Miracle-dz/UniFAR-FTUs huggingface dataset:
Celecoxib analogs that lack COX-2 inhibitory function: preclinical development of novel anticancer drugs

Celecoxib is an NSAID that was developed as a selective inhibitor of COX-2 and approved by the FDA for the treatment of various forms of arthritis and the management of acute or chronic pain. In addition, it was more recently approved as an oral adjunct to prevent colon cancer development in patients with familial adenomatous polyposis and is presently being investigated for its chemotherapeutic potential in the therapy of advanced cancers. However, in laboratory studies it was discovered that celecoxib was able to suppress tumor growth in the absence of any apparent involvement of COX-2, and additional pharmacologic activities associated with this drug were found. Intriguingly, the two pharmacologic effects, inhibition of COX-2 and suppression of tumor growth, were found to reside in different structural aspects of the celecoxib molecule and, therefore, could be separated. This dualism enabled the synthesis of close structural analogs of celecoxib that exhibited increased antitumor potency in the absence of COX-2 inhibition. In theory, such compounds should be superior to celecoxib for antitumor purposes because they might reduce gastrointestinal and cardiovascular risks and the life-threatening side effects that appear during the long-term use of selective COX-2 inhibitors. In this review, the authors present the status of preclinical development of anticancer analogs of celecoxib that are COX-2 inactive, with an emphasis on 2,5-dimethyl-celecoxib (DMC) and OSU-03012.
Impact of irrigation water scarcity on rural household food security and income in Pakistan

As Pakistan is currently facing a severe shortage of irrigation water, this paper analyzes the determinants of water scarcity and its impact on the yield of cereal crops (wheat, maize and rice), household income, food security and poverty levels by employing the propensity-score-matching approach. This study is based on a comprehensive set of cross-sectional data collected from 950 farmers from all four major provinces in Pakistan. The empirical analysis indicated that farmers with a water-scarcity problem have lower yield and household income, and are food insecure. Poverty levels were higher: in the range of 7–12% for a household facing a water-scarcity problem. The policy implications of the study are that the public and private sector in Pakistan needs to invest in irrigation water management to maintain the productivity of cereal crops which is important for household food security and poverty reduction.
Effects of Hemp seed soft capsule on colonic ion transport in rats

AIM To investigate the effect of Hemp seed soft capsule (HSCC) on colonic ion transport and its related mechanisms in constipation rats. METHODS Sprague-Dawley male rats were randomly divided into three groups: normal group, constipation group and HSSC group. Rats in the constipation and HSSC groups were administrated loperamide 3 mg/kg per day orally for 12 d to induce the constipation model. Then, the HSSC group was given HSSC 0.126 g/kg per day by gavage for 7 d. The normal and constipation groups were treated with distilled water. After the treatment, the fecal wet weight and water content were measured. The basal short-circuit current (Isc) and resistance were measured by an Ussing Chamber. Besides the in vivo drug delivery experiment above, an in vitro drug application experiment was also conducted. The accumulative concentrations of HSSC (0.1 mg/mL, 0.5 mg/mL, 1.0 mg/mL, 2.5 mg/mL, 5.0 mg/mL, 10.0 mg/mL and 25.0 mg/mL) were added to the normal isolated colonic mucosa and the Isc was recorded. Further, after the application of either ion (Cl- or HCO3-) substitution, ion channel-related inhibitor (N-phenylanthranilic acid, glybenclamide, 4,4-diisothiocyano-2,2-stilbenedisulfonic acid or bumetanide) or neural pathway inhibitor [tetrodotoxin (TTX), atropine, or hexamethonium], the Isc induced by HSSC was also measured. RESULTS In the constipation group, the fecal wet weight and the water content were decreased in comparison with the normal group (P < 0.01). After the treatment with HSSC, the fecal wet weight and the water content in the HSSC group were increased, compared with the constipation group (P < 0.01). In the constipation group, the basal Isc was decreased and resistance was increased, in comparison with the normal group (P < 0.01). After the treatment with HSSC, the basal Isc was increased (P < 0.05) and resistance was decreased (P < 0.01) in the HSSC group compared with the constipation group. In the in vitro experiment, beginning with the concentration of 1.0 mg/mL, differences in Isc were found between the experimental mucosa (with HSSC added) and control mucosa. The Isc of experimental mucosa was higher than that of control mucosa under the same concentration (1.0 mg/mL, P < 0.05; 2.5-25 mg/mL, P < 0.01). After the Cl- or HCO3- removal and pretreated with different inhibitors (cAMP-dependent and Ca2+-dependent Cl- channels, Na+-K+-2Cl- cotransporter (NKCC), Na+-HCO3- cotransporter or Cl-/HCO3- exchanger inhibitor), there were differences between experimental mucosa and control mucosa; the Isc of experimental mucosa was lower than that of control mucosa under the same concentration (P < 0.05). Meanwhile, after pretreatment with neural pathway inhibitor (TTX, atropine, or hexamethonium), there were no differences between experimental mucosa and control mucosa under the same concentration (P > 0.05). CONCLUSION HSSC ameliorates constipation by increasing colonic secretion, which is mediated via the coaction of cAMP-dependent and Ca2+-dependent Cl- channels, NKCC, Na+-HCO3- cotransporter or Cl-/HCO3- exchanger.
Introducing enteral feeding induces intestinal subclinical inflammation and respective chromatin changes in preterm pigs.

