Miracle-dz/UniFAR-FTUs huggingface dataset:
ON THE STABILITY OF RANDOMLY VARYING SYSTEMS

Abstract : This analysis is concerned with the stability of random systems, that is, systems whose internal characteristics are governed by probability laws. Concepts of stability appropriate to random differential systems are formulated and discussed. Precise definitions of stability are stated and theorems interrelating these definitions are proven. Some particular types of stability investigated are, in the mean norm, in the ith moment, in probability, almost sure, and almost uniform-in-omega. Particular attention is focused on the random linear (vector) differential equation with piecewise constant parameters.
G α q Reduces cAMP Production by Decreasing G α s Protein Abundance

The heterotrimeric guanine nucleotide-binding protein G α q transduces signals from heptahelical transmembrane receptors (e.g., α 1 -adrenergic, endothelin 1A, and angiotensin II) to stimulate generation of inositol-1,4,5-trisphosphate and diacylglycerol. In addition, G α q decreases cAMP production, through unknown mechanisms, and thus affects physiological responsiveness of cardiac myocytes and other cells. Here, we provide evidence that G α q expression increases G α s ubiquitination, decreases G α s protein content, and impairs basal and β 1 -adrenergic receptor-stimulated cAMP production. These biochemical and functional changes are associated with Akt activation. Expression of constitutively active Akt also decreases G α s protein content and inhibits basal and β 1 -adrenergic receptor-stimulated cAMP production. Akt knockdown inhibits G α q-induced reduction of G α s protein. In addition, MDM2, an E3 ubiquitin ligase, binds G α s and promotes its degradation. Therefore, increased expression of G α q decreases cAMP production through Akt-mediated G α s protein ubiquitination and proteasomal degradation.
Management of pulpal ﬂ oor perforation and grade II Furcation involvement using mineral trioxide aggregate and platelet rich ﬁ brin: A clinical report

To report the management of an iatrogenic perforation of pulpal ﬂ oor in the furcation of mandibular ﬁ rst molar, using Mineral Trioxide Aggregate (MTA) and platelet rich ﬁ brin (PRF). Unpredictable endodontic root/pulp chamber ﬂ oor perforations resulting in unacceptable high rate of clinical failure has now been a lesser threat with the advent of new technologies and biocompatible materials that utilize the applications of basic research along with tissue engineering concept in clinical practice. Present case report illustrates the use of MTA and platelet rich ﬁ brin (PRF) for the repair of the perforation defect and regeneration of the lost periodontium in furcation area. Although, histologic events and reaction of MTA with PRF is not studied so far, however, the autologous and biocompatible nature of the components used for present treatment modalities seems to be bene ﬁ cial for the long term clinical results obtained in our case.
Preanalytical Sample Handling Conditions and Their Effects on the Human Serum Metabolome in Epidemiologic Studies

Many epidemiologic studies use metabolomics for discovery-based research. The degree to which sample handling may influence findings, however, is poorly understood. In 2016, serum samples from 13 volunteers from the US Department of Agriculture’s Beltsville Human Nutrition Research Center were subjected to different clotting (30 minutes/120 minutes) and refrigeration (0 minutes/24 hours) conditions, as well as different numbers (0/1/4) and temperatures (ice/refrigerator/room temperature) of thaws. The median absolute percent difference (APD) between metabolite levels and correlations between levels across conditions were estimated for 628 metabolites. The potential for handling artifacts to induce false-positive associations was estimated using variable hypothetical scenarios in which 1% – 100% of case samples had different handling than control samples.All handling conditions influenced metabolite levels.Across metabolites, the median APD when extending clotting time was 9.08%. When increasing the number of thaws from 0 to 4, the median APD was 10.05% for ice and 5.54% for room temperature. Metabolite levels were correlated highly across conditions (all r ’s ≥ 0.84), indicating that relative ranks were preserved. However, if handling varied even modestly by case status, our hypotheticals showed that results can be biased and can result in false-positive findings.Sample handling affects levels of metabolites, and special care should be taken to minimize effects. Shorter room-temperature thaws should be preferred over longer ice thaws, and handling should be meticulously matched by case status.
An Iterative Scheme for Linear Complementarity Problems.

