Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Rho-kinase and Src protein tyrosine kinase inhibition on agonist-induced vasoconstriction of arteries and veins of the equine laminar dermis.

OBJECTIVE To determine the effects of inhibition of Rho-kinase or Src-family protein tyrosine kinases (srcPTK) on agonist-induced contractile responses in equine laminar arteries and veins. SAMPLE POPULATION Laminar arteries and veins obtained from 13 adult mixed-breed horses. PROCEDURES Laminar vessels were mounted on myographs and exposed to phenylephrine (PE), 5-hydroxytryptamine (5-HT), prostaglandin F(2) (PGF(2)), and endothelin-1 (ET-1) with or without the Rho-kinase inhibitor Y-27632 (10 microM), srcPTK inhibitor PP2 (10 microM), or a negative control analogue for PP2 (PP3; 10 microM). RESULTS Responses to PE were reduced by use of Y-27632 in laminar vessels (approx inhibition, 55%). However, Y-27632 reduced responses to 5-HT to a greater degree in veins than in arteries (approx inhibition of 55% and 35%, respectively). The Y-27632 also reduced responses of laminar veins to ET-1 by approximately 40% but had no effect on maximum responses of laminar arteries to ET-1, although a rightward shift in the concentration response curve was evident. Addition of PP2 reduced responses to PE, 5-HT, and PGF(2) in laminar veins by approximately 40%, 60%, and 65%, respectively, compared with responses after the addition of PP3; PP2 had no effect on responses to ET-1. In laminar arteries, PP2 reduced 5-HT-induced contractions by approximately 50% but did not affect responses to PE or ET-1. CONCLUSIONS AND CLINICAL RELEVANCE Results of the study were consistent with activation of Rho-kinase being important during agonist-induced constriction in laminar vessels, activation of srcPTK being an agonist-dependent event, and more prominent roles for Rhokinase and srcPTK in veins than in arteries.
Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y

The master regulator of MHC-II gene transcription, class II transactivator (CIITA), acts as a potent inhibitor of human T cell leukemia virus type 2 (HTLV-2) replication by blocking the activity of the viral Tax-2 transactivator. Here, we show that this inhibitory effect takes place at the nuclear level and maps to the N-terminal 1–321 region of CIITA, where we identified a minimal domain, from positions 64–144, that is strictly required to suppress Tax-2 function. Furthermore, we show that Tax-2 specifically cooperates with cAMP response element binding protein-binding protein (CBP) and p300, but not with p300/CBP-associated factor, to enhance transcription from the viral promoter. This finding represents a unique difference with respect to Tax-1, which uses all three coactivators to transactivate the human T cell leukemia virus type 1 LTR. Direct sequestering of CBP or p300 is not the primary mechanism by which CIITA causes suppression of Tax-2. Interestingly, we found that the transcription factor nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR transactivation. Thus, CIITA may inhibit Tax-2 function, at least in part, through nuclear factor Y. These findings demonstrate the dual defensive role of CIITA against pathogens: it increases the antigen-presenting function for viral determinants and suppresses HTLV-2 replication in infected cells.
Cis-trimethoxy resveratrol induces intrinsic apoptosis via prometaphase arrest and prolonged CDK1 activation pathway in human Jurkat T cells

