Miracle-dz/UniFAR-FTUs huggingface dataset:
Divalent Cation Sensitivity of BK Channel Activation Supports the Existence of Three Distinct Binding Sites

Mutational analyses have suggested that BK channels are regulated by three distinct divalent cation-dependent regulatory mechanisms arising from the cytosolic COOH terminus of the pore-forming α subunit. Two mechanisms account for physiological regulation of BK channels by μM Ca2+. The third may mediate physiological regulation by mM Mg2+. Mutation of five aspartate residues (5D5N) within the so-called Ca2+ bowl removes a portion of a higher affinity Ca2+ dependence, while mutation of D362A/D367A in the first RCK domain also removes some higher affinity Ca2+ dependence. Together, 5D5N and D362A/D367A remove all effects of Ca2+ up through 1 mM while E399A removes a portion of low affinity regulation by Ca2+/Mg2+. If each proposed regulatory effect involves a distinct divalent cation binding site, the divalent cation selectivity of the actual site that defines each mechanism might differ. By examination of the ability of various divalent cations to activate currents in constructs with mutationally altered regulatory mechanisms, here we show that each putative regulatory mechanism exhibits a unique sensitivity to divalent cations. Regulation mediated by the Ca2+ bowl can be activated by Ca2+ and Sr2+, while regulation defined by D362/D367 can be activated by Ca2+, Sr2+, and Cd2+. Mn2+, Co2+, and Ni2+ produce little observable effect through the high affinity regulatory mechanisms, while all six divalent cations enhance activation through the low affinity mechanism defined by residue E399. Furthermore, each type of mutation affects kinetic properties of BK channels in distinct ways. The Ca2+ bowl mainly accelerates activation of BK channels at low [Ca2+], while the D362/D367-related high affinity site influences both activation and deactivation over the range of 10–300 μM Ca2+. The major kinetic effect of the E399-related low affinity mechanism is to slow deactivation at mM Mg2+ or Ca2+. The results support the view that three distinct divalent-cation binding sites mediate regulation of BK channels.
SCALAR FIELDS COUPLED TO FOUR-DIMENSIONAL LATTICE GRAVITY

I discuss some results we have obtained recently in a lattice model for quantized gravity coupled to scalar matter in four dimensions. We have looked at how the continuous phase transition separating the smooth from the rough phase of gravity is inuenced by the presence of the scalar eld. We nd that close to the critical point, where the average curvature approaches zero, the eects of the scalar eld are small and the coupling of matter to gravity seems to be weak. The nature of the phase diagram and the values for the critical exponents would suggest that gravitational interactions increase with distance.
Comparative analysis of the transcriptional responses to low and high temperatures in three rice planthopper species

The brown planthopper (Nilaparvata lugens, BPH), white‐backed planthopper (Sogatella furcifera, WBPH) and small brown planthopper (Laodelphax striatellus, SBPH) are important rice pests in Asia. These three species differ in thermal tolerance and exhibit quite different migration and overwintering strategies. To understand the underlying mechanisms, we sequenced and compared the transcriptome of the three species under different temperature treatments. We found that metabolism‐, exoskeleton‐ and chemosensory‐related genes were modulated. In high temperature (37 °C), heat shock protein (HSP) genes were the most co‐regulated; other genes related with fatty acid metabolism, amino acid metabolism and transportation were also differentially expressed. In low temperature (5 °C), the differences in gene expression of the genes for fatty acid synthesis, transport proteins and cytochrome P450 might explain why SBPH can overwinter in high latitudes, while BPH and WBPH cannot. In addition, other genes related with moulting, and membrane lipid composition might also play roles in resistance to low and high temperatures. Our study illustrates the common responses and different tolerance mechanisms of three rice planthoppers in coping with temperature change, and provides a potential strategy for pest management.
A high-speed dynamic instruction scheduling scheme for supersealar processors

