Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidemiological tracing of bovine tuberculosis in Switzerland, multilocus variable number of tandem repeat analysis of Mycobacterium bovis and Mycobacterium caprae

Background After 15 years of absence, in 2013 bovine tuberculosis (bTB), caused by Mycobacterium (M.) bovis and M. caprae, reemerged in the Swiss dairy cattle population. In order to identify the sources of infection as well as the spread of the agents, molecular-epidemiologic tracing by MIRU-VNTR analysis in combination with spoligotyping was performed. A total of 17 M. bovis and 7 M. caprae isolates were cultured from tuberculous bovine lymph nodes and analyzed with a set of 49 genetic markers by using automated capillary electrophoresis. Results The outbreak in the western part of Switzerland was caused by M. bovis spoligotype SB0120. With the exception of four single-locus variations observed in MIRU 20, the MIRU-VNTR profiles of the 17 M. bovis isolates were identical, indicating a single source of infection. M. bovis detected in one archival bovine specimen from the outbreak region showed an identical MIRU-VNTR profile, suggesting persistence of the agent in a dairy herd for nearly fifteen years. The outbreak in the eastern part of Switzerland was caused by M. caprae spoligotype SB0418. All Swiss M. caprae isolates showed the Lechtal-type MIRU-VNTR profile, described as endemic in wild ruminants and in dairy cattle in Austrian bordering regions. This suggests the agent was most likely introduced by Swiss dairy cattle summering on Austrian pastures. Conclusions The present study is the first MIRU-VNTR analysis of Swiss bTB mycobacterial isolates. The genotyping assay was found to be highly discriminating and suitable for the epidemiological tracing of further outbreaks. These findings will contribute to the development of an international MIRU-VNTR database aiming to improve bTB surveillance.
Assaying for hydroxyl radicals: hydroxylated terephthalate is a superior fluorescence marker than hydroxylated benzoate.

Generation of hydroxyl radicals in terephthalate (benzene-1,4-dicarboxylic acid) solution yields fluorescent 2-hydroxy-terephthalate. The reaction product is stable for hours and can readily be assessed using standard fluorimeters. The efficiency, i.e. the relative increase of fluorescence per *OH radical, is about three times higher than that of the formation of salicylate (2-hydroxy-benzoate) from benzoic acid and approximately hundred-fold higher than that of the hydroxylation of phenylalanine. As the terephthalate molecule is symmetric with respect to ring-hydroxylation, only one isomer is formed; hence, mechanistic interpretation of the hydroxylation reaction is facilitated. The scavenging rate constant of terephthalate for *OH yielding the hydroxycyclohexadienyl adduct as first intermediate is close to the diffusion controlled limit (k = 3.3 x 10(9) M(-1) s(-1)). Therefore, competition of the detector molecule with biomolecules being present under physiological conditions is expected to be efficient. The assay can be used to detect 'free' *OH radicals produced by the radiolysis of water as well as 'hydroxyl analogous species' that have been suggested to arise from the interaction of complex-bound reduced metal with either oxygen or hydrogen peroxide, e.g. from Fenton reactions. Based on calibration with radiolytically generated hydroxyl radicals the detection limit of the method is estimated to be around 50 nmol/dm3. Terephthalate is classified non-toxic and hence may also prove useful for microdialysis and continuous flow experiments as observation of fluorescence is 'non-destructive' and the reporter substance does not necessarily have to be subjected to HPLC.
Why governments may opt for financial repression policies: selective credits and endogenous growth

Abstract Financial repression policies (lowering real interest rates, selective credits and other restrictions on financial markets, products and institutions) have been widely discussed in the economic literature during the last four decades. A key question is ‘why governments would opt for financial repression policies in the first place’? As an answer, governments’ desire to obtain rents from the financial system or to manage public debt servicing have been suggested as the typical underlying incentives. It has been argued in 1970s and 1980s that especially in developing economies, financial repression would have negative consequences on economic growth and financial development, although more recently financial repression policies are back as governments in the developed economies aim at obtaining low-cost funds from the financial markets in the aftermath of the global financial crises.In this article, a simple two-sector model is set up in order to show that governments may institute financial repression policies to internalise production and investment externalities. It is shown that such a government policy is welfare improving and abolishment of selective credits may cause welfare loss. The model also provides a case where financial policy is designed according to the priorities of industrial policy.
Loss of E-cadherin-dependent cell-cell adhesion due to mutation of the beta-catenin gene in a human cancer cell line, HSC-39

