Miracle-dz/UniFAR-FTUs huggingface dataset:
Multistate equilibrium unfolding of Escherichia coli dihydrofolate reductase: thermodynamic and spectroscopic description of the native, intermediate, and unfolded ensembles.

The thermodynamic and spectroscopic properties of a cysteine-free variant of Escherichia coli dihydrofolate reductase (AS-DHFR) were investigated using the combined effects of urea and temperature as denaturing agents. Circular dichroism (CD), absorption, and fluorescence spectra were recorded during temperature-induced unfolding at different urea concentrations and during urea-induced unfolding at different temperatures. The first three vectors obtained by singular-value decomposition of each set of unfolding spectra were incorporated into a global analysis of a unique thermodynamic model. Although individual unfolding profiles can be described as a two-state process, a simultaneous fit of 99 vectors requires a three-state model as the minimal scheme to describe the unfolding reaction along both perturbation axes. The model, which involves native (N), intermediate (I), and unfolded (U) states, predicts a maximum apparent stability, DeltaG degrees (NU), of 6 kcal mol(-)(1) at 15 degrees C, an apparent m(NU) value of 2 kcal mol(-)(1) M(-)(1), and an apparent heat capacity change, DeltaC(p)()(-NU), of 2.5 kcal mol(-)(1) K(-)(1). The intermediate species has a maximum stability of approximately 2 kcal mol(-)(1) and a compactness closer to that of the native than to that of the unfolded state. The population of the intermediate is maximal ( approximately 70%) around 50 degrees C and falls below the limits of detection of > or =2 M urea or at temperatures of <35 or >65 degrees C. The fluorescence properties of the equilibrium intermediate resemble those of a transient intermediate detected during refolding from the urea-denatured state, suggesting that a tryptophan-containing hydrophobic cluster in the adenosine-binding domain plays a key role in both the equilibrium and kinetic reactions. The CD spectroscopic properties of the native state reveal the presence of two principal isoforms that differ in ligand binding affinities and in the packing of the adenosine-binding domain. The relative populations of these species change slightly with temperature and do not depend on the urea concentration, implying that the two native isoforms are well-structured and compact. Global analysis of data from multiple spectroscopic probes and several methods of unfolding is a powerful tool for revealing structural and thermodynamic properties of partially and fully folded forms of DHFR.
Distinction between inhibition of purine nucleotide synthesis and the delayed cytotoxic reaction of 6-mercaptopurine.

Brief exposure to 6-mercaptopurine (MP) elicits a delayed cytotoxic reaction in cultures of mouse lymphoma L5178Y cells; the effects of such exposure on the soluble purine ribonucleotides of these cells were investigated. Concentrations of purine ribonucleotides were reduced in cultured L5178Y cells during short exposure to MP, but cells continued to proliferate; after drug exposure was terminated, nucleotide pool sizes returned to their usual values while concentrations of acid-soluble thiopurine derivatives declined. At the time of the delayed cytotoxic reaction to MP exposure, the pool sizes of purine ribonucleotides in the enlarged, degenerating cells were similar to those in untreated cells. The presence of thymidine in culture medium during exposure to MP had no effect on MP-induced reductions in purine ribonucleotide pools, but it partially protected cells against the delayed lethal effects of MP. That inhibition of purine nucleotide synthesis by MP was alone insufficient to account for its cytotoxic effects was evident in the following experiments. Treatment of L5178Y cells with methylthioinosine resulted in reductions in purine ribonucleotide pools and proliferation rates greater than those caused by exposure to MP, but did not affect cell viability; cell proliferation rates returned to control values after 6-methylthioinosine was removed. In contrast, brief exposure to 6-thioguanine elicited a delayed cytotoxic reaction in cultures of L5178Y cells, but had only slight effects on cellular purine ribonucleotide pools. It was concluded that inhibitions of purine nucleotide synthesis were not centrally involved in the delayed cytotoxic activity of MP. Similarity between the delayed cytotoxic effects of MP and 6-thioguanine suggested that toxic effects of MP were mediated by MP-derived 6-thioguanine nucleotides, presumably through incorporation into DNA.
Movement Primitive Segmentation for Human Motion Modeling: A Framework for Analysis

