Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of p38 MAPK Activity in Regulatory T Cells after Tolerance with Anti-DNA Ig Peptide in (NZB × NZW)F1 Lupus Mice1

Treatment of (NZB × NZW)F1 (NZB/W) lupus-prone mice with the anti-DNA Ig-based peptide pConsensus prolongs the survival of treated animals and effectively delays the appearance of autoantibodies and glomerulonephritis. We have previously shown that part of these protective effects associated with the induction of CD4+CD25+Foxp3+ regulatory T cells (Tregs) that suppressed autoantibody responses. Because the effects of pConsensus appeared secondary to qualitative rather than quantitative changes in Tregs, we investigated the molecular events induced by tolerance in Tregs and found that signaling pathways including ZAP70, p27, STAT1, STAT3, STAT6, SAPK, ERK, and JNK were not significantly affected. However, peptide tolerization affected in Tregs the activity of the MAPK p38, whose phosphorylation was reduced by tolerance. The pharmacologic inhibition of p38 with the pyridinyl imidazole inhibitor SB203580 in naive NZB/W mice reproduced in vivo the effects of peptide-induced tolerance and protected mice from lupus-like disease. Transfer experiments confirmed the role of p38 in Tregs on disease activity in the NZB/W mice. These data indicate that the modulation of p38 activity in lupus Tregs can significantly influence the disease activity.
In Defense of All-Active Manager Structures

When it comes to active equity manager selection, many investors focus their efforts on identifying managers that can beat their benchmarks. But investors may overlook the fact that the structure of their equity manager portfolios can be just as important as the managers they choose when it comes to outperforming the market and generating alpha. Two common portfolio structures are the “donut” structure, typically composed of four or more high-conviction managers diversified by style, capitalization, or strategy, and the “core-satellite” structure, which pairs the donut structure with a large passive core. Due to the donut structure’s reliance on concentrated, high-active-share managers (which typically generate higher tracking error and come at a higher fee), there is a common misperception that the large passive element of the core-satellite structure reduces risk and makes the portfolio both less expensive and less aggressive than the donut structure. But over the 17-year period in this analysis, the more concentrated donut structure offered higher returns, net of fees, with comparable levels of risk to the core-satellite structure. Investors may consider reassessing whether a core-satellite structure is as likely to help them earn superior returns as using the donut structure.
Wybrane determinanty przedsiębiorczości indywidualnej - zarys stanu badań

Individual entrepreneurship is among the key factors of social and economic development of regions in various scales of spatial settings. It is also an important way of increasing the flexibility of the labor market. Specialist literature clearly shows that there is a multitude of determinants influencing an individual’s willingness to become self-employed. They include both economic factors (e.g. the level of economic development, labor market situation, fiscal policy) and non-economic ones (e.g. the person’s gender, age, education level, marital status, whether or not the person has children, the person’s previous experience on the labor market). This paper serves the following purposes: a review of Polish and foreign theoretical studies on the determinants of individual entrepreneurship; a synthesis of the findings of studies verifying the impact of non-economic factors on an individual’s decision to become self-employed. Literature studies on the economic factors’ role on individuals’ decision to become self-employed show that, internationally, the scale of self-employment is essentially in close correlation with the GDP. Among the non-economic factors, gender, age, marital status and education level have been demonstrated to significantly influence the willingness to start one’s own business.
Effects of 24-hr nicotine replacement on sleep and daytime activity during smoking cessation.

