Miracle-dz/UniFAR-FTUs huggingface dataset:
Abnormalities of calcium cycling in the hypertrophied and failing heart.

Progressive deterioration of cardiac contractility is a central feature of congestive heart failure (CHF) in humans. In this report we review those studies that have addressed the idea that alterations of intracellular calcium (Ca(2+)) regulation is primarily responsible for the depressed contractility of the failing heart. The review points out that Ca(2+)transients and contraction are similar in non-failing and failing myocytes at very slow frequencies of stimulation (and other low stress environments). Faster pacing rates, high Ca(2+)and beta-adrenergic stimulation reveal large reductions in contractile reserve in failing myocytes. The underlying cellular basis of these defects is then considered. Studies showing changes in the abundance of L-type Ca(2+)channels, Ca(2+)transport proteins [sarcoplasmic reticulum Ca(2+)ATPase (SERCA2), phospholamban (PLB), Na(+)/Ca(2+) exchanger (NCX)] and Ca(2+) release channels (RYR) in excitation-contraction coupling and Ca(2+)release and uptake by the sarcoplasmic reticulum (SR) are reviewed. These observations support our hypotheses that (i) defective Ca(2+)regulation involves multiple molecules and processes, not one molecule, (ii) the initiation and progression of CHF inolves defective Ca(2+)regulation, and (iii) prevention or correction of Ca(2+)regulatory defects in the early stages of cardiac diseases can delay or prevent the onset of CHF.
Community : a powerful label? Connecting wind energy to rural Ireland

Much of the research on the social sustainability of renewable technologies has focused on local acceptance issues, community benefits from exogenous developments, and matters related to the planning and development process. Grassroots-initiated wind energy schemes as a form of rural enterprise have received less attention, especially in the Irish context. Using a case study approach, this paper analyses the challenges and opportunities faced in progressing community wind energy projects in rural Ireland. Such an analysis is especially relevant given Ireland’s commitment to developing a fair and sustainable society as advocated in its Sustainable Development Framework. With the decline of agriculture and considerable outmigration from rural areas, wind energy represents an opportunity to revitalize rural economies. More generally, as opposition to wind turbines and associated infrastructure is common in Ireland, it is clear that the relevant authorities must engage local stakeholders more meaningfully in the planning and development process. In this vein, community energy initiatives have the potential to boost rural economies, enhance acceptance, and develop knowledge networks at the local level. Drawing lessons from a community wind energy case study, it is argued that community projects can be nurtured in Ireland by (i) engaging communities, especially weak stakeholders, in both agenda setting and the planning and development process for individual projects, and (ii) ensuring that technical and financial support is available to communities, while (iii) being careful to apply the ‘community’ label only to initiatives that can meet the expectations of such a project.
CD40 ligand is functionally expressed on human eosinophils

CD40 ligand (CD40L), a surface molecule which can be expressed by T cells, mast cells and basophils, has been shown to be involved in the control of B cell proliferation, immunoglobulin class switching as well as in the activation of monocytes and T cells. We demonstrate that CD40L can also be expressed constitutively by eosinophils from an hypereosinophilic patient or, upon activation, by the eosinophilic cell line EOL‐3 and normal blood eosinophils. Eosinophils were able to induce, in conjunction with IL‐4, CD40L‐dependent B cell proliferation in vitro. These results suggest that CD40L could play a role in the inflammatory processes during which eosinophil infiltration and activation are observed.
Colocalization of thrombospondin and syndecan during murine development

Thrombospondin is an adhesive glycoprotein that is thought to play a role in tissue genesis and repair. We have used a monoclonal anti‐thrombospondin antibody, designated 5G11, to localize thrombospondin in paraformaldehyde fixed, paraffin‐embedded sections of developing mouse embryos. Thrombospondin expression is observed in uterine smooth muscle, endometrial glands, the decidua, and trophoblastic giant cells during the initial phase of post‐implantation development in the embryo. Cardiac myocytes and neuroepithelial cells show positive staining for thrombospondin at day 8.5 of gestation, and this expression continues throughout the development of the myocardium and central nervous system. Strong staining for thrombospondin is seen in developing bone and in the liver. Thrombospondin is also observed in developing smooth muscle and skeletal muscle, as well as in a variety of epithelia, including the epidermis, small intestinal epithelium, lens epithelium, renal tubular epithelium, and the epithelium of the developing tooth. Comparison of thrombospondin staining with that of two known cell surface receptors for thrombospondin, syndecan and the vitronectin receptor, reveals remarkable colocalization of thrombospondin and syndecan in all tissues, but almost no coexpression with the vitronectin receptor. Coexpression of thrombospondin and syndecan may play an important role in cell‐cell or cell‐matrix interactions during development. © 1992 Wiley‐Liss, Inc.
Mitochondrial DNA sequence variation within the remnant populations of the endangered numbat (Marsupialia: Myrmecobiidae: Myrmecobius fasciatus)

