Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of UGT1A1 genotype on the pharmacokinetics, pharmacodynamics, and toxicities of belinostat administered by 48‐hour continuous infusion in patients with cancer

The histone deacetylase inhibitor belinostat is eliminated through glucuronidation by UGT1A1. Polymorphisms that reduce UGT1A1 function could result in increased belinostat exposure and toxicities. We wanted to determine which single‐nucleotide polymorphisms alter belinostat exposure and toxicity. In a phase 1 trial (belinostat over 48 hours in combination with cisplatin and etoposide), belinostat (400, 500, 600, or 800 mg/m2/24 h, 48‐hour continuous infusion) was administered to patients with cancer in combination with cisplatin and etoposide (n = 25). Patients were genotyped for UGT1A1 variants associated with reduced function: UGT1A1*6, UGT1A1*28, and UGT1A1*60. End points were associations between UGT1A1 genotype and belinostat pharmacokinetics (PK), toxicities, and global protein lysine acetylation (AcK). Belinostat AUC was increased (P = .003), and t1/2 increased (P = .0009) in UGT1A1*28 and UGT1A1*60 carriers who received more than 400 mg/m2/24 h. The incidence of grades 3–4 thrombocytopenia (P = .0081) was associated with UGT1A1 polymorphisms. The US Food and Drug Administration–approved package insert recommends dose adjustment of belinostat for UGT1A1*28. However, our data suggest dose adjustment is also necessary for UGT1A1*60. UGT1A1 polymorphisms were associated with increased systemic belinostat exposure, increased AcK, and increased incidence of toxicities, particularly at doses > 400 mg/m2/24 h.
Complement Components in Normal Serum and Plasma Quantitated by Electroimmunoassay

The concentrations of Clq, Cls, C3, C4, C5, C3 proactivator, and Cl̄ inactivator in serum and EDTA plasma from 100 normal adults were determined by electroimmunoassay. The normal range of each of the proteins is given. The Clq values varied more closely with the Cls values than with the levels of the other complement components. C3, C5, and C3 proactivator seemed to form a fairly interdependent group. The reproducibility of double determinations (interplate variation) was 4.9% to 7.9%. The variation of the complement component levels on repeated sampling from normal individuals was investigated. Also, repeated freezing and thawing and storage at room temperature of serum and plasma were studied for their effect on the quantitation of the complement components. C3 and C4 values obtained by electroimmunoassay were in agreement with the values obtained by single radial immunodiffusion.
Predicting First-Year Returns of Health Care IPOs

Prior empirical work shows that IPOs generally earn positive excess first-day returns yet subsequently underperform. Many researchers examine the determinants of post-first-day IPO success, however these studies do not test for first-year IPO return predictability due to unavailability of pre-IPO data with which to predict first-year performance. In this study we utilize strictly pre-IPO financial data manually obtained from corporate IPO registrations to predict the first-year post-IPO performance of health care firms. We do so by utilizing firm size, free cash flows, discretionary accruals, and Altman’s Z. Results suggest that each metric is a significant determinant of first-year raw cumulative and excess cumulative returns, and we are able to reliably identify which firms will be in the top and bottom performance quartiles 30 days, 6 months, and 12 months after the IPO.
Large-Scale Dynamical Models and Estimation for Permeation in Biological Membrane Ion Channels

Biological ion channels are water-filled angstrom-unit (1 angstrom unit=10-10 m)sized pores formed by proteins in the cell membrane. They are responsible for regulating the flow of ions into and out of a cell and hence they control all electrical activities in a cell. This paper deals with constructing large scale stochastic dynamical models for explaining ion permeation; that is, how individual ions interact with the protein atoms in an ion channel and travel through the channel. These permeation models capture the dynamics of the ions at a femto-second time scale and angstrom-unit spatial scale. We review large scale multiparticle simulation methods such as Brownian dynamics for modeling permeation. Then we present a novel multiparticle simulation methodology, which we call adaptive controlled Brownian dynamics, for estimating the force experienced by a permeating ion at each discrete position along the ion-conducting pathway. The profile of this force, commonly known as the potential of mean force, results from the electrostatic interactions between the ions in the conduit and all the charges carried by atoms forming the channel the protein, as well as the induced charges on the protein wall. We illustrate the use of adaptive controlled Brownian dynamics in gramicidin channels and shape estimation of sodium channels.
Credit and the crisis: access to finance for innovative small firms

