Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic Organization and Expression Analysis of B7-H4, an Immune Inhibitory Molecule of the B7 Family 1

B7-H4 is a recently identified B7 family member that negatively regulates T cell immunity by the inhibition of T cell proliferation, cytokine production, and cell cycle progression. In this study, we report that the genomic DNA of human B7-H4 is mapped on chromosome 1 comprised of six exons and five introns spanning 66 kb, of which exon 6 is used for alternative splicing to generate two different transcripts. Similar B7-H4 structure is also found in mouse genomic DNA in chromosome 3. A human B7-H4 pseudogene is identified in chromosome 20p11.1 with a single exon and two stop codons in the coding region. Immunohistochemistry analysis using B7-H4-specific mAb demonstrates that B7-H4 is not expressed on the majority of normal human tissues. In contrast, up to 85% (22 of 26) of ovarian cancer and 31% (5 of 16) of lung cancer tissues constitutively express B7-H4. Our results indicate a tight regulation of B7-H4 expression in the translational level in normal peripheral tissues and a potential role of B7-H4 in the evasion of tumor immunity.
Association study of the common polymorphisms in the folate-methionine pathway with retinoblastoma

ABSTRACT Background: Folate and methionine metabolism enzymes could affect DNA synthesis and repair, and their methylation and polymorphisms have been associated with some forms of cancer. This study was carried out to investigate whether the MTHFR C677T (rs1801133), MTHFR A1298C (rs1801131) and TYMS 2R/3R (rs34743033) polymorphisms are associated with susceptibility to retinoblastoma in an Iranian population. Methods: A case-control study was conducted involving 96 patients with retinoblastoma and 204 healthy controls. Genotyping of the MTHFR C677T, MTHFR A1298C, and TYMS 2R/3R polymorphism were assessed by PCR-RFLP, high resolution melting curve (HRM), and PCR methods, respectively. Results: The frequencies of MTHFR 677CT and 677TT genotypes were significantly lower in cases than controls (p values, 0.012 and 0.034, respectively). The MTHFR 677T allele was significantly lower in patients than in the control group (p = 0.003). In contrast, no association was observed with respect to the MTHFR A1298C and TYMS 2R/3R polymorphisms. Conclusions: The MTHFR C677T polymorphism was associated with the risk of retinoblastoma in this Iranian population and the T allele had a protective effect on the susceptibility to retinoblastoma.
Zolpidem arousing effect in persistent vegetative state patients: autonomic, EEG and behavioral assessment.

OBJECTIVE To study the Zolpidem arousing effect in persistent vegetative state (PVS) patients combining clinical evaluation, autonomic assessment by heart rate variability (HRV), and EEG records. METHODS We studied a group of 8 PVS patients and other 8 healthy control subjects, matched by age and gender. The patients and controls received drug or placebo in two experimental sessions, separated by 10-14 days. The first 30 minutes of the session were considered the basal record, and then Zolpidem was administered. All participants were evaluated clinically, by EEG, and by HRV during the basal record, and for 90 minutes after drug intake. RESULTS We found in all patients, time-related arousing signs after Zolpidem intake: behavioral (yawns and hiccups), activation of EEG cortical activity, and a vagolytic chronotropic effect without a significant increment of the vasomotor sympathetic tone. CONCLUSIONS We demonstrated time-related arousing signs after Zolpidem intake. We discussed possible mechanisms to explain these patho-physiological findings regarding EEG cortical activation and an autonomic vagolytic drug effect. As this autonomic imbalance might induce cardiocirculatory complications, which we didn't find in any of our patients, we suggest developing future trials under control of physiological indices by bedside monitoring. However, considering that this arousing Zolpidem effect might be certainly related to brain function improvement, it should be particularly considered for the development of new neuro-rehabilitation programs in PVS cases. According to the literature review, we claim that this is the first report about the vagolitic effect of Zolpidem in PVS cases.
Suggested Guidelines for Assessment of DG Unintentional Islanding Risk