Movement primitive segmentation enables long sequences of human movement observation data to be segmented into smaller components, termed movement primitives, to facilitate movement identification, modeling, and learning. It has been applied to exercise monitoring, gesture recognition, human-machine interaction, and robot imitation learning. This paper proposes a segmentation framework to categorize and compare different segmentation algorithms considering segment definitions, data sources, application-specific requirements, algorithm mechanics, and validation techniques. The framework is applied to human motion segmentation methods by grouping them into online, semionline, and offline approaches. Among the online approaches, distance-based methods provide the best performance, while stochastic dynamic models work best in the semionline and offline settings. However, most algorithms to date are tested with small datasets, and algorithm generalization across participants and to movement changes remains largely untested.
Antibacterial activity of Sargassum Ilicifolium and Kappaphycus alvarezii

Microorganisms, of late have developed resistance to existing antibiotics, thereby leading to an increasing demand for new antibiotics. Since seaweeds offer a rich source of bioactive molecules, the present study was carried out to investigate its antibacterial potential. Two species of seaweeds namely, Sargassum ilicifolium and Kappaphycus alvarezii collected from different coastal regions of Rameshwaram (southeastern coast of Tamil Nadu, India) were used in the present study. For microbiological testing of the seaweed extracts, agar well diffusion method was used. The zone of inhibition was measured for all the different crude algal extracts against three strains of microorganisms namely, Escherichia coli, Salmonella sp. and Klebsiella sp. that cause diseases and disorders in human beings, animals and plants. Crude extracts prepared from chloroform, ethanol and methanol revealed a wide range of antibacterial activity against the test pathogens. Maximum inhibition was noticed with ethanol extracts in case of S. ilicifolium but all the three extracts showed varied results in case of K. alvarezii. However, no specific solvent exhibited activity against all the test organisms effectively. The overall antibacterial activity assessed from the above results indicates the presence of active constituents in the extractions of seaweeds which can be exploited for the production of lead molecules which are of use in pharmaceutical industry.
Cognitive Functioning in Bipolar Patients Receiving Lamotrigine: Preliminary Results

Abstract: Despite the increasing use of lamotrigine (LTG) in bipolar disorder, little is known about its impact on cognition in bipolar patients. Therefore, we have evaluated 33 bipolar I and II patients on cognitive measures (verbal memory, attention, executive functions) while receiving either LTG (n = 15) or another anticonvulsant (carbamazepine or valproate; n = 18). Patients receiving LTG were generally diagnosed as having bipolar II disorder, had experienced more depressive episodes but a lesser number of hospitalizations, and had better performance than the patients receiving carbamazepine or valproate on the verbal fluency task. A moderate effect size also suggests that both groups may differ on the immediate verbal memory test (California Verbal Learning Test). These preliminary results suggest a safer neurocognitive profile of LTG on bipolar patients, as compared with other anticonvulsants.
Visual Categorization of Natural Movies by Rats

Visual categorization of complex, natural stimuli has been studied for some time in human and nonhuman primates. Recent interest in the rodent as a model for visual perception, including higher-level functional specialization, leads to the question of how rodents would perform on a categorization task using natural stimuli. To answer this question, rats were trained in a two-alternative forced choice task to discriminate movies containing rats from movies containing other objects and from scrambled movies (ordinate-level categorization). Subsequently, transfer to novel, previously unseen stimuli was tested, followed by a series of control probes. The results show that the animals are capable of acquiring a decision rule by abstracting common features from natural movies to generalize categorization to new stimuli. Control probes demonstrate that they did not use single low-level features, such as motion energy or (local) luminance. Significant generalization was even present with stationary snapshots from untrained movies. The variability within and between training and test stimuli, the complexity of natural movies, and the control experiments and analyses all suggest that a more high-level rule based on more complex stimulus features than local luminance-based cues was used to classify the novel stimuli. In conclusion, natural stimuli can be used to probe ordinate-level categorization in rats.
Methylprednisolone acetate injection plus casting versus casting alone for the treatment of de Quervain's tenosynovitis.

