Miracle-dz/UniFAR-FTUs huggingface dataset:
L-TYPE Ca 2 + CURRENT IN FISH CARDIAC MYOCYTES : EFFECTS OF THERMAL ACCLIMATION AND β-ADRENERGIC STIMULATION

, A patch-clamp analysis of L-type Ca2+ current in ventricular myocytes of coldand warm-acclimated rainbow trout ( Oncorhynchus mykiss ) and crucian carp (Carassius carassius ) hearts was performed. Trout were acclimated at 4 and 17 °C and carp at 4 and 24 °C for a minimum of 4 weeks. Ventricular myocytes were isolated by enzymatic dissociation using collagenase and trypsin. Marked species-specific differences were noted in Ca 2+
National and sub-national analysis of the health benefits and cost-effectiveness of strategies to reduce maternal mortality in Afghanistan.

BACKGROUND Afghanistan has one of the highest rates of maternal mortality in the world. We assess the health outcomes and cost-effectiveness of strategies to improve the safety of pregnancy and childbirth in Afghanistan. METHODS Using national and sub-national data, we adapted a previously validated model that simulates the natural history of pregnancy and pregnancy-related complications. We incorporated data on antenatal care, family planning, skilled birth attendance and information about access to transport, referral facilities and quality of care. We evaluated single interventions (e.g. family planning) and strategies that combined several interventions packaged as integrated services (transport, intrapartum care). Outcomes included pregnancy-related complications, maternal deaths, maternal mortality ratios, costs and cost-effectiveness ratios. FINDINGS Model-projected reduction in maternal deaths between 1999-2002 and 2007-08 approximated 20%. Increasing family planning was the most effective individual intervention to further reduce maternal mortality; up to 1 in 3 pregnancy-related deaths could be prevented if contraception use approached 60%. Nevertheless, reductions in maternal mortality reached a threshold (∼30% to 40%) without strategies that assured women access to emergency obstetrical care. A stepwise approach that coupled improved family planning with incremental improvements in skilled attendance, transport, referral and appropriate intrapartum care and high-quality facilities prevented 3 of 4 maternal deaths. Such an approach would cost less than US$200 per year of life saved at the national level, well below Afghanistan's per capita gross domestic product (GDP), a common benchmark for cost-effectiveness. Similar results were noted sub-nationally. INTERPRETATION Our findings reinforce the importance of early intensive efforts to increase family planning for spacing and limiting births and to provide control of fertility choices. While significant improvements in health delivery infrastructure will be required to meet Millennium Development Goal 5, a paced systematic effort that invests in scaling up capacity for integrated maternal health services as the total fertility rate declines appears feasible and cost-effective.
Toeplitz Compressed Sensing Matrices With Applications to Sparse Channel Estimation

Compressed sensing (CS) has recently emerged as a powerful signal acquisition paradigm. In essence, CS enables the recovery of high-dimensional sparse signals from relatively few linear observations in the form of projections onto a collection of test vectors. Existing results show that if the entries of the test vectors are independent realizations of certain zero-mean random variables, then with high probability the unknown signals can be recovered by solving a tractable convex optimization. This work extends CS theory to settings where the entries of the test vectors exhibit structured statistical dependencies. It follows that CS can be effectively utilized in linear, time-invariant system identification problems provided the impulse response of the system is (approximately or exactly) sparse. An immediate application is in wireless multipath channel estimation. It is shown here that time-domain probing of a multipath channel with a random binary sequence, along with utilization of CS reconstruction techniques, can provide significant improvements in estimation accuracy compared to traditional least-squares based linear channel estimation strategies. Abstract extensions of the main results are also discussed, where the theory of equitable graph coloring is employed to establish the utility of CS in settings where the test vectors exhibit more general statistical dependencies.
Allopurinol Use Yields Potentially Beneficial Effects on Inflammatory Indices in Those With Recent Ischemic Stroke: A Randomized, Double-Blind, Placebo-Controlled Trial