Cis-trimethoxy resveratrol (cis-3M-RES) induced dose-dependent cytotoxicity and apoptotic DNA fragmentation in Jurkat T cell clones (JT/Neo); however, it induced only cytostasis in BCL-2-overexpressing cells (JT/BCL-2). Treatment with 0.25 μM cis-3M-RES induced G2/M arrest, BAK activation, Δψm loss, caspase-9 and caspase-3 activation, and poly (ADP-ribose) polymerase (PARP) cleavage in JT/Neo cells time-dependently but did not induce these events, except G2/M arrest, in JT/BCL-2 cells. Moreover, cis-3M-RES induced CDK1 activation, BCL-2 phosphorylation at Ser-70, MCL-1 phosphorylation at Ser-159/Thr-163, and BIM (BIMEL and BIML) phosphorylation irrespective of BCL-2 overexpression. Enforced G1/S arrest by using a G1/S blocker aphidicolin completely inhibited cis-3M-RES-induced apoptotic events. Cis-3M-RES-induced phosphorylation of BCL-2 family proteins and mitochondrial apoptotic events were suppressed by a validated CDK1 inhibitor RO3306. Immunofluorescence microscopy showed that cis-3M-RES induced mitotic spindle defects and prometaphase arrest. The rate of intracellular polymeric tubulin to monomeric tubulin decreased markedly by cis-3M-RES (0.1-1.0 μM). Wild-type Jurkat clone A3, FADD-deficient Jurkat clone I2.1, and caspase-8-deficient Jurkat clone I9.2 exhibited similar susceptibilities to the cytotoxicity of cis-3M-RES, excluding contribution of the extrinsic death receptor-dependent pathway to the apoptosis. IC50 values of cis-3M-RES against Jurkat E6.1, U937, HL-60, and HeLa cells were 0.07-0.17 μM, whereas those against unstimulated human peripheral T cells and phytohaemagglutinin A-stimulated peripheral T cells were >10.0 and 0.23 μM, respectively. These results indicate that the antitumor activity of cis-3M-RES is mediated by microtubule damage, and subsequent prometaphase arrest and prolonged CDK1 activation that cause BAK-mediated mitochondrial apoptosis, and suggest that cis-3M-RES is a promising agent to treat leukemia.
A Preliminary Assessment of Outsider Assistance as a Knowledge Resource: The Longer-Term Impact of New Venture Counseling

Using resource-based theory to explain why outside assistance might influence new venture performance, we track the longer-term performance of two samples of entrepreneurs who received SBDC counseling and subsequently started businesses. Results indicate that the ventures had higher than expected rates of survival, growth, and innovation, suggesting that outsider assistance during the early stages of a venture's development can influence its subsequent development. Public policy implications of the SBDC's counseling strategy are discussed.
Innate PI3K p110δ Regulates Th1/Th17 Development and Microbiota-Dependent Colitis

The p110δ subunit of class IA PI3K modulates signaling in innate immune cells. We previously demonstrated that mice harboring a kinase-dead p110δ subunit (p110δKD) develop spontaneous colitis. Macrophages contributed to the Th1/Th17 cytokine bias in p110δKD mice through increased IL-12 and IL-23 expression. In this study, we show that the enteric microbiota is required for colitis development in germfree p110δKD mice. Colonic tissue and macrophages from p110δKD mice produce significantly less IL-10 compared with wild-type mice. p110δKD APCs cocultured with naive CD4+ Ag-specific T cells also produce significantly less IL-10 and induce more IFN-γ– and IL-17A–producing CD4+ T cells compared with wild-type APCs. Illustrating the importance of APC–T cell interactions in colitis pathogenesis in vivo, Rag1−/−/p110δKD mice develop mild colonic inflammation and produced more colonic IL-12p40 compared with Rag1−/− mice. However, CD4+CD45RBhigh/low T cell Rag1−/−/p110δKD recipient mice develop severe colitis with increased percentages of IFN-γ– and IL-17A–producing lamina propria CD3+CD4+ T cells compared with Rag1−/− recipient mice. Intestinal tissue samples from patients with Crohn’s disease reveal significantly lower expression of PIK3CD compared with intestinal samples from non–inflammatory bowel disease control subjects (p < 0.05). PIK3CD expression inversely correlates with the ratio of IL12B:IL10 expression. In conclusion, the PI3K subunit p110δ controls homeostatic APC–T cell interactions by altering the balance between IL-10 and IL-12/23. Defects in p110δ expression and/or function may underlie the pathogenesis of human inflammatory bowel disease and lead to new therapeutic strategies.
Havispora longyearbyenensis gen. et sp. nov.: an arctic marine fungus from Svalbard, Norway

Information on the diversity and ecology of arctic marine fungi is lacking. During a short visit to Longyearbyen (78°13′N 15°33′E), Svalbard, Norway, a new marine fungus growing on driftwood collected at the shore was encountered. This taxon belongs to the Halosphaeriales (Ascomycota), a fungal order of mostly marine species. Havispora longyearbyenensis gen. et sp. nov. is morphologically similar to Nautosphaeria and Nereiospora, all with tufts of appendages at polar and equatorial positions of the ascospore but differing in color and septation of the ascospore and morphology and ontogeny of the ascospore appendage.
Perceptions of Postsecondary Education in a Northern Ontario Community

