Miracle-dz/UniFAR-FTUs huggingface dataset:
Cystic Fibrosis Transmembrane Conductance Regulator Regulates Luminal Cl−/HCO3 −Exchange in Mouse Submandibular and Pancreatic Ducts*

We have demonstrated previously the regulation of Cl−/HCO3 − exchange activity by the cystic fibrosis transmembrane conductance regulator (CFTR) in model systems of cells stably or transiently transfected with CFTR (Lee, M. G., Wigley, W. C., Zeng, W., Noel, L. E., Marino, C. R., Thomas, P. J., and Muallem, S. (1999)J. Biol. Chem. 274, 3414–3421). In the present work we examine the significance of this regulation in cells naturally expressing CFTR. These include the human colonic T84 cell line and the mouse submandibular gland and pancreatic ducts, tissues that express high levels of CFTR in the luminal membrane. As in heterologous expression systems, stimulation of T84 cells with forskolin increased the Cl−/HCO3 − exchange activity independently of CFTR Cl− channel activity. Freshly isolated submandibular gland ducts from wild type mice showed variable Cl−/HCO3 −exchange activity. Measurement of [Cl−] i revealed that this was largely the result of variable steady-state [Cl−] i . Membrane depolarization with 5 mm Ba2+ or 100 mmK+ increased and stabilized [Cl−] i . Under depolarized conditions wild type and ΔF/ΔF mice had comparable basal Cl−/HCO3 − exchange activity. Notably, stimulation with forskolin increased Cl−/HCO3 − exchange activity in submandibular gland ducts from wild type but not ΔF/ΔF mice. Microperfusion of the main pancreatic duct showed Cl−/HCO3 − exchange activity in both the basolateral and luminal membranes. Stimulation of ducts from wild type animals with forskolin had no effect on basolateral but markedly stimulated luminal Cl−/HCO3 − exchange activity. By contrast, forskolin had no effect on either basolateral or luminal Cl−/HCO3 −exchange activity of ducts from ΔF/ΔF animals. We conclude that CFTR regulates luminal Cl−/HCO3 − exchange activity in CFTR-expressing cells, and we discuss the possible physiological significance of these findings regarding cystic fibrosis.
The severity of oxygen desaturation is predictive of carotid wall thickening and plaque occurrence.

STUDY OBJECTIVES To characterize carotid intima-media thickness (IMT) and plaque occurrence in patients with newly diagnosed obstructive sleep apnea (OSA) without known cardiovascular disease. DESIGN Prospective study. SETTING Sleep Laboratory and Department of Cardiology of Grenoble University Hospital. PATIENTS AND INTERVENTION OSA syndrome is associated with an increased cardiovascular risk. Carotid IMT is recognized as a marker of preclinic atheroma. A small number of studies have analyzed large-artery wall modifications in OSA syndrome. Eighty-three patients (74 men; mean age +/- SD, 48 +/- 11 years; mean body mass index, 27.4 +/- 4.2 kg/m(2)) were included. Mean respiratory disturbance index was 40.7 +/- 19.2/h, mean nocturnal arterial oxygen saturation (Sao(2)) was 93.1 +/- 2.0%, and mean percentage of recording time spent at Sao(2) < 90% was 8.6 +/- 16.8%. Clinical BP was measured following European Society of Hypertension/European Society of Cardiology recommendations, and 24-h ambulatory BP monitoring was assessed. Ultrasonography was used to determine the carotid IMT and atheromatous plaque occurrence. MEASUREMENTS AND RESULTS Twenty-five of 83 patients (30%) had carotid wall hypertrophy (IMT > 0.8 mm). In a logistic regression model, mean nocturnal Sao(2) < 92% (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.1 to 12.7) was associated with carotid wall hypertrophy. ORs were even higher after adjustment for BP status (OR, 10.6; 95% CI, 1.6 to 50.9 in normotensive patients) and glucose levels (OR, 4.5; 95% CI, 1.0 to 20.9). Mean nocturnal Sao(2) < 92% and minimal nocturnal Sao(2) < 80% (ORs, 3.1 and 3.1; 95% CIs, 1.0 to 9.4 and 1.0 to 8.5, respectively) were associated with the presence of carotid plaque formation independently of the BP status (hypertensive or normotensive). CONCLUSIONS The severity of oxygen desaturation appears to be one of the best predictors for carotid IMT and plaque occurrence in OSA patients without known cardiovascular disease. Thus, carotid IMT and plaque formation appeared as early cardiovascular consequences in OSA patients.
Association of paternal IQ in early adulthood with offspring mortality and hospital admissions for injuries: a cohort study of 503 492 Swedish children

