Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of mutations involving cysteine residues distal to the S281HCC motif at the C-terminus on the functional characteristics of a truncated ectodomain-only thyrotropin receptor anchored on glycosylphosphatidyl-inositol.

BACKGROUND Cysteine (Cys) residues pair to form disulfide bonds that are important in maintaining structure and function of the thyrotropin receptor (TSHR). There are 11 Cys residues in the ectodomain (ECD). Cys 41 at the N-terminus and Cys 283 at the SHCC motif have been identified as important for ligand binding. The present study evaluated the effects of mutating Cys distal to the S281HCC motif at the C-terminus of the ECD on the functional characteristics of TSHR. METHODS We introduced (i) individual Cys and (ii) consecutive cumulative Cys mutations into the starting template SHCS-TSHR, a truncated TSHR-ECD moiety previously shown to behave like the wild-type TSHR. Each mutant receptor was evaluated for relative specific binding (RSB), calculated as a measure of TSH-binding ability after normalization with receptor surface expression. RESULTS In the first approach, RSB was severely affected when Cys 390 and Cys 398 were individually switched to serine. Failed receptor trafficking occurred with Cys 408 mutation. These findings were likely results of altered receptor conformation due to illegitimate disulfide bridge formation. Only SHCS-301 TSHR bound TSH in a specific manner, and it formed the base for sequential Cys mutations. Through this second approach, both Cys 301 and 390 could be removed simultaneously without hindering TSH binding significantly. Cys 398, however, was shown to be critical. Its absence resulted in huge loss of TSH binding. Leaving Cys 283 and 398 as the only Cys pair in the C-terminus alone could support 40% of the total ligand-binding capacity. CONCLUSIONS From these data, we proposed Cys 398 as a stable disulfide bond partner of Cys 283, corroborating with a model based on evolutionary history of TSHR across species. This pairing of Cys 283 and Cys 398 also provides an objective alternative to conventional hypotheses on Cys coupling based on other predictive models.
TANK2, a New TRF1-associated Poly(ADP-ribose) Polymerase, Causes Rapid Induction of Cell Death upon Overexpression*

Tankyrase (TANK1) is a human telomere-associated poly(ADP-ribose) polymerase (PARP) that binds the telomere-binding protein TRF1 and increases telomere length when overexpressed. Here we report characterization of a second human tankyrase, tankyrase 2 (TANK2), which can also interact with TRF1 but has properties distinct from those of TANK1. TANK2 is encoded by a 66-kilobase pair gene (TNKS2) containing 28 exons, which express a 6.7-kilobase pair mRNA and a 1166-amino acid protein. The protein shares 85% amino acid identity with TANK1 in the ankyrin repeat, sterile α-motif, and PARP catalytic domains but has a unique N-terminal domain, which is conserved in the murine TNKS2 gene. TANK2 interacted with TRF1 in yeast and in vitro and localized predominantly to a perinuclear region, similar to the properties of TANK1. In contrast to TANK1, however, TANK2 caused rapid cell death when highly overexpressed. TANK2-induced death featured loss of mitochondrial membrane potential, but not PARP1 cleavage, suggesting that TANK2 kills cells by necrosis. The cell death was prevented by the PARP inhibitor 3-aminobenzamide. In vivo, TANK2 may differ from TANK1 in its intrinsic or regulated PARP activity or its substrate specificity.
Masterclass: Spinal manipulative thrust technique using combined movement theory

Spinal Manipulative Thrust Technique (SMTT) is employed by all manual therapy professions using different rationales for the selection of technique. A method of rationally selecting particular SMTT’s is described with a view to integrating SMTT into the practice of manual therapists familiar with Combined Movement Theory (CMT), a corollary of the Maitland Concept. The similarities of CMT and SMTT methodologies are described and two examples of how CMT can be utilized for SMTT selection in the cervical spine are detailed. # 2001 Harcourt Publishers Ltd.
Atherosclerosis in premenopausal women with antiphospholipid syndrome and systemic lupus erythematosus: a controlled study.

