Miracle-dz/UniFAR-FTUs huggingface dataset:
EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients.

BACKGROUND Standardized conditions to distinguish subpopulations of colorectal cancer (CRC) patients more and less sensitive to cetuximab therapy remain undefined. MATERIALS AND METHODS We retrospectively analyzed epidermal growth factor receptor (EGFR) copy number by fluorescence in situ hybridization (FISH) in paraffin-embedded tumor blocks from 85 chemorefractory CRC patients treated with cetuximab. Results were analyzed according to different score systems previously reported in colorectal and lung cancers. The primary end point of the study was identification of the EGFR FISH score that best associates with response rate (RR). RESULTS Using receiver operating characteristic (ROC) analysis, the cut-off that best discriminated responders versus nonresponders to cetuximab was a mean of 2.92 EGFR gene copies per cell. This model showed sensitivity of 58.6% [95% confidence interval (CI) = 47.1-70.1) and specificity of 93.3% (95% CI = 80.6-100). EGFR FISH-positive patients (N = 43, 50.6%) had significantly higher RR (P = 0.0001) and significantly longer time to disease progression (P = 0.02) than EGFR FISH negative (N = 42, 49.4%). Other scoring systems resulted less accurate in discriminating patients with the highest likelihood of response to cetuximab therapy. CONCLUSIONS CRC patients with high EGFR gene copy number have an increased likelihood to respond to cetuximab therapy. Prospective clinical trials with a careful standardization of assay conditions and pattern interpretation are urgently needed.
Behavior regulation and mood predict social functioning among healthy young adults

Impulsive behavior is thought to lead to both positive and negative psychosocial outcomes. However, little is known about the potential consequences of subclinical expressions of behavior dysregulation on everyday functioning. To examine this relationship, global social functioning was measured in 89 healthy, young adults who also completed the Degraded Stimulus Continuous Performance Test, Color–Word Interference Test, Barratt Impulsiveness Scale, 11th Edition, and Behavior Rating Inventory of Executive Functioning–Adult. Better self-reported executive functioning and mood were significant independent predictors of higher social functioning, even in a sample of healthy adults. The results of this study may serve as a foundation for comparison with clinical populations who demonstrate greater behavior dysregulation and mood instability.
Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders.

Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis associated with tumors and other pathological conditions, including proliferative diabetic retinopathy and age-related macular degeneration. The murine anti-human VEGF monoclonal antibody (muMAb VEGF) A.4. 6.1 has been shown to potently suppress angiogenesis and growth in a variety of human tumor cells lines transplanted in nude mice and also to inhibit neovascularization in a primate model of ischemic retinal disease. In this report, we describe the humanization of muMAb VEGF A.4. 6.1. by site-directed mutagenesis of a human framework. Not only the residues involved in the six complementarity-determining regions but also several framework residues were changed from human to murine. Humanized anti-VEGF F(ab) and IgG1 variants bind VEGF with affinity very similar to that of the original murine antibody. Furthermore, recombinant humanized MAb VEGF inhibits VEGF-induced proliferation of endothelial cells in vitro and tumor growth in vivo with potency and efficacy very similar to those of muMAb VEGF A.4. 6.1. Therefore, recombinant humanized MAb VEGF is suitable to test the hypothesis that inhibition of VEGF-induced angiogenesis is a valid strategy for the treatment of solid tumors and other disorders in humans.
Multi-objective particle swarm optimization for ontology alignment

