Miracle-dz/UniFAR-FTUs huggingface dataset:
Epigenetic heredity of human height

Genome‐wide SNP analyses have identified genomic variants associated with adult human height. However, these only explain a fraction of human height variation, suggesting that significant information might have been systematically missed by SNP sequencing analysis. A candidate for such non‐SNP‐linked information is DNA methylation. Regulation by DNA methylation requires the presence of CpG islands in the promoter region of candidate genes. Seventy two of 87 (82.8%), height‐associated genes were indeed found to contain CpG islands upstream of the transcription start site (USC CpG island searcher; validation: UCSC Genome Browser), which were shown to correlate with gene regulation. Consistent with this, DNA hypermethylation modules were detected in 42 height‐associated genes, versus 1.5% of control genes (P = 8.0199e−17), as were dynamic methylation changes and gene imprinting. Epigenetic heredity thus appears to be a determinant of adult human height. Major findings in mouse models and in human genetic diseases support this model. Modulation of DNA methylation are candidate to mediate environmental influence on epigenetic traits. This may help to explain progressive height changes over multiple generations, through trans‐generational heredity of progressive DNA methylation patterns.
Characterization of Two Signal Transduction Systems Involved in Intracellular Macrophage Survival and Environmental Stress Response in Enterococcus faecalis

The intracellular survival in mouse peritoneal macrophages of 8 Enterococcus faecalis response regulator mutants was tested to assess if the corresponding 2-component signal transduction systems (TCS) are involved in the ability of E. faecalis to survive in macrophages. Three mutants (err04, err05 and err06) are more susceptible than the wild-type JH2-2 strain and 1 is more resistant (err10). Then, characterization of the TCS Err04-Ehk04 and Err06-Ehk06 reveals that the first (homolog of PhoP-PhoR of Bacillus subtilis) is induced in phosphate deprivation conditions, regulates its own expression and plays a role in the expression of pstF encoding a phosphate-binding protein. The Err06-Ehk06 is involved in oxidative stress response. A mutation in the err06 gene increases sensitivity of the bacterium to H2O2. The err06-ehk06 operon is induced by H2O2 stress and controlled by 2 transcriptional start sites, of which 1 is specifically active in oxidative stress conditions. We also demonstrated that the expression of the catalase gene (kat) is partly dependant of the Err06-Ehk06 TCS.
Rerupture of a Blister Aneurysm After Treatment With a Single Flow-Diverting Stent.

BACKGROUND AND IMPORTANCE As the use of flow-diverting stents (FDSs) for intracranial aneurysms expands, a small number of case reports have described the successful treatment of blister aneurysms of the internal carotid artery with flow diversion. Blister aneurysms are uncommon and fragile lesions that historically have high rates of morbidity and mortality despite multiple treatment strategies. We report a case of rebleeding after treatment of a ruptured blister aneurysm with deployment of a single FDS. CLINICAL PRESENTATION A 29-year-old man presented with subarachnoid hemorrhage and a ruptured dorsal variant internal carotid artery aneurysm. Despite a technically successful treatment with a single FDS, a second catastrophic hemorrhage occurred during the course of his hospitalization. CONCLUSION This case highlights the risk of hemorrhage during the period after deployment of a single FDS. Ruptured aneurysms, especially of the blister type, are at risk for rehemorrhage while the occlusion remains incomplete after flow diversion. ABBREVIATIONS FDS, flow-diverting stentICA, internal carotid arterySAH, subarachnoid hemorrhage.
Market Knowledge Dimensions and Cross-Functional Collaboration: Examining the Different Routes to Product Innovation Performance

