Miracle-dz/UniFAR-FTUs huggingface dataset:
The Q-rich Subdomain of the Human AhReceptor Transactivation Domain Is Required for Dioxin-mediated Transcriptional Activity*

The aryl hydrocarbon receptor (AhR), a basic helix-loop-helix/Per-Arnt-Sim transcription factor, mediates many of the toxic and biological effects of the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin, which include the transcriptional activation of dioxin-responsive genes such as CYP1A1. Many aspects of this process are known; however, the mechanism of transcriptional activation and the proteins that are key to this process remain to be determined. The hAhR has a complex transactivation domain, composed of three potentially distinct subdomains. Deletional analysis of the hAhR transactivation domain indicates that removal of the P/S/T-rich subdomain enhances transcriptional activity, whereas the Q-rich subdomain is critical for hAhR transactivation potential, and the acidic subdomain by itself fails to activate a dioxin response element-driven reporter gene. Deletional analysis of the Q-rich subdomain identified a critical stretch of 23 amino acids between residues 666 and 688 of the hAhR, which are required for transactivation potential. Alanine scanning mutagenesis of this region identified a leucine residue (Leu-678), which is required for hAhR activity. Functional analysis of this point mutant revealed that it is capable of binding ligand, heterodimerization, and subsequent binding to dioxin response elements. Further, when hAhR/L678A and hAhR containing only the acidic subdomain were overexpressed they acted as dominant negative receptors and repressed wild-type hAhR activity. In addition, the hAhR/L678A failed to activate CYP1A1 gene transcription in transfected BP-8 cells and exhibited reduced binding to RIP140 in vitro. Thus, Leu-678 appears to be critical for efficient transactivation activity of the hAhR and appears to disrupt recruitment of co-regulators.
Associations of squaric acid and its anions as multiform building blocks of hydrogen-bonded molecular crystals.

Squaric acid, H(2)C(4)O(4) (H(2)SQ), is a completely flat diprotic acid that can crystallize as such, as well as in three different anionic forms, i.e. H(2)SQ.HSQ(-), HSQ(-) and SQ(2-). Its interest for crystal engineering studies arises from three notable factors: (i) its ability of donating and accepting hydrogen bonds strictly confined to the molecular plane; (ii) the remarkable strength of the O-H.O bonds it may form with itself which are either of resonance-assisted (RAHB) or negative-charge-assisted [(-)CAHB] types; (iii) the ease with which it may donate a proton to an aromatic base which, in turn, back-links to the anion by strong low-barrier N-H+. O(1/2-) charge-assisted hydrogen bonds. Analysis of all the structures so far known shows that, while H(2)SQ can only crystallize in an extended RAHB-linked planar arrangement and SQ(2-) tends to behave much as a monomeric dianion, the monoanion HSQ(-) displays a number of different supramolecular patterns that are classifiable as beta-chains, alpha-chains, alpha-dimers and alpha-tetramers. Partial protonation of these motifs leads to H(2)SQ.HSQ(-) anions whose supramolecular patterns include ribbons of dimerized beta-chains and chains of emiprotonated alpha-dimers. The topological similarities between the three-dimensional crystal chemistry of orthosilicic acid, H(4)SiO(4), and the two-dimensional one of squaric acid, H(2)C(4)O(4), are finally stressed.
Nexus Strength: A Novel Metric for Assessing the Global Resource Nexus

The limited access to natural resources is a major constraint for sustainability at various spatial scales. This challenge has sparked scholarly interest in the linkages or nexus between resources, with a view to helping anticipate unforeseen consequences, identify trade‐offs and co‐benefits, and find optimal solutions. Yet, despite decades of research, limitations in the scope and focus of studies remain. Recently constructed multiregional input‐output (MRIO) databases, which cover the global economy and its use of resources in unprecedented detail, allow systematically investigation of resource use by production as well as consumption processes at various levels and garner new insights into global resource nexus (GRN) issues. This article addresses the question of how to prioritize such issues. Using the MRIO database, EXIOBASE, we address the GRN considering five key resources: blue water, primary energy, land, metal ores, and minerals. We propose a metric of nexus strength, which relies on linear goal programming to rank industries and products based on its associated combined resource use and various weighting schemes. Our results validate current research efforts by identifying water, energy, and land as the strongest linkages globally and at all scales and, at the same time, lead to novel findings into the GRN, in that (1) it appears stronger and more complex from the consumption perspective, (2) metals and minerals emerge as critical, yet undervalued, components, and (3) it manifests with a considerable diversity across countries owing to differences in the economic structure, domestic policy, technology, and resource endowments.
A survey of medical image processing tools

