Miracle-dz/UniFAR-FTUs huggingface dataset:
Lck Phosphorylates the Activation Loop Tyrosine of the Itk Kinase Domain and Activates Itk Kinase Activity*

The Tec family tyrosine kinase Itk has been implicated in T cell receptor (TCR) signaling, yet its precise role and mechanism of activation remain undefined. To investigate these issues, we examined the biochemical response of Itk to TCR stimulation. We found that Itk is tyrosine-phosphorylated after TCR cross-linking and that this phosphorylation depends on the presence of functional Lck. To determine if this Lck dependence results from direct phosphorylation of Itk by Lck, we generated recombinant Itk and Lck using a baculovirus expression system and used these proteins in subsequent biochemical analyses. We found that Lck phosphorylates Itk upon co-expression in insect cells and, further, that this phosphorylation of Itk results in increased Itk in vitro kinase activity. The major site of Lck phosphorylation on Itk was mapped to the conserved tyrosine (Tyr511) in the activation loop of the Itk kinase domain. Substitution of this tyrosine with phenylalanine abolishes Itk kinase activity in insect cells, indicating that phosphorylation at this site plays a critical role in regulating Itk function.
SPECIFIC AND NON-SPECIFIC IMMUNITY IN EXPERIMENTAL CRYPTOCOCCOSIS IN MICE

The course of lethal cryptococcosis in mice was modified by immunization with the same strain or different strains of Cryptococcus neoformans. Protection was associated with a definite decrease in tissue fungus multiplication over the initial 7 days of infection. Such immunity was species-specific and did not protect against heterologous challenge with Staphylococcus aureus, Klebsiella pneumoniae, or Mycobacterium tuberculosis. Similar modification of lethal cryptococcosis was produced by intraperitoneal inoculation of 100 to 200 µg. of Salmonella endotoxin 7 days prior to challenge. In non-specifically (endotoxin) immunized mice there was only a minimal reduction in tissue cryptococcus census during the 1st week of infection. When small numbers of virulent cryptococci were injected intravenously into normal mice, tissue populations rose markedly in all organs studies during the first 7 days. A progressive fall in tissue fungus census was then observed in most mice during the next 6 months. The increase in resistance to cryptococcal challenge following specific immunization, the non-specific protection conferred by injection of bacterial endotoxin and the ability to control and eventually reduce infections with small inocula may well be dependent in each case on the development of specific antibody.
The Applicability and Outcome of Constraint Induced Language Therapy (CILT) in Early Aphasia Rehabilitation

Background: Oral text production reflects a more natural communication aspect of language than most standardised aphasia tests. Several methods for text analysis have been developed; however, clinical application in speech-language therapy has so far been limited. Further, exploration of the generalisation effect of specific impairment-based treatment forms to spontaneous speech and everyday communication is still warranted. Aims: The present study explores the relevance of oral text production for measurement of aphasia treatment outcome with constraint induced language therapy (CILT). The study investigates if improvement on standardised tests generalises to connected speech production with a focus on vocabulary and content. Methods & procedures: Analyses are based on the preand post-intervention transcriptions of conversational interviews with three speakers with aphasia participating in a clinical CILT treatment study in early aphasia rehabilitation. The analyses include quantitative measurements of the speech production (number of words, number of utterances, and mean length of utterance), of the lexical production of nouns and verbs (proportion, variation, frequency and specificity), and of the content (proportion of informative utterances and meta- communicative utterances). In addition, the analyses include a qualitative evaluation of the
Modulation of growth factor induced fiber outgrowth in rat pheochromocytoma (PC12) cells by a fibronectin receptor antibody

Rat pheochromocytoma PC12 cells respond to the binding of nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) by extending neurites in a manner resembling sympathetic neurons. This response requires cell attachment to an appropriate substratum (Fujii et al., J. Neurosci., 2:1157, 1982); attachment factors which function in this capacity include the adhesive proteins fibronectin and laminin. Incubating PC12 cells with a ployclonal antiserum directed against a putative 140‐kDa fibroblast cell surface fibronectin receptor (anti‐gp140) perturbed spreading but not attachment of the cells to fibronectin and laminin substrates. However, in the presence of anti‐gp 140 or its Fab fragments, NGF‐stimulated neurite outgrowth was dramatically reduced. The antibody also caused a retraction of previously extended neurites. SDS‐PAGE analysis of immunoprecipitates of PC12 cells surface labeled with 125I identified a prominent 120–140‐kDa band, suggesting that the site of anti‐gp 140 action in PC12 cells is also through a fibronectin receptor.
MicroRNAs in normal and malignant hematopoiesis