AIM To analyze how enteral food introduction affects intestinal gene regulation and chromatin structure in preterm pigs. MATERIALS & METHODS Preterm pigs were fed parenteral nutrition plus/minus slowly increasing volumes of enteral nutrition. Intestinal gene-expression and chromatin structure were analyzed 5 days after birth. RESULTS Enteral feeding led to differential upregulation of inflammatory and pattern recognition receptor genes, including IL8 (median: 5.8, 95% CI: 3.9-7.8 for formula; median: 2.2, 95% CI: 1.3-3.3 for colostrum) and TLR4 (median: 3.7, 95% CI: 2.6-4.8 for formula; no significant differences for colostrum) with corresponding decondensed chromatin configurations. On histology this correlated with mild mucosal lesions, particularly in formula-fed pigs. In CaCo-2 cells, histone hyperacetylation led to a marked increase in TLR4 mRNA and increased IL8 expression upon stimulation with lipopolysaccharide (median: 7.0; interquartile range: 5.63-8.85) compared with naive cells (median 4.2; interquartile range: 2.45-6.33; p = 0.03). CONCLUSION Enteral feeding, particular with formula, induces subclinical inflammation in the premature intestine and more open chromatin structure in key inflammatory genes. This may increase the susceptibility for necrotizing enterocolitis.
Contract as Evil

Contract is, of course, often good. It permits parties to negotiate terms that are specific to their needs, something statutes can’t do. But contract is often evil and used for evil ends, particularly because much of contract theory and doctrine is unconcerned with the distribution of power; information and shrewdness between the parties and is based, in part, on a romantic view of contract, emphasizing its basis in free will and liberty. This almost deification of Contract blinds those who follow it to the very absence of free will and liberty when the ability to deal in contract is unbalanced. The current dialogue about contracts of adhesion and the question whether they should even be considered contracts requires us to take a new look at contract. The use of contract to limit constitutional and other rights based on a notion of voluntary waiver raises serious issues about whether we should be skeptical about the assumed good of contract. We need contracts, but we need also to rethink what we mean by contract and whether the formalistic conservative libertarian approach to it needs to be reined in.This Article looks at Margaret Jane Radin’s argument that adhesion contracts are not really contracts and should be treated more through tort law, and looks briefly at the progression of product liability from contract to tort to strict liability. The Article also consider whether the model of agency regulation should be applied when traditional contract reasoning is overwhelmed by the actual facts of a supposed bargain. The Article then examines judicial approval through contract reasoning of unfair or even dishonest conduct in a number of quite different contexts. Sometimes the good guys win, but too often they don’t because contract is said to beat them.Contract often aids evil. Government regulation — thoughtful but serious regulation by Congress, legislatures, administrative agencies and courts — is not antithetical to freedom of contract. It is needed to protect those who lack power and skill and consequently, the very free will and liberty that are supposedly the basis of contract.
Student learning strategies, mental models and learning outcomes in problem-based and traditional curricula in medicine

