Miracle-dz/UniFAR-FTUs huggingface dataset:
CA3 NMDA receptors are crucial for rapid and automatic representation of context memory

It is argued that the hippocampus contributes to acquisition of context‐specific memory although neural mechanisms have not been clarified. To evaluate the role of CA3 in context‐specific memory, we developed one‐trial context discrimination tasks to test acquisition and retrieval of contextual memory in CA3 pyramidal cell‐restricted N‐methyl‐d‐aspartate (NMDA) receptor knockout mice. Mutants were unable to discriminate conditioned and no‐shock contexts 3 h after one‐trial avoidance training. These phenotypes were not evident 24 h after one‐trial training or 3 h after multi‐trial training. Following one‐trial contextual fear conditioning, mutants showed a selective deficit in context discrimination during a retention test 3 h after acquisition, although overall freezing levels were similar to those of the control mice. As in the avoidance task, this context discrimination impairment was not observed 24 h after initial conditioning. Interestingly, extending the post‐shock period to 3 min during the one‐trial fear conditioning task eliminated the discrimination deficit observed at the 3 h retention interval. These results suggest that: (i) impaired rapid context discrimination during the recall test is dependent on the duration of post‐shock period during conditioning; (ii) CA3 NMDA receptors are critically involved in rapid and automatic formation of a unified context memory representation from the sensory information; (iii) CA3 NMDA receptors support contextual pattern separation; (iv) fear memory to foot‐shock is acquired without CA3 NMDA receptors. It appears that rapid and automatic context memory representations from one‐time experience are mediated, at least in part, by CA3 NMDA receptors.
Prevalence of hepatitis C in a chemically dependent population.

BACKGROUND Drug abuse is the major risk factor for hepatitis C in the United States. The objective of this study was to determine the prevalence of hepatitis C virus (HCV), to identify risk factors for HCV, and to correlate HCV and liver function in patients presenting for inpatient detoxification of substances of abuse. METHODS A total of 687 patients were tested for the presence of antibody to HCV (anti-HCV). Histories related to drug use, sexually transmitted diseases, blood transfusion, and human immunodeficiency virus were obtained, as were serum tests for human immunodeficiency virus, syphilis, hepatitis B, aminotransferases, total bilirubin, and alkaline phosphatase. RESULTS The overall prevalence of anti-HCV was 63%: 68% in men vs 54% in women (P < .001), with no difference by race. Remarkably, 86% of injecting drug users tested positive for anti-HCV. Identified risk factors for anti-HCV were injecting drug use (P < .001), human immunodeficiency virus infection (P = .003), exposure to hepatitis B virus (P < .001), and a positive rapid plasma reagin test (P = .04). Previous transfusion and history of previous infection with gonorrhea or syphilis did not correlate with the presence of anti-HCV. Patients positive for anti-HCV had significant elevations in aspartate aminotransferase and alanine aminotransferase levels when compared with patients negative for anti-HCV: 50.8 vs 36.7 U/L (P = .002) and 56.0 vs 36.9 U/L (P < .001), respectively. CONCLUSION Injecting drug users have an extremely high prevalence of anti-HCV. This is the first demonstration, to our knowledge, that the presence of anti-HCV in drug users is associated with significantly increased levels of serum aminotransferases.
The Nine Lives of Cosmic Rays in Galaxies

© 2015 by Annual Reviews. Cosmic-ray astrophysics has advanced rapidly in recent years, and its impact on other astronomical disciplines has broadened. Many new experiments measuring these particles, both directly in the atmosphere or space and indirectly via γ rays and synchrotron radiation, have widened the range and quality of the information available on their origin, propagation, and interactions. The impact of low-energy cosmic rays on interstellar chemistry is a fast-developing topic, including the propagation of these particles into the clouds in which the chemistry occurs. Cosmic rays, via their γ-ray production, also provide a powerful way to probe the gas content of the interstellar medium. Substantial advances have been made in the observations and modelling of the interplay between cosmic rays and the interstellar medium. Focusing on energies up to 1 TeV, these interrelating aspects are covered at various levels of detail, giving a guide to the state of the subject.
A prospective study of exercise and incidence of diabetes among US male physicians.

