map the frequency, location, and severity of lightning throughout the United States. Over time, such a data base will help utilities refine their decisions on how much surge protection equipment to buy and where to install it. In the near term, however, the LDN is being used by participating utilities as a storm tracking service. By accessing the LDN computer in Albany, New York, utilities can continuously monitor the location of lightning as it approaches and passes through an area. This knowledge helps them decide when and where to mobilize repair crews before the storm arrives. Those utilities already subscribing to this service ($7000 a year for data communications and other nonresearch costs) find that it pays for itself very quickly in more efficient use of manpower and in more rapid restoration of customer service following lightning-related outages.
Solubilization of lignin by the ruminal anaerobic fungus Neocallimastix patriciarum

The ability of the ruminal anaerobic phycomycete Neocallimastix patriciarum to digest model lignin compounds and lignified structures in plant material was studied in batch culture. The fungus did not degrade or transform model lignin compounds that were representative of the predominant intermonomer linkages in lignin, nor did it solubilize acid detergent lignin that had been isolated from spear grass. In a stem fraction of sorghum, 33.6% of lignin was apparently solubilized by the fungus. Solubilization of ester- and either-linked phenolics accounted for 9.2% of the lignin released. The amounts of free phenolic acids detected in culture fluid were equivalent to the apparent loss of ester-linked phenolics from the sorghum substrate. However, the fungus was unable to cleave the ether bond in hydroxycinnamic acid bridges that cross-link lignin and polysaccharide. It is suggested that the majority of the solubilized lignin fraction was a lignin carbohydrate complex containing ether-linked hydroxycinnamic acids. The lignin carbohydrate complex was probably solubilized through dissolution of xylan in the lignin-xylan matrix rather than by lignin depolymerization.