Miracle-dz/UniFAR-FTUs huggingface dataset:
Ligand Binding and Modulation of Cyclic AMP Levels Depend on the Chemical Nature of Residue 192 of the Human Cannabinoid Receptor 1

Abstract: The human cannabinoid receptor associated with the CNS (CB1) binds Δ9‐tetrahydrocannabinol, the psychoactive component of marijuana, and other cannabimimetic compounds. This receptor is a member of the seven transmembrane domain G protein‐coupled receptor family and mediates its effects through inhibition of adenylyl cyclase. An understanding of the molecular mechanisms involved in ligand binding and receptor activation requires identification of the active site residues and their role. Lys192 of the third transmembrane domain of the receptor is noteworthy because it is the only nonconserved, charged residue in the transmembrane region. To investigate the properties of this residue, which are important for both ligand binding and receptor activation, we generated mutant receptors in which this amino acid was changed to either Arg (K192R), Gln (K192Q), or Glu (K192E). Wild‐type and mutant receptors were stably expressed in Chinese hamster ovary cells and were evaluated in binding assays with the bicyclic cannabinoid CP‐55,940 and the aminoalkylindole WIN 55,212‐2. We found that only the most conservative change of Lys to Arg allowed retention of binding affinity to CP‐55,940, whereas WIN 55,212‐2 bound to all of the mutant receptors in the same range as it bound the wild type. Analysis of the ligand‐induced inhibition of cyclic AMP production in cells expressing each of the receptors gave an EC50 value for each agonist that was comparable to its binding affinity, with one exception. Although the mutant K192E receptor displayed similar binding affinity as the wild type with WIN 55,212‐2, an order of magnitude difference was observed for the EC50 for cyclic AMP inhibition with this compound. The results of this study indicate that binding of CP‐55,940 is highly sensitive to the chemical nature of residue 192. In contrast, although this residue is not critical for WIN 55,212‐2 binding, the data suggest a role for Lys192 in WIN 55,212‐2‐induced receptor activation.
Neonatal herpes virus infection: Duration of extracorporeal support and the dose of acyclovir

To the Editor: Prodhan et al (1) provide challenging information about the outcome when neonates with disseminated herpes simplex virus (HSV) infection were put on extracorporeal membrane oxygenation (ECMO): 75% of the babies died, and the authors “consider ECMO support almost futile in this population. ” However, the outcome might be improved if infants without evidence of severe encephalopathy were allowed longer on ECMO to recover from the infection, and if a higher dose of acyclovir were used. The severe tissue damage caused by disseminated HSV infection is unlikely to recover in less than 1 to 2 wks. Of 24 neonates with HSV in the extracorporeal life support organization registry who were given ECMO for 7 days, only three (12.5%) survived compared with seven (36.8%) of 19 neonates who were on ECMO for 7 days or more. Unfortunately, we do not know how often ECMO was withdrawn because of severe encephalitis. However, we do know that seven (70%) of the ten survivors were offered ECMO for 7 days or more; the duration of ECMO in the survivors was 89, 123, 135, 168, 204, 210, 218, 224, 300, and 482 hrs. In the United States, term neonates with disseminated HSV infection are usually treated with 20 mg/kg acyclovir given intravenously every 8 hrs (2) This regimen is based on an open-label study of acyclovir: mortality decreased from 61% with a dose of 10 mg/kg to 57% with 15 mg/kg, and 31% with 20 mg/kg every 8 hrs. Unfortunately, higher doses were not studied (2). In our intensive care unit and some hospitals in the United Kingdom (3), the usual dose of acyclovir is 500 mg/m given every 8 hrs, which is 33 mg/kg every 8 hrs for a 3.5 kg neonate with a surface area of 0.25 m. The higher dose seems appropriate for infants with overwhelming HSV infection (3). Prodhan et al generously provided information to us when we put a term neonate on ECMO recently. HSV-2 virus was detected by polymerase chain reaction in blood, bronchoalveolar lavage, and skin, but not cerebrospinal fluid. The baby developed fever at 42 hrs of age, was transferred to a neonatal intensive care unit at 63 hrs, started acyclovir at 96 hrs, and went on open-chest ECMO in our intensive care unit at 121 hrs with flows of up to 250 mL/kg/min. He had septic shock with disseminated intravascular coagulation and cardiac, respiratory, renal, and hepatic failure. He was weaned off ECMO after 13 days, and received mechanical ventilation for 9 days followed nasal continuous positive airflow pressure. A magnetic resonance image of the brain was normal, but computer tomography of the lung showed two pneumatoceles. He was discharged at 2 months of age, on intranasal oxygen for 2 months, and acyclovir for 6 months. Neurologic examination was normal at 6 months of age. We suggest that term neonates with severe disseminated HSV infection should be treated with 500 mg/m acyclovir intravenously every 8 hrs. If an infant does not have severe encephalitis and ECMO is offered, it will usually need to be provided for at least 1 to 2 wks. The authors have not disclosed any potential conflicts of interest.
Role of Phosphoinositide 3-Kinase &agr;, Protein Kinase C, and L-Type Ca2+ Channels in Mediating the Complex Actions of Angiotensin II on Mouse Cardiac Contractility

