Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondria Efficiently Buffer Subplasmalemmal Ca2+Elevation during Agonist Stimulation*

In endothelial cells, local Ca2+ release from superficial endoplasmic reticulum (ER) activates BKCa channels. The resulting hyperpolarization promotes capacitative Ca2+ entry (CCE), which, unlike BKCa channels, is inhibited by high Ca2+. To understand how the coordinated activation of plasma membrane ion channels with opposite Ca2+ sensitivity is orchestrated, the individual contribution of mitochondria and ER in regulation of subplasmalemmal Ca2+ concentration ([Ca2+]pm) was investigated. For organelle visualization, cells were transfected with DsRed and yellow cameleon targeted to mitochondria and ER. The patch pipette was placed far from any organelle (L1), close to ER (L3), or mitochondria (L2) and activity of BKCa channels was used to estimate local [Ca2+]pm. Under standard patch conditions (130 mm K+ in the bath), histamine increased [Ca2+]pm at L1 and L3 to ∼1.6 μm, whereas close to mitochondria [Ca2+]pm remained unchanged. If mitochondria moved apart from the pipette or in the presence of carbonyl cyanide-4-trifluoromethoxyphenylhyrazone, [Ca2+]pm at L2 increased in response to histamine. Under standard patch conditions Ca2+ entry was negligible due to cell depolarization. Using a physiological patch approach (5.6 mm K+ in the bath), changes in [Ca2+]pm to histamine could be monitored without cell depolarization and, thus, in conditions where Ca2+ entry occurred. Here, histamine induced an initial transient Ca2+ elevation to ≥3.5 μm followed by a long lasting plateau at ∼1.2 μm in L1 and L3, whereas mitochondria kept neighboring [Ca2+]pm low during stimulation. Thus, superficial mitochondria and ER generate local domains of low and high Ca2+ allowing simultaneous activation of BKCaand CCE, despite their opposite Ca2+sensitivity.
Rapid loss of efficacy to the antiseizure drugs lamotrigine and carbamazepine: A novel experimental model of pharmacoresistant epilepsy

Kindling is a well‐established model of secondarily generalized partial seizures that is widely employed in the search for novel antiseizure drugs. During the kindling and postkindling acquisition phase, an active process of neuronal remodeling occurs. We tested the hypothesis that exposure to the voltage‐gated sodium channel blockers lamotrigine (LTG) and carbamazepine (CBZ) during the period of active remodeling will lead to a diminished therapeutic effect.
Does CTCF mediate between nuclear organization and gene expression?

The multifunctional zinc‐finger protein CCCTC‐binding factor (CTCF) is a very strong candidate for the role of coordinating the expression level of coding sequences with their three‐dimensional position in the nucleus, apparently responding to a “code” in the DNA itself. Dynamic interactions between chromatin fibers in the context of nuclear architecture have been implicated in various aspects of genome functions. However, the molecular basis of these interactions still remains elusive and is a subject of intense debate. Here we discuss the nature of CTCF‐DNA interactions, the CTCF‐binding specificity to its binding sites and the relationship between CTCF and chromatin, and we examine data linking CTCF with gene regulation in the three‐dimensional nuclear space. We discuss why these features render CTCF a very strong candidate for the role and propose a unifying model, the “CTCF code,” explaining the mechanistic basis of how the information encrypted in DNA may be interpreted by CTCF into diverse nuclear functions.
Notch controls proliferation and differentiation of stem cells in a dose‐dependent manner

Self‐renewal and differentiation of CNS stem cells are regulated by still poorly understood cell–cell interactions. Notch is a well‐known cell surface protein that can promote both cell cycle progression and mitotic arrest but the molecular mechanism controlling these opposite effects is unknown. Here we demonstrate that, in CNS stem cells, the level of active Notch1 determines the cellular response. Specifically, low levels of the active form of Notch1 promote proliferation whereas high levels lead to growth arrest. Here we provide the first evidence that Notch effects on proliferation and differentiation are a function of dose, and propose a hypothesis on how oncogenes may also act as tumor suppressors.
Predictors of Institutionalisation in Incident Dementia – Results of the German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe Study)