Since the 2008 financial crisis there has been a significant tightening in credit conditions and a dramatic reduction in bank lending to small firms. Government policy – such as the new Business Bank – has been focused on addressing this problem. A consensus has emerged that access to finance to small firms is one of the key factors holding back the national economy. Yet only a minority of small firms will actually drive the economic recovery – most small firms have little impact on job creation. In a time of limited resources, government policy needs to prioritise the needs of innovative small firms: firms which bring new products and processes to market and which are more likely to grow. The success of these firms will be vital for the long-term health of the UK economy.
Expression of Constitutively Active Guanylate Cyclase in Cardiomyocytes Inhibits the Hypertrophic Effects of Isoproterenol and Aortic Constriction on Mouse Hearts*

Evidence from several rodent models has suggested that a reduction of either atrial natriuretic peptide or its receptor in the heart affects cardiac remodeling by promoting the onset of cardiac hypertrophy. The atrial natriuretic peptide receptor mediates signaling at least in part via the generation of intracellular cyclic GMP. To directly test whether accumulation of intracellular cyclic GMP conveys protection against cardiac hypertrophy, we engineered transgenic mice that overexpress a catalytic fragment of constitutively active guanylate cyclase domain of the atrial natriuretic peptide receptor in a cardiomyocyte-specific manner. Expression of the transgene increased the intracellular concentration of cyclic GMP specifically within cardiomyocytes and had no detectable effect on cardiac performance under basal conditions. However, expression of the transgene attenuated the effects of the pharmacologic hypertrophic agent isoproterenol on cardiac wall thickness and prevented the onset of the fetal gene expression program normally associated with cardiac hypertrophy. Likewise, expression of the transgene inhibited the hypertrophic effects of abdominal aortic constriction, since it abolished its effects on ventricular wall thickness and greatly attenuated its effects on cardiomyocyte size. Altogether, our results suggest that cyclic GMP is a cardioprotective agent against hypertrophy that acts via a direct local effect on cardiomyocytes.
CULTIVATION OF RICKETTSIAE OF THE ROCKY MOUNTAIN SPOTTED FEVER, TYPHUS AND Q FEVER GROUPS IN THE EMBRYONIC TISSUES OF DEVELOPING CHICKS.

Cultivation of Rickettsiae of the Rocky Mountain Special Articles: Spotted Fever, Typhus and Q Fever Groups in the P-Aminobenzoic Acid Prevents the Growth-InhibiEmbryonic Tissues of Developing Chicks: DR. tory Action of Sulfanilamide: DR. NAOMI S. HERALD R. Cox . 399 DIMOND. The Inhibition of Brain Oxidations by a Rafinesque's Interests-a Century Later: Medicinal Convulsant Barbiturate: DR. F. A. FUHRRMAN, Plants: DR. H. B. HAAG . 403 PROFESSOR A. W. MARTIN and PROFESSOR J. M. Obituary: DILLE. Indications of an Increase in Number of August H. Wittenborg: PROFESSOR 0. W. HYMAN C-Atoms in Acids and Number of Acids in Seed and OTHERS. Deaths and Memorials . 407 Fats with Advance in Evolutionary Position:
A review of statin use in patients with acute coronary syndrome in Western and Japanese populations