The wakeup logic is a part of the issuing window and is responsible to manage the ready flags of the operands for dynamic instruction scheduling. The conventional wakeup logic is based on association, and composed of a RAM and a CAM. Since the logic is not pipelinable and the delays of these memories are dominated by the wire delays, the logic will be more critical with deeper pipelines and smaller feature sizes. This paper describes a new scheduling scheme not based on the association but on matrices which represent the dependences between instructions. Since the update logic of the matrices detects the dependencies between instructions as the register renaming logic does, the wakeup operation is realized by just reading the matrices. This paper also describes a technique to reduce the effective size of the matrices for small IPC penalties. We designed the layouts of the logics guided by a 0. 18µm CMOS design rule provided by Fujitsu Limited, and calculated the delays. We also evaluated the penalties by cycle-level simulation. The results show that our scheme achieves 2.7GHz clock speed for the IPC degradation of about 1%.
Investigation of SOA nonlinearities on the amplification of DWDM channels with spectral efficiency up to 2.5 b/s/Hz

We have investigated and compared the effect of semiconductor optical amplifier (SOA) nonlinearities on the amplification of 14 dense wavelength-division-multiplexing channels using return-to-zero on-off keying [(RZ-OOK) 1 b/symbol], RZ differential quadrature phase-shift keying [(DQPSK) 2 b/symbol], and polarization (bit interleaved) multiplexed RZ-DQPSK (4 b/symbol) formats with aggregate data rates up to 50 Gb/s per channel. The channel spacing was 20 GHz with spectral efficiency from 0.625 up to 2.5 b/s/Hz. Our results have shown that while RZ-OOK format performs better at lower SOA input powers, RZ-DQPSK suffers less degradation from SOA nonlinearities at higher input powers. Overall, polarization-bit-interleaved RZ-DQPSK format was found to have the best tolerance to SOA nonlinearities.
On Convergence Rate of a Class of Genetic Algorithms

Studying convergence rate of a genetic algorithm is a very important but a nontrivial task. The more accurate estimation of convergence rate for genetic algorithms can be used to design the more efficient control parameters of algorithms, and to point out the correct direction to improve the algorithms. Moreover, one good measure of convergence rate can be used to judge the efficiency of different algorithms. The existing results about the convergence rate for genetic algorithms can be classified into two types. One type is based on Doeblin condition in which some parameters should be estimated. The other type needs to estimate the eigenvalues of the state transition matrix. However, these parameters are difficult to estimate. In this paper, we first formulate a model for a class of genetic algorithms, and then analyze the convergence rate of such an algorithm in a different way. It shows that their convergence rate is linear based on property of Markov chain.
Golimumab, a human antibody to tumour necrosis factor α given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study

Objective: The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy. Methods: Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n = 133), golimumab 100 mg injections plus placebo capsules (group 2, n = 133), golimumab 50 mg injections plus methotrexate capsules (group 3, n = 89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n = 89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24. Results: The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively. Conclusion: The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function.
Dependency Tree Abstraction for Long-Distance Reordering in Statistical Machine Translation

Word reordering is a crucial technique in statistical machine translation in which syntactic information plays an important role. Synchronous context-free grammar has typically been used for this purpose with various modifications for adding flexibilities to its synchronized tree generation. We permit further flexibilities in the synchronous context-free grammar in order to translate between languages with drastically different word order. Our method pre-processes a parallel corpus by
Distribution of insulin receptor and insulin-like growth factor-1 receptor in the digital laminae of mixed-breed ponies: an immunohistochemical study.