Purpose of reviewThe discovery of a novel class of gene regulators, named microRNAs, has changed the landscape of human genetics. In hematopoiesis, recent work has improved our understanding of the role of microRNAs in hematopoietic differentiation and leukemogenesis. Recent findingsUsing animal models engineered to overexpress miR-150, miR-17∼92 and miR-155 or to be deficient for miR-223, miR-155 and miR-17∼92 expression, several groups have now shown that miRNAs are critical for B-lymphocyte development (miR-150 and miR-17∼92), granulopoiesis (miR-223), immune function (miR-155) and B-lymphoproliferative disorders (miR-155 and miR-17∼92). Distinctive miRNA signatures have been described in association with cytogenetics and outcome in acute myeloid leukemia. SummaryThere is now strong evidence that miRNAs modulate not only hematopoietic differentiation and proliferation but also activity of hematopoietic cells, in particular those related to immune function. Extensive miRNA deregulation has been observed in leukemias and lymphomas and mechanistic studies support a role for miRNAs in the pathogenesis of these disorders.
RNA Interference Characterization of Proteins Discovered by Proteomic Analysis of Pancreatic Cancer Reveals Function in Cell Growth and Survival

Objectives There is a clear need for better therapeutics and diagnostics for pancreatic cancer. We aimed to discover plasma membrane-associated proteins overexpressed in pancreatic cancer using quantitative proteomics and apply RNA interference (RNAi) to uncover proteins associated with cancer cell survival. Methods Cell surface glycoproteins from 5 pancreatic cancer cell lines were isolated, and differential analyses were performed using mass spectrometry and the “normoid” cell line Hs766T as the comparator. For validation, immunohistochemistry was performed on tissues from 10 independent patients and 2 normal donors. Correlation of protein and mRNA expression level was determined, and functional activity characterized using RNAi. Results Integrin &bgr;6, CD46, tissue factor, and a novel protein, chromosome 14 open reading frame 1, were identified as overexpressed on pancreatic cancer cell lines. Immunohistochemistry demonstrated the 4 targets were overexpressed in 20% to 70% of primary pancreatic tumor specimens. Small interfering RNA knockdown resulted in a reduction of cellular proliferation by inhibiting DNA synthesis, blocking S-phase progression or induction of apoptosis. Conclusions By combining a mass spectrometry identification platform and an RNAi validation platform, we have identified a panel of cell surface glycoproteins that not only are overexpressed, but also play a functional role in pancreatic tumor cell survival.
Do Peer Reviews Predict Impact? Evidence from the American Sociological Review, 1978 to 1982

The authors investigate how well peer reviews of articles published in the journal American Sociological Review between 1978 and 1982 predict the articles’ citation impact in the following 32 years. The authors find no evidence of a relationship between review outcomes and citation impact at any time after publication, even when citations are normalized by subfield. Qualitative analysis of the review texts rules out the interpretation that reviewers focused on potential impact but failed to predict it. Instead, reviewers focused on the soundness of the manuscripts’ arguments. The authors discuss how organizational characteristics of review can decouple reviewers’ judgments from impact.
Should FPGAS abandon the pass-gate?

Pass-transistors have been the key building block for field-programmable gate array (FPGA) circuitry for many years due to the very small switch they enable. However, passtransistor performance and reliability have been degrading with technology scaling. Transmission gates are an alternative to pass-transistors; while larger, they are more robust. We develop a new FPGA circuit optimization flow and use it to investigate the area, delay and power impact of building FPGAs out of transmission gates instead of pass-transistors in a 22nm process. Our results show that transmission gate FPGAs are 15% larger than pass-transistor FPGAs but are 10-25% faster depending on the allowable level of “gate boosting”. Without gate boosting, transmission gate FPGAs are the better option with 14% lower area-delay product. If 200mV of gate boosting is possible however, pass-transistor FPGAs remain the slightly better choice with a 2% better area-delay product. We also show that transmission gates with a separate power supply for their gate terminal enable a low-voltage FPGA with 50% less power and good delay.
Treatment Options for Age-Related Macular Degeneration: A Budget Impact Analysis from the Perspective of the Brazilian Public Health System