Detachment of cell-cell adhesion is indispensable for the first step of invasion and metastasis of cancer. This mechanism is frequently associated with the impairment of either E-cadherin expression or function. However, mechanisms of such abnormalities have not been fully elucidated. In this study, we demonstrated that the function of E-cadherin was completely abolished in the human gastric cancer cell line HSC-39, despite the high expression of E-cadherin, because of mutations in one of the E-cadherin-associated cytoplasmic proteins, beta-catenin. Although immunofluorescence staining of HSC-39 cells by using an anti-E-cadherin antibody (HECD-1) revealed the strong and uniform expression of E-cadherin on the cell surface, cell compaction and cell aggregation were not observed in this cell. Western blotting (immunoblotting) using HECD-1 exhibited a 120-kDa band which is equivalent to normal E-cadherin. Northern (RNA) blotting demonstrated a 4.7-kb band, the same as mature E-cadherin mRNA. Immunoprecipitation of metabolically labeled proteins with HECD-1 revealed three bands corresponding to E-cadherin, alpha-catenin, and gamma-catenin and a 79-kDa band which was apparently smaller than that of normal beta-catenin, indicating truncated beta-catenin. The 79-kDa band was immunologically identified as beta-catenin by using immunoblotting with anti-beta-catenin antibodies. Examination of beta-catenin mRNA by the reverse transcriptase-PCR method revealed a transcript which was shorter than that of normal beta-catenin. The sequencing of PCR product for beta-catenin confirmed deletion in 321 bases from nucleotides +82 to +402. Southern blotting of beta-catenin DNA disclosed mutation at the genomic level. Expression vectors of Beta-catenin were introduced into HSC-39 cells by transfection. In the obtained transfectants, E-cadherin-dependent cell-cell adhesiveness was recovered, as revealed by cell compaction, cell aggregation, and immunoflourescence staining. From these results, it was concluded that in HSC-39 cells, impaired cell-cell adhesion is due to mutations in beta-catenin which results in the dysfunction of E-cadherin.
Vaccination of stage III/IV melanoma patients with long NY-ESO-1 peptide and CpG-B elicits robust CD8+ and CD4+ T-cell responses with multiple specificities including a novel DR7-restricted epitope

ABSTRACT Long synthetic peptides and CpG-containing oligodeoxynucleotides are promising components for cancer vaccines. In this phase I trial, 19 patients received a mean of 8 (range 1–12) monthly vaccines s.c. composed of the long synthetic NY-ESO-179–108 peptide and CpG-B (PF-3512676), emulsified in Montanide ISA-51. In 18/18 evaluable patients, vaccination induced antigen-specific CD8+ and CD4+ T-cell and antibody responses, starting early after initiation of immunotherapy and lasting at least one year. The T-cells responded antigen-specifically, with strong secretion of IFNγ and TNFα, irrespective of patients' HLAs. The most immunogenic regions of the vaccine peptide were NY-ESO-189–102 for CD8+ and NY-ESO-183–99 for CD4+ T-cells. We discovered a novel and highly immunogenic epitope (HLA-DR7/NY-ESO-187–99); 7/7 HLA-DR7+ patients generated strong CD4+ T-cell responses, as detected directly ex vivo with fluorescent multimers. Thus, vaccination with the long synthetic NY-ESO-179–108 peptide combined with the strong immune adjuvant CpG-B induced integrated, robust and functional CD8+ and CD4+ T-cell responses in melanoma patients, supporting the further development of this immunotherapeutic approach.
Clinical genetic testing for male factor infertility: current applications and future directions

