Miracle-dz/UniFAR-FTUs huggingface dataset:
Ionized calcium‐binding adaptor molecule 1 positive macrophages and HO‐1 up‐regulation in intestinal muscularis resident macrophages

Small intestinal muscularis externa macrophages have been associated with interstitial cells of Cajal. They have been proposed to play various roles in motility disorders and to take part in a microbiota‐driven regulation of gastrointestinal motility. Our objective was to understand the reaction of resident macrophages of the musculature to a pro‐inflammatory stimulator, lipopolysaccharide (LPS). Mice were injected with LPS or saline and sacrificed after 6 hr. Whole mounts were stained with antibodies toward CD169, ionized calcium‐binding adaptor molecule 1 (iba1) (microglial/macrophage marker) and heme oxygenase‐1 (HO‐1). Cell densities were measured using unbiased stereology. Results: iba1pos cells showed an overall higher density than CD169pos and HO‐1pos cells. Most HO‐1pos and iba1pos cells were positive for CD 169 in serosa and at Auerbach's plexus (AP). At the deep muscular plexus, mainly iba1pos cells were present, and were mostly CD169neg; a few HO‐1pos cells were present. Conclusions: A new subset of resident macrophages in the intestinal muscularis externa was discovered, identified as iba1pos CD169neg. HO‐1 is constitutively present in most macrophages in serosa and at AP, suggesting a M2 phenotype. LPS‐treatment results in an up‐regulation of HO‐1pos/CD169neg cells in serosa and at AP. Anat Rec, 300:1114–1122, 2017. © 2016 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists
Synthesis of CdS/CeO2 hetero nanostructures for Photocatalytic H2 production and simultaneous Removal of phenol and Cr(VI)

Harvesting visible light of the solar spectrum by coupled semiconductor based systems where sensitization of a wide band gap semiconductor with a small band gap semiconductor advantageous for photocatalytic as well as photovoltaic applications. A facile one pot synthesis of several CdS/CeO2 hetero nanostructures has been carried out without using expensive surfactants, capping agents and molecular linkers. Various techniques such as Xray diffraction (XRD), Transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), diffuse reflectance UV-Vis spectroscopy, Raman spectroscopy and BET surface area were used to characterize the samples. XRD and Raman spectroscopic data provided the information about the presence of both CdS and CeO2 phases. TEM proves the proper dispersion and well connectivity between the CdS and CeO2 which may be due to the single step synthesis of the composites. XPS gives the information about the presence of elements such as Cd, Ce, O, S, C and N, where the presence of latter two elements can be attributed to the in-situ C and N doping during the combustion synthesis. UV-visible spectroscopy reveals the absorption in both UV and visible regions due to the presence of both CeO2 and CdS. The visible light activity of the composites have been ascribed by the H2 production from water by using sacrificial reagents, simultaneous removal of phenol and Cr(VI) from aqueous streams. Among the synthesized composites CdS/CeO2 (1:1) has shown superior activity which can be attributed to the optimum sensitization of CeO2 which induces enhanced electron transfer from CdS to CeO2 that decreases the exciton recombination.
Associations of fat and muscle tissue with cognitive status in older adults: the AGES-Reykjavik Study

Background/Objective studies on the association of dementia with specific body composition (BC) components are scarce. Our aim was to investigate associations of BC measures with different levels of cognitive function in late-life. Methods we studied 5,169 participants (mean age 76 years, 42.9% men) in the AGES-Reykjavik Study of whom 485 (9.4%) were diagnosed with mild cognitive impairment (MCI) and 307 (5.9%) with dementia. Visceral fat, abdominal and thigh subcutaneous fat, and thigh muscle were assessed by computed tomography. MCI and dementia were based on clinical assessment and a consensus meeting; those without MCI or dementia were categorised as normal. Multinomial regression models assessed the associations stratified by sex and in additional analyses by midlife body mass index (BMI). Results among women, there was a decreased likelihood of dementia per SD increase in abdominal subcutaneous fat (OR 0.72; 95% CI: 0.59-0.88), thigh subcutaneous fat (0.81; 0.67-0.98) and thigh muscle (0.63; 0.52-0.76), but not visceral fat, adjusting for demographics, vascular risk factors, stroke and depression. Inverse associations of fat with dementia were attenuated by weight change from midlife and were strongest in women with midlife BMI <25. In men, one SD increase in thigh muscle was associated with a decreased likelihood of dementia (0.75; 0.61-0.92). BC was not associated with MCI in men or women. Conclusion a higher amount of abdominal and thigh subcutaneous fat were associated with a lower likelihood of dementia in women only, while more thigh muscle was associated with a lower likelihood of dementia in men and women.
Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by Transmembrane O-methyltransferase (Tomt)

