Miracle-dz/UniFAR-FTUs huggingface dataset:
Inducible HSP70 Is Critical in Preventing the Aggregation and Enhancing the Processing of PMP22

Chaperones, also called heat shock proteins (HSPs), transiently interact with proteins to aid their folding, trafficking, and degradation, thereby directly influencing the transport of newly synthesized molecules. Induction of chaperones provides a potential therapeutic approach for protein misfolding disorders, such as peripheral myelin protein 22 (PMP22)-associated peripheral neuropathies. Cytosolic aggregates of PMP22, linked with a demyelinating Schwann cell phenotype, result in suppression of proteasome activity and activation of proteostatic mechanisms, including the heat shock pathway. Although the beneficial effects of chaperones in preventing the aggregation and improving the trafficking of PMP22 have been repeatedly observed, the requirement for HSP70 in events remains elusive. In this study, we show that activation of the chaperone pathway in fibroblasts from PMP22 duplication-associated Charcot–Marie–Tooth disease type 1A patient with an FDA-approved small molecule increases HSP70 expression and attenuates proteasome dysfunction. Using cells from an HSP70.1/3−/− (inducible HSP70) mouse model, we demonstrate that under proteotoxic stress, this chaperone is critical in preventing the aggregation of PMP22, and this effect is aided by macroautophagy. When examined at steady-state, HSP70 appears to play a minor role in the trafficking of wild-type-PMP22, while it is crucial for preventing the buildup of the aggregation-prone Trembler-J-PMP22. HSP70 aids the processing of Trembler-J-PMP22 through the Golgi and its delivery to lysosomes via Rab7-positive vesicles. Together, these results demonstrate a key role for inducible HSP70 in aiding the processing and hindering the accumulation of misfolded PMP22, which in turn alleviates proteotoxicity within the cells.
Prions on the run: How extracellular vesicles serve as delivery vehicles for self-templating protein aggregates

ABSTRACT Extracellular vesicles (EVs) are actively secreted, membrane-bound communication vehicles that exchange biomolecules between cells. EVs also serve as dissemination vehicles for pathogens, including prions, proteinaceous infectious agents that cause transmissible spongiform encephalopathies (TSEs) in mammals. Increasing evidence accumulates that diverse protein aggregates associated with common neurodegenerative diseases are packaged into EVs as well. Vesicle-mediated intercellular transmission of protein aggregates can induce aggregation of homotypic proteins in acceptor cells and might thereby contribute to disease progression. Our knowledge of how protein aggregates are sorted into EVs and how these vesicles adhere to and fuse with target cells is limited. Here we review how TSE prions exploit EVs for intercellular transmission and compare this to the transmission behavior of self-templating cytosolic protein aggregates derived from the yeast prion domain Sup 35 NM. Artificial NM prions are non-toxic to mammalian cell cultures and do not cause loss-of-function phenotypes. Importantly, NM particles are also secreted in association with exosomes that horizontally transmit the prion phenotype to naive bystander cells, a process that can be monitored with high accuracy by automated high throughput confocal microscopy. The high abundance of mammalian proteins with amino acid stretches compositionally similar to yeast prion domains makes the NM cell model an attractive model to study self-templating and dissemination properties of proteins with prion-like domains in the mammalian context.
Efficacy of two different thiol-modified crosslinked hyaluronate formulations as vitreous replacement compared to silicone oil in a model of retinal detachment

The efficacy of two novel artificial vitreous body substitutes (VBS) consisting of highly biocompatible thiolated cross-linked hyaluronic acid (HA)-based hydrogels in comparison to silicone oil in a model of retinal detachment was investigated. Pars plana vitrectomy (23G) was performed in the right eye of 24 pigmented rabbits. Retinal detachment of two quadrants was induced by creating a small retinotomy near the vascular arcade and injecting balanced salt solution (BSS) subretinally. The retina was reattached by injecting air, which was followed by increasing the infusion pressure, and the retinal tear was treated by endolaser photocoagulation. At the end of the procedure, the eye was filled either with 5000-cs silicone oil (after fluid air exchange) or the respective hydrogel (with two different viscosities). Follow-up examination included slit lamp examination, funduscopy, intraocular pressure measurements (IOP), optical coherence tomography (OCT) and electroretinogram (ERG) measurements. After a maximum follow-up of four weeks both eyes were removed, examined macroscopically, photographed, and prepared for histology. Of the eight rabbits that received silicone oil, seven (87.5%) developed a recurrent retinal detachment with pronounced proliferative vitreoretinopathy within the first two weeks after surgery. In contrast, in the hydrogel treated eyes, the retina stayed attached in the majority of the cases (73.3%). IOP and retinal morphology were normal as long as the retina remained re-attached. In conclusions, this model of retinal detachment, both thiolated crosslinked hyaluronate hydrogels showed superior efficacy when compared to silicone oil. These hydrogels have a promising potential as novel vitreous body substitutes.
Interaction between Syntax Processing in Language and in Music: An ERP Study

