Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic mechanisms of evolved physiological plasticity in killifish distributed along an environmental salinity gradient

Adaptive variation tends to emerge clinally along environmental gradients or discretely among habitats with limited connectivity. However, in Atlantic killifish (Fundulus heteroclitus), a population genetic discontinuity appears in the absence of obvious barriers to gene flow along parallel salinity clines and coincides with a physiologically stressful salinity. We show that populations resident on either side of this discontinuity differ in their abilities to compensate for osmotic shock and illustrate the physiological and functional genomic basis of population variation in hypoosmotic tolerance. A population native to a freshwater habitat, upstream of the genetic discontinuity, exhibits tolerance to extreme hypoosmotic challenge, whereas populations native to brackish or marine habitats downstream of the discontinuity lose osmotic homeostasis more severely and take longer to recover. Comparative transcriptomics reveals a core transcriptional response associated with acute and acclimatory responses to hypoosmotic shock and posits unique mechanisms that enable extreme osmotic tolerance. Of the genes that vary in expression among populations, those that are putatively involved in physiological acclimation are more likely to exhibit nonneutral patterns of divergence between freshwater and brackish populations. It is not the well-known effectors of osmotic acclimation, but rather the lesser-known immediate-early responses, that appear important in contributing to population differences.
Cost Savings Attributable to Reductions in Intensive Care Unit Length of Stay for Mechanically Ventilated Patients

Objectives:To estimate the actual cost savings that could be achieved through reductions in intensive care unit (ICU) length of stay and duration of mechanical ventilation by determining the short-run marginal variable cost of an ICU and ventilator day. Research Design:Retrospective cohort study in a university-affiliated teaching hospital. Subjects:All patients receiving mechanical ventilation in the ICU for more than 48 hours (n = 1778) from July 1, 2005 to June 30, 2006. Measures:The hospital's administrative and cost databases were used to determine total costs, variable costs, and direct-variable costs for each patient on each individual ICU and hospital day. Results:Direct-variable costs comprised 19.3% of total ICU costs and 18.4% of total hospital costs. Marginal direct-variable costs (the cost of each additional ICU day) were small compared with the average daily total cost ($649 to $839 vs. $1751, in US dollars). In survivors with ICU lengths of stay more than 3 days, the mean direct-variable cost of the last ICU day was $397, while the mean direct-variable cost of the first ward day was $279, for a mean cost difference of $118 (95% CI, $21–$190). Reducing ICU and hospital length of stay by 1 day in all survivors with ICU lengths of stay more than 3 days would result in an immediate cost savings of only 0.2% of all hospital expenditures for these patients. Conclusions:Marginal variable ICU costs are relatively small compared with average total costs and are only slightly greater than the cost of a ward day.
Using computers to narrowcast health messages: The role of audience segmentation, targeting, and tailoring in health promotion.

Given the vast amount of information that individuals are exposed to on a daily basis public health campaigns face enormous challenges in reaching their audience with messages that are relevant comprehensible and effective in promoting and sustaining healthy behaviors. Careful use of segmentation targeting and tailoring can improve the likelihood of success. To employ these techniques effectively we need to understand audience characteristics channel capabilities and message properties respectively. Although achieving an understanding of these is daunting in and of itself the greater challenge lies in developing theoretical perspectives that take into account how these three factors interact with each other to determine exposure to and reception of campaign messages. In other words it is not sufficient to study these factors individually; rather we must develop models that take into account their collective impact. In future research for example we might segment audience members according to their risk perception differentiate channels according to their reach and tailor messages according to their level of specificity but we also need to investigate how these three factors combine to influence message processing. Otherwise it is unlikely that campaigns will benefit much from such studies. A more fruitful line of research may be to map out whether for example the nature of information sought through the Internet as opposed to interpersonal sources differs according to individuals risk perceptions. In this example we can identify tailoring effects (the nature of the information sought) targeting effects (use of the Internet or interpersonal sources) and segmentation effects (high or low perceived risk). Similarly we might examine the relative effectiveness of various message frames (tailoring) among those with different levels of risk perception (segmentation) holding the channel constant (targeting). The important point here is that audience segmentation channel targeting and message tailoring decisions should be made by considering how each of these factors informs and is informed by the other two. This line of inquiry we believe not only is useful for theory development but also has practical implications. (excerpt)
Fine‐tuning scaffolds for tissue regeneration: effects of formic acid processing on tissue reaction to silk fibroin

