Miracle-dz/UniFAR-FTUs huggingface dataset:
Cholangiocyte proliferation and liver fibrosis

Cholangiocyte proliferation is triggered during extrahepatic bile duct obstruction induced by bile duct ligation, which is a common in vivo model used for the study of cholangiocyte proliferation and liver fibrosis. The proliferative response of cholangiocytes during cholestasis is regulated by the complex interaction of several factors, including gastrointestinal hormones, neuroendocrine hormones and autocrine or paracrine signalling mechanisms. Activation of biliary proliferation (ductular reaction) is thought to have a key role in the initiation and progression of liver fibrosis. The first part of this review provides an overview of the primary functions of cholangiocytes in terms of secretin-stimulated bicarbonate secretion – a functional index of cholangiocyte growth. In the second section, we explore the important regulators, both inhibitory and stimulatory, that regulate the cholangiocyte proliferative response during cholestasis. We discuss the role of proliferating cholangiocytes in the induction of fibrosis either directly via epithelial mesenchymal transition or indirectly via the activation of other liver cell types. The possibility of targeting cholangiocyte proliferation as potential therapy for reducing and/or preventing liver fibrosis, and future avenues for research into how cholangiocytes participate in the process of liver fibrogenesis are described.
Globalization, Spending and Income Inequality in Asia Pacific

ABSTRACT This paper provides an overview of the patterns of government spending and income distribution in the Asia-Pacific region under globalization. Previous studies have not placed much emphasis on the underlying policy mechanisms. Not only does this article take the change in public spending into account, it also allows for different factors and distributive outcomes to be associated with distinct types of spending (education, welfare and health). Health-related spending is found to reduce income inequality, while the reverse is true for welfare expenses. The results also suggest that globalization strongly exacerbates income inequality even after controlling for economic, demographic and political factors. The results carry significant implications for governments in the Asia-Pacific region.
Properties of the phosphorylation reaction catalyzed by SpoIIAB that help to regulate sporulation of Bacillus subtilis

Phosphorylation of SpoIIAA on Ser-58 catalyzed by SpoIIAB is important in the regulation of sporulation of Bacillus subtilis. Nucleotide binding experiments showed that the affinity of SpoIIAB for ATP was greatly increased in the presence of SpoIIAA or a mutant SpoIIAA in which Ser-58 had been changed to alanine. Study of the phosphorylation reaction showed that the Km for ATP and the Ki for ADP were both about 1 microM. The kinetics of phosphorylation of SpoIIAA by SpoIIAB were biphasic, comprising a rapid phase (leading to phosphorylation of 1 mol of SpoIIAA/mol of SpoIIAB) followed by a slower, steady-state phase. In the steady state, the rate-determining step proved to be the dissociation of a SpoIIAB-ADP complex. The rate of this dissociation was not affected significantly by changes in the concentration of ATP.
Cardiovascular , Pulmonary , and Renal Pathology Renal Accumulation of Biglycan and Lipid Retention Accelerates Diabetic Nephropathy

Hyperlipidemia worsens diabetic nephropathy, although the mechanism by which renal lipids accumulate is unknown. We previously demonstrated that renal proteoglycans have high low-density lipoprotein (LDL) binding affinity, suggesting that proteoglycan-mediated LDL retention may contribute to renal lipid accumulation. The aim of this study was to determine the relative effect of diabetes and hyperlipidemia on renal proteoglycan content. Diabetic and non-diabetic LDL receptor–deficient mice were fed diets containing 0% or 0.12% cholesterol for 26 weeks, and then kidneys were analyzed for renal lipid and proteoglycan content. Diabetic mice on the high-cholesterol diet had accelerated development of diabetic nephropathy with elevations in urine albumin excretion, glomerular and renal hypertrophy, and mesangial matrix expansion. Renal lipid accumulation was significantly increased by consumption of the 0.12% cholesterol diet, diabetes, and especially by both. The renal proteoglycans biglycan and decorin were detectable in glomeruli, with a significant increase in renal biglycan content in diabetic mice on the high-cholesterol diet. Renal biglycan and renal apolipoprotein B were colocalized, and regression analyses showed a significant relation between renal biglycan and renal apolipoprotein B content. The increased renal biglycan content in diabetic nephropathy probably contributes to renal lipid accumulation and the development of diabetic nephropathy. (Am J Pathol 2011, 179:1179–1187; DOI: 10.1016/j.ajpath.2011.05.016)
Comparison of Speech Intelligibility Parameter in Cochlear Implants by Spatial Filtering and Coherence Function Methods

This paper evaluates the speech intelligibility parameter of electrical hearing with a Cochlear implant where a multi-electrode array implanted in the cochlea transfers the electrical impulses to the brain. Compared to normal listeners, a CI user requires higher signal to noise ratio for similar speech recognition. Generalized side-lobe cancellers using directional microphones have shown good results when there is a single noise source. But the performance deteriorates as the number of noise sources increase. This paper reviews two techniques one based on spatial filtering and the other based on coherence function and discusses the possibility of combining them for better speech intelligibility as both the methods complement each other. In both the algorithms, estimation of noise is not required and they have the capability of handling multiple sources and speakers. Better intelligibility results were obtained by the researchers using these techniques.
Evaluation of collagen crosslinking techniques.