The present study investigated simultaneous processing of language and music using visually presented sentences and auditorily presented chord sequences. Music-syntactically regular and irregular chord functions were presented synchronously with syntactically correct or incorrect words, or with words that had either a high or a low semantic cloze probability. Music-syntactically irregular chords elicited an early right anterior negativity (ERAN). Syntactically incorrect words elicited a left anterior negativity (LAN). The LAN was clearly reduced when words were presented simultaneously with music-syntactically irregular chord functions. Processing of high and low cloze-probability words as indexed by the N400 was not affected by the presentation of irregular chord functions. In a control experiment, the LAN was not affected by physically deviant tones that elicited a mismatch negativity (MMN). Results demonstrate that processing of musical syntax (as reflected in the ERAN) interacts with the processing of linguistic syntax (as reflected in the LAN), and that this interaction is not due to a general effect of deviance-related negativities that precede an LAN. Findings thus indicate a strong overlap of neural resources involved in the processing of syntax in language and music.
A new queue-status resource allocation scheme for backhaul link in relay enhanced networks

Recently, distributed resource allocation for relay enhanced cellular networks has gained increasing attention. However, it poses a new challenge for the backhaul link scheduling. In this paper, we propose a queue-status-based resource allocation scheme for the backhaul link in a distributed manner in relay enhanced networks. By applying this scheme, the evolved Node B (eNB) adjusts the data rate for each user equipment (UE) in the backhaul link according to its queue status at the relay node (RN). It can guarantee the rate match between the backhaul and access links while minimizing feedback signaling. Simulation results show that the proposed scheme can achieve a good tradeoff between the spectral efficiency and the signaling overhead.
Internal IT Knowledge and Expertise as Antecedents of ERP System Effectiveness: An Empirical Investigation

The literature shows that contingency factors such as organizational culture and structure, organization size, top management support, external expertise, and internal support are critical for the effectiveness of Enterprise Research Planning (ERP) systems in adopting organizations. Research on the effect of in-house computer and information technology (IT) knowledge and expertise on the success of such packages is rare. The purpose of this study was to explore the influence of computer/IT skills as antecedents of ERP system effectiveness. Using relevant theoretical foundations, a research model was developed to test eight relevant hypotheses. Data was collected in a cross-sectional field survey of 109 firms in two European countries. The partial least squares (PLS) technique was used for data analysis. The PLS results confirmed six out of the eight hypotheses. The study's conceptualization supported the view that in-house computer/IT skills are indeed pertinent to ERP system success in adopting organizations. The research implications for practice and research conclude this study.
Russian Higher Education: Who Can Afford It?

The article explores the issue of access and equity in the Russian higher education system by examining recent government initiatives. While recently introduced measures such as the Unified State Examination and student loan project are designed to aid students and expand participation, they alone cannot ensure equitable access to higher education in Russia. To address the growing social stratification in education, the government needs to create formal assistance programs to mitigate existing socioeconomic and institutional barriers.
Accurate Computations on Inertial Manifolds

An algorithm is implemented for the computation of inertial manifolds to arbitrary accuracy. It is applied to the Kuramoto--Sivashinsky equation to recover the high wave number components of elements on the global attractor. The computational results demonstrate that this algorithm is significantly more accurate than previous methods, when compared after just a few iterations. An essential feature of the algorithm is that it does not require that the entire manifold be constructed. Hence the algorithm is particularly suited for computing trajectories on the manifold, and its computational complexity is independent of the dimension.
Non-melanoma skin cancers and glucocorticoid therapy

Non-melanoma skin cancer (NMSC) is an important cause of morbidity and long-term mortality in organ transplant recipients receiving immunosuppressive drugs such as azathioprine and cyclosporin, often combined with adrenocortical steroids (glucocorticoids). At lower doses, glucocorticoids alone are prescribed for other conditions including musculoskeletal, connective tissue and respiratory disorders. Presently, it is unknown whether patients taking glucocorticoids are at an increased risk of skin malignances. In a population-based case-control study in New Hampshire, USA, we compared use of glucocorticoids in 592 basal cell carcinoma (BCC) and 281 squamous cell carcinoma (SCC) cases and in 532 age and gender matched controls; neither cases nor controls had a history of organ transplantation. Participants underwent a structured personal interview regarding history of medication use and skin cancer risk factors. We used unconditional logistic regression analysis to compute odds ratios associated with glucocorticoid use for 1 month or longer while controlling for potential confounding factors. Risk of SCC was increased among users of oral glucocorticoids (adjusted odds ratio = 2.31; 95% CI = 1.27, 4.18), and risk of BCC was elevated modestly (adjusted odds ratio = 1.49; 95% CI = 0.90, 2.47). In contrast, risk of both SCC and BCC were unrelated to use of inhaled steroids. Our data suggest that use of oral glucocorticoids may increase risk of NMSC, and SCC in particular, among patients other than organ transplant recipients. We hypothesize that immunosuppression induced by oral glucocorticoids may allow these cancers to emerge from immunosurveillance. © 2001 Cancer Research Campaign www.bjcancer. com
Effects of Baicalin on Oral Pharmacokinetics of Caffeine in Rats