OBJECTIVE To evaluate whether premenopausal women with antiphospholipid syndrome (APS) or systemic lupus erythematosus (SLE) have increased prevalence of atherosclerosis after adjustment has been made for known cardiovascular risk factors. METHODS We evaluated premenopausal women with APS in comparison with age-matched groups of patients with SLE [positive or negative for anticardiolipin (aCL) antibodies] or rheumatoid arthritis (RA), and healthy subjects. Thirty-three subjects in each group were assessed for cardiovascular risk factors, including a detailed lipid profile. Ultrasonography of carotid and femoral arteries assessed the intima-media thickness (IMT) and the presence of atherosclerotic plaque. RESULTS Atherosclerotic plaques were detected in 5, 2, 4, 1 and 1 subject in the five groups respectively. APS patients had significantly more affected vessels than RA patients and healthy controls (P=0.042 and P=0.016, respectively), but not compared with SLE patients. No consistent differences in IMT, traditional cardiovascular risk factors or lipid parameters were detected among the five groups. The odds for atherosclerosis independently increased 1.19-fold per year of increasing age [95% confidence interval (CI) 1.08-1.31; P=0.001), 1.019-fold per 1 mg/dl increase in low-density lipoprotein (LDL) (95% CI 1.003-1.036; P=0.020), 1.035-fold per additional 1 g of methylprednisolone equivalent cumulative corticosteroid dose (95% CI, 0.996-1.074; P=0.074), and 4.35-fold in the presence of APS or SLE (95% CI 0.75-25.2; P=0.10). Neither aCL nor anti-beta(2)GPI antibodies were associated with atherosclerosis. CONCLUSION Premenopausal APS and SLE women have an increased prevalence of carotid and femoral plaque that is not accounted for by other predictors of atherosclerosis, including age, lipid parameters and cumulative steroid dose.
Noun Verb Dissociation in Parkinson's Disease

A noun/verb dissociation with a relative verb deficit was found in patients affected by Parkinson's disease, even in relatively early stages, when mental deterioration is not severe. This finding is compatible with earlier observations, according to which verbs are dealt with in more anterior regions with respect to nouns. It also supports the speculation that the co-ordination and the manipulation of information associated with a verb world rely on the frontostriatal system.
AD-A 282 657 Science DI 1 IIIIIJIII 1 ffui On Predictable Operating System Protocol Processing

Distributed continuous media applications that incorporate digital audio and video require predictable response from the operating system and the network. Much recent research in communication networks focuses on providing predictable service at the network level, but current operating systems do not typically provide end-to-end predictability. Our aim is to offer operating system support for predictability while still maintaining the dynamic, easy-to-use environment of a general purpose operating system. We explore the use of a resource reservation mechanism in the operating system with the idea that this mechanism can be used to support higher level quality of service management policies. We also employ a protocol software structure that uses priorities, preemptive packet servicing, and reservation enforcement to allow the reservation scheduling policy to make fine-grained scheduling decisions to control the protocol processing activities. By reserving resources such as buffers, computation time for application-level activities, and computation time for protocol processing, our system can support predictable behavior for distributed real-time application programs. We implemented our reservation mechanism using the Real-Time Mach operating system as a base, and we present performance results which demonstrate that our approach provides predictable network service to distributed multimedia applications.
Regularized phase tomography enables study of mineralized and unmineralized tissue in porous bone scaffold

Regularized phase tomography was used to image non‐calcified fibrous matrix in in vitro cell‐cultivated porous bone scaffold samples. 3D micro‐architecture of bone and bone scaffold has previously been studied by micro‐computed tomography, synchrotron radiation (SR) micro‐computed tomography and microdiffraction. However, neither of these techniques can resolve the low‐calcified immature pre‐bone fibrous structures. Skelite porous scaffold discs were seeded with osteoblasts, a combination of osteoblast and pre‐osteoclasts and, as controls, with pre‐osteoclasts only, and then cultivated for 8 weeks. They were subsequently imaged using SR propagation‐based phase contrast imaging. Reconstructions using a regularized holographic phase tomography approach were compared to standard (absorption) SR micro‐computed tomography, which show that quantitative analysis, such as volume and thickness measurements, of both the calcified fraction and the immature bone matrix in the reconstructed volumes is enabled. Indications of the effect of this type of culture on Skelite, such as change in mineralization and deposit of mature bone on the walls of the scaffold, are found. The results are verified with a histological study.
Influence of Body-Biasing, Supply Voltage, and Temperature on the Detection of Resistive Short Defects in FDSOI Technology