The Assembly of First Nations has maintained their emphasis on the importance of postsecondary education for strengthening self-determination in First Nation Communities. From my position as ally to an Anishnawbe community in Northern Ontario, I explored the relationships of community members to postsecondary education. Ten participants (including a teacher at the school and a band councilor) shared with me their experiences and their knowledge about the Community and its school system. The stories which emerged from the data were arranged into mindmaps, which allowed the connections between ideas to emerge. Through the data, it became clear that in Northern Ontario, the transition from the on-reserve school system at any level is very difficult for Community members, and is exacerbated by family violence and tensions and a perception of lower quality teaching and resources in the community schools. From their stories, it was clear to me that the decisions participants were making about where to go to school and what to pursue were based on what degree of transition they thought they could handle. Participants also chose more college programs when first entering postsecondary education, and attended the college in the nearby town most frequently.
MiCOMP: Mitigating the Compiler Phase-Ordering Problem Using Optimization Sub-Sequences and Machine Learning

Recent compilers offer a vast number of multilayered optimizations targeting different code segments of an application. Choosing among these optimizations can significantly impact the performance of the code being optimized. The selection of the right set of compiler optimizations for a particular code segment is a very hard problem, but finding the best ordering of these optimizations adds further complexity. Finding the best ordering represents a long standing problem in compilation research, named the phase-ordering problem. The traditional approach of constructing compiler heuristics to solve this problem simply cannot cope with the enormous complexity of choosing the right ordering of optimizations for every code segment in an application. This article proposes an automatic optimization framework we call MiCOMP, which Mi tigates the Com piler P hase-ordering problem. We perform phase ordering of the optimizations in LLVM’s highest optimization level using optimization sub-sequences and machine learning. The idea is to cluster the optimization passes of LLVM’s O3 setting into different clusters to predict the speedup of a complete sequence of all the optimization clusters instead of having to deal with the ordering of more than 60 different individual optimizations. The predictive model uses (1) dynamic features, (2) an encoded version of the compiler sequence, and (3) an exploration heuristic to tackle the problem. Experimental results using the LLVM compiler framework and the Cbench suite show the effectiveness of the proposed clustering and encoding techniques to application-based reordering of passes, while using a number of predictive models. We perform statistical analysis on the results and compare against (1) random iterative compilation, (2) standard optimization levels, and (3) two recent prediction approaches. We show that MiCOMP’s iterative compilation using its sub-sequences can reach an average performance speedup of 1.31 (up to 1.51). Additionally, we demonstrate that MiCOMP’s prediction model outperforms the -O1, -O2, and -O3 optimization levels within using just a few predictions and reduces the prediction error rate down to only 5%. Overall, it achieves 90% of the available speedup by exploring less than 0.001% of the optimization space.
The Habit Habit

I survey the macro-finance literature related to "By Force of Habit. " I show how many models reflect the same rough ideas, each with strengths and weaknesses. I outline how such models may illuminate macroeconomics, by putting time-varying risk aversion, risk-bearing capacity, and precautionary savings at the center of recessions, rather than constraints on flows as in old Keynesian models, or intertemporal substitution and riskfree rate variation as in new Keynesian models. Throughout I emphasize unsolved questions and profitable avenues for research.
Trade liberalization, urban-rural remittances and income inequalities in Senegal: lessons from a CGE analysis

