Miracle-dz/UniFAR-FTUs huggingface dataset:
Polymorphisms in OATP-C

The human organic anion transporting polypeptide-C (OATP-C) (gene SLC21A6) is a liver-specific transporter importantly involved in the hepatocellular uptake of a variety of endogenous and foreign chemicals. In this study, we demonstrate the presence of multiple functionally relevant single-nucleotide polymorphisms (SNPs) in OATP-C in a population of African- and European-Americans. Moreover, examination of 14 nonsynonymous polymorphisms indicated that genotypic frequencies were dependent on race. Functional assessment of 16OATP-C alleles in vitro revealed that several variants exhibited markedly reduced uptake of the OATP-C substrates estrone sulfate and estradiol 17β-d-glucuronide. Specifically, alterations in transport were associated with SNPs that introduce amino acid changes within the transmembrane-spanning domains (T217C (Phe-73 → Leu), T245C (Val-82 → Ala), T521C (Val-174 → Ala), and T1058C (Ile-353 → Thr)) and also with those that modify extracellular loop 5 (A1294G (Asn-432 → Asp), A1385G (Asp-462 → Gly), and A1463C (Gly-488 → Ala)). Cell surface biotinylation experiments indicated that the altered transport activity of some OATP-C variants was due, in part, to decreased plasma membrane expression. Given the relatively high genotypic frequency of the T521C (14%) transition in European-Americans and the G1463C (9%) transversion in African-Americans, SNPs in OATP-C may represent a heretofore unrecognized factor influencing drug disposition.
Use of genetic technologies to compare medicines

In order to ensure that patients receive the safest and most effective medicines possible, it is often necessary to compare medicines and assess the extent to which they are similar in their clinical impact. Full clinical trials with appropriate endpoints remain the only method to compare the clinical impact of two medicines with absolute certainty. Other available methods (including physicochemical analysis, genomics, and transcriptomics) can provide partial information about certain aspects of a medicine's biological impact, with possible clinical implications. Especially for biologics and non‐biological complex drugs, which are more difficult to characterize by physicochemical means than small molecules, genomics and transciptomic studies can yield valuable insights for physicians, regulators, and drug developers. In this review, we cite and summarize a variety of studies that exemplify the emerging science of applying genomics and transcriptomics technologies to compare medicines. We discuss key aspects of experimental design, conduct of genetic assays, and advanced data analysis, all of which are critical for the successful execution of such studies. Finally, we propose new areas for which such studies can be applied to maximize patient benefit and reduce safety issues.
Illustrating dynamical symmetries in classical mechanics: The Laplace–Runge–Lenz vector revisited

The inverse square force law admits a conserved vector that lies in the plane of motion. This vector has been associated with the names of Laplace, Runge, and Lenz, among others. Many workers have explored aspects of the symmetry and degeneracy associated with this vector and with analogous dynamical symmetries. We define a conserved dynamical variable α that characterizes the orientation of the orbit in two-dimensional configuration space for the Kepler problem and an analogous variable β for the isotropic harmonic oscillator. This orbit orientation variable is canonically conjugate to the angular momentum component normal to the plane of motion. We explore the canonical one-parameter group of transformations generated by α(β). Because we have an obvious pair of conserved canonically conjugate variables, it is desirable to use them as a coordinate-momentum pair. In terms of these phase space coordinates, the form of the Hamiltonian is nearly trivial because neither member of the pair can occur explicitly in the Hamiltonian. From these considerations we gain a simple picture of dynamics in phase space. The procedure we use is in the spirit of the Hamilton–Jacobi method.
Hypoxia Influences the Vascular Expansion and Differentiation of Embryonic Stem Cell Cultures Through the Temporal Expression of Vascular Endothelial Growth Factor Receptors in an ARNT‐Dependent Manner

