Miracle-dz/UniFAR-FTUs huggingface dataset:
Biosynthesis of UDP-Xylose. Cloning and Characterization of a Novel Arabidopsis Gene Family, UXS, Encoding Soluble and Putative Membrane-Bound UDP-Glucuronic Acid Decarboxylase Isoforms

UDP-xylose (Xyl) is an important sugar donor for the synthesis of glycoproteins, polysaccharides, various metabolites, and oligosaccharides in animals, plants, fungi, and bacteria. UDP-Xyl also feedback inhibits upstream enzymes (UDP-glucose [Glc] dehydrogenase, UDP-Glc pyrophosphorylase, and UDP-GlcA decarboxylase) and is involved in its own synthesis and the synthesis of UDP-arabinose. In plants, biosynthesis of UDP-Xyl is catalyzed by different membrane-bound and soluble UDP-GlcA decarboxylase (UDP-GlcA-DC) isozymes, all of which convert UDP-GlcA to UDP-Xyl. Because synthesis of UDP-Xyl occurs both in the cytosol and in membranes, it is not known which source of UDP-Xyl the different Golgi-localized xylosyltransferases are utilizing. Here, we describe the identification of several distinct Arabidopsis genes (named AtUXS for UDP-Xyl synthase) that encode functional UDP-GlcA-DC isoforms. The Arabidopsis genome contains fiveUXS genes and their protein products can be subdivided into three isozyme classes (A–C), one soluble and two distinct putative membrane bound. AtUxs from each class, when expressed inEscherichia coli, generate active UDP-GlcA-DC that converts UDP-GlcA to UDP-Xyl. Members of this gene family have a large conserved C-terminal catalytic domain (approximately 300 amino acids long) and an N-terminal variable domain differing in sequence and size (30–120 amino acids long). Isoforms of class A and B appear to encode putative type II membrane proteins with their catalytic domains facing the lumen (like Golgi-glycosyltransferases) and their N-terminal variable domain facing the cytosol. Uxs class C is likely a cytosolic isoform. The characteristics of the plant Uxs support the hypothesis that unique UDP-GlcA-DCs with distinct subcellular localizations are required for specific xylosylation events.
Broadband cross-polarized bowtie antenna for breast cancer detection

Currently, various approaches to microwave breast cancer detection are being investigated by several research groups. Microwave approaches are expected to provide complementary information to that obtained with mammography, the gold standard method for breast imaging. Microwave images are related to the electrical properties of tissues, and there is some evidence to suggest that a contrast exists between normal healthy breast tissues and malignant tumors. In this paper, we investigate the frequency responses of tumors in a simple breast model using computer simulations over the frequency range of 2 to 4.25 GHz. Also, the influence of a variety of parameters (e.g. tumor shape, size, location and depth) on the frequency response is examined.
Identification and Characterization of a Novel Protein Kinase, TESK1, Specifically Expressed in Testicular Germ Cells (*)

We have isolated cDNA clones encoding the rat and human forms of a novel protein kinase, termed TESK1 (testis-specific protein kinase 1). Sequence analysis indicates that rat TESK1 contains 628 amino acid residues, composed of an N-terminal protein kinase consensus sequence followed by a C-terminal proline-rich region. Human TESK1 contains 626 amino acids, sharing 92% amino acid identity with its rat counterpart. The protein kinase domain of TESK1 is structurally similar to those of LIMK (LIM motif-containing protein kinase)-1 and LIMK2, with 49-50% sequence identity. Phylogenetic analysis of the protein kinase domains revealed that TESK1 is most closely related to a LIMK subfamily. Chromosomal localization of human TESK1 gene was assigned to 9p13. Anti-TESK1 antibody raised against the C-terminal peptide of TESK1 recognized two polypeptides of 68 and 80 kDa in cell lysates of COS cells transfected with human TESK1 cDNA expression plasmid. TESK1 protein expressed in COS cells exhibited serine/threonine kinase activity, when myelin basic protein was used as a substrate. Northern blot analysis revealed that TESK1 mRNA was specifically expressed in rat and mouse testicular germ cells. The TESK1 mRNA in the testis was detectable only after the 18th day of postnatal development of mice and was mainly expressed in the round spermatids. These observations suggest that TESK1 has a specific function in spermatogenesis.
Clinical, biological, and endoscopic responses to adalimumab in antitumor necrosis factor-naive Crohn’s disease: predictors of efficacy in clinical practice