As increasing numbers of Distributed Generation (DG) systems are connected to utility systems, distribution engineers are becoming increasingly interested in evaluating the risk of unintentional islanding. Utilities desire to keep their systems secure, while not imposing unreasonable burdens on customers wishing to connect DG. However, utility experience with these systems is still relatively sparse, so distribution engineers often are uncertain as to when additional protective measures, such as direct transfer trip, are needed to avoid unintentional islanding. Utilities tend to err on the side of caution, which in some cases may lead to the unnecessary requirement of additional protection. The purpose of this document is to provide distribution engineers with guidance on when additional measures or a more in-depth evaluation may be prudent. The guide also describes situations in which utilities may be able to ascertain that the risk of an unintentional island is extremely low and no additional mitigation or study are needed. The goal is to reduce the unnecessary application of additional protection for DG interconnection. While the content applies to any DG, this document has a focus on photovoltaic (PV) installations.
Managing Target Coverage Lifetime in Wireless Sensor Networks with Greedy Set Cover

The lifetime maximization problem in target coverage application can be addressed by the following question: how to partition sensors into an optimal number of sets and schedule their operating intervals so that the coverage requirement can be satisfied and the network lifetime can be maximized? In this paper, we address this problem by using cover set approach. A greedy algorithm that produces disjoints and non-disjoints set covers is proposed. Simulation results show good performance over some other solutions found in the literature that used the same paradigm.
HER-2 is an independent prognostic factor in endometrial cancer: association with outcome in a large cohort of surgically staged patients.

PURPOSE To evaluate HER-2 expression and amplification in a large cohort of endometrial cancer with complete surgical staging and outcome data. PATIENTS AND METHODS A tissue microarray was constructed of 483 patients with endometrial cancer of diverse histologic type and stage and tested for HER-2 expression and amplification using current standards of practice. There was outcome data for 83% of all patients and 81% with complete surgical staging. RESULTS Both expression and amplification of HER-2 was associated with high-grade (P = .0001) and high stage (P = .0001) endometrial cancer. The highest rate of HER-2 expression and amplification was seen in serous carcinoma (43% and 29%), while grade 1 endometrioid adenocarcinoma showed the lowest levels (3% and 1%). For all histologic types, the rate of HER-2 expression and amplification was remarkably different (P < .0001) for grade 3 cancers (31% and 15%) versus grade 2 (7% and 3%) and grade 1 cancers (3% and 1%), with similar results for endometrioid type (P < .0001). Both HER-2 expression and amplification correlated with disease-specific survival and progression-free survival in univariate analyses. By multivariate analysis HER-2 expression in the presence of amplification (P = .012) correlated with overall survival, but not expression in the absence of amplification. Overall survival was significantly shorter (P = .0001) in patients who overexpressed (median, 5.2 years) and/or showed amplification of HER-2 (median, 3.5 years) versus those that did not (median of all cases, 13 years). CONCLUSION Our results would suggest that HER-2 is an important oncogene in high grade and stage endometrial cancer, but plays only a minor role in the much more common low grade and stage tumors that encompass the majority of clinical practice.
The Zero-Truncated Poisson With Right Censoring: An Application to Translational Breast Cancer Research

We propose to analyze positive count data with right censoring from Behbod et al. (2009) using the censored zero-truncated Poisson (CZTP) model. The comparison in truncated means across subgroups in each cell line is carried out through a log-linear model that links the untruncated Poisson parameter and regression covariates. We also perform simulation to evaluate the performance of the CZTP model in finite and large sample sizes. In general, the CZTP model provides accurate and precise estimates. However, for data with small means and small sample sizes, it may be more proper to make inference based on the mean counts rather than on the regression coefficients. For small sample sizes and moderate means, the likelihood ratio test is more reliable than the Wald test. We also demonstrate how power analysis can be used to justify and/or guide the choice of censoring thresholds in study design. A SAS macro is provided in the Appendix for readers’ reference.
Turning the Pyramid of Prenatal Care

