Miracle-dz/UniFAR-FTUs huggingface dataset:
Validation of an LC–MS/MS Method for Quantitative Analysis of the 5 Bioactive Components of Wuzhi Capsule in Human Plasma Samples

Background: Wuzhi capsule (WZC) is an ethanol extract from the ripe fruit of Schisandra sphenanthera in traditional Chinese medicine that has long been used to treat viral and drug-induced hepatitis in China. The principal active components in WZC are Schisandra lignans. The clinical pharmacokinetics of these components in the form of an oral WZC preparation is unknown. To optimize the WZC dosage and develop WZC-related combination therapies, it is necessary to conduct a comprehensive pharmacokinetic study of the Schisandra lignans. Methods: A method was developed for simultaneous quantification of multiple bioactive lignans in WZC in human plasma through liquid–liquid extraction followed by multiple reaction monitoring liquid chromatography/tandem mass spectrometry with positive-mode electrospray ionization. The 5 bioactive constituents were separated by isocratic elution using a mobile phase consisting of acetonitrile, methanol, and 0.1% aqueous formic acid at a flow rate of 0.3 mL/min. The total run time was 3.5 minutes. Results: All analytes showed good linearity over a wide concentration range with a lower limit of quantification at 0.5 ng/mL. Using this method, we determined the 5 bioactive lignans in WZC from human plasma simultaneously and performed a pharmacokinetic study on the Schisandra lignans in healthy volunteers. Conclusions: Owing to simplicity, quickness, high sensitivity, and selectivity, and a sufficient lower limit of detection of the new liquid chromatography/tandem mass spectrometry method, it may be used as a routine technique for clinical monitoring of WZC, and for understanding interactions between herbal and conventional drug therapies.
An efficient test-data compaction for low power VLSI testing

This paper presents an input test data compaction and scan power reduction technique. We present new design for testability (DFT) method to hold values when some of test data in test cubes are not need to be changed. In our implementation, we present new algorithm called 2-D compaction to compact test cubes as less as possible and fill unspecified bits with specified value when necessary. Experimental results show a high compaction ratio improvement and amount of test data bits is close to compression effect. Itpsilas suggested that our method is promising for greatly reduce peak power and heat dissipation.
Clinical and Angiographic Outcomes after Intracoronary Bare-Metal Stenting

Background Data from a large patient population regarding very long-term outcomes after BMS implantation are inadequate. This study aimed to evaluate the very long-term (8–17 years) clinical and long-term (3–5 years) angiographic outcomes after intracoronary bare-metal stenting (BMS). Methods and Results From the Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions (CAPTAIN) registry, a total of 2391 patients with 2966 lesions treated with 3190 BMSs between November 1995 and May 2004 were evaluated. In total, 1898 patients with 2364 lesions, and 699 patients with 861 lesions underwent 6-month and 3- to 5- year angiographic follow-up, respectively. During a mean follow-up period of 149±51 months, 18.6% of the patients died (including 10.8% due to cardiac death), 6.1% developed reinfarction, 16.2% had target lesion revascularization (including 81% of the patients within the first year), 14.5% underwent new lesion stenting (including 72% of the patients after 3 years), 2.4% underwent coronary bypass surgery, and 1.6% had definite stent thrombosis. The overall cardiovascular event-free survival rate was 58.5%. The 6-month angiographic study indicated a 20% restenosis rate. The minimal luminal diameter increased from 0.65±0.44 mm to 3.02±0.46 mm immediately after stenting, decreased to 2.06±0.77 mm at the 6-month follow-up, and increased to 2.27±0.68 mm at the 3- to 5-year follow-up. Conclusions This study provides clinical and angiographic results from a large population of patients who underwent BMS implantations after a long-term follow-up period (149±51 months). The progression of coronary atherosclerosis developed over time, and presented with new lesion required stent implantation. The follow-up angiographic findings reconfirmed the late and sustained improvement in luminal diameter between 6 months and 3–5 years.
Dietary Cocoa Powder Improves Hyperlipidemia and Reduces Atherosclerosis in apoE Deficient Mice through the Inhibition of Hepatic Endoplasmic Reticulum Stress

