Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Bioinformatics‐Based Identification of EGFR Inhibitor Gefitinib as a Putative Lead Compound for BACE

β‐secretase (BACE‐1) is a potential target for the treatment of Alzheimer's disease (AD). Despite its potential, only few compounds targeting BACE have entered the clinical trials. Herein, we describe the identification of Gefitinib as a potential lead compound for BACE through an integrated approach of structural bioinformatics analysis, experimental assessment and computational analysis. In particular, we performed ELISA and western analysis to assess the effect of Gefitinib using N2a human APP695 cells. In addition, we investigated the binding mechanism of Gefitinib with BACE through molecular docking coupled with molecular dynamics simulations. The computational analyses revealed that hydrophobic contact is a major contributing factor to the binding of Gefitinib with BACE. The results obtained in the study have rendered Gefitinib as a putative lead compound for BACE. Further optimization studies are warranted to improve its potency and pharmacological properties against BACE for potential AD treatment.
The ‘ Nest Egg ’ Effect ? Housing , the Welfare State , and Political Incentives

Whereas the decades from 1960 to 1990 were marked by volatile price and wage fluctuations, since 1990, inflation in the goods and services markets appears to have been tamed. Yet contemporaneously, fluctuations in asset markets, particularly in equities and housing prices have grown substantially, and indeed, are largely thought responsible for the last two recessions. We know surprisingly little about how fluctuations in asset markets affect political behavior, though they have large income effects on consumption and savings. In this paper, I analyze two political effects of price fluctuations in the housing market: firstly the preferences of citizens over welfare spending, and secondly, opportunistic election holding by politicians. We see powerful effects of the housing market both on citizens’ attitude towards policies and on policymakers’ views of when they should subject themselves to the the voting preferences of citizens.
Jumping the ORDER BY Barrier in Large-Scale Pattern Matching

Event-series pattern matching is a major component of large-scale data analytics pipelines enabling a wide range of system diagnostics tasks. A precursor to pattern matching is an expensive ``shuffle the world'' stage wherein data are ordered by time and shuffled across the network. Because many existing systems treat the pattern matching engine as a black box, they are unable to optimizing the entire data analytics pipeline, and in particular, this costly shuffle. This paper demonstrates how to optimize such queries. We first translate an expressive class of regular-expression like patterns to relational queries such that they can benefit from decades of progress in relational optimizers, and then we introduce the technique of abstract pattern matching, a linear time preprocessing step which, adapting ideas from symbolic execution and abstract interpretation, discards events from the input guaranteed not to appear in successful matches. Abstract pattern matching first computes a conservative representation of the output-relevant domain of every transition in a pattern based on the (unary) predicates of that transition. It then further refines these domains based on the structure of the pattern (i.e., paths through the pattern) as well as any of the pattern's join predicates across transitions. The outcome is an abstract filter that when applied to the original stream excludes events that are guaranteed not to participate in a match. We implemented and applied abstract pattern matching in COSMOS/Scope to an industrial benchmark where we obtained up to 3 orders of magnitude reduction in shuffled data and 1.23x average speedup in total processing time.
Optimization Models for Training Belief-Rule-Based Systems

A belief rule-base inference methodology using the evidential reasoning approach (RIMER) has been developed recently, where a new belief rule representation scheme is proposed to extend traditional IF-THEN rules. The belief rule expression matrix in RIMER provides a compact framework for representing expert knowledge. However, it is difficult to accurately determine the parameters of a belief rule base (BRB) entirely subjectively, particularly, for a large-scale BRB with hundreds or even thousands of rules. In addition, a change in rule weight or attribute weight may lead to changes in the performance of a BRB. As such, there is a need to develop a supporting mechanism that can be used to train, in a locally optimal way, a BRB that is initially built using expert knowledge. In this paper, several new optimization models for locally training a BRB are developed. The new models are either single- or multiple-objective nonlinear optimization problems. The main feature of these new models is that only partial input and output information is required, which can be either incomplete or vague, either numerical or judgmental, or mixed. The models can be used to fine tune a BRB whose internal structure is initially decided by experts' domain-specific knowledge or common sense judgments. As such, a wide range of knowledge representation schemes can be handled, thereby facilitating the construction of various types of BRB systems. Conclusions drawn from such a trained BRB with partially built-in expert knowledge can simulate real situations in a meaningful, consistent, and locally optimal way. A numerical study for a hierarchical rule base is examined to demonstrate how the new models can be implemented as well as their potential applications.
Revision Tympanoplasty Using Scar Tissue Graft