Background Higher intelligence (IQ) has been related to a lower risk of mortality and hospital admissions for injuries, but little is known about the effect of parental IQ on offspring outcomes. We explored associations of paternal IQ with mortality and hospitalisations for injuries from all external causes in offspring. Methods A cohort of 503 492 Swedish children under 5 years of age with information on paternal IQ was obtained by record linkage of national registers. HR with 95% CIs were estimated using Cox regression. Results There was some evidence that paternal IQ was inversely associated with total and external-cause mortality in offspring, although the effects were modest and disappeared when controlling for parents’ socioeconomic position (SEP). The only robust gradient was found between paternal IQ and hospital admissions for injuries (HRper 1-SD increase in IQ 0.93, 95% CI 0.92 to 0.94; p<0.001), which was slightly attenuated but retained statistical significance after adjustment for SEP (0.95, 95% CI 0.94 to 0.97; p<0.001). Conclusions Children to fathers with lower IQ may have an increased risk of injury by external causes. Messages on family safety and injury prevention might be tailored according to parental cognitive abilities.
A Comparison of a New Skin Closure Device and Intradermal Sutures in the Closure of Full-Thickness Surgical Incisions

Background: A novel topical skin adhesive system was developed to close the outermost layer of skin in an expeditious manner. To determine its clinical utility, a clinical investigation was undertaken to demonstrate equivalence of a new adhesive skin closure system (Prineo Skin Closure System) to intradermal sutures in wound closure. Methods: The investigation included 83 patients who underwent elective abdominoplasty, circumferential body lift procedures, and breast reconstruction with deep inferior epigastric perforator flaps. Incisions were divided in half, and each half was randomized to wound closure with the new skin closure system, including a pressure-sensitive adhesive mesh tape for wound edge approximation and next-generation cyanoacrylate or intradermal sutures. Postoperative evaluations took place at 24 hours, 7 days, 12 to 25 days, 90 days, 6 months, and 12 months. Results: The new skin closure system was found to be equivalent to intradermal sutures for the continuous approximation of wounds. The upper limit of the two-sided 90 percent confidence interval for difference in proportions was 10.9 percent. The mean time to closure for the new skin closure system was 1.46 minutes, approximately 5 minutes faster than that for intradermal sutures (p < 0.0001). Both treatments had similar incision healing and cosmetic outcomes. No quantitative or qualitative differences of clinical significance were evident between the treatment groups. Conclusions: The Prineo Skin Closure System can be considered equivalent to intradermal sutures for full-thickness surgical incisions with regard to safety and effectiveness. The ease and speed of application contribute to shortened operative times (4.5 times faster than intradermal sutures). CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.
Split genes and their expression in Kaposi's sarcoma‐associated herpesvirus

A split or interrupted gene is defined as a gene consisting of introns and exons. Removal (splicing) of the intron(s) from a primary transcript (pre‐mRNA) is essential for creating a mRNA. Initial assignment of a potential protein coding region in the KSHV genome was based on the initiation codon context and predicted protein size larger than 100 amino acids, but the gene discontinuity was disregarded. Experimental investigation of the assigned ORFs has demonstrated that there are up to 25 split genes, more than one fourth of the total KSHV genes described in the KSHV genome. This includes the genes involved in all phases (latent, immediate early, early and late) of KSHV infection. The complexity of a split gene expression depends upon the availability of a proximal promoter and polyadenylation (pA) signal. Sharing a single promoter or a single pA signal by two or three genes is not uncommon in the expression of KSHV split genes and the resulting transcripts are usually polycistronic. Among those of KSHV split genes, 15 genes express a bicistronic or tricistronic RNA and 10 genes express a monocistronic RNA. Alternative RNA splicing could happen in a particular pre‐mRNA due to intron or exon inclusion or skipping or the presence of an alternative 5′ splice site or 3′ splice site. This may, respectively, result in at least 8 species of K8 and 14 species of K15 transcripts. This appears to be related to cell differentiation and stages of the virus infection, presumably involving viral cis elements and trans splicing factors. Published in 2003 by John Wiley & Sons, Ltd.
Compartmentalization of bicarbonate‐sensitive adenylyl cyclase in distinct signaling microdomains