Spermatogenesis involves the aggregated action of up to 2300 genes, any of which, could, potentially, provide targets for diagnostic tests of male factor infertility. Contrary to the previously proposed common variant hypothesis for common diseases such as male infertility, genome‐wide association studies and targeted gene sequencing in cohorts of infertile men have identified only a few gene polymorphisms that are associated with male infertility. Unfortunately, the search for genetic variants associated with male infertility is further hampered by the lack of viable animal models of human spermatogenesis, difficulty in robustly phenotyping infertile men and the complexity of pedigree studies in male factor infertility. In this review, we describe basic genetic principles involved in understanding the genetic basis of male infertility and examine the utility and proper clinical use of the proven genetic assays of male factor infertility, specifically Y chromosome microdeletions, chromosomal translocations, karyotype, cystic fibrosis transmembrane conductance regulator mutation analysis and sperm genetic tests. Unfortunately, these tests are only able to diagnose the cause of about 20% of male factor infertility. The remainder of the review will be devoted to examining novel tests and diagnostic tools that have the potential to explain the other 80% of male factor infertility that is currently classified as idiopathic. Those tests include epigenetic analysis of the spermatozoa and the evaluation of rare genetic variants and copy number variations in patients. Success in advancing to the implementation of such areas is not only dependent on technological advances in the laboratory, but also improved phenotyping in the clinic.
Mode of Action: Neurotoxicity Induced by Thyroid Hormone Disruption During Development—Hearing Loss Resulting From Exposure to PHAHs

An increasing incorporation of mode of action (MOA) information into risk assessments has led to examination of animal MOAs to determine relevance to humans. We examined a specific MOA for developmental neurotoxicity using the MOA/Human Relevance Framework (Meek et al., 2003). The postulated MOA of ototoxicity in rats involves early postnatal exposure to polychlorinated biphenyls (PCBs) via lactation, an upregulation of hepatic uridine diphosphoglucuronyltransferases (UGTs), and subsequent hypothyroxinemia during a critical period of cochlear development, with the ultimate neurotoxic consequence of hearing loss. This review concludes with high confidence in the animal MOA and medium confidence for the interspecies concordance for the key events in the MOA. Possible interspecies differences in toxicodynamic factors moderate confidence in some key events. In addition, there is a question of whether ambient human exposures are large enough to cause human fetal hypothyroxinemia to the degree needed to cause hearing loss. Data gaps identified by this analysis include a need to characterize the induciblity of human fetal UGTs and the comparative sensitivity of UGT induction by xenobiotics in rats and humans. Research on these areas of uncertainty will increase confidence that this MOA for PCBs is not likely to not occur in humans, assuming normal conditions of limited ambient exposure.
On the causes of the changes in income shares: Some reflections in the light the United States experience

ABSTRACT The last 30 years have witnessed a dramatic change in the distribution of income, with the wage share falling in all major industrialized countries. Main-stream analyses, including New Keynesian ones, which retain the notion of factor substitution leading to a “factor intensity” inversely related to its rate of return, have encountered some difficulties in the interpretation of this change. Nonmainstream approaches present an advantage in the explanation of the phenomenon, consisting in the fact that they entail no a priori connections between the changes in distribution and the changes factor proportions. Hence if a change in institutions or in the bargaining strength of the parties affects distribution, income shares may vary significantly (i.e., changes in wages need not be accompanied by changes in labor to output ratio in the opposite direction as in mainstream analyses). Yet empirical observation may question also some of the analyses that have been advanced outside the mainstream. The article will explore the ways in which nonmainstream approaches have interpreted the described changes in distribution, and assess them from an analytical viewpoint and with reference to U.S. data. The purpose is that of pointing at some open questions and problems.
Transplantation of bone marrow fibroblastoid stromal cells in mice via the intravenous route

Summary. Kinetics of fibroblastic colony‐forming cells (CFU‐F) were studied in mouse bone marrow after lethal total body irradiation and intravenous bone marrow transplantation. After an initial decrease, CFU‐F numbers recovered, and plateaued 5 weeks post‐treatment at 10% of normal values.
The Caenorhabditis elegans Cathepsin Z-like Cysteine Protease, Ce-CPZ-1, Has a Multifunctional Role during the Worms' Development*