Transmembrane O-methyltransferase (TOMT/LRTOMT) is responsible for non-syndromic deafness DFNB63. However, the specific defects that lead to hearing loss have not been described. Using a zebrafish model of DFNB63, we show that the auditory and vestibular phenotypes are due to a lack of mechanotransduction (MET) in Tomt-deficient hair cells. GFP-tagged Tomt is enriched in the Golgi of hair cells, suggesting that Tomt might regulate the trafficking of other MET components to the hair bundle. We found that Tmc1/2 proteins are specifically excluded from the hair bundle in tomt mutants, whereas other MET complex proteins can still localize to the bundle. Furthermore, mouse TOMT and TMC1 can directly interact in HEK 293 cells, and this interaction is modulated by His183 in TOMT. Thus, we propose a model of MET complex assembly where Tomt and the Tmcs interact within the secretory pathway to traffic Tmc proteins to the hair bundle. DOI: http://dx.doi. org/10.7554/eLife.28474. 001
Effects of high ambient temperature on ambulance dispatches in different age groups in Fukuoka, Japan

ABSTRACT Background: The elderly population has been the primary target of intervention to prevent heat-related illnesses. According to the literature, the highest risks have been observed among the elderly in the temperature–mortality relationship. However, findings regarding the temperature–morbidity relationship are inconsistent. Objectives: This study aimed to examine the association of temperature with ambulance dispatches due to acute illnesses, stratified by age group. Specifically, we explored the optimum temperature, at which the relative health risks were found to be the lowest, and quantified the health risk associated with higher temperatures among different age groups. Methods: We used the data for ambulance dispatches in Fukuoka, Japan, during May and September from 2005 to 2012. The data were grouped according to age in 20-year increments. We explored the pattern of the association of ambulance dispatches with temperature using a smoothing spline curve to identify the optimum temperature for each age group. Then, we applied a distributed lag nonlinear model to estimate the risks of the 85th–95th percentile temperature relative to the overall optimum temperature, for each age group. Results: The relative risk of ambulance dispatches at the 85th and 95th percentile temperature for all ages was 1.08 [95% confidence interval (CI): 1.05, 1.12] and 1.12 (95% CI: 1.08, 1.16), respectively. In comparison, among age groups, the optimum temperature was observed as 25.0°C, 23.2°C, and 25.3°C for those aged 0–19, 60–79, and ≥80, respectively. The optimum temperature could not be determined for those aged 20–39 and 40–59. The relative risks of high temperature tended to be higher for those aged 20–39 and 40–59 than those for other age groups. Conclusions: We did not find any definite difference in the effect of high temperature on ambulance dispatches for different age groups. However, more measures should be taken for younger and middle-aged people to avoid heat-related illnesses.
Stereotactic Radiosurgery for Brainstem Arteriovenous Malformations: A Multicenter Study

BACKGROUND The management of brainstem arteriovenous malformations (bAVMs) is a formidable challenge. bAVMs harbor higher morbidity and mortality compared to other locations. OBJECTIVE To review the outcomes following stereotactic radiosurgery (SRS) of bAVMs in a multicenter study. METHODS Six medical centers contributed data from 205 patients through the International Gamma Knife Research Foundation. Median age was 32 yr (6-81). Median nidus volume was 1.4 mL (0.1-69 mL). Favorable outcome (FO) was defined as AVM obliteration and no post-treatment hemorrhage or permanent symptomatic radiation-induced complications. RESULTS Overall obliteration was reported in 65.4% (n = 134) at a mean follow-up of 69 mo. Obliteration was angiographically proven in 53.2% (n = 109) and on MRA in 12.2% (n = 25). Actuarial rate of obliteration at 2, 3, 5, 7, and 10 yr after SRS was 24.5%, 43.3%, 62.3%, 73%, and 81.8% respectively. Patients treated with a margin dose >20 Gy were more likely to achieve obliteration (P = .001). Obliteration occurred earlier in patients who received a higher prescribed margin dose (P = .05) and maximum dose (P = .041). Post-SRS hemorrhage occurred in 8.8% (n = 18). Annual postgamma knife latency period hemorrhage was 1.5%. Radiation-induced complications were radiologically evident in 35.6% (n = 73), symptomatic in 14.6% (n = 30), and permanent in 14.6% (n = 30, which included long-tract signs and new cranial nerve deficits). FO was achieved in 64.4% (n = 132). Predictors of an FO were a higher Virginia radiosurgery AVM scale score (P = .003), prior hemorrhage (P = .045), and a lower prescribed maximum dose (P = .006). CONCLUSION SRS for bAVMs results in obliteration and avoids permanent complications in the majority of patients.
A Phase 1 Study of the PARP Inhibitor Veliparib in Combination with Temozolomide in Acute Myeloid Leukemia

