Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting a neuropeptide to discrete regions of the motor arborizations of a single neuron

SUMMARY The heart excitor (HE) motor neuron in the leech Hirudo releases acetylcholine (ACh) and a peptide, FMRFamide, to regulate the contractile activity of the heart tube and associated side vessels. Consistent with Dale's principle, it was assumed that both neurotransmitters were localized to all presynaptic varicosities. However, we found discrete peptide-positive and peptide-negative varicosities associated with particular sites of innervation on the heart tube. We produced dual-labeled HE neurons by pressure injecting Neurobiotin into single HE cell bodies and applied anti-FMRFamide antibodies on the same preparations. Consistent with initial expectations, peptide-labeled varicosities were numerous and widely distributed along the heart tube and at one of the three side vessels, the latero-abdominal vessel. Nevertheless, some Neurobiotin-labeled varicosities along the heart tube lacked peptide label entirely. Moreover, there were dense and distinct peptide-negative innervations at the valve junctions of the latero-dorsal and latero-lateral vessels at each segment. Nevertheless, the peptide label was found in HE axons and varicosities that projected distally along the side vessels. Therefore, the more proximal peptide-negative clusters cannot simply be the result of restricted transport or deficient staining of peptide. Rather, we infer that FMRFamide is transported to (or selectively excluded from) discrete locations and that ACh is present in varicosities that lacked peptide. Such targeting of neurotransmitters could be described using a discrete targeting model of synaptic transmission. Compared with Dale's principle, this model may provide a more complete perspective of chemical communication than previously understood.
An expanded phenotype of maternal SSA/SSB antibody-associated fetal cardiac disease

Objectives. Conventional manifestations of fetal Sjögren's antibodies (SSA/SSB) associated cardiac disease include atrioventricular block (AVB), transient sinus bradycardia, endocardial fibroelastosis (EFE) and dilated cardiomyopathy. We describe other manifestations of cardiac disease. Methods. We describe three fetuses with unique myocardial and conduction system disease. Results. One had isolated EFE with subsequent mitral and tricuspid valve chordal avulsion, the second had sinoatrial and infrahissian conduction system disease, and in both, neonatal progression to life threatening disease occurred. The third had sinus node dysfunction and atrial flutter. Conclusion. These findings expand the clinical phenotype of maternal SSA/SSB antibody associated fetal cardiac disease.
Involvement of M2‐polarized macrophages in the ascites from advanced epithelial ovarian carcinoma in tumor progression via Stat3 activation

Ascites macrophages in advanced epithelial ovarian cancer (AdEOC) are involved in cancer metastasis and progression by modifying the tumor microenvironment. However, the precise mechanisms of cell‐to‐cell interaction between macrophages and tumor cells are still unclear. This study focused on the activation of signal transducer and activator of transcription 3 (Stat3) which is a critical signal transduction molecule at a point of convergence for numerous oncogenic signaling pathways as well as controlling the M2‐poralization of macrophages. AdEOC ascites, in which high concentration of interleukin (IL)‐6, IL‐10, growth‐related oncogene‐alpha and vascular endothelial growth factor were detected, stimulated the proliferation of SKOV3 cells, a human ovarian cancer cell line. The simultaneous blocking of IL‐6 and IL‐10 by neutralizing antibodies suppressed ascites‐induced tumor cell proliferation. Stat3 activation in SKOV3 cells was induced by co‐culture with macrophages especially with macrophage colony stimulating factor‐primed M2 macrophages but lesser extent with granulocyte‐macrophage colony stimulating factor‐primed immature macrophages. Cyclin‐D1 expression in SKOV3 cells was also significantly induced by co‐culture with macrophages. Blocking of Stat3 in macrophages by small interfering RNA inhibited the production of IL‐6 and IL‐10 by macrophages, and suppressed Stat3 activation and cyclin‐D1 induction in co‐cultured SKOV3 cells. Stat3 activation in SKOV3 cells was abrogated by simultaneous neutralization of IL‐6 and IL‐10. These results indicate that Stat3 activation by IL‐6 and IL‐10 plays an important role in cell‐to‐cell interaction between tumor cells and macrophages in the ascites of AdEOC. (Cancer Sci 2010)
Clinical Bacteriology