This paper aims at assessing how domestic urban-rural remittances can mitigate macroeconomic shocks in a developing country. When trade liberalization occurs, it may affect the national income structure and increase regional poverty, especially in a vulnerable economy where the volatility of prices and incomes are unavoidable. As underlined by Cox (1990, 2002), Cox and Jimenez (1998) and Morduch (1995), private transfers can significantly help households deal with exogenous risk and similar studies also find evidence of an efficient risk sharing between the poorest households thanks to private cash exchange (Deaton 1997, Townsend 1995, Jalan and Ravallion 1997). In order to deepen the theoretical foundations of micro-economic determinants of remittances, we design a single-country computable general equilibrium (CGE) to capture all the redistributive channels implied by domestic transfers. We then calibrate our CGE model on a recent social accounting matrix of Senegal dated from 2006. We base our work on three important Senegalese household surveys: ESAM I (1996), ESAM II (2002) and ESPS (2005) which provide specific data on disaggregated households such as: spending structures, income structures, and domestic transfers. To assess the mitigating impact of remittances on economic shocks we face two significant challenges: the theoretical ambiguity of remittance decision models and the credibility of transfer data. Identifying the determinants of remittances is puzzling and controversial within the theoretical literature. Numerous theoretical models have been developed based successively on “altruistic motive” (Becker, 1974; Stark, 1985) and “mutual exchange strategy” (Cox, 1987; Cox, Eiser et Jimenez 1998), the latter being especially relevant in the case of intergenerational transfers (Laferrere and Wolff, 2001). Other common models rely on “strategic game” analysis (Stark and Wang, 2002), “insurance strategy”, “moral hazard” (Stark and Levhari , 1982;.
Databases for research on recognition of handwritten characters of Indian scripts

Three image databases of handwritten isolated numerals of three different Indian scripts namely Devnagari, Bangla and Oriya are described in this paper. Grayscale images of 22556 Devnagari numerals written by 1049 persons, 12938 Bangla numerals written by 556 persons and 5970 Oriya numerals written by 356 persons form the respective databases. These images were scanned from three different kinds of handwritten documents - postal mails, job application form and another set of forms specially designed by the collectors for the purpose. The only restriction imposed on the writers is to write each numeral within a rectangular box. These databases are free from the limitations that they are neither developed in laboratory environments nor they are non-uniformly distributed over different classes. Also, for comparison purposes, each database has been properly divided into respective training and test sets.
Buren of Hospital Admissions for Cervical Cancer in Spain During 1999-2002

Population-based retrospective epidemiological study to estimate the burden of hospitalizations by cervical cancer in Spain. It was conducted by using hospital discharge data from the national surveillance system for hospital data, Conjunto Mínimo Básico de Datos (CMBD). Records of all patients admitted to hospital with a diagnosis of malignant neoplasm of the cervix (ICD-9-MC codes 180.0-180.9) or carcinoma in situ of cervix (ICD-9-MC code 233.1) during a 4-year period (1999-2002), were selected. An annual average of 4,151 hospitalizations with a primary or secondary diagnosis of cervical cancer and 2,761 hospitalizations due to carcinoma in situ were identified. Annually there were 25.5 and 17.0 hospitalizations by cervical cancer and carcinoma in situ per 100,000 women ≥20 years of age, respectively. Hospitalization rate by cervical cancer and carcinoma in situ peaks in women between 45 and 59 years of age (39.4 admissions per 100,000 women) and 30 to 44 years of age (32.2 per 100,000 women), respectively. The mean cost of a hospitalization by cervical cancer and carcinoma in situ was 3,098€ and 2,192€, respectively. The estimated annual cost of hospitalizations for cervical cancer and carcinoma in situ in Spain was 19 million €.
Following the Rules: Why Small Groups of Tamarins Do Not Reconcile Conflicts

Reconciliation is the post-conflict friendly reunion between opponents. A series of conditions and rules in order for reconciliation to take place has been recently proposed. One critical condition is that the relationship between opponents must be disrupted. We tested this condition using post-conflict and matched-control observations on 4 small groups of tamarins (Saguinus labiatus). Our previous lack of evidence for reconciliation was confirmed. No post-conflict relationship damage was therefore expected. We found evidence that relationships were disturbed following conflicts over food but, as in other primates, no evidence for reconciliation following such conflicts was found. For non-food-related conflicts there was no evidence that relationships were disturbed, as opponents were in close proximity to each other and resumed the exact same activity as frequently in the post-conflict observations as they did in the matched-control observations. We conclude that ‘everyday’ aggression may not disrupt the relationships among individuals from the same family group and therefore reconciliation is not needed.
Bacterial adhesins and host factors: role in the development and outcome of Escherichia coli bacteremia.