There is consensus in the marketing literature that market knowledge and cross-functional collaboration are two fundamental resources for successful product innovation. However, few studies examine the dimensions or characteristics of market knowledge and how and why these resources influence product innovation performance. Drawing on contingency theory and the knowledge-based view of the firm, the authors argue that knowledge integration mechanisms may account for the effects of market knowledge dimensions (i.e., breadth, depth, tacitness, and specificity) and cross-functional collaboration on product innovation performance. They find that market knowledge specificity and cross-functional collaboration affect product innovation performance through knowledge integration mechanisms. In contrast, whereas the effect of market knowledge depth is partially mediated, market knowledge breadth has a direct, unmediated effect on product innovation performance. A test of an alternative moderating perspective shows that the effects of market knowledge depth and cross-functional collaboration on product innovation are negatively moderated by knowledge integration mechanisms. By showing the differential effects of market knowledge dimensions on product innovation performance, the authors provide a more refined understanding of the interplay among market knowledge, its integration, and the firm's performance in product innovation. The authors also conclude that by overlooking the role of knowledge integration mechanisms, previous research may have provided an overly optimistic view of the value of cross-functional collaboration in product innovation.
Concealed renal failure and adverse drug reactions in older patients with type 2 diabetes mellitus.

BACKGROUND In elderly patients serum creatinine may be normal despite decreased glomerular filtration rate (GFR). The aim of this study was to evaluate the prevalence of this "concealed" renal failure, i.e., renal failure with normal serum creatinine levels, in elderly diabetic patients, and to verify whether it is a risk factor for adverse drug reactions (ADR) to hydrosoluble drugs. METHODS We used data on 2257 hospitalized patients with type 2 diabetes mellitus enrolled in the Gruppo Italiano di Farmacovigilanza nell'Anziano study. On the basis of serum creatinine and calculated GFR, patients were grouped as follows: normal renal function (normal serum creatinine levels and normal GFR), concealed (normal serum creatinine levels and reduced GFR), or overt (increased creatinine levels and reduced GFR) renal failure. GFR was calculated using the Modification of Diet in Renal Disease (MDRD) equation. The outcome of the study was the incidence of ADR to hydrosoluble drugs during the hospital stay. The relationship between renal function and ADR was evaluated using Cox regression analysis including potential confounders. RESULTS Concealed renal failure was observed in 363 (16.1%) of patients studied. Patients with concealed or overt renal failure were older, had more frequently cognitive impairment and polypharmacy, and had lower serum albumin levels than did those with normal renal function. Both concealed (hazard ratio = 1.90; 95% confidence interval, 1.04-3.48; p =.036) and overt (hazard ratio = 2.23; 95% confidence interval, 1.40-3.55; p =.001) renal failure were significantly associated with ADR to hydrosoluble drugs. The use of more than four drugs also qualified as an independent risk factor for ADRs to hydrosoluble drugs during hospital stay. CONCLUSIONS Older diabetic patients should be systematically screened to ascertain the presence of concealed renal failure in an attempt to optimize the pharmacological treatment and reduce the risk of ADRs.
A Robust Bisection-Based Estimator for TOA-Based Target Localization in NLOS Environments

This letter addresses the problem of target localization in harsh indoor environments based on range measurements. To mitigate the non-line-of-sight (NLOS) bias, we propose a novel robust estimator by transforming the localization problem into a generalized trust region sub-problem framework. Although still non-convex in general, this class of problems can be readily solved exactly by means of bisection procedure. The new approach does not require to make any assumptions about the statistics of NLOS bias, nor to try to distinguish which links are NLOS and which are not. Unlike the existing algorithms, the computational complexity of the proposed algorithm is linear in the number of reference nodes. Our simulation results corroborate the effectiveness of the new algorithm in terms of NLOS bias mitigation and show that the performance of our estimator is highly competitive with the performance of the state-of-the-art algorithms. In fact, they show that the novel estimator outperforms slightly the existing ones in general, and that it always provides a feasible solution.
How scent and nectar influence floral antagonists and mutualists