The current approach to prenatal care, which involves visits at 16, 24, 28, 30, 32, 34 and 36 weeks and then weekly until delivery, was established 80 years ago. The high concentration of visits in the third trimester implies, firstly, that most complications occur at this late stage of pregnancy and, secondly, that most adverse outcomes are unpredictable during the first or even second trimester. This review presents evidence that many pregnancy complications can now be predicted at an integrated first hospital visit at 11–13 weeks by combining data from maternal characteristics and history with findings of biophysical and biochemical tests. It is therefore proposed that the traditional pyramid of care should be inverted with the main emphasis placed in the first rather than third trimester of pregnancy.
A LuxR/LuxI-Type Quorum-Sensing System in a Plant Bacterium, Mesorhizobium tianshanense, Controls Symbiotic Nodulation

ABSTRACT The ability of rhizobia to symbiotically fix nitrogen from the atmosphere when forming nodules on their plant hosts requires various signal transduction pathways. LuxR-LuxI-type quorum-sensing systems have been shown to be one of the players in a number of rhizobium species. In this study, we found that Mesorhizobium tianshanense, a moderate-growth Rhizobium that forms nodules on a number of licorice plants, produces multiple N-acyl homoserine lactone (AHL)-like molecules. A simple screen for AHL synthase genes using an M. tianshanense genomic expression library in Escherichia coli, coupled with a sensitive AHL detector, uncovered a LuxI-type synthase, MrtI, and a LuxR-type regulator, MrtR, in M. tianshanense. Deletions of the mrtI or mrtR locus completely abolished AHL production in M. tianshanense. Using lacZ transcriptional fusions, we found that expression of the quorum-sensing regulators is autoinduced, as mrtI gene expression requires MrtR and cognate AHLs and mrtR expression is dependent on AHLs. Compared with the wild-type strains, quorum-sensing-deficient mutants showed a marked reduction in the efficiency of root hair adherence and, more importantly, were defective in nodule formation on their host plant, Glycyrrhiza uralensis. These data provide strong evidence that quorum sensing plays a critical role in the M. tianshanense symbiotic process.
Techniques for Calibration of the Scale Factor and Image Center for High Accuracy 3-D Machine Vision Metrology

Techniques are described for calibrating certain intrinsic camera parameters for machine vision. The parameters to be calibrated are the horizontal scale factor, and the image center. The scale factor calibration uses a one-dimensional fast Fourier transform and is accurate and efficient. It also permits the use of only one coplanar set of calibration points for general camera calibration. Three groups of techniques for center calibration are presented: Group I requires using a laser and a four-degree-of-freedom adjustment of its orientation, but is simplest in concept and is accurate and reproducible; Group II is simple to perform, but is less accurate than the other two; and the most general, Group II, is accurate and efficient, but requires a good calibration plate and accurate image feature extraction of calibration points. Group II is recommended most highly for machine vision applications. Results of experiments are presented and compared with theoretical predictions. Accuracy and reproducibility of the calibrated parameters are reported, as well as the improvement in actual 3-D measurement due to center calibration. >
Neutralization epitopes on rotavirus SA11 4fM outer capsid proteins

The VP7 and VP4 genes of seven antigenic mutants of simian rotavirus SA11 4fM (serotype 3) selected after 39 passages in the presence of SA11 4fM hyperimmune antiserum, were sequenced. Nucleotide sequence analysis indicated the following. (i) Twice as many amino acid substitutions occurred in the VP7 protein than in VP4, which has a molecular weight twice that of VP7. (ii) Most amino acid changes that occurred clustered in six variable regions of VP7 and in two variable regions of VP4; these variable regions may represent immunodominant epitopes. (iii) Most amino acid substitutions that occurred in VP7 and VP4 of these mutants were also observed in antigenic mutants selected with neutralizing monoclonal antibodies (NMAbs); however, some amino acid substitutions occurred that were not selected for NMAbs. (iv) On VP7, some of the neutralization epitopes appeared to be interrelated because amino acid substitution in one site affected binding of specific NMAbs to other sites, while other neutralization epitopes on VP7 appeared to be independent, in that amino acid substitution in one site did not affect the binding of NMAbs to another distant site.
SC29EK, a Peptide Fusion Inhibitor with Enhanced α-Helicity, Inhibits Replication of Human Immunodeficiency Virus Type 1 Mutants Resistant to Enfuvirtide