To assess the contributions of bacterial virulence factors and defects in host defense to Escherichia coli bacteremia, we examined isolates and available medical records from 169 episodes at two hospitals. Adhesins and hemolysin virulence factors were documented in 84% of bacteremia-associated isolates originating from the urinary and respiratory tracts and in 50% of such isolates originating from other extraurinary foci. Of the evaluable episodes of bacteremia involving 35 adhesin-negative isolates, 21 (60%) were in patients who had mucocutaneous defects at the primary site of infection, and another 13 (37%) were in patients who had comorbid systemic diseases (i.e., chronic renal failure or alcoholism) associated with impaired leukocyte function. In contrast, of 93 evaluable episodes with adhesin-positive isolates, 22 (24%) were in patients who had none of these host conditions (P = .008). Overall, of evaluable episodes of bacteremia involving 128 isolates, 71 (55%) had both bacterial virulence-associated and host-related risk factors. Mortality was related to the severity of comorbid illnesses and was not affected by the presence of the bacterial virulence factors assessed.
Phenolic metabolites of anthocyanins following a dietary intervention study in post-menopausal women.

SCOPE Numerous studies feeding anthocyanin-rich foods report limited bioavailability of the parent anthocyanins. The present study explores the identity and concentration of the phenolic metabolites of anthocyanins in humans. METHODS AND RESULTS Anthocyanin metabolites were quantified in samples collected from a previously conducted 12-wk elderberry intervention study in healthy post-menopausal women. Individual 1-, 2- and 3-h post-bolus urine samples and pooled plasma samples following acute (single bolus) and chronic (12-wk supplementation) anthocyanin consumption (500 mg/day) were analysed using HPLC-ESI-MS/MS. Twenty-eight anthocyanin metabolites were identified in urine and 21 in plasma (including sulfates of vanillic, protocatechuic and benzoic acid). Phenolic metabolites reached peak concentrations of 1237 nM in plasma, while anthocyanin conjugates only reached concentrations of 34 nM. Similarly, in urine, phenolic metabolites were detected at concentrations of 33,185 ± 2549 nM/mM creatinine, while anthocyanin conjugates reached concentrations of 548 ± 219 nM/mM creatinine. There was no evidence that chronic exposure had any impact on either the profile or quantity of metabolites recovered relative to acute exposure. CONCLUSION An extensive range of phenolic metabolites of anthocyanin was identified following elderberry consumption in humans, including 11 novel metabolites, which were identified at much higher concentrations than their parent compounds.
Identification of roles for H264, H306, H439, and H635 in acid-dependent lipoprotein release by the LDL receptor[S]

Lipoproteins internalized by the LDL receptor (LDLR) are released from this receptor in endosomes through a process that involves acid-dependent conformational changes in the receptor ectodomain. How acidic pH promotes this release process is not well understood. Here, we assessed roles for six histidine residues for which either genetic or structural data suggested a possible role in the acid-responsiveness of the LDLR. Using assays that measured conformational change, acid-dependent lipoprotein release, LDLR recycling, and net lipoprotein uptake, we show that H635 plays important roles in acid-dependent conformational change and lipoprotein release, while H264, H306, and H439 play ancillary roles in the response of the LDLR to acidic pH.
Increases in weight of growth hormone‐deficient and immunodeficient (lit/scid) dwarf mice after grafting of hGH‐ secreting, primary human keratinocytes

Primary human keratinocytes, stably transduced with the human growth hormone (hGH) gene (under control of the retroviral LTR promoter) and selected via geneticin secreted as much as 7 μg hGH/106 cells/day. Their grafting onto immunodeficient dwarf mice (lit/scid) led to hGH levels in the circulation that did not go below 0.2‐0.3 ng/ml during a 12 day period (peak value, 1.5 ng/ml at 4 h). This phenomenon was associated with a body weight increase of the grafted animals (0.060 g/animal/day) significantly higher (P<0.01) than that of controls (0.023 g/animal/day). This is the first report describing successful utilization of immunodeficient dwarf mice (lit/scid) in keratinocyte‐based hGH gene therapy.