Objective: To evaluate the success rate of subcutaneous postsurgical scar tissue as graft material for revision tympanoplasty operations. Study Design: Retrospective case review. Setting: Tertiary referral center. Patients: Thirty-five patients who underwent revision tympanoplasty with or without mastoidectomy procedures and 36 patients undergoing primary operations who had all the data necessary for the study and a minimum follow-up of 6 months. The mean follow-up period was 12 months (range, 6-18 mo). Mean age, perforation size, cholesteatoma presence, time required for harvesting, and adjunctive mastoidectomies were similar between the two groups. Intervention: The patients undergoing revision tympanoplasty had graft material harvested from the subcutaneous scar tissue. In the control group, temporalis fascia graft was used as graft tissue. Main Outcome Measures: The rate of perforation closure and postoperative hearing change was measured. Results: In the scar tissue tympanoplasty group, 32 of 35 patients (91%) had successful closure of the tympanic membrane perforation, whereas in the control group, the success rate was 92% (p > 0.05). Mean postoperative pure-tone average improvement was 21 dB in the scar tissue tympanoplasty group and 18 dB in the control group (p > 0.05). Conclusion: Subcutaneous scar tissue is as successful in perforation closure and hearing improvement as temporalis fascia graft. The use of subcutaneous scar tissue graft is advantageous to other graft materials used in revision tympanoplasty operations in that it can be harvested through the same incision, does not add to the operative time, and does not carry the cost or risk of acellular dermis.
The cross-sectional association between snacking behaviour and measures of adiposity: the Fenland Study, UK

Abstract Unhealthy dietary behaviours may contribute to obesity along with energy imbalance. Both positive and null associations of snacking and BMI have been reported, but the association between snacking and total adiposity or pattern of fat deposition remains unevaluated. The objective of this study was to investigate the associations between snacking frequency and detailed adiposity measurements. A total of 10 092 adults residing in Cambridgeshire, England, self-completed eating pattern snacking frequency, FFQ and physical activity questionnaires. Measurements included anthropometry, body composition using dual-energy X-ray absorptiometry scan and ultrasound and assessment of physical activity energy expenditure using heart rate and movement sensing. Linear regression analyses were conducted adjusted for age, socio-demographics, dietary quality, energy intake, PAEE and screen time by sex and BMI status. Among normal-weight individuals (BMI<25 kg/m2), each additional snack was inversely associated with obesity measures: lower total body fat in men and women (−0·41 (95 % CI −0·74, −0·07) %, −0·41 (−0·67, −0·15) %, respectively) and waist circumference (−0·52 (−0·90, −0·14) cm) in men. In contrast, among the overweight/obese (BMI≥25 kg/m2), there were positive associations: higher waist circumference (0·80 (0·34, 0·28) cm) and subcutaneous fat (0·06 (0·01, 0·110) cm) in women and waist circumference (0·37 (0·00, 0·73) cm) in men. Comparing intakes of snack-type foods showed that participants with BMI≥25 kg/m2 had higher intakes of crisps, sweets, chocolates and ice-creams and lower intakes of yoghurt and nuts compared with normal-weight participants. Adjusting for these foods in a model that included a BMI–snacking interaction term attenuated all the associations to null. Snacking frequency may be associated with higher or lower adiposity, with the direction of association being differential by BMI status and dependent on snack food choice. Improving snack choices could contribute to anti-obesity public health interventions.
Negative impact of bone metastasis on outcome in clear-cell renal cell carcinoma treated with sunitinib.

