Miracle-dz/UniFAR-FTUs huggingface dataset:
The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia

Recent studies have shown that activating mutations of NOTCH1 are responsible for the majority of T cell acute lymphoblastic leukemia (T-ALL) cases. Most of these mutations truncate its C-terminal domain, a region that is important for the NOTCH1 proteasome-mediated degradation. We report that the E3 ligase FBW7 targets NOTCH1 for ubiquitination and degradation. Our studies map in detail the amino acid degron sequence required for NOTCH1–FBW7 interaction. Furthermore, we identify inactivating FBW7 mutations in a large fraction of human T-ALL lines and primary leukemias. These mutations abrogate the binding of FBW7 not only to NOTCH1 but also to the two other characterized targets, c-Myc and cyclin E. The majority of the FBW7 mutations were present during relapse, and they were associated with NOTCH1 HD mutations. Interestingly, most of the T-ALL lines harboring FBW7 mutations were resistant to γ-secretase inhibitor treatment and this resistance appeared to be related to the stabilization of the c-Myc protein. Our data suggest that FBW7 is a novel tumor suppressor in T cell leukemia, and implicate the loss of FBW7 function as a potential mechanism of drug resistance in T-ALL.
Diabetes, major depression, and functional disability among U.S. adults.

OBJECTIVE The goal of this study was to determine prevalence and odds of functional disability in individuals with diabetes and comorbid major depression compared with individuals with either diabetes or major depression alone. RESEARCH DESIGN AND METHODS Data on 30,022 adults aged > or = 18 years from the 1999 National Health Interview Survey (NHIS) were analyzed. Four disease categories were created: no diabetes and no major depression, major depression alone, diabetes alone, and diabetes and comorbid major depression. Prevalence of functional disability was calculated for each disease category. Multiple logistic regression was used to determine the odds and correlates of functional disability by disease category controlling for age, sex, race/ethnicity, education, income, census region, and disability-associated comorbidity. STATA was used for all analyses to account for the complex survey design of NHIS. RESULTS Irrevalence of functional disability by disease category was as follows: no diabetes and no major depression (24.5%); major depression (51.3%); diabetes (58.1%); and diabetes and comorbid major depression (77.8%). With no diabetes and no major depression as reference and after adjusting for relevant covariates, the odds of functional disability was 3.00 (95% CI 2.62-3.42) for major depression, 2.42 (2.10-2.79) for diabetes, and 7.15 (4.53-11.28) for diabetes and comorbid major depression. CONCLUSIONS Individuals with diabetes and comorbid major depression have higher odds of functional disability compared with individuals with either diabetes or major depression alone. Additional studies are needed to establish a causal relationship.
L’approche territoriale du " développement durable ", condition d’une prise en compte de sa dimension sociale

Apres une longue periode de scepticisme ou d’indifference, le "developpement durable" commence aujourd’hui a susciter une certaine curiosite bienveillante, et a influencer, de maniere plus ou moins concrete, les pratiques des entreprises ou des institutions publiques. C’est en particulier le cas dans les domaines de l’amenagement du territoire et des politiques urbaines et locales – ou l’on constate que cette preoccupation est en effet progressivement integree ; souvent sous la pression des realites de terrain ou des evenements – comme la catastrophe recente de Toulouse, mais aussi sous l’impulsion conjointe des gouvernements, des autorites locales ou meme, de plus en plus, des instances europeennes ou internationales.
Automatic Induction of Projection Pursuit Indices

Projection techniques are frequently used as the principal means for the implementation of feature extraction and dimensionality reduction for machine learning applications. A well established and broad class of such projection techniques is the projection pursuit (PP). Its core design parameter is a projection index, which is the driving force in obtaining the transformation function via optimization, and represents in an explicit or implicit way the user's perception of the useful information contained within the datasets. This paper seeks to address the problem related to the design of PP index functions for the linear feature extraction case. We achieve this using an evolutionary search framework, capable of building new indices to fit the properties of the available datasets. The high expressive power of this framework is sustained by a rich set of function primitives. The performance of several PP indices previously proposed by human experts is compared with these automatically generated indices for the task of classification, and results show a decrease in the classification errors.
Inducible Synthesis of Bacterial Luciferase: Specificity and Kinetics of Induction