This paper presents an in-depth analysis of the impact of body-biasing, supply voltage, and temperature on the detection of resistive short defects in FDSOI technology. Three types of short defects are considered for our investigation, namely resistive short to ground terminal, resistive short to power supply terminal (VDD), and intergate resistive bridging defect. The two implementation options offered by the technology, i.e., low VT (LVT) and regular VT (RVT) devices are also studied. Defect detectability is evaluated in the context of logic test using the concept of critical resistance. The optimal body-biasing, supply voltage, and temperature settings to achieve the maximum defect coverage are determined through HSPICE simulations using a didactic circuit implemented with 28-nm UTBB FDSOI gate library. An analytical analysis is also proposed based on the on-resistance model of P and N networks, which permits to evaluate the value of the critical resistance without performing fault simulations. In addition, this paper quantifies the individual as well as the combined improvements in detection brought by body-biasing, supply voltage, and temperature settings for the different defect types and different implementations.
Design of coreless PCB transformers for power and signal isolation in a modular ADC system for power quality data acquisition

Available industrial energy meters offer high accuracy and reliability, but are typically expensive and low-bandwidth, making them poorly suited to multi-sensor data acquisition schemes and power quality analysis. An alternative measurement system is proposed in this paper that is highly modular, extensible and compact. To minimise cost, the device makes use of planar coreless PCB transformers to provide galvanic isolation for both power and data. Samples from multiple acquisition devices may be concentrated by a central processor before integration with existing host control systems. This paper focusses on the practical design and implementation of planar coreless PCB transformers to facilitate the module's isolated power, clock and data signal transfer. Calculations necessary to design coreless PCB transformers, and circuits designed for the transformer's practical application in the measurement module are presented. The designed transformer and each application circuit have been experimentally verified, with test data and conclusions made applicable to coreless PCB transformers in general.
Molecular Characterization of a Human BRCA2 Homolog in Leishmania donovani

The breast cancer susceptibility protein BRCA2 is implicated in the DNA double-strand break (DSB) repair pathway through its association with Rad51. It is almost a ubiquitous eukaryotic protein; homologs of the BRCA2 gene (BRH2) have been identified in many mammals, as well as nonmammals. As a part of our quest to understand the DNA damage, repair, and recombination process in the parasitic protozoan, Leishmania sp. , we have cloned and characterized a BRCA2 homolog from Leishmania sp. (LBRH2). LBRH2 is coded by a single-copy gene (ORF = 3,498 bp) located at the 700-kb chromosome 16. The transcripts in both the promastigotes and the amastigotes are ∼3.9 kilonucleotides (knt) in size, corresponding to a protein with a calculated molecular mass of 128 kDa. The primary transcript of the gene is alternatively trans-spliced to produce 3 distinct mRNAs with altered folded structures at their 5′ ends. This study will contribute toward the understanding of a potential RAD51-mediated DNA recombination/repair pathway in Leishmania sp.
Superovulation and related phenomena in the beef cow. II. Effect of oestrogen administration on production of ova.

Eighty Hereford heifers were injected to induce superovulation with 3000 or 5000 i.u. of purified pregnant mares' serum (pms) in one, two or three doses, administered on Day 12, 14, 16 or 18 of the oestrous cycle, with or without enucleation of corpus luteum ; 2000 i.u. of human chorionic gonadotrophin (hcg) were given 3, 4, 5, 6 or 7 days after the first pms injection; clay models of the ovaries were constructed daily following palpation per rectum. The animals were bred and slaughtered 2 to 5 days after ovulation. The reproductive tracts were flushed and the ova recovered and examined microscopically; fertilized
Binary contingency table method for analysing gene mutation in cancer genome