Scutellaria baicalensis is one of the most widely used herbal medicines in East Asia. Because baicalein and baicalin are major components of this herb, it is important to understand the effects of these compounds on drug metabolizing enzymes, such as cytochrome P450 (CYP), for evaluating herb-drug interaction. The effects of baicalin and baicalein on activities of ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), benzyloxyresorufin O-debenzylase (BROD), p-nitrophenol hydroxylase and erythromycin N-demethylase were assessed in rat liver microsomes in the present study. In addition, the pharmacokinetics of caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) in baicalin-treated rats were compared with untreated control. As results, EROD, MROD and BROD activities were inhibited by both baicalin and baicalein. However, there were no significant differences in the pharmacokinetic parameters of oral caffeine and its three metabolites between control and baicalin-treated rats. When the plasma concentration of baicalin was determined, the maximum concentration of baicalin was below the estimated IC50 values observed in vitro. In conclusion, baicalin had no effects on the pharmacokinetics of caffeine and its metabolites in vivo, following single oral administration in rats.
Thinking, Fast and Slow, by D. Kahneman

The very same biological machinery that enables us to reason also biases our judgments and slants us toward irrational behavior, leading to predictable human errors that may be impossible to correct. These are the insights of psychologists Daniel Kahneman and Amos Tversky, who collaborated over a quarter century and influenced the theory and practice of economics, finance and political science as well as public policy. Their research earned Kahneman a Nobel Prize in Economics in 2002. Tversky would have shared the Prize had it not been for his untimely death in 1996. The story of Kahneman and Tversky’s friendship is recounted with affection and interwoven with the details of their scientific inquiries in Thinking, Fast and Slow, which is a scholarly work masquerading as a popular book. It has been on mainstream best-seller lists for months.
The Origins of Human Rights Regimes: Democratic Delegation in Postwar Europe

Most formal international human rights regimes establish international committees and courts that hold governments accountable to their own citizens for purely internal activities. Why would governments establish arrangements so invasive of domestic sovereignty? Two views dominate the literature. “Realist” theories assert that the most powerful democracies coerce or entice weaker countries to accept norms; “ideational” theories maintain that transnational processes of diffusion and persuasion socialize less-democratic governments to accept norms. Drawing on theories of rational delegation, I propose and test a third “republican liberal” view: Governments delegate self-interestedly to combat future threats to domestic democratic governance. Thus it is not mature and powerful democracies, but new and less-established democracies that will most strongly favor mandatory and enforceable human rights obligations. I test this proposition in the case of the European Convention on Human Rights—the most successful system of formal international human rights guarantees in the world today. The historical record of its founding—national positions, negotiating tactics, and confidential deliberations—confirms the republican liberal explanation. My claim that governments will sacrifice sovereignty to international regimes in order to dampen domestic political uncertainty and “lock in” more credible policies is then generalized theoretically and applied to other human rights regimes, coordination of conservative reaction, and international trade and monetary policy.
Finding a Fit: Recruitment and Hiring for Urban Teacher Retention