Adaptive responses to low oxygen (O2) tension (hypoxia) are mediated by the heterodimeric transcription factor hypoxia inducible factor (HIF). When stabilized by hypoxia, bHLH‐PAS α‐ and β‐ (HIF‐1β or ARNT) HIF complex regulate the expression of multiple genes, including vascular endothelial growth factor (VEGF). To investigate the mechanism(s) through which hypoxia contributes to blood vessel development, we used embryonic stem cell (ESC) differentiation cultures that develop into embryoid bodies (EBs) mimicking early embryonic development. Significantly, low O2 levels promote vascular development and maturation in wild‐type (WT) ESC cultures measured by an increase in the numbers of CD31+ endothelial cells (ECs) and sprouting angiogenic EBs, but refractory in Arnt−/− and Vegf−/− ESC cultures. Thus, we propose that hypoxia promotes the production of ECs and contributes to the development and maturation of vessels. Our findings further demonstrate that hypoxia alters the temporal expression of VEGF receptors Flk‐1 (VEGFR‐2) and the membrane and soluble forms of the antagonistic receptor Flt‐1 (VEGFR‐1). Moreover, these receptors are distinctly expressed in differentiating Arnt−/− and Vegf−/− EBs. These results support existing models in which VEGF signaling is tightly regulated during specific biologic events, but also provide important novel evidence that, in response to physiologic hypoxia, HIF mediates a distinct stoichiometric pattern of VEGF receptors throughout EB differentiation analogous to the formation of vascular networks during embryogenesis. STEM CELLS 2010;28:799–809
Comparative Study of Oral and Written Picture Description in Patients with Alzheimer's Disease

Oral and written picture descriptions were compared in 22 patients with Alzheimer's disease (AD) and 24 healthy elderly subjects. AD patients had a significant reduction of all word categories, which, similarly to controls, was more pronounced in written than in oral texts. They also reported fewer information units than controls, but without task difference. At the syntactic level, written descriptions of AD subjects were characterized by a diminution of subordinate clauses and a reduction of functors. More grammatical errors were present in written descriptions by AD and control subjects. AD and control groups produced an equivalent number of semantic errors in both tasks. However, in oral description, AD patients had more word-finding difficulties. In sum, AD descriptions were always shorter and less informative than control texts. Additionally, written descriptions of AD patients appeared shorter and more syntactically simplified than, but as informative as oral descriptions. Whereas no phonemic paraphasias were observed in either group, AD patients produced many more graphemic paragraphias than controls produced. Furthermore, written descriptions had more irrelevant semantic intrusions. Thus, as compared to oral descriptions, written texts appeared to be a more reliable test of semantic and linguistics difficulties in AD.
Do Intergovernmental Organizations Promote Peace?

A basic debate in world politics involves the impact of intergovernmental organizations (IGOs) on international conflict. Liberals, functionalists, and others see IGOs as capable of transforming global anarchy, while realists emphasize the essential irrelevance of IGOs in managing such fundamental processes as war and peace. Recent quantitative studies also yield disparate conclusions depending on particular econometric assumptions, implying variously that IGOs foster pacific relations among states, have no impact on dispute behavior, or even increase dispute propensity. At least part of the problem is a lack of theoretical and empirical specificity. The authors apply bargaining theory to develop a "middle path" between the realist and liberal perspectives. Only some IGOs, those with security mandates and the most sophisticated institutional structures, are likely to influence dispute behavior. The authors combine the theory with two improvements in research design. First, IGOs vary in capability, mandate, and cohesion. The authors construct a dataset of IGO institutional heterogeneity and member cohesiveness. Second, states join IGOs for reasons that are not unrelated to why states fight. The authors control for the level of international involvement among countries and find support for their arguments in initial tests.
Compensatory Trunk Movements in Patients with Hip Osteoarthritis: Accuracy and Reproducibility of a Body‐Fixed Sensor‐Based Assessment