Somatic mutations are considered to initiate several disorders such as cancer and neurological disease. Hence, a number of computational methods have been developed to find loci subject to frequent mutations in cancer cells. Since normal cells turn into cancer cells through the accumulation of gene mutations, the elucidation of interactive relationships among loci has great potential to reveal the cause of cancer progression; however, only a few methods have been proposed for measuring statistical significance of pairs of loci that are co-mutated or exclusively mutated. In this study, we proposed a novel statistical method to find such significantly interactive pairs of loci by employing the framework of binary contingency tables. Using Markov chain Monte Carlo procedure, the statistical significance is evaluated by sampling null matrices whose marginal sums are equal to those of the input matrix. We applied the proposed method to mutation data of colon cancer patients and successfully obtained significant pairs of loci.
Halving the cost of quantum addition

We improve the number of T gates needed to perform an n-bit adder from 8n+O(1) to 4n+O(1). We do so via a "temporary logical-AND" construction which uses four T gates to store the logical-AND of two qubits into an ancilla and zero T gates to later erase the ancilla. This construction is equivalent to one by Jones, except that our framing makes it clear that the technique is far more widely applicable than previously realized. Temporary logical-ANDs can be applied to integer arithmetic, modular arithmetic, rotation synthesis, the quantum Fourier transform, Shor's algorithm, Grover oracles, and many other circuits. Because T gates dominate the cost of quantum computation based on the surface code, and temporary logical-ANDs are widely applicable, this represents a significant reduction in projected costs of quantum computation. In addition to our n-bit adder, we present an n-bit controlled adder circuit with T-count of 8n+O(1), a temporary adder that can be computed for the same cost as the normal adder but whose result can be kept until it is later uncomputed without using T gates, and discuss some other constructions whose T-count is improved by the temporary logical-AND.
Prediction of the Clinical Risk of Drug-Induced Cholestatic Liver Injury Using an In Vitro Sandwich Cultured Hepatocyte Assay

Drug-induced liver injury (DILI) is of concern to the pharmaceutical industry, and reliable preclinical screens are required. Previously, we established an in vitro bile acid–dependent hepatotoxicity assay that mimics cholestatic DILI in vivo. Here, we confirmed that this assay can predict cholestatic DILI in clinical situations by comparing in vitro cytotoxicity data with in vivo risk. For 38 drugs, the frequencies of abnormal increases in serum alkaline phosphatase (ALP), transaminases, gamma glutamyltranspeptidase (γGT), and bilirubin were collected from interview forms. Drugs with frequencies of serum marker increases higher than 1% were classified as high DILI risk compounds. In vitro cytotoxicity was assessed by monitoring lactate dehydrogenase release from rat and human sandwich-cultured hepatocytes (SCRHs and SCHHs) incubated with the test drugs (50 μM) for 24 hours in the absence or presence of a bile acids mixture. Receiver operating characteristic analyses gave optimal cutoff toxicity values of 19.5% and 9.2% for ALP and transaminases in SCRHs, respectively. Using this cutoff, high- and low-risk drugs were separated with 65.4–78.6% sensitivity and 66.7–79.2% specificity. Good separation was also achieved using SCHHs. In conclusion, cholestatic DILI risk can be successfully predicted using a sandwich-cultured hepatocyte–based assay.
Disruption of the yeast nuclear PET54 gene blocks excision of mitochondrial intron aI5 beta from pre‐mRNA for cytochrome c oxidase subunit I.

The nuclear PET54 gene of Saccharomyces cerevisiae was cloned and a pet54::LEU2 gene disruption strain was constructed. Analysis of the phenotype of this strain revealed a defect in expression of two mitochondrial genes: COX1, which encodes cytochrome c oxidase subunit I, and COX3, which encodes cytochrome c oxidase subunit III. The defect in COX1 gene expression in the pet54 mutant was shown to be the result of inefficient excision of COX1 intron aI5 beta. Two lines of evidence indicate that inefficient excision of intron aI5 beta is the sole defect in COX1 gene expression. First, a pet54::LEU2 cytoductant bearing the ‘short’ mitochondrial genome that lacks both COX1 introns aI5 alpha and aI5 beta is defective only in COX3 gene expression and not in COX1 mRNA splicing or mRNA translation. Second, Northern analysis of COX1 transcipts from the pet54 mutant showed that a 3.8 kb COX1 transcript containing unexcised intron aI5 beta and lacking intron aI5 alpha is accumulated while the amount of 2.2 kb mature COX1 mRNA is diminished. In an effort to relate the role of the PET54 gene product in splicing of COX1 pre‐mRNA to the previously characterized role for PET54 in translation of mitochondrial COX3 mRNA, the sequence of the PET54‐responsive portion of the COX3 5′ untranslated leader region was compared to the COX1 intron aI5 beta sequence. Two blocks of RNA sequence present in COX3 have similar counterparts within intron aI5 beta of COX1. The possibility that the PET54 protein binds to one or the other of these blocks of RNA sequence and the potential consequences of this interaction are discussed.
Detection of bovine leukaemia virus proviral DNA in paraffin sections, tissue smears, and peripheral blood leucocytes by in situ PCR