Formic acid (FA) plays a key role in the preparation of silk fibroin (SF) scaffolds from cocoons of Bombyx mori and is used for fibre distribution. In this study, we used a subcutaneous implantation model in Wistar rats to examine SF scaffolds prepared by treating the degummed cocoon with FA for either 30 or 60 min. The tissue reaction and inflammatory response to SF was assessed by qualitative histology at intervals from 3 to 180 days. Additionally, dynamic biomaterial‐induced vascularization and biomaterial degradation were quantified using a technique for analysing an image of the entire implanted biomaterial. Varying the FA treatment time led to different scaffold morphologies and resulted in two distinct peri‐implant tissue reactions. The 30 min‐treated scaffold was integrated into the surrounding tissue beginning at day 3 after implantation and vascularization increased 10‐fold from 15 to 180 days, while the scaffold was continuously degraded throughout the first 90 days. In contrast, the 60 min‐treated SF scaffold appeared as bulk for the first 90 days after implantation, after which a rapid degradation and vascularization process began. After 180 days, the tissue response was similar for both scaffolds, with eventual formation of a well vascularized connective tissue integrating the SF fibres. This study indicates that by modifying the FA treatment time, the tissue reaction to SF scaffolds can be tailored for different tissue‐engineering applications. The tunability and biocompatibility of SF make it an attractive scaffold for exploration in regenerative medicine and clinical tissue engineering. Copyright © 2010 John Wiley & Sons, Ltd.
P2Y12 Reaction Units: Effect on Hemorrhagic and Thromboembolic Complications in Patients With Cerebral Aneurysms Treated With the Pipeline Embolization Device.

BACKGROUND The main concern with the use of the pipeline embolization device (PED) in treating cerebral aneurysms is the risk of hemorrhagic and thromboembolic complications. OBJECTIVE To investigate if P2Y12 reaction unit (PRU) values are associated with hemorrhagic and thromboembolic complications after treatment with the PED and to find an optimal range of preprocedural PRU values. METHODS Two hundred thirty-one patients with 248 cerebral aneurysms treated with the PED were retrospectively identified. Patients were started on dual-antiplatelet treatment at least 10 days before the intervention. PRU values were checked. Univariate and multivariate logistic regression were performed. Youden Indices were calculated to determine cutoffs for optimal PRU values. RESULTS Mean patient age was 57 years. Mean last preprocedural PRU was 132 (range: 1-382). The combined rate of major hemorrhagic complications (4%) and major thromboembolic complications (5.6%) was 9.6%. Analysis using Youden indices suggested an optimal PRU range of 70 to 150 with higher odds of complications outside this range (P = .01, odds ratio [OR] = 3 [1.2-7.5]). PRU <60 was a significant predictor of hemorrhagic complications (P = .04, OR = 2.45 [1.01-5.9]) and PRU >240 was a significant predictor of any thromboembolic complication (P = .04, OR = 3.6 [1.04-12]) and cerebral thromboembolic complications (P = .02, OR = 4 [1.2-14]). CONCLUSION Target preoperative PRU values should be between 60 and 240 and ideally between 70 and 150. Values below this range and above it carry higher odds of hemorrhagic and thromboembolic complications, respectively.
AMLODIPINE PREVENTS MONOCROTALINE‐INDUCED PULMONARY ARTERIAL HYPERTENSION AND PROLONGS SURVIVAL IN RATS INDEPENDENT OF BLOOD PRESSURE LOWERING

