Miracle-dz/UniFAR-FTUs huggingface dataset:
Thymic selection and thymic major histocompatibility complex class II expression are abnormal in mice undergoing graft-versus-host reactions

The graft-vs.-host reaction (GVHR) results in damage to the epithelial and lymphoid compartments of the thymus and thus in abnormal maturation and function of thymocytes in mice undergoing GVHR. In this report, the effects of GVHR on thymic T cell receptor (TCR) expression and usage have been investigated. GVHR was induced in unirradiated F1 hybrid mice by the intravenous transfer of parental lymphoid cells. Expression of the CD3/TCR complex on thymocyte subsets defined by CD4 and CD8 was studied by three-color flow cytometry. The level of CD3/TCR was decreased on CD4+CD8-, but not CD4-CD8+, mature thymocytes. The lack of upregulation of CD3/TCR on CD4 single-positive thymocytes, but not on their CD8+ counterparts, suggested an abnormality of class II major histocompatibility complex (MHC) expression in the thymuses of mice undergoing GVHR. Immunofluorescence staining of thymic frozen sections revealed that MHC class II expression was dramatically decreased in GVH- reactive mice. GVHR-induced changes in positive and negative selection were evaluated by determining the incidence of specific V beta TCR segment usage in the thymus. In normal mice, thymocyte usage of any given V beta segment was highly consistent between individuals of the same strain and age; however, a marked divergence in the incidence of TCR V beta 6hi and V beta 8hi cells between GVH-reactive littermate mice was observed, suggesting that thymic positive selection had become disregulated in these animals. Furthermore, negative selection was defective; the incidence of phenotypically self-reactive V beta 6hi T cells was significantly greater in the thymuses of GVH-reactive mice bearing the endogenous superantigen Mls-1a than in untreated controls. Thus, mice undergoing GVHR showed defective TCR upregulation on CD4+CD8- thymocytes and changes in TCR usage reflecting aberrant thymic selection, in conjunction with decreased expression of MHC class II. Most abnormalities of TCR expression and usage on CD4+ thymocytes observed in GVH-reactive mice were analogous to those of class II knockout mice.
Reduction of switching losses and increase in efficiency of power converters using predictive control

To achieve high efficiency without performance deterioration is a desired objective in power conversion. This work presents a novel method to reduce switching losses, based on predictive control, which can be applied to a wide variety of switched-mode power converters. The idea is to predict switching losses for every valid switching state of the converter if applied during the next sampling time and then select the optimum state based on the evaluation of a quality function. The proposed strategy was experimentally tested on a matrix converter and induction machine setup, reducing energy losses, thus increasing efficiency, without affecting the performance of the drive.
Plasma Membrane Protein Profiling in Beta‐Amyloid‐Treated Microglia Cell Line

In the responsiveness of microglia to toxic stimuli, plasma membrane proteins play a key role. In this study we treated with a synthetic beta amyloid peptide murine microglial cells metabolically differently labelled with stable isotope amino acids (SILAC). The plasma membrane was selectively enriched by a multi‐stage aqueous two‐phase partition system. We were able to identify by 1D‐LC‐MS/MS analyses 1577 proteins, most of them are plasma membrane proteins according to the Gene Ontology annotation. An unchanged level of amyloid receptors in this data set suggests that microglia preserve their responsiveness capability to the environment even after 24‐h challenge with amyloid peptides. On the other hand, 14 proteins were observed to change their plasma membrane abundance to a statistically significant extent. Among these, we proposed as reliable biomarkers of the inflammatory microglia phenotype in AD damaged tissues MAP/microtubule affinity‐regulating kinase 3 (MARK3), Interferon‐induced transmembrane protein 3 (IFITM3), Annexins A5 and A7 (ANXA5, ANXA7) and Neuropilin‐1 (NRP1), all proteins known to be involved in the inflammation processes and in microtubule network assembly rate.
Effective Analysis for Engineering Real-Time Fixed Priority Schedulers

