Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and pharmacodynamics of intravenous romifidine and propranolol administered alone or in combination for equine sedation.

OBJECTIVE Propranolol has been suggested for anxiolysis in horses, but its sedation efficacy and side effects, both when administered alone and in combination with α2-adrenoceptor agonists, remain undetermined. This study aimed to document the pharmacokinetics and pharmacodynamics of propranolol, romifidine and their combination. STUDY DESIGN Randomized, crossover study. ANIMALS Six adult horses weighing 561 ± 48 kg. METHODS Propranolol (1 mg kg-1; treatment P), romifidine (0.1 mg kg-1; treatment R) or their combination (treatment PR) were administered intravenously with a minimum of 1 week between treatments. Alertness, behavioral responsiveness (visual and tactile) and physiologic variables were measured before and up to 960 minutes after drug administration. Blood was collected for blood gas and acid-base analyses and measurement of plasma drug concentrations. Data were analyzed using repeated-measures analysis of variance or Friedman with Holm-Sidak and Wilcoxon rank-sum tests (p < 0.05). RESULTS Systemic clearance significantly decreased and the area under the concentration-time curve significantly increased for both drugs in PR compared with P and R. Both PR and R decreased behavioral responsiveness and resulted in sedation for up to 240 and 480 minutes, respectively. Sedation was deeper in PR for the first 16 minutes. Heart rate significantly decreased in all treatments for at least 60 minutes, and PR significantly increased the incidence of severe bradycardia (<20 beats minute-1). CONCLUSIONS AND CLINICAL RELEVANCE Although not associated with reduced behavioral responsiveness or sedation alone, propranolol augmented romifidine sedation, probably through alterations in romifidine pharmacokinetics, in horses administered PR. The occurrence of severe bradycardia warrants caution in the co-administration of these drugs at the doses studied.
A ligand for peroxisome proliferator activated receptor γ inhibits cell growth and induces apoptosis in human liver cancer cells

Background and aims: Induction of apoptosis of cancer cells through ligands of nuclear hormone receptors (NHRs) is a new approach in cancer therapy. Recently, one of the NHRs, peroxisome proliferator activated receptor γ (PPARγ), has been shown to influence cell growth in certain cancer cells although its effect on hepatocellular carcinoma (HCC) has not been analysed. Methods: Experiments were conducted using three human liver cancer cell lines, PLC/PRF/5, Hep G2 and HuH-7, in vitro. These cells were exposed to troglitazone, a synthetic ligand for PPARγ, and the effects on cell growth were analysed. Results: Expression of PPARγ mRNA was detected in all three liver cancer cell lines. Activation of PPARγ by troglitazone caused a marked growth inhibition in a dose dependent manner in three hepatoma cell lines. The DNA fragmentation ELISA assay and Hoechst 33258 staining revealed that the growth inhibitory effect by adding troglitazone was due to apoptosis of PLC/PRF/5, which strongly expressed PPARγ. Troglitazone also induced activation of the cell death protease, caspase 3, but not caspase 8, in PLC/PRF/5 cells. However, expression levels of antiapoptotic factor bcl-2 and apoptosis inducing factor bax were not affected. Conclusion: Our study showed that PPARγ was expressed in human liver cancer cells and that the ligand for PPARγ, troglitazone, inhibited the growth of these cells by inducing apoptosis through caspase 3 activation, indicating that troglitazone could be potentially useful as an apoptosis inducer for the treatment of HCC.
PKA phosphorylation of SUR 2 B subunit underscores vascular KATP channel activation by beta-adrenergic receptors

