Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of the death receptor CD95 (Fas) expression by dendritic cells protects from a chronic viral infection

Significance Chronic viral infections evolved to avoid destruction by the immune system. Lymphocytic choriomeningitis virus (LCMV) clone 13, which causes a chronic infection, induces expression of Fas death receptor protein by antigen-presenting cells, such as dendritic cells (DCs). When Fas is ligated by Fas ligand expressed by T cells, DCs die. This event blocks further T-cell activation. To break this mechanism and to sustain antiviral T-cell responses, we used mice that lost Fas from DCs. These animals cleared the infection, whereas Fas-sufficient mice did not. Moreover, a transfer of Fas-negative DCs into infected mice supported the clearance of LCMV infection. Thus, we suggest a novel strategy for stimulation of T cells to achieve the clearance of persistent viruses in infected animals and humans. Chronic viral infections incapacitate adaptive immune responses by “exhausting” virus-specific T cells, inducing their deletion and reducing productive T-cell memory. Viral infection rapidly induces death receptor CD95 (Fas) expression by dendritic cells (DCs), making them susceptible to elimination by the immune response. Lymphocytic choriomeningitis virus (LCMV) clone 13, which normally establishes a chronic infection, is rapidly cleared in C57Black6/J mice with conditional deletion of Fas in DCs. The immune response to LCMV is characterized by an extended survival of virus-specific effector T cells. Moreover, transfer of Fas-negative DCs from noninfected mice to preinfected animals results in either complete clearance of the virus or a significant reduction of viral titers. Thus, DC-specific Fas expression plays a role in regulation of antiviral responses and suggests a strategy for stimulation of T cells in chronically infected animals and humans to achieve the clearance of persistent viruses.
[Children's and adolescent's use of medicine for aches and psychological problems: secular trends from 1988 to 2006].

INTRODUCTION Medicine use for aches and psychological problems is common among adolescents. Medicines are toxic and may have harmful side effects. It is therefore important to study change over time and patterns of medicine use. The objective of this paper is to describe self-reported medicine use for headaches, stomach-aches, difficulties in falling asleep, and nervousness among 11-, 13-, and 15-year-old boys and girls from 1968 to 2006. MATERIAL AND METHODS The data material is 6 comparable and representative cross-sectional studies of 11-, 13-, and 15-year-olds from 1988, 1991, 1994, 1998, 2002, and 2006, total n = 23,871. Data were collected by a validated self-report method for medicine use and prevalence of the corresponding complaints. RESULTS The proportion of students who used medicine for headaches within the previous month increased from 24.6% in 1988 to 42.0% in 2002 and 41.5% in 2006. The proportion who used medicine for stomach-aches increased from 7.5% in 1988 to 16.2% in 2002 and 15.2% in 2006. The proportion who used medicine for difficulties in falling asleep increased from 2.2% to 5.1%, and the proportion who used medicine for nervousness increased from 0.7% to 3.8%. There were increasing proportions of users in most sex- and age-specific subgroups. In the same period, the proportion who reported headaches and stomach-aches within the previous month decreased. The proportion who reported nervousness and difficulties in falling asleep did not change much in this period. CONCLUSION There was a significant increase in 11-, 13-, and 15-year-old student's use of medicine for aches and psychological problems from 1988 to 2006. In the same period, there was a decrease in the prevalence of students who reported pains monthly.
Connecting Reovirus Oncolysis and Ras Signaling

Reovirus is a benign virus with innate oncolytic activity and is a potential novel therapeutic for a number of cancers. Reovirus can replicate in, and induce death of cancerous cells having an activated Ras pathway. Ras activation leads to the inactivation of cellular antiviral mechanisms, specifically removing the translation block on reovirus transcripts. This review outlines recent progress towards elucidating the molecular connection between the Ras-signaling pathway and reovirus replication.
Temporal expression of hepatic inducible nitric oxide synthase in liver cirrhosis.

