Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of hypothermia as a model of 5-hydroxytryptamine1A receptor-mediated activity in the rat: a pharmacological characterization of the actions of novel agonists and antagonists.

In this study, we examined the localization of the 5-hydroxytryptamine (5-HT)1A receptors mediating hypothermia in the rat, evaluated the pharmacological specificity of this response and examined the influence of a series of novel 5-HT1A receptor ligands upon core temperature. Administered s.c. , 8-hydroxy-(2-di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), an agonist at both pre- and postsynaptic 5-HT1A receptors, elicited pronounced hypothermia. In contrast, BMY 7378, which shows low efficacy at postsynaptic 5-HT1A receptors but high efficacy at presynaptic 5-HT1A receptors, elicited only mild hypothermia. Similarly, 8-OH-DPAT was more efficacious than BMY 7378 in eliciting corticosterone secretion, a response mediated by postsynaptic 5-HT1A receptors, whereas BMY 7378 was as efficacious as 8-OH-DPAT in inhibiting striatal accumulation of 5-hydroxytryptophan, a response mediated by presynaptic 5-HT1A receptors. These data suggest, by analogy, that postsynaptic 5-HT1A receptors mediate hypothermia, an interpretation supported by the observation that destruction of central 5-HT neurons with 5,7-dihydroxytryptamine failed to reduce 8-OH-DPAT-induced hypothermia (DIH). Agonists at 5-HT1B, 5-HT1C, 5-HT2 and/or 5-HT3 receptors did not elicit hypothermia, and drugs releasing 5-HT elicited hyperthermia. In contrast, DIH was fully mimicked by the novel 5-HT1A receptors agonists, eltoprazine, WY 48,723, MDL 72832, tandospirone, S 14671, S 14506 and WY 50,324, whereas the novel partial agonist, zalospirone, was less efficacious. DIH was blocked by (-)-alprenolol, (+/-)-pindolol and the novel beta-blocker, (-)-tertatolol, which also has high affinity for 5-HT1A receptors; in distinction, betaxolol and ICI 118,551, antagonists at beta-1 and beta-2 adrenoceptors, respectively, were inactive. Spiperone, NAN-190 and BMY 7378 also inhibited DIH whereas ritanserin, SCH 39166, raclopride and prazosin, antagonists at 5-HT2 receptors, D1 and D2 dopamine receptors and alpha-1 adrenoceptors, respectively, were inactive. The novel 5-HT1A antagonists, WAY 100,135, MDL 73005 EF and (very potently) SDZ 216-525 all blocked DIH. Potency for induction of hypothermia and inhibition of DIH correlated well with affinity for 5-HT1A binding sites. In conclusion, hypothermia is a highly specific and sensitive response to activation of postsynaptic 5-HT1A receptors. Furthermore, DIH is inhibited by their selective blockade. At postsynaptic 5-HT1A receptors mediating hypothermia, eltoprazine, WY 48,723, MDL 72832 and tandospirone are agonists, zalospirone is a partial agonist and (-)-tertatolol, WAY 100,135, MDL 73005 EF and SDZ 216-525 are antagonists.
IL-4 and IFN-γ induced by human immunodeficiency virus vaccine in a schistosome infection model

The co-infection of HIV and helminth parasites, such as Schistosoma spp, has increased in sub-Saharan Africa. Many HIV vaccine candidate studies have been completed or are in ongoing clinical trials, but it is not clear how HIV vaccines might affect the course of schistosome infections. In this study, we immunized S. mansoni-infected mice with an efficient DNA vaccine that included HIV gag. Using this model, we found that Th2 cytokines, such as IL-4 and IL-13, were highly induced after schistosome infection. Treatment of infected mice with the HIV DNA vaccine resulted in a significant attenuation of this rise in IL-13 expression and an increase in expression of the Th1 cytokine, TNF-α. However, vaccine administration did not significantly influence the expression of IL-4, or IFN-γ, and did not affect T cell proliferative capacity. Interestingly, the IL-4+IFN-γ+ phenotype appears in schistosome-infected mice that received HIV vaccination, and is associated with the expression of transcription factors GATA3+T-bet+ in these mice. These studies indicate that DNA vaccination can have an impact on ongoing chronic infection.
On the Hamilton-Jacobi-Bellman Equation for an Optimal Consumption Problem: II. Verification Theorem