Cocoa powder is rich in flavonoids, which have many beneficial effects on human health, including antioxidative and anti-inflammatory effects. The aim of our study was to investigate whether the intake of cocoa powder has any influence on hyperlipidemia and atherosclerosis and examine the underlying molecular mechanisms. We fed apoE knockout mice a Western diet supplemented with either 0.2% (low group) or 2% (high group) cocoa powder for 12 weeks. The groups fed dietary cocoa powder showed a significant reduction in both plasma cholesterol levels and aortic atherosclerosis compared to the control group. Analysis of mRNA profiling of aortic atherosclerotic lesions revealed that the expression of several genes related to apoptosis, lipid metabolism, and inflammation was significantly reduced, while the antiapoptotic gene Bcl2 was significantly increased in the cocoa powder group compared to the control. RT-PCR analysis along with Western blotting revealed that a diet containing cocoa powder inhibited the expression of hepatic endoplasmic reticulum stress. These data suggest that cocoa powder intake improves hyperlipidemia and atherosclerosis, and such beneficial effects are possibly mediated through the suppression of hepatic endoplasmic reticulum stress.
The Drosophila HNF4 nuclear receptor promotes glucose-stimulated insulin secretion and mitochondrial function in adults

Although mutations in HNF4A were identified as the cause of Maturity Onset Diabetes of the Young 1 (MODY1) two decades ago, the mechanisms by which this nuclear receptor regulates glucose homeostasis remain unclear. Here we report that loss of Drosophila HNF4 recapitulates hallmark symptoms of MODY1, including adult-onset hyperglycemia, glucose intolerance and impaired glucose-stimulated insulin secretion (GSIS). These defects are linked to a role for dHNF4 in promoting mitochondrial function as well as the expression of Hex-C, a homolog of the MODY2 gene Glucokinase. dHNF4 is required in the fat body and insulin-producing cells to maintain glucose homeostasis by supporting a developmental switch toward oxidative phosphorylation and GSIS at the transition to adulthood. These findings establish an animal model for MODY1 and define a developmental reprogramming of metabolism to support the energetic needs of the mature animal. DOI: http://dx.doi. org/10.7554/eLife.11183. 001
Principles of experience-dependent neural plasticity: implications for rehabilitation after brain damage.

PURPOSE This paper reviews 10 principles of experience-dependent neural plasticity and considerations in applying them to the damaged brain. METHOD Neuroscience research using a variety of models of learning, neurological disease, and trauma are reviewed from the perspective of basic neuroscientists but in a manner intended to be useful for the development of more effective clinical rehabilitation interventions. RESULTS Neural plasticity is believed to be the basis for both learning in the intact brain and relearning in the damaged brain that occurs through physical rehabilitation. Neuroscience research has made significant advances in understanding experience-dependent neural plasticity, and these findings are beginning to be integrated with research on the degenerative and regenerative effects of brain damage. The qualities and constraints of experience-dependent neural plasticity are likely to be of major relevance to rehabilitation efforts in humans with brain damage. However, some research topics need much more attention in order to enhance the translation of this area of neuroscience to clinical research and practice. CONCLUSION The growing understanding of the nature of brain plasticity raises optimism that this knowledge can be capitalized upon to improve rehabilitation efforts and to optimize functional outcome.
Types of cooperation partners as determinants of innovation failures

ABSTRACT In this paper we analyse if specific R&D cooperation partners are related to an increase in the probability of innovation failures in terms discontinuing innovation projects. We distinguish between seven different R&D cooperation partner types, and we discriminate between product innovation failures and process innovation failures. Using German Community Innovation Survey data we find that, firstly, each type of R&D cooperation partner has a different effect on innovation failures. Secondly, we show that product innovation failures and process innovation failures are not affected in equal measure by the same type of R&D cooperation partner. Our results suggest that while R&D cooperation with public research institutes is significantly and negatively related to the probability to cancel a process innovation project, the coefficient is positive but insignificant for product innovation failures. Firms conducting partnerships with suppliers, however, run the risk of both product and process innovation failures. In turn, cooperation with competitors is positively correlated only to process innovation failures.
The significance of major and stable molecular responses in chronic myeloid leukemia in the tyrosine kinase inhibitor era