AIM Nitric oxide (NO) has been implicated in the pathogenesis of liver cirrhosis. We have found inducible nitric oxide synthase (iNOS) can be induced in hepatocytes of cirrhotic liver. This study further investigated the temporal expression and activity of hepatic iNOS in cirrhosis development. METHODS Cirrhosis was induced in rats by chronic bile duct ligation (BDL). At different time points after the operation, samples were collected to examine NO concentration, liver function, and morphological changes. Hepatocytes were isolated for determination of iNOS mRNA, protein and enzymatic activity. RESULTS Histological examination showed early cirrhosis 1-2 wk after BDL, with advanced cirrhosis at 3-4 wk. Bilirubin increased dramatically 3 d after BDL, but decreased by 47% on d 14. Three weeks after BDL, it elevated again. Systemic NO concentration did not increase significantly until 4 wk after BDL, when ascites developed. Hepatocyte iNOS mRNA expression was identified 3 d after BDL, and enhanced with time to 3 wk, but reduced thereafter. iNOS protein showed a similar pattern to mRNA expression. iNOS activity decreased from d 3 to d 7, but increased again thereafter till d 21. CONCLUSION Hepatic iNOS can be induced in the early stage, which increases with time as cirrhosis develops. Its enzymatic activity is significantly correlated with protein expression and histological alterations of the liver, but not with systemic NO levels, nor with absolute values of liver function markers.
What does an embryo need?

This review argues that the question ‘What does an embryo need? ’ cannot be adequately answered in quantitative terms to allow the formulation of media for culturing early mammalian embryos. It can be shown experimentally that ‘needs’ in terms of the nutrients an embryo chooses to consume, and their rates of consumption, vary widely, as they are determined by the concentration of the nutrients under consideration and other constituents in the culture medium. Similarly, it is impossible to define ‘needs’ from knowledge of the kinetic properties of nutrient transport systems. Measurements of nutrient consumption, are, however, valuable in determining overall metabolic activity and the balance between oxidative and glycolytic metabolism, in demonstrating qualitative requirements for specific nutrients and in providing markers of normality or abnormality against which to devise methods for diagnosing embryo health. On the basis of these and other considerations, a strategy is proposed for the formulation of embryo culture media that promotes metabolism that is ‘quiet’ rather than ‘active’, reduces the concentrations of nutrients to match those in the Fallopian tube, selects the ‘quietest’ embryos for transfer, and trusts the autonomy of the embryo.
A Survey of Methodological Variation in the Crohn's Disease Activity Index

Background: The Crohn's disease activity index (CDAI) is the most widely used Crohn's disease activity instrument, yet little is known about the methodological variation in its use. Methods: A MEDLINE search was performed to identify authors of articles published from 1976 to 1997 in which the CDAI was used. A multiple‐choice questionnaire was sent to all of the authors identified. Questions covered investigators' practice and research characteristics, and details of definitions and techniques applied in scoring the CDAI. Results: A total of 208 authors were identified, and 100 valid responses were obtained. The respondents were experienced investigators, with 63% of the authors having used the CDAI for ≥7 years. Of these authors, 70% characterized themselves as working in an academic clinical practice, and 72% had participated in industry‐sponsored drug studies in which the CDAI was used as an end point. Considerable variation was noted in the administration and scoring of the CDAI, including disagreement on the definition of “liquid or very soft stools,” the recording of the number of stools, the recording of pain ratings, and the scoring of extraintestinal manifestations and fistulas. The recording of fever, the scoring for the use of opiates, and the standard for the weight variable also varied widely among respondents. Conclusion: Considerable variation exists in the administration and implementation of the CDAI score among the pool of experienced researchers who were surveyed. This variation may affect the comparability of studies and may introduce random error into the measurement of the CDAI.
Colorimetric Method for Identifying Plant Essential Oil Components That Affect Biofilm Formation and Structure