Background/Aims: In the past few decades, a number of studies investigated risk factors of nursing home placement (NHP) in dementia patients. The aim of the study was to investigate risk factors of NHP in incident dementia cases, considering characteristics at the time of the dementia diagnosis. Methods: 254 incident dementia cases from a German general practice sample aged 75 years and older which were assessed every 1.5 years over 4 waves were included. A Cox proportional hazard regression model was used to determine predictors of NHP. Kaplan-Meier survival curves were used to evaluate the time until NHP. Results: Of the 254 incident dementia cases, 77 (30%) were institutionalised over the study course. The mean time until NHP was 4.1 years. Significant characteristics of NHP at the time of the dementia diagnosis were marital status (being single or widowed), higher severity of cognitive impairment and mobility impairment. Conclusion: Marital status seems to play adecisive role in NHP. Early initiation of support of sufferers may ensure remaining in the familiar surroundings as long as possible.
A multi‐ingredient dietary supplement abolishes large‐scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice

Transgenic growth hormone mice (TGM) are a recognized model of accelerated aging with characteristics including chronic oxidative stress, reduced longevity, mitochondrial dysfunction, insulin resistance, muscle wasting, and elevated inflammatory processes. Growth hormone/IGF‐1 activate the Target of Rapamycin known to promote aging. TGM particularly express severe cognitive decline. We previously reported that a multi‐ingredient dietary supplement (MDS) designed to offset five mechanisms associated with aging extended longevity, ameliorated cognitive deterioration and significantly reduced age‐related physical deterioration in both normal mice and TGM. Here we report that TGM lose more than 50% of cells in midbrain regions, including the cerebellum and olfactory bulb. This is comparable to severe Alzheimer's disease and likely explains their striking age‐related cognitive impairment. We also demonstrate that the MDS completely abrogates this severe brain cell loss, reverses cognitive decline and augments sensory and motor function in aged mice. Additionally, histological examination of retinal structure revealed markers consistent with higher numbers of photoreceptor cells in aging and supplemented mice. We know of no other treatment with such efficacy, highlighting the potential for prevention or amelioration of human neuropathologies that are similarly associated with oxidative stress, inflammation and cellular dysfunction. Environ. Mol. Mutagen. 57:382–404, 2016. © 2016 Wiley Periodicals, Inc.
Caudate and Hippocampal Volumes, Intelligence, and Motor Impairment in 7-Year-Old Children Who Were Born Preterm

Children who survive very preterm birth without major disability have a high prevalence of learning difficulty, attention deficit, and minor motor impairment (MMI). To determine whether these difficulties are associated with structural brain abnormalities, we studied 105 preterm children (<32 wk) at 7 y with tests of IQ and MMI (Movement ABC) and detailed magnetic resonance brain scans. Scans were assessed qualitatively for visible cerebral lesions. Volume measurements of the caudate nuclei and hippocampal formations were made. Total brain volume (TBV) was estimated from the head circumference. Qualitative assessment of the scans showed evidence of cerebral lesions in 20 (19%), which were associated with lower IQ and more frequent MMI. IQ correlated with right and left caudate volume (Spearman's ρ 0.304 and 0.349; p < 0.01). This association persisted (except for verbal IQ) when caudate volume was expressed as a percentage of estimated TBV to allow for overall brain size. No significant correlations with hippocampal volumes were observed. These differences persisted when only scans from children without visible lesions on scan were considered. MMI was significantly associated only with TBV and was more common in children with evidence of thinning of the posterior corpus callosum, although most children with MMI have a normal corpus callosum. Lower IQs in children who were born preterm are related to poorer development of the caudate relative to the rest of the brain, independent of other lesions. These findings suggest abnormal brain development after perinatal injury or postnatal nutritional deficits is responsible for cognitive deficits in preterm children.
Is combination rituximab with cyclophosphamide better than rituximab alone in the treatment of lupus nephritis?