There has been considerable activity in recent years in developing analytical techniques for hard real-time systems. Inevitably these techniques make simplifying assumptions so as to reduce the complexity of the problem to be solved. Unfortunately this leads to a gap between theory and engineering practice. The paper presents new analysis that enables the costs of the scheduler (clock overheads, queue manipulations and release delays) to be factored into the standard equations for calculating worst-case response times. As well as predicting the true behavior of realistic systems, the analysis also allows free parameters, such as clock interrupt rate, to be determined. >
Estimation of price elasticity and taxation in the U.S. cigarette industry

Abstract Based on our empirical estimates, the data did not suggest that federal tax has a larger impact on the retail price of cigarettes than does state tax since the state tax is susceptible to bootlegging bias among adjacent states. The price elasticities of demand for cigarettes are –0.675 and –0.308 in the long term and in the short term, respectively. With current price elasticity stabilizing between –0.3 and –0.5 —a value below profit-maximizing value — there is indeed considerable room for future cigarettes tax hikes to meet the shortfall in the budgets of both federal and state governments.
Sequence requirement for expression of the Drosophila melanogaster heat shock protein hsp22 gene during heat shock and normal development

A 14-base-pair sequence element present in almost all Drosophila melanogaster heat shock genes has been implicated in the heat inducibility of transcription. The D. melanogaster gene encoding the smallest heat shock protein, hsp22, contains within its 5' flanking sequences three such repeats, two close to the transcription start site and a distally located third one 101 base pairs further upstream. Deletion analyses reveal that the 5' flanking sequences required for full expression of the hsp22 gene extend beyond the distal repeat. Deletion of the furthest upstream repeat results in a five to sixfold reduction of gene expression. The small heat shock genes are transiently expressed in the late third instar larval and early pupal stages without external stimulation. A deletion of 5' flanking sequences to position -194, which includes two nucleotides of the distal heat shock element, has no effect on the developmental expression, whereas removal of an additional 18 nucleotides, including 12 nucleotides of the distal heat shock element, severely reduces developmental expression.
Evaluation of four affibody-based near-infrared fluorescent probes for optical imaging of epidermal growth factor receptor positive tumors.

UNLABELLED The epidermal growth factor receptor 1 (EGFR) has become an attractive target for cancer molecular imaging and therapy. An Affibody protein with strong binding affinity for EGFR, ZEGFR:1907, has been reported. We are interested in translating Affibody molecules to potential clinical optical imaging of EGFR positive cancers. In this study, four anti-EGFR Affibody based near-infrared (NIR) fluorescent probes were thus prepared, and their in vivo performance was evaluated in the mice bearing EGFR positive subcutaneous A431 tumors. METHODS The Affibody analogue, Ac-Cys-ZEGFR:1907, was synthesized using solid-phase peptide synthesis method. The purified small protein was then site-specifically conjugated with four NIR fluorescent dyes, Cy5.5-monomaleimide, Alex-Fluor-680-maleimide, SRfluor680-maleimide, or IRDye-800CW-maleimide, to produce four optical probes-Cy5.5-ZEGFR:1907, Alexa680-ZEGFR:1907, SR680-ZEGFR:1907, and 800CW-ZEGFR:1907. The EGFR binding property and specificity of the four NIR fluorescent Affibody probes were studied by fluorescence microscopy using high EGFR expressing A431 cells and low expressing MCF7 cells. The binding affinities of the probes (KD) to EGFR were further determined by flow cytometry. In vivo optical imaging of the four probes was performed in the mice bearing subcutaneous A431 tumors. RESULTS The four NIR optical probes were prepared in high purity. In vitro cell imaging studies demonstrated that all of them could specifically bind to EGFR positive A431 cells while showing minimum uptake in low EGFR expressing MCF7 cells. Flow cytometry showed that Cy5.5-ZEGFR:1907 and Alexa680-ZEGFR:1907 possessed high binding affinity in low nanomolar range (43.6 ± 8.4 and 28.3 ± 4.9, respectively). In vivo optical imaging of the four probes revealed that they all showed fast tumor targeting ability and good tumor-to-normal tissue contrast as early as 0.5 h postinjection (p.i.). The tumor-to-normal tissue ratio reached a peak at 2 to 4 h p.i. by regional of interest (ROI) analysis of images. Ex vivo studies further demonstrated that the four probes had high tumor uptakes. Particularly, Cy5.5-ZEGFR:1907 and Alex680-ZEGFR:1907 displayed higher tumor-to-normal tissue ratios than those of the other two probes. CONCLUSION This work demonstrates that Affibody proteins can be modified with different NIR fluorescent dyes and used for imaging of EGFR expressing tumors. Different NIR fluorescent dyes have variable impact on the in vitro binding and in vivo performance of the resulting Affibody based probes. Therefore, selection of an appropriate NIRF label is important for optical probe development. The probes developed are promising for further tumor imaging applications and clinical translation. Particularly, Alex680-ZEGFR:1907 and Cy5.5-ZEGFR:1907 are excellent candidates as EGFR-targeted probes for optical imaging.
Generation of Human Islets Through Expansion and Differentiation of Non-islet Pancreatic Cells Discarded (Pancreatic Discard) After Islet Isolation