Many plants attract and reward pollinators with floral scents and nectar, respectively, but these traits can also incur fitness costs as they also attract herbivores. This dilemma, common to most flowering plants, could be solved by not producing nectar and/or scent, thereby cheating pollinators. Both nectar and scent are highly variable in native populations of coyote tobacco, Nicotiana attenuata, with some producing no nectar at all, uncorrelated with the tobacco's main floral attractant, benzylacetone. By silencing benzylacetone biosynthesis and nectar production in all combinations by RNAi, we experimentally uncouple these floral rewards/attractrants and measure their costs/benefits in the plant's native habitat and experimental tents. Both scent and nectar increase outcrossing rates for three, separately tested, pollinators and both traits increase oviposition by a hawkmoth herbivore, with nectar being more influential than scent. These results underscore that it makes little sense to study floral traits as if they only mediated pollination services. DOI: http://dx.doi. org/10.7554/eLife.07641. 001
Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism

Reductions in cerebral blood flow and extracranial perfusion, induced by dehydration during prolonged exercise in the heat, may be coupled to fatigue. However, cerebral metabolism remains stable through enhanced O2 and glucose extraction. Thus, fatigue developed during prolonged exercise with dehydration is related to reductions in cerebral blood flow rather than to the cerebral metabolic rate for O2.
Experimental systemic murine aspergillosis: treatment with polyene and caspofungin combination and G-CSF.

OBJECTIVES In view of the poor therapy outcomes of invasive aspergillosis, the objective of this study was to evaluate the efficacy of combination treatment consisting of the polyene amphotericin-B-intralipid, the echinocandin caspofungin and granulocyte-colony stimulating factor (G-CSF) in experimental murine systemic aspergillosis. With inhibition of synthesis of 1,3-beta-d-glucan in the fungal cell wall by caspofungin and an effect on the cell membrane by amphotericin-B-intralipid, this treatment may result in a synergic effect against Aspergillus fumigatus. Addition of G-CSF may further contribute to therapy of aspergillosis. METHODS ICR mice were immunosuppressed by intraperitoneal administration of cyclophosphamide. Three days later, the mice were inoculated intravenously (iv) with A. fumigatus conidia. Infection and treatment were evaluated during an observation period of 30 days in terms of mortality (survival rate and mean survival time) and morbidity (quantitative determination of fungal burden, histopathology, and detection of serum galactomannan). RESULTS Combination of caspofungin + G-CSF or addition of G-CSF to the combination of caspofungin + amphotericin-B-intralipid increased the survival rate of infected mice up to 78.9% and prolonged their mean survival time to 25 days. These combinations also resulted in a reduction in fungal burden in organs, and a decrease in serum galactomannan. CONCLUSIONS The successful results obtained in the experimental model may possibly open the way to more effective management of aspergillosis in humans.
A HU‐like gene mutation in Rhizobium leguminosarum bv. viciae affects the expression of nodulation genes

NodD is the major regulator of nod genes expression in rhizobia. Previously, a HU‐like protein in Rhizobium leguminosarum bv. viciae has been identified to bind specifically with nod promoters and be involved in in vitro nodD transcription, but its in vivo function remained unknown. In this work we have cloned and sequenced the R. leguminosarum bv. viciae gene, named hurL, for this HU‐like protein. Using the E. coli‐expressed HurL proteins, we proved that HurL had high affinity to several nod promoters and showed a stimulation effect on in vitro nodD transcription at appropriate concentration. The R. leguminosarum bv. viciae hurL gene was mutated by insertion of a kanamycin resistance cassette. The obtained hurL mutant strain M704 exhibited poor growth under free‐living conditions and failed to induce nodules on Pisum sativum cv. Frisson and Vicia hirsuta. Further studies of NodD production and nod genes‐lacZ fusions expression in the hurL mutant revealed that inactivation of hurL led to severe impairment in the nodD expression, repression in the inducible expression of nodA and nodF, and slight enhancement in the expression of px2, a gene identified earlier in this lab. These results suggested that hurL might be required for maintaining the normal expression of nod genes in R. leguminosarum bv. viciae.
WATERTIGHT DURAL CLOSURE: IS IT NECESSARY? A PROSPECTIVE RANDOMIZED TRIAL IN PATIENTS WITH SUPRATENTORIAL CRANIOTOMIES