Intracellular targets of the ubiquitous second messenger cAMP are located at great distances from the most widely studied source of cAMP, the G protein responsive transmembrane adenylyl cyclases. We previously identified an alternative source of cAMP in mammalian cells lacking transmembrane spanning domains, the “soluble” adenylyl cyclase (sAC). We now demonstrate that sAC is distributed in specific subcellular compartments: mitochondria, centrioles, mitotic spindles, mid‐bodies, and nuclei, all of which contain cAMP targets. Distribution at these intracellular sites proves that adenylyl cyclases are in close proximity to all cAMP effectors, suggesting a model in which local concentrations of cAMP are regulated by individual adenylyl cyclases targeted to specific microdomains throughout the cell.
Manipulation of Endogenous Trypsin Proteinase Inhibitor Production in Nicotiana attenuata Demonstrates Their Function as Antiherbivore Defenses1[w]

Evidence for the in planta defensive function of trypsin protease inhibitors (TPIs) comes from observations of enhanced herbivore resistance after heterologous TPI expression or the manipulation of signal cascades that activate numerous defense responses, including TPI production; no studies have altered the expression of an endogenous pi gene to examine defensive function. We isolated two genes with seven- and six-repeat TPI domains from Nicotiana attenuata from the potato (Solanum tuberosum) PI-II family. To determine whether endogenous TPIs in N. attenuata function defensively against the native herbivores, hornworm (Manduca sexta) and mirids (Tupiocoris notatus), we expressed 175 bp of the seven-domain pi from N. attenuata in an antisense orientation in a TPI-producing genotype to reduce TPI expression and expressed the full-length seven-domain pi in a sense orientation under control of a constitutive promoter to restore TPI activity in a natural genotype from Arizona unable to produce TPIs. Constitutive and inducible TPI production in two antisense lines were diminished by 80% to 90% and 33% to 52%, respectively, and sense expression restored 67% of the activity found in the TPI-producing genotype after caterpillar attack in the TPI-deficient A genotype. Hornworm larvae fed on genotypes with low or no TPI activity grew faster, had higher survivorship, and produced heavier pupae than those that fed on genotypes with high TPI activity. T. notatus showed higher preference for genotypes with low or no TPI activity than for genotypes with high TPI levels. We conclude that endogenous TPIs are an effective defense against these native herbivores.
Copy number variations in affective disorders and meta-analysis

In two recent studies 10 copy number variants (CNV) were found to be overrepresented either among patients suffering from affective disorders in an Amish family or in the Wellcome Trust Case–Control Consortium study. Here, we investigate if these variants are associated with affective disorders in a combined analysis of three case–control samples from Denmark, Norway and Iceland. A total of 1897 cases (n=1223 unipolar and n=463 bipolar) and 11 231 controls were analyzed for CNVs at the 10 genomic loci, but we found no combined association between these CNVs and affective disorders.
The Open Security Architecture

Outlines the Open Security Architecture (OSA). OSA is an architecture which will provide the basis for the selection, design and integration of products providing security and control for a network of desktop personal computers, “mobile” notebook computers, servers and mainframes. States that the purpose of this architecture is to provide an environment where: acceptable and workable controls can be placed on sensitive data; user productivity and existing investments in applications are not negatively impacted by the addition of control and security; data flow around the organization, and the investment that has been put in place to support this capability (e.g. local‐area, wide‐area, and telephonebased networks) can still be used to enhance information exchange between users; and all workstations, regardless of their location, operating system, or capability to connect to a network, can be included and easily administered under this architecture.
Connoisseurship Consumption and Market Evolution: An Instituional Theory Perspective on the Growth of Specialty Coffee Consumption in the USA