Abstract : The linear complementarity problem (LCP) is an important problem in mathematical programming for solving linear programming, quadratic programming and bimatrix games. This work gives a new scheme for solving the LCP. Based on the scheme different algorithms may be designed for finding approximate solutions of very large scale problems or exact solutions of moderate LCPs. A specific algorithm for the latter is given, together with some numerical results. These indicate that the method is more effective than other existing methods.
Implementation Strategies for Telestroke: A Qualitative Study of Telestroke Networks in North Carolina

Background: Telestroke services allow under-resourced hospitals to gain access to stroke specialists to improve the timeliness and quality of stroke care. However, limited research is available on how telestroke networks are developed, implemented, and sustained. Understanding the process of telestroke network implementation is critical for developing implementation guidance and for evaluating determinants of implementation effectiveness. Objective: This study examines the adoption decision process and strategies employed during telestroke network development, implementation, and sustainability. Research Design: We interviewed representatives from five telestroke networks in North Carolina. Each network consisted of a distant site from which stroke consultation was provided and multiple originating sites at which the patient presented. Subjects: The sample included 24 telestroke representatives (i.e., 5 network representatives and 19 hospital representatives) and 4 hospital representatives who do not participate in telestroke (i.e., nonadopters). Measures: The qualitative measures used in this study were based on Roger’s stages of the innovation process in organizations. Stages included agenda setting and matching (pre-implementation), restructuring, redefining, and clarifying (implementation), and routinizing (sustainability). Results: Distant and originating sites employed various strategies in the pre-implementation, implementation, and sustainability stages. Although there are many commonalities across networks, there are also important differences, for example in terms of network structure, quality monitoring, and performance feedback. Some nonadopter hospitals reported difficulty accessing information about telestroke, suggesting that some hospitals are not reached by telestroke network marketing efforts. Conclusions: Identifying and/or tailoring strategies to support the needs of hospitals in different telestroke network models should be a priority for future research.
Effect of 3 weeks of continuous positive airway pressure treatment on mood in patients with obstructive sleep apnoea: a randomized placebo-controlled study

Background— Patients with obstructive sleep apnoea (OSA) commonly have mood symptoms such as depression and anxiety. However, the results of randomized controlled trials on the therapeutic effect of CPAP on mood symptoms have been inconsistent. The present study examined whether 3 weeks of CPAP treatment had specific therapeutic effects on mood symptoms in patients with OSA compared with placebo. Methods— A double-blind, parallel, randomized controlled trial using therapeutic and placebo CPAP was performed in 71 patients newly diagnosed with OSA [apnoea-hypopnoea index (AHI) ≥ 10]. Mood was assessed by the Center for Epidemiologic Studies-Depression (CES-D) Scale, the Profile of Mood States (POMS) and the Brief Symptom Inventory (BSI) before and after 3 weeks of treatment. AHI was used to assess the severity of apnoea. The two groups were compared using a simple comparison of the changes within each arm and repeated measures analysis of variance. Results— Fifty-six subjects completed the study: 26 in the CPAP group and 30 in the placebo group. The two groups were well matched at baseline, with no significant differences in demographic, mood and apnoea variables. Both groups had severe apnoea, and mild depression and anxiety at baseline. After 3 weeks of treatment, AHI decreased significantly in the CPAP group. The mean change in AHI was − 30.7 [standard deviation (SD) 23.1] in the CPAP group and − 5.8 (SD 18.3) in the placebo group (difference between groups P <0.001). However, after 3 weeks of treatment, there were no significant time by treatment effects in relation to mood, as assessed by the CES-D, POMS Depression, POMS Tension, BSI Depression or BSI Anxiety (all P >0.05). Conclusion— In conclusion, 3 weeks of CPAP treatment did not show a specific therapeutic effect on mood symptoms in patients with OSA.
The association of aspirin use with age-related macular degeneration progression in the Age-Related Eye Disease Studies: AREDS2 Report No. 20