A nitrate-utilizing strain of marine bacteria was isolated in which luciferase was inducible by l-arginine. The induction was highly specific; structural analogues of arginine were ineffective, as were other natural amino acids. Several metabolites of arginine acted as weak inducers but did not affect the rate of induction in limiting concentrations of arginine. Hence, these compounds probably exerted a sparing effect on intracellular arginine. The kinetics of induction were followed by measurement of light output from intact cells, under conditions in which in vivo light output was determined only by the luciferase level. No enzyme appeared in the cells for 12 min after the addition of inducer, although the primary structure of the luciferase molecule was apparently synthesized within 2 to 4 min. It is proposed that during the remaining 8 to 10 min a precursor of luciferase was converted to active enzyme. The differential rate of synthesis rose during the first 5 min of induction, apparently as messenger ribonucleic acid accumulates in the cells; thereafter it remained constant for approximately 100 min.
Krill herd based clustering algorithm for wireless sensor networks

Wireless sensor networks are principally categorized by insufficient energy resource. Naturally, communication between the nodes is the utmost energy consuming act that they perform. Hence, development of a well-organized clustering algorithm can play a vital part in enhancing the lifetime of network. Currently, nature inspired methodologies are very common in dealing with it. This work presents a centralized approach that deals with energy-awareness of wireless sensor networks using the Krill Herd algorithm. The performance of the suggested algorithm is assessed with famous clustering protocols. The simulation results show that suggested approach can maximize sensor network lifetime over other algorithms of the same category.
Proteasome inhibitors – molecular basis and current perspectives in multiple myeloma

Inhibition of proteasome, a proteolytic complex responsible for the degradation of ubiquitinated proteins, has emerged as a powerful strategy for treatment of multiple myeloma (MM), a plasma cell malignancy. First‐in‐class agent, bortezomib, has demonstrated great positive therapeutic efficacy in MM, both in pre‐clinical and in clinical studies. However, despite its high efficiency, a large proportion of patients do not achieve sufficient clinical response. Therefore, the development of a second‐generation of proteasome inhibitors (PIs) with improved pharmacological properties was needed. Recently, several of these new agents have been introduced into clinics including carfilzomib, marizomib and ixazomib. Further, new orally administered second‐generation PI oprozomib is being investigated. This review provides an overview of main mechanisms of action of PIs in MM, focusing on the ongoing development and progress of novel anti‐proteasome therapeutics.
Towards a Case-Based Reasoning Method for openEHR-Based Clinical Decision Support

In 2007, a team of informaticians and specialists in dentistry in Sweden started a project to develop a CDSS based on openEHR for an oral disease named dry mouth. Since openEHR is an emerging standard, designing a clinical decision support system (CDSS) based on it is an un-explored research area. According to our findings, so far, very few (almost none) openEHR-based CDSSs have been released. The methodological approach applied in developing an openEHR-based CDSS is presented in this paper. This includes typical activities in developing CDSSs in addition to the activities one needs to carry out in order to develop an openEHR-based system. In the first phase of this project, the focus has been on openEHR archetype design, knowledge acquisition, and choosing a suitable KRR method based on the available legacy patient records, i.e. a knowledge intensive case-based reasoning method, and the extracted general domain knowledge. We also propose an architecture for such a system with the aim of benefiting from the structured openEHR-based patient data in reasoning.
The VacA and the CagA of Helicobacter pylori : Two Multitasking Proteins of a Multitasking Bacterium