Although angiotensin II (Ang II) plays an important role in heart disease associated with pump dysfunction, its direct effects on cardiac pump function remain controversial. We found that after Ang II infusion, the developed pressure and +dP/dtmax in isolated Langendorff-perfused mouse hearts showed a complex temporal response, with a rapid transient decrease followed by an increase above baseline. Similar time-dependent changes in cell shortening and L-type Ca2+ currents were observed in isolated ventricular myocytes. Previous studies have established that Ang II signaling involves phosphoinositide 3-kinases (PI3K). Dominant-negative inhibition of PI3K&agr; in the myocardium selectively eliminated the rapid negative inotropic action of Ang II (inhibited by ≈90%), whereas the loss of PI3K&ggr; had no effect on the response to Ang II. Consistent with a link between PI3K&agr; and protein kinase C (PKC), PKC inhibition (with GF 109203X) reduced the negative inotropic effects of Ang II by ≈50%. Although PI3K&agr; and PKC activities are associated with glycogen synthase kinase-3&bgr; and NADPH oxidase, genetic ablation of either glycogen synthase kinase-3&bgr; or p47phox (an essential subunit of NOX2-NADPH oxidase) had no effect on the inotropic actions of Ang II. Our results establish that Ang II has complex temporal effects on contractility and L-type Ca2+ channels in normal mouse myocardium, with the negative inotropic effects requiring PI3K&agr; and PKC activities.
Sparse Camera Network for Visual Surveillance -- A Comprehensive Survey

Technological advances in sensor manufacture, communication, and computing are stimulating the development of new applications that are transforming traditional vision systems into pervasive intelligent camera networks. The analysis of visual cues in multi-camera networks enables a wide range of applications, from smart home and ofﬁce automation to large area surveillance and trafﬁc surveillance. While dense camera networks - in which most cameras have large overlapping ﬁelds of view - are well studied, we are mainly concerned with sparse camera networks. A sparse camera network undertakes large area surveillance using as few cameras as possible, and most cameras have non-overlapping ﬁelds of view with one another. The task is challenging due to the lack of knowledge about the topological structure of the network, variations in the appearance and motion of speciﬁc tracking targets in different views, and the difﬁculties of understanding composite events in the network. In this review paper, we present a comprehensive survey of recent research results to address the problems of intra-camera tracking, topological structure learning, target appearance modeling, and global activity understanding in sparse camera networks. A number of current open research issues are discussed.
Cis binding between inhibitory receptors and MHC class I can regulate mast cell activation

Allergy is caused by immune effector cells, including mast cells and basophils. Cellular signaling that activates these effector cells is regulated by different inhibitory receptors on their surface. We show that human leukocyte immunoglobulin (Ig)-like receptor (LILR) B2 and its mouse orthologue, paired Ig-like receptor (PIR)–B, constitutively associate to major histocompatibility complex (MHC) class I on the same cell surface (in cis). The IgE-mediated effector responses were augmented in β2-microglobulin (β2m) and PIR-B–deficient mast cells. In addition, the increased cytokine production of β2m-deficient mast cells was not affected by the co-culture with MHC class I–positive mast cells, showing that less cis interaction between PIR-B and MHC class I on mast cells led to the increased cytokine release. Thus, the constitutive cis binding between LILRB2 or PIR-B and MHC class I has an essential role in regulating allergic responses.
Color from Motion: Separate Contributions of Chromaticity and Luminance