OBJECTIVE To assess if combination rituximab and cyclophosphamide is more effective than rituximab monotherapy as an induction therapy for proliferative lupus nephritis. METHODS A randomized open-label pilot study in which 9 patients received rituximab alone and 10 patients received two doses rituximab + intravenous cyclophosphamide. The clinical, laboratory and renal histological changes were assessed after 48 weeks of treatment. RESULTS At week 48, four patients had a complete response, 11 patients achieved partial response, 2 patients remained the same or stable and 2 worsened. There were no statistical differences in the proportion of patients with complete or partial response between the two groups. None of the variables was an independent predictor of response at week 48. Nine patients had significant improvement in activity indices in renal biopsies, but there were no significant differences between the two groups. Overall, 18 out of 19 patients were found to have effective B-cell depletion. The median duration of complete B-cell depletion in all patients was 22 weeks. There were no statistically significant differences in the proportion of patients with complete depletion at weeks 4, 8, 24 and 48 between the two groups except at week 2. CONCLUSIONS Rituximab monotherapy appears to be effective as induction therapy in lupus nephritis. The addition of cyclophosphamide offers no additional improvement in clinical, laboratory and renal histological assessment or the duration of B-cell depletion at 48 weeks. Large-scale studies with longer duration are needed to confirm these findings.
Targeting fatty acid metabolism to improve glucose metabolism

Disturbances in fatty acid metabolism in adipose tissue, liver, skeletal muscle, gut and pancreas play an important role in the development of insulin resistance, impaired glucose metabolism and type 2 diabetes mellitus. Alterations in diet composition may contribute to prevent and/or reverse these disturbances through modulation of fatty acid metabolism.
Adhesion of Listeria monocytogenes to silica surfaces after sequential and competitive adsorption of bovine serum albumin and beta-lactoglobulin

Adsorbed bovine serum albumin was resistant to exchange with beta-lactoglobulin, and when albumin was adsorbed from a mixture, its surface concentration increased with time. The passivating character of adsorbed albumin and its resistance to desorption were consistent with the level of Listeria monocytogenes adhesion evoked by albumin-containing protein films.
Fluoroscopically guided balloon dilation of anastomotic strictures after total gastrectomy: long-term results.

OBJECTIVE The purpose of this study was to evaluate the radiologic and clinical effectiveness and long-term results of fluoroscopically guided balloon dilation of anastomotic strictures after total gastrectomy. CONCLUSION Fluoroscopically guided balloon dilation is effective and safe and has encouraging long-term results in the management of benign anastomotic strictures after total gastrectomy.
Induction of CD14 Expression and Differentiation to Monocytes or Mature Macrophages in Promyelocytic Cell Lines: New Approach.

PURPOSE CD14, one of the main differentiation markers on the surface of myeloid lineage cells, acts as a key role in activation of LPS-induced monocytes. LPS (lipopolysaccharide) binds to LPS-binding protein in plasma and are delivered to the cell surface receptor CD14. In this study, Various stimuli [Dimethyl Sulfoxide (DMSO), active 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and LPS], either alone or in combination, have been recognized that have an effect on the level of CD14 expression in the human HL-60 and U937 promonocytic cell lines and therefore induce their terminal differentiation into monocytes or mature macrophages. METHODS U937 and HL-60 cells were cultured in RPMI 1640 supplemented with 10% FBS. For each cell line, 1Ã106 cells were seeded for 72 hours with DMSO, 14 days with LPS and 18 days with 1, 25-D3 in each well plate; then ELISA method was used to study their responses to the factors by means of anti-CD14. RESULTS ELISA assay demonstrated that U937 and HL-60 cells were induced by both [1,25(OH)2D3] and DMSO to obtain characteristics of adherent cells and express CD14 protein; moreover, LPS at a low dose increased CD14 expression on surface of this cells. CONCLUSION According to the our results, it is speculated that CD14 gene expression may be induced in human U937 and HL-60 cell lines by different factors including 1,25-D3, DMSO and LPS.
Towards Speech Emotion Recognition "in the Wild" Using Aggregated Corpora and Deep Multi-Task Learning