BACKGROUND There is no consensus in the treatment of de Quervain's tenosynovitis, but wrist support with or without local corticosteroid injection has been considered as an effective treatment modality. Some patients have expressed reluctance for steroid injections because of the fear of probable adverse reactions. This study was performed to compare the outcome of methylprednisolone acetate injection plus thumb spica cast versus cast alone for the treatment of de Quervain's tenosynovitis. METHODS This randomized prospective study was conducted from January 2005 to July 2008 in the orthopedic clinics of our hospital and private offices. A total of 73 patients with de Quervain's tenosynovitis were managed with either of these methods: 1) injection of methylpredmisolone acetate in the first dorsal compartment of the wrist followed by wrist thumb spica cast. 2) casting alone. Wrist casting duration in both groups was one month and the patients were followed for 6 months. RESULTS In the first group, a total of 37 patients were included (injection plus wrist immobilization by cast), and 36 patients in the second group (wrist casting alone). The mean age was 32.6 years (21 - 61 years) in all patients. There were 63 women and 10 men. Overall success rate was 86.5% in the first and 36.1% in the second groups, with a significant difference for both groups with respect to pain score and cure rate (P<0.05). Temporary pain was the most common adverse reaction at the site of injection and was noted in 40% of patients. Despite this adverse reaction which was related to methylprednisolone injection, a higher success rate was seen in the injection group in comparison to patients treated solely by casting. CONCLUSION Support of the wrist with casting alone had less favorable outcome in de Quervain's tenosynovitis. Adding methylprednisolone acetate injection into the first dorsal compartment of the wrist is necessary for more optimal results.
Fund Mobilization by Insurance Companies and Fixed Capital Formation: Evidence from the Nigerian Economy

This paper is an empirical investigation into the relationship between fund mobilization by insurance companies and gross fixed capital formation (GFCF) in Nigeria and specifically how the latter responds to stimuli emanating from the insurance companies. A five variable-predictor multivariate regression model was estimated and analyzed. The short run results reveal that four explanatory variables namely: premium from fire, accidents, motor vehicles and employee liabilities insurance policies positively and insignificantly correlate with Gross Fixed Capital Formation while the relationship between premium from marine insurance policies and GFCF is both negative and insignificant. In the long run, the fund mobilization variables by insurance companies positively and significantly impact on the growth of gross fixed capital formation. In addition, the Granger causality test provides no evidence of causality among the variables. The paper therefore recommends the formulation and implementation of policy measures that will increase insurance penetration, improve insurance fund mobilization and enlarge the insurance market in Nigeria.
Metabolic Regulation of Leaf Senescence in Sunflower (Helianthus annuus L.) Plants

The leaf is the main photosynthetic organ of plants and its development a complex process governed by a combination of environmental factors and intrinsic and genetically regulated signals (Van Lijsebettens & Clarke, 1998). Usually, leaf ontogeny includes an early phase of increasing photosynthetic rates while the leaf is actively expanding, a mature phase where such rates peak and a senescence phase where they decline (Gepstein, 1988; Miller et al., 2000). During early development, the leaf is a sink receiving nutrients from the rest of the plant; however, as soon as it reaches full photosynthetic capacity, it becomes the main source organ of the plant. After this productive period, the leaf enters the senescence phase, during which most compounds present in it are removed and reused (Hortensteiner & Feller, 2002; Buchanan-Wollaston et al., 2003a). Leaf senescence, which is last stage in leaf development, is a highly regulated and programmed degeneration process governed by a variety of developmental and environmental signals (Lim et al., 2003). This important phase in the leaf lifespan period may last as long as leaf maturation and involves a shift from nutrient assimilation to nutrient remobilization and recycling (Guiboileau et al., 2010). In senescent leaf metabolism, carbon and nitrogen assimilation are replaced by catabolism of chlorophyll and macromolecules such as proteins, RNA and membrane lipids, the degradation of which marks the senescence phase. Unsurprisingly, senescence alters the expression of many genes. These senescence-associated genes include regulatory genes encoding transcription factors; genes involved in degradative processes that code for hydrolytic enzymes such as proteases, lipases and ribonucleases; and genes with secondary functions in senescence that code for proteins involved in nutrient remobilization (e.g. glutamine synthetase, which catalyses the conversion of ammonium into glutamine to enable nitrogen recycling in senescing cells) (Taiz & Zeiger, 2010). Environmental cues such as day length and temperature, and various biotic and abiotic sources of stress, can also affect the initiation and progress of such a high complex as leaf senescence.
Profiling Without the Writer ’ s Text