The numbat has been reduced to two populations in Western Australia. To better understand the effects of range reduction on gene flow and genetic variation, and to address questions crucial for the species’ management, we analysed mitochondrial DNA (mtDNA) sequences of free‐ranging individuals and museum specimens. The results suggest recent connectivity between the remnant populations, although one of those may have lost significant amounts of genetic diversity during the recent population size reduction. We propose that for management purposes the remnant populations should be treated as a single historical lineage and that, subject to certain caveats, consideration should be given to population augmentation by translocation.
A phylogeny and classification of the Muhlenbergiinae (Poaceae: Chloridoideae: Cynodonteae) based on plastid and nuclear DNA sequences.

UNLABELLED PREMISE OF THE STUDY To understand the origins of C(4) grasslands, we must have a better interpretation of plant traits via phylogenetic reconstruction. Muhlenbergiinae, the largest subtribe of C(4) grasses in Mexico and the southwestern United States (with 176 species), is taxonomically poorly understood. • METHODS We conducted a phylogenetic analysis of 47 genera and 174 species using six plastid regions (ndhA intron, ndhF, rps16-trnK, rps16 intron, rps3, and rpl32-trnL) and the nuclear ITS 1 and 2 (ribosomal internal transcribed spacer) regions to infer evolutionary relationships and revise the classification. • KEY RESULTS In our analyses, Muhlenbergia (ca. 153 species) is paraphyletic, with nine genera (Aegopogon, Bealia, Blepharoneuron, Chaboissaea, Lycurus, Muhlenbergia, Pereilema, Redfieldia, Schaffnerella, and Schedonnardus) found nested within. We recognized the following five well-supported monophyletic lineages within Muhlenbergia: subg. Muhlenbergia, with species that have phosphoenolpyruvate carboxykinase-like leaf anatomy and long, scaly rhizomes; subg. Trichochloa with long-lived species that are relatively tall (up to 3 m); subg. Clomena with 3-nerved upper glumes; sect. Pseudosporobolus species with narrow panicles and plumbeous spikelets; and sect. Bealia species with lemmas with hairy margins and midveins. • CONCLUSIONS We propose expanding the circumscription of Muhlenbergia to include the other nine genera in this subtribe and make the following new combinations: Muhlenbergia subg. Bealia, M. diandra, M. geminiflora, M. paniculata, M. phleoides, M. subg. Pseudosporobolus (also lectotipified), M. solisii, M. tricholepis. We also propose several new names: M. ammophila, M. columbi, M. plumosa. Our phylograms suggest that Muhlenbergia originated in North America because the sister (Sohnsia filifolia and Scleropogoninae) is composed of predominantly North American species.
Adaptive frequency-domain equalization for underwater acoustic communications

In this paper, frequency-domain equalization approach is proposed to deal with the intersymbol interference in underwater acoustic communications. To track the time-varying underwater acoustic channel, an adaptive algorithm is considered using overlap-and-save method. This technique makes it possible to remove the overhead due to the transmission of cyclic prefix over each block of data, such as in usual frequency-domain equalization systems. We compare both schemes through simulations to select the best one. The transmission scheme is validated in the Atlantic Ocean over a distance up to 2 kilometers in shallow water with high data rate single carrier QPSK communications (10 kbps). The receiver includes an efficient timing recovery tracking scheme followed by equalization. The results of simulations and experiments are evaluated in terms of bit error rate (BER) and mean square error (MSE).
Possible Differential Induction of Phase 2 Enzyme and Antioxidant Pathways by American Ginseng, Panax quinquefolius