One of the challenges in Speech Emotion Recognition (SER) "in the wild" is the large mismatch between training and test data (e.g. speakers and tasks). In order to improve the generalisation capabilities of the emotion models, we propose to use Multi-Task Learning (MTL) and use gender and naturalness as auxiliary tasks in deep neural networks. This method was evaluated in within-corpus and various cross-corpus classification experiments that simulate conditions "in the wild". In comparison to Single-Task Learning (STL) based state of the art methods, we found that our MTL method proposed improved performance significantly. Particularly, models using both gender and naturalness achieved more gains than those using either gender or naturalness separately. This benefit was also found in the high-level representations of the feature space, obtained from our method proposed, where discriminative emotional clusters could be observed.
Refresh-Aware Write Recovery Memory Controller

Current computer systems require large memory capacities to manage the tremendous volume of datasets. A DRAM cell consists of a transistor and a capacitor, and their size has a direct impact on DRAM density. While technology scaling can provide higher density, this benefit comes at the expense of low drivability, due to the increase in series resistance of the smaller transistor, which slows the process of restoring the charge in cells. DRAM operations require recovery processes due to the destructive nature of DRAM cells. Among such operations, the write recovery process has the most difficulty in meeting the timing constraints. In this paper, we explore an intrinsic mechanism in the DRAM write operation, and find a relation between restoration and retention times. Based on our observation, we propose a practical mechanism, Relaxed Refresh with Compensated Write Recovery (RRCW), which efficiently mitigates refresh overheads by providing longer restoration periods. Furthermore, to minimize the penalty of the longer restoration, we also introduce another mechanism, Refresh-Aware Write Recovery (RAWR), which appropriately curtails longer recovery time according to the waiting time until being refreshed. Lastly, we introduce a scheduling policy to efficiently utilize RAWR. Evaluations show that the benefits of our mechanisms increase as memory intensity increases.
The external networking behaviour of public managers - the missing link of weak ties

ABSTRACT There has been an increasing focus on managerial external networking behaviour within public administration. While most previous quantitative research has analysed such behaviour one dimensionally, we suggest a two-dimensional conceptualization based on the concepts of weak and strong ties. Utilizing measures resembling previous research, we explore the utility of the approach in an exploratory study of Danish local government. Our findings suggest that the two dimensions of external networking behaviour are distinct. We discuss our approach compared to previous approaches and argue that a conceptualization based on the distinction between strong and weak ties provides a promising framework for future research.
Pengaruh Risiko Litigasi dan Tingkat Kesulitan Keuangan Perusahaan terhadap Hubungan antara Konflik Kepentingan dan Konservatisme Akuntansi

The aim of this research is to examine the effect of interest conflict on accounting conservatism and the effect of litigation risk on the positive relation between conflict of interest and accounting conservatism, and the effect of company’s financial distress on the positive relation between conflict of interest and accounting conservatism.The sample of this research was extracted with purposive sampling method. The populations of this research are all of the manufacturing company, which are listed at Indonesian Capital Market Directory (ICMD). The 125 corporate financial statements were analyzed as a sample. The technique for examining hypothesis is simple regression analysis to examining the first hypothesis and Moderated Regression Analysis (MRA) to examining the second dan the third hypothesis by using SPSS 17.00 program.The results of the research show that: firstly, conflict of interest has a signification positive effect on accounting conservatism. Secondly, litigation risk has a significant positive effect on the positive relation between conflict of interest and accounting conservatism. And the third, company’s financial distress have a significant positive effect on the positive relation between conflict of interest and accounting conservatism.
Signaling Pathways for Early Brain Injury after Subarachnoid Hemorrhage

Few studies have examined the signaling pathways that contribute to early brain injury after subarachnoid hemorrhage (SAH). Using a rat SAH model, the authors explored the role of vascular endothelial growth factor (VEGF) and mitogen-activation protein kinase (MAPK) in early brain injury. Male Sprague-Dawley rats (n = 172) weighing 300 to 350 g were used for the experimental SAH model, which was induced by puncturing the bifurcation of the left anterior cerebral and middle cerebral arteries. The blood–brain barrier (BBB), brain edema, intracranial pressure, and mortality were evaluated at 24 hours after SAH. The phosphorylation of VEGF and different MAPK subgroups (ERK1/2, p38, and JNK) were examined in both the cortex and the major cerebral arteries. Experimental SAH increased intracranial pressure, BBB permeability, and brain edema and produced high mortality. SAH induced phosphorylation of VEGF and MAPKs in the cerebral arteries and, to a lesser degree, in the cortex. PP1, an Src-family kinase inhibitor, reduced BBB permeability, brain edema, and mortality and decreased the phosphorylation of VEGF and MAPKs. The authors conclude that VEGF contributes to early brain injury after SAH by enhancing the activation of the MAPK pathways, and that the inhibition of these pathways might offer new treatment strategies for SAH.
Drug-Using Male Clients of Female Sex Workers Who Report Being Paid for Sex: HIV/Sexually Transmitted Infection, Demographic, and Drug Use Correlates