Social network users may wish to preserve their anonymity online by masking their identity and not using language associated with any particular demographics or personality. However, they have no control over the language in incoming communications. We show that linguistic cues in public comments directed at a user are sufficient for an accurate inference of that user’s gender, age, religion, diet, and even personality traits. Moreover, we show that directed communication is even more predictive of a user’s profile than the user’s own language. We then conduct a nuanced analysis of what types of social relationships are most predictive of users’ attributes, and propose new strategies on how individuals can modulate their online social relationships and incoming communications to preserve their anonymity.
Trends in health care resource utilization and pharmacological management of COPD in Taiwan from 2004 to 2010

Rationale COPD has attracted widespread attention worldwide. The prevalence of COPD in Taiwan has been reported, but little is known about trends in health care resource utilization and pharmacologic management in COPD treatment. Objective The objective of this article was to study trends in health care resource utilization, pharmacologic management, and medical costs of COPD treatment in Taiwan. Materials and methods Reimbursement claims in the Taiwan National Health Insurance System from 2004 to 2010 were collected. The disease burden of COPD, including health care resource utilization and medical costs, was evaluated. Results The pharmacy cost of COPD increased from 2004 to 2010 due to the increased utilization of long-acting muscarinic antagonist (LAMA) and fixed-dose combination of long-acting β2-agonist and inhaled corticosteroid (LABA/ICS), whereas the cost of all other COPD-related medications decreased. The average outpatient department (OPD) cost per patient increased 29.3% from 1,070 USD in 2004 to 1,383 USD in 2010. The highest average total medical cost per patient was 3,434 USD in 2005, and it decreased 12.4% to 3,008 USD in 2010. There was no significant difference in the average number of OPD visits and emergency department visits per patient. The highest average number of hospital admissions was 0.81 in 2005, and it decreased to 0.65 in 2010. The average number of intensive care unit (ICU) admissions decreased from 0.52 in 2005 to 0.31 in 2010. Conclusion From 2004 to 2010, the average total medical cost per patient of COPD was slightly decreased because of the decreased average number of hospital admissions and ICU admissions. The costs of both LAMA and LABA/ICS increased, while the cost for all other COPD-related medications decreased. These findings suggest that the increased utilization of LAMA and LABA/ICS may have contributed to the decreased average number of hospital admissions and ICU admissions in COPD patients from 2004 to 2010.
Biochemical Evaluation of Oxidative Stress in Type 1 Diabetes

Diabetes mellitus is considered to be one of the most common chronic diseases worldwide, and recognized as one of the leading causes of morbidity and mortality (American Diabetes Association, 2010). It has been reported that the prevalence of diabetes mellitus will increase from 6% to over 10% in the next decade (Rosen et al., 2001). According to the World Health Organization in 2000, a total of 171 million people in all age groups worldwide (2.8% of the global population) have been affected by diabetes mellitus, and the number of persons is ex‐ pected to increase to 366 million (4.4% of the global population) by 2030 (Wild et al., 2004).
VDT Workstation Design: Preferred Settings and Their Effects

A field study was conducted to assess the preferences of VDT operators with regard to their body posture and the settings of an adjustable VDT workstation. Subjects came from four different companies, and the study took place during subjects' customary working activities. Means and ranges of the preferred settings are given. The operators preferred body postures that are distinctly different from those recommended in textbooks and other publications. Some of the workstation settings they preferred also strongly deviate from such recommendations.
Evaluation of hepatocyteprotective and anti-hepatitis B virus properties of Cichoric acid from Cichorium intybus leaves in cell culture.