REASONS FOR PERFORMING STUDY Hyperinsulinaemia has been implicated in the pathogenesis of laminitis; however, laminar cell types responding to insulin remain poorly characterised. OBJECTIVES To identify laminar cell types expressing insulin receptor (IRc) and/or insulin-like growth factor-1 receptor (IGF-1R); and to evaluate the effect of dietary nonstructural carbohydrate (NSC) on their expression. METHODS Mixed-breed ponies (n = 22) received a conditioning hay chop diet (NSC ∼6%); following acclimation, ponies were stratified into lean (n = 11, body condition score [BCS]≤4) or obese (n = 11, BCS ≥7) groups and each group further stratified to remain on the low NSC diet (n = 5 each for obese and lean) or receive a high NSC diet (total diet ∼42% NSC; n = 6 each for obese and lean) for 7 days. Laminar samples were collected at the end of the feeding protocol and stained immunohistochemically for IRc and IGF-1R. The number of IRc(+) cells was quantified; distribution of IGF-1R was qualitatively described. Laminar IRc content was assessed via immunoblotting. RESULTS The number of IRc(+) cells was greater in the laminae of high NSC ponies than low NSC ponies (P = 0.001); there was a positive correlation between the change in serum insulin concentration and number of IRc(+) cells (r(2) = 0.74; P<0.0001). No epithelial IRc(+) cells were observed; IRc(+) cells were absent from the deep dermis. Analysis of serial sections identified IRc(+) cells as endothelial cells. The distribution of IGF-1R was more extensive than that of IRc, with signal in vascular elements, epithelial cells and fibroblasts. CONCLUSIONS Increased dietary NSC results in increased laminar endothelial IRc expression. Laminar keratinocytes do not express IRc, suggesting that insulin signalling in laminar epithelial cells must be mediated through other receptors (such as IGF-1R). POTENTIAL RELEVANCE Manipulation of signalling downstream of IRc and IGF-1R may aid in treatment and prevention of laminitis associated with hyperinsulinaemia.
Enigmatic dual symbiosis in the excretory organ of Nautilus macromphalus (Cephalopoda: Nautiloidea)

Symbiosis is an important driving force in metazoan evolution and the study of ancient lineages can provide an insight into the influence of symbiotic associations on morphological and physiological adaptations. In the ‘living fossil’ Nautilus, bacterial associations are found in the highly specialized pericardial appendage. This organ is responsible for most of the excretory processes (ultrafiltration, reabsorption and secretion) and secretes an acidic ammonia-rich excretory fluid. In this study, we show that Nautilus macromphalus pericardial appendages harbour a high density of a β-proteobacterium and a coccoid spirochaete using transmission electron microscopy, comparative 16S rRNA sequence analysis and fluorescence in situ hybridization (FISH). These two bacterial phylotypes are phylogenetically distant from any known bacteria, with ammonia-oxidizing bacteria as the closest relatives of the β-proteobacterium (above or equal to 87.5% sequence similarity) and marine Spirochaeta species as the closest relatives of the spirochaete (above or equal to 89.8% sequence similarity), and appear to be specific to Nautilus. FISH analyses showed that the symbionts occur in the baso-medial region of the pericardial villi where ultrafiltration and reabsorption processes take place, suggesting a symbiotic contribution to the excretory metabolism.
Use of Bayesian Markov Chain Monte Carlo Methods to Model Cost-of-Illness Data

It is well known that the modeling of cost data is often problematic due to the distribution of such data. Commonly observed problems include 1) a strongly right-skewed data distribution and 2) a significant percentage of zero-cost observations. This article demonstrates how a hurdle model can be implemented from a Bayesian perspective by means of Markov Chain Monte Carlo simulation methods using the freely available software WinBUGS. Assessment of model fit is addressed through the implementation of two cross-validation methods. The relative merits of this Bayesian approach compared to the classical equivalent are discussed in detail. To illustrate the methods described, patient-specific nonhealth-care resource-use data from a prospective longitudinal study and the Norfolk Arthritis Register (NOAR) are utilized for 218 individuals with early inflammatory polyarthritis (IP). The NOAR database also includes information on various patient-level covariates.
Imaging and Behavioral Correlates of the Anterior Cingulate in Pediatric Traumatic Brain Injury