1 The present study was designed to examine the role of amlodipine in preventing and reversing monocrotaline (MCT)‐induced pulmonary arterial hypertension (PAH) in rats. 2 Rats were injected with MCT (40 mg/kg, s.c.) and randomly given either 6 mg/kg per day of amlodipine in drinking water or placebo for 3 weeks. Any animals treated with MCT that survived for 3 weeks were given either amlodipine or placebo for the next 3 weeks. 3 Blood pressure was not different between the groups. Amlodipine immediately following MCT markedly inhibited PAH with severe pulmonary vascular remodelling. The survival rate at 3 weeks after treatment was increased significantly in the amlodipine group compared with the placebo group (77%vs 43%; P < 0.01). The placebo group showed markedly diminished expression of endothelial nitric oxide synthase (eNOS) protein and mRNA levels, increased numbers of proliferating cell nuclear antigen‐positive cells, enhanced mRNA expression of matrix metalloproteinase‐2 and pro‐inflammatory cytokines in the lung tissue and upregulation of P‐selectin on the endothelium of the pulmonary arteries, whereas these effects were suppressed in the amlodipine‐treated group. Furthermore, late treatment with amlodipine did not palliate PAH or improve survival. 4 Amlodipine inhibited the development of PAH and improved survival in rats independent of its effect on lowering blood pressure. These effects were associated with marked inhibition of the downregulation of eNOS and improvement of pulmonary vascular endothelial activation, as well as anti‐inflammatory, antiproliferative and antifibrotic effects in the lung tissue. However, amlodipine failed to reverse established PAH. This study may provide an insight into therapeutic strategy of amlodipine in PAH.
Housing and appendicitis in Anglesey.

STUDY OBJECTIVE--The aim was to test the hypothesis that provision of household amenities such as domestic hot water systems and bathrooms changed hygiene which thereby triggered the epidemic of appendicitis in Anglesey after the second world war. DESIGN--The study was a cross sectional survey with histories of housing and appendicectomy obtained from Anglesey residents by postal questionnaire. The main outcome measure was reported appendicectomy. SETTING--Four general practices in Anglesey. SUBJECTS--2531 men and women born during 1923-62 and randomly selected from age-sex registers. Overall response rate was 73.7%. MAIN RESULTS--Subjects born into households with amenities--piped water, hot water systems, and bathrooms had, if anything, a reduced risk of appendicectomy. However, those who subsequently moved to houses that lacked amenities were at significantly higher risk than people born into houses without amenities who later acquired them. CONCLUSIONS--Provision of household amenities was not the important trigger to the epidemic of appendicitis which occurred in Anglesey after the second world war. Rather, the trigger may have been reduction in domestic crowding caused by the falling birth rate. Findings among those who moved house support other evidence that after infancy household amenities protect against appendicitis and contributed to the fall in appendicitis rates in Anglesey after 1965.
Synthetic Nanoparticles That Promote Tumor Necrosis Factor Receptor 2 Expressing Regulatory T Cells in the Lung and Resistance to Allergic Airways Inflammation

Synthetic glycine coated 50 nm polystyrene nanoparticles (NP) (PS50G), unlike ambient NP, do not promote pulmonary inflammation, but instead, render lungs resistant to the development of allergic airway inflammation. In this study, we show that PS50G modulate the frequency and phenotype of regulatory T cells (Treg) in the lung, specifically increasing the proportion of tumor necrosis factor 2 (TNFR2) expressing Treg. Mice pre-exposed to PS50G, which were sensitized and then challenged with an allergen a month later, preferentially expanded TNFR2+Foxp3+ Treg, which further expressed enhanced levels of latency associated peptide and cytotoxic T-lymphocyte associated molecule-4. Moreover, PS50G-induced CD103+ dendritic cell activation in the lung was associated with the proliferative expansion of TNFR2+Foxp3+ Treg. These findings provide the first evidence that engineered NP can promote the selective expansion of maximally suppressing TNFR2+Foxp3+ Treg and further suggest a novel mechanism by which NP may promote healthy lung homeostasis.
What makes political authorities legitimate? Students’ ideas about legitimacy in five European democracies and hybrid regimes