Kelson and Distlehorst (2000) state the PBL outcomes should be discussed on a broad basis including a useable knowledge base, skills in problem solving, self-directed learning and collaboration. The present research compares students in a PBL programme and in a traditional program on learning strategies, mental models and outcomes. Learning strategies and metal models of learning were measured for two student groups in 2001 using an adaption of Vermunt's (1994) “Inventory of learning styles”. Learning outcomes were measured for the same groups in 2002 using a test of medical knowledge. PBL-students showed significantly more self-regulated learning and more constructive conceptions of learning. No significant differences in learning outcomes were found between the two groups. Students in the PBL-programme perceived students as more active contributors to group learning process and made use of a broader range of resources than students in the traditional programme. The findings confirm effects of educational programmes on student learning strategies (Vermetten 1999) and also confirm lack of significant differences in medical knowledge (Albanese 2000, Colliver 2000, Norman & Schmidt 2000, Wiers-Jensen & Aasland ). The curricular influence on students' learning strategies challenges educators to design approaches that promote lifelong learning skills as well as disciplinary knowledge. Practice points•Problem-based programmes can affect student learning strategies and mental models of learning. •Problem-based programmes can promote more active engagement in group activities than traditional programmes. •Problem-based learning can promote more active and broad use of resources than traditional programmes. •Self-regulated learning and constructive conception of learning may be promoted through educational activities. •Future studies of differences between students in problem-based and traditional programmes should consider a broad scope of learning outcomes.
Information retrieval in context - IRiX: workshop at SIGIR 2004 - Sheffield

There is a growing realisation that relevant information will be accessible increasingly across media and genres, across languages and across modalities. The retrieval of such information will depend on time, place, history of interaction, task in hand, and a range of other factors that are not given explicitly but are implicit in the interaction and ambient environment, namely the context. IR research is now conducted in multimedia, multi-lingual, and multi-modal environments but largely out of context (Jarvelin & Ingwersen, 2004; Ingwersen & Jarvelin, forthcoming). However, such contextual data can be used effectively to constrain retrieval of information thereby reducing the complexity of the retrieval process. To achieve this, context models for different modalities will need to be developed so that they can be deployed effectively to enhance retrieval performance. Thus truly context-aware and -dependent retrieval will become feasible.
Performance analysis of cognitive two-way AF relaying systems with wireless energy harvesting over Nakagami-m fading channels

Wireless energy harvesting (EH) is regarded as a promising energy supply alternative for energy-constrained wireless networks. In this paper, a new wireless EH protocol is proposed for an underlay cognitive radio (CR) network with multiple transceivers in a primary network (PN). Utilizing two-way amplify-and-forward (AF) relaying system as a secondary network (SN), both end-sources can harvest energy from relay. Closed-form expression for outage probability (OP) of this system is derived by considering CR interference temperature over independent and non-identically distributed (i.n.i.d.) Nakagami-m fading channels. To simplify our analysis, we consider the asymptotically low outage regime and derive the OP at high signal-to-noise-ratios (SNRs). The numerical results have demonstrated that the wireless EH, compared to the conventional scenarios, enhances the outage performance significantly.
Association between BclI polymorphism in the NR3C1 gene and in vitro individual variations in lymphocyte responses to methylprednisolone.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT In vitro lymphocyte steroid sensitivity has been suggested as a useful tool to predict in vivo response to glucocorticoid treatment in different inflammatory chronic diseases. A correlation between genetic polymorphisms and clinical response to glucocorticoids has been demonstrated in these patients. WHAT THIS STUDY ADDS The BclI polymorphism in the glucocorticoid receptor (NR3C1) gene is associated with higher methylprednisolone potency in vitro. The combined evaluation of the in vitro sensitivity to methylprednisolone and BclI polymorphism could represent an aid for physicians to adjust therapy a priori. AIM To evaluate the association between the in vitro sensitivity of peripheral blood mononuclear cells (PBMCs) to methylprednisolone (MP) and the presence of genetic polymorphisms involved in glucocorticoid (GC) response. METHODS In vitro MP inhibition of the proliferation of lymphocytes stimulated with concanavalin A was determined. Non linear regression of dose-response data was performed computing the MP concentration required to reduce proliferation to 50% (IC(50) ). The maximum inhibition achievable at the highest MP concentration (I(max) ) was also calculated. Moreover, the Taqman technique was used to analyze the BclI polymorphism in the NR3C1 gene and the Leu155His polymorphism in the NALP1 gene. RESULTS A significant association between the BclI mutated genotype and an increased in vitro sensitivity to GCs was observed. CONCLUSIONS The a priori evaluation of the BclI polymorphism, associated with a lymphocyte proliferation assay, could represent a useful diagnostic tool for the optimization of steroid treatment.
HAVE LARGE BUDGET DEFICITS CAUSED RISING TRADE DEFICITS