ABSTRACT The specific biofilm formation (SBF) assay, a technique based on crystal violet staining, was developed to locate plant essential oils and their components that affect biofilm formation. SBF analysis determined that cinnamon, cassia, and citronella oils differentially affected growth-normalized biofilm formation by Escherichia coli. Examination of the corresponding essential oil principal components by the SBF assay revealed that cinnamaldehyde decreased biofilm formation compared to biofilms grown in Luria-Bertani broth, eugenol did not result in a change, and citronellol increased the SBF. To evaluate these results, two microscopy-based assays were employed. First, confocal laser scanning microscopy (CLSM) was used to examine E. coli biofilms cultivated in flow cells, which were quantitatively analyzed by COMSTAT, an image analysis program. The overall trend for five parameters that characterize biofilm development corroborated the findings of the SBF assay. Second, the results of an assay measuring growth-normalized adhesion by direct microscopy concurred with the results of the SBF assay and CLSM imaging. Viability staining indicated that there was reduced toxicity of the essential oil components to cells in biofilms compared to the toxicity to planktonic cells but revealed morphological damage to E. coli after cinnamaldehyde exposure. Cinnamaldehyde also inhibited the swimming motility of E. coli. SBF analysis of three Pseudomonas species exposed to cinnamaldehyde, eugenol, or citronellol revealed diverse responses. The SBF assay could be useful as an initial step for finding plant essential oils and their components that affect biofilm formation and structure.
Wideband space-time coded systems with non-collocated antennas

In this paper we consider space-time coded wideband transmission from multiple base-stations. These systems can provide improved resistance to shadowing and extended range. An inherent challenge with these systems, however, is asynchronous reception of the signal elements. We describe three full space diversity approaches for wideband transmission from non-collocated antennas, with throughput, diversity, receiver-complexity trade-offs. Common to all systems are OFDM-type signaling, bit interleaved coded modulation, and iterative decoding. The lowest data-rate lowest complexity system employs an inner orthogonal space- time block code with embedded OFDM transmission, while the highest data-rate highest complexity scheme does not employ an inner code. The latter scheme can provide even higher data rates at reduced space diversity.
Work or Schooling? On the Return to Gaining In‐School Work Experiences

Wages are a composite measure of the return to education and the return to work experiences. Work experiences are often defined as workers who gain experiences on-the-job. However, work experiences can also be part of a study curriculum in vocational secondary education. We estimate the return to in-school work experiences by comparing the Heckman selection model and the Rubin matching model. First, we show that students with in-school work experiences earn +16% more in the first years of labour than their theoretical peers. Second, we indicate that both empirical models do not appropriately deal with censored observations in the presence of an informal market. Including information on a set of censored observations increases the effect to +22%.
Synergistic anti-tumor effect of recombinant human endostatin adenovirus combined with gemcitabine

Endostatin is an important endogenous inhibitor of neovascularization, which has been widely used in anti-angiogenesis therapy for cancer. To fully explore the potential of endostatin, we evaluated the anti-tumor efficacy of the combination of recombinant human endostatin adenovirus and low-dose gemcitabine in nude mice. We injected recombinant human endostatin adenovirus intratumorally plus a low dose of gemcitabine i.p. routinely. The combination treatment produced no side-effects, and resulted in marked suppression in tumor formation and growth of established human lung carcinoma xenografts in nude mice, with decreased microvessel density and increased apoptosis percentage. Our data support the idea of synergistic anti-tumor properties of endostatin plus low-dose chemotherapy against human lung cancer in vivo.
In vivo spin trapping of nitric oxide in mice.

We report here an in vivo spin-trapping technique combined with electron paramagnetic resonance (EPR) spectroscopy to measure nitric oxide (.NO) production in the blood circulation of conscious mice. The method is based on the trapping of nitric oxide (.NO) by a metal-chelator complex consisting of N-methyl-D-glucamine dithiocarbamate (MGD) and reduced iron (Fe2+) to form a stable and water-soluble [(MGD)2-Fe(2+)-NO] complex, which gives rise to a characteristic three-line EPR spectrum of a mononitrosyl-Fe2+ complex (aN = 12.5 G and g(iso) = 2.04) at ambient temperatures. After simultaneous intravenous injection of sodium nitroprusside (an .NO donor) and the [(MGD)2-Fe2+] complex into the lateral vein of the mouse tail, the appearance of the three-line spectrum in the blood circulation of the mouse tail was monitored continuously by using an S-band EPR spectrometer, operating at 3.5 GHz. This represents the first spin trapping of . NO in living animals.
SSMCB: Low-Power Variation-Tolerant Source-Synchronous Multicycle Bus