Purpose— To analyze the potential association between aspirin use and progression of agerelated macular degeneration (AMD). Design— Two prospective cohort studies within two controlled clinical trials of oral supplementation for age-related eye disease. Participants— Age-Related Eye Disease Study (AREDS) participants, aged 55 to 80 years, and AREDS2 participants, aged 50 to 85 years. Methods— Propensity scores for aspirin use were calculated for AREDS and AREDS2 participants, separately, by logistic regression. Of the participants without late AMD (geographic atrophy (GA) or neovascular AMD) in either eye at study baseline, aspirin users were matched 1:1 with non-users by propensity score (separately for AREDS and AREDS2). Proportional hazards regression was performed, adjusting for age, on the matched participants to evaluate associations between aspirin propensity score and progression to late AMD (and its subtypes). Main outcome measures— Progression to late AMD on color fundus photographs, graded centrally. Results— Of the 3734 eligible AREDS participants, 1049 (28.1%) were taking aspirin and 2685 (71.9%) were not. The equivalent figures in AREDS2 were 1198 (49.9%) and 1205 (50.1%), respectively. Following matching by propensity score, the characteristics of the users and non-users were similar, in both studies. Of the 1950 matched AREDS participants and 1694 matched AREDS2 participants, over median follow-up of 10.1 years (AREDS) and 5.0 years (AREDS2), the numbers who progressed to late AMD, GA, or neovascular AMD were 454 (23.3%), 345 (17.7%), and 278 (14.3%), respectively, in AREDS, and 643 (38.0%), 402 (24.6%), and 341 (20.1%), in AREDS2. The hazard ratios of progression in quintile 5 (highest propensity for aspirin use) versus 1 (reference) were 1.17 (p=0.35), 1.24 (p=0.25), and 0.95 (p=0.81), respectively, in AREDS, and 1.26 (p=0.09), 1.46 (p=0.03), and 1.12 (p=0.58), in AREDS2. No significant association with progression to late AMD was observed for any quintile 2–5, for any of the three outcomes, in either study. significantly late AMD, or its subtypes, in either the AREDS or the AREDS2. Patients with AMD need aspirin for this reason, when its medically
Does the female advantage in verbal memory contribute to underestimating AD pathology in women versus men?

There is a growing recognition of sex differences in Alzheimer’s disease (AD). Females show an advantage over males on tests of verbal memory, which are used to diagnose AD and its precursor, amnestic mild cognitive impairment (aMCI). Women retain this advantage in aMCI despite reduced hippocampal volume and temporal lobe glucose metabolism. Here we examined whether this female advantage endures despite evidence of AD-specific pathology, cortical amyloid- β (A β ) deposition measured with [ 18 F]AV45 (florbetapir) positron emission tomography. Participants with normal cognition (N=304), aMCI (N=515), and AD dementia (N=175) were drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Across and within diagnostic groups, we conducted linear regressions to examine the interaction of sex with cortical A β burden on immediate and delayed recall on the Rey Auditory Verbal Learning Test (RAVLT) adjusting for age, education, and APOE4. In the overall group, sex by cortical A β interaction was significant for delayed recall only. Overall, delayed recall performance was significantly better in women versus men among those with low to moderate A β burden, but women and men performed similarly among those with high A β burden. In diagnosis-stratified analyses, a significant sex by cortical A β interaction was observed for delayed recall in the aMCI group, but not in the normal or AD dementia groups. Thus, women maintain a verbal memory advantage over men in aMCI despite similar levels of AD pathology. Although this advantage may benefit women by delaying verbal memory impairment until more advanced pathology, it may also delay diagnosis of aMCI and treatment intervention.
Do Stress Eating or Compulsive Eating Influence Metabolic Health in a Mindful Eating Intervention?