Human immunodeficiency virus (HIV)‐infected patients often take herbal medicines, which may interact with antiretrovirals. American ginseng induces phase 2 and antioxidant enzymes in vitro and might increase the clearance of zidovudine and/or enhance antioxidant activity. Ten healthy volunteers received 300 mg of zidovudine orally before and after 2 weeks of treatment with a ginsenoside‐enriched American ginseng extract 200 mg twice daily. This ginseng extract induced the phase 2 enzyme quinone reductase with an average concentration of doubling of enzyme activity of 190 μg/mL. Total ginsenoside content was 8.5 ± 0.5%. Pharmacokinetic profiles of zidovudine and oxidative stress marker concentrations were measured post‐zidovudine dose. American ginseng does not significantly affect the formation clearance of zidovudine to its glucuronide (ratio post‐ to pre‐American ginseng = 1.17; 90% confidence interval: 0.95–1.45; P = .21), total clearance (ratio = 0.97; 0.82–1.14; P = .70), or plasma zidovudine AUC0–8 (ratio = 1.03; 0.87–1.21; P = .77). Oxidative stress biomarkers are reduced post‐American ginseng (F2‐isoprostane ratio = 0.79; 0.72–0.86; P < .001; 8‐hydroxy‐deoxyguanosine ratio = 0.74; 0.59–0.92; P = .02). Two weeks of American ginseng does not alter zidovudine pharmacokinetics but reduces oxidative stress markers.
A lyophilized sterically stabilized liposome-containing docetaxel: in vitro and in vivo evaluation

Abstract Objectives: In this study, an improved lyophilized PEGylated liposomal formulation of docetaxel (DOC) has been developed. Methods: PEGylated docetaxel liposome (PL-DOC) was prepared by thin-film evaporation method and lyophilization. The effect of various components of the lipids and their compatibility with DOC on the entrapment efficiency (EE) of liposome was investigated. The lyophilized PL-DOC was characterized by morphology, particle size, zeta potential, EE, release in vitro and stability. Pharmacokinetics and biodistribution in vivo of lyophilized PL-DOC were also investigated. Results: The optimal liposome formulation was egg phosphatidylcholine (EPC):cholesterol (CH):DSPE-PEG2000:DOC = 56:40:4:4 (molar ratio). Sucrose and mannitol were chosen as cryoprotectant in the lyophilization (cryoprotectant-to-lipid (C/L) mass ratio = 8:1). The size of lyophilized PL-DOC was 152.3 ± 1.0 nm with negative charge and the EE was 89.75 ± 1.79%. Compared with nonlyophilized PL-DOC, the lyophilized PL-DOC was more stable at 4 °C for six months. The lyophilized PL-DOC also showed the good stability after reconstituted by 5% glucose injection. In vitro release study of PL-DOC showed that PL-DOC had a sustained release effect. After i.v. administration at the dose of 10 mg/kg in rats, a significant increase in the AUC0-∞, MRT0-∞ and t1/2 was observed in PL-DOC group compared with conventional docetaxel liposome (CL-DOC) and DOC injection (DOC-I) group. Biodistribution studies in mice showed that PL-DOC significantly decreased the uptake by the organs of mononuclear phagocytic system (MPS), such as liver and spleen, while prolonging the retention time of DOC in the plasma. Conclusion: Our PEGylated liposome formulation reported in this study could potentially produce viable clinical strategies for improved delivery of DOC for the treatment of human cancer.
Transient stability of power systems using robust nonlinear second order sliding mode controller

The objective of this paper is to design a nonlinear second order sliding mode control for stabilizing the power angle of synchronous generator modeled by a standard third order model. The Standard Sliding Mode (SSM) controller produces oscillations (or “chattering”) in the closed-loop system. The new approach High Order Sliding Mode (HOSM) is proposed to reduce this phenomenon. The designed controller is smooth and robust with respect to different transient faults and enables to compensate the inherent nonlinearities of the generator. The responses of the system with the proposed controller are compared with those obtained with some other kinds of power stabilizers when the system is subjected to a variety of disturbances. Simulations on a single-machine in bus power system have demonstrated better performances compared with existing controllers. They show that the power system can keep transiently stable and achieve voltage regulation indirectly.
Lack of drug interaction between cyclosporine and telaprevir in a liver transplant recipient