Helicobacter pylori infects 50% of the population and 10-20% of the infected individuals develop various gastroduodenal illness, which include gastritis, duodenal ulcer, gastric ulcer, distal gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue lymphoma. The bacterium was classified as type I carcinogen by WHO in 1994. Most of the pathogenic potentials of H. pylori have been attributed to two virulence factors, namely the vacuolating cytotoxin (vacA) and the cytotoxin-associated gene A (cagA). For some geographical regions, however, carrying the virulence specific genes and expressing them may not correlate with the H. pylori associated clinical manifestations. Moreover, most of the H. pylori infections are benign and eradication of the bacterium may increase the probability of having other diseases, like esophageal cancer. The reason for these extreme variations in clinical outcomes in relation to H. pylori infection is unknown, which underscores the need for studying the mechanism of developing these diseases by multidisciplinary approach. Corresponding authors: Santanu Chattopadhyay, Ph. D Microbiome Research Facility, Rajiv Gandhi Centre for Biotechnology, Thycaud Post, Poojappura, Thiruvananthapuram 695 014, Kerala, India. Phone : +91471-2529400 Fax : + 91471-2348096; E-mail: santanu@rgcb.res.in Received Date: June 1, 2015 Accepted Date: June 15, 2015 Published Date: June 19, 2015 Citation: Chattopadhyay, S. , et al. The VacA and The CagA of Helicobacter Pylori: Two Multitasking Proteins of a Multitasking Bacterium. (2015) J Gastrointest Disord Liver Func 1(1): 1-6. www.ommegaonline. com
Horizontal alveolar bone loss: A periodontal orphan

Background: Attempts to successfully regenerate lost alveolar bone have always been a clinician’s dream. Angular defects, at least, have a fairer chance, but the same cannot be said about horizontal bone loss. The purpose of the present study was to evaluate the prevalence of horizontal alveolar bone loss and vertical bone defects in periodontal patients; and later, to correlate it with the treatment modalities available in the literature for horizontal and vertical bone defects. Materials and Methods: The study was conducted in two parts. Part I was the radiographic evaluation of 150 orthopantomographs (OPGs) (of patients diagnosed with chronic periodontitis and seeking periodontal care), which were digitized and read using the AutoCAD 2006 software. All the periodontitis-affected teeth were categorized as teeth with vertical defects (if the defect angle was ≤45° and defect depth was ≥3 mm) or as having horizontal bone loss. Part II of the study comprised search of the literature on treatment modalities for horizontal and vertical bone loss in four selected periodontal journals. Results: Out of the 150 OPGs studied, 54 (36%) OPGs showed one or more vertical defects. Totally, 3,371 teeth were studied, out of which horizontal bone loss was found in 3,107 (92.2%) teeth, and vertical defects were found only in 264 (7.8%) of the teeth, which was statistically significant (P<.001). Search of the selected journals revealed 477 papers have addressed the treatment modalities for vertical and horizontal types of bone loss specifically. Out of the 477 papers, 461 (96.3%) have addressed vertical bone loss, and 18 (3.7%) have addressed treatment options for horizontal bone loss. Two papers have addressed both types of bone loss and are included in both categories. Conclusion: Horizontal bone loss is more prevalent than vertical bone loss but has been sidelined by researchers as very few papers have been published on the subject of regenerative treatment modalities for this type of bone loss. This study should be an impetus for greater attention to an otherwise ubiquitous periodontal challenge.
Generation of immature retinal neurons from proliferating cells in the pars plana after retinal histogenesis in mice with retinal degeneration

Purpose To study the differentiation of immature retinal neurons/retinal precursors in the ciliary epithelium after retinal histogenesis in mice with inherited or acquired retinal degeneration. Methods Immunoreactivity to anti-recoverin, rhodopsin, and Pax6 antibodies and binding to peanut agglutinin were analyzed histologically. The distribution and differentiation of immature retinal neurons/retinal precursors in the ciliary epithelium of mice with inherited (C3H/HeJ) and acquired (C57BL mice injected with 60 mg/kg N-methyl-N-nitrosourea) retinal degeneration were assessed. Proliferating retinal progenitors were labeled with bromodeoxyuridine (BrdU), and they were studied histologically using retinal markers. Results Many cells of rod and cone photoreceptor lineage were identified within the ciliary epithelium of the pars plana in adult mice with inherited retinal degeneration. Tracking experiments using BrdU indicated that some of recoverin-positive cells in the pars plana (approximately 3%) were generated after retinal histogenesis, and few were produced at or after postnatal day 24 (P24). The induction of acquired retinal degeneration in adult wild-type mice (P30) increased the number of BrdU-positve cells by roughly fourfold and recoverin-positive cells by approximately 17-fold in the pars plana. Moreover, some (approximately 1.5%) of the recoverin-positive cells were newly generated from dividing retinal progenitors in the adult pars plana. Conclusions In response to retinal damage, an increased number of immature retinal neurons/retinal precursors was observed in the pars plana of mice with acquired and inherited retinal degeneration. Some of these cells differentiated from proliferating cells even after retinal histogenesis.
Hepatoprotective activity of aerial parts of Otostegia persica against carbon tetrachloride-induced liver damage in rats