Shi Y, Wu Z, Cui N, Shi W, Yang Y, Zhang X, Rojas A, Ha BT, Jiang C. PKA phosphorylation of SUR2B subunit underscores vascular KATP channel activation by beta-adrenergic receptors. Am J Physiol Regul Integr Comp Physiol 293: R1205–R1214, 2007. First published June 27, 2007; doi:10.1152/ajpregu.00337. 2007. —ATPsensitive K (KATP) channels are activated by several vasodilating hormones and neurotransmitters through the PKA pathway. Here, we show that phosphorylation at Ser1387 of the SUR2B subunit is critical for the channel activation. Experiments were performed in human embryonic kidney (HEK) 293 cells expressing the cloned Kir6.1/ SUR2B channel. In whole cell patch, the Kir6.1/SUR2B channel activity was stimulated by isoproterenol via activation of 2 receptors. This effect was blocked in the presence of inhibitors for adenylyl cyclase or PKA. Similar channel activation was seen by exposing inside-out patches to the catalytic subunit of PKA. Because none of the previously suggested PKA phosphorylation sites accounted for the channel activation, we performed systematic mutational analysis on Kir6.1 and SUR2B. Two serine residues (Ser1351, Ser1387) located in the NBD2 of SUR2B were critical for the channel activation. In vitro phosphorylation experiments showed that Ser1387 but not Ser1351 was phosphorylated by PKA. The PKA-dependent activation of cell-endogenous KATP channels was observed in acutely dissociated mesenteric smooth myocytes and isolated mesenteric artery rings, where activation of these channels contributed significantly to the isoproterenol-induced vasodilation. Taken together, these results indicate that the Kir6.1/SUR2B channel is a target of 2 receptors and that the channel activation relies on PKA phosphorylation of SUR2B at Ser1387.
MRI features of breast lymphoma: preliminary experience in seven cases.

PURPOSE We aimed to evaluate the imaging features of breast lymphoma using magnetic resonance imaging (MRI). METHODS This retrospective study consisted of seven patients with pathologically confirmed breast lymphoma. The breast lymphomas were primary in six patients and secondary in one patient. All patients underwent preoperative dynamic contrast-enhanced MRI and one underwent additional diffusion-weighted imaging (DWI) with a b value of 600 s/mm2. Morphologic characteristics, enhancement features, and apparent diffusion coefficient (ADC) values were reviewed. RESULTS On MRI, three patients presented with a single mass, one with two masses, two with multiple masses, and one with a single mass and a contralateral focal enhancement. The MRI features of the eight biopsied masses in seven patients were analyzed. On MRI, the margins were irregular in six masses (75%) and spiculated in two (25%). Seven masses (87.5%) displayed homogeneous internal enhancement, while one (12.5%) showed rim enhancement. Seven masses (87.5%) showed a washout pattern and one (12.5%) showed a plateau pattern. The penetrating vessel sign was found in two masses (25%). One patient with two masses underwent DWI. Both masses showed hyperintense signal on DWI with ADC values of 0.867×10-3 mm2/s and 0.732×10-3 mm2/s, respectively. CONCLUSION Breast lymphoma commonly presents as a homogeneously enhancing mass with irregular margins and displays a washout curve pattern on dynamic MRI. A low ADC value may also indicate a possible diagnosis of breast lymphoma.
The complete mitochondrial genome of Eurasian water shrew (Neomys fodiens)

Abstract The complete mitogenome sequence of Eurasian water shrew (Neomys fodiens) was determined using long PCR. The genome was 17,260 bp in length and contained 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 control region. The overall base composition of the heavy strand is A (33.0%), C (23.2%), T (30.9%) and G (12.9%). The base compositions present clearly the A–T skew, which is most obviously in the control region and protein-coding genes. The extended termination-associated sequence domain, the central conserved domain and the conserved sequence block domain are defined in the mitochondrial genome control region of Eurasian water shrew. Mitochondrial genomes analyses based on MP, ML, NJ and Bayesian analyses yielded identical phylogenetic trees. Neomys elegans, Soriculus fumidus, and N. fodiens formed a monophyletic group with the high bootstrap value (100%) in all examinations. This clade with the Anourosorex squamipes as the sister taxon to Sorex.
SAT02-6: Application of the 3D Polarization Concept in Satellite MIMO Systems

In contrast to a plane-wave situation electromagnetic wave polarization is a 3-dimensional phenomenon in multipath scatter environments. Recently there is much research work done in order to utilize this fact in MIMO antennas. E.g. it is shown that with appropriate antenna arrangement increase in capacity can be as much as 4-fold or so in terrestrial rich scattering environments. In this paper satellite systems are investigated from this point of view. It is shown that it is hard to achieve an increase of capacity. However, diversity gain (or order of diversity) can be increased and in principle diversity gain of 6 or more is possible while this gain is at most 4 in the 2D (i.e. plane wave) case.
Patient Portal Adoption Rates: A Systematic Literature Review and Meta-Analysis