BACKGROUND The aim of our study was to determine whether the presence of bone metastases affects outcomes in patients with metastatic clear-cell renal cell carcinoma (m-ccRCC) receiving sunitinib. PATIENTS AND METHODS We reviewed the charts of all patients in four academic centers in Belgium and France who started first-line sunitinib (50 mg/day; 4 weeks on and 2 weeks off) between January 2005 and December 2008. Data were collected on known prognostic factors for metastatic renal cell carcinoma and metastatic sites. Response and progression were evaluated by computed tomography scan (according to RECIST). RESULTS Two hundred twenty-three patients were identified. With a median follow-up of 40 months, median progression-free survival (PFS) and median overall survival (OS) were significantly shorter in patients with bone metastases than in those without: respectively, 8.2 versus 19.1 months (P<0.0001) and 19.5 versus 38.5 months (P<0.0001). On multivariate analysis, taking on account platelet count, Eastern Cooperative Oncology Group performance status, number of metastatic sites, neutrophil count, corrected serum calcium, time from diagnosis to systemic treatment, and the presence of bone metastases, bone metastasis was the independent variable most significantly associated with poor PFS (P<0.0001) and OS (P=0.001). CONCLUSION The presence of bone metastases in m-ccRCC patients has a significant and clinically relevant negative impact on outcome on sunitinib.
Mapping of the basal forebrain cholinergic system of the dog: A choline acetyltransferase immunohistochemical study

In an effort to produce a canine model of basal forebrain ischemia with memory deficits, we have shown that dogs possess a medial striate artery that perfuses basal forebrain territory, homologous to the human recurrent artery of Heubner. In the present study, we set out to delineate the precise topography of the cholinergic neurons in the canine forebrain, a neuronal system implicated in cognitive and memory functions. Floating coronal sections, derived from the head of the caudate nucleus to the rostral border of the hippocampus, were stained for choline acetyltransferase using a monoclonal antibody. Representative sections from one dog brain were drawn. These outlines were used for measurement of cell density, cell size, number of processes, and cell roundness. Choline acetyltransferase‐positive neurons constituted four major subdivisions within the basal forebrain. A relatively dense population of cholinergic neurons was present in the medial septal nucleus (Ch1). A continuum of densely packed cells was also delineated within the vertical (Ch2) and horizontal (Ch3) nuclei of the diagonal band of Broca. A fourth group of heterogeneously packed cholinergic neurons represented the nucleus basalis magnocellularis (Ch4). Except for the caudal component of the Ch4 population, the forebrain cholinergic corticopetal system was located within the perfusion territory of the medial striate arteries. The Ch4 cell group in dogs is better defined than that of rodents but is not as sharply demarcated as in human and nonhuman primates. Our findings indicate that the dog may serve as an excellent model for assessing neurological and memory deficits, which, in humans, results from hypoperfusion of the recurrent artery of Heubner. © 1996 Wiley‐Liss, Inc.
Pseudozyma aphidis induces ethylene-independent resistance in plants

Species of the epiphytic fungus Pseudozyma are not pathogenic to plants and can be used as biocontrol agents against plant pathogens. Deciphering how they induce plant defense might contribute to their use for plant protection and expand our understanding of molecular plant–pathogen interactions. Here we show that Pseudozyma aphidis isolate L12, which is known to induce jasmonic acid- and salicylic acid-independent systemic resistance, can also activate local and systemic resistance in an ethylene-independent manner. We also show that P. aphidis localizes exclusively to the surface of the plant leaf and does not penetrate the mesophyll cells of treated leaves. We thus propose that P. aphidis acts via several mechanisms, and is an excellent candidate biocontrol agent.
MultiView model for object-oriented database