Objective: To evaluate the hepatoprotective properties of Otostegia persica (O. persica) ethanol extract on carbon tetrachloride-induced liver damage in rats. Materials and Methods: Fifty adult male Wistar rats were randomly divided into five groups. Group I served as normal control and was given only olive oil intraperitoneally (i.p.). Group II, III, IV, and V were administered CCl4 mixed with olive oil 1:1 (1 ml/kg) i.p., twice a week for 8 weeks. Group II was maintained as CCl4-intoxicated control (hepatotoxic group). Group III, IV, and V received O. persica extract at a dose of 40, 80, and 120 mg/kg for 8 weeks every 48 h orally, respectively. Biochemical parameters including aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TB), albumin (ALB), total protein (TP), and lipid peroxidation marker (Malonaldialdehyde, (MDA) were determined in serum. After 8 weeks, animals were sacrificed, livers dissected out, and evaluated for histomorphological changes. Results: The administration of CCl4 increased AST, ALT, ALP, TB, and MDA in serum but it decreased TP , and ALB compared with normal control. Treatment with O. persica extract at three doses resulted in decreased enzyme markers, bilirubin levels, and lipid peroxidation marker (MDA) and increased TP and ALB compared with CCl4 group. The results of pathological study also support the hepatoprotective effects which were observed at doses of 80 and 120 mg/kg. Conclusion: The results of the present study indicate that ethanol extract of O. persica may have hepatoprotective effect which is probably due to its antioxidant property.
THE EFFECTS OF HEADINGS IN TEXT ON RECALL, SEARCH AND RETRIEVAL

Summary. This paper summarises the results from nine experiments on headings. The experiments centre on three main variables (i) the purpose of the task (recall, search or retrieval from familiar and unfamiliar text); (ii) the position of the headings (marginal or embedded); and (iii) the nature of the headings (statements or questions). The results showed that headings aided recall, search and retrieval from the text used in these experiments, but that the position of the headings (marginal or embedded) had no effect. The kind of headings (questions or statements) had no differential effect with readers of different ability but low-ability participants appeared to do better with headings as questions in the recall tasks.
Factors associated with uptake of measles, mumps, and rubella vaccine (MMR) and use of single antigen vaccines in a contemporary UK cohort: prospective cohort study