Despite the increasing availability of online patient portals that provide access to electronic health records, little is known about their adoption by patients. We systematically reviewed the literature to investigate adoption of patient portals across studies. We searched MEDLINE and Scopus to identify relevant papers. We included 40 studies: 24 were controlled experiments, with prospective data collection in an actively recruited population; 16 were real-world experiments, with adoption being evaluated retrospectively after system deployment in clinical practice. Our meta-analysis showed an overall mean adoption rate of 52% (95% Confidence Interval [CI], 42 to 62%). Rates differed markedly between study types: controlled experiments yielded a mean adoption rate of 71% (95% CI 64 to 79%), compared to 23% (95% CI, 13 to 33%) in real-world experiments. This difference was confirmed in a meta-regression analysis of the influence of study characteristics on adoption rates. Our findings suggest that adoption rates reported in controlled studies do not reflect those in everyday clinical practice. Until we understand how to effectively increase adoption, patient portals are unlikely to consistently lead to improvements in care processes and health outcomes.
Interactions between Two Informal Sector Lenders and Interest Rate Determination in the Informal Credit Market: A Theoretical Analysis

The paper provides a theory of interest rates determination in the informal credit market in backward agriculture highlighting the interactions between two informal sector lenders (a professional money lender and a trader-interlocker) and explains the prevalence of different interest rates in the rural credit market. The trader and the moneylender play a non-cooperative game in choosing the extent of interlinkage and the non-interlinked informal interest rate, respectively. In the interlinked credit-product contract, the trader offers the interlockees a product price equal to the open market price and his entire surplus comes from his activities in the credit market. These results are completely opposite to those found in the existing literature on interlinkage. A price subsidy policy reduces the extent of interlinkage chosen by the trader while a credit subsidy policy may raise it. Besides, the subsidy policies unequivocally raise the non-interlinked informal interest rate of the moneylender but may lower the welfare of the farmers and the agricultural productivity. In this context, an alternative credit policy of forging a vertical linkage between the formal and informal credit markets has been considered. It has been found that a credit subsidy policy under the new system is able to raise the agricultural productivity and improve the welfare of the farmers by ameliorating their borrowing terms in the credit market.
ATP Hydrolysis and Pristinamycin IIA Inhibition of the Staphylococcus aureus Vga(A), a Dual ABC Protein Involved in Streptogramin A Resistance*

In Gram-positive bacteria, a large subfamily of dual ATP-binding cassette proteins confers acquired or intrinsic resistance to macrolide, lincosamide, and streptogramin antibiotics by a far from well understood mechanism. Here, we report the first biochemical characterization of one such protein, Vga(A), which is involved in streptogramin A (SgA) resistance among staphylococci. Vga(A) is composed of two nucleotide-binding domains (NBDs), separated by a charged linker, with a C-terminal extension and without identified transmembrane domains. Highly purified Vga(A) displays a strong ATPase activity (Km = 78 μm, Vm = 6.8 min-1) that was hardly inhibited by orthovanadate. Using mutants of the conserved catalytic glutamate residues, the two NBDs of Vga(A) were shown to contribute unequally to the total ATPase activity, the mutation at NBD2 being more detrimental than the other. ATPase activity of both catalytic sites was essential for Vga(A) biological function because each single Glu mutant was unable to confer SgA resistance in the staphylococcal host. Of great interest, Vga(A) ATPase was specifically inhibited in a non-competitive manner by the SgA substrate, pristinamycin IIA (PIIA). A deletion of the last 18 amino acids of Vga(A) slightly affected the ATPase activity without modifying the PIIA inhibition values. In contrast, this deletion reduced 4-fold the levels of SgA resistance. Altogether, our results suggest a role for the C terminus in regulation of the SgA antibiotic resistance mechanism conferred by Vga(A) and demonstrate that this dual ATP-binding cassette protein interacts directly and specifically with PIIA, its cognate substrate.
Divisionalization, Franchising, and Divestiture Incentives in Oligopoly