‘Color from motion’ describes the perception of a spread of subjective color over achromatic regions seen as moving. The effect is produced with a stimulus display consisting of colored dots, randomly placed upon a white field, with dots in the test region differing in both chromaticity and luminance from those in the surround. Evidence is presented suggesting that color from motion may be regulated by mechanisms different from those for contour formation and color contrast. (1) Results based on ratings show that, in the absence of luminance differences between the dots in the test and those in the surround regions, chromaticity differences alone are sufficient to produce color spread from motion. As the equiluminance point is approached, subjective color spread is seen despite a reduction in the strength of the subjective contour. Thus, contour formation is not likely to be a prerequisite for color from motion. (2) Color matches show that the hue and saturation of the subjective color spread are determined largely by the chromaticity and the luminance of the dots in the test region, not by those of the dots in the surround for the values explored. This suggests that color from motion may arise in sites distinct from those responsible for the regulation of color contrast.
Protective effects of fermented rice vinegar sediment (Kurozu moromimatsu) in a diethylnitrosamine-induced hepatocellular carcinoma animal model

Kurozu moromimatsu is the sediment of Kurozu, a jar-fermented Japanese black vinegar produced from unpolished rice. Here, we examined the protective effects of Kurozu moromimatsu in a diethylnitrosamine-induced model of hepatocellular carcinoma. Thirty-two F344 rats were divided into two groups; the control group received basal CE-2 diet, and the Kurozu moromimatsu group received CE-2 diet containing Kurozu moromimatsu. At 16 weeks after initial intraperitoneal administration of diethylnitrosamine (150 mg/kg/week), serum was collected from half the rats. These rats were sacrificed and the liver was resected for histological examination of hematoxylin-eosin-stained sections and assay of matrix metalloproteinase-2 and matrix metalloproteinase-9 levels in tumor tissues. Glutathione S-transferase placental form-positive foci were evaluated by immunostaining for glutathione S-transferase placental form. The remaining rats were maintained for evaluation of survival. There were no significant differences of serum transaminases, tumor necrosis factor-alpha, and also no marked hepatic histological differences, between the two groups. However, the size of hepatocellular carcinomas was greatly decreased and the levels of activated matrix metalloproteinase-2 and -9 were significantly reduced in the Kurozu moromimatsu group. Further, survival was significantly prolonged in the Kurozu moromimatsu group compared with the control. These results indicate that Kurozu moromimatsu inhibited the growth of hepatocellular carcinoma.
Oral corticosteroid use and the risk of acute myocardial infarction in chronic obstructive pulmonary disease.

BACKGROUND Given the limited efficacy of oral corticosteroids in treating chronic obstructive pulmonary disease (COPD), the possible cardiac side effects of oral corticosteroids are of particular concern in an elderly population. The impact of the use of oral corticosteroids on the risk of acute myocardial infarction (AMI) in a cohort of patients with COPD was studied. METHODS The Saskatchewan health services databases were used to form a population-based cohort of 5648 patients aged 55 years or older who received a first treatment for COPD between 1990 and 1997. A nested case-control analysis was conducted: 371 cases presenting with a first myocardial infarction were matched with 1864 controls according to the length of follow-up, the date of cohort entry and age. Conditional logistic regression was used to adjust for sex, severity of COPD, systemic hypertension, diabetes and prior cardiovascular disease. RESULTS Only the current use of corticosteroids was associated with an increased risk of AMI (adjusted RR=2.01 [95% CI 1.13 to 3.58]), particularly when the current dose was larger than 25 mg/day of prednisone or the equivalent (adjusted RR=3.22 [95% CI 1.42 to 7.34]). This observed increase in risk rapidly returned to baseline after the cessation of the medication, suggesting that the use of such high doses reflected the treatment of acute exacerbations of the disease. CONCLUSIONS An association was found between the current use of oral corticosteroids and the occurrence of an AMI, suggesting that acute exacerbations of COPD are associated with an increased risk of acute coronary syndromes.
Numerical resolution of an anisotropic non-linear diffusion problem