Objective: We aimed to understand the role of stress eating (SE) and compulsive eating (CE) in metabolic health among adults with obesity, and whether mindful eating training may buffer these associations. Method: We used data from a trial in which we randomized 194 participants with obesity to a diet-exercise intervention with either mindful eating training plus mindfulness-based stress management (n=100) or active control components (n=94). We measured SE, CE, weight and fasting blood glucose (FBG) at baseline, 12 months, and 18 months. We tested SE and CE as both moderators and mediators of intervention effects on changes in metabolic health. Results: Participants higher (+1 SD) in CE at baseline randomized to mindful eating (vs. control) had greater improvements in FBG at 18 months (p=.05). Twelve-month reductions in CE mediated an association between intervention and changes in FBG and weight at 12 and 18 months post-baseline (p ≤. 05). Furthermore, those higher (+1 SD) in SE at baseline were nearly 2 BMI points higher than those lower (−1 SD) in stress eating (p < .01). Decreases in SE (F=3.42, obesity interventions should consider tailoring treatment towards trait-level characteristics, such as compulsive eating.
Nucleic Acids Research

The left end of rat Li (LlRn, long interspersed repeated) DNA which is a CpG island can function as a promoter ABSTRACT Here we report that the 600 bp promoter-like region at the left end of a newly isolated and characterized rat Li DNA element can activate the prokaryotic chloramphenicol acyltransferase gene in a rat cell line. Activation only occurs when the promoter region is oriented to the transferase gene as it is to the Li protein encoding sequences and is 75% inhibited by methylation of just 5 of the 22 CpGs present in the promoter. The G + C rich promoter contains enough CpGs to qualify it as a CpG island, but in contrast to other CpG islands, genomic Li promoters are fully methylated in both somatic cell and sperm DNA as judged by restriction enzyme analysis. Partial demethylation of the genomic promoters by treatment with 5-azacytidine failed to produce discrete Li transcripts. The relationship of methylation to the evolutionary history and fate of the rat Li promoter is discussed.
Inhibition of the proteasome β 2 site sensitizes triple-negative breast cancer cells to β 5 inhibitors through a mechanism involving Nrf1 suppression

Summary The proteasome inhibitors Carfilzomib (Cfz) and Bortezomib (Btz) are used successfully to treat MM, but have not shown clinical efficacy in solid tumors. Here we show that clinically achievable inhibition of the β 5 site of the proteasome by Cfz and Btz does not result in loss of viability of triple-negative breast cancer cell lines. We use site-specific inhibitors and CRISPR-mediated genetic inactivation of β 1 and β 2 to demonstrate that inhibiting a second site of the proteasome, particularly the β 2 site, sensitizes cell lines to Btz and Cfz in vitro and in vivo. Inhibiting both β 5 and β 2 suppresses production of the soluble, active form of the transcription factor Nrf1 and prevents the recovery of proteasome activity through induction of new proteasomes. These findings provide a strong rationale for the development of dual β 5 and β 2 inhibitors for the treatment of solid tumors. Although the proteasome inhibitors Btz and Cfz have been clinically tested in solid tumors, they have not been effective. Our work demonstrates that clinically relevant concentrations of Btz and Cfz are not active in cell lines derived from TNBC or solid tumors of different organs. This finding suggests that stronger inhibition of the proteasome is necessary for efficacy in human patients. We show stronger anti-neoplastic effects can be achieved by co-inhibiting the β 5 and β 2 active sites, a combination that is not targeted by FDA-approved agents. We generate cell lines with CRISPR-Cas9 inactivation of β 1 and β 2, and use them to confirm the findings obtained with inhibitors. Inactivation of β 2 additionally sensitizes TNBC tumors in vivo to Cfz. The CRISPR-Cas9 cell lines are also used to demonstrate the high specificity of our active site-specific inhibitors, setting a standard for small molecule inhibitor validation. We find that co-inhibition of β 5 and β 2 causes aggregation of Nrf1, which blocks upregulation of proteasome genes and prevents recovery of proteasome activity. Overall, this work proposes that solid tumors have an intrinsic level of resistance to FDA-approved proteasome inhibitors. The ability of these cells to robustly recover proteasome activity contributes to resistance. Recovery involves Nrf1-mediated expression of proteasome genes, but can be blocked by co-inhibiting β 2 to cause Nrf1 aggregation and inactivation. In summary, this
Racial Disparity in Death from Colorectal Cancer: Does Vitamin D Deficiency Contribute?