Purpose: In preclinical studies, the PARP inhibitor veliparib enhanced the antileukemic action of temozolomide through potentiation of DNA damage. Accordingly, we conducted a phase 1 study of temozolomide with escalating doses of veliparib in patients with relapsed, refractory acute myeloid leukemia (AML) or AML arising from aggressive myeloid malignancies. Experimental Design: Patients received veliparib [20–200 mg once a day on day 1 and twice daily on days 4–12 in cycle 1 (days 1–8 in cycle ≥2)] and temozolomide [150–200 mg/m2 daily on days 3–9 in cycle 1 (days 1–5 in cycle ≥2)] every 28 to 56 days. Veliparib pharmacokinetics and pharmacodynamics [ability to inhibit poly(ADP-ribose) polymer (PAR) formation and induce H2AX phosphorylation] were assessed. Pretreatment levels of MGMT and PARP1 protein, methylation of the MGMT promoter, and integrity of the Fanconi anemia pathway were also examined. Results: Forty-eight patients were treated at seven dose levels. Dose-limiting toxicities were oral mucositis and esophagitis lasting >7 days. The MTD was veliparib 150 mg twice daily with temozolomide 200 mg/m2 daily. The complete response (CR) rate was 17% (8/48 patients). Veliparib exposure as well as inhibition of PAR polymer formation increased dose proportionately. A veliparib-induced increase in H2AX phosphorylation in CD34+ cells was observed in responders. Three of 4 patients with MGMT promoter methylation achieved CR. Conclusions: Veliparib plus temozolomide is well tolerated, with activity in advanced AML. Further evaluation of this regimen and of treatment-induced phosphorylation of H2AX and MGMT methylation as potential response predictors appears warranted. Clin Cancer Res; 23(3); 697–706. ©2016 AACR.
The role of Cdk5‐mediated Drp1 phosphorylation in Aβ1‐42 induced mitochondrial fission and neuronal apoptosis

Alzheimer's disease, one of the most common neurodegenerative diseases, is pathologically characterized by Amyloid beta containing plaques and neurofibrillary tangles. Amyloid beta (Aβ) induces neuronal apoptosis through the intracellular Ca2+ increase, subsequent hyperactivation of cyclin‐dependent kinase 5 (Cdk5) and mitochondrial abnormality. Recently, Cdk5 was identified as an upstream regulator of mitochondrial fission during neuronal apoptosis, but the underlying mechanism remains unclear. Here, in vitro phosphorylation assays showed that Cdk5 could phosphorylate the recombinant Drp1 at Serine 579. Aβ1‐42 stimulation increased the phosphorylation level of Drp1 at Serine 579 in mouse cortical neurons. Cdk5 inhibitor roscovitine and knockdown of Cdk5 by a lentiviral vector expressing shRNA targeting Cdk5 (Lenti‐Cdk5‐shRNA) efficiently prevented Aβ1‐42 induced Drp1 phosphorylation in neurons. In addition, Aβ1‐42 stimulation induced markedly mitochondrial fission in neurons. Roscovitine, Lenti‐Cdk5‐shRNA and expression of phospho‐defect mutatant GFP‐Drp1‐S579A in neurons attenuated Aβ1‐42 induced mitochondrial fission, whereas expression of phospho‐mimetic mutant GFP‐Drp1‐S579D alone resulted in mitochondiral fission similar to Aβ1‐42 stimulation. Moreover, Roscovitine and Lenti‐Cdk5‐shRNA suppressed the cleavage of caspase‐3 and protected neurons against Aβ1‐42 induced neuronal apoptosis.Thus, our data indicate that Drp1 is a direct target of Cdk5, and Cdk5‐mediated phosphorylation of Drp1 at Serine 579 regulates Aβ1‐42 induced mitochondrial fission and neuronal toxicity.
Effect of cumin essential oil usage on fermentation quality, aerobic stability and in vitro digetibility of alfalfa silage