Background and aims Endoscopic healing and clinical remission are important parameters to evaluate therapeutic efficacy in Crohn’s disease. The aim of this study was to investigate the clinical effectiveness of adalimumab in terms of clinical and endoscopic response and to identify predictors of efficacy in clinical practice. Materials and methods A prospective analysis was carried out of 68 antitumor necrosis factor-naive Crohn’s disease patients treated with adalimumab for 2 years. Clinical and endoscopic response was assessed using the Harvey–Bradshaw index and the Simple Endoscopic Score for Crohn’s disease, respectively. Results Adalimumab treatment was associated with clinical remission in 76.6, 90.6, and 87.5% of patients at 6, 12, and 24 months. Loss of efficacy occurred in 17.6% of cases after 24 months of therapy. Clinical remission with normal C-reactive protein at 2 months or with endoscopic response at 6 months was predictive of better outcomes. Mucosal healing rates were 17.2, 44.7, and 39.5% and endoscopic responses were 55.1, 76.6, and 76.3% at the respective time points. Mucosal healing was higher in the early treatment group than in the group with disease of at least 5 years’ duration (64.7 vs. 19.1%, P=0.004). Inflammatory phenotype showed a higher percentage of mucosal healing (70%) than stricturing (29.4%) or penetrating (27.3%) disease. Conclusion Adalimumab was effective in providing sustained clinical remission. In patients in clinical remission, the C-reactive protein level at 2 months, endoscopic response at 6 months, or inflammatory phenotype and short disease duration could be considered as good predictors of efficacy.
Clinical progression of breast cancer malignant behavior: what to expect and when to expect it.

PURPOSE Seemingly localized breast cancer is a heterogeneous mix of truly localized cancers and cancers with occult metastases. Our purpose is to determine the parameters of metastatic proclivity for the different clinical presentations of operable breast cancer and to present quantitative prognostic information useful to both doctors and patients. PATIENTS AND METHODS A series of regionally treated breast cancer patients was analyzed to determine the likelihood and time of the appearance of clinical metastases for different clinical subgroups. Patients operated on at the University of Chicago from 1927 to 1987 for clinically regionally localized breast cancer, who received no systemic therapy as a part of their initial treatment, were included. Overall survival and distant disease-free survival in this mature series are analyzed. RESULTS Metastagenicity, the metastatic proclivity of a tumor, increases with both tumor size and nodal involvement. This is also true for virulence, which is the rate at which these metastases appear. Each clinical group has a cured population, even those with extensive nodal involvement. A table provides a tool for determining the proportion of risk expended in each clinical group as a function of the distant disease-free survival. Whereas the likelihood of metastasis increases with tumor size and nodal involvement, the time to their appearance decreases. CONCLUSIONS Breast cancer metastagenicity and virulence are heterogeneous even within clinically similar groups of operable breast cancer patients. Tumor progression is correlated with increasing tumor size and nodal involvement. Markers are needed to identify individual tumor virulence and metastagenicity.
Multivariate Tests of Mean-Variance Efficiency and Spanning With a Large Number of Assets and Time-Varying Covariances

We develop a finite-sample procedure to test the mean-variance efficiency and spanning hypotheses, without imposing any parametric assumptions on the distribution of model disturbances. In so doing, we provide an exact distribution-free method to test uniform linear restrictions in multivariate linear regression models. The framework allows for unknown forms of nonnormalities as well as time-varying conditional variances and covariances among the model disturbances. We derive exact bounds on the null distribution of joint F statistics to deal with the presence of nuisance parameters, and we show how to implement the resulting generalized nonparametric bounds tests with Monte Carlo resampling techniques. In sharp contrast to the usual tests that are not even computable when the number of test assets is too large, the power of the proposed test procedure potentially increases along both the time and cross-sectional dimensions.
Demonstration of the Phenotype Le(a+b+) in Infants and in Adults