A two-stage game is used to model firms' strategic incentives to divide production among autonomous competing units through divisionalization, franchising, or divestiture. Firms simultaneously choose their number of competing units, which then engage in Cournot competition. While it is costly to form autonomous units, each firm does so in equilibrium, thus reducing firm profits and increasing social welfare relative to the case where firms cannot form competing units. With linear demand and costs, duopolists choose the socially optimal number of competing units; oligopolies with larger numbers of firms choose too many. The case of nonlinear demand is also examined. Copyright 1996 by American Economic Association.
Streptococcus Gallolyticus Subsp. Pasteurianus Infection In A Neonatal Intensive Care Unit

We report nosocomial transmission of Streptococcus gallolyticus subsp. pasteurianus among 3 neonates, 1 of whom died. Genome analysis of the strains showed a specific pattern of metabolic and regulatory functions as well as of expressed antigens and antibiotic resistance genes that might have contributed to their specific virulence.
FUT2 genetic variants as predictors of tumor development with hepatocellular carcinoma

Lewis antigens related to the ABO blood group are fucosylated oligosaccharides and are synthesized by specific glycosyltransferases (FUTs). FUTs are involved in various biological processes including cell adhesion and tumor progression. The fucosyltransferase-2 gene (FUT2) encodes alpha (1,2) fucosyltransferase, which is responsible for the addition of the alpha (1,2)-linkage of fucose to glycans. Aberrant fucosylation occurs frequently during the development and progression of hepatocellular carcinoma (HCC). However, the association of FUT2 polymorphisms with HCC development has not been studied. Therefore, we aimed to investigate the association of FUT2 polymorphisms with demographic, etiological, and clinical characteristics and with susceptibility to HCC. In this study, a total of 339 patients and 720 controls were recruited. The genotypes of FUT2 at four single-nucleotide polymorphisms (SNPs; rs281377, rs1047781, rs601338, and rs602662) were detected by real-time polymerase chain reaction from these samples. Compared with the wild-type genotype at SNP rs1047781, which is homozygous for nucleotides AA, at least one polymorphic T allele (AT or TT) displayed significant association with clinical stage (p = 0.048) and tumor size (p = 0.022). Our study strongly implicates the polymorphic locus rs1047781 of FUT2 as being associated with HCC development.
Rise of the Warrior Cop: The Militarization of America's Police Forces

The last days of colonialism taught America's revolutionaries that soldiers in the streets bring conflict and tyranny. As a result, our country has generally worked to keep the military out of law enforcement. But according to investigative reporter Radley Balko, over the last several decades, America's cops have increasingly come to resemble ground troops. The consequences have been dire: the home is no longer a place of sanctuary, the Fourth Amendment has been gutted, and police today have been conditioned to see the citizens they serve as an other--an enemy. Today's armored-up policemen are a far cry from the constables of early America. The unrest of the 1960s brought about the invention of the SWAT unit--which in turn led to the debut of military tactics in the ranks of police officers. Nixon's War on Drugs, Reagan's War on Poverty, Clinton's COPS program, the post--9/11 security state under Bush and Obama: by degrees, each of these innovations expanded and empowered police forces, always at the expense of civil liberties. And these are just four among a slew of reckless programs. In Rise of the Warrior Cop, Balko shows how politicians' ill-considered policies and relentless declarations of war against vague enemies like crime, drugs, and terror have blurred the distinction between cop and soldier. His fascinating, frightening narrative shows how over a generation, a creeping battlefield mentality has isolated and alienated American police officers and put them on a collision course with the values of a free society.
Assessment of some imported apple fruits ( Malus domestica ) commonly sold in Nigeria for alkaline and trace metal contents

Three different apples were analysed for their heavy metal and alkaline metal contents. Results of this study using Flame Atomic Absorption Spectrophotometer and flame photometer indicated heavy metal ranges from 0.04 – 0.08 µg/g (Zn), 3.20 – 3.70 µg/g (Pb), 1.62 – 1.76 µg/g (Ni), 0.09 – 0.21 µg/g (Cr), 2.70 – 2.80 µg/g (Ca), 0.37 – 0.52 µg/g (Fe), 0.04 – 0.06 µg/g (Cd) and 0.12 – 0.17 µg/g (Cu). This study showed that Pb, Ni, Cr, Fe and Cu have objectionable concentrations that are higher than the acceptable permissible limits by WHO. Cultivation of these apples may have occurred on polluted soils. Keywords : Flame photometer, apples, heavy metals, alkaline metals, AAS.
Approximations to viability kernels for sustainable macroeconomic policies

Maintaining an open economy within certain bounds on inflation, output gap and exchange rate can help sustainable economic development. Macroeconomics proposes monetary-policy models that describe evolution of the above quantities. We use one such model, constituted by a four-metastate one-control system, to compute viability kernel approximations that one can use to assist the central bank to establish "sustainable" policies. We propose a simple heuristic algorithm that leads to kernel approximations for this and similar models.
Auditing access to specialty care for children with public insurance.