Following introductory chapters on the nature, structure and function of bacteria, diagnostic methods and antibiotic use, the principles are then applied to each organ system. Here relevant aspects of epidemiology, pathogenesis, diagnosis, treatment and public health are covered. There are chapters on infection is a modern society, including the immuncompromised patient, and infection control in the hospital and community.
Serelaxin: insights into its haemodynamic, biochemical, and clinical effects in acute heart failure.

This editorial refers to ‘A randomized, double-blind, placebo-controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failure’, by P. Ponikowski et al. doi:10.1093/eurheartj/eht459 Treatment for acute heart failure (AHF) has not changed much in the last two decades.1 Intravenous (i.v.) drugs such as levosimendan, nesiritide, rolofylline, and tezosentan have been studied in phase III randomized controlled trials (RCTs) with disappointing results. None of these drugs improved dyspnoea, worsening heart failure, readmissions to hospital, cardiovascular mortality, or all-cause mortality in AHF patients, mostly during short-term follow-up.1 These drugs increased the probability of ventricular and atrial arrhythmias or symptomatic hypotension (levosimendan, nesiritide), or seizures and strokes (rolofylline). Ularitide, a novel natriuretic peptide, is undergoing a phase III RCT focused on symptoms and cardiovascular mortality. Several reasons for negative results are possible, including high heterogeneity of patients with AHF, several sources of bias in RCTs, scarcity of outcomes, and incomplete pre-clinical evaluation of drugs. Serelaxin, a recombinant human relaxin-2 peptide, regulates maternal adaptations to pregnancy, including arterial vasodilation, increased cardiac output, and increased renal blood flow.2 Given its potential for the treatment of AHF, this drug has been tested in phase II (Pre-RELAX-AHF)3 and phase III (RELAX-AHF)4 RCTs. These trials aimed to improve the design issues of other i.v. drugs for AHF. In the dose-finding Pre-RELAX-AHF trial,3 234 patients with AHF, dyspnoea, congestion on chest X-ray, increased brain natriuretic peptide (BNP) or N-terminal pro-hormone of BNP (NT-proBNP), mild to moderate renal insufficiency, and systolic blood pressure (SBP) >125 mmHg received a 48 h i.v. infusion of serelaxin vs. placebo. The authors felt that these patients had more chances to obtain benefit from serelaxin, with lower chances of harmful effects. Indeed, they found improvements in dyspnoea (as measured by a visual analogue scale …
Social factors affecting ART adherence in rural settings in Zambia

Abstract The purpose of this study was to assess the factors that influence ART adherence arising in rural settings in Zambia. A survey was conducted with face-to-face interviews using a semi-structured questionnaire and written informed consent was obtained at ART sites in Mumbwa District in rural Zambia. The questionnaire included items such as the socio-demographic characteristics of respondents, support for adherence, ways to remember when to take ARVs at scheduled times, and the current status of adherence. Valid responses were obtained from 518 research participants. The mean age of the respondents was 38.3 years and the average treatment period was 12.5 months. More than half of the respondents (51%) were farmers, about half (49%) did not own a watch, and 10% of them used the position of the sun to remember when to take ARVs. Sixteen percent of respondents experienced fear of stigma resulting from taking ARVs at work or home, and 10% felt pressured to share ARVs with someone. Eighty-eight percent of the participants reported that they had never missed ARVs in the past four days. Multivariable logistic regression analysis identified age (38 years old or less, odds ratio (OR) = 2.5, 95% confidence interval (CI): 1.3–4.8, p=0.005), “remembering when to take ARVs based on the position of the sun” (OR = 3.3, 95% CI: 1.3–8.8, p=0.016), and “feeling pressured to share ARVs with someone” (OR = 4.4, 95% CI: 1.6–12.0, p=0.004) as independent factors for low adherence. As ART services expand to rural areas, program implementers should pay more attention to more specific factors arising in rural settings since they may differ from those in urban settings.
Impact of using different laboratory assays to detect human leukocyte antigen antibodies in female blood donors