Objective This study was carried out to determine the effects of cumin essential oil on the silage fermentation, aerobic stability and in vitro digestibility of alfalfa silages. Methods Alfalfa was harvested at early bloom (5th cutting) stage in October and wilted for about 3 hours. The research was carried out at three groups which were the control group where no additive control was done (CON), cumin essential oil (CMN3) with 300 mg/kg and CMN5 with 500 mg/kg cumin essential oil addition. Alfalfa was ensiled in plastic bags. The packages were stored at 8°C±2°C under laboratory conditions. All groups were sampled for physical, chemical and microbiological analysis 120th day after ensiling. At the end of the ensiling period, all silages were subjected to an aerobic stability test for 7 days. In addition, enzimatic solubility of organic matter (ESOM), metabolizable energy (ME), and relative feed value (RFV) of these silages were determined. Results pH level decreased in the cumin groups compared to CON (p<0.05), thus inhibiting proteolytic enzymes from breaking down proteins into ammonia. In addition, it increased ESOM amount, and concordantly provided an increase of ME contents. Similarly, dry matter intake and RFV ratio increased. After opening the silage, it kept its aerobic stability for three days. Conclusion Cumin essential oil improved fermentation, and affected chemical and microbiological characteristics of silages. Especially the addition of 300 mg/kg cumin provided cell wall fractionation through stimulating the activities of enzymes responsible. It also increased the number and activity of lactic acid bacteria (LAB) through providing a development of LAB.
A new perspective on environmental controls of marine nitrogen fixation

Growing slowly, marine N2 fixers are generally expected to be competitive only where nitrogen (N) supply is low relative to that of phosphorus (P) with respect to the cellular N:P ratio (R) of nonfixing phytoplankton. This is at odds with observed high N2 fixation rates in the oligotrophic North Atlantic where the ratio of nutrients supplied to the surface is elevated in N relative to the average R (16:1). In this study, we investigate several mechanisms to solve this puzzle: iron limitation, phosphorus enhancement by preferential remineralization or stoichiometric diversity of phytoplankton, and dissolved organic phosphorus (DOP) utilization. Combining resource competition theory and a global coupled ecosystem‐circulation model, we find that the additional N and energy investments required for exoenzymatic breakdown of DOP give N2 fixers a competitive advantage in oligotrophic P‐starved regions. Accounting for this mechanism expands the ecological niche of N2 fixers also to regions where the nutrient supply is high in N relative to R, yielding, in our model, a pattern consistent with the observed high N2 fixation rates in the oligotrophic North Atlantic.
Analysis of software cost models with rejuvenation

Software rejuvenation is a preventive maintenance technique that has been extensively studied in the recent literature. In this paper we extend the classical result by Huang et al. (1995), and in addition propose a modified stochastic model to generate the software rejuvenation schedule. More precisely, the software rejuvenation models are formulated via the semi-Markov process, and the optimal software rejuvenation schedule which minimizes the expected costs per unit time in the steady-state are derived analytically for respective cases. Further we develop non-parametric algorithms to estimate the optimal software rejuvenation schedules, provided that the statistical complete (unsensored) sample data of failure time is given. In numerical examples, we compare two models in terms of economic justification, and examine asymptotic properties for the statistical estimation algorithms.
ON WATER QUALITY MODELLING OF DIANCHI LAKE , YUNNAN PROVINCE , SOUTH WEST CHINA

The main aim of this work was to construct and validate a mathematical water quality model of the Dianchi lake, so that by altering input total phosphate (TP) loads the projected changes in the lake water TP concentrations could be estimated. Historical information had indicated deteriorating lake water quality with increasing TP concentrations. The model was based on a simple annual mass balance, relying on 3 years (wet, average and dry) data with all TP loads quantified, 7 years of lake water quality, and 36 years of flow data. All lake processes were considered within a single variable, R. Planning TP removal at STWs and within fertilizer plants, coupled with interventions to reduce non-point TP loads from all land runoff by 50%, suggested future lake water TP concentrations could be stabilised at about 0.3 ing TP/1, i.e. the estimated limit for producing algal concentrations that would cause major problems in water treatment plants. The TP load reductions envisaged as realistic would only stabilise the lake water quality by about the year 2008; interventions, unfortunately, could not return the lake to its former pristine condition. The accuracy of the predictions was ± 0.1 mg TP/1, so collection of better data was needed. © 1999 1AWQ Published by Elsevier Science Ltd. All rights reserved.
Plastic response of the native oxide on Cr and Al thin films from in situ conductive nanoindentation