The properties of collagen films crosslinked by physical and chemical techniques were compared to the properties of films crosslinked with glutaraldehyde (GTA). Physical techniques studied include exposure to short wave (254 nm) u.v. irradiation and severe dehydration. Chemical techniques studied include immersion of collagen films in aqueous solutions of cyanamide or GTA. Collagen films exposed to combinations of aqueous solutions of cyanamide and severe dehydration had moduli of elasticity, swelling ratios and resistance to bacterial collagenase similar to films crosslinked with GTA. Theoretical calculations based on amino acid composition indicate that approximately seven times as many amino acid residues are capable of forming crosslinks using cyanamide or severe dehydration procedures as compared to GTA crosslinking. In addition, using severe dehydration or cyanamide forms crosslinks involving both amino and carboxyl residues which may allow these procedures to act synergistically. Based on our studies this two-step procedure effectively crosslinks collagen-based biomaterials while the only by-product of this reaction is water-soluble urea. Preliminary biocompatibility studies suggest that this crosslinking procedure may allow for pronounced tissue ingrowth.
Effect of 8-hydroxyquinoline and derivatives on human neuroblastoma SH-SY5Y cells under high glucose

8-Hydroxyquinoline and derivatives exhibit multifunctional properties, including antioxidant, antineurodegenerative, anticancer, anti-inflammatory and antidiabetic activities. In biological systems, elevation of intracellular calcium can cause calpain activation, leading to cell death. Here, the effect of 8-hydroxyquinoline and derivatives (5-chloro-7-iodo-8-hydroxyquinoline or clioquinol and 8-hydroxy-5-nitroquinoline or nitroxoline) on calpain-dependent (calpain-calpastatin) pathways in human neuroblastoma (SH-SY5Y) cells was investigated. 8-Hydroxyquinoline and derivatives ameliorated high glucose toxicity in SH-SY5Y cells. The investigated compounds, particularly clioquinol, attenuated the increased expression of calpain, even under high-glucose conditions. 8-Hydroxyquinoline and derivatives thus adversely affected the promotion of neuronal cell death by high glucose via the calpain-calpastatin signaling pathways. These findings support the beneficial effects of 8-hydroxyquinolines for further therapeutic development.
Prolonged Antagonism of Opioid Action with Intravenous Nalmefene in Man

To identify the opioid antagonist activity of nalmefene and to determine its duration in man, six healthy male subjects were pretreated on separate days with a saline placebo, 0.5 mg, 1 mg, or 2 mg nalmefene intravenously in a randomized double-blind fashion. Opioid challenges with fentanyl, 2 μg/kg, then were administered 1,2,4,6, and 8 h afterward. Respiratory depression was monitored by ventilatory and occlusion pressure responses during CO2 re-breathing, while analgesia to experimental pain was identified with the submaximal effort tourniquet ischemia test. One hour following placebo pretreatment, the initial fentanyl dose produced marked respiratory depression. Minute ventilation and occlusion pressure at a PCO2 60 mmHg during rebreathing (VE60 and P0.160) were reduced to 29 and 41% of control, respectively. The slopes of the ventilatory and occlusion pressure responses also decreased significantly to 51 and 55% of control. Respiratory effects were similar with all subsequent fentanyl doses. Pretreatment with 2 mg nalmefene completely prevented the subjective and respiratory effects of fentanyl for the entire 8 h of the experiment. Nalmefene, 1 mg, significantly blunted the fentanyl effects for the same period, but VE60 values at 6 and 8 h were depressed significantly (P < 0.05) to 66 and 61% of control. The antagonist effects of the lowest nalmefene dose, 0.5 mg, persisted for about 4 h, at which time V E60 was 64% of control. Fentanyl administration produced consistent increases in pain tolerance (44–55% above control) throughout the experiment. Nalmefene pretreatment abolished this analgesic response in a dose-related time course that mirrored the respiratory effects almost exactly. These findings demonstrate that nalmefene is an effective opioid antagonist with a duration of action far in excess of naloxone and more clearly related to dose.
The Role of Pilot Studies in the Economic Evaluation of Health Technologies