Background Research has focused on male clients of female sex workers (FSWs) and their risk for HIV/sexually transmitted infections (STIs). However, it is unclear whether the commercial sex behaviors of these men are limited to paying for sex or whether they may also be paid for sex themselves. Methods We analyzed the interview data and HIV/STI test results from 170 drug-using male clients of FSWs in Tijuana, Mexico, to determine the extent to which these men report being paid for sex and the association with positive HIV/STI results. Results More than one quarter of men reported having been paid for sex in the past 4 months. In a multivariate logistic regression model, reporting having been paid for sex was significantly associated with testing positive for any HIV/STI (adjusted odds ratio [AdjOR], 3.53; 95% confidence interval [CI], 1.33–9.35), being bisexual (AdjOR, 15.59; 95% CI, 4.81–50.53), injection drug use in the past 4 months (AdjOR, 2.65; 95% CI, 1.16–6.03), and cocaine use in the past 4 months (AdjOR, 2.93; 95% CI, 1.22–7.01). Conclusions Findings suggest that drug-using male clients of FSWs may be characterized by unique risk profiles that require tailored HIV prevention interventions.
Characterisation and in vitro antimicrobial activity of biosynthetic silver-loaded bacterial cellulose hydrogels

Abstract Wounds that remain in the inflammatory phase for a prolonged period of time are likely to be colonised and infected by a range of commensal and pathogenic microorganisms. Treatment associated with these types of wounds mainly focuses on controlling infection and providing an optimum environment capable of facilitating re-epithelialisation, thus promoting wound healing. Hydrogels have attracted vast interest as moist wound-responsive dressing materials. In the current study, biosynthetic bacterial cellulose hydrogels synthesised by Gluconacetobacter xylinus and subsequently loaded with silver were characterised and investigated for their antimicrobial activity against two representative wound infecting pathogens, namely S. aureus and P. aeruginosa. Silver nitrate and silver zeolite provided the source of silver and loading parameters were optimised based on experimental findings. The results indicate that both AgNO3 and AgZ loaded biosynthetic hydrogels possess antimicrobial activity (p < .05) against both S. aureus and P. aeruginosa and may therefore be suitable for wound management applications.
Breast cancer underestimation rate of atypical ductal hyperplasia diagnosed by core-needle biopsy under imaging guidance.

OBJECTIVE To evaluate breast cancer underestimation rate of atypical ductal hyperplasia (ADH) diagnosed by core-needle biopsy (CNB) under imaging guidance in Ramathibodi Hospital and to determine the difference between the malignant and benign groups in terms of clinical and imaging characteristics. MATERIAL AND METHOD The pathological records of 1521 patients who underwent CNB under imaging guidance were reviewed. Thirty-nine patients diagnosed with ADH were enrolled into the present study. Clinical data, imaging features, biopsy technique and result of excisional biopsy as well as follow-up data were retrospectively reviewed. RESULTS Of 39 ADH cases, eight (20.5%) were found to have malignancy on subsequent excisional biopsy. The majority of these were ductal carcinoma in situ (DCIS) (62.5%). Lesion categorized as category 5 according to BI-RADS (Breast imaging reporting and data system) was the only feature which was statistically different between the benign and malignant groups. No statistically significant difference was found between the benign and malignant groups in terms of age, personal and family history of breast cancer, clinical finding, mammographic lesion type, size of lesion, image-guided technique and percentage of lesion removal. CONCLUSION The underestimation rate of ADH in the present study was comparable to other studies. The finding of Bl-RADS category 5 in patients with ADH diagnosed from CNB is a strong indication for subsequent excisional biopsy.