This study examined the accuracy and reproducibility of a body‐fixed sensor‐based assessment for quantifying frontal plane angular movements of the (upper) thorax and pelvis of patients with hip osteoarthritis at different walking speeds. To evaluate accuracy, the angular movements of sensors attached to the thorax and pelvis of three patients were compared with results based on an optical motion analysis system. Accuracy was high, with small and consistent mean differences (<1.0 degree) and corresponding standard deviations (<1.3 degrees) between optical motion analysis system and body‐fixed sensor data. To evaluate reproducibility, angular trunk movements were assessed twice in 15 patients. Reproducibility was high (intraclass correlation coefficients ranged from 0.86 to 0.97), and the values of the mean differences between the test and retest were small, with the 95% confidence interval containing zero. This body‐fixed sensor‐based assessment is an accurate and reproducible method for quantifying frontal plane compensatory trunk movements during gait of patients with hip osteoarthritis at different walking speeds.
SOME BASIC ASPECTS OF TEXT PROCESSING

The concept of text processing was devised and developed to achieve a systematic treatment of all the ways of producing a text on the basis of an existent text and at least partially retaining the meaning of that text. Translation is one such way and an instance of text processing of particular interest in that it aims at preserving the meaning as well as many structural features of a given text although providing an entirely new and different linguistic expression. Most of the other cases of text processing involve serious alterations in the meaning and structure of the original as well as in its linguistic expression. There are cases of translation which, more than just reworking a given text into a new one by translating it into a different linguistic medium of expression, make use of several earlier translations of the same text or even other texts or
Short-Term Psychological Impact of Predictive Testing for Machado-Joseph Disease: Depression and Anxiety Levels in Individuals at Risk from the Azores (Portugal)

Objective: The short-term impact of the pre-symptomatic genetic test (PT) for Machado-Joseph disease (MJD) in the Azores (Portuguese Islands) was assessed in 46 individuals at risk who completed the PT Program. Methods: Scores for depression and anxiety were used as indicators of the subjects’ emotional status immediately before the PT and 1 year after disclosure of the results. Results: Global levels of participation in the Azorean PT Program for MJD were high (20.7%), particularly in Flores Island (35.8%). For the total sample, mean scores of depression and anxiety before and after the PT presented without clinical significance. No differences were found for depression and anxiety scores before and after the PT. Furthermore, when grouped by test results (carriers/non-carriers), there were no differences between pre- and post-test levels. Conclusions: Results indicate that the test result did not cause a decrease in the psychological well-being of the individuals tested. The high number of participants performing the PT in the small and isolated community of Flores Island, where MJD represents a source of stigma, was interpreted as an indication that in this particular population the PT offers the individuals at risk the possibility of liberating from a stigma, and, hence, from exclusion.
Exploring the Factors Determining Individuals' SNS Continuance: An Empirical Study in the Chinese Context

IS continuance is important for IS providers to increase both their revenues and profits, and to achieve success. With the penetration of SNS into people’ lives, SNS has attracted the attentions of IS researchers and become a hot topic. This study develops a model to explore the factors determining individuals’ continuous intention and use of SNS. Based on 221 useful questionnaires, the research model is empirically tested together with a number of hypotheses. The results show that satisfaction together with perceived usefulness, perceived playfulness and social influence positively impact users’ continuance intention. Continuance intention and satisfaction are found to have positive influences on users’ continuous use of SNS, and continuous intention exerts a stronger influence on continuous use than satisfaction. The implications to theories and practice are discussed as well.
Prolonged Survival with Imatinib Mesylate Combined with Chemotherapy and Allogeneic Stem Cell Transplantation in de novo Ph+ Acute Myeloid Leukemia