ABSTRACT Because the legitimacy of political authorities exists only in the eyes of citizens, this study investigates which criteria citizens use to decide that an authority is legitimate. By comparing ideas about what makes political authorities legitimate, this study in five European democracies and hybrid regimes illuminates the ‘demand side of political legitimacy’. Using original student survey data, this article compares expectations of students from the Netherlands, France, Poland, Ukraine, and Russia about how political authorities should acquire the right to rule and how they ought to behave when in office. The analysis shows that the respondents across the five countries use similar criteria for granting legitimacy. Across the five countries, throughput and input were more important criteria for legitimacy than the output produced by authorities. Although several country differences were found, these differences did not align with regime type. The findings challenge the widespread view that what kind of authorities people consider legitimate is determined by their socialization in a particular political regime.
Deciphering the Role of Multiple Betaine-Carnitine-Choline Transporters in the Halophile Vibrio parahaemolyticus

ABSTRACT Vibrio parahaemolyticus is a halophile that is the predominant cause of bacterial seafood-related gastroenteritis worldwide. To survive in the marine environment, V. parahaemolyticus must have adaptive strategies to cope with salinity changes. Six putative compatible solute (CS) transport systems were previously predicted from the genome sequence of V. parahaemolyticus RIMD2210633. In this study, we determined the role of the four putative betaine-carnitine-choline transporter (BCCT) homologues VP1456, VP1723, VP1905, and VPA0356 in the NaCl stress response. Expression analysis of the four BCCTs subjected to NaCl upshock showed that VP1456, VP1905, and VPA0356, but not VP1723, were induced. We constructed in-frame single-deletion mutant strains for all four BCCTs, all of which behaved similarly to the wild-type strain, demonstrating a redundancy of the systems. Growth analysis of a quadruple mutant and four BCCT triple mutants demonstrated the requirement for at least one BCCT for efficient CS uptake. We complemented Escherichia coli MHK13, a CS synthesis- and transporter-negative strain, with each BCCT and examined CS uptake by growth analysis and 1H nuclear magnetic resonance (NMR) spectroscopy analyses. These data demonstrated that VP1456 had the most diverse substrate transport ability, taking up glycine betaine (GB), proline, choline, and ectoine. VP1456 was the sole ectoine transporter. In addition, the data demonstrated that VP1723 can transport GB, proline, and choline, whereas VP1905 and VPA0356 transported only GB. Overall, the data showed that the BCCTs are functional and that there is redundancy among them.
WHITE STRIPE LEAF4 Encodes a Novel P-Type PPR Protein Required for Chloroplast Biogenesis during Early Leaf Development

Pentatricopeptide repeat (PPR) proteins comprise a large family in higher plants and perform diverse functions in organellar RNA metabolism. Despite the rice genome encodes 477 PRR proteins, the regulatory effects of PRR proteins on chloroplast development remains unknown. In this study, we report the functional characterization of the rice white stripe leaf4 (wsl4) mutant. The wsl4 mutant develops white-striped leaves during early leaf development, characterized by decreased chlorophyll content and malformed chloroplasts. Positional cloning of the WSL4 gene, together with complementation and RNA-interference tests, reveal that it encodes a novel P-family PPR protein with 12 PPR motifs, and is localized to chloroplast nucleoids. Quantitative RT-PCR analyses demonstrate that WSL4 is a low temperature response gene abundantly expressed in young leaves. Further expression analyses show that many nuclear- and plastid-encoded genes in the wsl4 mutant are significantly affected at the RNA and protein levels. Notably, the wsl4 mutant causes defects in the splicing of atpF, ndhA, rpl2, and rps12. Our findings identify WSL4 as a novel P-family PPR protein essential for chloroplast RNA group II intron splicing during early leaf development in rice.
High sensitive C-reactive protein (HsCRP) as a cardiovascular risk factor in hypertensive Nigerians.