BACKGROUND This study uses wrist actigrapy to assess the effects of 24-hr transdermal nicotine replacement on the sleep and daytime activity of smokers during smoking cessation. METHODS Seventy-one subjects grouped as light (n = 23), moderate (n = 24), or heavy (n = 24) smokers were randomly assigned to placebo or 11, 22, or 44 mg/day doses of transdermal nicotine for 1 week of intensive inpatient treatment of nicotine dependence. Outpatient patch therapy continued for 7 weeks following the inpatient stay. Those initially on placebo were randomly assigned to 11 or 22 mg/day, and those initially on 44 mg/day were reduced to 22 mg/day at Week 4. RESULTS There was a significant decrease in daytime wrist activity during patch therapy and the 1st week off patch therapy. These changes in daytime wrist activity were positively correlated with percentage of nicotine and cotinine replacement. No changes from baseline in sleep (sleep efficiency or wrist activity) were detected, nor were there differences in sleep among the four patch doses. CONCLUSIONS Using wrist actigraphy, this study failed to show any disturbing effects of 24-hr high-dose nicotine replacement on sleep. Lower levels of nicotine replacement were associated with a decrease from baseline in daytime wrist activity.
The C‐terminal domain of eukaryotic protein synthesis initiation factor (eIF) 4G is sufficient to support cap‐independent translation in the absence of eIF4E.

The foot and mouth disease virus, a picornavirus, encodes two forms of a cysteine proteinase (leader or L protease) that bisects the EIF4G polypeptide of the initiation factor complex eIF4F into N‐terminal (Nt) and C‐terminal (Ct) domains. Previously we showed that, although in vitro cleavage of the translation initiation factor, eIF4G, with L protease decreases cap‐dependent translation, the cleavage products themselves may directly promote cap‐dependent protein synthesis. We now demonstrate that translation of uncapped mRNAs normally exhibits a strong requirement for eIF4F. However, this dependence is abolished when eIF4G is cleaved, with the Ct domain capable of supporting translation in the absence of the Nt domain. In contrast, the efficient translation of the second cistron of bicistronic mRNAs, directed by two distinct Internal Ribosome Entry Segments (IRES), exhibits no requirement for eIF4E but is dependent upon either intact eIF4G or the Ct domain. These results demonstrate that: (i) the apparent requirement for eIF4F for internal initiation on IRES‐driven mRNAs can be fulfilled by the Ct proteolytic cleavage product; (ii) when eIF4G is cleaved, the Ct domain can also support cap‐independent translation of cellular mRNAs not possessing an IRES element, in the absence of eIF4E; and (iii) when eIF4G is intact, translation of cellular mRNAs, whether capped or uncapped, is strictly dependent upon eIF4E. These data complement recent work in other laboratories defining the binding sites for other initiation factors on the eIF4G molecule.
Increased rates of decay and reduced levels of accumulation of the major poly(A)-associated proteins of Dictyostelium during heat shock and development.

Two major polypeptide species, 31,000 Mr (p31) and 31,500 Mr (p31.5), are associated with the 3' poly(A) tails of Dictyostelium mRNAs. We have measured the accumulation of newly synthesized p31 and p31.5 and the decay of preexisting p31 and p31.5 during heat shock and early development. Only trace amounts of newly synthesized p31 and p31.5 accumulate at elevated temperatures, indicating that these polypeptides are not heat shock proteins. In addition, preexisting p31 and p31.5 are rapidly degraded in heat-shocked cells. This degradation is selective and occurs simultaneously with a sharp drop in the rate of translational initiation. Similarly, in early development, a time when the rate of translational initiation is also sharply reduced, only trace amounts of newly synthesized p31 and p31.5 accumulate and most of the preexisting p31 and p31.5 is rapidly degraded. When translational elongation is inhibited with cycloheximide, preexisting p31 and p31.5 remain stable. Therefore, a correlation seems to exist between the abundance and stability of these poly(A)-associated proteins and the rate of translational initiation. Our results are consistent with the proposed role of the poly(A)-protein complex in translation and do not support the findings of Schönfelder et al. [Schönfelder, M. , Horsch, A. & Schmid, H. -P. (1985) Proc. Natl. Acad. Sci. USA 82, 6884-6888] that the 73,000 Mr HeLa cell poly(A)-binding protein and the major 73,000 Mr mammalian heat shock protein (i.e., hsp70) are identical.
Structure and Food Price Inflation