OBJECTIVE To examine prospectively the association between regular exercise and the subsequent development of non-insulin-dependent diabetes mellitus (NIDDM). DESIGN Prospective cohort study including 5 years of follow-up. PARTICIPANTS 21,271 US male physicians participating in the Physicians' Health Study, aged 40 to 84 years and free of diagnosed diabetes mellitus, myocardial infarction, cerebrovascular disease, and cancer at baseline. Morbidity follow-up was 99.7% complete. MAIN OUTCOME MEASURE Incidence of NIDDM. RESULTS At baseline, information was obtained about frequency of vigorous exercise and other risk indicators. During 105,141 person-years of follow-up, 285 new cases of NIDDM were reported. The age-adjusted incidence of NIDDM ranged from 369 cases per 100,000 person-years in men who engaged in vigorous exercise less than once weekly to 214 cases per 100,000 person-years in those exercising at least five times per week (P, trend, less than .001). Men who exercised at least once per week had an age-adjusted relative risk (RR) of NIDDM of 0.64 (95% Cl, 0.51 to 0.82; P = .0003) compared with those who exercised less frequently. The age-adjusted RR of NIDDM decreased with increasing frequency of exercise: 0.77 for once weekly, 0.62 for two to four times per week, and 0.58 for five or more times per week (P, trend, .0002). A significant reduction in risk of NIDDM persisted after adjustment for both age and body-mass index: RR, 0.71 (95% Cl, 0.56 to 0.91; P = .006) for at least once per week compared with less than once weekly, and P, trend, . 009, for increasing frequency of exercise. Further control for smoking, hypertension, and other coronary risk factors did not materially alter these associations. The inverse relation of exercise to risk of NIDDM was particularly pronounced among overweight men. CONCLUSIONS Exercise appears to reduce the development of NIDDM even after adjusting for body-mass index. Increased physical activity may be a promising approach to the primary prevention of NIDDM.
Multimodal reference resolution for mobile spatial interaction in urban environments

We present results of a study on referring to the outside environment from within a moving vehicle. Reference resolution is the first necessary step in integrating the outside environment into the interactive system in the car. It is the problem of finding out which of the objects outside the users is interested in. In our study, we explored eye gaze, head pose, pointing gesture with a smart phone, and the user's view field. We implemented and tested everything in a moving vehicle in a real-life traffic. For safety reasons, the front-seat passenger used the system while the driver was concentrating completely on driving. For analysis and visualization of the user's interaction with the environment, 528 buildings of the city were modeled in 2.5D by using an airborne LIDAR scan, Google Earth, and a spatial database. As a result of our study, we propose in this paper a new algorithm for spatial reference resolution together with a scanning mechanism.
Esmolol and Landiolol, Selective &bgr;1-Adrenoreceptor Antagonists, Provide Neuroprotection Against Spinal Cord Ischemia and Reperfusion in Rats

BACKGROUND:Paraplegia is a devastating and unpredictable complication occasionally resulting from surgery of the thoracic and thoracoabdominal aorta. Because ultrashort-acting selective &bgr;1-adrenoreceptor antagonists provide neuroprotective effects after brain ischemia, we hypothesized that they would also ameliorate spinal cord injury after transient ischemia and reperfusion in rats. METHODS:Male Sprague-Dawley rats were randomly assigned to one of the following 4 groups: saline (received IV infusion of 0.9% saline at a rate of 0.5 mL/h, n = 8), esmolol (esmolol 200 &mgr;g/kg/min, n = 8), landiolol (landiolol 50 &mgr;g/kg/min), or sham surgical (n = 6). Infusion of saline or drugs was initiated 30 minutes before spinal cord ischemia and continued for the subsequent 24-hour reperfusion. Spinal cord ischemia was induced by intraaortic balloon occlusion combined with proximal arterial hypotension for 10 minutes. The spinal cord was then reperfused for 24 hours. Ischemic injury was assessed in terms of the motor deficit index score of the hindlimb and the number of viable motor nerve cells in the anterior spinal cord at 24 hours after reperfusion. RESULTS:The motor deficit index scores were significantly lower in the esmolol and landiolol groups compared with the saline group (P < 0.05). Histopathologic evaluation of the spinal cord showed less damage in the esmolol and landiolol groups than in the saline group (P < 0.05). CONCLUSIONS:These data show that ultrashort-acting selective &bgr;1-adrenoreceptor antagonists can reduce neurological injury in a rat model of spinal cord ischemia-reperfusion.
Cerebellar anodal tDCS increases implicit learning when strategic re-aiming is suppressed in sensorimotor adaptation

Neurophysiological and neuroimaging work suggests that the cerebellum is critically involved in sensorimotor adaptation. Changes in cerebellar function alter behaviour when compensating for sensorimotor perturbations, as shown by non-invasive stimulation of the cerebellum and studies involving patients with cerebellar degeneration. It is known, however, that behavioural responses to sensorimotor perturbations reflect both explicit processes (such as volitional aiming to one side of a target to counteract a rotation of visual feedback) and implicit, error-driven updating of sensorimotor maps. The contribution of the cerebellum to these explicit and implicit processes remains unclear. Here, we examined the role of the cerebellum in sensorimotor adaptation to a 30° rotation of visual feedback of hand position during target-reaching, when the capacity to use explicit processes was manipulated by controlling movement preparation times. Explicit re-aiming was suppressed in one condition by requiring subjects to initiate their movements within 300ms of target presentation, and permitted in another condition by requiring subjects to wait approximately 1050ms after target presentation before movement initiation. Similar to previous work, applying anodal transcranial direct current stimulation (tDCS; 1.5mA) to the right cerebellum during adaptation resulted in faster compensation for errors imposed by the rotation. After exposure to the rotation, we evaluated implicit remapping in no-feedback trials after providing participants with explicit knowledge that the rotation had been removed. Crucially, movements were more adapted in these no-feedback trials following cerebellar anodal tDCS than after sham stimulation in both long and short preparation groups. Thus, cerebellar anodal tDCS increased implicit remapping during sensorimotor adaptation, irrespective of preparation time constraints. The results are consistent with the possibility that the cerebellum contributes to the formation of new visuomotor maps that correct perturbations in sensory feedback, even when explicit processes are suppressed during sensorimotor adaptation.
Antimicrobial activity of some Hypericum species.