Background: De novo Philadelphia chromosome-positive (Ph+) acute myeloid leukemia (AML) is a rare disease with a poor prognosis. Imatinib mesylate (IM) is the standard treatment for Ph+ chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia; however, its role in Ph+ AML has not been extensively investigated. Methods: Two patients aged of 46 and 19 years were diagnosed with de novo Ph+ AML according to the WHO Classification of Myeloid Neoplasms (2002) and the French-American-British (FAB) classification systems (1989). Cytogenetic analysis confirmed the presence of t(9;22). Standard RT-PCR was used to detect expression of the BCR-ABL1 fusion gene. Minimal residual disease was monitored by RQ-PCR for the BCR-ABL1/ABL ratio. Both patients received initial IM therapy combined with daunorubicin-based chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) and IM maintenance treatment after allo-HSCT. Results: Both patients achieved long-term disease-free survival with complete hematologic response, complete molecular response, and complete cytogenetic response for 44 and 48 months, respectively. Conclusions: Our cases indicate that IM combined with daunorubicin-based chemotherapy followed by allo-HSCT and IM maintenance treatment is associated with a favorable outcome for de novo Ph+ AML, especially when IM is used in an early phase of AML.
Promoting Energy-Balance Behaviors Among Ethnically Diverse Adolescents

The Central Texas Coordinated Approach To Child Health (CATCH) Middle School Project is a 3.5-year school-based project aimed at promoting physical activity (PA), healthy eating, and obesity prevention among public middle school students in Texas. This article describes the CATCH intervention model and presents baseline findings from spring 2009. CATCH comprises six core components: CATCH Team, CATCH PE, CATCH Classroom, CATCH Eat Smart Cafeteria, CATCH Family, and CATCH Social Marketing. A group randomized serial cross-sectional design is being employed to test the effect of three program support conditions (n = 10 schools each) on energy-balance behaviors: Basic (training and curriculum only), Basic Plus (training and curriculum plus CATCH facilitator support), and Basic Plus Social Marketing (all inputs plus social marketing component). The study sample is composed of a cross-sectional sample of eighth-grade students (primary outcome evaluation sample) and sixth- and seventh-grade students (PE process evaluation sample) who are selected and measured each year. At baseline, 37.9% of eight-grade students (n = 2,841; 13.9 years) were overweight/obese and 19.2% were obese. Eighth-grade students reported, on average, consuming sugar-sweetened beverages more than two times on the previous day and fruits and vegetables roughly three times on the previous day; only two of five school districts surpassed the recommended 50% cut-point for class time spent in moderate-and-vigorous PA as measured in classes of sixth- and seventh-grade students. Additional behavioral findings are reported. Body mass index and behaviors were comparable across conditions. Baseline findings underscore the need to promote student energy-balance behaviors.
Parameter Estimation of DC Motor using Adaptive Transfer function based on Nelder-Mead Optimisation

This paper explains an adaptive method for estimation of unknown parameters of transfer function model of any system for finding the parameters. The transfer function of the model with unknown model parameters is considered as the adaptive model whose values are adapted with the experimental data. The minimization of error between the experimental data and the output of the adaptive model have been realised by choosing objective function based on different error criterions. Nelder-Mead optimisation Method is used for adaption algorithm. To prove the method robustness and for students learning, the simple system of separately excited dc motor is considered in this paper. The experimental data of speed response and corresponding current response are taken and transfer function parameters of dc motors are adapted based on Nelder-Mead optimisation to match with the experimental data. The effectiveness of estimated parameters with different objective functions are compared and validated with machine specification parameters.
Closed loop steering of unicycle like vehicles via Lyapunov techniques

With a special choice for the system state equations, the use of the simplest quadratic form as candidate Lyapunov function directly leads to the definition of very simple, smooth and effective closed loop control laws for unicycle-like vehicles, suitable to be used for steering, path following, and navigation. The authors provide simulation examples to show the effectiveness and, in a sense, the "natural behavior" of the obtained closed loop motions (when compared with everyday driving experience). >
Matrix metalloproteinase‐9 promotes nerve growth factor‐induced neurite elongation but not new sprout formation in vitro