A precise analysis of medical image is an important stage in the contouring phase throughout radiotherapy preparation. Medical images are mostly used as radiographic techniques in diagnosis, clinical studies and treatment planning. Medical image processing tool are also similarly as important. With a medical image processing tool, it is possible to speed up and enhance the operation of the analysis of the medical image. This paper describes medical image processing software tool which attempts to secure the same kind of programmability advantage for exploring applications of the pipelined processors. These tools simulate complete systems consisting of several of the proposed processing components, in a configuration described by a graphical schematic diagram. In this paper, fifteen different medical image processing tools will be compared in several aspects. The main objective of the comparison is to gather and analysis on the tool in order to recommend users of different operating systems on what type of medical image tools to be used when analysing different types of imaging. A result table was attached and discussed in the paper.
A study of the biomechanical properties of the adult equine linea alba: relationship of tissue bite size and suture material to breaking strength.

The purposes of this study were to mechanically determine the optimal tissue bite size and to evaluate seven suture materials at their largest commercially available size for breaking strength and stiffness using cadaveric adult equine linea alba. Soft tissues were removed from the abdominal fascia of 16 adult horses. Individual test sections were created from the entire linea alba and labeled (1 through 6) starting at the umbilicus and extending craniad. A single biomechanical test was performed on each test section. Tissue bite size (3, 6, 9, 12, 15, 18, and 21 mm) significantly altered breaking strength directly in a logarithmic fashion (P < .0001; R2 = 0.94). Tissue bite size accounted for 44% and linea alba thickness for 24% of the variability in breaking strength of the equine linea alba. The optimal tissue bite size for adult horse was 15 mm from the edge of the linea alba based on lack of significant gain in breaking strength. There were no differences in breaking strength among horses, horses weight, or left and right test sections. Test sections taken from near or at the umbilicus had greater breaking strength (P < .005) and thicker linea alba (P < .001) when compared with more cranial test sections. Linea alba thickness alone accounted for 34% of the variability in breaking strength associated with test section position. There were no differences in linea alba stiffness among tissue bite sizes. All suture loops failed before complete fascial disruption, and 52 of 56 (93%) suture loops failed at the knot. (ABSTRACT TRUNCATED AT 250 WORDS)
Food Sovereignty, Agroecology and Biocultural Diversity : Constructing and contesting knowledge

Regenerative food systems and the conservation of change Nov 09, 2021 · There is a pressing need to rapidly redesign global food systems around practices that can meet ambitious goals for ecological sustainability and social justice (Rockström et al. 2020). Global food systems have succeeded in consistently increasing food production, both in sum and per capita, since the 1960s, while also keeping food .
Emotional Exhaustion in Primary Care During Early Implementation of the VA’s Medical Home Transformation: Patient-aligned Care Team (PACT)

Objective:Transformation of primary care to new patient-centered models requires major changes in healthcare organizations, including interprofessional expectations and organizational policies. Emotional exhaustion (EE) among workers can accompany major organizational change, threatening its success. Yet little guidance exists about the magnitude of associations with EE during primary care transformation. We assessed EE during the initial phase of national primary care transformation in the Veterans Health Administration. Research Design:Cross-sectional online surveys of primary care clinicians (PCCs) and staff in 23 primary care clinics within 5 healthcare systems in 1 veterans administration administrative region. We used descriptive, bivariate, and multivariable analyses adjusted for clinic membership and weighted for nonresponse. Participants:515 veterans administration employees (191 PCCs and 324 other primary care staff). Measures:Outcome is the EE subscale of the Maslach Burnout Inventory. Predictors include clinic characteristics (from administrative data) and self-reported efficacy for change, experiences with transformation, and perspectives about the organization. Results:The overall response rate was 64% (515/811). In total, 53% of PCCs and 43% of staff had high EE. PCCs (vs. other primary care staff), female (vs. male), and non-Latino (vs. Latino) respondents reported higher EE. Respondents reporting higher efficacy for change and participatory decision making had lower EE scores, adjusting for sex and race. Conclusions:Recognition by healthcare organizations of the potential for clinician and staff EE during primary care transformation is critical. Methods for reducing EE by increasing clinician and staff change efficacy and opportunities to participate in decision making should be considered, with attention to PCCs, and women.
Pdx-1 Activates Islet α- and β-Cell Proliferation via a Mechanism Regulated by Transient Receptor Potential Cation Channels 3 and 6 and Extracellular Signal-Regulated Kinases 1 and 2