We have analyzed the expression and function of Cecpz-1, a Caenorhabditis elegans cathepsin Z-like cysteine protease gene, during development of the worm. The cpz-1 gene is expressed in various hypodermal cells of all developmental stages and is specifically expressed in the gonads and the pharynx of adult worms. Disruption of cpz-1 function by RNA interference or cpz-1(ok497) deletion mutant suggests that cpz-1 has a role in the molting pathways. The presence of the native CPZ-1 protein in the hypodermis/cuticle of larval and adult stages and along the length of the pharynx of adult worms, as well as the cyclic expression of the transcript during larval development, supports such function. We hypothesize that the CPZ-1 enzyme functions directly as a proteolytic enzyme degrading cuticular proteins before ecdysis and/or indirectly by processing other proteins such as proenzymes and/or other proteins that have an essential role during molting. Notably, an impressive level of the CPZ-1 native protein is present in both the new and the old cuticles during larval molting, in particular in the regions that are degraded prior to shedding and ecdysis. The similar localization of the related Onchocerca volvulus cathepsin Z protein suggests that the function of CPZ-1 during molting might be conserved in other nematodes. Based on the cpz-1 RNA interference and cpz-1 (ok497) deletion mutant phenotypes, it appears that cpz-1 have additional roles during morphogenesis. Deletion of cpz-1 coding sequence or inhibition of cpz-1 function by RNA interference also caused morphological defects in the head or tail region of larvae, improperly developed gonad in adult worms and embryonic lethality. The CPZ-1 native protein in these affected regions may have a role in the cuticular and the basement membrane extracellular matrix assembly process. The present findings have defined a critical role for cathepsin Z in nematode biology.
Multicenter retrospective study of endoscopic ultrasound‐guided biliary drainage for malignant biliary obstruction in Japan

Endoscopic ultrasound‐guided biliary drainage (EUS‐BD) is considered to be an effective salvage procedure for failed endoscopic retrograde cholangiopancreatography in patients with unresectable malignant biliary obstruction. The aim of this retrospective study was to evaluate the efficacy and feasibility of EUS‐BD.
EFL Teachers’ Conceptions of Learner Autonomy:Developing a Glocalized Model

Learner autonomy (henceforth LA) has become a buzz word in education in general and language education, in particular, for more than a decade now. Focusing on investigating Iranian EFL teachers’ conceptions of LA, the current study, taking a mixed method approach, attempted to illustrate how Iranian EFL teachers’ conceptions of leaner autonomy mapped out. To that end, 7 teachers, purposefully cluster sampled, were interviewed. After data saturation, the result of the interviews and the data gleaned from the literature were fed into the development of a questionnaire. The questionnaire, having being validated through a pilot study, was administered to 585 EFL teachers snowball-sampled, 2 of whom were, later on through negative case analysis, interviewed, and were required to provide the researchers with a narrative. Running a number of factor analyses, the researchers modeled the participants’ mindsets toward LA, which can be quite significant as it can have some theoretical and pedagogical implications, including, inter alia, situating LA promotion into the pedagogy of TEFL in Iran by running LA promotion workshops as well as developing a pool of LA promotion activities and software programs available to the stakeholders, especially the teachers.
Interim Reviews and the Association between Partner Rotations and Audit Fees

This paper considers whether the association between partner rotation and audit fees varies based on whether the partner is rotated before the interim review or annual report audit. Consistent with prior literature, there is some evidence of higher fees in the year of rotation, but we find this effect is driven by partner rotations that occur before the interim review, which are 7.14% higher on average. We argue that rotations before the annual report audit are less likely to be planned, and thus audit firms cannot pass on increased costs due to a weaker bargaining position. Supporting evidence is provided, as results only persist when client bargaining power is low, and in contrast there are lower fees for rotations that occur before the annual report audit when client bargaining power is high.
Degradation of Cdt1 during S Phase Is Skp2-independent and Is Required for Efficient Progression of Mammalian Cells through S Phase*