In computer science design and implementation of high-tech areas in the modern society is accompanied by increasing the role of ontological knowledge base. Accumulation of shared ontologies is seen as a mechanism of unlimited knowledge acquisition about the world. However, the problem of integration, matching and alignment of ontologies is not solved yet. The problem of ontology alignment is to find such a structure and permissible parameters that provide the optimal values for one or more quality criteria. It should be noted that today there are many methods to compute the similarity between two discrete elements of different ontologies. Integration of up-to-date similarity computation techniques allows obtaining a versatile and accurate result. One of approach is based on the weights. Typically, the weights are assigned manually or by specific approaches. The main shortcoming of existing approaches is the lack of optimality. This article proposes a new combined approach for ontology alignment based on Latent Semantic Indexing and multi-objective particle swarm optimization method. For objective functions two criteria were chosen: the accuracy and recall. To obtain an optimal population the method of local search was employed to replace the worst of the population in the new generation. Experimental research of the suggested approach confirms the effectiveness of it.
VEGF in the Crosstalk between Human Adipocytes and Smooth Muscle Cells: Depot-Specific Release from Visceral and Perivascular Adipose Tissue

Adipose tissue secrets adipokines and fatty acids, which may contribute to obesity-associated vascular dysfunction and cardiovascular risk. This study investigated which factors are responsible for the synergistic effect of adipokine and oleic acid- (OA-) induced proliferation of human vascular smooth muscle cells (VSMC). Adipocyte-conditioned medium (CM) from human adipocytes induces proliferation of VSMC in correlation to its vascular endothelial growth factor (VEGF) content. CM increases VEGF-receptor (VEGF-R) 1 and 2 expression and VEGF secretion of VSMC, while OA only stimulates VEGF secretion. VEGF neutralization abrogates CM- and OA-induced proliferation and considerably reduces proliferation induced by CM and OA in combination. VEGF release is higher from visceral adipose tissue (VAT) of obese subjects compared to subcutaneous adipose tissue (SAT) and VAT from lean controls. Furthermore, VEGF release from VAT correlates with its proliferative effect. Perivascular adipose tissue (PAT) from type 2 diabetic patients releases significantly higher amounts of VEGF and induces stronger proliferation of VSMC as compared to SAT and SAT/PAT of nondiabetics. In conclusion, VEGF is mediating CM-induced proliferation of VSMC. As this adipokine is released in high amounts from VAT of obese patients and PAT of diabetic patients, VEGF might link adipose tissue inflammation to increased VSMC proliferation.
Non-molting glossy/shroud encodes a short-chain dehydrogenase/reductase that functions in the ‘Black Box’ of the ecdysteroid biosynthesis pathway

In insects, the precise timing of molting and metamorphosis is strictly guided by a principal steroid hormone, ecdysone. Among the multiple conversion steps for synthesizing ecdysone from dietary cholesterol, the conversion of 7-dehydrocholesterol to 5β-ketodiol, the so-called ‘Black Box’, is thought to be the important rate-limiting step. Although a number of genes essential for ecdysone synthesis have recently been revealed, much less is known about the genes that are crucial for functioning in the Black Box. Here we report on a novel ecdysteroidgenic gene, non-molting glossy (nm-g)/shroud (sro), which encodes a short-chain dehydrogenase/reductase. This gene was first isolated by positional cloning of the nm-g mutant of the silkworm Bombyx mori, which exhibits a low ecdysteroid titer and consequently causes a larval arrest phenotype. In the fruit fly, Drosophila melanogaster, the closest gene to nm-g is encoded by the sro locus, one of the Halloween mutant members that are characterized by embryonic ecdysone deficiency. The lethality of the sro mutant is rescued by the overexpression of either sro or nm-g genes, indicating that these two genes are orthologous. Both the nm-g and the sro genes are predominantly expressed in tissues producing ecdysone, such as the prothoracic glands and the ovaries. Furthermore, the phenotypes caused by the loss of function of these genes are restored by the application of ecdysteroids and their precursor 5β-ketodiol, but not by cholesterol or 7-dehydrocholesterol. Altogether, we conclude that the Nm-g/Sro family protein is an essential enzyme for ecdysteroidogenesis working in the Black Box.
Differential response to dexamethasone on the TXB2 release in guinea-pig alveolar macrophages induced by zymosan and cytokines