Background Age-related macular degeneration (AMD) is a disease that causes reduced visual acuity and blindness. The new treatment options for AMD are not provided by the Brazilian public health system. Objective To conduct a budget impact analysis of three scenarios for the introduction of AMD treatments: all the medications (verteporfin, ranibizumab, and bevacizumab–the reference scenario), ranibizumab alone, and bevacizumab alone. Methods The basic assumption was that the Brazilian public health system would treat the entire target population with AMD aged > 70 years between 2008 and 2011. The size of the population of interest was estimated from official population projections and the prevalence of the disease was obtained from a systematic review. Medication prices were estimated by weighting their market values with correction factors to take account of the public procurement policy. The possibility of aliquoting bevacizumab was also considered. A panel of experts was consulted to estimate the market share of the different medications for the reference scenario. The incremental costs of the ranibizumab-alone and bevacizumab-alone scenarios compared to the reference scenario were calculated. Univariate sensitivity analyses were run to check the robustness of the model. Results In four years, the Brazilian public health system would have treated 1,136,349 individuals with AMD. The annual costs of treating one patient would have been US$476.65 for bevacizumab, US$11,469.39 for ranibizumab, and US$4,376.28 for verteporfin. The incremental cost of the ranibizumab-alone scenario would have been US$1,878,318,056.00 in four years, while the incremental cost for the bevacizumab-alone scenario would have been a reduction of US$4,978,326,359.00 (i.e., a cost saving) in the same period. The bevacizumab-alone option was found to represent a cost saving across sensitivity analyses. Conclusion The introduction of bevacizumab for the treatment of AMD is recommended for the Brazilian Public Health System.
Ramond sector of superconformal algebras via quantum reduction

Quantum hamiltonian reduction of affine superalgebras is studied in the twisted case. The Ramond sector of ``minimal'' superconformal W-algebras is described in detail, the determinant formula is obtained. Extensive list of examples includes all the simple Lie superalgebras of rank up to 2. The paper generalizes the results of Kac and Wakimoto to the twisted case.
Phytoextraction Potential of the Nickel Hyperaccumulators Leptoplax emarginata and Bornmuellera tymphaea

Leptoplax emarginata and Bornmuellera tymphaea are nickel hyperaccumulators of the Brassicaceae family endemic to serpentine soils in Greece. The aims of this work were to compare the growth and uptake behavior of these plants with the Ni hyperaccumulator species Thlaspi caerulescens and Alyssum murale, and to evaluate their effect on soil Ni availability. Plants were grown for 3 mo on three soils that differ in Ni availability. Ni availability in soils was measured by isotopic exchange kinetics and DTPA-TEA extractions. Results showed that L. emarginata produced significantly more biomass than other plants. On the serpentine soil, B. tymphaea showed the highest Ni concentration in shoots. However, Ni phytoextraction on the three soils was maximal with L. emarginata. The high initial Ni availability of soil Serp (470.5 mg kg −1 ) was the main explanation for the high Ni concentrations measured in plant shoots grown on this soil, compared to those grown on soils Calc and Silt. A. murale was the least efficient in reducing Ni availability on the serpentine soil. L. emarginata appeared as the most efficient species for Ni phytoextraction and decrease of the Ni available pool.
Epigenetic dysregulation of the DAP kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in acute leukaemias

Background: Dysregulation of apoptosis is important in carcinogenesis. Aim and Methods: To analyse the potential inactivation of the DAP kinase/p14/HDM2/p53/Apaf-1 pathway by aberrant promoter methylation in acute leukaemias. Results: Of five leukaemic lines examined, p14 was unmethylated in Raji, HL60 and U937, but completely deleted in Jurkat and NB4. DAP kinase was totally methylated in Raji and NB4, but unmethylated in HL60, Jurkat and U937. Apaf-1 was unmethylated in all the lines. At diagnosis, DAP kinase methylation occurred in eight (25%) APL patients and none of the other AML patients (8/32 vs 0/50, p = 0.001). DAP kinase methylation was detected in four (16%) ALL patients. p14 and Apaf-1 methylation was not detected in any of the 32 cases of acute promyelocytic leukaemia (APL), 50 cases of other subtypes of acute myeloid leukaemia (AML), and 25 cases of acute lymphoblastic leukaemia. Conclusion: Among AML subtypes, DAP kinase is preferentially hypermethylated in APL.
Impact of flow control on quality of service driven packet scheduling disciplines