IT is generally held that the Lea gene behaves as a recessive Mendelian character, so far as the rcd-cell characteristics of adults are concerned; that is to say, only red cells of the genotype LeaLea react in vitro with anti-Lea sera. Red cells from infants of the genotype LpLeb may rcact with anti-Lea sera at a time when their reactions with anti-Leb sera are negative or only weak (Andresen, 1947, 1948; Jordal and Lyndrup, 1952). Thus it is postulated that the Leb genc in some way inhibits the expression of the Lea gene in the red cells of adults. It has been claimed that samples of red cells from occasional adult donors of the presumed genotype LeaLeb do react with potent agglutinating anti-Lea sera (Grubb and Morgan, 1949; Andresen, Andersen, Jordal and Henningsen, 1950; Grubb, 195 I ; Simmons and Jakobowicz, 1951). However, it has been suggested that these reactions may be due to the presence of anti-Leb in certain anti-Lea sera (Miller, Rosenfield, Vogel, Haber and Gibbel, 1954). The observations reported in the present paper were made in the course of treating a leukaemic patient (W.B.) whose serum contained anti-Lea. The patient required frequent transfusions and advantagc was taken of the opportunity of measuring the post-transfusion survival of many different samples of red cells. It was soon found that when red cells from some donors of the apparent phenotype Le(ab+ ) were injected, a proportion of them was rapidly removed from the circulation. Evidence was obtained that this destruction was due to the specific action of anti-Lea, and this evidence forms the substance of the present paper. It was found that the serum of W.B. reacted well with the red cells of newborn infants. Since comparatively little has been published on the Lewis groups of infants, some observations were made on a small number of blood samples taken from infants during the first 6 weeks of life.
Molecular Indicators of Hypoxia in the Blue Crab Callinectes sapidus

Occurrence of hypoxia in estuarine waters is increasing, and recovery of impacted estu- aries is slow. Detection of early effects of hypoxia is needed for timely remedial action to be taken. Here we examine the use of hypoxia-responsive gene and protein expression profiles in the blue crab Callinectes sapidus as early indicators of impacts of hypoxia. We cloned 23 potential hypoxia- responsive genes, which were used to construct gene macroarrays. Crabs exposed to chronic hypoxia (2.5 ppm dissolved oxygen (DO)) for 15 d showed significant (p < 0.05) changes in gene expression of heat shock protein 70 (Hsp70), copper metallothionein (CuMt3), cytosolic MnSOD (cyt-MnSOD) and ribosomal proteins S15 and L23. In all cases except for CuMt3, gene expression decreased after 5 d exposure to hypoxia. Expression of Hsp70, CuMt3 and cyt-MnSOD also increased (p < 0.05) in nor- moxic crabs held for 15 d, suggesting confounding effects from confinement stress. Hemocyanin pro- tein concentrations changed significantly (p = 0.005) across the 15 d chronic hypoxia exposure. Hemocyanin in crabs exposed to 10 d intermittent hypoxia (2.5 to 8 ppm DO over a 24 h cycle) did not change, but cyt-MnSOD gene expression increased significantly (p = 0.037), whereas cytochrome c oxidase subunit 1 (ccox1) showed a 2.2-fold downregulation. Blue crabs collected from Pensacola Bay, Florida, showed significant (p < 0.006) downregulation of ccox1 and cyt-MnSOD gene ex- pression as well as hemocyanin protein levels at a diurnally hypoxic marsh site. Several hypoxia- responsive genes (elongation factor 2, cryptocyanin, hemocyanin) were also significantly elevated (p < 0.006) in intermolt versus premolt normoxic crabs. The identification of hypoxia-responsive genes and proteins in the blue crab is a promising first step towards the development of sensitive molecular tools for the detection of sublethal effects of hypoxia in estuarine-resident species.
The polymorphism ( Gln 261 Arg ) of 12-lipoxygenase and cancer risk : a meta-analysis

Background: Many studies suggest that the Gln261Arg polymorphism in 12-lipoxygenase gene is assicated with cancer susceptibility, but the results are inconclusive. This meta-analysis aimed to investigate the overall association between the Gln261Arg polymorphism in 12-lipoxygenase gene and cancer risk. Methods: Literature search was performed in Pubmed, Embase and other databases for studies evaluating the association between the Gln261Arg polymorphism in 12-lipoxygenase gene and cancer risk. Data were extracted and statistical analysis was performed using STATA 12.0 software. Results: A total of eight publications involving 8,379 subjects were included in this meta-analysis. Combined analysis revealed a significant association between this polymorphism and cancer susceptibility with an OR of 1.19 (95% CI: 1.09-1.31, P=0.000 for Gln/Gln vs. Arg/Gln + Arg/Arg). Subgroup analysis by ethnicity showed that the cancer risk associated with the Gln261Arg polymorphism in 12-lipoxygenase gene was significantly elevated among Asians (OR=1.21, 95% CI: 1.10-1.34, P=0.000 for Gln/Gln vs. Arg/Gln + Arg/ Arg), but not among Caucasians. Subgroup analysis by cancer type suggested that the Gln261Arg polymorphism in 12-lipoxygenase gene is not a risk factor for colon cancer or rectal cancer. Conclusion: This meta-analysis suggests that the Gln261Arg polymorphism in 12-lipoxygenase gene contributes to cancer susceptibility, specifically in Asian populations. More studies are needed to validate our findings.
Tree species distributions and local habitat variation in the Amazon: large forest plot in eastern Ecuador