Tyrosine kinase inhibitors have changed the management and outcomes of chronic myeloid leukemia patients. Quantitative polymerase chain reaction is used to monitor molecular responses to tyrosine kinase inhibitors. Molecular monitoring represents the most sensitive tool to judge chronic myeloid leukemia disease course and allows early detection of relapse. Evidence of achieving molecular response is important for several reasons: 1. early molecular response is associated with major molecular response rates at 18-24 months; 2. patients achieving major molecular response are less likely to lose their complete cytogenetic response; 3. a durable, stable major molecular response is associated with increased progression-free survival. However, standardization of molecular techniques is still challenging.
The complexity of the two dimensional curvature-constrained shortest-path problem

The motion planning problems for non-holonomic car-like robots have been extensively studied in the literature. The curvature-constrained shortest-path problem is to plan a path from an initial con guration to a nal con guration (where a con guration is de ned by a location and an orientation), in the presence of obstacles, such that the path is a shortest among all paths with a prescribed curvature bound. The curvature-constrained shortest-path problem can also be seen as nding a shortest path for a point car-like robot moving forward at constant speed with a radius of curvature bounded from above by some constant. Previously, there is no known hardness result for the 2D curvature constrained shortest-path problem. This paper shows that the above problem in two dimensions is NP-hard, when the obstacles are polygons with a total of N vertices and the vertex positions are given withinO(N) bits of precision. Our reduction is computed by a family of polynomial-size circuits. This NP-hardness result provides evidence that there are no eÆcient exact algorithms for curvature-constrained shortest-path planning in arbitrary environments, and it justi es the approaches based on approximation and discretization used in most of the previous papers on curvature-constrained path planning. Surface address: INRIA Lorraine-Loria, 615, rue du Jardin Botanique, B.P. 101, 54602 Villers-ls-Nancy cedex, FRANCE E-mail: lazard@loria.fr Surface address: Department of Computer Science, Duke University, Durham, NC 27708-0129. E-mail: reif@cs.duke. edu. Supported in part by Grants NSF/DARPA CCR9725021, CCR-96-33567, NSF IRI9619647, ARO contract DAAH-04-96-1-0448, and ONR contract N00014-99-1-0406. This paper was presented in the Workshop on the Algorithmic Foundations of Robotics (WAFR98), Houston, Texas,June, 1998.
Minimal hepatic encephalopathy.

Minimal hepatic encephalopathy (MHE) is a condition in which patients with cirrhosis of liver that has normal mental and neurological status on standard clinical examination exhibit a number of neuropsychiatric and neurophysiological defects. Its prevalence varies up to 80% in cirrhotics . It is characterized by a specific, complex cognitive dysfunction which is independent of sleep dysfunction or problems with overall intelligence. Increasing evidence indicates that MHE is an important disorder that may seriously impair a patients daily functioning and quality of life. Psychomotor slowing, visuoconstructive disabilities, attention deficits are among the few key features while fine motor performance is also impaired. MHE may predict the development of overt hepatic encephalopathy. Various tools have been evaluated for the correct diagnosis of MHE, however, in the absence of a "gold standard", combination of test methods is recommended to most reliably diagnosed MHE. Presently, lactulose is the mainstay of treatment for MHE. However various therapies like probiotics and ornithine aspartate are under evaluation as an alternative to lactulose.
Symptoms and haematologic features in consecutive adult coeliac patients.