In this paper we investigate the interaction between window based flow control and a recently proposed packet scheduling discipline designed for real-time services. The scheduling discipline, called the dual queue discipline, has been shown to provide greater flexibility than other scheduling disciplines such as fair queueing. However, its performance on non real-time services has not been previously investigated. We show that the dual queue's performance for non real-time services is again better than that of alternative approaches, which indicates that it will perform well in an environment of mixed real-time and non real-time traffic, such as the current Internet.
Characterization of a Defensin from the Oyster Crassostrea gigas

In invertebrates, defensins were found in arthropods and in the mussels. Here, we report for the first time the identification and characterization of a defensin (Cg-Def) from an oyster. Cg-def mRNA was isolated from Crassostrea gigas mantle using an expressed sequence tag approach. To gain insight into potential roles of Cg-Def in oyster immunity, we produced the recombinant peptide in Escherichia coli, characterized its antimicrobial activities, determined its solution structure by NMR spectroscopy, and quantified its gene expression in vivo following bacterial challenge of oysters. Recombinant Cg-Def was active in vitro against Gram-positive bacteria but showed no or limited activities against Gram-negative bacteria and fungi. The activity of Cg-Def was retained in vitro at a salt concentration similar to that of seawater. The Cg-Def structure shares the so-called cystine-stabilized α-β motif (CS-αβ) with arthropod defensins but is characterized by the presence of an additional disulfide bond, as previously observed in the mussel defensin (MGD-1). Nevertheless, despite a similar global fold, the Cg-Def and MGD-1 structures mainly differ by the size of their loops and by the presence of two aspartic residues in Cg-Def. Distribution of Cg-def mRNA in various oyster tissues revealed that Cg-def is mainly expressed in mantle edge where it was detected by mass spectrometry analyses. Furthermore, we observed that the Cg-def messenger concentration was unchanged after bacterial challenge. Our results suggest that Cg-def gene is continuously expressed in the mantle and would play a key role in oyster by providing a first line of defense against pathogen colonization.
Fatigue estimation with a multivariable myoelectric mapping function

A novel approach to muscle fatigue assessment is proposed. A function is used to map multiple myoelectric parameters representing segments of myoelectric data to a fatigue estimate for that segment. An artificial neural network is used to tune the mapping function and time-domain features are used as inputs. Two fatigue tests were conducted on five participants in each of static, cyclic and random conditions. The function was tuned with one data set and tested on the other. Performance was evaluated based on a signal to noise metric which compared variability due to fatigue factors with variability due to nonfatiguing factors. Signal to noise ratios for the mapping function ranged from 7.89 under random conditions to 9.69 under static conditions compared to 3.34-6.74 for mean frequency and 2.12-2.63 for instantaneous mean frequency indicating that the mapping function tracks the myoelectric manifestations of fatigue better than either mean frequency or instantaneous mean frequency under all three contraction conditions.
Differentiation of Mycobacterium ulcerans, M. marinum, and M. haemophilum: Mapping of Their Relationships to M. tuberculosis by Fatty Acid Profile Analysis, DNA-DNA Hybridization, and 16S rRNA Gene Sequence Analysis