The crude methanolic extracts of six species of Hypericum [H. caprifoliatum Cham. & Schlecht. , H. carinatum Griseb. , H. connatum Lam. , H. ternum A. St. Hil. , H. myrianthum Cham. & Schlecht. and H. polyanthemum Klotzsch ex Reichardt] growing in southern Brazil were analyzed for antimicrobial activity against several microorganisms (bacteria and fungi). The most active plant was H. caprifoliatum, which showed activity against Staphylococcus aureus. Only H. polyanthemum and H. ternum extracts were active against Bacillus subtilis. None of the crude methanolic extracts showed activity against S. epidermidis, Escherichia coli or Saccharomyces cerevisiae. Extracts from these species were evaluated chemically and tannin, flavonoid and phenolic acids were the prominent compounds. The plants contained quercitrin, hyperoside (except H. connatum) and, less frequently, isoquercitrin and chlorogenic acid. In contrast to H. perforatum, which has high concentrations of rutin, these species do not produce this flavonoid or it appears as traces. The tannin concentration varied between 5.1 and 16.7% in H. myrianthum and H. ternum, respectively.
Effects of progesterone administration on follicle‐stimulating hormone and prolactin release in estrogen treated eugonadal adult men

Summary. In order to investigate the modulatory effect of steroids on FSH secretion in vivo, we studied 16 human males, aged 51–81 years, affected by prostatic carcinoma. They were given estradiol or E2 plus progesterone (P), added at different times during E2 treatment. Daily blood samples were collected in order to determine LH, FSH, and PRL levels; moreover, blood samples were collected at 2 h intervals for 12 h on the day of P administration. We observed the expected biphasic effect on LH secretion, whereas daily basal FSH levels, during E2 treatment, decreased gradually and progressivly from the first day until the end of the study. FSH levels exhibited, after P administration, wide fluctuations, with peak levels observed from 2 to 6 h after P in 4 of 6 patients studied (at 72 h during E2 treatment). A clear trend toward FSH increase was also observed in 3 out of 5 patients in whom P was administrated 96 h after starting E2 administration. In this case, FSH increases were delayed, becoming evident between 8th and 10th h after P injection. Finally, during E2 administration basal PRL levels showed a progressive increase, which was significant in all three groups. In conclusion, these data confirm the biphasic effects of estrogen administration on LH secretion in eugonadal adult human males; while estrogens alone showed an inhibitory effect on FSH secretion, the addition of P induced also a positive action, resulting in a clear FSH peak in some patients tested. The time course of E2 and P administration seems to be critical for the hormone response pattern. This “positive” effect of P, previously shown in pre‐ and postmenopausal women and in castrated men, is therefore evocable also in the presence of testicular secretions, underlying that positive feedback effects on gonadotropins are not suppressed in adult male human subjects.
First-calving age and first-lactation milk production on Dutch dairy farms

Abstract Farmers attempting to reduce first-calving age (FCA) need to understand which rearing management factors influence FCA and first-lactation milk production (FLP). Reduced FCA might be associated with lower FLP. This study describes the association between herd FCA, FLP, and several herd-level health and rearing management variables and describes the association between FCA and FLP at the cow level. It uses data from a 2010 survey of 100 Dutch dairy farms about general management, colostrum and milk feeding, housing, cleanliness, healthcare, disease, and breeding. It also used available data on FCA and 305-d FLP at both cow and herd level. The associations between median FCA and median FLP of the herd and herd-level health and rearing management variables were determined using multivariate regression analysis. The median FCA was associated with minimum age of first insemination, feeding of waste milk, and the amount of milk given preweaning. The median FLP was associated with median FCA and vaccination status for bovine respiratory syncytial virus. The association between FCA and FLP (based on 8,454 heifers) was analyzed with a single-effect linear mixed model, where the dependent variable was either FCA or relative FCA (defined as the difference between FCA of the heifer and median FCA of the herd to which they belonged). Heifers having an FCA of 24mo produced, on average, 7,164kg of milk per 305d, and calving 1mo earlier gave 143kg less milk per 305d. When FCA did not deviate from the median herd FCA, heifers produced, on average, 7,272kg of milk per 305d. From the median FCA of the herd, heifers calving 1mo earlier produced 90kg of milk per 305d less, and heifers calving 1mo later produced 86kg per 305d more. This is the first study that explained FLP using relative FCA. It assumes that heifers raised within the same farm have similar development because they are similarly managed. Similar management is reflected by the median FCA of the herd, with a deviation of the heifer’s FCA from median FCA reflecting the heifer’s development relative to the herd’s average. The advantage of using relative FCA was that it accounts for between-farm differences in rearing management. It showed that earlier insemination without adjusting management to ensure sufficient development lowers FLP. An economic optimum exists between rearing costs, FCA, and FLP and, as a consequence, decisions with regard to young stock management should be made with care.
Diabetes mellitus as a risk factor for death from stroke. Prospective study of the middle-aged Finnish population.

