Miracle-dz/UniFAR-FTUs huggingface dataset:
Autoimmune Tubulointerstitial Nephritis: Insight from Experimental Models

Many forms of tubulointerstitial nephritis (TIN) may have an autoimmune origin. To understand the pathogenesis of autoimmune TIN it is important to examine suitable animal models where the initiation and development of tubulointerstitial diseases can be assessed with precision. Experimental models of autoimmune anti-tubular basement membrane (anti-TBM) disease for example have allowed to define the nephritogenic role of antibodies which target tubulointerstitial moieties. Several tubulointerstitial antigens which are recognized by specific anti-TBM antibodies have been characterized at a molecular level in these models. The CBA/CaH-kdkd mouse strain represents another model of TIN where complex T-cell networks are uniquely altered, resulting in cell-mediated interstitial nephritis. Characteristic tubular alterations (up-regulation of adhesion molecules and CD44, cytokine and chemokine secretion) are prominent in several models of experimental TIN, promoting T-cell and monocyte infiltration. The complex interplay between tubular epithelial cells and immune cells is probably a prerequisite for a coordinated immune response in many forms of TIN, resulting in autoimmune renal tubulointerstitial injury and ultimately in renal failure.
Translation affects immunoglobulin mRNA stability

When termination codons were introduced into exons of the gene for Ig m̈ chain, steady‐state levels of m̈ mRNA were reduced, both at the pre‐B cell stage and at the plasma cell stage. A termination codon in the variable region gene segment and a termination codon in the second exon of the constant region gene segment had effects of similar magnitude. When the termination codon was deleted, the original level of mRNA was restored. The rate of m̈ gene transcription was the same whether or not a termination codon was present. Therefore, the termination codons must reduce the amount of the mRNA by reducing its stability. Since the introduced termination codons prematurely terminate translation and, in so doing, change the ribosome load on the mRNA, we conclude that m̈ mRNA stability is conferred in part by ribosomal protection from enzymatic degradation. We propose that the differences in m̈ mRNA stability during B lymphocyte differentiation are due to different amounts of ribosomes available for translation.
Understanding What the 2% Know: A Mixed Methods Study on Grit, Growth Mindset and Vulnerability Among Thriving Community College Students

iii ACKNOWLEDGEMENTS . v LIST OF TABLES . xi LIST OF FIGURES . xii CHAPTER ONE: INTRODUCTION Problem Statement . 1 Purpose Statement . 6 Research Questions . 7 Significance of the Study . 8 Conceptual Framework . 9 Assumptions . 10 Limitations . 10 Delimitations . 11 Definition of Key Terms . 12 Summary . 16 CHAPTER TWO: LITERATURE REVIEW Introduction . 17 Community College Mission and Struggles . 18 California Community College Master Plan . 20 Demographics of Community College Students . 22 Community College Students’ Barriers . 23 Student Services Shortcomings and Failures . 34 ix Assets of Community College Students . 39 Thriving Students . 40 Theories of Emerging Assets . 48 Significance of the Research on Potential New Assets . 75 Summary . 79 CHAPTER THREE: RESEARCH DESIGN AND METHODOLOGY Introduction . 81 Research Design . 84 Research Setting . 87 Research Sample . 88 Data Collection . 90 Data Analysis . 92 Trustworthiness . 95 Limitations . 96 Positionality of the Researcher . 99 Summary . 103 CHAPTER FOUR: FINDINGS AND RESULTS Introduction . 105 Findings from the Quantitative Phase . 106 Findings from the Qualitative Phase . 136 Mixed Methods Discussion . 156 Commonalities between the Quantitative and Qualitative Findings and Summary of Results . 159
Expression of Cell-Cycle-Regulating Transcription Factor E2F-1 in Colorectal Carcinomas