We consider an optimal consumption problem where an investor tries to maximize the infinite horizon expected discounted hyperbolic absolute risk aversion utility of consumption. We treat a stochastic factor model such that the mean returns of risky assets depend on underlying economic factors formulated as the solution of a stochastic differential equation. Using a dynamic programming principle, we derive the Hamilton--Jacobi--Bellman (HJB) equation and study its solutions. In part I, we prove the existence of a classical solution for HJB equation under suitable conditions. In part II, we consider the verification theorem stating a candidate of optimal strategy derived from a solution of HJB equation is indeed optimal. We prove the result under two sets of conditions. One is a linear model, and one is a nonlinear model. In both cases, the HJB equations do not have analytical solutions.
Carcinogenic tobacco-specific N-nitrosamines in US cigarettes: three decades of remarkable neglect by the tobacco industry

Background Modification of tobacco curing methods and other changes in cigarette manufacturing techniques could substantially reduce the levels of tobacco-specific nitrosamines (TSNA), a group of potent carcinogens, in cigarette smoke. In 1999, two major US cigarette manufacturers stated their intent to move towards using tobaccos low in TSNA. There is no information available on current TSNA levels in tobacco of various cigarettes available in the US, particularly in the newer varieties introduced over the past decade. Methods Seventeen brands of cigarettes were purchased in April of 2010 from retail stores in Minnesota. TSNA levels were measured in the tobacco filler and smoke of these cigarettes. Results In all brands, the sum of two potent carcinogenic TSNA - 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N'-nitrosonornicotine - in cigarette filler averaged 2.54 (±1.05) μg/g tobacco. This value is virtually identical to the sum of these two carcinogens reported for the tobacco of a US filtered cigarette in 1979. TSNA levels in smoke positively correlated with those in tobacco filler of the same cigarettes. Conclusion We found no indication that any meaningful attempt was made to reduce or at least control TSNA levels in the new varieties of the popular brands Marlboro and Camel introduced over the last decade. In light of the recently granted regulatory authority to the FDA over tobacco products, regulation of TSNA levels in cigarette tobacco should be strongly considered to reduce the levels of these potent carcinogens in cigarette smoke.
Development of c-MET pathway inhibitors

Introduction: The aberrantly upregulated c-mesenchymal-epithelia transition factor (c-MET) signaling pathway has been considered to be an attractive target for cancer intervention owing to the important roles it plays in tumor formation, progression, metastasis, angiogenesis and drug resistance. Based on the historical preclinical evidence, a number of c-MET pathway targeted agents are being developed in the clinic, and recent clinical data have begun to provide some insight into which tumor types and patient populations a c-MET pathway inhibitor may be beneficial for. Areas covered: Through reviewing recent publications in the literature and information disclosed in other public forums, we describe the current understanding of c-MET biology in human malignancies and discuss the latest progress in the development of c-MET pathway inhibitors for cancer treatment. Expert opinion: The c-MET pathway inhibitors currently being evaluated in the clinic have demonstrated compelling evidence of clinical activity in different cancer types and may provide significant therapeutic opportunities. The challenges, however, are to identify the tumor types and patient populations that benefit most, and find the most effective combinations of therapies while minimizing potential toxicity.
Federalism: Prospects for the Philippines

The paper aims to consider potential benefits of federalism to the Philippines within the context of two major development constraints, namely, weak economic growth and poverty. The governance and institutional aspects of these development constraints point to how continued centralization of fiscal powers and the resulting common resource pool problem have weakened government capacity to bring about inclusive development. Critical to the success of decentralization and fiscal federalism efforts is a strong middle level government, which is absent in the current setup. The establishment of regional governments, its powers and functions and its relation to the national government and local governments, is the most crucial element in the shift from a unitary to a federal form of government. It is recommended that the proposed shift be carried out in two stages. The first stage will deal with assignment of competencies and the relationship between the national government and regional government, with the power to organize the local governments being one of the competencies exclusively assigned to the latter. The second stage will tackle the regional government and its local governments. Each regional government should come up with its own regional constitution or organic act that could be drafted through a regional constitutional convention.
Drug Resistance and R Plasmids in Salmonella typhi Isolated in Korea