Objectives: Islet transplantation is hampered by the shortage of donor tissues. Our objective was to generate islet-like cell clusters (ICCs) from cultures of non-islet pancreatic cells. Methods: The starting cultured cells came from the non-islet fractions of human pancreases after enzymatic digestion and purification for the purpose of islet isolation. Initially, these cells expanded in monolayer cultures and became confluent on collagen-coated flasks. After trypsination and suspension of these cells in a defined islet differentiation medium, the cells aggregated to form ICCs. Results: The initial cell population consisted of less than 1% of insulin-positive cells, 44% amylase-positive cells, and 41% cytokeratin (CK) 7-positive, or CK19+ cells, but PDX-1+ cells were absent. Cells from later stages of the monolayer cultures showed signs of dedifferentiation/transdifferentiation. At the time of harvesting, more than 90% of the cells were positive for CK 7/19 and PDX-1, but less than 1% of the cells were insulin-positive. After aggregation, the ICCs appeared redifferentiated, and contained glucose-responsive, insulin-secreting cells with an insulin content measuring 20% of that found in freshly isolated islets isolated from the same pancreas. ICCs transplanted into athymic mice and removed after 4 months did acquire the morphology of mature islets, indicating further maturation of the ICCs in vivo after transplantation. Human C-peptide was detected in recipient animal sera. Conclusion: Using the specified culture methods, non-islet pancreas cells can generate cell clusters resembling islets. These ICCs, obtained from fractions of the pancreas that are otherwise discarded, continue to differentiate after transplantation to become mature islets.
Under-reporting of infectious gastrointestinal illness in British Columbia, Canada: who is counted in provincial communicable disease statistics?

SUMMARY Under-reporting of infectious gastrointestinal illness (IGI) in British Columbia, Canada was calculated using simulation modelling, accounting for the uncertainty and variability of input parameters. Factors affecting under-reporting were assessed during a cross-sectional randomized telephone survey. For every case of IGI reported to the province, a mean of 347 community cases occurred (5th and 95th percentile estimates ranged from 181 to 611 community cases, respectively). Vomiting [odds ratio (OR) 2·15, 95% confidence interval (CI) 1·03–4·49] and antibiotic use in the previous 28 days (OR 3·59, 95% CI 1·17–10·97) significantly predicted health-care visits in a logistic regression model. In bivariate analyses, physicians were significantly less likely to request stool samples from patients with vomiting (RR 0·09, 95% CI 0·01–0·65) and patients of North American as opposed to non-North American cultural groups (RR 0·38, 95% CI 0·15–0·96). Physicians were more likely to request stool samples from older patients (P=0·003), patients with fewer household members (P=0·002) and those who reported anti-diarrhoeal use following illness (RR 3·33, 95% CI 1·32–8·45). People with symptoms of vomiting were under-represented in provincial communicable disease statistics. Differential degrees of under-reporting must be understood before biased surveillance data can be adjusted.
Development of structural and functional connectivity in the thalamocortical somatosensory pathway in the wallaby