How does the increasing prevalence of connoisseurship consumption affect the market? Drawing from institutional theory, we develop answers to this question. Inspired by the legitimacy concept, we evaluate the specialty coffee consumption context in order to advance and systematically analyze the role of connoisseurship consumption in the market. In extensive qualitative study, 542 newspaper articles from 1980 to 2013 were collected
Association of coffee drinking with all-cause mortality: a systematic review and meta-analysis

Abstract Objective We aimed to use the meta-analysis method to assess the relationship between coffee drinking and all-cause mortality. Design Categorical and dose–response meta-analyses were conducted using random-effects models. Setting We systematically searched and identified eligible literature in the PubMed and Scopus databases. Subjects Seventeen studies including 1 054 571 participants and 131 212 death events from all causes were included in the present study. Results Seventeen studies were included and evaluated in the meta-analysis. A U-shaped dose–response relationship was found between coffee consumption and all-cause mortality (P for non-linearity <0·001). Compared with non/occasional coffee drinkers, the relative risks for all-cause mortality were 0·89 (95 % CI 0·85, 0·93) for 1–<3 cups/d, 0·87 (95 % CI 0·83, 0·91) for 3–<5 cups/d and 0·90 (95 % CI 0·87, 0·94) for ≥5 cups/d, and the relationship was more marked in females than in males. Conclusions The present meta-analysis of prospective cohort studies indicated that light to moderate coffee intake is associated with a reduced risk of death from all causes, particularly in women.
The Coming of Age of International Monetary and Financial Law after the Global Financial Crisis

John Jackson’s legacy as one of the founding fathers of International Trade Law is widely recognized. His formidable mind, work ethic, and sheer brilliance radiated throughout his career. His contribution to theory (whether in the understanding of the different dimension of sovereignty or in debates about WTO dispute settlement procedures) and practice (nationally and internationally) made him a unique scholar, universally respected and revered. What is perhaps less well-known is the passion with which he embraced the challenges faced by the international community—policy makers, lawyers, economists, market practitioners—in the immediate aftermath of the global financial crisis. He was a renaissance man, always ready to move beyond established parameters in order to break new ground. He approached novel themes with the enthusiasm of a child. His desire to contribute to a world ruled by norms and institutions rather than by force or by the ‘law of the jungle’ led him to embrace the evolution of international economic law—this time in the area of international money and finance—with boundless optimism and energy. The birth of WTO was for him the fulfillment of an intellectual dream, which he had designed in part. And it is those dreams of a better World that also led him to link with younger academics, to reach out to other disciplines, to think conventionally and unconventionally in order to solve the complex issues involved in the proper functioning of the international financial system. Different areas of International Economic Law (IEL) have grown at different speeds over the past decades and are characterized by different degrees of
Histone macroH2A1.2 is concentrated in the XY compartment of mammalian male meiotic nuclei

We show here that histone macroH2A1.2 concentrates at the transcriptionally silent XY body, normally being formed during male meiosis in the mouse. A similar accumulation has earlier been observed on the inactive X chromosomes of somatic adult female mammalian cells by Costanzi and Pehrson (1998). This correspondence in the nature of heterochromatinization of the X chromosomes in males and females adds another property of X chromosome inactivation that is shared by males and females at different phases of their life cycle.
Replication of B19 parvovirus in highly enriched hematopoietic progenitor cells from normal human bone marrow

The target cell specificity of the B19 parvovirus infection was examined by isolating highly enriched hematopoietic progenitor and stem cells from normal human bone marrow. The efficiency of the B19 parvovirus replication in enriched erythroid progenitor cells was approximately 100-fold greater than that in unseparated bone marrow cells. The more-primitive progenitor cells identical to or closely related to the human pluripotent hematopoietic stem cells, on the other hand, did not support viral replication. The B19 progeny virus produced by the enriched erythroid progenitor cells was infectious and strongly suppressed erythropoiesis in vitro. The susceptibility of both the more-primitive erythroid progenitors (burst-forming units-erythroid) and the more-mature erythroid progenitors (CFU-erythroid) to the cytolytic response of the virus and the lack of effect on the myeloid progenitors (CFU-granulocyte-macrophage) further give evidence to the remarkable tropism of the B19 parvovirus for human hematopoietic cells of erythroid lineage.
Smoker networks and the "typical smoker": a prospective analysis of smoking cessation.