Abstract An increasing number of economic evaluations are being conducted alongside clinical trials. While this practice offers the prospect of collecting comprehensive and accurate cost data, it requires considerable time and effort. In the case of clinical data, key analytic decisions such as which data to collect and sample size are often made with reference to smaller (pilot) trials. However, this approach is not normally followed in the case of economic evaluation. This study was based on a recently completed health technology assessment comparing conventional radiotherapy with continuous hyperfractionated accelerated radiotherapy (CHART) for patients with head and neck cancer or carcinoma of the bronchus. In the full health technology assessment, cost data were available for 526 head and neck patients (314 CHART and 212 conventional therapy) and 286 bronchus patients (175 CHART and 109 conventional therapy). In order to simulate a pilot study, data were extracted for the patients recruited to both trials in the first 3 months. These were then compared with the full data set in order to assess whether such a pilot study would have given useful guidance on: a) the usefulness of undertaking a full study; b) the sample size required; and c) the important resource items for which comprehensive data collection would be required. Pilot studies can be helpful in determining the likely advantages of undertaking full economic evaluations and in identifying important resource items. Therefore, it is important that clinical researchers and research funding bodies create the necessary time window to enable such studies to take place. However, formal sample size calculations are more difficult to perform on limited data, since they also require knowledge of the unit cost (or prices) to be attached to the resource items and the correlation between costs and clinical effects.
A review of the health problems of the internally displaced persons in Africa

Globally, over 40 million people were displaced as a result of wars and violence due to religious and ethnic conflicts in 2015 while 19.2 million were displaced by natural disasters such as famine and floods. In Africa, 12 million people were displaced by armed conflict and violence and there were hundreds of thousands of people displaced by natural disasters. Despite these large numbers of internally displaced persons (IDPs) in Sub-Saharan African countries and the potentially negative impact of displacement on the health of these populations, there is limited information on the health problems of IDPs in the region. The previous studies have mainly focused on the health problems of refugees and single disease entities among IDPs. However, a more comprehensive picture is required to inform the provision of adequate healthcare services for this vulnerable population. The objective of this review was to fill this knowledge gap. Bibliographic databases were searched and screened, and nine studies were selected and reviewed. The major physical health problems and symptoms were fever/malaria (85% in children and 48% in adults), malnutrition in children (stunting 52% and wasting 6%), malnutrition in adult males (24%), diarrhoea (62% in children and 22% in adults) and acute respiratory infections (45%). The prevalent mental health problems were post-traumatic stress disorder (range: 42%-54%) and depression (31%-67%). Most of the studies reviewed focused on mental health problems. Limited evidence suggests that IDPs experience various health problems but more research is required to inform the provision of adequate and comprehensive healthcare services for this group of individuals.
On the Association between Current Period Budget Target Achievability and the Properties of Nonfinancial Measures

ABSTRACT: Firms usually employ nonfinancial performance metrics (NFPMs) to measure progress toward long-term outcomes. They also often evaluate current performance by comparing outcomes on financial measures with budgeted targets. Thus, they can motivate actions that sacrifice current profit for favorable future outcomes directly by increasing the rewards for such actions and indirectly by reducing their opportunity cost. Combining these arguments, we examine the relation between the properties (congruity and measurability) of NFPMs used in incentive contracting and the achievability of the current period budget target, where achievability is the probability of obtaining the incentive payment tied to current period performance. Survey data from 179 divisions in Chinese firms support our prediction of a positive (negative) association between the congruity (measurability) of NFPMs and budget achievability. We also document an expected positive interaction effect between congruity and measurability.
The Future of Work in the ‘Sharing Economy’. Market Efficiency and Equitable Opportunities or Unfair Precarisation?

This critical and scoping review essay analyses digital labour markets where labour-intensive services are traded by matching requesters (employers and/or consumers) and providers (workers). It focuses on digital labour markets which allow the remote delivery of electronically transmittable services (i.e. Amazon Mechanical Turk, Upwork, Freelancers, etc.) and those where the matching and administration processes are digital but the delivery of the services is physical and requires direct interaction. The former broad type is called Online Labour Markets (OLMs) and is potentially global. The latter broad type is termed Mobile Labour Markets (MLMs) and is by definition localised. The essay defines and conceptualises these markets proposing a typology which proves to be empirically valid and heuristically useful. It describes their functioning and the socio-demographic profiles of the participants, reviews their economic and social effects, discusses the possible policy implications, and concludes with a research agenda to support European level policy making. It alternates the discussion of â€˜hardâ€™ findings from experimental and quasi-experimental studies with analysis of â€˜softerâ€™ issues such as rhetorical discourses and media â€˜hypedâ€™ accounts. This triangulation is inspired by, and a tribute to, the enduring legacy of the work of Albert O. Hirschman and his view that ideas and rhetoric can become endogenous engines of social change, reforms, and policies. This essay tries to disentangle the rhetoric with available empirical evidence in order to enable a more rational debate at least in the discussion of policies, if not in the public arena. To do so, an in depth analysis of 39 platforms was undertaken together with a formal review of 70 scientific sources. These two main sources have been integrated with: a) an exploration of 100 media accounts (business press, newspapers, magazines, and blogs); b) 50 reports and surveys produced by â€˜interested partiesâ€™ (industrial associations, platforms own reports and public relation materials, think tanks with a clear political orientation, NGOs, trade unions, etc.); and c) about 200 indirectly relevant scientific contributions and policy reports (used as sources to contextualise and integrate the above sources, and to derive theoretical and interpretative insights). While the evidence is limited and inconclusive with respect to various dimensions, the findings of this essay show, among other things, that: a) individuals engage in these activities primarily for money, for a large segment of them this work is their primary source of income, and most are under-employed and self-employed and fewer are unemployed and inactive; b) matching frictions and hiring inefficiencies are widespread and even the OLMs are far from being globalised online meritocracies; c) a behavioural approach to big data exploration should be further applied because there is emerging evidence of heuristic and biases contributing to hiring inefficiencies.
A 56.4-to-63.4GHz spurious-free all-digital fractional-N PLL in 65nm CMOS