Neuronal activity is implicated as a driving force in the development of sensory systems. In order for it to play a developmental role, however, the pathways involved must be capable of transmitting this activity. The relationship between afferent arrival, synapse formation and the onset of chemical neurotransmission has been examined using the advantageous model of a marsupial mammal, the wallaby (Macropus eugenii), to determine at what stage activity has the capacity to influence cortical development. It is known that thalamocortical afferents arrive in the somatosensory cortex on postnatal day (P)15 and that their growth cones reach to the base of the compact cell zone of the cortical plate. However, electronmicroscopy showed that thalamocortical synapses were absent at this stage. Glutamatergic responses were recorded in the cortex following stimulation of the thalamus in slices at this time but only in magnesium‐free conditions. The responses were mediated entirely by N‐methyl‐d‐aspartate (NMDA) receptors. From P28, responses could be recorded in normal magnesium and comprised a dominant NMDA‐mediated component and a non‐NMDA mediated component. At this time thalamocortical synapses were first identified and they were in the cortical plate. By P63 the non‐NMDA‐mediated component had increased relative to the NMDA‐mediated component, and by P70 layer IV began to emerge and contained thalamocortical synapses. By P76 a fast non‐NMDA‐mediated peak dominated the response. This coincides with the appearance of cortical whisker‐related patches and the onset in vivo of responses to peripheral stimulation of the whiskers.
Proportional Hazards Regression for Cancer Studies

Summary. There has been some recent work in the statistical literature for modeling the relationship between the size of cancers and probability of detecting metastasis, i.e., aggressive disease. Methods for assessing covariate effects in these studies are limited. In this article, we formulate the problem as assessing covariate effects on a right‐censored variable subject to two types of sampling bias. The first is the length‐biased sampling that is inherent in screening studies; the second is the two‐phase design in which a fraction of tumors are measured. We construct estimation procedures for the proportional hazards model that account for these two sampling issues. In addition, a Nelson–Aalen type estimator is proposed as a summary statistic. Asymptotic results for the regression methodology are provided. The methods are illustrated by application to data from an observational cancer study as well as to simulated data.
Toward Quality Care in ADHD

Objective: Therapeutic goals for chronic mental disorders like major depressive disorder (MDD) and schizophrenia have evolved in parallel with the growing medical knowledge about the course and treatment of these disorders. Although the knowledge base regarding the clinical course of ADHD, a chronic psychiatric disorder, has evolved beyond symptomatic improvement and short-term treatment response, long-term goals, such as functional remission, have not yet been clearly defined. Method: A PubMed literature search was conducted to investigate the therapeutic goals of pharmacologic treatment referenced in the published literature from January 1998 through February 2010 using the following commonly used ADHD treatments as keywords: amphetamine, methylphenidate, atomoxetine, lisdexamfetamine, guanfacine, and clonidine. This search was then combined with an additional search that included the following outcome keywords: remission, relapse, remit, response, normal, normalization, recovery, and effectiveness. Results: Our search identified 102 publications. The majority (88.2% [90/102]) of these contained predefined criteria for treatment response. Predefined criteria for normalization and remission and/or relapse were presented in 4.9% (5/102), 12.7% (13/102), and 3.9% (4/102) of publications, respectively. There was a lack of consistency between the instruments used to measure outcomes as well as the criteria used to define treatment response, normalization, and remission as well as relapse. Conclusion: The therapeutic goals in treating ADHD should address optimal treatment outcomes that go beyond modest reductions of ADHD symptoms to include syndromatic, symptomatic, and functional remission. Future work should focus on reliable and valid tools to measure these outcomes in the clinical trial setting.
Improved model predictive control with loss energy awareness of a 3L-ANPC voltage source converter

This paper shows a predictive current control with DC-Link voltage balance feature. A restriction in the voltage vectors generated by the 3L converter is explained, which leads to a better 3L voltage pattern, reducing double commutations and accelerating the calculation routine. On the other hand an estimation of the switching losses is considered in the selection of the future voltage vector, which will optimize the switching losses in the entire converter. These new features are proposed in order to contribute to the development of a better control technique to make the converter as efficient as possible and to encourage the use of predictive control for power converters.
Development and Assessment of Human Adenovirus Type 11 as a Gene Transfer Vector