BACKGROUND: HLA antibodies passively transferred to transfused recipients may cause transfusion reactions such as transfusion‐related acute lung injury (TRALI), but in many of the reported TRALI incidents, no white blood cell antibodies have been identified. We investigated whether a higher number of anti‐HLA would be detected in donor's plasma by using a method with potential higher sensitivity rate.
Statins and stroke

It is well known that drugs that bring down the bad cholesterol in the blood (statins) can reduce the risk of a second heart attack after a first heart attack occurs. We do not know whether this is also true for stroke. Heart attacks happen when the heart muscle does not get enough blood and oxygen because of a blocked blood vessel. A similar problem happens with stroke, when blood vessels to the brain are blocked. Therefore, it is reasonable to think that statins may help prevent second strokes as well. Until recently, there was little information about whether statins can reduce stroke risk. Lately, one new study1 did test this question and found that the risk of a second stroke after a first one was lowered by statins. However, it is not clear whether this is only true of the statin that was tested, or if it is an effect that can be seen with all statins. In a study in this issue of Neurology ®, the records of 794 first-time stroke patients were reviewed.2 Records for all of these patients tracked what happened to them over the next 10 years. The study team carefully recorded all of their test results and all of their risk factors for stroke such as smoking and high blood pressure. All patients had experienced a stroke, and it was …
Proteomic Screening and Lasso Regression Reveal Differential Signaling in Insulin and Insulin-like Growth Factor I (IGF1) Pathways *

Insulin and insulin-like growth factor I (IGF1) influence cancer risk and progression through poorly understood mechanisms. To better understand the roles of insulin and IGF1 signaling in breast cancer, we combined proteomic screening with computational network inference to uncover differences in IGF1 and insulin induced signaling. Using reverse phase protein array, we measured the levels of 134 proteins in 21 breast cancer cell lines stimulated with IGF1 or insulin for up to 48 h. We then constructed directed protein expression networks using three separate methods: (i) lasso regression, (ii) conventional matrix inversion, and (iii) entropy maximization. These networks, named here as the time translation models, were analyzed and the inferred interactions were ranked by differential magnitude to identify pathway differences. The two top candidates, chosen for experimental validation, were shown to regulate IGF1/insulin induced phosphorylation events. First, acetyl-CoA carboxylase (ACC) knock-down was shown to increase the level of mitogen-activated protein kinase (MAPK) phosphorylation. Second, stable knock-down of E-Cadherin increased the phospho-Akt protein levels. Both of the knock-down perturbations incurred phosphorylation responses stronger in IGF1 stimulated cells compared with insulin. Overall, the time-translation modeling coupled to wet-lab experiments has proven to be powerful in inferring differential interactions downstream of IGF1 and insulin signaling, in vitro.
Lithium for bipolar disorder: a review of the recent literature

Lithium is a commonly prescribed treatment for bipolar disorder. Many early studies on which its use has been historically based no longer meet current research standards. A large number of studies with more modern designs have been recently published warranting a review. New research adds to the evidence for lithium’s efficacy in mania and maintenance. There is also additional evidence, albeit less robust, to support its benefit in bipolar depression and mixed episodes. Meta-analyses of mainly observational data have found reduced suicidal behavior in bipolar patients taking lithium. Careful monitoring and prescribing can reduce the risk of adverse effects.
Numerical investigation of boiling and forced convection heat transfer in inclined porous enclosure using modified enthalpy formulation