Hepatitis B is the most common serious liver infection in the world. To date, there is still no complete cure for chronic hepatitis B. Natural caffeic acid analogues possess prominent antiviral activity, especially anti-hepatitis B virus (HBV) and anti-human immunodeficiency virus effects. Cichoric acid is a caffeic acid derivative from Cichorium intybus. In the study, the anti-hepatitis B property of cichoric acid was evaluated by the D-galactosamine (D-GalN)-induced normal human HL-7702 hepatocyte injury model, the duck hepatitis B virus (DHBV)-infected duck fetal hepatocytes and the HBV-transfected cell line HepG2.2. 15 cells, respectively. The results showed that cichoric acid attenuated significantly D-GalN-induced HL-7702 hepatocyte injury at 10-100 µg/mL and produced a maximum protection rate of 56.26%. Moreover, cichoric acid at 1-100 µg/mL inhibited markedly DHBV DNA replication in infected duck fetal hepatocytes. Also, cichoric acid at 10-100 µg/mL reduced significantly the hepatitis B surface and envelope antigen levels in HepG2.2. 15 cells and produced the maximum inhibition rates of 79.94% and 76.41%, respectively. Meanwhile, test compound at 50-100 µg/mL inhibited markedly HBV DNA replication. In conclusion, this study verifies the anti-hepatitis B effect of cichoric acid from Cichorium intybus leaves. In addition, cichoric acid could be used to design the antiviral agents.
Clinical Evaluation of Nine Free Thyroxine Assays: Persistent Problems in Particular Populations

Abstract Over the past decade, numerous papers have addressed the various methodological problems encountered with free thyroxine (FT4) assays. We evaluated the clinical performance of nine FT4 assays in five centres, using a panel of 310 sera: 156 from euthyroid controls; 27 from hyperthyroid patients; 34 from untreated hypothyroidism; 22 from patients with renal failure; 30 from women in the last trimester of pregnancy; 23 from patients on thyroid substitutive therapy; and 18 from patients treated with amiodarone. Only three methods showed a Gaussian distribution of FT4 concentrations. Reference ranges were calculated using the 2.5th and 97.5th percentiles. A significant difference was observed between FT4 values in men and women. The areas under the receiver operating characteristic (ROC) curves ranged from 0.996 to 1 for hyperthyroidism and from 0.973 to 1 for hypothyroidism. In sera from patients with renal failure and from pregnant women, method-dependent biases were observed and confirmed with dilution experiments. In conclusion, current FT4 assays show good performance regarding the diagnosis of overt dysthyroidism. Nevertheless, FT4 measurements are still vulnerable to method-dependent artefacts in particular populations such as patients with renal failure and pregnant women.
The Residues Determining Differences in Ion Affinities among the Alternative Splice Variants F, A, and B of the Mammalian Renal Na-K-Cl Cotransporter (NKCC2)*

Three alternatively spliced variants of the renal Na-K-Cl cotransporter (NKCC2) are found in distinct regions of the thick ascending limb of the mammalian kidney; these variants mediate Na+K+2Cl- transport with different ion affinities. Here, we examine the specific residues involved in the variant-specific affinity differences, utilizing a mutagenic approach to change the NKCC2B variant into the A or F variant, with functional expression in Xenopus oocytes. The splice region contains the second transmembrane domain (TM2) and the putative intracellular loop (ICL1) connecting TM2 and TM3. It is found that the B variant is functionally changed to the F variant by replacement of six residues, half of the effect brought about by three TM2 residues and half by three ICL1 residues. The involvement of the ICL1 residues strongly suggests that this region of ICL1 may actually be part of a membrane-embedded domain. Changing six residues is also sufficient to bring about the smaller functional change from the B to the A variant; three residues in TM2 appear to be primarily responsible, two of which correspond to residues involved in the B-to-F changes. A B-variant mutation reported in a mild case of Bartter disease was found to render the cotransporter inactive. These results identify the combination of amino acid variations responsible for the differences among the three splice variants of NKCC2, and they support a model in which a reentrant loop following TM2 contributes to the chloride binding and translocation domains.