Previous reports have shown that the N terminus of Cdt1 is required for its degradation during S phase (Li, X., Zhao, Q., Liao, R., Sun, P., and Wu, X. (2003) J. Biol. Chem. 278, 30854–30858; Nishitani, H. , Lygerou, Z. , and Nishimoto, T. (2004) J. Biol. Chem. 279, 30807–30816). The stabilization was attributed to deletion of the cyclin binding motif (Cy motif), which is required for its phosphorylation by cyclin-dependent kinases. Phosphorylated Cdt1 is subsequently recognized by the F-box protein Skp2 and targeted for proteasomal mediated degradation. Using phosphopeptide mapping and mutagenesis studies, we found that threonine 29 within the N terminus of Cdt1 is phosphorylated by Cdk2 and required for interaction with Skp2. However, threonine 29 and the Cy motif are not necessary for proteolysis of Cdt1 during S phase. Mutants of Cdt1 that do not stably associate with Skp2 or cyclins are still degraded in S phase to the same extent as wild type Cdt1, indicating that other determinants within the N terminus of Cdt1 are required for degrading Cdt1. We localized the region necessary for Cdt1 degradation to the first 32 residues. Overexpression of stable forms of Cdt1 significantly delayed entry into and completion of S phase, suggesting that failure to degrade Cdt1 prevents normal progression through S phase. In contrast, Cdt1 mutants that fail to interact with Skp2 and cyclins progress through S phase with similar kinetics as wild type Cdt1 but stimulate the re-replication caused by overexpressing Cdt1. Therefore, a Skp2-independent pathway that requires the N-terminal 32 residues of Cdt1 is critical for the degradation of Cdt1 in S phase, and this degradation is necessary for the optimum progression of cells through S phase.
Evocative Advocates and Stirring Statesmen: Law, Politics, and the Weaponization of Imagery

Abstract This article shows how descriptive imagery can be used to hijack evolved psychological instincts and prejudice the judgment of others, particularly in the legal and political domains. By mimicking the cues that represented threats to our ancestors, those wishing to color the perception of others can subtly trigger the affective responses that evolved to help navigate ancestral threats. When this happens, logic may be unseated in favor of deep-seated instinctual responses, often to a problematic degree. In this way, lawyers, politicians, and activists, taking a page out of the playbook of novelists and other storytellers, can weaponize words, images, descriptions, and narratives to, often improperly, sway the opinions of others.
A Review of the Tribal Grazing Land Policy in Botswana

This paper examines the Tribal Grazing Land Policy (FGLP) which was developed in the 1970s to address the growing number of cattle in Botswana. The historir.al development of the TGLP is examined. The policy considerations which influenced the introduction of the TGLP are considered. and the impact that the introduction of the TGLP has had on the traditional utilization of grazing land in the country is assessed. It is argued that the TGLP has not been successfUl in preventing over-utilization of grazing land, and steps which can be taken by the government in addressing the management of grazing land in order to prevent environmental degradation, are discussed.
Regression for skewed biomarker outcomes subject to pooling

Epidemiological studies involving biomarkers are often hindered by prohibitively expensive laboratory tests. Strategically pooling specimens prior to performing these lab assays has been shown to effectively reduce cost with minimal information loss in a logistic regression setting. When the goal is to perform regression with a continuous biomarker as the outcome, regression analysis of pooled specimens may not be straightforward, particularly if the outcome is right‐skewed. In such cases, we demonstrate that a slight modification of a standard multiple linear regression model for poolwise data can provide valid and precise coefficient estimates when pools are formed by combining biospecimens from subjects with identical covariate values. When these x ‐homogeneous pools cannot be formed, we propose a Monte Carlo expectation maximization (MCEM) algorithm to compute maximum likelihood estimates (MLEs). Simulation studies demonstrate that these analytical methods provide essentially unbiased estimates of coefficient parameters as well as their standard errors when appropriate assumptions are met. Furthermore, we show how one can utilize the fully observed covariate data to inform the pooling strategy, yielding a high level of statistical efficiency at a fraction of the total lab cost.