A total of 949 strains of Salmonella typhi isolated in Korea from 1968 to 1975 were tested for drug resistance and distribution of R plasmids. Resistance was mostly restricted to streptomycin (SM) and sulfisomidine (SA), singly or in combination, at a low degree. A small number of strains (1.5%) were resistant to four or more drugs: chloramphenicol (CM), tetracycline (TC), SM, SA, ampicillin (AP), and kanamycin (KM). No strain was resistant to nalidixic acid or to a 1:20 mixture of trimethoprim and sulfamethoxazole. Nor was there any strain singly resistant to CM, TC, AP, or KM. Transfer experiments of multiple-drug resistance to Escherichia coli ML1410 showed that all the strains resistant to four or more drugs carried R plasmids, whereas those weakly resistant to three or less drugs did not. The quadruply resistant strains carried one R plasmid determining CM, TC, SM, and SA resistance, and sextuply resistant ones carried two plasmids, one determining CM, TC, SM, and SA resistance and the other determining AP and KM resistance. One strain carrying a plasmid determining AP and KM resistance was also found. The transfer frequency of CM, TC, SM, and SA resistance was much higher than that of AP and KM resistance. The resistance of S. typhi was more efficiently transferred to E. coli at 25°C than at 37°C.
Shadows of an Absent Partner

Background: Spf1 belongs to the least characterized group of P5-ATPases. Results: GFP-Spf1 hydrolyzes ATP and forms a phosphoenzyme that rapidly decays in the presence of ADP. Conclusion: The Spf1 performs well the E1 steps of the reaction cycle, but progression to the E2 forms is slow. Significance: The study extends the understanding of the catalytic mechanism of P5-ATPases. The P5-ATPases are important components of eukaryotic cells. They have been shown to influence protein biogenesis, folding, and transport. The knowledge of their biochemical properties is, however, limited, and the transported ions are still unknown. We expressed in Saccharomyces cerevisiae the yeast Spf1 P5A-ATPase containing the GFP fused at the N-terminal end. The GFP-Spf1 protein was localized in the yeast endoplasmic reticulum. Purified preparations of GFP-Spf1 hydrolyzed ATP at a rate of ∼0.3–1 μmol of Pi/mg/min and formed a phosphoenzyme in a simple reaction medium containing no added metal ions except Mg2+. No significant differences were found between the ATPase activity of GFP-Spf1 and recombinant Spf1. Omission of protease inhibitors from the purification buffers resulted in a high level of endogenous proteolysis at the C-terminal portion of the GFP-Spf1 molecule that abolished phosphoenzyme formation. The Mg2+ dependence of the GFP-Spf1 ATPase was similar to that of other P-ATPases where Mg2+ acts as a cofactor. The addition of Mn2+ to the reaction medium decreased the ATPase activity. The enzyme manifested optimal activity at a near neutral pH. When chased by the addition of cold ATP, 90% of the phosphoenzyme remained stable after 5 s. In contrast, the phosphoenzyme rapidly decayed to less than 20% when chased for 3 s by the addition of ADP. The greater effect of ADP accelerating the disappearance of EP suggests that GFP-Spf1 accumulated the E1∼P phosphoenzyme. This behavior may reflect a limiting countertransported substrate needed to promote turnover or a missing regulatory factor.
Opsonin-independent phagocytosis of group B streptococci: role of complement receptor type three

The role of complement receptor type 3 (CR3) in nonopsonic recognition of group B streptococci (GBS) by macrophages was investigated. Monoclonal anti-CR3 (anti-Mac-1) inhibited phagocytosis of GBS strains by as much as 50% in serum-free cultures of both mouse peritoneal macrophages and the macrophage cell line PU5-1.8. GBS uptake was unaffected by the presence of anti-C3 or salicylhydroxamate, an inhibitor of the covalent binding reaction of C3. Soluble antibodies to LFA-1 or to the common beta-chain (CD18) of the LFA-1/CR3/p150,95 family of cell adhesion molecules did not inhibit GBS uptake. Down-modulation of surface Mac-1 on macrophages following adherence to anti-Mac-1- or anti-CD18-coated surfaces also inhibited uptake of GBS. Further evidence for GBS interaction with CR3 was demonstrated by reduction of EC3bi rosette formation in macrophages adherent to GBS-coated plates. These studies suggest that GBS can interact with macrophage CR3, promoting phagocytosis in a C3-independent fashion. In the absence of specific immunity in neonates, this recognition mechanism may be a significant virulence determinant for GBS which poorly activate the alternate complement pathway.
The cytogenetic scenario of chronic myeloid leukemia.