Abstract We pair Nielsen TDLinx data, 2004–2014, with Consumer Price Index data to investigate how changes in food retail market structure drive food price inflation. We find, in corroboration with much of the evidence to date, that market concentration is positively and significantly associated with higher food prices. We find the same to be true for store format concentration, or the homogeneity of food markets. As the market shares, or penetration, of supercenters, warehouse stores, limited assortment stores, and superettes increase at expense of traditional supermarkets, food price inflation decreases.
Treatment of intermediate and advanced stage Hodgkin's disease with modified baseline BEACOPP regimen: a Hellenic Co‐operative Oncology Group Study

Abstract: The purpose of this prospective phase II trial was to investigate the safety and efficacy of a modified baseline BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen in the treatment of intermediate and advanced stage Hodgkin's disease (HD). From October 1997 to November 2001, 51 consecutive, previously untreated patients with stage IIA (bulky), IIB, III, and IV disease were treated with a modified baseline BEACOPP regimen with the etoposide administered i.v. on day 1 and orally at a dose of 100 mg/m2, on days 2 and 3. Each patient was scheduled to receive eight courses of BEACOPP with consolidation radiotherapy to bulky (≥5 cm) or residual disease. There were 25 males and 26 females with a median age of 32 yr (16–65 yr); 80.3% of the patients had nodular sclerosis HD, 41% had bulky disease (≥5 cm), 10 were in stage IIA (bulky ≥10 cm), 15 in stage IIB, 19 in stage III, and seven in stage IV. Thirty‐seven patients (72.5%) achieved a complete response and 17.6% partial response. No significant difference in overall response rate was observed between patients with: (i) 0–2 vs. ≥3 negative prognostic factors, (ii) in stage II vs. stages III/IV, LDH level, and bulky disease. With a median follow up period of 39.5 months, actuarial 3‐yr survival rate is 82% and time to progression rate 72.5%. Treatment with this combination was well tolerated. Grades 3 and 4 leukopenia and neutropenia occured in 26% and 28% of the patients, respectively, whereas in 16.3% of the patients infection was observed. Support with granulocyte colony‐stimulating factor was given to 59% of the patients. No case of secondary MDS/leukemia has been observed. The results of the present study demonstrate that the modified baseline BEACOPP regimen with radiotherapy used in our patients was well tolerated and effective therapy for intermediate and advanced stage HD. Further follow up time is required to evaluate long‐term toxicity.
Central neural mechanisms of progesterone action: application to the respiratory system.

Around the turn of the century, it was recognized that women hyperventilate during the luteal phase of the menstrual cycle and during pregnancy. Although a causative role for the steroid hormone progesterone in this hyperventilation was suggested as early as the 1940s, there has been no clear indication as to the mechanism by which it produces its respiratory effects. In contrast, much mechanistic information has been obtained over the same period about a different effect of progesterone, i.e., the facilitation of reproductive behaviors. In this case, the bulk of the evidence supports the hypothesis that progesterone acts via a genomic mechanism with characteristics not unlike those predicted by classic models for steroid hormone action. We recently, therefore, undertook a series of experiments to test predictions of those same models with reference to the respiratory effects of progesterone. Here we highlight the results of those studies; as background to and precedent for our experiments, we briefly review previous work in which effects of progesterone on respiration and reproductive behaviors have been studied. Our results indicate that the respiratory response to progesterone is mediated at hypothalamic sites through an estrogen- (E2) dependent progesterone receptor- (PR) mediated mechanism requiring RNA and protein synthesis, i.e., gene expression. The E2 dependence of the respiratory response to progesterone is likely a consequence of the demonstrated induction of PR mRNA and PR in hypothalamic neurons by E2. In short, we found that neural mechanisms underlying the stimulation of respiration by progesterone were similar to those mediating its reproductive effects.
Importance of E‐selectin (ELAM‐1) and sialyl lewisa in the adhesion of pancreatic carcinoma cells to acttvated endothelium