Glucocorticosteroids reduce the production of inflammatory mediators but this effect may depend on the stimulus. We have compared the time course of the effect of dexamethasone on the thromboxane B2 (TXB2) release induced by cytokine stimulation and zymosan in guinea-pig alveolar macrophages. Interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and opsonized zymosan (OZ), all stimulate TXB2 release. High concentrations of dexamethasone (1–10 μM) inhibit the TXB2 production induced by both cytokines and OZ, but the time course of this response is different. Four hours of incubation with dexamethasone reduce the basal TXB2 release and that induced by IL-1β and TNF-α, but do not modify the TXB2 release induced by OZ. However, this stimulus was reduced after 24 h incubation. Our results suggest that the antiinflammatory activity of glucocorticosteroids shows some dependence on stimulus and, therefore, may have more than one mechanism involved.
Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissio

Toxicities of high-dose conditioning regimens have limited the use of conventional unrelated donor hematopoietic cell transplantation (HCT) to younger, medically fit patients. Based on preclinical studies, an HCT approach has been developed for elderly or medically infirm patients with HLA-matched or mismatched unrelated donors. In this study, 52 patients with hematological diseases were included. Most (88%) had preceding unsuccessful conventional HCT or refractory/advanced disease. Patients were treated with fludarabine 30 mg/m(2)/d from days -4 to -2, 2 Gy total body irradiation on day 0, cyclosporine at 6.25 mg/kg twice daily from day -3, and mycophenolate mofetil at 15 mg/kg twice daily from day 0. Durable donor chimerism was attained in 88% of the patients. By day 28, a median of 100% of CD56(+) cells were of donor origin. Granulocyte and T-cell donor chimerism increased to medians of 100% on day 56 and day 180 (range, 55%-100%), respectively. Acute GVHD, grade II, was seen in 42% (CI, 29%-56%); grade III in 8% (CI, 0%-15%); and grade IV in 13% (CI, 4%-23%) of patients; it was fatal in 9%. The 100-day transplantation-related mortality was 11%. Complete remissions, including molecular remissions, were seen in 45% of patients with measurable disease before transplantation. Mortality from disease progression was 27% at one year. With a median follow-up of 19 months, 18 of the 52 patients (35%) were alive and 25% were in remission. HCT from HLA-matched or mismatched unrelated donors can be performed with a reduced intensity conditioning regimen in patients ineligible for conventional HCT.
Evaluating retinal function in age-related maculopathy with the ERG photostress test.

PURPOSE To evaluate the diagnostic potential of the electroretinogram (ERG) photostress test and the focal cone ERG in age-related maculopathy (ARM). METHODS The cohort comprised 31 patients with ARM and 27 age-matched control subjects. The ERG photostress test was used to monitor cone adaptation after intense light adaptation. Focal 41- and 5-Hz cone ERGs were recorded monocularly (central 20 degrees) to assess steady state retinal function. Univariate analysis identified electrophysiological parameters that differed between groups, and receiver operating characteristic (ROC) curves were constructed to assess their diagnostic potential. Logistic regression analysis determined the diagnostic potential of a model incorporating several independent predictors of ARM. RESULTS The rate of recovery of the ERG photostress test was reduced (recovery was slower) in subjects with ARM. The parameter exhibited good diagnostic potential (P = 0.002, area under ROC curve = 0.74). The implicit times of the 5-Hz (a-wave, P = 0.002; b-wave, P < 0.001) and the 41-Hz (P < 0.001) focal cone ERGs were increased, and the 41-Hz focal cone ERG amplitude (P = 0.003) and focal to full-field amplitude ratio (P = 0.001) were reduced in the ARM group. Logistic regression analysis identified three independent predictors of ARM, including the rate of recovery of the ERG photostress test. CONCLUSIONS Early ARM has a marked effect on the kinetics of cone adaptation. The clinical application of the ERG photostress test increases the sensitivity and specificity of a model for the diagnosis of ARM. Improved assessment of the functional integrity of the central retina will facilitate early diagnosis and evaluation of therapeutic interventions.
Evaluating several path-based partial dynamic analysis methods for selecting black-box generated test cases