Background and Purpose— Elevated serum uric acid level is associated with poor outcome and increased risk of recurrent events after stroke. The xanthine oxidase inhibitor allopurinol lowers uric acid but also attenuates expression of inflammatory adhesion molecules in murine models, reduces oxidative stress in the vasculature, and improves endothelial function. We sought to investigate whether allopurinol alters expression of inflammatory markers after acute ischemic stroke. Methods— We performed a randomized, double-blind, placebo-controlled trial to investigate the safety, tolerability, and effect of 6 weeks' treatment with high- (300 mg once a day) or low- (100 mg once a day) dose allopurinol on levels of uric acid and circulating inflammatory markers after ischemic stroke. Results— We enrolled 50 patients with acute ischemic stroke (17, 17, and 16 in the high, low, and placebo groups, respectively). Mean (±SD) age was 70 (±13) years. Groups had similar characteristics at baseline. There were no serious adverse events. Uric acid levels were significantly reduced at both 7 days and 6 weeks in the high-dose group (by 0.14 mmol/L at 6 weeks, P=0.002). Intercellular adhesion molecule-1 concentration (ng/mL) rose by 51.2 in the placebo group, rose slightly (by 10.6) in the low-dose allopurinol group, but fell in the high-dose group (by 2.6; difference between groups P=0.012, Kruskal-Wallis test). Conclusion— Allopurinol treatment is well tolerated and attenuates the rise in intercellular adhesion molecule-1 levels seen after stroke. Uric acid levels were lowered with high doses. These findings support further evaluation of allopurinol as a preventive measure after stroke.
Development and plasticity of the Drosophila larval neuromuscular junction

The Drosophila larval neuromuscular system is relatively simple, containing only 32 motor neurons in each abdominal hemisegment, and its neuromuscular junctions (NMJs) have been studied extensively. NMJ synapses exhibit developmental and functional plasticity while displaying stereotyped connectivity. Drosophila Type I NMJ synapses are glutamatergic, while the vertebrate NMJ uses acetylcholine as its primary neurotransmitter. The larval NMJ synapses use ionotropic glutamate receptors (GluRs) that are homologous to AMPA‐type GluRs in the mammalian brain, and they have postsynaptic scaffolds that resemble those found in mammalian postsynaptic densities. These features make the Drosophila neuromuscular system an excellent genetic model for the study of excitatory synapses in the mammalian central nervous system. The first section of the review presents an overview of NMJ development. The second section describes genes that regulate NMJ development, including: (1) genes that positively and negatively regulate growth of the NMJ, (2) genes required for maintenance of NMJ bouton structure, (3) genes that modulate neuronal activity and alter NMJ growth, (4) genes involved in transsynaptic signaling at the NMJ. The third section describes genes that regulate acute plasticity, focusing on translational regulatory mechanisms. As this review is intended for a developmental biology audience, it does not cover NMJ electrophysiology in detail, and does not review genes for which mutations produce only electrophysiological but no structural phenotypes. WIREs Dev Biol 2013, 2:647–670. doi: 10.1002/wdev.108
Flow softening of 7075 aluminum alloy under hot compression

Hot deformation of 7075 aluminum alloy was studied in compression in the temperature range of 723 to 803 K and at constant true strain rate from 5.4×lO -6 to O.8s -1 . The flow characteristics were classified into lyzed in each region of testing conditions, as follows; L, M, and H. In region H where flow stresses were above high temperature yield point phenomenon appeared
Intact perceptual memory in the absence of conscious memory.

Declarative memory enables conscious recollection of the past and has been proposed to be distinct from priming, a perceptual form of memory that operates nonconsciously and improves the ability to detect or identify recently presented stimuli. Yet, it has been difficult to obtain unambiguous evidence for the independence of declarative memory and priming. The authors report the first demonstration, using matched tests, of fully intact perceptual memory (priming) in a profoundly amnesic patient (E.P.), despite at-chance recognition memory. The priming and recognition tests included tests that were matched with respect to test materials, length of the study and test lists, and the kind of cues available at test. Priming appears to reflect neural changes within perceptual processing systems that occur before information reaches the brain systems that transform visual perception into conscious visual memory.
Genetics of Type III Bartter Syndrome in Spain, Proposed Diagnostic Algorithm