For the United States, the 1980s have been years of both large and unprecedented trade deficits as well as massive federal budget deficits. The trade deficit rose from $25 billion in 1980 to $124 billion in 1985. During this same period, federal budget deficits soared from $74 billion in 1980 to more than $212 billion in 1985. It is widely believed that the U.S. trade deficit rose mainly because of the skyrocketing federal budget deficit. Presenting such a view are, for example, Hutchison and Pigott [25], Hutchison and Pyle [26], Clark [11], Modigliani [30], and Aschauer [2]. Besides economists, many labor unions (i.e., AFL-CIO) and official government documents (see, The Economic Report of the President, particularly of 1984) have all shared similar views. ' The issues involved have important policy implications. Suppose that the basic reason for rising trade deficits is indeed the escalating federal budget deficit. In this case, policy makers may focus on curtailing the budget deficit in order to resolve the trade deficit problem that has adversely affected several sectors such as manufacturing industries and agriculture. However, if such a view concerning the "causal" role of the budget deficit is incorrect, then reductions in the federal budget deficit may not resolve the trade deficit dilemma and, moreover, attention will be diverted from more relevant and urgently needed policy options [6]. The purpose of this paper is to empirically investigate the conventional argument that high federal budget deficit has been the prime "cause" of the escalating U.S. trade deficit, finding only partial empirical evidence to support it. In section II, I argue that most of previous studies in this area appear flawed by a methodological error rendering their tests unreliable for discriminating between a number of equally plausible hypotheses. Section III describes the data and methodology used in the paper. Section IV presents the empirical results. Section V summarizes and concludes the paper.
Atherogenic Lipoproteins Enhance Murine Cortical Epithelial Cell Fibronectin Protein Synthesis and Gene Expression

Tubulointerstitial changes, characterized by the accumulation of extracellular matrix proteins (ECM) and fibrosis, are often associated with primary glomerular injury. Furthermore, these changes may be better prognostic indicators for decline in renal function than the anatomical changes seen within the glomerulus itself. Although hyperlipidemia and the increased renal accumulation of atherogenic lipoproteins are commonly seen in both human and experimental models of renal disease, the possible role that atherogenic lipoproteins may play in the cellular and molecular events associated with the development of tubulointerstitial injury remains unclear. Since atherogenic lipoproteins have been shown to be mediators of renal injury, we examined the effects of native LDL and oxidatively-modified LDL (ox-LDL, a more atherogenic form of LDL) on fibronectin protein synthesis and gene expression in proximal tubular epithelial cells (TEC). Human LDL was freshly isolated and ox-LDL prepared by incubation of LDL with 100 µM CuSO4. Incubation of TEC with LDL or ox-LDL (25–50 µg/ml) for 24 h increased the steady-state mRNA expression of fibronectin by 16–135% over control as measured by Northern blot analysis and the effect was greater with ox-LDL than native LDL. Additional studies were done to examine whether the increased fibronectin message in response to lipoprotein activation was translated into TEC protein synthesis. The activation of TEC by LDL or ox-LDL stimulated the synthesis and secretion of fibronectin (52–150%, over control) as measured by Western blot analysis. The data show that LDL and ox-LDL stimulate TEC fibronectin gene message and protein synthesis supporting a pathobiological role for these atherogenic lipoproteins in tubulointerstitial fibrosis.
Association of shorter telomere length with essential hypertension in Indian population