BACKGROUND The aim of this study was to determine in a homogeneous adult population from Denmark, which is known to have very low incidence rates of coeliac disease, 1) the percentage of patients presenting with mild or atypical symptoms; 2) a possible change in clinical pattern over time; and 3) the delay in diagnosis and the age and sex distribution. METHODS The symptoms, delay in diagnosis, age, sex, and haematologic features of 50 consecutive adult coeliac patients, diagnosed by the same person in a uniform manner, are presented. RESULTS The median age was 40.5 (range, 17-82) years. The male to female sex ratio was 1:2.8. The median delay in diagnosis was 3 years. Fifty-eight per cent reported symptoms that could be attributed to coeliac disease during childhood. Presenting symptoms were tiredness, 78%; borborygmus, 72%; abdominal pain, 64%; diarrhoea, 56%; weight loss, 44%; vomiting, 16%; constipation, 12%; bone pain, 12%; and dermatitis herpetiformis, 10%. Weight gain after treatment was experienced by 84%. As a group the coeliac patients had many abnormal blood analysis results, but many patients had several test results inside the normal range. Only 22% had anemia. Liver involvement was not an uncommon feature (19% had increased transaminase levels). Low values were registered in s-iron (32%), p-folate (49%), c-folate (35%), p-vitamin B12 (11%), p-coagulation factors (II, VII, X) (32%), s-protein (21%), s-albumin (26%), s-calcium (43%), p-magnesium (13%), and s-zinc (31%). High/low IgG levels were 3%/8%; high, IgA 21%; high/low IgM, 65%/14%; and high IgE, 71%. The gliadin antibody test was the best screening test (81% positive). No changes in clinical pattern were demonstrated during the period. CONCLUSION The percentage of patients presenting with anaemia (22%) and other haematologic signs of malabsorption was one of the lowest reported ever. This emphasizes the highly variable and subtle clinical expression of adult coeliac disease.
Solving Multi-Item Capacitated Lot-Sizing Problems with Setup Times by Branch-and-Cut

Instances of the multi-item capacitated lot-sizing problem with setup times (MCL) often appear in practice, either in standard form or with additional constraints, but they have generally been difficult to solve to optimality. In MCL demand for multiple items must be met over a time horizon, items compete for a shared capacity, and each setup uses up some of this capacity. In this paper we use results concerning the polyhedral structure of simplified models obtained from a single time period of MCL to obtain strong valid inequalities for MCL. To the best of our knowledge, these inequalities are the first to consider demand for multiple items and the joint capacity restriction simultaneously. We also discuss how to implement these inequalities successfully in a branch-and-cut algorithm. Our computational results suggest that our contributions represent significant progress in solving instances of MCL.
Opposing Effects of Inhibiting Cap Addition and Cap Methylation on Polyadenylation during Vesicular Stomatitis Virus mRNA Synthesis

ABSTRACT The multifunctional large (L) polymerase protein of vesicular stomatitis virus (VSV) contains enzymatic activities essential for RNA synthesis, including mRNA cap addition and polyadenylation. We previously mapped amino acid residues G1154, T1157, H1227, and R1228, present within conserved region V (CRV) of L, as essential for mRNA cap addition. Here we show that alanine substitutions to these residues also affect 3′-end formation. Specifically, the cap-defective polymerases produced truncated transcripts that contained A-rich sequences at their 3′ termini and predominantly terminated within the first 500 nucleotides (nt) of the N gene. To examine how the cap-defective polymerases respond to an authentic VSV termination and reinitiation signal present at each gene junction, we reconstituted RNA synthesis using templates that contained genes inserted (I) at the leader-N gene junction. The I genes ranged in size from 382 to 1,098 nt and were typically transcribed into full-length uncapped transcripts. In addition to lacking a cap structure, the full-length I transcripts synthesized by the cap-defective polymerases lacked an authentic polyadenylate tail and instead contained 0 to 24 A residues. Moreover, the cap-defective polymerases were also unable to copy efficiently the downstream gene. Thus, single amino acid substitutions in CRV of L protein that inhibit cap addition also inhibit polyadenylation and sequential transcription of the genome. In contrast, an amino acid substitution, K1651A, in CRVI of L protein that completely inhibits cap methylation results in the hyperpolyadenylation of mRNA. This work reveals that inhibiting cap addition and cap methylation have opposing effects on polyadenylation during VSV mRNA synthesis and provides evidence in support of a link between correct 5′ cap formation and 3′ polyadenylation.
Polyploidy in large-headed sperm: FISH study of three cases.