Two-Phase flow in an inclined rectangular porous media, under unsteady-state condition, has been numerically investigated in this article, based on the modified h- formulation of Two-Phase Mixture Model (TPMM). The governing equations have been discretised using Finite Volume Method (FVM) and solved iteratively in a SIMPLE-like manner. Effects of various parameters on the flow and temperature fields have been investigated, which clearly demonstrated that the inclination angle strongly affect the boiling initiation. Recirculating flow has been observed when the inclination angle θ>0˚. The results clearly indicated that the operating conditions and the porous medium properties have significant effects on the initiation and termination of phase change process. A closer inspection of the results reveals that the presence of a critical inclination angle depending on the value of K * and, Re 1 which correspond to a maximum values of vapour volume. The modified h-formulation requires significantly less computational time as compared with the existing H- formulation of TPMM.
Networks, cognition and management of tacit knowledge

Knowledge is a magic term with multiple connotations and interpretations. It is an issue of academic discourse as well as one with important implications for business institutions. How we define and frame knowledge carries implications for the way we try to manage knowledge in organizations and the de facto knowledge in organizations also carries implications for the knowledge existing in organizations. Within the last few decades, there has been an increasing interest in the tacit dimension of knowledge, which is perhaps hardest to manage, as it cannot be formally communicated, and is often embedded in the routines and standard operating procedures of the organization. Focuses on characteristics of this strategic important knowledge and how it can be organized in networks. Should be read as a case for paying more attention to knowledge and networks and how to manage these in organizations.
Interactions of the PPARγ2 Polymorphism with Fat Intake Affecting Energy Metabolism and Nutritional Outcomes in Obese Women

Background/Aims: To determine the influence of the Pro12Ala polymorphism of the PPARγ2 gene and the dietary lipid intake on energy metabolism and nutritional outcomes in obese women after an acute fat load or following a low-calorie diet for 10 weeks. Methods: Sixty obese women (aged 30–46 years) participated in the study and were assigned to 2 groups depending on the genotype: Pro12Pro and Pro12Ala/Ala12Ala carriers. At baseline and after 2 nutritional (short- or long-term) interventions, measurement of anthropometrical and body composition (bioelectrical impedance) variables, dietary assessments, energy metabolism (indirect calorimetry) measurements as well as biochemical and molecular (PPARγ2 genotype) analyses were performed. All women received a high-fat test meal to determine the postprandial metabolism (short term) and an energy-restricted diet for 10 weeks (long term). Results: The frequencies of the Pro12Pro and Pro12Ala/Ala12Ala genotypes were 83.33 and 16.67%, respectively, and reached Hardy-Weinberg equilibrium. Interestingly, the postprandial energy expenditure after the fat load was higher in subjects carrying the Ala allele. At baseline, the habitual monounsaturated fatty acid (MUFA) intake inversely correlated with fat oxidation and body mass index in the obese Pro12Ala/Ala12Ala carriers, while a lower PUFA intake (%) in the long-term trial was associated with an increase in the respiratory quotient only in Ala carriers but not in the Pro12Pro genotyped group. Conclusions: The Pro12Ala polymorphism in the PPARγ2 gene influenced energy metabolism in the assayed short- and long-term situations since the response to both nutritional interventions differed according to the genotype. The results suggest that fat oxidation and energy expenditure may be lower in Pro12Pro carriers compared to Pro12Ala/Ala12Ala genotypes, while in obese women with Pro12Ala/Ala12Ala polymorphisms in the PPARγ2 gene fat oxidation was negatively correlated with the MUFA and PUFA (%) intake.
Kisspeptin–GPR54 Signaling Is Essential for Preovulatory Gonadotropin-Releasing Hormone Neuron Activation and the Luteinizing Hormone Surge