Author(s): Thompson, Alisun | Advisor(s): Bartlett, Lora | Abstract: The distribution of well-prepared and experienced teacher has been a policy concerns for decades. Research has established that schools serving concentrations of historically underserved students struggle disproportionately to attract and retain teachers, resulting in the most vulnerable students being taught by the least qualified teachers--teachers with minimal professional preparation or experience (Boyd, Lankford, Loeb, a Wyckoff, 2005; Lankford, Loeb a Wycoff, 2002). These schools have also been found to struggle the most with high degrees of teacher turnover (Borman a Dowling, 2008; Shen, 1997). However, research has also documented that while many schools serving high-need student populations struggle mightily with teacher turnover, some do not, and turnover differences between schools with similar student demographics are more significant than between schools with different student demographics (DeAngelis a Presley, 2011; Ingersoll,1995; Johnson, Kraft a Papay, 2011). Furthermore, a compelling link between teacher turnover and student achievement (Ronfeldt, Loeb a Wyckoff, 2013) has incited policy interest on how to recruit and retain more well-prepared and experienced teachers to the schools that need them the most. This dissertation examines teacher recruitment and retention at one high-need urban school that demonstrates all of the markers of high teacher turnover but, in fact, does not struggle to attract and retain experienced teachers. The study utilizes a single-case case-study design and ethnographic methods to investigate what attracts teachers to the school, how teachers are recruited and hired, and what organizational conditions contribute to their decisions to remain teaching at the school (i.e., retention). The study was conducted over the course of an academic year and data sources include thirty-two semi-structured interviews with teachers and administrators, field notes of observations, and school-related documents. Findings revealed that a hiring orientation to finding teachers that "fit" at the school played a significant role in teachers experiencing job satisfaction and demonstrating high organizational commitment, two variables that are associated with retention. Findings also found that the school's culture and organizational identity were fundamental in attracting teachers to the school who shared the school's orientation to urban teaching, contributing to the phenomenon of "fit. " This dissertation makes a contribution to two bodies of literature. First, it contributes to studies on urban teacher hiring by documenting the mechanisms that bring experienced teachers to a high-need school. It also adds to organizational analyses of schools as workplaces by investigating the conditions that support and retain teachers.
Performance, Personality, and Energetics: Correlation, Causation, and Mechanism*

The study of phenotypic evolution should be an integrative endeavor that combines different approaches and crosses disciplinary and phylogenetic boundaries to consider complex traits and organisms that historically have been studied in isolation from each other. Analyses of individual variation within populations can act to bridge studies focused at the levels of morphology, physiology, biochemistry, organismal performance, behavior, and life history. For example, the study of individual variation recently facilitated the integration of behavior into the concept of a pace-of-life syndrome and effectively linked the field of energetics with research on animal personality. Here, we illustrate how studies on the pace-of-life syndrome and the energetics of personality can be integrated within a physiology-performance-behavior-fitness paradigm that includes consideration of ecological context. We first introduce key concepts and definitions and then review the rapidly expanding literature on the links between energy metabolism and personality traits commonly studied in nonhuman animals (activity, exploration, boldness, aggressiveness, sociability). We highlight some empirical literature involving mammals and squamates that demonstrates how emerging fields can develop in rather disparate ways because of historical accidents and/or particularities of different kinds of organisms. We then briefly discuss potentially interesting avenues for future conceptual and empirical research in relation to motivation, intraindividual variation, and mechanisms underlying trait correlations. The integration of performance traits within the pace-of-life-syndrome concept has the potential to fill a logical gap between the context dependency of selection and how energetics and personality are expected to interrelate. Studies of how performance abilities and/or aspects of Darwinian fitness relate to both metabolic rate and personality traits are particularly lacking.
Why does futures trading succeed or fail : an analysis of selected commodities.

Let me assure you that it was not my idea that you be subjected to a doublebarrelled attack by me. Regretably this is not the over-and-under type, with two different sizes of barrels—the second barrel is the same large bore as the first. If you have ever hunted rabbits in Illinois you know that a doublebarrelled shotgun is a ridiculous instrument anyway—you only get one chance. I feel somewhat the same way about this second appearance; having spent my best ammunition in the first, if I missed the little rabbit the only thing that will get him now is a heart attack. So I'll fire away and hope to frighten him to death.
Role Perception Study of School Counselors.

MF01/PCO2 Plus Postage. Administrator Attitudes; *Administrators; Attitudes; Counselor Attitmdes; Differences; *Role Perception; Scheduling; *School Counselors; Secondary Education; Teacher Attitudes; *Teachers This study was designed to identify any differences in the perceptions of administrators, counselors, and teachers regarding the role of secondary school counselors. A literature review found that different groups had varying expectations of school counselors. The null hypothesis for the study is: There is no significant difference in the expectations of administrators, counselors, and teachers regarding the role of secondary school counselors. A questionnaire was distributed to a sample of 40 principals, counselors, and teachers employed by the Bryan Independent School District in order to solicit their opinions regarding the various roles of school counselors. Results from the 34 returned questionnaires indicated that there were no significant differences in the perceptions of the aforementioned groups regarding the role of secondary school counselors in performing personal counseling, group counseling, and academic counseling. However, the data showed that there was a significant difference in the exper:tations of teachers as compared to administrators and counselors regarding the issue of planning the master schedule, scheduling . students, and/or balancing class loads. Appendixes include: cover letter, questionnaire, and unused tables. (JBJ) *********************************************************************** * Reproductions supplied by EDRS are the best tnat can be made * from the original document. ***********************************************************************