Background— The reasons Blacks have higher mortality rates from colorectal cancer (CRC) than non-Hispanic Whites are not fully understood. Blacks have higher rates of vitamin D deficiency than non-Hispanic Whites, and vitamin D deficiency has been associated with CRC. We investigated the association of vitamin D deficiency with excess risk for CRC mortality for Blacks in the third National Health and Nutrition Examination Survey (NHANES III) 1988-1994. Methods— We examined the association of serum 25(OH) D levels with CRC mortality and its contribution to elevated risk among Blacks using baseline data from NHANES III and CRC mortality through 2006 from the National Death Index. Using survival models, we examined the adjusted risk for African Americans for CRC death with and without adjusting for vitamin D deficiency, defined as less 25(OH)D < 20 ng/dl. Results— Black race (Hazard Ratio [HR] 2.03; 95% Confidence Interval [CI] 1.04-3.95), age (HR 1.12; 95% CI 1.09-1.15), not having health insurance (HR 2.45; 95% CI 1.12-5.36), and history of CRC (HR 7.22; 95% CI 2.12-24.6) predicted CRC mortality. When added to the model, vitamin D deficiency was significantly associated with CRC mortality (HR 2.11; 95% CI 1.11-4.00) and the effect of race was decreased (HR 1.60; 95% 0.87-2.93); the 40% attenuation was statistically significant (F[1, 49] = 4.85, p = 0.03). Similar results were seen when participants with a history of CRC were excluded from the analysis. Conclusion— Our findings are consistent with the hypothesis that vitamin D deficiency contributes to excess African American mortality from CRC.
Light-sheet fluorescence microscopy for the in vivo study of microtubule dynamics in the zebrafish embryo

: During its first hours of development, the zebrafish embryo presents a large microtubule array in the yolk region, essential for its development. Despite of its size and dynamic behavior, this network has been studied only in limited field of views or in fixed samples. We designed and implemented different strategies in Light Sheet Fluorescence microscopy for imaging the entire yolk microtubule (MT) network in vivo . These have allowed us to develop a novel image analysis from which we clearly observe a cyclical re-arrangement of the entire MT network in synchrony with blastoderm mitotic waves. These dynamics also affect a previously unreported microtubule array deep within the yolk, here described. These findings provide a new vision of the zebrafish yolk microtubules arrangement, and offers novel insights in the interaction between mitotic events and microtubules reorganization.
Quadrupole Scan Measurements in the Beam Transport Line between DESY II and PETRA III

PETRA III is a 6GeV third generation synchrotron light source in Hamburg, Germany. The storage ring is operated with a typical beam current of 100mA and is running in topup mode. The beam delivered to PETRA III is accelerated by a fast cycling booster synchrotron (DESY II), extracted in a 203m long beam transport line (E-Weg) and injected afterwards into PETRA III. In the framework of PETRA IV upgrade scenarios the potential for decreasing the extracted emittance from DESY II has been investigated which can be achieved by lowering the extraction energy to 5GeV and increasing the focusing in DESY II. In addition measuring the emittance of the extracted beam from DESY II and the optics in the beam transport line can help to better understand and improve the injection efficiency of PETRA III. By changing the quadrupole strength and measuring the beam size downstream on a screen monitor in the E-Weg the emittance of DESY II and the Twiss functions at a quadrupole in the E-Weg have been determined. Measurements at different energies of DESY II will be shown and compared with calculations.
Belief Free Equilibria

The repeated game literature studies long run/repeated interactions, aiming to understand how repetition may foster cooperation. Conditioning future behavior on past play is crucial in this endeavor. For most situations of interest a given player does not directly observe the actions chosen by other players and must rely on noisy signals he receives about those actions. This is typically incorporated into models by defining a monitoring structure, that is, a collection of probability distributions over the signals each player receives (one distribution for each action profile players may play). Although this is simply meant to capture the fact that players don.t directly observe the actions chosen by others, constructed equilibria often depend on players precisely knowing the distributions, somewhat unrealistic in most problems of interest. This paper aims to show the fragility of belief free equilibrium constructions when one adds shocks to the monitoring structure in repeated games.