Adhesion molecules involved in attachment between human pancreatic carcinoma and activated endothelial cells in vitro were investigated. Basal adhesion occurred between 6 pancreatic carcinoma cell lines and unstimulated human umbilical vein endothelial cells (HUVEC), and augmented basal adhesion to activated HUVEC was only seen when pancreatic cancer cells expressed sialyl Lewisa (SLea) and sialyl Lewisx (SLex). Activation of HUVEC with interleukin l‐β (IL‐Iβ) or tumor necrosis factor‐α (TNF‐α), but not with interferon‐γ (IFN‐γ), generated the augmentative basal adhesion. Dose dependence and additive effect were observed in augmentation of the basal adhesion induced by IL‐I β and/or TNF‐α. Increase in adhesion correlated with up‐regulation of the surface E‐selectin (or ELAM‐I) on HUVEC, and was evident at both 25°C and 4°C. Anti‐E‐selectin and anti‐SLea blocked the augmented attachment, whereas anti‐SLex, an antibody against another known ligand for E‐selectin, did not. The collective evidence indicates that attachment between pancreas carcinoma cells and activated endothelial cells is regulated by cytokines such as IL‐1 β and TNF‐α, and is mediated by SLea on pancreas carcinoma and E‐selectin on endothelial cells. These molecules may be of significant importance in blood‐borne metastasis of pancreatic carcinoma cells to inflamed sites.
Preoperative Medical Optimization : Identifying “ At-Risk ” Patients

A n enhanced recovery program (ERP) is a set of multimodal, multidisciplinary interventions that are geared toward mitigating the undesirable effects of the surgical stress response.1 The purpose of an ERP is to accelerate postoperative surgical recovery by attenuating the factors that lead to surgical stress. Successful execution of an ERP requires coordination of the multidisciplinary teams, including surgery, anesthesiology, nursing, nutrition, physical therapy, and hospital team members.1 Together, these individuals combine best practices, namely, organization of care and effective clinical management in an evidenced-based framework. Other terminologies have been used to describe this coordination of care. These include enhanced recovery after surgery (ERAS), enhanced recovery pathways, and perioperative surgical home.1 Although there are some variations in focus, the main objectives of these practices are to improve patient care and potentially reduce health care costs.1 Colorectal surgery is among the earliest surgical models to which ERP principles were applied.1 The various elements of an ERP include preoperative patient education, modified preoperative fasting guidelines, preoperative medical optimization, fluid management, the role of bowel preparation, early oral intake, early ambulation, and standardized multimodal analgesic regimens. Specifically, 4 areas of patient care—preoperative medical optimization, pain management, use of bowel Enhanced Recovery: Perioperative Pathways Leading to Better Outcomes
More than "mountain guides" of science: a questionnaire survey of professional science communicators in Denmark

This article sums up key results of a web-based questionnaire survey targeting the members of the Danish Science Journalists' Association. The association includes not only science journalists but also other types of science communicators. The survey shows that science communicators have a nuanced and multidimensional view on science communication, science, and technology. Science communicators are thus more than the "mountain guides" of science, as a recent definition describes it. The survey respondents are not just interested in helping the public at large to a wider recognition of scientific knowledge, but also want to contribute to democratic debate and social legitimisation of science and technology. The respondents exhibit a certain amount of optimism in relation to science and technology, yet also take a sceptical stance when confronted with overly positive statements regarding science and technology. Finally they have a predominantly social constructivist perception of science and technology when it comes to external relations to society, while they lean towards a hypothetical-deductive science understanding when it concerns the internal dynamics of science.
International Standards for Tuberculosis Care: revisiting the cornerstones of tuberculosis care and control

Tuberculosis (TB) remains an enormous global health problem. There are 8–9 million new cases and 2 million deaths from TB annually. Despite the overwhelming burden of disease, the basic principles of care for persons with, or suspected of having, TB are the same worldwide: a diagnosis should be established promptly and accurately, standardized treatment regimens of proven efficacy should be used together with appropriate treatment support and supervision, the response to treatment should be monitored, and the essential public health responsibilities must be carried out. As an approach to improving the care of patients with TB, an evidence-based document, the International Standards for Tuberculosis Care (ISTC) was developed and has been endorsed by more than 30 international and national agencies. This special report introduces the ISTC and discusses the fact that accurate diagnosis and effective treatment are not only essential for good patient care, they are the key elements in the public health response to TB and are the cornerstone of TB control. With the recent emergence of extensively drug-resistant TB, there is an urgent need to ensure globally that standards of TB care are based on rigorous scientific findings, are clear and well understood, and are accessible to and applied by all types of healthcare providers in all corners of the world.
A method of deciding force feedback gain against external force for biped robot