OBJECTIVE The aim of the current study was to prospectively analyze complication rates and costs associated with dural closure in patients undergoing supratentorial craniotomies, randomized for watertight and adaptive dural closures. METHODS One hundred fifty consecutive patients with supratentorial lesions who were between 18 and 70 years of age were prospectively included. A watertight dural closure was the primary goal (Group A). Whenever this goal could not be achieved, patients were intraoperatively randomized for secondary watertight (Group B) or adaptive dural closure (Group C). Within a follow-up period of 4 weeks, study end points were the occurrence of complications such as subcutaneous fluid collections, impaired wound healing with and without cerebrospinal fluid leakage, and infection. Moreover, we analyzed costs for dural closure for each group separately. RESULTS Of 150 eligible patients, 13 were excluded according to predefined criteria (Group A, n = 3; Group B, n = 7; Group C, n = 3). From those patients, a primary watertight dural closure could be obtained in 44 (29.4%) patients. A secondary watertight dural closure was performed in 53 (35.3%) patients, and an adaptive dural closure was performed in 53 (35.3%) patients. Complications that were related to dural closure or wound closure were found in 7 patients in Group A, 6 patients in Group B, and 12 patients in Group C (all not significant). The mean total costs, based on time and additional material required in Group A (US $436 ± 119) or Group B (US $681 ± 286) were significantly greater compared with adaptive dural closure in Group C (US $213 ± 142, P < 0.05). CONCLUSION In supratentorial craniotomies, an adaptive dural closure may represent a safe and cost-effective alternative to watertight dural closure.
Climate Change Across Seasons Experiment (CCASE): A new method for simulating future climate in seasonally snow-covered ecosystems

Climate models project an increase in mean annual air temperatures and a reduction in the depth and duration of winter snowpack for many mid and high latitude and high elevation seasonally snow-covered ecosystems over the next century. The combined effects of these changes in climate will lead to warmer soils in the growing season and increased frequency of soil freeze-thaw cycles (FTCs) in winter due to the loss of a continuous, insulating snowpack. Previous experiments have warmed soils or removed snow via shoveling or with shelters to mimic projected declines in the winter snowpack. To our knowledge, no experiment has examined the interactive effects of declining snowpack and increased frequency of soil FTCs, combined with soil warming in the snow-free season on terrestrial ecosystems. In addition, none have mimicked directly the projected increase in soil FTC frequency in tall statured forests that is expected as a result of a loss of insulating snow in winter. We established the Climate Change Across Seasons Experiment (CCASE) at Hubbard Brook Experimental Forest in the White Mountains of New Hampshire in 2012 to assess the combined effects of these changes in climate on a variety of pedoclimate conditions, biogeochemical processes, and ecology of northern hardwood forests. This paper demonstrates the feasibility of creating soil FTC events in a tall statured ecosystem in winter to simulate the projected increase in soil FTC frequency over the next century and combines this projected change in winter climate with ecosystem warming throughout the snow-free season. Together, this experiment provides a new and more comprehensive approach for climate change experiments that can be adopted in other seasonally snow-covered ecosystems to simulate expected changes resulting from global air temperature rise.
Impact of Epidural Analgesia on Mortality and Morbidity After Surgery: Systematic Review and Meta-analysis of Randomized Controlled Trials