The p.Ala204Thr mutation (exon 7) of the CLCNKB gene is a "founder" mutation that causes most of type III Bartter syndrome cases in Spain. We performed genetic analysis of the CLCNKB gene, which encodes for the chloride channel protein ClC-Kb, in a cohort of 26 affected patients from 23 families. The diagnostic algorithm was: first, detection of the p.Ala204Thr mutation; second, detecting large deletions or duplications by Multiplex Ligation-dependent Probe Amplification and Quantitative Multiplex PCR of Short Fluorescent Fragments; and third, sequencing of the coding and flanking regions of the whole CLCNKB gene. In our genetic diagnosis, 20 families presented with the p.Ala204Thr mutation. Of those, 15 patients (15 families) were homozygous (57.7% of overall patients). Another 8 patients (5 families) were compound heterozygous for the founder mutation together with a second one. Thus, 3 patients (2 siblings) presented with the c. -19-? _2053+? del deletion (comprising the entire gene); one patient carried the p.Val170Met mutation (exon 6); and 4 patients (3 siblings) presented with the novel p.Glu442Gly mutation (exon 14). On the other hand, another two patients carried two novel mutations in compound heterozygosis: one presented the p.Ile398_Thr401del mutation (exon 12) associated with the c. -19-? _2053+? del deletion, and the other one carried the c.1756+1G>A splice-site mutation (exon 16) as well as the already described p.Ala210Val change (exon 7). One case turned out to be negative in our genetic screening. In addition, 51 relatives were found to be heterozygous carriers of the described CLCNKB mutations. In conclusion, different mutations cause type III Bartter syndrome in Spain. The high prevalence of the p.Ala204Thr in Spanish families thus justifies an initial screen for this mutation. However, should it not be detected further investigation of the CLCNKB gene is warranted in clinically diagnosed families.
Prevention of glucocorticoid induced osteoporosis with alendronate or alfacalcidol: relations of change in bone mineral density, bone markers, and calcium homeostasis.

OBJECTIVE To explore the relation of changes in measures of bone turnover and changes in bone mineral density (BMD) of the lumbar spine and total hip over 18 months in a double-blinded, randomized trial, comparing the effect of alfacalcidol (101 patients) versus alendronate (100 patients) on BMD in patients who recently started treatment with glucocorticoids for various rheumatic diseases. METHODS Associations between changes in serum procollagen type I C-propeptide (P1CP), fasting urine N-terminal telopeptide of type I collagen (NTx), serum calcium, parathyroid hormone (PTH), osteocalcin, and change from baseline in BMD over 18 months were explored with regression and correlation analyses. RESULTS In both treatment groups, there was a statistically significant decrease in NTx. In the alfacalcidol group there was also a significant increase in P1CP and osteocalcin, in contrast to the alendronate group, but BMD in the alfacalcidol decreased versus an increase in the alendronate group (p < 0.001). In neither treatment group were changes in biochemical measures correlated with the change in BMD, with the exception of a negative correlation in the alendronate group between changes in total hip BMD and NTx. Use of alendronate resulted in an increased PTH in 27 patients, but the increase in BMD of these patients was not statistically significantly different compared to patients taking alendronate with normal PTH levels. CONCLUSION Changes in BMD were not associated with changes in bone measures, with the exception of NTx in the alendronate group. For the patient taking glucocorticoids in clinical practice, the value of serial assessment of bone markers is low; changes in markers are no substitute for changes in BMD. ClinicalTrials.gov number: NCT00138983.
Lethal morphine intoxication in a patient with a sickle cell crisis and renal impairment: Case report and a review of the literature

Morphine-6-glucuronide, the active metabolite of morphine, and to a lesser extent morphine itself are known to accumulate in patients with renal failure. A number of cases on non-lethal morphine toxicity in patients with renal impairment report high plasma concentrations of morphine-6-glucuronide, suggesting that this metabolite achieves sufficiently high brain concentrations to cause long-lasting respiratory depression, despite its poor central nervous system penetration. We report a lethal morphine intoxication in a 61-year-old man with sickle cell disease and renal impairment, and we measured concentrations of morphine and morphine-6-glucuronide in blood, brain and cerebrospinal fluid. There were no measurable concentrations of morphine-6-glucuronide in cerebrospinal fluid or brain tissue, despite high blood concentrations. In contrast, the relatively high morphine concentration in the brain suggests that morphine itself was responsible for the cardiorespiratory arrest in this patient. Given the fatal outcome, we recommend to avoid repeated or continuous morphine administration in renal failure.
Pharmacokinetics of Antiretroviral Regimens Containing Tenofovir Disoproxil Fumarate and Atazanavir-Ritonavir in Adolescents and Young Adults with Human Immunodeficiency Virus Infection