In this paper, a variation-tolerant low-power source-synchronous multicycle bus (SSMCB) interconnect scheme is proposed. This scheme is scalable and suitable for transferring data across different clock domains such as those in "many-core" SoCs and in 3-D ICs. SSMCB replaces intermediate flip-flops by a source-synchronous synchronization scheme. Removing the intermediate flip-flops in the SSMCB scheme enables better averaging of delay variations across the whole interconnect, which reduces bit-rate degradation due to within-die process variations. Monte Carlo circuit simulations show that SSMCB eliminates 90% of the variation-induced performance degradation in a six-cycle 9-mm-long 16-bit conventional bus. The proposed multicycle bus scheme also leads to significant energy savings due to the elimination of power-hungry flip-flops and the efficient design of the source synchronization overhead. Moreover, eliminating the intermediate flip-flops avoids the timing overhead of the setup time, the flip-flop delay, and the single-cycle clock jitter. This delay slack can then be translated into further energy savings by downsizing the repeaters. The significant delay jitter due to capacitive coupling has been addressed, and solutions are put forward to alleviate it. Circuit simulations in a 65-nm process environment indicate that energy savings up to 20% are achievable for a six-cycle 9-mm-long 16-bit bus.
The breakthrough phenomenon during alpha-interferon therapy of chronic hepatitis C: incidence, management, and outcome.

OBJECTIVES Some patients treated with alpha-interferon (alpha-IFN) for chronic hepatitis C (CHC) initially respond with normalization of ALT only to encounter a rise in ALT while still on the drug. This phenomenon is called breakthrough (BT). We reviewed our experience with BT to clarify its incidence, pathogenesis, management, and outcome. METHODS Charts from 71 consecutive patients with CHC treated with alpha-IFN were reviewed. Forty of these patients were part of a study of 1-yr escalating dose alpha-IFN, initiated at 2 million units (MU) 3 times per week. Endpoints that were evaluated were: reachievement of normal ALT, complete response (CR) (defined as normal ALT at the end of therapy), and sustained CR maintained for 6 months after therapy. RESULTS Twenty-one (29.5%) patients sustained 28 BT events. Thirteen (46.4%) BT events occurred during the first 6 months of a course of alpha-IFN therapy, and 15 (53.6%) occurred during months 7 through 12. Of patients experiencing BT, six (28.6%) completed their course of therapy with a CR, of which two (9.5%) were sustained. By comparison, of 22 patients who normalized ALT without BT, all completed their course with a CR by definition (p < 0.0001), and nine (40.9%, p < 0.05) had a sustained CR. Of 28 BT events, 13 (46.4%) were followed by reattainment of normal ALT. Of 16 BT events managed with continuation of the same dose of alpha-IFN, normal ALT was reachieved in seven (43.8%). Of 12 BT events managed with an escalation in alpha-IFN dose, six (50%) reachieved normal ALT. A full sequential series of hepatitis C virus RNA PCR from periods of elevated, normal, and again elevated ALT was available for 12 BT events. The pattern was +/+/+ in six, +/-/+ in five, and +/-/- in one. In one additional patient, an apparent BT was attributable to alpha-IFN-induced autoimmune hepatitis. CONCLUSIONS BT is a common event that may occur at any point during alpha-IFN therapy of CHC. This may limit the benefits of maintenance strategies. After a BT event, normal ALT can be reestablished in about 50% of cases, although the chance of a sustained CR falls to less than 10%. No advantage was demonstrated for escalating the alpha-IFN dose after a BT event. Therefore, we recommend continuation of the same dose as the initial approach. We suspect that BT relates to nonspecific ALT fluctuation in some patients and to emergence of resistant hepatitis C virus strains in others. Other causes of ALT elevation must also be considered in patients with apparent BT.
Adenocarcinoma on needle prostatic biopsies: does reactive stroma predicts biochemical recurrence in patients following radical prostatectomy?