1 We mapped and identified all trees ≥ 10 mm in diameter in 25 ha of lowland wet forest in Amazonian Ecuador, and found 1104 morphospecies among 152 353 individuals. The largest number of species was mid‐sized canopy trees with maximum height 10–20 m and understorey treelets with maximum height of 5–10 m.
Effects of the tyrosine‐kinase inhibitor geldanamycin on ligand‐induced HER‐2/NEU activation, receptor expression and proliferation of HER‐2‐positive malignant cell lines

Geldanamycin belongs to the family of benzoquinoid ansamycin tyrosine‐kinase inhibitors. We have examined its effects on Her‐2/neu kinase activity, protein expression level, and proliferation of Her‐2+ malignant cells. In SK‐BR‐3 breast‐cancer cells, short‐time treatment with geldanamycin completely abrogated gp30‐ligand‐induced activation of Her‐2 without a change of receptor‐expression level. Longer treatment of intact cells with geldanamycin induced decreased steady‐state Her‐2 autophosphorylation activity, which correlated with reduction of Her‐2 protein expression and phosphotyrosine content of several proteins. The decrease was time‐ and dose‐dependent, starting after 1 hr at 100 nM concentration and reaching completion by 24 hr. The reduction of the Her‐2 protein level probably resulted from increased degradation, since the Her‐2 mRNA level remained constant. Geldanamycin effects were not specific for Her‐2, since the non‐receptor tyrosine‐kinase fyn was inhibited equally. In contrast to these results, protein‐kinase‐C activity was not affected. In 3 other malignant cell lines expressing different amounts of Her‐2 (SK‐BR‐3 > SK‐OV‐3 > OVCAR3 > MCF7), geldanamycin also effectively reduced Her‐2‐kinase activity proportionally to the decrease of protein expression. In contrast, in a [3H]‐thymidine‐uptake assay, cell growth was meaningfully inhibited by geldanamycin at nanomolar concentrations only in SK‐BR‐3 (IC50 2nM) and MCF7 (IC50 20nM), while OVCAR3 was only moderately sensitive (IC50 2μM) and SK‐OV‐3 was clearly resistant to geldanamycin. In direct comparison with herbimycin A, another benzoquinoid ansamycin that has been more thoroughly characterized, the biologic effects of geldanamycin were more pronounced. Int. J. Cancer, 70:221–229, 1997. © 1997 Wiley‐Liss, Inc.
Model-Based Feature Compensation for Robust Speech Recognition

This paper proposes a novel robust speech recognition approach based on the model-based feature compensation. The approach combines the GMM-based feature compensation and the HMM-based feature compensation together and employs the multiple recognition passes to achieve the best performance. In the initial recognition procedure, the GMM-based feature compensation approach is employed to give better clean model and noise model. Then we further refine these models by employing the HMM-based feature compensation approach. The statistical model of the clean speech and the noise is combined by using vector Taylor series (VTS) approximation. The experimental results show that the novel approach makes a significant improvement compared to the GMM-based feature compensation and the HMM-based feature compensation without any compensation in the initial pass.
The Role of Family Empowerment and Family Resilience on Recovery from Psychosis

Most of the studies on the family of psychotic illness focus on the negative sides of family life, such as high expressed emotion, family burden and stigma. Very few studies look at the positive aspects of the family such as empowerment and resilience. This study aims at investigating the role of family‟s empowerment, and well-being on predicting the recovery of the patients. Ninety nine families of psychotic patients were assessed using the Family Empowerment Scale, and the Connor-Davison Resilience Scale. Meanwhile the patients‟ recovery was assessed using Brief Psychiatric Rating Scale. Regression analysis yield result that family empowerment and resilience accounted for a significant amount of variance in patient‟s recovery. It is concluded that family condition influences patient‟s recovery. This research suggests that it is important to increase family empowerment and resilience as part of the treatment for psychotic patients.
An approximate randomisation-respecting adjustment to the hazard ratio for time-dependent treatment switches in clinical trials