Perceptions of the typical smoker (i.e., prototype) were assessed in a sample of 174 adult smokers when they first joined a cessation clinic and were used to predict smoking status at 6-month follow-up. As predicted, consistent with a prototype-based model of health risk behavior (F. X. Gibbons & M. Gerrard, 1995, in press), smokers with more favorable perceptions were more likely to have relapsed at follow-up. Also as predicted, this prospective effect was moderated by smokers' social networks: Prototypes did not predict status among those who had a lot of friends and family members who smoked, suggesting that these other smokers were inhibiting smokers' attempts to distance themselves psychologically from the prototype. Implications of the results for interventions that use prototypes to discourage smoking are discussed.
Computer-Vision-Guided Human Pulse Rate Estimation: A Review

Human pulse rate (PR) can be estimated in several ways, including measurement instruments that directly count the PR through contact- and noncontact-based approaches. Over the last decade, computer-vision-assisted noncontact-based PR estimation has evolved significantly. Such techniques can be adopted for clinical purposes to mitigate some of the limitations of contact-based techniques. However, existing vision-guided noncontact-based techniques have not been benchmarked with respect to a challenging dataset. In view of this, we present a systematic review of such techniques implemented over a uniform computing platform. We have simultaneously recorded the PR and video of 14 volunteers. Five sets of data have been recorded for every volunteer using five different experimental conditions by varying the distance from the camera and illumination condition. Pros and cons of the existing noncontact image- and video-based PR techniques have been discussed with respect to our dataset. Experimental evaluation suggests that image- or video-based PR estimation can be highly effective for nonclinical purposes, and some of these approaches are very promising toward developing clinical applications. The present review is the first in this field of contactless vision-guided PR estimation research.
Ultrasound-induced cavitation: applications in drug and gene delivery

Ultrasound, which has been conventionally used for diagnostics until recently, is now being extensively used for drug and gene delivery. This transformation has come about primarily due to ultrasound-mediated acoustic cavitation – particularly transient cavitation. Acoustic cavitation has been used to facilitate the delivery of small molecules, as well as macromolecules, including proteins and DNA. Controlled generation of cavitation has also been used for targeting drugs to diseased tissues, including skin, brain, eyes and endothelium. Ultrasound has also been employed for the treatment of several diseases, including thromboembolism, arteriosclerosis and cancer. This review provides a detailed account of mechanisms, current status and future prospects of ultrasonic cavitation in drug and gene delivery applications.
Assessment of the vulnerable carotid atherosclerotic plaque using contrast-enhanced ultrasonography

Carotid atherosclerosis represents a primary cause for cerebrovascular ischemic events and its contemporary management includes surgical revascularization for moderate to severe symptomatic stenoses. However, the role of invasive therapy seems to be questioned lately for asymptomatic cases. Numerous reports have suggested that the presence of neovessels within the atherosclerotic plaque remains a significant vulnerability factor and over the last decade imaging modalities have been used to identify intraplaque neovascularization in an attempt to risk-stratify patients and offer management guidance. Contrast-enhanced ultrasonography of the carotid artery is a relatively novel diagnostic tool that exploits resonated ultrasound waves from circulating microbubbles. This property permits vascular visualization by producing superior angiography-like images, and allows the identification of vasa vasorum and intraplaque microvessels. Moreover, plaque neovascularization has been associated with plaque vulnerability and ischemic symptoms lately as well. At the same time, attempts have been made to quantify contrast-enhanced ultrasonography signal using sophisticated software packages and algorithms, and to correlate it with intraplaque microvascular density. The aim of this review was to collect all recent data on the characteristics, performance, and prognostic role of contrast-enhanced ultrasonography regarding carotid stenosis management, and to produce useful conclusions for clinical practice.