OBJECTIVE There is evidence that reactive stroma in different cancers may regulate tumor progression. The aim of this study is to establish any possible relation of reactive stroma grading on needle prostatic biopsies to biochemical recurrence. MATERIALS AND METHODS The study group comprised 266 biopsies from consecutive patients submitted to radical prostatectomy. Reactive stroma was defined as stroma surrounding neoplastic tissue and graded as 0 (absent), 1 (slight), 2 (moderate), and 3 (intense) according to tumor stroma area relative to total tumor area. RESULTS From the total of 266 needle prostatic biopsies, 143 (53.8%), 55 (20.7%), 54 (20.3%), and 14 (5.3%) showed grades 0, 1, 2, and 3, respectively. Increasing reactive stroma grade was significantly associated with clinical stage T2, higher preoperative PSA, higher biopsy and radical prostatectomy Gleason score, more extensive tumors in radical prostatectomy, and pathologic stage > T2. Only grade 3 was significantly associated with time and risk to biochemical recurrence. On multivariate analysis only preoperative PSA and 2 methods of biopsy tumor extent evaluation were independent predictors. CONCLUSION Increasing reactive stroma grade on biopsies is significantly associated with several clinicopathologic adverse findings, however, only grade 3 predicts time and risk to biochemical recurrence following radical prostatectomy on univariate but not on multivariate analysis. We have not been able to show that reactive stroma grade 3 on biopsies is an independent predictor of biochemical recurrence beyond that of preoperative PSA and other pathologic findings on biopsy.
Guiding underprepared students to success in higher education

Students are entering institutions across the country unprepared to meet the demands of higher education. While Kansas is above the national average for students prepared for higher education, only twenty-nine percent of Kansas seniors are considered “prepared” for college in the four determined benchmark areas, compared to the twenty-five percent national average (ACT, 2012). With this statistic, ACT indicates that only one fourth of students complete high school requirements in such a way that leads to success post-graduation. Students are not ready for the expectations of higher education, and as a result this population is less likely to succeed. Further, development opportunities targeted at underprepared students are largely unsuccessful at reaching the population. This report looks at the unprepared student population, the role of higher education, and the projected future for underprepared students in higher education. In an effort to encourage holistic development and successful support initiatives, recommendations for higher education practices and research are discussed.
Innate immune response of corneal epithelial cells to Staphylococcus aureus infection: role of peptidoglycan in stimulating proinflammatory cytokine secretion.

PURPOSE This study sought to elucidate the innate immune responses of cultured human corneal epithelial cells (HCECs) to infection by the Gram-positive bacterium Staphylococcus aureus and to determine the underlying mechanisms. METHODS HUCL, a telomerase-immortalized HCEC line, and primary cultures of HCECs were challenged with live or heat-killed S. aureus, its exoproducts, or cell wall components lipoteichoic acid (LTA) and peptidoglycan (PGN). IkappaB-alpha phosphorylation and degradation as well as phosphorylation of MAPKs, p38, and JNK-1/2, were assessed by Western blot analysis. The expression of interleukin (IL)-6, IL-8, TNF-alpha, and beta-defensin-2 were determined using RT-PCR and secretion of IL-6, IL-8, TNF-alpha, and beta-defensin were measured using enzyme-linked immunosorbent assay and immunoblot analysis of culture medium. RESULTS Exposure of HUCL cells to live, but not heat-killed, S. aureus resulted in NF-kappaB activation in a time-dependent manner, as assessed by the increase in IkappaB-alpha phosphorylation and degradation. Live bacteria also activated the p38 and JNK pathways. The effects of live bacteria on HUCL cells may be attributable to bacterial exoproducts, since the conditioned medium of S. aureus also effectively stimulated these signaling pathways. PGN, but not LTA, activated the NF-kappaB and MAPK pathways in a dose- and time-dependent manner. Concomitant with activation of NF-kappaB and MAPKs, transcriptional expression of IL-6, IL-8, TNF-alpha, and beta-defensin-2 were induced in cells challenged with bacterial exoproducts and PGN. Secretion of IL-6, IL-8, TNF-alpha, and beta-defensin-2 were also significantly increased in HCECs in response to bacterial exoproducts and PGN challenge. CONCLUSIONS Corneal epithelial cells possess the ability to recognize the presence of Gram-positive bacteria and to initiate the innate immune responses by the expression and/or release of proinflammatory cytokines and beta-defensin-2 in the cornea.