ABSTRACT Adenovirus vectors based on human serotype 5 (Ad5) have successfully been used as gene transfer vectors in many gene therapy-based approaches to treat disease. Despite their widespread application, many potential therapeutic applications are limited by the widespread prevalence of vector-neutralizing antibodies within the human population and the inability of Ad5-based vectors to transduce important therapeutic target cell types. In an attempt to circumvent these problems, we have developed Ad vectors based on human Ad serotype 11 (Ad11), since the prevalence of neutralizing antibodies to Ad11 in humans is low. E1-deleted Ad11 vector genomes were generated by homologous recombination in 293 cells expressing the Ad11-E1B55K protein or by recombination in Escherichia coli. E1-deleted Ad11 genomes did not display transforming activity in rodent cells. Transduction of primary human CD34+ hematopoietic progenitor cells and immature dendritic cells was more efficient with Ad11 vectors than with Ad5 vectors. Thirty minutes after intravenous injection into mice that express one of the Ad11 receptors (CD46), we found, in a pattern and at a level comparable to what is found in humans, Ad11 vector genomes in all analyzed organs, with the highest amounts in liver, lung, kidney, and spleen. Neither Ad11 genomes nor Ad11 vector-mediated transgene expression were, however, detected at 72 h postinfusion. A large number of Ad11 particles were also found to be associated with circulating blood cells. We also discovered differences in in vitro transduction efficiencies and in vivo biodistributions between Ad11 vectors and chimeric Ad5 vectors possessing Ad11 fibers, indicating that Ad11 capsid proteins other than fibers influence viral infectivity and tropism. Overall, our study provides a basis for the application of Ad11 vectors for in vitro and in vivo gene transfer and for gaining an understanding of the factors that determine Ad tropism.
Sequence capture using PCR‐generated probes: a cost‐effective method of targeted high‐throughput sequencing for nonmodel organisms

Recent advances in high‐throughput sequencing library preparation and subgenomic enrichment methods have opened new avenues for population genetics and phylogenetics of nonmodel organisms. To multiplex large numbers of indexed samples while sequencing predominantly orthologous, targeted regions of the genome, we propose modifications to an existing, in‐solution capture that utilizes PCR products as target probes to enrich library pools for the genomic subset of interest. The sequence capture using PCR‐generated probes (SCPP) protocol requires no specialized equipment, is highly flexible and significantly reduces experimental costs for projects where a modest scale of genetic data is optimal (25–100 genomic loci). Our alterations enable application of this method across a wider phylogenetic range of taxa and result in higher capture efficiencies and coverage at each locus. Efficient and consistent capture over multiple SCPP experiments and at various phylogenetic distances is demonstrated, extending the utility of this method to both phylogeographic and phylogenomic studies.
Stroke volume variation during hemorrhage and after fluid loading: impact of different tidal volumes

Background: Previous studies have shown that stroke volume variation (SVV) may be used to assess preload and fluid responsiveness. It is currently under debate, if SVV reliably displays changes in preload during ventilation with clinically used tidal volumes. This study was designed to evaluate whether the predictive value of SVV depends on the tidal volume applied particularly during acute changes of preload.
Prognostic value of uPA, PAI-1 and PAI-2 mRNA expression in primary breast cancer.

BACKGROUND The prognostic value of uPA, PAI-1 and PAI-2 mRNA expression was studied in a retrospective series of 130 primary breast cancer patients (median follow-up 8.1 years). MATERIALS AND METHODS UPA, PAI-1 and PAI-2 mRNA were quantified by means of real-time quantitative RT-PCR. Comparison with the corresponding protein levels determined by ELISA was performed in 21 cases. RESULTS Higher uPA protein values were found in cases with high mRNA values, but the relationship was of borderline significance. PAI-1 and PAI-2 mRNA were positively correlated to protein values. The mRNA expression of uPA, PAI-1 and PAI-2 was significantly correlated with one another. Higher uPA and PAI-1 mRNA values were significantly associated with shorter disease-free survival (DFS) (p = 0.002; p = 0.03, respectively). Low and very high PAI-2 mRNA values tended to be associated with longer DFS. In Cox multivariate analyses, higher uPA and PAI-1 mRNA values were independently associated with shorter DFS. PAI-2 was not retained as a significant variable in the Cox model. CONCLUSION These preliminary results indicate that, in breast cancer, uPA, PAI-1 and PAI-2 mRNA analysis by quantitative RT-PCR give results comparable to those obtained at the protein level.