Telaprevir is a novel NS3A/4A protease inhibitor approved in combination with ribavirin and peg‐interferon alfa for the treatment of genotype‐1 chronic hepatitis C. This drug is also known to be a potent cytochrome P450 3A and drug efflux protein ATP‐binding cassette B1 (also called P‐glycoprotein) inhibitor, and could therefore interact with immunosuppressive drugs. For this reason, a decrease in cyclosporine (CsA) dosage has been proposed when combining this drug with telaprevir. We report herein the case of an unpredictable lack of interaction between CsA and telaprevir in a liver transplant recipient. The decrease in CsA dosage, conducted as recommended in the literature, did not result in stable CsA concentrations but decreased them. However, the decrease in CsA exposure could have been unseen without the measurement of CsA concentrations 2 h after the administration (C2) of the drug, because it mainly resulted from the decrease in CsA peak. The mechanism leading to this lack of drug interaction in this patient has not been fully elucidated yet, but is likely to affect the absorption phase. Therapeutic drug monitoring using only CsA trough concentrations could be falsely reassuring, and the addition of the measurement of the C2 may add useful information to adapt CsA dosage in patients co‐treated with telaprevir.
Hydrocephalus ex vacuo and clasp thumb deformity due to congenital cytomegalovirus infection

A case of congenital hydrocephalus in a male infant with flexion deformity of the thumbs and great toes is reported. A maternal uncle had undefined intellectual impairment and X‐linked hydrocephalus was considered among the differential diagnoses. However, this diagnosis was considered unlikely as the pyramids were preserved at autopsy. In addition, postmortem histopathology and viral culture established cytomegalovirus (CMV) infection as the underlying cause of the hydrocephalus. Although CMV infection is a well recognized cause of congenital hydrocephalus, the associated flexion deformities of the thumbs and great toes have not been previously described and may reflect injury to the corticospinal tracts.
Population Intervention Causal Effects Based on Stochastic Interventions

Summary Estimating the causal effect of an intervention on a population typically involves defining parameters in a nonparametric structural equation model ( Pearl, 2000 , Causality: Models, Reasoning, and Inference) in which the treatment or exposure is deterministically assigned in a static or dynamic way. We define a new causal parameter that takes into account the fact that intervention policies can result in stochastically assigned exposures. The statistical parameter that identifies the causal parameter of interest is established. Inverse probability of treatment weighting (IPTW), augmented IPTW (A‐IPTW), and targeted maximum likelihood estimators (TMLE) are developed. A simulation study is performed to demonstrate the properties of these estimators, which include the double robustness of the A‐IPTW and the TMLE. An application example using physical activity data is presented.
Data — Driven visualisations that make sense

An obstacle for users engaged in data analysis task is determining the most useful way to visually represent their particular datasets. For users with little background in data analytics, this is mostly done through a trial-and-error process. My focus is on investigating appropriate techniques for automatically generating visualisations that help in identifying inconsistencies in data; explicit modelling and visualisation of user hypotheses; and automatically generating and selecting visualisations that would help users accomplish data analysis tasks. The resulting platform would be a software prototype that would ingest data, understand user hypothesis, and then intelligently recommend dashboards with the best-suited visualisations to form a visual story-telling scenario.
Southern Border Recession Predictability in the United States: 1990-2015

Prior research establishes that the spread between longand short-term bond yields often provides valuable information for predicting business cycle downturns. This study examines the predictive capacity of the yield spread for United States metropolitan economies situated along the border with Mexico. Because of the location of these urban economies and various economic ties linking them with twin cities across the border, the Mexico yield spread, and the real dollar/peso exchange rate are also employed as potential recession predictors. Results suggest that a flattening of the yield curve for either country tends to increase the probability of recessions in border economies. Furthermore, declines in the real value of the peso, which are typically associated with greater cross-border manufacturing activity, are found to reduce recession likelihoods in the metropolitan economies examined on the north side of the international boundary. JEL Categories: E32, Business Cycles; E43, Interest Rates; R15, Regional Econometric Models
Extruded Platinum Coils from Recurrent Previously Coiled Intracranial Aneurysms Discovered at the Time of Microsurgical Clip Ligation

CE of brain aneurysms is safer with better outcomes than microsurgical clip ligation. However, the higher recurrence rate may nullify the acute benefits of coiling. Reported here are three patients who underwent surgery to treat their recurrent, previously coiled aneurysm. Intraoperatively, coils were seen extruding from the recurrent regions of each aneurysm and adherent to the surrounding neurovascular structures. These interesting findings question the premise that observation of a recurrent aneurysm is safe.
Factors That Influence Police Conceptualizations of Girls Involved in Prostitution in Six U.S. Cities: Child Sexual Exploitation Victims or Delinquents?