Many systematic methods help to produce a comprehensive repository of test cases that contain no redundancy from the specification point of view. When the repository cannot be tested in its entirety owing to resource constraints, there is a need to select a smaller subset of test cases that are effective with respect to a given implementation. One way of doing so is to select only one from each pair of test cases that are judged to be processed similarly by the given implementation, as determined by partial dynamic analysis. This work examines several path-based partial dynamic analysis methods for the selection of specification-based test cases, and evaluates their effectiveness by experiments.
Pyramid Representation for Face Recognition

In this paper we propose a new face recognition system based o n a biologically-inspired filtering method. Our work differs from previous proposals in (1) the multi-st age filtering method employed, in (2) the pyramid structure used, and most importantly, in (3) the prototype c onstruction scheme to determine the models stored in memory. The method is much simpler than previous proposal s and relatively inexpensive computationally, while attaining error rates as low as 5%, very close to the bes t r ported results.
miR-378b Promotes Differentiation of Keratinocytes through NKX3.1

MicroRNA (miRNA) is a kind of short non-coding RNA, involved in various cellular processes. During keratinocyte differentiation, miRNAs act as important regulators. In this study, we demonstrated by microarray assay that the expression of miR-378b significantly increased during keratinocytes differentiation. Our findings showed that miR-378b could inhibit proliferation, migration and differentiation in keratinocytes. Luciferase reporter assays showed that miR-378b directly target NKX3.1. Silencing of NKX3.1 could coincide with the effects of miR-24 overexpression. In conclusion, our results demonstrate miR-378b promote keratinocytes differentiation by targeting NKX3.1. Manipulation of miR-378b may afford a new strategy to clinic treatment of skin injury and repair.
Analysis of Intracellular State Based on Controlled 3D Nanostructures Mediated Surface Enhanced Raman Scattering

Near-infrared surface-enhanced Raman spectroscopy (SERS) is a powerful technique for analyzing the chemical composition within a single living cell at unprecedented resolution. However, current SERS methods employing uncontrollable colloidal metal particles or non-uniformly distributed metal particles on a substrate as SERS-active sites show relatively low reliability and reproducibility. Here, we report a highly-ordered SERS-active surface that is provided by a gold nano-dots array based on thermal evaporation of gold onto an ITO surface through a nanoporous alumina mask. This new combined technique showed a broader distribution of hot spots and a higher signal-to-noise ratio than current SERS techniques due to the highly reproducible and uniform geometrical structures over a large area. This SERS-active surface was applied as cell culture system to study living cells in situ within their culture environment without any external preparation processes. We applied this newly developed method to cell-based research to differentiate cell lines, cells at different cell cycle stages, and live/dead cells. The enhanced Raman signals achieved from each cell, which represent the changes in biochemical compositions, enabled differentiation of each state and the conditions of the cells. This SERS technique employing a tightly controlled nanostructure array can potentially be applied to single cell analysis, early cancer diagnosis and cell physiology research.
Distress and risk-taking in borderline personality disorder: An examination of neurocognitive mechanisms

Title of Document: DISTRESS AND RISK TAKING IN BORDERLINE PERSONALITY DISORDER: AN EXAMINATION OF NEUROCOGNITIVE MECHANISMS Alexis K. Matusiewicz, Master of Science, 2012 Directed By: Carl W. Lejuez, Professor, Department of Psychology Borderline personality disorder (BPD) is a severe mental illness characterized by high rates of engagement in distress-induced risk behavior. Unfortunately, extant laboratory-based risk paradigms have failed to account for the role of distress in precipitating risk behavior, so many questions remain about processes mechanisms that underlie this behavior. The current study examined affect as a moderator of the relationship between diagnostic status and risk behavior, as measured by a behavioral risk task, and affective and non-affective neurocognitive functioning as potential mediators of this relationship. Results indicated that individuals with BPD engaged in more risk behavior in the distress condition than in the neutral condition, whereas individuals without BPD showed a decrease in risk behavior across the two conditions. However, corresponding changes in executive functioning were not observed, suggesting the need for continued research to identify alternative mechanisms (e.g., neurocognitive, motivational) to explain this effect. DISTRESS AND RISK TAKING IN BORDERLINE PERSONALITY DISORDER: AN EXAMINATION OF NEUROCOGNITIVE MECHANISMS
Modeling Term Translation for Document-informed Machine Translation