Essential hypertension is known to be associated with growth, development, and aging of humans. Telomeres are specialized nucleoprotein complexes consisting of tandem repeats of DNA sequences (TTAGGG)n that serve as protective caps of human chromosomes. Telomere length is considered as a biomarker of aging in somatic cells. In the present investigation, leukocyte telomere length was determined among hypertensive and normal individuals to find out the association, if any, with hypertension.
Effects of time and temperature during attachment of sections to microscope slides on immunohistochemical detection of antigens

To study the effects of time and temperature on attachment of tissue sections to microscope slides, we examined the intensity of immunohistochemical staining of selected antigens in nine different neoplastic and normal tissues after attaching sections at different times and temperatures. Typically, both the temperature and time are minimized when tissue sections attached to slides; however, suboptimal times and temperatures during attachment may result in either loss of tissue due to poor attachment or the necessity for inconvenient staining regimens. Using standard immunohistochemical techniques, 5 μm tissue sections were attached at 58°C for 1, 4 and 24 hr. In a separate study, 5 μm tissue sections were attached for 16 hr at 58, 68 and 80°C. The intensity of staining decreased slightly when the tissue sections were heated at 80°C for 16 hr, but there was little or no decrease when tissues were heated at 6°C or lower for 16 hr, or at 58°C for up to 24 hr.
Who are the Eurofittest?

INTRODUCTION Despite several studies highlighting differences in aerobic test performance among age-matched children and adolescents from different countries, little is known about the geographic variability in children's performances on tests measuring other fitness components. By cumulating studies reporting Eurofit data for children and adolescents, the aim of this study was to describe the variability in fitness test performance among children and adolescents from different parts of Europe. METHODS Sixty-seven studies reporting on the Eurofit test performances of healthy European children and adolescents were included in the analysis. Following corrections for methodological variation where appropriate, all data for each test were expressed in a common metric. Raw data were combined with pseudodata generated using Monte Carlo simulation. Performances on each fitness test were expressed as z-scores relative to all children of the same age and sex from all countries. For each Eurofit test, sample-weighted mean z-scores were calculated for each country across all age x sex groups for which data were available. RESULTS Data were collated on 1,185,656 Eurofit test performances by 7- to 18-year-old Europeans from 23 countries. There was considerable variability in the mean z-scores among countries, with the variability among countries differing by test. Overall, the best performing children came from northern and central European countries (0.3-0.4 standard deviations above the overall European average). DISCUSSION/CONCLUSION There is evidence that performance was related to socio-cultural factors, such as the place of exercise and sport in the national psyche.
Dynamic matrix predictive control on DC-AC modular multilevel converter: Design, control and real-time simulation

This paper presents an indirect model predictive control to develop a direct power regulator for a modular multilevel converter connected to a high voltage direct current bus line, where the main task is to bidirectionally transfer active power to the grid and simultaneously compensate reactive power. The main advantage, of the proposed dynamic matrix control methodology, is to capture the system dynamics instated of use a mathematical model with the purpose of dealing with some issues like coupled variable states and non-minimum phase behavior. The use of long-length horizons as well as the low control frequency are other relevant characteristics. Other essential part of the control scheme is the nearest level modulation technique that together with the phase disposition pulse-width modulation allow to naturally balance the capacitor voltages of the converter. In order to illustrate the performance of all stages and the viability of controlling a high combinational converter with a predictive methodology, the full power converter, the modulation technique and the control scheme are tested on the real-time simulation environment OPAL-RT. ®.