Up till now, a few secure models of object oriented databases have been proposed. Most of them support multilevel entities and more or less cover stories. In this paper, we undertake a more natural approach to model object oriented databases supporting multilevel entities which cope with the shortcomings of the previous models, viz the need of trusted mechanisms, the management of polyinstantiated objects and the inconsistency it may introduce in the database. The central idea is to decompose a multilevel object oriented database into a collection of single level databases. Hence, we split up the real universe into worlds corresponding to each security level. These worlds are the views of the universe by users at the corresponding levels, that was the reason of "MultiView" appellation. We present an animation of the MultiView model through creation, updating and consultation of objects. We show how we make use of cover stories without any specific problem. We also give a comparison with previous work and show how difficulties encountered in the earlier models can be avoided by the MultiView model. <<ETX>>
Treatment of plaque psoriasis with the two-compound product calcipotriol/betamethasone dipropionate versus both monotherapies: An immunohistochemical study

The combination of calcipotriol (Cp) and topical corticosteroids increases efficacy and reduces side effects as compared to monotherapies. Previous studies suggest that such combinations may have an added value with respect to reduction of T-cell subsets. A two-compound product consisting of Cp and betamethasone dipropionate (BD) has become available for the treatment of psoriasis and is clinically superior to both monotherapies. No immunohistochemical data are available on the in vivo effects of the two-compound formulation versus monotherapy with respect to the three key processes in psoriasis pathogenesis: epidermal proliferation, epidermal differentiation and inflammation. Therefore, 18 patients were treated with the two-compound product, Cp monotherapy or BD monotherapy for 6 weeks and biopsies were taken before and after 4 and 6 weeks of treatment. These biopsies were stained immunohistochemically and analysed (semi)quantitatively. All treatments decreased the number of Ki-67+ cells and increased the keratin 15+ staining. A more pronounced reduction of epidermal and dermal T-cell markers and human beta defensin-2 was seen following combination treatment, compared with both monotherapies. In conclusion, the investigated markers of the skin immune system and epidermal proliferation indicated an added value of the two-compound product over both monotherapies.
Determining the Identity and Structure of Recombinant Proteins

In this unit peptide mapping protocols with separation of the constituent peptides by high‐performance liquid chromatography (HPLC) analysis and by high‐resolution SDS‐PAGE are presented. Peptide mapping is ideally suited for comparative purposes‐‐for example, combined analysis of the recombinant protein and its natural counterpart (or some other well‐characterized standard). This unit also outlines the general strategy used to determine the linkage pattern of a monomeric recombinant protein containing two intramolecular disulfide bonds. The approach is an extension of peptide mapping, where the aim is to isolate and characterize peptides containing only a single disulfide bond. A two‐dimensional electrophoretic method is also described in which the protein isoelectric point is displayed as a function of pH to yield an electrophoretic titration curve. This method is especially useful for checking for deamidation (e.g., of Asn to Asp) in which additional negative charge is introduced into the modified protein.
Induction of Estrogen Receptor α Expression with Decoy Oligonucleotide Targeted to NFATc1 Binding Sites in Osteoblasts

The nuclear factor of activated T cell cytoplasmic 1 (NFATc1) is a member of the NFAT family and is strictly implicated in the growth and development of bone. Most studies have focused on the effects of NFATc1 activation on osteoclastogenesis. On the contrary, the specific roles of NFAT in osteoblast differentiation are not well understood and, in some instances, reports of its role are contradictory. In the present study, we demonstrated that NFATc1 was involved in the transcriptional regulation of human estrogen receptor α (ERα) gene in SaOS-2 osteoblastic like cells. NFATc1 was specifically recruited “in vivo” at C and F distal promoters of ERα gene. In addition, it is here identified as the negative transcription factor removed by the RA4-3′decoy oligonucleotide able to induce ERα expression in osteoblasts. Ca2+/calcineurin-NFAT-mediated signaling pathways and ERα-dependent signals are involved in diverse cellular reactions by regulating gene expression under both physiological and pathological conditions. Therefore, our data might be useful for proper manipulation of NFATc1- and ERα-mediated cellular reactions in different bone disorders, such as osteoporosis.
Nerve Growth Factor Receptors on Dissociated Neurofibroma Schwann-like Cells 12