We consider a clinical trial with a survival outcome, in which subjects may switch in a non-randomised manner from their randomised treatment to control treatment during follow-up. We extend a method for binary outcomes, due to Sommer and Zeger, by viewing a survival outcome as a sequence of binary outcomes. This leads to a simple expression for the hazard ratio among non-switchers at each time in terms of the unadjusted hazard ratio and the proportion of switchers among subjects who experience events. We also estimate an overall adjusted hazard ratio. Although our method is approximate, it has the advantage of preserving the significance level of the log rank test. A simulation study shows that the method works well for the overall adjusted hazard ratio but that interval-specific estimates are under-adjusted as the degree of switching increases and as the association between switching and events becomes stronger. The method is illustrated using data from the Concorde trial of immediate versus deferred treatment in HIV infection.
Wnt signalling pathways in chronic lymphocytic leukaemia and B‐cell lymphomas

In this review, we discuss the intricate roles of the Wnt signalling network in the development and progression of mature B‐cell‐derived haematological malignancies, with a focus on chronic lymphocytic leukaemia (CLL) and related B‐cell lymphomas. We review the current literature and highlight the differences between the β‐catenin‐dependent and ‐independent branches of Wnt signalling. Special attention is paid to the role of the non‐canonical Wnt/planar cell polarity (PCP) pathway, mediated by the Wnt‐5–receptor tyrosine kinase‐like orphan receptor (ROR1)–Dishevelled signalling axis in CLL. This is mainly because the Wnt/PCP co‐receptor ROR1 was found to be overexpressed in CLL and the Wnt/PCP pathway contributes to numerous aspects of CLL pathogenesis. We also discuss the possibilities of therapeutically targeting the Wnt signalling pathways as an approach to disrupt the crucial interaction between malignant cells and their micro‐environment. We also advocate the need for research in this direction for other lymphomas, namely, diffuse large B‐cell lymphoma, Hodgkin lymphoma, mantle cell lymphoma, Burkitt lymphoma and follicular lymphoma where the Wnt signalling pathway probably plays a similar role.
Material and process challenges for interconnects in nanoelectronics era

Cu/low-k interconnects have been used in LSI fabrication. However, several difficult challenges need to be overcome for 22-nm node devices and beyond. These challenges include an increase in resistivity, degradation of the electromigration reliability, and the low mechanical strength of low-k dielectrics. To overcome these problems, it is essential to not only improve Cu/low-k fabrication processes but also to develop alternative approaches based on emerging technologies such as 3D interconnects, nanocarbon interconnects, and optical interconnects. This paper reviews the problems and potential solutions, and describes approaches such as supercritical (SC) annealing for grain growth enhancement, CoWP caps for electromigration (EM) reliability improvement, and electroless barrier deposition for ultrathin barrier layer.
From Mechanisms to Management: Translating the Neuropathic Pain Consensus Recommendations Into Clinical Practice

Chronic neuropathic pain poses a treatment challenge, and is associated with significant psychologic distress, physical disability, and impaired functioning, which impact the activities of daily living. Efforts to provide relief are often inadequate and/or require polypharmacy. This has spurred interest among researchers and clinicians alike to develop early, intensive treatments that target the molecular and cellular mechanisms involved in pain transduction, transmission, and modulation, or ideally, that prevent neuropathic pain from occurring in the first place. Currently, researchers are attempting to capitalize on our understanding of neuropathic pain pathophysiology to develop drugs that interrupt distinct activities involved in its perpetuation. In this regard, several potential agents (eg, NMDA and AMPA/kainate antagonists) are in phase 2 and 3 clinical trials. In the interim, evolving data and evidence-based neuropathic treatment recommendations provide guidance for selecting first- and second-line medications that alone or in combination offer acceptable neuropathic pain control and allow clinicians to bridge the gap between current knowledge and its application in the clinical setting. Hopefully, as basic and clinical science progresses, further treatment advances and management tools will be found to improve the care of patients who live with neuropathic pain.