Objectives To estimate uptake of the combined measles, mumps, and rubella vaccine (MMR) and single antigen vaccines and explore factors associated with uptake and reasons for not using MMR. Design Nationally representative cohort study. Setting Children born in the UK, 2000-2. Participants 14 578 children for whom data on immunisation were available. Main outcome measures Immunisation status at 3 years defined as “immunised with MMR,” “immunised with at least one single antigen vaccine,” and “unimmunised. ” Results 88.6% (13 013) were immunised with MMR and 5.2% (634) had received at least one single antigen vaccine. Children were more likely to be unimmunised if they lived in a household with other children (risk ratio 1.74, 95% confidence interval 1.35 to 2.25, for those living with three or more) or a lone parent (1.31, 1.07 to 1.60) or if their mother was under 20 (1.41, 1.08 to 1.85) or over 34 at cohort child’s birth (reaching 2.34, 1.20 to 3.23, for ≥40), more highly educated (1.41, 1.05 to 1.89, for a degree), not employed (1.43, 1.12 to 1.82), or self employed (1.71, 1.18 to 2.47). Use of single vaccines increased with household income (reaching 2.98, 2.05 to 4.32, for incomes of ≥£52 000 (€69 750, $102 190)), maternal age (reaching 3.04, 2.05 to 4.50, for ≥40), and education (reaching 3.15, 1.78 to 5.58, for a degree). Children were less likely to have received single vaccines if they lived with other children (reaching 0.14, 0.07 to 0.29, for three or more), had mothers who were Indian (0.50, 0.25 to 0.99), Pakistani or Bangladeshi (0.13, 0.04 to 0.39), or black (0.31, 0.14 to 0.64), or aged under 25 (reaching 0.14, 0.05 to 0.36, for 14-19). Nearly three quarters (74.4%, 1110) of parents who did not immunise with MMR made a “conscious decision” not to immunise. Conclusions Although MMR uptake in this cohort is high, a substantial proportion of children remain susceptible to avoidable infection, largely because parents consciously decide not to immunise. Social differentials in uptake could be used to inform targeted interventions to promote uptake.
The Use of Osteotomies in the Treatment of Asymmetric Ankle Joint Arthritis

Osteoarthrosis (OA) of the ankle joint is common and found in 1% of the world’s population. In contrast to OA of the hip or knee (mainly primary arthritis), the etiology at the ankle is posttraumatic in a large majority of patients. As a result, they become symptomatic 12 to 15 years earlier than arthritic hip or knee patients. This underlines the importance of long-lasting treatment options for this patient group. Surgical treatments for ankle joint arthritis are divided into 2 categories: procedures that preserve the joint and those that do not. Although ankle arthrodesis and total ankle replacement (TAR) show good shortand mid-term results, several complications have been reported in long-term data. For arthrodesis, this may include OA of adjacent joints. The overall survival rate after TAR is around 80% after 10 years, and therefore ankle replacement in many cases does not present a lifelong solution. Two-thirds of the patients with ankle joint arthritis present with an asymmetric wear pattern, for example, more wear on either the medial or the lateral side of their tibiotalar joint. As the ankle is part of a kinematic chain, the intra-articular load distribution is not only influenced by the alignment of the tibiotalar joint itself but is highly dependent on extrinsic forces that are present because of the alignment of the subtalar (ST) joint, the medial column of the foot, and soft tissue balance. The present review provides an overview of the jointpreserving possibilities to balance the forces in the ankle joint by performing osteotomies around the ankle joint.
Characterization of laplacian surface electromyographic signals during isometric contraction in biceps brachii

Surface electromyography (sEMG) is a noninvasive technique for monitoring the electrical activity produced by the muscles. Usually, sEMG is performed by carrying out monopolar or bipolar recordings by means of conventional Ag/AgCl electrodes. In contrast, Laplacian recordings of sEMG could also be obtained by using coaxial ring electrodes. Laplacian recordings increase spatial resolution and attenuate other distant bioelectric interferences. Nevertheless, the spectral characteristics of this kind of recordings have been scarcely studied. The objective of this paper is to characterize the sEMG signals recorded with a Laplacian ring electrode and to compare them with traditional bipolar recordings with disc electrodes. Both kinds of signals were collected simultaneously in two healthy subjects during resting and sustained isometric voluntary contraction activities in biceps brachii. The conducted study computed the cumulative percentage of the power spectrum of sEMG so as to determine the energy bandwidth of the two kinds of recordings and the signal to noise ratio in different bands of the sEMG spectrum. Also, muscle fatigue, a condition when muscle force is reduced, was assessed using indexes from amplitude and frequency domain. The results of this study suggest that Laplacian sEMG has higher spectral bandwidth but a lower signal to noise ratio in comparison to bipolar sEMG. In addition, frequency fatigue indexes showed that Laplacian recording had better response than bipolar recording, which suggests that Laplacian electrode can be useful to study muscular fatigue due to better spatial resolution.