Imaging and Behavioral Correlates of the Anterior Cingulate in Pediatric Traumatic Brain Injury Tricia L. Merkley Department of Psychology, BYU Doctor of Philosophy The anterior cingulate has been implicated in a number of cognitive processes that are at risk following traumatic brain injury (TBI), such as executive function and emotional processing. While the cingulate is believed to play a role in the above-mentioned cognitive processes, the relative roles of gray and white matter in functional outcomes post-TBI are not fully understood. The current study investigated various quantifiable brain properties (e.g., cortical thickness and volume, volume of underlying white matter, and white matter integrity) of the caudal anterior cingulate (CAC) gyrus and their relationships with behavioral measures of cognitive control following pediatric TBI. Parent ratings at three months post-injury indicated that TBI children demonstrated greater difficulty inhibiting inappropriate behavior and effectively transitioning between tasks. Reductions of CAC white matter integrity were observed in TBI participants, in the absence of significant morphometric group differences in this region. Neither CAC morphometrics nor fractional anisotropy (FA) were associated with experimental measures of cognitive control. The current findings indicate that DTI metrics may be more sensitive to brain changes in the region of the CAC following TBI. While strong relationships were not observed between CAC properties and measures of cognitive control, it is possible that study limitations may have obscured potential findings.
Microstructural Modeling and Computational Homogenization of the Physically Linear and Nonlinear Constitutive Behavior of Micro-Heterogeneous Materials

Most engineering materials show a pronounced heterogeneity on a smaller scale that influences the macroscopic constitutive behavior. In order to examine this relation, the concept of model microstructures is introduced. Algorithms for the periodic discretization are presented for use in thermomechanical homogenization based on the finite element method. Polycrystalline metals, metal ceramic composites and porous materials are investigated. The microstructures are used in the Nonuniform Transformation Field Analysis (NTFA). The NTFA is an order reduction based nonlinear homogenization method with micro-mechanical background. Theoretical and numerical aspects of the method are discussed and its efficiency is validated. Further, Monte Carlo type simulations on periodic porous aggregates are performed in order to predict the macroscopic yield surface of such materials. The thereby generated yield curves are compared to existing models.
CFH Y402H and ARMS2 A69S Polymorphisms and Oral Supplementation with Docosahexaenoic Acid in Neovascular Age-Related Macular Degeneration Patients: The NAT2 Study

Purpose Genetic susceptibility could be modified by environmental factors and may also influence differential responses to treatments for age-related macular degeneration (AMD). We investigated whether genotype could influence response to docosahexaenoic acid (DHA)-supplementation in the occurrence of choroidal new vessels (CNV). Methods The Nutritional AMD Treatment 2 (NAT2) study was a randomized, placebo-controlled, double-blind, parallel, comparative study, including 250 patients aged 55 to 85 years with early lesions of age-related maculopathy, visual acuity better than 0.4 Logarithm of Minimum Angle of Resolution units in the study eye and neovascular AMD in the fellow eye. Patients were randomized at baseline to receive either 3 daily fish-oil capsules, each containing 280 mg DHA, 90 mg EPA and 2 mg Vitamin E, or placebo. Results Patients carrying the risk allele (C) for CFH Y402H had no statistically significant increased risk for developing CNV in the study eye (Hazard Ratio (HR)=0.97; 95% Confidence Interval (CI): 0.54-1.76 for heterozygous and HR=1.29; 95%CI: 0.69-2.40 for homozygous). Patients carrying the risk allele (T) for ARMS2 A69S had no statistically significant increased risk for developing CNV in the study eye (HR=1.68; 95%CI: 0.91-3.12) for heterozygous and HR=1.78; 95%CI: 0.90-3.52 for homozygous). A significant interaction was observed between CFH Y402H and DHA-supplementation (p=0.01). We showed a protective effect of DHA-supplementation among homozygous non-risk patients. Among these patients, occurrence of CNV was 38.2% in placebo group versus 16.7% in DHA group (p=0.008). Conclusions These results suggest that a genetic predisposition to AMD conferred by the CFH Y402H variant limits the benefit provided by DHA supplementation. Trial Registration ISRCTN registry 98246501
Unsupervised Induction of Labeled Parse Trees by Clustering with Syntactic Features