This paper is devoted to the numerical resolution of an anisotropic non-linear diffusion problem involving a small parameter e, defined as the anisotropy strength reciprocal. In this work, the anisotropy is carried by a variable vector function b. The equation being supplemented with Neumann boundary conditions, the limit e → 0 is demonstrated to be a singular perturbation of the original diffusion equation. To address efficiently this problem, an Asymptotic-Preserving scheme is derived. This numerical method does not require the use of coordinates adapted to the anisotropy direction and exhibits an accuracy as well as a computational cost independent of the anisotropy strength.
Qualitative Analysis of Cognitive Interviews With School Children: A Web-Based Food Intake Questionnaire

Background The use of computers to administer dietary assessment questionnaires has shown potential, particularly due to the variety of interactive features that can attract and sustain children’s attention. Cognitive interviews can help researchers to gain insights into how children understand and elaborate their response processes in this type of questionnaire. Objective To present the cognitive interview results of children who answered the WebCAAFE, a Web-based questionnaire, to obtain an in-depth understanding of children’s response processes. Methods Cognitive interviews were conducted with children (using a pretested interview script). Analyses were carried out using thematic analysis within a grounded theory framework of inductive coding. Results A total of 40 children participated in the study, and 4 themes were identified: (1) the meaning of words, (2) understanding instructions, (3) ways to resolve possible problems, and (4) suggestions for improving the questionnaire. Most children understood questions that assessed nutritional intake over the past 24 hours, although the structure of the questionnaire designed to facilitate recall of dietary intake was not always fully understood. Younger children (7 and 8 years old) had more difficulty relating the food images to mixed dishes and foods eaten with bread (eg, jam, cheese). Children were able to provide suggestions for improving future versions of the questionnaire. Conclusions More attention should be paid to children aged 8 years or below, as they had the greatest difficulty completing the WebCAAFE.
Fast Domain Adaptation for Neural Machine Translation

Neural Machine Translation (NMT) is a new approach for automatic translation of text from one human language into another. The basic concept in NMT is to train a large Neural Network that maximizes the translation performance on a given parallel corpus. NMT is gaining popularity in the research community because it outperformed traditional SMT approaches in several translation tasks at WMT and other evaluation tasks/benchmarks at least for some language pairs. However, many of the enhancements in SMT over the years have not been incorporated into the NMT framework. In this paper, we focus on one such enhancement namely domain adaptation. We propose an approach for adapting a NMT system to a new domain. The main idea behind domain adaptation is that the availability of large out-of-domain training data and a small in-domain training data. We report significant gains with our proposed method in both automatic metrics and a human subjective evaluation metric on two language pairs. With our adaptation method, we show large improvement on the new domain while the performance of our general domain only degrades slightly. In addition, our approach is fast enough to adapt an already trained system to a new domain within few hours without the need to retrain the NMT model on the combined data which usually takes several days/weeks depending on the volume of the data.
The Short Form-36 is preferable to the SIP as a generic health status measure in patients undergoing elective total hip arthroplasty.