Early high-dose statin therapy to reduce low-density lipoprotein cholesterol (LDL-C) is associated with improved cardiovascular outcomes in Western patients with stable coronary heart disease or acute coronary syndromes (ACS), but many patients remain undertreated and do not attain LDL-C treatment goals. Early statin therapy has also been shown to improve cardiovascular outcomes in Japanese patients with ACS, and pretreatment with high-dose statin prior to percutaneous coronary intervention has been shown to reduce cardiovascular events in these patients. As is the case in Western populations, many Japanese patients may be undertreated and a residual cardiovascular risk remains. While differences in treatment practice, dosing and genetic factors exist between Japan and Western countries, similarities are also evident when Japanese statin studies are compared with those performed in Western populations. With the increasing prevalence of cardiovascular risk factors in Japan, aggressive statin treatment may be beneficial in achieving optimal cardiovascular outcomes.
The effect of the existential approach through group practices on reducing the frustration of disabled SCI

Objective: Existential psychotherapy is a philosophical approach that deals with the man and his world. This kind of approach is a kind of perspective towards some of the concepts rather than a range of techniques and methods. Present study investigated the effect of the existential approach through group practices on reducing the frustration of disabled SCI. Methods: This is done through an experimental study in which the existential theory tactics were taught to two experimental groups in 10 sessions. Each session lasted for an hour and 30 minutes. In addition, the study used Becks despair questionnaire to gather the data. Results: Group counseling with existential approach was found to have a significant impact on reducing subscales of despair (despair in achieving the desires, hopelessness about the future, attitudes towards the future, and life outlook) in disabled SCI in the city of Shiraz. However, it didn’t have any effect on the subscale confidence in the future. Conclusions: group counseling with existential approach can be effective in reducing the despair in these people. The mechanism that is influential in reducing the disappointment and despair in disabled SCI is probably in the way this method helps the patients not to concentrate on what they have lost but to search for meaning.
Aligning identity in legal services firms : do senior partners in legal services firms possess the core characteristics of identity to work in alignment within the firm?

This exploratory study used grounded theory to discover whether senior partners in legal services firms in the UK held the core characteristics of identity to work in alignment in the changing context. Using a combination of participant interviews and secondary analysis of published material, knowledge was generated to review some changes resulting from the Legal Services Act, the components of identity, and individual and peer alignment in these senior partners. The term ‘alignment’ is used in this study to describe both a state and a process. The study suggests that senior partners do not currently display many of the attributes to take their firms into a successful future. Senior partners reported living a facade, having difficulties with boundaries and the complex role of partner. They seem to focus on eliminating problems rather than striving to achieve goals, and are more interested in ‘I’ than ‘we’. All of this presents huge challenges for a successful response by the firms to deregulation. There was little evidence of simultaneous identification with the firm and the profession, and this with other findings left a gap between the individual and the collective as well as a gap between the role and core identities of the individual. More positively, there is some evidence of identity negotiation and where participants were doing some personal change work, this was driven by the hindrances to, and supporting beliefs about, the required behaviour at work, and possibly informed by an imagined image of best ‘self’ or ‘group member’. The findings support a practitioner model; ‘CONTRIBUTIONS’ which is useful for coaching and facilitation of individuals and teams. The study offers original contributions to academic knowledge including; building on the ‘identification’ literature, linking in the concept of ‘secondary gain’, specific evidence from the legal partner group against generic concepts of identity literature.
Cortico-muscular coherence increases with tremor improvement after deep brain stimulation in Parkinson's disease

Deep brain stimulation on the subthalamic nucleus has been used to relieve Parkinsonian motor symptoms. However, the underlying physiological mechanism has not been fully understood. Beta-band cortico-muscular coherence increases when healthy humans perform isometric contraction. We hypothesized that this might be a measure of symptomatic improvement in motor performance after subthalamic nucleus deep brain stimulation. Here, we measured the &bgr;-band cortico-muscular coherence with magnetoencephalography from three Parkinson's disease patients. We then compared the coherence values for stimulator on-state and off-state. We found that when the stimulator is on, the &bgr; cortico-muscular coherence elevates significantly for the tremorous hand compared with that when the stimulator is off. This suggests that deep brain stimulation resulted in better cortico-muscular coordination.
Islamic Finance and Financial Inclusion: Measuring Use of and Demand for Formal Financial Services among Muslim Adults