We present an algorithm for unsupervised induction of labeled parse trees. The algorithm has three stages: bracketing, initial labeling, and label clustering. Bracketing is done from raw text using an unsupervised incremental parser. Initial labeling is done using a merging model that aims at minimizing the grammar description length. Finally, labels are clustered to a desired number of labels using syntactic features extracted from the initially labeled trees. The algorithm obtains 59% labeled f-score on the WSJ10 corpus, as compared to 35% in previous work, and substantial error reduction over a random baseline. We report results for English, German and Chinese corpora, using two label mapping methods and two label set sizes.
Identification by site-directed mutagenesis of amino acid residues contributing to serologic and CTL-defined epitope differences between HLA-A2.1 and HLA-A2.3.

Site-directed mutagenesis of HLA-A2.1 has been used to identify the amino acid substitutions in HLA-A2.3 that are responsible for the lack of recognition of the latter molecule by the HLA-A2/A28 specific antibody, CR11-351, and by HLA-A2.1 specific CTL. Three genes were constructed that encoded HLA-A2 derivatives containing one of the amino acids known to occur in HLA-A2.3: Thr for Ala149, Glu for Val152, and Trp for Leu156. Three additional genes were constructed that encoded the different possible combinations of two amino acid substitutions at these residues. Finally, a gene encoding all three substitutions and equivalent to HLA-A2.3 was constructed. These genes were transfected into the class I negative, human cell line Hmy2.C1R. Analysis of this panel of cells revealed that recognition by the antibody CR11-351 was completely lost when Thr was substituted for Ala149, whereas substitutions at amino acids 152 and 156, either singly or in combination, had no effect on the binding of this antibody. The epitopes recognized by the allogeneic and xenogeneic HLA-A2.1 specific CTL clones used in this study were all affected by either one or two amino acid substitutions. Of those epitopes sensitive to single amino acid changes, none were affected by the substitution of Thr for Ala149, whereas all of them were affected by at least one of the substitutions of Glu for Val 152 or Trp for Leu156. Overall, amino acid residue 152 exerted a stronger effect on the epitopes recognized by HLA-A2.1 specific CTL than did residue 156. Of those epitopes affected only by multiple amino acid substitutions, double substitutions at residues 149 and 152 or at 152 and 156 resulted in a loss of recognition, whereas a mutant with substitutions at residues 149 and 156 was recognized normally. This reemphasizes the importance of residue 152 and indicates that residue 149 can affect epitope formation in conjunction with another amino acid substitution. These results are discussed in the context of current models for the recognition of alloantigens and in light of the recently published three-dimensional structure of the HLA-A2.1 molecule.
Feasibility of Using the Sony PlayStation 2 Gaming Platform for an Individual Poststroke: A Case Report

Rationale: Many Americans live with physical functional limitations stemming from stroke. These functional limitations can be reduced by task-specific training that is repetitive, motivating, and augmented with feedback. Virtual reality (VR) is reported to offer an engaging environment that is repetitive, safe, motivating, and gives task-specific feedback. The purpose of this case report was to explore the use of a low-cost VR device [Sony PlayStation 2 (PS2) EyeToy] for an individual in the chronic phase of stroke recovery. Case: An individual two years poststroke with residual sensorimotor deficits completed 20 one-hour sessions using the PS2 EyeToy. The game's task requirements included target-based motion, dynamic balance, and motor planning. The feasibility of using the gaming platform was explored and a broad selection of outcomes was used to assess change in performance. Outcomes: Device use was feasible. Clinically relevant improvements were found on the Dynamic Gait Index and trends toward improvement on the Fugl-Meyer Assesment, Berg Balance Scale, UE Functional Index, Motor Activity Log, and Beck Depression Inventory. Conclusion: A low-cost VR system was easily used in the home. In the future it may be used to improve sensory/motor recovery following stroke as an adjunct to standard care physical therapy.