Kisspeptin and its receptor GPR54 have recently been identified as key signaling partners in the neural control of fertility in animal models and humans. The gonadotropin-releasing hormone (GnRH) neurons represent the final output neurons of the neural network controlling fertility and are suspected to be the primary locus of kisspeptin–GPR54 signaling. Using mouse models, the present study addressed whether kisspeptin and GPR54 have a key role in the activation of GnRH neurons to generate the luteinizing hormone (LH) surge responsible for ovulation. Dual-label immunocytochemistry experiments showed that 40–60% of kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) expressed estrogen receptor α and progesterone receptors. Using an ovariectomized, gonadal steroid-replacement regimen, which reliably generates an LH surge, ∼30% of RP3V kisspeptin neurons were found to express c-FOS in surging mice compared with 0% in nonsurging controls. A strong correlation was found between the percentage of c-FOS-positive kisspeptin neurons and the percentage of c-FOS-positive GnRH neurons. To evaluate whether kisspeptin and/or GPR54 were essential for GnRH neuron activation and the LH surge, Gpr54- and Kiss1-null mice were examined. Whereas wild-type littermates all exhibited LH surges and c-FOS in ∼50% of their GnRH neurons, none of the mutant mice from either line showed an LH surge or any GnRH neurons with c-FOS. These observations provide the first evidence that kisspeptin–GPR54 signaling is essential for GnRH neuron activation that initiates ovulation. This broadens considerably the potential roles and therapeutic possibilities for kisspeptin and GPR54 in fertility regulation.
Delay-dependent guaranteed cost control for T-S fuzzy systems with time delays

This study introduces a guaranteed cost control method for nonlinear systems with time-delays which can be represented by Takagi-Sugeno (T-S) fuzzy models with time-delays. The state feedback and generalized dynamic output feedback approaches are considered. The generalized dynamic output feedback controller is presented by a new fuzzy controller architecture which is of dual indexed rule base. It considers both the dynamic part and the output part of T-S fuzzy model which guarantees that the controller without any delay information can stabilize time-delay T-S fuzzy systems. Based on delay-dependent Lyapunov functional approach, some sufficient conditions for the existence of state feedback controller are provided via parallel distributed compensation (PDC) first. Second, the corresponding conditions are extended into the generalized dynamic output feedback closed-loop system via so-called generalized PDC technique. The upper bound of time-delay can be obtained using convex optimization such that the system can be stabilized for all time-delays whose sizes are not larger than the bound. The minimizing method is also proposed to search the suboptimal upper bound of guaranteed cost function. The effectiveness of the proposed method can be shown by the simulation examples.
An efficient SQL-based querying method to RDF schemata

Applications based on knowledge engineering require operations on semantic data. Modern systems have to deal with large data volumes and the challenge is to process and search these data effectively. One of the aspects of efficiency is the ability to query those data with respect to their semantics. In this area an RDF data model and a SPARQL query language gained the highest popularity and are de facto standards. The problem is that most data in modern systems are stored in relational databases and have no formal and precisely expressed semantics, although operations on those data are fast and scalable. Traditionally, in this area relational data are transformed to a form expected by reasoning and querying systems (usually RDF based). In this work a method of query rewrit- ing is presented that translates a query to an RDF data structure (i.e. SPARQL query) to a SQL query executed by RDBMS. Trans- forming queries instead of data has many advantages and might lead to significant increase of data extraction efficiency.
A Review of Hybrid Brain-Computer Interface Systems

Increasing number of research activities and different types of studies in brain-computer interface (BCI) systems show potential in this young research area. Research teams have studied features of different data acquisition techniques, brain activity patterns, feature extraction techniques, methods of classifications, and many other aspects of a BCI system. However, conventional BCIs have not become totally applicable, due to the lack of high accuracy, reliability, low information transfer rate, and user acceptability. A new approach to create a more reliable BCI that takes advantage of each system is to combine two or more BCI systems with different brain activity patterns or different input signal sources. This type of BCI, called hybrid BCI, may reduce disadvantages of each conventional BCI system. In addition, hybrid BCIs may create more applications and possibly increase the accuracy and the information transfer rate. However, the type of BCIs and their combinations should be considered carefully. In this paper, after introducing several types of BCIs and their combinations, we review and discuss hybrid BCIs, different possibilities to combine them, and their advantages and disadvantages.