ABSTRACT Peptides derived from the α-helical domains of human immunodeficiency virus (HIV) type 1 (HIV-1) gp41 inhibit HIV-1 fusion to the cell membrane. Enfuvirtide (T-20) is a peptide-based drug that targets the step of HIV fusion, and as such, it effectively suppresses the replication of HIV-1 strains that are either wild type or resistant to multiple reverse transcriptase and/or protease inhibitors. However, HIV-1 variants with T-20 resistance have emerged; therefore, the development of new and potent inhibitors is urgently needed. We have developed a novel HIV fusion inhibitor, SC34EK, which is a gp41-derived 34-amino-acid peptide with glutamate (E) and lysine (K) substitutions on its solvent-accessible site that stabilize its α-helicity. Importantly, SC34EK effectively inhibits the replication of T-20-resistant HIV-1 strains as well as wild-type HIV-1. In this report, we introduce SC29EK, a 29-amino-acid peptide that is a shorter variant of SC34EK. SC29EK blocked the replication of T-20-resistant HIV-1 strains and maintained antiviral activity even in the presence of high serum concentrations (up to 50%). Circular dichroism analysis revealed that the α-helicity of SC29EK was well maintained, while that of the parental peptide, C29, which showed moderate and reduced inhibition of wild-type and T-20-resistant HIV-1 strains, was lower. Our results show that the α-helicity in a peptide-based fusion inhibitor is a key factor for activity and enables the design of short peptide inhibitors with improved pharmacological properties.
Real-time Alert Correlation Using Stream Data Mining Techniques

With the large volume of alerts produced by low-level detectors, management of intrusion alerts is becoming more challenging. Alert Correlation addresses this issue by providing a condensed, yet more useful view of the network from the intrusion standpoint. In this paper, we propose a new framework for real-time alert correlation that incorporates novel techniques for aggregating alerts into structured patterns and incremental mining of frequent structured patterns. In the proposed framework, time-sensitive statistical relationships between alerts are maintained in an efficient data structure and are updated incrementally to reflect the latest trends of patterns. The results of experiments with synthetic and real-world datasets demonstrate the efficiency of the proposed techniques. Our Frequent Structure Mining algorithm scales linearly with the size of the dataset and the proposed framework can cope with the throughput of a large-scale network. The ability to answer time-sensitive queries about patterns is another advantage of this work compared to other methods.
Nuclear actin activates human transcription factor genes including the OCT4 gene

RNA microarray analyses revealed that nuclear actin activated many human transcription factor genes including OCT4, which is required for gene reprogramming. Oct4 is known to be activated by nuclear actin in Xenopus oocytes. Our findings imply that this process of OCT4 activation is conserved in vertebrates and among cell types and could be used for gene reprogramming of human cells.
Drug induced QT prolongation Wojciech