Neurofibromatosis is a disorder which predominantly involves cellular elements of peripheral neural sheaths. Little is known about the regulation of differentiation and proliferation of cells comprising neurofibromas. Because nerve growth factor-like ac tivity may be present in neurofibromas and the cells comprising neurofibromas are neural crest derivatives, we have investigated whether nerve growth factor (NGF) receptors are present on cells from dissociated dermal neurofibromas. Using 125I-NGFto measure binding to cultured cells in suspension and for autoradiography, we identified a population of cells having character istics of Schwann cells which exhibited saturable 125I-NGFbind ing. This binding is characteristic of the "fast" (low affinity) NGF receptor, having a Ka of approximately 1 nM and a Bmaxof at least 120 fmol/106 cells. Less than 20% of the bound 125I-NGF (5 ng/ml) is not displaced when transferred to 0Â°Cby an excess of unlabeled NGF (10 u.g/m\) and is therefore bound to either "slow" (high affinity) sites or is rapidly internalized. NGF receptors with characteristics of fast sites have recently been reported on Schwann-like cells from chick dorsal root ganglia [Zimmerman, A. , and Sutler, A. Beta nerve growth factor (beta NGF) receptors on glial cells. Cell-cell interaction between neurones and Schwann cells in culture of chick sensory ganglia. EMBO J., 2: 879-885, 1983]. The identification of NGF receptors on both fetal chick dorsal root ganglia and neurofibroma Schwann-like cells suggests that NGF may have a role in the regulation of Schwann cell function in both normal development and in neu-
A case study of Short Term Cell-Flipping technique for mitigating NBTI degradation on cache

Negative Bias Temperature Instability (NBTI) is one of the major reliability problems in advanced technologies. NBTI causes threshold voltage shift in a PMOS transistor which is biased to negative voltage. In an SRAM cell, due to NBTI, threshold voltage shifts in the load transistors. The degradation has the impact on Static Noise Margin (SNM), which is a measure of read stability of a 6-T SRAM cell. Because an SRAM cell consists of two inverters, one of the load transistors is always stressed. In order to mitigate NBTI degradation, we proposed Short Term Cell-Flipping technique (STCF) for SRAM cell. This technique makes the stress probability on load transistors in an SRAM cell close to 50%. In this paper, we apply STCF technique to cache memories, and discuss its potential to mitigate NBTI degradation.
Salvia miltiorrhiza ) extract attenuates hepatic injury in Isoniazid induced hepatotoxicity in rats

Oxidative stress is suggested as a mechanism underlying diabetes mellitus complications. The main objective of this study was to investigate the effect of sage leaves extract on oxidative stress of hepatic tissue in isoniazid-induced diabetic rats. The lipid peroxidation product, malondialdehyde (MDA) and reduced glutathione (GSH) content was measured to assess free radical activity in the liver tissues. The enzymatic activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) were measured as indicators of antioxidation in liver tissue. Wistar rats were made diabetic with a single injection of STZ (75 mg/kg i.p.). Rats were randomly separated into four groups, of 10 animals each: Group 1, healthy control rats; Group 2 non-diabetic rats treated with 50 mg/kg b.w. /day intraperitoneal injection of sage extract; Group 3, diabetic rats; Group 4, diabetic rats treated with sage extract (50 mg/kg b.w./day, i.p.) for 8 weeks. At the end of experiment, MDA contents of the liver tissue in Groups 3 was found to be significantly increased as compared with Group 1 (P<0.05) and liver MDA level in Group 4 were significantly decreased as compared with Group 3 (P<0.05). The GSH, SOD, CAT and GSH-Px contents of the liver in Group 3 were significantly decreased as compared to Groups 1 (P<0.05) and were increased in Group 4 as compared to Group 3 (P<0.05). The results obtained, demonstrated that sage extract alleviate oxidative stress of hepatic tissue in streptozotocin-induced diabetic rats. [Eilyad Issabeagloo, Mohammad Taghizadieh, Jafar Asadi. Sage leaves (Salvia miltiorrhiza) extract attenuates hepatic injury in Isoniazid induced hepatotoxicity in rats. Life Sci J 2013;10(6s):495-500] (ISSN:1097-8135). http://www.lifesciencesite. com. 76