Term translation is of great importance for statistical machine translation (SMT), especially document-informed SMT. In this paper, we investigate three issues of term translation in the context of documentinformed SMT and propose three corresponding models: (a) a term translation disambiguation model which selects desirable translations for terms in the source language with domain information, (b) a term translation consistency model that encourages consistent translations for terms with a high strength of translation consistency throughout a document, and (c) a term bracketing model that rewards translation hypotheses where bracketable source terms are translated as a whole unit. We integrate the three models into hierarchical phrase-based SMT and evaluate their effectiveness on NIST ChineseEnglish translation tasks with large-scale training data. Experiment results show that all three models can achieve significant improvements over the baseline. Additionally, we can obtain a further improvement when combining the three models.
Logistic informatics modelling using concept of stratification (CST)

The concept of stratification (CST) is a reform in problem solving approaches in computer science introduced and developed by Lotfi Zadeh [1]. In this approach, the target set is a set of the initial states. The environment around the target is then systematically identified and strata around the target are gradually built using the concept of ‘incremental target enlargement’. We advocate that this approach is useful in different areas; however, it is essential to highlight the potential applicability of the approach by presenting different examples. In this paper illustrative examples in Information Dominance (ID) and in requirement elicitation in contracting, are structured using CST. These examples show the application of the concept in the contexts of logistic informatics and contracting and assists the modelling process. Of particular relevance are Example 4 and 5. Example 4 exposes situations that are not dealt with in the current form of CST. The study, therefore, extends CST by considering the possibility of occasional state repetition while using the same input. Further, a 3D version of CST is structured and examined through example 5. This proposed version of the concept illustrates how the Fuzzy Inference System (FIS) benefits the user when applying CST.
Reversion of a Moloney murine leukemia virus RNase H mutant at a second site restores enzyme function and infectivity

The reverse transcriptase of retroviruses contains an RNase H activity essential for the proper synthesis of the viral DNA copy of the RNA genome. We have previously characterized a number of point mutations altering the RNase domain of the Moloney murine leukemia virus reverse transcriptase (S. W. Blain and S. P. Goff, J. Biol. Chem. 268:23585-23592, 1993). One such mutation, Y586F (a Y-to-F change at position 586), reduced RNase H activity, as assayed by in situ gel analysis, to about 5% of the wild-type level and prevented viral replication. We have now recovered a revertant virus with near-normal infectivity and in vitro enzymatic activity. The revertant contains a single substitution, N613H, distant in the primary sequence of the protein, but modeling with the Escherichia coli RNase H structure suggests that the reverted residue is close in space to the original substituted residue. Examination of the structure permits some suggestions as to how this second-site revertant restores enzyme activity.
ViDaX: an interactive semantic data visualisation and exploration tool

We present the Visual Data Explorer (ViDaX), a tool for visualising and exploring large RDF data sets. ViDaX enables the extraction of information from RDF data sources and offers functionality for the analysis of various data characteristics as well as the exploration of the corresponding ontology graph structure. In addition to some basic data mining features, our interactive semantic data visualisation and exploration tool offers various types of visualisations based on the type of data. In contrast to existing semantic data visualisation solutions, ViDaX also offers non-expert users the possibility to explore semantic data based on powerful automatic visualisation and interaction techniques without the need for any low-level programming. To illustrate some of ViDaX's functionality, we present a use case based on semantic data retrieved from DBpedia, a semantic version of the well-known Wikipedia online encyclopedia, which forms a major component of the emerging linked data initiative.