BACKGROUND Health care reform has expanded eligibility to public insurance without fully addressing concerns about access. We measured children's access to outpatient specialty care to identify disparities in providers' acceptance of Medicaid and the Children's Health Insurance Program (CHIP) versus private insurance. METHODS Between January and May 2010, research assistants called a stratified, random sample of clinics representing eight specialties in Cook County, Illinois, which has a high proportion of specialists. Callers posed as mothers of pediatric patients with common health conditions requiring outpatient specialty care. Two calls, separated by 1 month, were placed to each clinic by the same person with the use of a standardized clinical script that differed by insurance status. RESULTS We completed 546 paired calls to 273 specialty clinics and found significant disparities in provider acceptance of Medicaid-CHIP versus private insurance across all tested specialties. Overall, 66% of Medicaid-CHIP callers (179 of 273) were denied an appointment as compared with 11% of privately insured callers (29 of 273) (relative risk, 6.2; 95% confidence interval [CI], 4.3 to 8.8; P<0.001). Among 89 clinics that accepted both insurance types, the average wait time for Medicaid-CHIP enrollees was 22 days longer than that for privately insured children (95% CI, 6.8 to 37.5; P=0.005). CONCLUSIONS We found a disparity in access to outpatient specialty care between children with public insurance and those with private insurance. Policy interventions that encourage providers to accept patients with public insurance are needed to improve access to care.
Optimally Investing to Reach a Bequest Goal

We determine the optimal strategy for investing in a Black-Scholes market in order to maximize the probability that wealth at death meets a bequest goal $b$, a type of goal-seeking problem, as pioneered by Dubins and Savage (1965, 1976). The individual consumes at a constant rate $c$, so the level of wealth required for risklessly meeting consumption equals $c/r$, in which $r$ is the rate of return of the riskless asset. Our problem is related to, but different from, the goal-reaching problems of Browne (1997). First, Browne (1997, Section 3.1) maximizes the probability that wealth reaches $b
Effect of concurrent anxiety on response to sertraline and imipramine in patients with chronic depression

Anxiety commonly complicates the clinical presentation of depression and has been associated with poorer long‐term outcome, but little information is available on the clinical correlates, and comparative effect on treatment response, of subsyndromic or secondary anxiety. Patients diagnosed with chronic major or double depression were randomized to 12 weeks of double‐blind treatment with either sertraline or imipramine in a 2:1 ratio. A high anxiety subgroup was operationally defined by a HAM‐D anxiety/somatization factor score ≥ 7. The effect of study treatment was measured utilizing the HAM‐D, CGI, HAM‐D anxiety/somatization factor, as well as a quality of life measure (Q‐LES‐Q) and a measure of psychosocial functioning (the MOS‐SF‐36). Two hundred nine patients were treated with imipramine and 426 patients were treated with sertraline. Thirty‐six percent of the total met criteria for the high anxiety subgroup. According to Kaplan‐Meier probability estimates, patients with significant concurrent anxiety symptoms were more likely to respond by 12 weeks (66.4%) than those without significant anxiety symptoms (54.2%). There was no significant difference in response rates for sertraline vs. imipramine. Both drugs were effective at treating high baseline levels of anxiety, with 60% of sertraline patients and 58% of imipramine patients having 50% or greater reduction from baseline in HAM‐D anxiety/somatization factor scores, and only 4.6% and 9.9%, respectively, reporting treatment‐emergent worsening in anxiety at study endpoint. Despite the chronicity of depressive illness, acute treatment with both sertraline and imipramine significantly improved psychosocial and quality of life measures. High baseline levels of anxiety did not reduce overall antidepressant response but did somewhat delay the onset of response to sertraline or imipramine in patients with chronic depression. Depression and Anxiety 13:18–27, 2001. © 2001 Wiley‐Liss, Inc.