The drug-induced QT prolongation predisposes to development of torsades de pointes (TdP) ventricular tachycardia and sudden death. The association between specific drug and development of TdP is difficult to document, therefore, QT prolongation is considered as a surrogate marker of the proarrhythmia risk. Most of the drugs prolong QT interval usually by blocking the potassium IKr current or altering trafficking of proteins forming the channel. Improved understanding of ion channel structure and kinetics and its role in repolarization has tremendous impact on understanding of the mechanisms of drug-induced QT prolongation and TdP. Proarrhythmia caused by a QT-prolonging drug occurs infrequently, and usually multiple factors need to operate to precipitate such an event including a combination of two or more drugs affecting the same pathway, hypokalemia, and possibly genetic predisposition. ECG provides unique opportunity to ensure safety of administered therapy. QT measurement is the most routine approach to a drug safety monitoring, however, there are many challenges related to methodology of measurements, accuracy of measurements, or optimal heart rate correction. Since drugs affecting repolarization not only prolong QT but also they alter T wave morphology, novel computerized methods quantifying these changes are being developed to assist physicians and drug manufacturers in monitoring safety of the drugs. The response of a patient to a drug is very individual and therefore an individualized system of drug administration and monitoring needs to be developed, which takes into account baseline QTc duration and its changes after a drug was introduced. (Cardiol J 2007; 14: 523–533)
Impact of bifurcation target lesion on angiographic, electrocardiographic, and clinical outcomes of patients undergoing primary percutaneous coronary intervention (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI] trial).

AIMS Using the database from the large-scale, prospective, randomised HORIZONS-AMI trial, the authors sought to assess the impact of bifurcation target lesions (BTL) on angiographic, electrocardiographic, and clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS In HORIZONS-AMI, bifurcation lesions in which a provisional approach was planned were eligible for enrolment. By angiographic core laboratory assessment of 3,306 patients with STEMI undergoing primary PCI, 333 patients (10%) had ≥1 BTL, and 2,973 patients had no BTL. There were no significant differences in baseline characteristics between the groups, except for lower left ventricular ejection fraction and more frequent left anterior descending infarct artery in the BTL group. BTLs required longer procedural and fluoroscopy times and higher contrast loads, but rates of TIMI 3 flow post PCI were similar in both groups (with vs. without BTL 99% vs. 87%, p=0.25). ST-segment resolution ≥70% by core laboratory analysis was similar in both groups (48% vs. 50%, p=0.47). Importantly, there was no difference between groups in the rate of death (6.1% vs. 6.7%, p=0.72), definite or probable stent thrombosis (4.2% vs. 5.2%, p=0.42), and ischaemic target vessel revascularisation (14.3% vs. 14.0%, p=0.86) during three-year follow-up. CONCLUSIONS Although the PCI procedure involving BTL was more complex, the acute results and late outcomes in patients with BTLs were comparable to those in patients without BTLs.
OFF-State Degradation of AlGaN/GaN Power HEMTs: Experimental Demonstration of Time-Dependent Drain-Source Breakdown

This paper reports the experimental demonstration of a novel degradation mechanism of high-power AlGaN/GaN high electron mobility transistors (HEMTs), that is, time-dependent drain-source breakdown. With current-controlled breakdown measurements and constant voltage stress experiments we demonstrate that: 1) when submitted to constant voltage stress, in the OFF-state, the HEMTs can show a significant degradation; 2) the degradation process is time-dependent, and consists of a measurable increase in subthreshold drain-source leakage; this effect is ascribed to the accumulation of positive charge in proximity of the gate, consistently with previous theoretical calculations; and 3) a catastrophic (and permanent) failure is observed for long stress times, possibly due to thermal runaway or to the increase in the electric field in proximity of the localized drain-source leakage paths.
Innovating Beyond the Fuzzy Front End: How to Use Reward-Based Crowdfunding to Co-create with Customers

Current research suggests that crowdfunding not only serves as an alternative source of capital but also as a flexible tool allowing start-ups to systematically integrate a crowd into their innovation processes. However, an adequate understanding of how start-ups can systematically leverage the co-creation potential of their early customers during crowdfunding is still nascent. Against this background, the aim of this research is to conceptualize and examine the concept of co-creation in the context of reward-based crowdfunding. In doing so, we distinguish it from other methods of user integration in the realm of open innovation and discuss how entrepreneurs can leverage reward-based crowdfunding to engage their customers in the development and deployment of their product and service offerings.