Abstract In recent years, the Islamic finance industry has attracted the attention of policymakers and international donors as a possible channel through which to expand financial inclusion, particularly among Muslim adults. Yet cross-country, demand-side data on actual usage and preference gaps in financial services between Muslims and non-Muslims have been scarce. This paper uses novel data to explore the use of and demand for formal financial services among self-identified Muslim adults. In a sample of more than 65,000 adults from 64 economies (excluding countries where less than 1% or more than 99% of the sample self-identified as Muslim), the analysis finds that Muslims are significantly less likely than non-Muslims to own a formal account or save at a formal financial institution after controlling for other individual- and country-level characteristics. But the analysis finds no evidence that Muslims are less likely than non-Muslims to report formal or informal borrowing. Finally, in an extended survey of adults in five North African and Middle Eastern countries with relatively nascent Islamic finance industries, the study finds little use of Sharia-compliant banking products, although it does find evidence of a hypothetical preference for Sharia-compliant products among a plurality of respondents despite higher costs.
Development of an analytical system for the simultaneous determination of anabolic macrocyclic lactones in aquatic environmental samples.

An analytical procedure that enables routine analysis for trace determination of six anabolic macrocyclic lactones (zearalenone, alpha- and beta-zearalenol, zearalanone, zeranol, and taleranol) in sewage treatment plant (STP) samples has been developed. The method uses solid-phase extraction, followed by high-performance liquid chromatography with on-line tandem mass spectrometry using atmospheric pressure chemical ionization (LC/APCI-MS/MS). The extraction of these compounds from filtered water samples was performed off-line with C(18) solid-phase cartridges. The detection was achieved by isocratic reversed-phase high-performance liquid chromatography coupled with an heated nebulizer (HN) APCI interface operating in negative ion mode. Mean recovery of the analytes in STP effluent samples generally exceeded 81%. This method was used to determine the occurrence of target analytes in the aquatic environment. In the selected STP effluent samples, zearalenone and alpha-zearalenol were detected in the ng/L range.
Cell Discohesion and Multifocality of Carcinoma In situ of the Bladder: New Insight From the Adhesion Molecule Profile (e-Cadherin, Ep-CAM, and MUC1)

Urothelial cell carcinoma in situ (CIS) of the bladder is a superficially diffusive and highly discohesive disease. The authors analyzed the expression of some adhesion molecules (e-cadherin and Ep-CAM) and MUC1 in 32 unifocal and multifocal bladder urothelial cell CIS in an attempt to clarify this discohesion. E-cadherin was strongly expressed, in more than 75% of the cases. The presence of methylation of the CDH1 e-cadherin promoter gene was also investigated, but methylation was found in only one case. Ep-CAM was present in all the cases with a heterogeneous staining pattern. Similarly, MUC1/episialin was variously present in 94% of the cases without a polarized staining pattern and was expressed more strongly in cases with multifocal disease. Because loss of MUC1 polarization leads to interference with cell—cell adhesion mechanisms mediated by cadherins, these findings help explain why bladder urothelial cell CIS often shows a discohesive morphology and multifocality despite a strongly expressed adhesion molecule profile. Finally, Ep-CAM expression might provide some support for future target therapy trials.
Genetic survey of polymorphic populations of Podarcis mu- ralis (Sauria: Lacertidae) using molecular markers

Color polymorphisms are widespread in nature and may show a high variability not only within the same population, but also among populations of the same species. , Color polymorphism is a common feature among reptiles and is often linked to evolution of alternative strategies. Alternative and discrete color morphs have been reported in the common wall lizard, Podarcis muralis, which show six different ventral colorations in both sexes: three pure phenotypes (i.e., white, yellow and red) and three intermediate phenotypes (i.e., white-yellow, white-red and yellow-red). The relative frequencies of color morphs show micro-geographic variations at local scale, which could be related to gene flow reduction among populations. Therefore, in this work I studied genetic polymorphism by using molecular markers in order to assess gene flow and dispersal among populations of common wall lizard, with the aim to describe the geographic structure of polymorphic populations at local scale. Moreover, nuclear markers were used to investigate the presence of genetic divergence among sympatric color morphs of common wall lizard.
Measuring Political Democracy