ABSTRACT The homeodomain transcription factor Pdx-1 has important roles in pancreatic development and β-cell function and survival. In the present study, we demonstrate that adenovirus-mediated overexpression of Pdx-1 in rat or human islets also stimulates cell replication. Moreover, cooverexpression of Pdx-1 with another homeodomain transcription factor, Nkx6.1, has an additive effect on proliferation compared to either factor alone, implying discrete activating mechanisms. Consistent with this, Nkx6.1 stimulates mainly β-cell proliferation, whereas Pdx-1 stimulates both α- and β-cell proliferation. Furthermore, cyclins D1/D2 are upregulated by Pdx-1 but not by Nkx6.1, and inhibition of cdk4 blocks Pdx-1-stimulated but not Nkx6.1-stimulated islet cell proliferation. Genes regulated by Pdx-1 but not Nkx6.1 were identified by microarray analysis. Two members of the transient receptor potential cation (TRPC) channel family, TRPC3 and TRPC6, are upregulated by Pdx-1 overexpression, and small interfering RNA (siRNA)-mediated knockdown of TRPC3/6 or TRPC6 alone inhibits Pdx-1-induced but not Nkx6.1-induced islet cell proliferation. Pdx-1 also stimulates extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation, an effect partially blocked by knockdown of TRPC3/6, and blockade of ERK1/2 activation with a MEK1/2 inhibitor partially impairs Pdx-1-stimulated proliferation. These studies define a pathway by which overexpression of Pdx-1 activates islet cell proliferation that is distinct from and additive to a pathway activated by Nkx6.1.
The effect of obesity on polycystic ovary syndrome: a systematic review and meta‐analysis

While many women with polycystic ovary syndrome (PCOS) are overweight, obese or centrally obese, the effect of excess weight on the outcomes of PCOS is inconsistent. The review aimed to assess the effects of overweight, obesity and central obesity on the reproductive, metabolic and psychological features of PCOS. MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PSYCINFO were searched for studies reporting outcomes according to body mass index categories or body fat distribution. Data were presented as mean difference or risk ratio (95% confidence interval). This review included 30 eligible studies. Overweight or obese women with PCOS had decreased sex hormone‐binding globulin (SHBG), increased total testosterone, free androgen index, hirsutism, fasting glucose, fasting insulin, homeostatic model assessment‐insulin resistance index and worsened lipid profile. Obesity significantly worsened all metabolic and reproductive outcomes measured except for hirsutism when compared to normal weight women with PCOS. Overweight women had no differences in total testosterone, hirsutism, total‐cholesterol and low‐density lipoprotein‐cholesterol compared to normal weight women and no differences in SHBG and total testosterone compared to obese women. Central obesity was associated with higher fasting insulin levels. These results suggest that prevention and treatment of obesity is important for the management of PCOS.
Great tits growing old: selective disappearance and the partitioning of senescence to stages within the breeding cycle

Deterioration of reproductive traits with age is observed in an increasing number of species. Although such deterioration is often attributed to reproductive senescence, a within-individual decline in reproductive success with age, few studies on wild animals have focused on direct fitness measures while accounting for selective disappearance and terminal effects, and to our knowledge none have determined how senescence effects arise from underlying reproductive traits. We show for female great tits that such an approach helps understanding of the onset, impact and architecture of senescence. Cross-sectional analysis of 49 years of breeding data shows annual recruit production to decline from 3.5 years of age, this decline affecting 9 per cent of females each year. Longitudinal analyses, however, show that selective disappearance of poor-quality breeders partly masks senescence, which in fact starts at 2.8 years and affects 21 per cent of females each year. There is no evidence for abrupt terminal effects. Analyses of underlying traits show no deterioration in clutch size, but significant declines in brood size and fledgling number. Furthermore, these traits contribute −9, 12 and 39 per cent to the senescent decline in recruit production, respectively. Besides providing detailed knowledge of the patterns and architecture of senescence in a natural population, these results illustrate the importance of modelling individual variation, and facilitate study of the underlying mechanisms of senescence.
Potential Cost-Effectiveness of Maternal and Infant Antiretroviral Interventions to Prevent Mother-to-Child Transmission During Breast-feeding