Objective:To quantify benefit and harm of epidural analgesia, compared with systemic opioid analgesia, in adults having surgery under general anesthesia. Background:It remains controversial whether adding epidural analgesia to general anesthesia decreases postoperative morbidity and mortality. Methods:We searched CENTRAL, EMBASE, PubMed, CINAHL, and BIOSIS till July 2012. We included randomized controlled trials comparing epidural analgesia (with local anesthetics, lasting for ≥24 hours postoperatively) with systemic analgesia in adults having surgery under general anesthesia, and reporting on mortality or any morbidity endpoint. Results:A total of 125 trials (9044 patients, 4525 received epidural analgesia) were eligible. In 10 trials (2201 patients; 87 deaths), reporting on mortality as a primary or secondary endpoint, the risk of death was decreased with epidural analgesia (3.1% vs 4.9%; odds ratio, 0.60; 95% confidence interval, 0.39–0.93). Epidural analgesia significantly decreased the risk of atrial fibrillation, supraventricular tachycardia, deep vein thrombosis, respiratory depression, atelectasis, pneumonia, ileus, and postoperative nausea and vomiting, and also improved recovery of bowel function, but significantly increased the risk of arterial hypotension, pruritus, urinary retention, and motor blockade. Technical failures occurred in 6.1% of patients. Conclusions:In adults having surgery under general anesthesia, concomitant epidural analgesia reduces postoperative mortality and improves a multitude of cardiovascular, respiratory, and gastrointestinal morbidity endpoints compared with patients receiving systemic analgesia. Because adverse effects and technical failures cannot be ruled out, individual risk–benefit analyses and professional care are recommended.
Methods for evaluating HER 2 status in breast cancer : comparison of IHC , FISH , and real-time PCR analysis of formalin-fixed paraffin-embedded tissue

Hans Olsson1,2 Agneta Jansson3 Birgitta Holmlund3 Cecilia Gunnarsson2,4 1Molecular and Immunological Pathology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; 2Department of Clinical Pathology and Clinical Genetics, Östergötland County Council, Linköping, Sweden; 3Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; 4Division of Genetics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
WT-1 expression in a spectrum of melanocytic lesions: Implication for differential diagnosis

A previous in vitro study revealed that Wilms's tumor 1 (WT-1) transcripts were detectable in 7 of 9 melanoma cell lines, but not in any of 5-normal melanocyte strains tested. Our current study assessed the expression levels of WT-1 protein in clinical samples, to determine whether the expression levels of the WT-1 protein may be used as a novel marker to assist differential diagnosis. Paraffin-embedded tissue sections from 15 cases of malignant melanomas and 25 cases of benign nevi were subjected to immunohistochemistry with a monoclonal antibody against the human WT-1 protein. The expression levels of WT-1 protein among normal, benign, and malignant melanocytes were semi-quantitatively assessed. Strong and uniform WT-1 immunoreactivities were seen in all or nearly all tumor cells in both the junctional and dermal components of all malignant melanomas, and also in a vast majority of the tumor cells of Spitz's (n = 8), recurrent (n = 2), and junction (n = 2) nevi. Distinct WT-1 immunoreactivities were also seen in some isolated individual tumor cells or tumor cell clusters in the junctional component of compound nevus (9) and in intradermal nevus (2). It is interesting to note that some isolated normal appearing melanocytes or cell clusters, and all morphologically distinct endothelial cells were strongly positive to WT-1. However, all tumor cells within the dermal component of compound (n = 9) or deep penetrating nevi (n = 1), or capsular nevus inclusion of lymph node (1) were devoid of WT-1 expression. Our findings suggest that the expression level of the WT-1 protein has no significant value in distinguishing between Spitz's nevi and malignant melanoma, but it may be a useful marker in differentiating between benign and malignant melanocytes within the dermal component. Our findings also suggest that aberrant WT-1 expression may have oncogenic properties that promote the initiation and progression of melanocytic lesions.
Beamforming for multi-group multicasting with statistical channel state information using second-order cone programming

We consider the problem of transmit beamforming in multi-group multicasting systems with covariance-based channel state information (CSI) available at the transmitter where the total transmitted power is minimized subject to quality-of-service (QoS) constraints at the receivers. Previous approaches for this problem are based on semidefinite relaxation (SDR) and require randomization and costly power scaling which is avoided in our approach. The proposed technique can be viewed as a non-trivial extension of the iterative second-order cone programming (SOCP) approach, which is restricted to the case of instantaneous (rank-one) CSI, to the beamforming problem with higher-rank channel covariance matrices. Computer simulations reveal that the proposed technique exhibits superior performance in terms of total transmitted power at a reduced computational complexity as compared to the SDR method.