BACKGROUND Macrocephalic or large headed sperm with multiflagella is a rare abnormality often associated with infertility. Sperm chromosomal abnormalities could be associated with this specific morphological abnormality. METHODS The cytogenetic content of large-headed sperm was assessed by dual and three-colour fluorescence in-situ hybridization in three patients carrying this specific morphological abnormality. RESULTS In all patients nearly all sperm contained at least one copy of each sex chromosome, and in more than half of them at least two copies of either chromosome 1 or 18 were identified. In some sperm a tetraploidy was found. CONCLUSIONS These observations suggested that both meiotic I and II divisions were affected by incomplete partition of homologous chromosomes during meiosis I and of sister chromatids during meiosis II associated with a failure of nuclear cleavage. Furthermore, they provide evidence for a clear relationship between a specific morphological abnormality of the sperm and their abnormal cytogenetic content. The treatment of infertility using ICSI would probably be unsuccessful and have a high genetic risk in these cases.
Modelling and experimental investigation of geometrically graded NiTi shape memory alloys

To improve actuation controllability of a NiTi shape memory alloy component in applications, it is desirable to create a wide stress window for the stress-induced martensitic transformation in the alloy. One approach is to create functionally graded NiTi with a geometric gradient in the actuation direction. This geometric gradient leads to transformation load and displacement gradients in the structure. This paper reports a study of the pseudoelastic behaviour of geometrically graded NiTi by means of mechanical model analysis and experimentation using three types of sample geometry. Closed-form solutions are obtained for nominal stress–strain variation of such components under cyclic tensile loading and the predictions are validated with experimental data. The geometrically graded NiTi samples exhibit a distinctive positive stress gradient for the stress-induced martensitic transformation and the slope of the stress gradient can be adjusted by sample geometry design.
Causalities among momentum, transparency and media in China

We studied the relationships among momentum, transparency, and media by causality detections in Chinese stock markets. Our results suggest that momentum strongly and individually attracts media coverage in China, as this effect exists both in the Granger test and the transfer entropy test. Media coverage causes momentum only in Granger test, which is consistent with Hillert et al. (2014). In other words, momentum and media coverage are tightly related to each other in China. In the Granger test, transparency causes momentum with the assistance of media coverage, and it receives media coverage with the assistance of momentum. These results suggest that transparency has to release its information because of the pushing power from momentum or media. In the transfer entropy test, transparency can individually cause momentum or media coverage, which implies that transparency indirectly releases information when there is no influence of momentum or media.
The HARMONY Trial: Combined Ranolazine and Dronedarone in the Management of Paroxysmal Atrial Fibrillation Mechanistic and Therapeutic Synergism

Background—Atrial fibrillation (AF) requires arrhythmogenic changes in atrial ion channels/receptors and usually altered atrial structure. AF is commonly treated with antiarrhythmic drugs; the most effective block many ion channels/receptors. Modest efficacy, intolerance, and safety concerns limit current antiarrhythmic drugs. We hypothesized that combining agents with multiple anti-AF mechanisms at reduced individual drug doses might produce synergistic efficacy plus better tolerance/safety. Methods and Results—HARMONY tested midrange ranolazine (750 mg BID) combined with 2 reduced dronedarone doses (150 mg BID and 225 mg BID; chosen to reduce dronedarone’s negative inotropic effect—see text below) over 12 weeks in 134 patients with paroxysmal AF and implanted pacemakers where AF burden (AFB) could be continuously assessed. Patients were randomized double-blind to placebo, ranolazine alone (750 mg BID), dronedarone alone (225 mg BID), or one of the combinations. Neither placebo nor either drugs alone significantly reduced AFB. Conversely, ranolazine 750 mg BID/dronedarone 225 mg BID reduced AFB by 59% versus placebo (P=0.008), whereas ranolazine 750 mg BID/dronedarone 150 mg BID reduced AFB by 43% (P=0.072). Both combinations were well tolerated. Conclusions—HARMONY showed synergistic AFB reduction by moderate dose ranolazine plus reduced dose dronedarone, with good tolerance/safety, in the population enrolled. Clinical Trial Registration—ClinicalTrials.gov; Unique identifier: NCT01522651.