Matrix metalloproteinase‐9 (MMP‐9) is a basal‐lamina‐degrading protease that we have recently shown to be localized in regenerating sciatic nerve. We now demonstrate that MMP‐9 colocalizes with growth‐associated protein GAP‐43 in regenerating nerves in vivo and is involved in vitro in axonal sprouting. By using a PC12 cell model for neuronal sprouting, we analyzed the effects of recombinant MMP‐9, MMP‐9‐neutralizing antibody, and a broad‐spectrum MMP inhibitor (Ro 31‐9790) on sprout formation, elongation, and branching. Quantitative phase‐contrast microscopy showed that MMP‐9 elongated neuronal sprouts by 67% and increased their branching by 14% but did not change the number of sprouts relative to nerve growth factor (NGF) treatment. Double immunofluorescence for GAP‐43, a marker for growth cones, and α‐tubulin, a marker for axonal microtubules, showed that MMP‐9‐treated cells had increased distribution of α‐tubulin but no effect on GAP‐43. Western blot analyses of cell lysates demonstrated that the NGF‐induced increase in GAP‐43 was unchanged with MMP‐9 treatment or inhibition, confirming that MMP‐9 had no effect on new sprout formation. However, Ro 31‐9790 reduced GAP‐43 levels to those seen in untreated cells, suggesting that an MMP other than MMP‐9 is important for sprout formation. Finally, phosphorylated neurofilament M (NFM‐p), a marker for regenerative elongation, was induced with MMP‐9 treatment and was inhibited by the anti‐MMP‐9 antibody treatment, confirming the role of MMP‐9 in axonal elongation. NFM‐p colocalized with MMP‐9 in regenerating sciatic nerve fibers. These findings suggest that MMP‐9 regulates neurite extension in regenerating peripheral nerve fibers and, therefore, might be of therapeutic value in promoting regeneration in vivo. © 2004 Wiley‐Liss, Inc.
Fish Oil Supplementation in Pregnancy Lowers F2-isoprostanes in Neonates at High Risk of Atopy

The anti-inflammatory properties of n-3 polyunsaturated fatty acids (n-3 PUFA) have suggested a potential role of these nutrients in dietary modification for prevention of allergic disease in early life. As oxidative stress is known to modify antigen presenting cell (APC) signalling and resulting immune responses, we examined the effects of maternal n-3 PUFA supplementation in pregnancy on markers of oxidative stress and APC function in neonates at high risk of allergy. Eighty-three pregnant atopic women were randomised to receive 4 g daily of either fish oil (n=40) or olive oil (n=43) capsules in a controlled trial from 20 weeks gestation until delivery. Plasma (cord blood) and urinary F2-isoprostanes were measured as markers of lipid peroxidation. Cord erythrocyte fatty acids and markers of APC function (HLA-DR expression and cytokine responses) were measured and related to levels of plasma F2-isoprostanes. Maternal fish oil supplementation lowered plasma (p<0.0001) and urinary (p=0.06) F2-isoprostanes. HLA-DR expression on APC was not different between the groups. In multiple regression analysis, 28.8% of the variance in plasma F2-isoprostanes was explained by positive relationships with erythrocyte arachidonic acid (AA) and monocyte HLA-DR expression and a negative relationship with erythrocyte eicosapentaenoic acid (EPA). This study shows that maternal supplementation with fish oil can attenuate neonatal lipid peroxidation. Clinical follow-up of these infants will help to determine if there are sustained effects on postnatal oxidative stress and expression of allergic disease.
Failure of Hvaluronidase to Increase the Invasiveness of Neoplasms*

In recent papers (1, 5) it was suggested that invasion of the adjacent normal tissues by malignant tumors may be facilitated by the presence of a spreading fac,tor such as hyaluronidase. In support of this hypothesis, it was reported that some human carcinomas have been found to contain a sprcading factor. Further support would bc given to this hypothesis if it could be shown that invasiveness of neoplasms is increased by injection of hyaluronidase into or near a neoplasm, since the connective tissue barrier would presumably be weakened, and penetration of tmnor cells facilitated. Accordingly, injections of hyaluronidase were made into tumors of two kinds, a transplantable mouse sarcoma and the Shope rabbit papilloma.