The expression of E2F-1 in human colorectal carcinomas was examined immunohistochemically, and the correlation of E2F-1 expression with clinicopathological findings and with the expression of p27Kip1 was analyzed to elucidate the role of E2F-1 in the development and progression of colorectal carcinomas. In nonneoplastic mucosa, a small number of epithelial cells in the proliferative zone were weakly positive for E2F-1. Weak expression of E2F-1 was detected in many adenoma cells. Most of the colorectal carcinomas expressed E2F-1 at various levels, and strong expression of E2F-1 was detected in 56% (49/88) of the cases. There was no correlation between the expression of E2F-1 and any clinicopathological parameters such as tumor stage, depth of tumor invasion and lymph node metastasis. Reduced expression of p27Kip1 was confirmed to be significantly correlated with deep tumor invasion and presence of metastasis. No correlation was evident between overexpression of E2F-1 and reduced p27Kip1 expression.
A Novel CDK7 Inhibitor of the Pyrazolotriazine Class Exerts Broad-Spectrum Antiviral Activity at Nanomolar Concentrations

ABSTRACT Protein kinases represent central and multifunctional regulators of a balanced virus-host interaction. Cyclin-dependent protein kinase 7 (CDK7) plays crucial regulatory roles in cell cycle and transcription, both connected with the replication of many viruses. Previously, we developed a CDK7 inhibitor, LDC4297, that inhibits CDK7 in vitro in the nano-picomolar range. Novel data from a kinome-wide evaluation (>330 kinases profiled in vitro) demonstrate a kinase selectivity. Importantly, we provide first evidence for the antiviral potential of the CDK7 inhibitor LDC4297, i.e., in exerting a block of the replication of human cytomegalovirus (HCMV) in primary human fibroblasts at nanomolar concentrations (50% effective concentration, 24.5 ± 1.3 nM). As a unique feature compared to approved antiherpesviral drugs, inhibition occurred already at the immediate-early level of HCMV gene expression. The mode of antiviral action was considered multifaceted since CDK7-regulated cellular factors that are supportive of HCMV replication were substantially affected by the inhibitors. An effect of LDC4297 was identified in the interference with HCMV-driven inactivation of retinoblastoma protein (Rb), a regulatory step generally considered a hallmark of herpesviral replication. In line with this finding, a broad inhibitory activity of the drug could be demonstrated against a selection of human and animal herpesviruses and adenoviruses, whereas other viruses only showed intermediate drug sensitivity. Summarized, the CDK7 inhibitor LDC4297 is a promising candidate for further antiviral drug development, possibly offering new options for a comprehensive approach to antiviral therapy.
The Calcineurin/Nuclear Factor of Activated T Cells Signaling Pathway Regulates Osteoclastogenesis in RAW264.7 Cells*

Although best known for its role in T lymphocyte activation, the calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway is also known to be involved in a wide range of other biological responses in a variety of different cell types. Here we have investigated the role of the calcineurin/NFAT signaling pathway in the regulation of osteoclast differentiation. Osteoclasts are bone-resorbing multinucleated cells that are derived from the monocyte/macrophage cell lineage after stimulation with a member of the tumor necrosis factor family of ligands known as receptor activator of nuclear factor-κB ligand (RANKL). We now report that inhibition of calcineurin with either the immunosuppressant drugs cyclosporin A and FK506, or the retrovirally mediated ectopic expression of a specific calcineurin inhibitory peptide, all potently inhibit the RANKL-induced differentiation of the RAW264.7 monocyte/macrophage cell line into mature multinucleated osteoclasts. In addition, we find that NFAT family members are expressed in RAW264.7 cells and that their expression is up-regulated in response to RANKL stimulation. Most importantly, we find that ectopic expression of a constitutively active, calcineurin-independent NFATc1 mutant in RAW264.7 cells is sufficient to induce these cells to express an osteoclast-specific pattern of gene expression and differentiate into morphologically distinct, multinucleated osteoclasts capable of inducing the resorption of a physiological mineralized matrix substrate. Taken together, these data define calcineurin as an essential downstream effector of the RANKL-induced signal transduction pathway leading toward the induction of osteoclast differentiation and furthermore, indicate that the activation of the NFATc1 transcription factor is sufficient to initiate a genetic program that results in the specification of the mature functional osteoclast cell phenotype.
Glutamate activation of a single NMDA receptorchannel produces a cluster of channel openings