The Philadelphia chromosome (Ph), i.e., the reciprocal translocation t(9;22)(q34;q11), is found with great specificity in bone marrow cells from patients with chronic myeloid leukemia (CML). Variant Ph-producing translocations, seen in 5-10% of all patients, are all complex and involve the same molecular rearrangement as the regular t(9;22). Patients with classic and variant Ph-producing translocations are clinically and hematologically identical, and as a group differ from Ph-negative CML patients. In all patient groups, the occurrence of additional chromosome changes is an ominous sign indicating that disease progression is imminent. The chromosome changes occurring in excess of the Ph in CML are clearly nonrandom and two pathways of cytogenetic evolution may be distinguished. Major route changes comprise trisomy 8, i(17q), trisomy 19, and an extra Ph; totally, 71% of Ph-positive CML patients have at least one of these four major route changes. Six minor route changes, including five numerical abnormalities (-7, -17, +17, +21, and -Y) but also one structural aberration, t(3;21) (q26;q22), have been identified. At least one of these changes is found in 15% of all Ph-positive CML cases. Altogether, the four major route aberrations and the six minor route changes are present as part of the clonal evolution in 86% of CML with cytogenetic abnormalities in addition to the Ph chromosome.
Intermediários Financeiros e Política de Crédito em um Modelo DSGE para o Brasil

Esse trabalho tem o objetivo de mostrar como a incorporacao de intermediarios financeiros num modelo DSGE influenciam na analise do ciclo economico, bem como uma politica de credito pode ser utilizada para mitigar os choques no mercado de credito sobre a atividade. As simulacoes mostraram que o modelo conseguiu reproduzir o comportamento esperado para um modelo com friccoes financeiras, quais sejam: maior amplificacao e persistencia nos ciclos economicos. Politica de credito mostrou-se efetiva para mitigar os efeitos recessivos de uma crise financeira que atinja a cotacao dos ativos privados ou o patrimonio das instituicoes financeiras.
In vivo measurement of fascicle length and pennation of the human anconeus muscle at several elbow joint angles

Ultrasound imaging has facilitated the reliable measure of the architectural variables fascicle length (LF) and pennation angle (PA), at rest and during static and dynamic contractions in many human skeletal muscles in vivo. Despite its small size and very modest contribution to elbow extension torque, the anconeus muscle has proven a useful model for the study of neuromuscular function in health and disease. Recent single motor unit (MU) studies in the anconeus have reported discrete and identifiable individual trains of MU potentials from intramuscular electromyography (EMG) recordings during dynamic elbow extensions. It is unknown whether the anconeus has unique architectural features related to alterations in LF and PA throughout the elbow joint range of motion that may help explain these high‐quality recordings. Previous anatomical studies have investigated this muscle in cadavers and at mainly one elbow joint angle. The purpose of this study was to measure in vivo PA and LF of the anconeus muscle in a relaxed state at different degrees of elbow flexion using ultrasonography. Ultrasound images were collected from 10 healthy males (25 ± 3 years) at 135°, 120°, 90°, 45°, and 0° of elbow flexion. Average values of LF decreased by 6 mm (10%), 6 mm (12%), and 4 mm (9%) from 135–120°, 120–90°, and 90–45° of elbow flexion, respectively, whereas average PA values increased by 1° (9%), 1° (8%), and 2° (14%) from 135–120°, 120–90°, and 45–0°, respectively. The results indicate that anconeus muscle architecture is dynamic, undergoing moderate changes with elbow joint excursion that are similar to other limb muscles reported elsewhere. The data obtained here are more comprehensive and representative of architectural changes at various elbow joint positions than those data reported in cadaveric studies. Furthermore, the results of this study indicate that despite experiencing similar relative changes in muscle architecture to other skeletal muscles about the elbow joint, the minimal absolute changes in LF of the anconeus likely contribute to the clarity of intramuscular EMG previously reported in this muscle.
[Vascular risk factors and cognitive impairment of patients with magnetic resonance imaging-defined subcortical ischemic depression].