Thin native oxide layers can dominate the mechanical properties of metallic thin films. However, to date there has been little quantification of how such overlayers affect yield and fracture during indentation in constrained film systems. To gain insight into such processes, electrical contact resistance was measured in situ during nanoindentation on constrained thin films of epitaxial Cr and polycrystalline Al, both possessing a native oxide overlayer. Measurements during loading of the films show both increases and decreases in current, which can then be used to distinguish between various sources of plasticity. Ex situ measurements of the oxide thickness are used to provide a starting point for elasticity simulations of stress in both systems. The results show that dislocation nucleation in the metal film can be differentiated from oxide fracture during indentation.
Role of LRP1 in the pathogenesis of Alzheimer’s disease: evidence from clinical and preclinical studies

Among the LDL receptor (LDLR) family members, the roles of LDLR-related protein (LRP)1 in the pathogenesis of Alzheimer’s disease (AD), especially late-onset AD, have been the most studied by genetic, neuropathological, and biomarker analyses (clinical studies) or cellular and animal model systems (preclinical studies) over the last 25 years. Although there are some conflicting reports, accumulating evidence from preclinical studies indicates that LRP1 not only regulates the metabolism of amyloid-β peptides (Aβs) in the brain and periphery, but also maintains brain homeostasis, impairment of which likely contributes to AD development in Aβ-independent manners. Several preclinical studies have also demonstrated an involvement of LRP1 in regulating the pathogenic role of apoE, whose gene is the strongest genetic risk factor for AD. Nonetheless, evidence from clinical studies is not sufficient to conclude how LRP1 contributes to AD development. Thus, despite very promising results from preclinical studies, the role of LRP1 in AD pathogenesis remains to be further clarified. In this review, we discuss the potential mechanisms underlying how LRP1 affects AD pathogenesis through Aβ-dependent and -independent pathways by reviewing both clinical and preclinical studies. We also discuss potential therapeutic strategies for AD by targeting LRP1.
Cohort profile: the Danish Web-based Pregnancy Planning Study--'Snart-Gravid'.

The Danish Web-based Pregnancy Planning Studywas initiated in 2007 by researchers from AarhusUniversity Hospital, Denmark and Boston University,USA, primarily to evaluate the feasibility of Internet-based recruitment and follow-up of a cohort ofreproductive age women. In this report, we describethe study design and present descriptive data basedon the pilot phase of this ongoing study.Several large-scale cohort studies of reproductive agewomen have been conducted, including the DanishNational Birth Cohort
Minimum sample size estimation in PLS‐SEM: The inverse square root and gamma‐exponential methods

Partial least squares‐based structural equation modelling (PLS‐SEM) is extensively used in the field of information systems, as well as in many other fields where multivariate statistical methods are used. One of the most fundamental issues in PLS‐SEM is that of minimum sample size estimation. The ‘10‐times rule’ has been a favourite because of its simplicity of application, even though it tends to yield imprecise estimates. We propose two related methods, based on mathematical equations, as alternatives for minimum sample size estimation in PLS‐SEM: the inverse square root method, and the gamma‐exponential method. Based on three Monte Carlo experiments, we demonstrate that both methods are fairly accurate. The inverse square root method is particularly attractive in terms of its simplicity of application. © 2016 John Wiley & Sons Ltd
Predictive Indicators to Identify High-Risk Paediatric Febrile Neutropenia in Paediatric Oncology Patients in a Middle-Income Country

Purpose To validate a clinical risk prediction score (Ammann score) to predict adverse events (AEs) in paediatric febrile neutropenia (FN). Patients and methods Patients <16 years of age were enrolled. A risk prediction score (based on haemoglobin ≥ 9 g/dl, white cell count (WCC) < 0.3 G/l, platelet count <50 G/l and chemotherapy more intensive than acute lymphoblastic leukaemia maintenance therapy) was calculated and AEs were documented. Results In total, 100 FN episodes occurred in 52 patients, male:female ratio was 1.8:1 and median age was 56 months. At reassessment, AEs occurred in 18 of 55 (45%) low-risk FN episodes (score < 9) and 21 of 42 (55%) high-risk episodes (score ≥9) (sensitivity 60%, specificity 65%, positive predictive value 53%, negative predictive value 71%). Total WCC and absolute monocyte count (AMC) were significantly associated with AEs. Conclusion This study identified total WCC and AMC as significantly associated with AEs but failed to validate the risk prediction score.