Activations of the N-methyl-d-aspartate (NMDA) receptor by glutamate were studied in outside-out patches from CA1 cells in rat hippocampal slices. Very low glutamate concentrations (20—100 nM) were used so that individual receptor activations would be well separated. The shut-time distribution contained at least five components, only the longest component being obviously concentration dependent. The three briefest shut-time components had time constants of 56 μs, 0.68 ms and 10.1 ms; all of these were independent of glutamate concentration. An individual activation of the receptor therefore produces a long cluster of channel openings that contains longer gaps than have been reported for receptor activations by other fast neurotransmitters. In addition, (i) some activations may contain still longer (mean 78 ms) shut periods generating ‘super clusters’, and (ii) a significant amount of NMDA current may be carried by prolonged (‘high Popen ’) periods during which the channel is open for most of the time. Such periods occur intermittently even at these very low glutamate concentrations. It is suggested that the slow time course of the NMDA receptor-mediated synaptic currents may be determined mainly by the channel activation kinetics.
Network of Hydrogenase Maturation in Escherichia coli: Role of Accessory Proteins HypA and HybF

ABSTRACT We have studied the roles of the auxiliary protein HypA and of its homolog HybF in hydrogenase maturation. A mutation in hypA leads to the nearly complete blockade of maturation solely of hydrogenase 3 whereas a lesion in hybF drastically but not totally reduces maturation and activity of isoenzymes 1 and 2. The residual level of matured enzymes in the hybF mutant was shown to be due to the function of HypA; HybF, conversely, was responsible for a minimal residual activity of hydrogenase 3 in the mutant hypA strain. Accordingly, a hypA ΔhybF double mutant was completely blocked in the maturation process. However, the inclusion of high nickel concentrations in the medium could restore limited activity of all three hydrogenases. The results of this study and of previous work (M. Blokesch, A. Magalon, and A. Böck, J. Bacteriol. 189:2817-2822, 2001) show that the maturation of the three functional hydrogenases from Escherichia coli is intimately connected via the activity of proteins HypA and HypC and of their homologs HybF and HybG, respectively. The results also support the suggestion of Olson et al. (J. W. Olson, N. S. Mehta, and R. J. Maier, Mol. Microbiol. 39:176-182, 2001) that HypA cooperates with HypB in the insertion of nickel into the precursor of the large hydrogenase subunit. Whereas HypA is predominantly involved in the maturation of hydrogenase 3, HybF takes over its function in the maturation of isoenzymes 1 and 2.
Usability and Effects of an Exergame-Based Balance Training Program.

Background: Post-stroke recovery benefits from structured, intense, challenging, and repetitive therapy. Exergames have emerged as promising to achieve sustained therapy practice and patient motivation. This study assessed the usability and effects of exergames on balance and gait. Subjects and Methods: Sixteen elderly participants were provided with the study intervention based on five newly developed exergames. The participants were required to attend 36 training sessions; lasting for 20 minutes each. Adherence, attrition and acceptance were assessed together with (1) Berg Balance Scale, (2) 7-m Timed Up and Go, (3) Short Physical Performance Battery, (4) force platform stance tests, and (5) gait analysis. Results: Thirteen participants completed the study (18.8 percent attrition), without missing a single training session (100 percent adherence). Participants showed high acceptance of the intervention. Only minor adaptations in the program were needed based on the users' feedback. No changes in center of pressure area during quiet stance on both stable and unstable surfaces and no changes of walking parameters were detected. Scores for the Berg Balance Scale (P=0.007; r=0.51), the 7-m Timed Up and Go (P=0.002; r=0.56), and the Short Physical Performance Battery (P=0.013; r=0.48) increased significantly with moderate to large effect sizes. Conclusion: Participants evaluated the usability of the virtual reality training intervention positively. Results indicate that the intervention improves gait- and balance-related physical performance measures in untrained elderly. The present results warrant a clinical explorative study investigating the usability and effectiveness of the exergame-based program in stroke patients.
The effect of a right-to-left intracardiac shunt on the rate of rise of arterial and end-tidal halothane in children.