ABSTRACT Although Mycobacterium ulcerans, M. marinum, and M. haemophilum are closely related, their exact taxonomic placements have not been determined. We performed gas chromatography of fatty acids and alcohols, as well as DNA-DNA hybridization and 16S rRNA gene sequence analysis, to clarify their relationships to each other and to M. tuberculosis. M. ulcerans and M. marinum were most closely related to one another, and each displayed very strong genetic affinities toM. tuberculosis; they are actually the two mycobacterial species outside the M. tuberculosis complex most closely related to M. tuberculosis. M. haemophilum was more distinct from M. ulcerans and M. marinum, and it appeared to be as related to these two species as to M. tuberculosis. These results are important with regard to the development of diagnostic and epidemiological tools such as species-specific DNA probes and PCR assays for M. ulcerans,M. marinum, and M. haemophilum. In addition, the finding that M. ulcerans and M. marinum are more closely related to M. tuberculosis than are other pathogenic mycobacterial species suggests that they may be evaluated as useful models for studying the pathogenesis of M. tuberculosis. M. marinum may be particularly useful in this regard since strains of this species grow much more rapidly than M. tuberculosis and yet can cause systemic disease in immunocompromised hosts.
Cost‐Effective In‐House Neutralization Assay for the Confirmation of HBeAg

Hepatitis B virus‐e‐antigen (HBeAg) is an affordable viral marker to assess viral replication kinetics and response to antiviral therapy. In the absence of confirmatory assays, discrepant or false‐positive HBeAg results are resolved by screening for other HBV markers. We standardized an in‐house HBeAg neutralization assay (HBeAg‐NT) to confirm HBeAg in clinical samples.
Novel prehospital monitor with injury acuity alarm to identify trauma patients who require lifesaving intervention

BACKGROUND A miniature wireless vital signs monitor (MWVSM, www.athena.gtx.com) has been designed according to US Special Operations Command specifications for field monitoring of combat casualties. It incorporates an injury acuity algorithm termed the Murphy Factor (MF), which is calculated from whatever vital signs are available at the moment and changes in the last 30 seconds. We tested the hypothesis that MF can identify civilian trauma patients during prehospital transport who will require a lifesaving intervention (LSI) upon hospital admission. METHODS From December 2011 to June 2013, a prospective trial was conducted in collaboration with prehospital providers. The MWVSM detects skin temperature, pulse oximetry (SpO2), heart rate (HR), pulse wave transit time, and MF. LSIs included: intubation, tube thoracostomy, central line insertion, blood product transfusion, and operative intervention. Prehospital MWVSM data were compared with simultaneous vital signs (SaO2, systolic blood pressure (SBP), and HR) from a conventional vital signs monitor. Sensitivity, specificity, negative predictive value, positive predictive value, and area under the receiving operating characteristic curves were calculated. RESULTS Ninety-six trauma patients experienced predominantly blunt trauma (n = 80, 84%), were mostly male (n = 79, 82%), and had a mean ± SD age of 48 ± 19 years and an Injury Severity Score (ISS) of 10 (17). Those who received an LSI (n = 48) had similar demographics but higher ISS (18 vs. 5) and mortality (23% vs. 0%) (all p < 0.05). The most common LSIs were intubation (n = 24, 25%), blood product transfusion (n = 19, 20%), and emergency surgery (n = 19, 20%). Compared with HR > 100 beats/min, SBP < 90 mm Hg, SaO2 < 95% alone or in combination, MF > 3 during the entire transport time had the largest area under the receiving operating characteristic curves (0.620, p = 0.081). MF greater than 3 had a specificity of 81%, sensitivity of 39%, positive predictive value of 68%, and negative predictive value of 57% for the need for LSI. CONCLUSION A single numeric value has the potential to summarize overall patient status and identify prehospital trauma patients who need an LSI. Prehospital monitoring combined with algorithms that include trends over time could improve prehospital care for both civilian and military trauma. LEVEL OF EVIDENCE Prospective observational, level II.
The Social Relations of the Classroom: A Moral and Political Perspective

Much of the continuing debate over radical teaching focuses on issues of pedagogical method or “technique. ” Non-traditional teachers ask themselves: Is it possible to break down “artificial” and destructive relationships of dominance and submission within my classroom? Can I assist students in an effort to cast off passive modes they have internalized as a result of years of socialization into deference towards authority? Shall I attempt to reorder dynamics in my classroom in order to undo the damage done to students within hierarchically structured classes? Can I engender and sustain a sense of “community” within my classroom? These imperatives are felt by all radical teachers but most particularly by those who identify themselves as feminists; indeed, “hierarchical,” so-called “traditional, male-dominant” classrooms are frequently castigated as constituent features of a repudiated male approach to teaching and learning, a mode linked to blustering and authoritarian displays of power.