BACKGROUND AND PURPOSE High blood pressure is the most important risk factor for stroke. It is also known that diabetic patients are at increased risk of both hypertension and stroke. The aim of this study was to assess the independent effect of diabetes as a risk factor for stroke. Results from the previous studies of this question have been somewhat inconclusive. METHODS We performed a prospective study (average follow-up, 16.4 years) of 8077 men and 8572 women who had participated in risk factor surveys in Eastern Finland in 1972 (20 years of follow-up) and 1977 (15 years of follow-up). Risk factors included in the current analyses were smoking, blood pressure, antihypertensive drug treatment, serum total cholesterol, and diabetes either at baseline or developed during the follow-up. Age- and risk factor-adjusted relative risks for death of stroke were determined with the Cox proportional hazards model. RESULTS Diabetes mellitus was the strongest risk factor for death from stroke among both men and women in univariate and multivariate analyses. In addition, smoking and systolic blood pressure appeared to be independent risk factors among both sexes, as did serum total cholesterol among men. Men with diabetes at baseline appeared to be at a sixfold increased risk of death from stroke, while relative risk for men who developed diabetes during the follow-up was 1.7. In women, those who were diabetic at baseline were at higher risk of stroke than women who developed diabetes later (relative risks, 8.2 and 3.7, respectively). Of stroke deaths, 16% in men and 33% in women were attributed to diabetes. CONCLUSIONS Diabetic subjects have a very high risk of death from stroke, particularly women. Our data also suggest that the duration of diabetes is an important factor contributing to the risk of stroke.
The energy profiles of atomic conformational transition intermediates of adenylate kinase

The elastic network interpolation (ENI) (Kim et al., Biophys J 2002;83:1620–1630) is a computationally efficient and physically realistic method to generate conformational transition intermediates between two forms of a given protein. However it can be asked whether these calculated conformations provide good representatives for these intermediates. In this study, we use ENI to generate conformational transition intermediates between the open form and the closed form of adenylate kinase (AK). Based on Cα‐only intermediates, we construct atomic intermediates by grafting all the atoms of known AK structures onto the Cα atoms and then perform CHARMM energy minimization to remove steric conflicts and optimize these intermediate structures. We compare the energy profiles for all intermediates from both the CHARMM force‐field and from knowledge‐based energy functions. We find that the CHARMM energies can successfully capture the two energy minima representing the open AK and closed AK forms, while the energies computed from the knowledge‐based energy functions can detect the local energy minimum representing the closed AK form and show some general features of the transition pathway with a somewhat similar energy profile as the CHARMM energies. The combinatorial extension structural alignment (Shindyalov et al., 1998;11:739–747) and the k‐means clustering algorithm are then used to show that known PDB structures closely resemble computed intermediates along the transition pathway. Proteins 2009. © 2009 Wiley‐Liss, Inc.
Pharmacokinetics of cefpiramide (SM-1652) in humans

The pharmacokinetics of cefpiramide (SM-1652) were studied after the intravenous administration of single or multiple doses to 21 healthy volunteers. The cefpiramide concentration in plasma at time zero after a bolus intravenous injection of 500 or 1,000 mg was 152 or 303 micrograms/ml, respectively. The maximum cefpiramide level in plasma at the end of a 1-h infusion of 1,000 or 2,000 mg was 166 or 317 micrograms/ml, respectively. The mean plasma half-life of cefpiramide in 15 subjects who received a single dose of 500 or 1,000 mg was 4.44 h. There was no evidence of drug accumulation in plasma when 500 or 1,000 mg of cefpiramide was administered 11 times at 12-h intervals. Urinary excretion of cefpiramide over a 24-h period was ca. 22.5%, regardless of the intravenous administration technique and the dosage. Fecal recoveries of cefpiramide varied from 0 to 36.9% in different subjects.