Introduction:One-third of maternal-to-child HIV transmission occurs during breast-feeding (BF). Several trials are currently evaluating the efficacy of postpartum antiretrovirals to reduce BF transmission. Methods:This study used Markov modeling to define the circumstances under which the following interventions would be cost-effective: BF for 6 months with daily infant nevirapine (NVP) prophylaxis; maternal combination antiretroviral therapy (ART) during pregnancy and for 6 months of BF; and maternal combination ART only for women who meet CD4 criteria. Each was compared to: BF for 12 months; BF for 6 months; and formula feeding for 12 months. Strategies were evaluated for a hypothetical cohort of 40,000 pregnant women in sub-Saharan Africa, in the context of available voluntary counseling and testing in antenatal care. Model estimates were derived from the literature and local sources. Sensitivity analyses were performed on uncertain estimates. The perspective used was that of a government health district. Results:Using base case estimates, BF for 6 months was the economically preferred strategy: it cost $806,995 and generated 446,208 quality-adjusted life-years (QALYs). Providing daily infant NVP cost an additional $93,638 and generated 1183 additional QALYs, but its incremental cost-effectiveness ratio (ICER) of $79/QALY exceeded the standard willingness to pay ($64/QALY) for most resource-poor settings. Maternal combination ART was potentially very effective but too costly for most resource-poor settings (ICER: $87/QALY). In order for daily infant NVP during BF to be preferred, it must have ≥44% relative efficacy or cost ≤$5.00/mo. If NVP were donated, it would only have to be minimally effective to be the economically preferred strategy. If ART cost ≤$34.50/mo, ART to all mothers would become the preferred strategy under our assumption of 82% efficacy. Conclusions:Providing antiretrovirals during BF represents a promising alternative, should their effectiveness, and feasibility be proven.
Faith‑based organizations and the state

Since Zanzibar and Tanganyika became the United Republic of Tanzania in 1964, African socialism called ujamaa spread widely in this country. The adoption of an African Socialist approach was accompanied by the nationalization of education and health facilities belonging to the religious institutions. However, since the collapse of ujamaa in the mid‑1980s, Tanzania saw the increased activity of various faith‑based organizations (FBOs) that were connected to the economic and political liberalization. The new system caused that FBOs have become part of a growing religious field which has repositioned itself toward the multiple opportunities and expectations of the established apex bodies to coordinate with each other and manage their relationships with the government. This article describes how religious actors in urban Tanzania have repositioned themselves in relation to the state as well as themselves during the liberalization era triggered by development.
Sexual Offender Recidivism Risk

Abstract: If all sexual offenders are dangerous, why bother assessing their risk to reoffend? Follow‐up studies, however, typically find sexual recidivism rates of 10%‐15% after five years, 20% after 10 years, and 30%‐40% after 20 years. The observed rates underestimate the actual rates because not all offences are detected; however, the available research does not support the popular notion that sexual offenders inevitably reoffend. Some sexual offenders are more dangerous than others. Much is known about the static, historical factors associated with increased recidivism risk (e.g., prior offences, age, and relationship to victims). Less is known about the offender characteristics that need to change in order to reduce that risk. There has been considerable research in recent years demonstrating that structured risk assessments are more accurate than unstructured clinical assessments. Nevertheless, the limitations of actuarial risk assessments are sufficient that experts have yet to reach consensus on the best methods for combining risk factors into an overall evaluation.
A Systematic Approach for Improving the Software Management Process

Information technology is an indispensable element in applications in today’s industrial era. In addition to modern management approaches, software just as well as hardware is of great importance to ensure competitive advantage if the company needs to keep pace with industrial requirements. Information sector can be seen as a competition opportunity for emerging countries. To be able to exploit this opportunity, companies need to be agile and innovative. In this paper, we suggest a process innovation which is intended to be a new model for designing an efficient and effective software process. The model was applied at a software company, and the results of this study are reported here. Lean and agile approaches were used, and as a result, the firm achieved significant improvements in cost, time, labor force, quality, internal and external customer satisfaction, speed, reliability and productivity.
Interferon‐γ in healthy subjects: selective modulation of inflammatory mediators

Background It is suggested that interferon‐γ (IFN‐γ), like other cytokines, is a mediator in the host inflammatory response, which could be of importance in the pathophysiology of sepsis. The role of IFN‐γ in human host inflammatory responses, however, has not been studied.
Conceptualizing and measuring performance orientation of research funding systems

In this article, we propose a synthetic indicator for the performance orientation of public R&D funding at the country level that allows for quantitative comparisons across countries and over time, and we illustrate the methodology for its computation and validation. The indicator characterizes R&D funding from the state in terms of the extent the beneficiaries’ performance is taken into account in the allocation of resources. By building on the literature on research funding, the indicator combines information on how funding is allocated with quantitative measures of funding volumes. It is operationalized in terms of a fine-grained decomposition of public R&D funding in instruments, each of them characterized by their mode and criteria of allocation. Building on a large-scale European project, we test the operationalization of the indicator for a sample of European countries, and we perform a set of sensitivity and robustness analyses to inquire the impact of definitions and of data issues, particularly for what concerns cross-country comparisons. We conclude with a discussion of the advantages and limitations of the indicator and by proposing a research agenda for its further development.