In situ PCR was developed for the detection of proviral DNA of bovine leukaemia virus in paraffin embedded tissues, tissue smears of experimentally inoculated sheep, as well in peripheral blood leukocytes of naturally infected cattle. The liver, spleen, lung, heart, kidney, and lymph node were collected from two infected sheep, which died or were euthanized due to lymphosarcoma and persistent lymphocytosis, respectively. Peripheral blood leukocytes (PBLs) were isolated from eleven cattle serologically positive for BLV. The presence of proviral DNA was confirmed in all paraffin embedded tissue sections and tissue smears as well in all PBLs preparations. In situ PCR results agreed 100% with those of provirus detection using conventional PCR. Newly developed in situ PCR would be recommended as a method to differentiate between EBL and other lymphosarcomas of unknown aetiology.
Phospholipid Composition of Human Amniotic Fluid During Gestation and at Term

The concentration, composition and fatty acid components of amniotic fluid phospholipids were determined in samples obtained at term and during the second trimester of gestation. The mean concentration of total phospholipids was significantly higher at term than during the second trimester. There was also a highly significant increase in the ratio phosphatidylcholine/sphingomyelin at term. Concomitantly the proportion of palmitic acid in the phosphatidylcholines rose to very high levels. Changes in the same direction were recorded in the fatty acid composition of the phosphatidylethanolamines. The present results indicate that analysis of amniotic fluid phospholipids may be of clinical significance in determining the pulmonary maturity of the foetus.
A Proposed Analytical Customer Satisfaction Prediction Model for Mobile Internet Networks

Subjective method (such as survey, interview,etc.) has been the most common and reliable method used in analyzing customer satisfaction.However, the subjective method is expensive, time consuming, lacks repeatability in real-time and may not capture the technical aspect of the telecoms network service performance in telecommunication industry.As a result, perceived quality of experience (QoE) has been traditionally used to evaluate the satisfaction of telecommunication services from both Internet service providers and customer’s perspective. However, the result of perceived QoE in relation to mean opinion score found not suitable enough to quantify customer satisfaction, and it eliminates the diversity of customer assessment while quantifying satisfaction.Therefore, this paper proposed an analytical customer satisfaction prediction model based on perceived QoE, perceived QoE influence factors, perceived QoE measurements and perceived QoE estimations to overcome the limitations of the subjective measurement.The paper presents how the mean opinion score can be used to quantify customer satisfaction by ensuring the diversity of customer’s assessment is not eliminated.
Mixture Models, Robustness, and the Weighted Likelihood Methodology

Summary. Problems associated with the analysis of data from a mixture of distributions include the presence of outliers in the sample, the fact that a component may not be well represented in the data, and the problem of biases that occur when the model is slightly misspecified. We study the performance of weighted likelihood in this context. The method produces estimates with low bias and mean squared error, and it is useful in that it unearths data substructures in the form of multiple roots. This in turn indicates multiple potential mixture model fits due to the presence of more components than originally specified in the model. To compute the weighted likelihood estimates, we use as starting values the method of moment estimates computed on bootstrap subsamples drawn from the data. We address a number of important practical issues involving bootstrap sample size selection, the role of starting values, and the behavior of the roots. The algorithm used to compute the weighted likelihood estimates is competitive with EM, and it is similar to EM when the components are not well separated. Moreover, we propose a new statistical stopping rule for the termination of the algorithm. An example and a small simulation study illustrate the above points.