ABSTRACT The primary objective of this study was to measure atazanavir-ritonavir and tenofovir pharmacokinetics when the drugs were used in combination in young adults with human immunodeficiency virus (HIV). HIV-infected subjects ≥18 to <25 years old receiving (≥28 days) 300/100 mg atazanavir-ritonavir plus 300 mg tenofovir disoproxil fumarate (TDF) plus one or more other nucleoside analogs underwent intensive 24-h pharmacokinetic studies following a light meal. Peripheral blood mononuclear cells were obtained at 1, 4, and 24 h postdose for quantification of intracellular tenofovir diphosphate (TFV-DP) concentrations. Twenty-two subjects were eligible for analyses. The geometric mean (95% confidence interval [CI]) atazanavir area under the concentration-time curve from 0 to 24 h (AUC0-24), maximum concentration of drug in serum (Cmax), concentration at 24 h postdose (C24), and total apparent oral clearance (CL/F) values were 35,971 ng·hr/ml (30,853 to 41,898), 3,504 ng/ml (2,978 to 4,105), 578 ng/ml (474 to 704), and 8.3 liter/hr (7.2 to 9.7), respectively. The geometric mean (95% CI) tenofovir AUC0-24, Cmax, C24, and CL/F values were 2,762 ng·hr/ml (2,392 to 3,041), 254 ng/ml (221 to 292), 60 ng/ml (52 to 68), and 49.2 liter/hr (43.8 to 55.3), respectively. Body weight was significantly predictive of CL/F for all three drugs. For every 10-kg increase in weight, there was a 10%, 14.8%, and 6.8% increase in the atazanavir, ritonavir, and tenofovir CL/F, respectively (P ≤ 0.01). Renal function was predictive of tenofovir CL/F. For every 10 ml/min increase in creatinine clearance, there was a 4.6% increase in tenofovir CL/F (P < 0.0001). The geometric mean (95% CI) TFV-DP concentrations at 1, 4, and 24 h postdose were 96.4 (71.5 to 130), 93.3 (68 to 130), and 92.7 (70 to 123) fmol/million cells. There was an association between renal function, tenofovir AUC, and tenofovir Cmax and intracellular TFV-DP concentrations, although none of these associations reached statistical significance. In these HIV-infected young adults treated with atazanavir-ritonavir plus TDF, the atazanavir AUC was similar to those of older adults treated with the combination. Based on data for healthy volunteers, a higher tenofovir AUC may have been expected, but was not seen in these subjects. This might be due to faster tenofovir CL/F because of higher creatinine clearance in this age group. Additional studies of the exposure-response relationships of this regimen in children, adolescents, and adults would advance our knowledge of its pharmacodynamic properties.
Improved Survival in Primary Nonmetastatic Pediatric Osteosarcoma of the Extremity

A prospective study using a dose-intensified neoadjuvant intra-arterial chemotherapy regimen was designed to improve survival rates of young patients with primary, nonmetastatic osteosarcoma of the extremity. Arteriography was implemented to individualize duration of therapy by serially assessing change in tumor neovascularity. Intravenous doxorubicin and intra-arterial cisplatin were administered repetitively at 3-week intervals until ≥ 90% reduction in tumor neovascularity was achieved. Surgery was delayed until this good arteriographic response was documented. After resection, prediction of tumor neovascularity was compared with tumor necrosis. Since 1987, 62 eligible patients younger than 22 years old were treated with an average of four neoadjuvant courses. Toxicities were manageable. Fifty-four (87%) patients had a good histologic response. The rate of limb preservation surgery was 93.5% (58/62). Accuracy and sensitivity of serial arteriography in predicting histologic response were 92% and 98% respectively, and greatly assisted surgical planning. With an average followup of 91 months, estimated Kaplan-Meier survival at 10 years was 93% and event-free survival was 86%. Osteosarcoma survival rates were significantly improved by the use of this regimen compared with previously reported results. Serial arteriography succeeded in individualizing duration of neoadjuvant therapy and led to a higher rate of good histologic response. Level of Evidence: Therapeutic study, level II-1 (prospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.
Utility-based rate control in the Internet for elastic traffic