UNLABELLED In this prospective study, we evaluated the effect of a right-to-left intracardiac shunt on the rate of rise of end-tidal and arterial halothane concentration in children. Six children aged 23-43 mo undergoing surgical closure of atrial fenestration after Fontan procedure were given 0.8% inspired halothane. End-tidal halothane was recorded at 1-min intervals after the introduction of halothane. Arterial halothane concentrations were determined 0, 1, 3, 5, 10, and 15 min after the introduction of halothane. The sampling was performed before and after closure of the atrial fenestration. The ratio of pulmonary to systemic blood flow (Qp/Qs) increased in this patient population, from 0.58 +/- 0.04 to 0.88 +/- 0.12 (P = 0.01). The rate of rise of end-tidal halothane did not change significantly with a decrease in the magnitude of the right-to-left intracardiac shunt after closure of the atrial fenestration. The ratio of arterial to inspired halothane concentrations at 1, 3, 5, 10, and 15 min were lower before closure of the atrial fenestration compared with after closure (P < 0.05). We conclude that the presence of a right-to-left intracardiac shunt significantly slows the rate of rise of arterial halothane in the face of a constant inspired concentration. The rate of rise of end-tidal halothane is not significantly affected in the presence of a right-to-left intracardiac shunt. IMPLICATIONS In this prospective study, we found a slower rate of rise of halothane in arterial blood in children with right-to-left intracardiac shunting. Induction of anesthesia by inhalation of volatile anesthetics may therefore be slower in these children.
Hybrid Exponential‐Hyperbolic Discounting and Growth Without Commitment

We analyse the timeâ€ consistent intertemporal behaviour of an individual who discounts the future hyperbolically (HD) in the absence of commitment. In continuousâ€ time, we extend Barro's (Quarterly Journal of Economics, Vol. 114 (1999), pp. 1125â€“1152) analysis of a â€˜sophisticatedâ€™ presentâ€ bias in a deterministic setup and characterize consumption in an analytically tractable way. Furthermore, we embed this analysis into a â€˜flexible AKâ€™ model. Greater present bias increases the consumptionâ€ capital ratio, decreases the steadyâ€ state growth rate, while it increases the interest rateâ€ growth rate wedge. Dynamically, as the interest rate fluctuates over the business cycle, a greater present bias causes the consumptionâ€ output ratio to be more procyclical and volatile, thus helping to resolve the â€˜consumptionâ€ output puzzleâ€™. In the transitional dynamics, greater present bias causes a lower steady state capital stock. All of these effects are only present or at least more pronounced under HD than present valueâ€ equivalent exponential discounting.
Comparative prospective randomized study comparing conservative treatment and percutaneous disk decompression for treatment of intervertebral disk herniation.

PURPOSE To compare short-, intermediate-, and long-term functional results concerning pain reduction and mobility improvement between conservative therapy and percutaneous disk decompression (PDD) in patients with intervertebral disk herniations. MATERIALS AND METHODS The study received approval from both the university ethics panel and the institutional review board. Patients provided informed consent for the study. Over the past 4 years, two randomized groups of 31 patients with sciatica due to intervertebral disk herniation were prospectively studied and compared with the t test. The control group underwent conservative therapy (administration of analgesics, antiinflammatory drugs, muscle relaxants, and physiotherapy) for 6 weeks. The decompression group underwent fluoroscopically guided PDD. Pain reduction and mobility improvement were recorded at 3-, 12-, and 24-month follow-up on a numeric visual scale (NVS) (range, 0-10). RESULTS The control group had a mean pain score of 6.9 NVS units ± 1.9 prior to conservative therapy. This was reduced to 0.9 NVS units ± 2.0 3 months after therapy; however, it increased to 4.0 NVS units ± 3.4 at 12-month follow-up and further increased to 4.0 NVS units ± 3.4 at 24-month follow-up. The decompression group had a mean pain score of 7.4 NVS units ± 1.4 prior to PDD. This was reduced to 3.0 NVS units ± 2.4 at 3-month follow-up and further reduced to 1.7 NVS units ± 2.4 at 12-month follow-up and 1.6 NVS units ± 2.5 at 24-month follow-up. No complications were noted. CONCLUSION When compared with conservative therapy, PDD shows improved amelioration of symptoms at 12- and 24-month follow-up.
News Shock Spillovers: How the Euro Area Responds to Expected Fed Policy