OBJECTIVE To assess the comparative usefulness of the Short Form-36 (SF-36) and the Sickness Impact Profile, (SIP) as generic health status measures in total hip arthroplasty. METHODS Analysis of preoperative and 3-month data of 54 consecutive patients undergoing total hip replacement for osteoarthritis or rheumatoid arthritis. Instruments were mailed to patients preoperatively and 3 months postoperatively. RESULTS In 10 of the 12 SIP subscales, but just 1 of the 8 SF-36 subscales, more than 40% of the patients had scores of zero. On a 100-point scale, the median global SIP was 12 (range 0-40) whereas the median global SF-36 was 50 (range 10-85). This indicates that many items of the SIP were not germane to patients undergoing joint arthroplasty. The global and, particularly, the physical dimensions of the SF-36 were more responsive than their SIP counterparts, as measured both by the standardized response mean (1.26 and 0.88, respectively) and the correlation with self-perceived improvement in quality of life (r = 0.37 and 0.26, respectively). The SF-36, but not the SIP, discriminated between patients with relatively good physical performance at 3 months with respect to their ability to work, to play sports, or to garden. CONCLUSION The SF-36 is briefer, more relevant, and more responsive than the SIP and is preferable as a generic health status measure in patients undergoing elective hip arthroplasty. The SF-36 should be tested in other populations as well as other conditions to determine whether it is a superior generic health status instrument for evaluative research in orthopedic surgery.
The ΔF508 Mutation in the Cystic Fibrosis Transmembrane Conductance Regulator Is Associated With Progressive Insulin Resistance and Decreased Functional β-Cell Mass in Mice

Cystic fibrosis (CF) is the result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CF-related diabetes affects 50% of adult CF patients. How CFTR deficiency predisposes to diabetes is unknown. Herein, we examined the impact of the most frequent cftr mutation in humans, deletion of phenylalanine at position 508 (ΔF508), on glucose homeostasis in mice. We compared ΔF508 mutant mice with wild-type (WT) littermates. Twelve-week-old male ΔF508 mutants had lower body weight, improved oral glucose tolerance, and a trend toward higher insulin tolerance. Glucose-induced insulin secretion was slightly diminished in ΔF508 mutant islets, due to reduced insulin content, but ΔF508 mutant islets were not more sensitive to proinflammatory cytokines than WT islets. Hyperglycemic clamps confirmed an increase in insulin sensitivity with normal β-cell function in 12- and 18-week-old ΔF508 mutants. In contrast, 24-week-old ΔF508 mutants exhibited insulin resistance and reduced β-cell function. β-Cell mass was unaffected at 11 weeks of age but was significantly lower in ΔF508 mutants versus controls at 24 weeks. This was not associated with gross pancreatic pathology. We conclude that the ΔF508 CFTR mutation does not lead to an intrinsic β-cell secretory defect but is associated with insulin resistance and a β-cell mass deficit in aging mutants.
Routing techniques in wireless sensor networks: a survey

Wireless sensor networks consist of small nodes with sensing, computation, and wireless communications capabilities. Many routing, power management, and data dissemination protocols have been specifically designed for WSNs where energy awareness is an essential design issue. Routing protocols in WSNs might differ depending on the application and network architecture. In this article we present a survey of state-of-the-art routing techniques in WSNs. We first outline the design challenges for routing protocols in WSNs followed by a comprehensive survey of routing techniques. Overall, the routing techniques are classified into three categories based on the underlying network structure: flit, hierarchical, and location-based routing. Furthermore, these protocols can be classified into multipath-based, query-based, negotiation-based, QoS-based, and coherent-based depending on the protocol operation. We study the design trade-offs between energy and communication overhead savings in every routing paradigm. We also highlight the advantages and performance issues of each routing technique. The article concludes with possible future research areas.
The effect of sex hormones on language processing

(compared to placebo) in both sexes increased production of real and novel irregular forms (break-broke, spling-splung) ðps < 0:05Þ, with no placebo/treatment by male/ female interaction. Performance at novel regulars (blick-blicked) decreased with hormone therapy (p < 0:05; no interaction with sex), likely due to increased irregularizations (blick-bluck). Importantly, accuracy at real regulars (swayed) increased in women ðp < 0:05Þ but decreased in men ðp < 0:01Þ. The study underscores the memorization of real regular past-tenses by women but not men and suggests that sex hormones (estrogen/testosterone) improve lexical retrieval/processing but not rulebased computations. These experiments support the language sex difference hypothesis, in expressive and receptive language, in morphology and at least in some aspects of syntax; experiment five implicates estrogen in these effects. No performance differences were found in the studies of healthy untreated adults, suggesting that the neurocognitive sex differences do not lead to obvious achievement differences. The data have educational and clinical implications, and strongly suggest that language studies should include sex as a design factor.