In a communication network, a good rate allocation algorithm should reflect the utilities of the users while being fair. We investigate this fundamental problem of achieving the system optimal rates in the sense of maximizing aggregate utility, in a distributed manner, using only the information available at the end hosts of the network. This is done by decomposing the overall system problem into subproblems for the network and for the individual users by introducing a pricing scheme. The users are to solve the problem of maximizing individual net utility, which is the utility less the amount they pay. We provide algorithms for the network to adjust its prices and the users to adjust their window sizes such that at an equilibrium the system optimum is achieved. Further, the equilibrium prices are such that the system optimum achieves weighted proportional fairness. It is notable that the update algorithms of the users do not require any explicit feedback from the network, rendering them easily deployable over the Internet. Our scheme is incentive compatible in that there is no benefit to the users to lie about their utilities.
HMM based approach for handwritten arabic word recognition using the IFN/ENIT - database

An offline recognition system for Arabic handwrittenwords is presented. The recognition system is based ona semi-continuous 1-dimensional HMM. From each binaryword image normalization parameters were estimated. Firstheight, length, and baseline skew are normalized, then featuresare collected using a sliding window approach. Thispaper presents these methods in more detail. Some parameterswere modified and the consequent effect on the recognitionresults are discussed. Significant tests were performedusing the new IFN/ENIT - database of handwritten Arabicwords. The comprehensive database consists of 26459Arabic words (Tunisian town/village names) handwrittenby 411 different writers and is free for non-commercial research.In the performed tests we achieved maximal recognitionrates of about 89% on a word level.
Artificial life and cellular automata based automated test case generator

Manual test data generation is carried out by using the ability of neurons to recognize patterns. The nervous system and the brain coordinate to generate test cases, which are capable of finding potential faults. Automated test data generators lack the ability to produce efficient test cases because they do not imitate natural processes. This paper proposes using Artificial Life based systems for generating test cases. Cellular Automata and Langton's loop have been used to accomplish the above task. Cellular Automata are parallel distributed systems capable of reproducing using self generated patterns. These fascinating techniques have been amalgamated with standard test data generation techniques to give rise to a methodology, which generates test cases for white box testing. Langton's Loops have been used to generate test cases for Black Box Testing. The approach has been verified on a set of 20 programs. The programs have been selected on the basis of their Lines of Code and utility. The results obtained have been verified using Average Probability of Fault Detection. This paper also proposes a new framework capable of crafting test cases taking into account the oracle cost.
Effects of Age on Brain Activation During Auditory-Cued Thumb-to-Index Opposition: A Positron Emission Tomography Study

Background and Purpose— Available data indicate a decline in fine finger movements with aging, suggesting changes in central motor processes. Thus far no functional neuroimaging study has assessed the effect of age on activation patterns during finger movement. Methods— We used high-resolution perfusion positron emission tomography to study 2 groups of 7 healthy right-handed subjects each: a young group (mean age, 24 years) and an old group (mean age, 60 years). The task was a thumb-to-index tapping, auditory-cued at 1.26 Hz with a metronome, with either the right or the left hand. The control condition was a resting state with the metronome on. Results— Significant differences between old and young subjects were found, suggesting significant overactivation in older subjects affecting the superior frontal cortex (premotor-prefrontal junction) ipsilateral to the moving fingers, as if the execution of this apparently simple motor task was judged more complex by the aged brain. Similar findings in previous perceptual and cognitive paradigms have been interpreted as a compensation process for the neurobiological changes of aging. Analysis of the control condition data in our sample showed, however, that this prefrontal overactivation in the old group was due at least in part to higher resting perfusion in anterior brain areas in the young subjects. Conclusions— The changes in brain function observed in this study may underlie the subtle decline in fine motor functions known to occur with normal aging. Our findings emphasize the importance of using an age-matched control group in functional imaging studies of motor recovery after stroke.