A biped robot has great difficulty in keeping stable walk because it has no fixed points to the ground. Enhancement of stability is one of the most important topics of a biped robot. If a robot can walk stably even under unexpected external force, we can say that its stability is remarkably improved. Robot motion should be changed by the amount of external force. If the external force is small, the trajectory does not need to be modified actively. It is desired that designers input the same command of robot motion and passive robot motion against external force is achieved. Compliance control is commonly applied to realize passive motion. The characteristics of compliance control is generally determined set to the definite value without considering the walking stability. In this paper, we propose a novel stabilizing method that modifies the body motion by the variable force feedback gain of compliance control based on the position control. This feedback gain is determined by ZMP trajectory and external force only when external force was recognized, so a robot can move keeping its stability under unexpected external force
Thyroid hormones and their effects: a new perspective

The thyroid hormones are very hydrophobic and those that exhibit biological activity are 3′,5′,3,5‐Ltetraiodothyronine (T4), 3′,5,3‐L‐triiodothyronine (T3), 3′,5′,3‐L‐triiodothyronine (rT3) and 3,5,‐Ldiiodothyronine (3,5‐T2). At physiological pH, dissociation of the phenolic ‐OH group of these iodothyronines is an important determinant of their physical chemistry that impacts on their biological effects. When non‐ionized these iodothyronines are strongly amphipathic. It is proposed that iodothyronines are normal constituents of biological membranes in vertebrates. In plasma of adult vertebrates, unbound T4 and T3 are regulated in the picomolar range whilst protein‐bound T4 and T3 are maintained in the nanomolar range. The function of thyroid‐hormone‐binding plasma proteins is to ensure an even distribution throughout the body. Various iodothyronines are produced by three types of membrane‐bound cellular deiodinase enzyme systems in vertebrates. The distribution of deiodinases varies between tissues and each has a distinct developmental profile. Thyroid hormones have many effects in vertebrates. It is proposed that there are several modes of action of these hormones. (1) The nuclear receptor mode is especially important in the thyroid hormone axis that controls plasma and cellular levels of these hormones. (2) These hormones are strongly associated with membranes in tissues and normally rigidify these membranes. (3) They also affect the acyl composition of membrane bilayers and it is suggested that this is due to the cells responding to thyroid‐hormone‐induced membrane rigidification. Both their immediate effects on the physical state of membranes and the consequent changes in membrane composition result in several other thyroid hormone effects. Effects on metabolism may be due primarily to membrane acyl changes. There are other actions of thyroid hormones involving membrane receptors and influences on cellular interactions with the extracellular matrix. The effects of thyroid hormones are reviewed and appear to be combinations of these various modes of action. During development, vertebrates show a surge in T4 and other thyroid hormones, as well as distinctive profiles in the appearance of the deiodinase enzymes and nuclear receptors. Evidence from the use of analogues supports multiple modes of action. Re‐examination of data from the early 1960s supports a membrane action. Findings from receptor ‘knockout’ mice supports an important role for receptors in the development of the thyroid axis. These iodothyronines may be better thought of as ‘vitamone’ ‐like molecules than traditional hormonal messengers.
DAMPAK KRISIS KEUANGAN GLOBAL TERHADAP PEREKONOMIAN DAERAH

This paper discusses the impact of global financial crisis to the Indonesia»s economy by using the simultaneous macro model approach.The analysis and simulation results of such model show that the impact of the global financial crisis is dominantly distributed through the trade line, which decreases the regional output.To the components of aggregate demand, the movement of exchange rate has major effect to the exports and imports, whereas to the consumption and investment, it gives relatively small effect.The impact of external shock, which causes the depreciation of Rupiah, is relatively small to the increase of inflation. JEL classification: C32, E44