Recent writings concerning measurement of political democracy offer sophisticated discussions of problems of conceptualization, operationalization, and aggregation. Yet they have less to say about the error that derives from the use of inaccurate, partial, or misleading data sources. Drawing on evidence from five Central American countries, the authors show this data-induced measurement error compromises the validity of the principal, long-term cross-national scales of democracy. They call for an approach to index construction that relies on case expertise and use of a wide range of data sources, and they employ this approach in developing an index of political democracy for the Central American countries during the 20th century. The authors’ index draws on a comprehensive set of secondary and primary sources as it rigorously pursues standards of conceptualization, operationalization, and aggregation. The index’s value is illustrated by showing how it suggests new lines of research in the field of Central American politics.
Comparative Epidemiology of Streptococcus pyogenes emm-Types Causing Invasive and Noninvasive Infections in French Children by Use of High-Resolution Melting-Polymerase Chain Reaction

Background: This study aims to analyze the epidemiology of Group A streptococci (GAS) emm-types causing invasive and noninvasive infections in French children. Methods: From September 2009 to May 2011, we analyzed GAS isolates from 585 pharyngitis, 125 invasive infections and, for the first time in France, 32 healthy carriers. M protein gene (emm) typing of the isolates was carried out by a new rapid technique, combining 3 multiplex-polymerase chain reactions (PCRs) coupled to high-resolution melting (HRM) curves, able to detect 13 major emm-types (emm 1, 3, 4, 6, 11, 12, 22, 28, 75, 77, 87, 89 and 102). Results: GAS belonging to emm-type 1 were more frequently found among invasive infections than among pharyngitis (24.0% vs. 11.5%, P < 0.001); emm 4 and 89 were more common in pharyngitis than in invasive infections (emm-type 4, 17.4% vs. 6.4%, P = 0.002 and emm-type 89, 9.9% vs. 2.4%, P = 0.006, respectively) and emm 3 and 4 were more common in cases of pharyngitis associated with scarlet fever (21.6% vs. 6.0%, P < 0.001 and 29.3% vs. 14.5%, P < 0.001, respectively). Conclusion: HRM method enables the rapid emm-typing of a large number of isolates in epidemiological studies. Comparison of GAS causing invasive and noninvasive infections in the same population of children displays an unbalanced repartition of emm-types.
Some Aspects of Model Theory and Finite Structures

Model theory is concerned mainly, although not exclusively, with infinite structures. In recent years, finite structures have risen to greater prominence, both within the context of mainstream model theory, e.g., in work of Lachlan, Cherlin, Hrushovski, and others, and with the advent of finite model theory, which incorporates elements of classical model theory, combinatorics, and complexity theory. The purpose of this survey is to provide an overview of what might be called the model theory of finite structures. Some topics in finite model theory have strong connections to theoretical computer science, especially descriptive complexity theory (see [26, 46]). In fact, it has been suggested that finite model theory really is, or should be, logic for computer science. These connections with computer science will, however, not be treated here. It is well-known that many classical results of ‘infinite model theory’ fail over the class of finite structures, including the compactness and completeness theorems, as well as many preservation and interpolation theorems (see [35, 26]). The failure of compactness in the finite, in particular, means that the standard proofs of many theorems are no longer valid in this context. At present, there is no known example of a classical theorem that remains true over finite structures, yet must be proved by substantially different methods. It is generally concluded that first-order logic is ‘badly behaved’ over finite structures. From the perspective of expressive power, first-order logic also behaves badly: it is both too weak and too strong. Too weak because many natural properties, such as the size of a structure being even or a graph being connected, cannot be defined by a single sentence. Too strong, because every class of finite structures with a finite signature can be defined by an infinite set of sentences. Even worse, every finite structure is defined up to isomorphism by a single sentence. In fact, it is perhaps because of this last point more than anything else that model theorists have not been very interested in finite structures. Modern model theory is concerned largely with complete first-order theories, which are completely trivial here.