AIMS AND OBJECTIVES The objective of this study is to determine the effect of plasma high sensitivity C-reactive protein (HsCRP) levels on hypertensive and apparently healthy normotensive Nigerians in the management of hypertension. This is a preliminary study; a study involving larger numbers of normotensives and hypertensives is in progress. SUBJECTS AND METHODS Plasma C-reactive protein level was determined in 150 hypertensive patients mean age 46.8±8.2 years and 30 apparently healthy normotensive individuals mean age 38.8 ±13.2years using the enzyme linked immunosorbent assay (ELISA) technique. RESULTS The hypertensive subjects had significantly higher body mass index (BMI) (p-value < 0.05) than the normotensive subjects (BMI=28.34 ±4.40kg/m2 Vs. 25.79±2.91kg/m2). The hypertensive subjects also had significantly higher C- reactive protein values (0.18 ± 0.1mg/dL Vs 0.08±0.04 mg/dL) (p-value < 0.0001). Among the hypertensive subjects, there was no significant difference in the level of C-reactive protein between the males and the females (0.17±0.10 mg/dL Vs 0.20±0.09 mg/dL). In the hypertensive patients, CRP positively correlated with atherogenic index (r = 0.551, p < 0.05) and coronary heart disease (CHD) risk (r= 0.589, p < 0.05). However, in normotensive patients, CRP was positively correlated with atherogenic index (r = 0.492, p < 0.01) but negatively correlated with CHD risk (r = -0.475, p < 0.01). CONCLUSION These results show that the plasma concentrations of HsCRP in hypertensive subjects were significantly higher than those of the normotensive subjects and HsCRP positively correlated with atherogenic index and CHD risk in hypertensive Nigerians.
Interleukin 12 Secretion Enhances Antitumor Efficacy of Oncolytic Herpes Simplex Viral Therapy for Colorectal Cancer

ObjectiveTo assess the strategy of combining oncolytic herpes simplex virus (HSV) therapy with immunomodulatory therapy as treatment for experimental colon cancer. The oncolytic HSV recombinant NV1023 and the interleukin 12 (IL-12)-secreting oncolytic NV1042 virus were evaluated in vitro and in vivo with respect to antitumor efficacy. Summary Background DataGenetically engineered, replication-conditional, attenuated HSVs have shown oncolytic activity against a wide variety of solid malignancies. Other strategies for treating cancer have involved immunomodulation and cytokine gene transfer using viral vectors. This study has combined both of these strategies by inserting the murine IL-12 gene into a replication-competent HSV. This approach allows oncolytic therapy to replicate selectively within and lyse tumor cells while providing the host immune system with the cytokine stimulus necessary to recruit and activate inflammatory cells needed to enhance the antitumor effect. MethodsNV1023 is a multimutant HSV based on the wild-type HSV-1 F strain. NV1042 was created by insertion of the mIL-12 gene into NV1023. Cytotoxicity and viral proliferation of both NV1023 and NV1042 within murine CT26 colorectal cancer cells were first shown. Cells infected with NV1042 were then shown to produce significant levels of IL-12. Using an experimental flank model of colon cancer, mice were treated with both high and low doses of NV1023 or NV1042 and were followed up for both cure and reduction in tumor burden. ResultsBoth viruses could replicate within and kill CT26 cells in vitro, with 100% cytotoxicity achieved after infection by either virus. Only NV1042 could produce mIL-12. Therapy using high viral doses to treat animals in vivo showed equal efficacy between NV1023 and NV1042, with five of seven cures for each virus. When viral doses were lowered, only the cytokine-producing NV1042 virus could reduce tumor burden and cure animals of their disease. ConclusionsBoth NV1023 and NV1042 have the oncolytic potential to kill colon cancer cells at higher doses. Cytokine production by NV1042 may allow lower doses of viral therapy to be used without losing antitumor efficacy. The combination of oncolytic viral therapy and immunomodulatory strategies should be further investigated as treatment for colon cancer.
A Fully Distributed Reactive Power Optimization and Control Method for Active Distribution Networks

This paper presents a fully distributed reactive power optimization algorithm that can obtain the global optimum solution of nonconvex problems for distribution networks (DNs) without requiring a central coordinator. Second-order conic relaxation is used to achieve exact convexification. A fully distributed second-order cone programming solver (D-SOCP) is formulated corresponding to the given division of areas based on the alternating direction method of multipliers (ADMM) algorithm, which is greatly simplified by exploiting the structure of active DNs. The problem is solved for each area with very little interchange of boundary information between neighboring areas. D-SOCP is extended by using a varying penalty parameter to improve convergence. A proof of its convergence is also given. The effectiveness of the method is demonstrated via numerical simulations using the IEEE 69-bus, 123-bus DNs, and a real 1066-bus distribution system.