OBJECTIVE To explore the vascular risk factors and neuropsychological profiles of patients with magnetic resonance imaging (MRI)-defined subcortical ischemic depression (SID). METHODS Thirty-five SID patients, 37 patients with subcortical ischemic vascular disease without depression (SIVD) and 40 normal controls (NC) participated in this case-control study. The SID and SIVD groups were recruited from the Department of Neurology, First Affiliated Hospital, Anhui Medical University between October 2010 and September 2011. And the NC group came from Medical Center, First Affiliated Hospital of Anhui Medical University over the same period. The vascular risk factors of all participants were assessed by the Framingham scale. Depression symptoms were assessed by the geriatric depression scale (GDS) and Hamilton depression scale (HAMD) while cognitive functions by the mini-mental state examination (MMSE) and Montreal cognitive clock drawing task (CDT). RESULTS Both the SID (12.3 ± 4.7) and SIVD (13.5 ± 3.4) groups showed significantly higher Framingham scores than the NC group (8.6 ± 1.8) (F = 20.850, P = 0.000). Compared with the NC group (28.3 ± 1.8; 23.1 ± 3.4; 8.0 ± 1.8), the MMSE, MoCA and CDT scores were significantly lower in the SID (26.7 ± 2.5; 20.0 ± 4.0; 2.0 ± 2.7) and SIVD (26.8 ± 1.9; 20.7 ± 3.0; 6.1 ± 2.1) groups (P < 0.05). There were significantly lower CAMCOG-C scores in the SID (82.7 ± 9.0) and SIVD (86.2 ± 6.9) groups versus the NC group (92.3 ± 6.2) (P < 0.05) and similarly in the SID group versus the SIVD group (P < 0.05). Among the subtests of CAMCOG-C, the orientation, language and memory scores in both SID (9.0 ± 1.4; 24.7 ± 4.0; 19.5 ± 3.4) and SIVD (9.4 ± 0.9; 25.5 ± 2.1; 20.3 ± 2.3) groups were significantly lower than those in the NC group (9.9 ± 0.4; 27.4 ± 1.9; 22.1 ± 2.4) (P < 0.05); the praxis scores in the SID group (9.4 ± 1.9) were significantly lower than those in the NC group (10.4 ± 1.5) (P < 0.05). And the thinking and perception scores in the SID group (5.4 ± 1.7; 6.3 ± 1.4) were significantly lower than those in the SIVD (6.2 ± 1.3; 7.0 ± 1.4) and NC (6.6 ± 1.3; 7.2 ± 1.4) groups. In the SID group, no significant correlation was found between the Framingham scores and neuropsychological assessments. There were a negative correlation between the GDS, HAMD scores and MMSE, MoCA, CAMCOG-C and CDT scores (P < 0.05). CONCLUSION The SID patients demonstrate multiple neuropsychological deficits, especially in thinking, perception and praxis. No significant correlation between vascular risk factors and depression symptoms is found in SID patients.
Adverse events associated with methicillin-resistant Staphylococcus aureus in a nursing home.

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) generates concern in nursing homes. Restrictive isolation precautions may be applied for indefinite periods. Adverse events driving these concerns include transmission and infection. METHODS The 721-bed Wisconsin Veterans Home in King performs approximately 645 cultures annually. The site, severity, and number of MRSA infections were determined for 69 months. Pulsed-field gel electrophoresis was performed on all initial isolates, followed by a statistical cluster analysis looking for evidence of transmission. RESULTS Sixty-seven MRSA infections were identified (1.6 per 100 residents per year); many were polymicrobial, and it was difficult to determine the proportionate role of MRSA in morbidity or mortality. There was an episode of rapidly fatal MRSA septicemia in which empiric antibiotic therapy was ineffective. Twenty-one genetic strains were encountered. Statistical analysis identified 13 clusters of genetically identical strains clustered in time and space (P<.05). CONCLUSIONS Infections with MRSA were identified at relatively low rates; however, the etiology of many serious nursing home infections is not determined, especially pneumonia. Statistical analysis revealed clustering and evidence of transmission. Nursing home practitioners should consider MRSA when applying empiric treatment to serious infections. We recommend a program including (1) judicious use of antibiotics, including topical agents, to reduce selection of resistant organisms; (2) obtaining and tracking cultures of infectious secretions to diagnose MRSA infections and focus antibiotic therapy; (3) universal standard secretion precautions because any resident could be a carrier; and (4) a detailed assessment and care plan for the carrier that maximizes containment of secretions and independence in activities. However, basic hygiene cannot be maintained in communal areas by some residents without restriction of activities of daily living.