Monetary policy increasingly relies on steering market expectations about future policy. This paper identifies a monetary policy news shock based on a VAR model. A monetary news shock is equivalent to new information about the Fed's future monetary policy becoming available today. One example of a monetary news shock is a Forward Guidance announcement, where the Fed unveils its prospectively (binding) monetary policy, today. In this paper, we study the spillover effects of news shocks. We estimate the response of the euro area to an expected future policy tightening of the Fed. The U.S. news shock improves sentiment and business cycle expectations in the euro area, which is consistent with the notion of the Fed revealing favorable news by a tightening announcement. We also distinguish the news shock from a conventional U.S. policy surprise and find that they lead to diverging responses in the euro area.
Is abstinence really the best option? Exploring the role of exercise in the treatment and management of eating disorders

ABSTRACT Exercise prescription is suggested to help manage exercise abuse and improve overall eating disorder (ED) prognosis. This study explored emerging perceptions of ED health professionals concerning the role of exercise as a supportive treatment for EDs. Semi-structured interviews were conducted with international health professionals (n=13) with expertise in ED treatment. Verbatim transcripts were analyzed through thematic analysis. Four themes were revealed and titled 1) understanding the current state; 2) gaining perspectives; 3) barriers and benefits; 4) one size does not fit all. Within these themes, participants described the current state of exercise in ED treatment and suggested there exists a gap in research knowledge and practice. Participants also identified the implications of incorporating exercise into treatment and how an exercise protocol may be designed. Results enhance the understanding of the role of exercise in ED treatment and how it may further benefit individuals with EDs.
Teratogenic effects of alcohol: A decade of brain imaging

Heavy alcohol exposure can have serious and long‐lasting effects on the developing fetal brain. In the last decade, researchers have utilized quantitative structural magnetic resonance imaging (MRI) to examine the brains of living children and adults with histories of heavy prenatal alcohol exposure. In addition to microcephaly, these studies indicated structural abnormalities in various regions of the brain, including the cerebellum, corpus callosum, and the basal ganglia. Most recently, we have utilized novel imaging and analytic techniques to study the brain as a whole in an effort to elucidate more subtle differences than was possible with earlier techniques. Results indicated displacements in the corpus callosum, increased gray matter densities in both hemispheres in the perisylvian regions, and altered gray matter asymmetry in portions of the temporal lobes in the brains of alcohol‐exposed subjects. In addition, prominent shape abnormalities were observed in the brains of these subjects, with narrowing in the temporal region and reduced brain growth in portions of the frontal lobe. These results imply that brain growth continues to be adversely affected long after the prenatal insult and that the brain regions most affected may be consistent with the neurocognitive deficits characteristic of individuals prenatally exposed to alcohol. © 2004 Wiley‐Liss, Inc.
Climate change, health care access and regional influence on components of U.S. agricultural productivity

ABSTRACT This article examines factors driving three components of total factor productivity change (TFPC) in U.S. agriculture – technical change (TC), technical efficiency change (TEC), and scale and mix efficiency change (SMEC). We also examine TFPC and contrast implications derived from the component models with those from a directly estimated TFPC model. Our results show that TC and SMEC are both significantly impacted by innovation through public research and improved human capital through education and health care access. TEC and SMEC are significantly affected by farm size, and the latter is significantly affected by public policy. The ratio of family-to-total labour, terms of trade and precipitation have significant impacts on all three components, but extension has no significant impact on any component. Climate change variables are the most impactful factors on each component as well as on TFPC. While the impact of climate change is heterogeneous across regions and components, its estimated historical impact is most often positive. Nearly all TFPC elasticities estimated directly are qualitatively the same as those calculated from the component models and quantitatively similar.