This study examined how the police conceptualize juveniles involved in prostitution as victims of child sexual exploitation (CSE) or delinquents. Case files from six police agencies in major U.S. cities of 126 youth allegedly involved in prostitution, who were almost entirely girls, provided the data for this inquiry. This study found that 60% of youth in this sample were conceptualized as victims by the police and 40% as offenders. Logistic regression predicted the youths’ culpability status as victims. The full model predicted 91% of youth’s culpability status correctly and explained 67% of the variance in the youths’ culpability status. The police considered youth with greater levels of cooperation, greater presence of identified exploiters, no prior record, and that came to their attention through a report more often as victims. In addition, the police may consider local youth more often as victims. It appears that the police use criminal charges as a paternalistic protective response to detain some of the youth treated as offenders, even though they considered these youth victims. Legislatively mandating this form of CSE as child abuse or adopting a ‘‘secure care’’ approach is needed to ensure these youth receive the necessary treatment and services.
In vitro characterization of constitutive CysB proteins from Salmonella typhimurium

Expression of the cysteine regulon in Salmonella typhimurium and Escherichia coli is controlled by the LysR‐type transcriptional activator CysB and by the inducer N‐acetyl‐l‐serine. Sulphide and thiosulphate are anti‐inducers. Two highly purified constitutive CysB proteins, CysB(T149M) and CysB(T149P), were found to bind to the cysJIHcysK and cysP promoters, to activate transcription from the cysJIH and cysK promoters in the absence of N‐acetyl‐l‐serine, and to be insensitive to the effects of anti‐inducers. At 10mM MgCl2, the in vitro transcription activity of CysB(T149M) was maximal without N‐acetyl‐l‐serine, but that of CysB(T149P) was increased by inducer. At 2mM MgCl2, both proteins were fully active without inducer. A third mutant protein, CysB(W166R), was totally inactive at 10mM MgCl2, but gave constitutive expression of the cysK and cysJIH promoters at 2 mM MgCl2. Surprisingly, wild‐type CysB was also constitutive for the cysK promoter at 2mM MgCl2 but not at 10mM MgCl2; it required inducer for cysJIH promoter activation at both concentrations. Mutagenic studies indicated that this difference between promoters is due to the distance between activation site half‐sites, which are separated by 1 bp in the cysJIH promoter and by 2 bp in the cysK promoter. We speculate that inducer acts to decrease the distance between the binding domains of two CysB subunits that interact with an activation site. In vitro activities of wild‐type and mutant CysB proteins correlated much better with in vivo behaviour at 2mM than at 10mM MgCl2, suggesting that the former is the more physiological concentration.
Practical aspects of including functional endpoints in developmental toxicity studies. Case study: immune function in HuCD4 transgenic mice exposed to anti-CD4 MAb in utero

Keliximab is a human-cynomolgus monkey chimeric (Primatized) monoclonal antibody with specificity for human and chimpanzee CD4. As the preclinical safety assessment of biopharmaceuticals requires evaluation in pharmacologically responsive species, comprehensive toxicology studies, including reproductive toxicity, of this antibody were conducted in a human CD4 transgenic mouse model. The reproductive toxicology studies included a preand postnatal development study that incorporated immunotoxicological evaluation of offspring (F1) mice. The potential effects of exposure to treating maternal mice (F0) with keliximab during pregnancy and lactation on offspring viability, physical growth, neurobehavioral development, reproductive function, lymphoid tissue morphological structure, lymphocyte subsets and host resistance to Candida albicans infection were assessed. The results showed no impairment of these functions. The use of F1 transgenic mice in study with keliximab provides an example of a novel practical approach to assess developmental immunotoxicity within a study of preand postnatal development designed in accordance with ICH Guidelines.