Frequency synthesis at mm-Waves is still dominated by analog PLLs, although all-digital PLLs (ADPLLs) [1] have been widely explored below 10GHz. The major obstacle has been the poor quality of digitally controlled oscillators (DCO) as MOS varactor Q-factor drops to <;10 at 60GHz. A mm-Wave digital transmitter (TX) based on a 60GHz fractional-N ADPLL with two-point FM is proposed here. The TX features extensive reconfigurability and permits the highest degree of integration of RF and baseband circuitry for low-cost, high-volume applications. To simplify the TX architecture, the synthesizer is capable of FM, hence a time-to-digital converter (TDC) is preferred over bang-bang phase detection. With the aid of autonomous calibrations of DCO and TDC gain, wideband two-point FM is achieved.
Evaluation of the Pathogenesis of Tumor Development from Endometriosis by Estrogen Receptor, P53 and Bcl-2 Immunohistochemical Staining

Objective: Endometriosis, one of the most common estrogen dependent gynecological disorders, can present as both benign and malignant disease. The prevalence of tumoral transformation is 0.7-1.6% and the most common tumors are clear cell and endometrioid carcinomas. Unfortunately, the pathogenesis of transformation is unknown. For this purpose, we examined molecular alterations in ovarian endometriosis and endometriosis-associated tumors. Methods: Using the data bank of Alzahra hospital pathology department and paraffin blocks from appropriate cases were identified. Sections were cut and stained for 3 markers: estrogen receptor, P53 and bcl2. Correlations between findings were investigated. Results: Nineteen cases of endometriosis-associated tumor and 19 cases of endometriosis were identified. Staining for bcl2 was documented in 14 of 19 (73.7%) of endometriosis-associated tumor cases and also 7 of 19 (36.8%) endometriosis cases (P=0.02). Only 3 of the 19 (15.8%) endometriosis-associated tumors exhibited positive staining for estrogen receptors, compared with 14 of 19 (73.7%) endometriosis cases (P<0.001). Positive staining for P53 was noted in 5 of 19 (31.6%) endometriosis-associated ovarian tumor samples but was absent in endometriosis samples (0%), (P =0.008). Conclusions: Endometriosis-associated tumors appear to be associated with overexpression of bcl2 and P53 and reduced expression of Estrogen receptor. These finding may help to diagnose tumoral transformation with a background of endometriosis.
Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance

BACKGROUND. Dietary intake of saturated fat is a likely contributor to nonalcoholic fatty liver disease (NAFLD) and insulin resistance, but the mechanisms that initiate these abnormalities in humans remain unclear. We examined the effects of a single oral saturated fat load on insulin sensitivity, hepatic glucose metabolism, and lipid metabolism in humans. Similarly, initiating mechanisms were examined after an equivalent challenge in mice. METHODS. Fourteen lean, healthy individuals randomly received either palm oil (PO) or vehicle (VCL). Hepatic metabolism was analyzed using in vivo 13C/31P/1H and ex vivo 2H magnetic resonance spectroscopy before and during hyperinsulinemic-euglycemic clamps with isotope dilution. Mice underwent identical clamp procedures and hepatic transcriptome analyses. RESULTS. PO administration decreased whole-body, hepatic, and adipose tissue insulin sensitivity by 25%, 15%, and 34%, respectively. Hepatic triglyceride and ATP content rose by 35% and 16%, respectively. Hepatic gluconeogenesis increased by 70%, and net glycogenolysis declined by 20%. Mouse transcriptomics revealed that PO differentially regulates predicted upstream regulators and pathways, including LPS, members of the TLR and PPAR families, NF-&kgr;B, and TNF-related weak inducer of apoptosis (TWEAK). CONCLUSION. Saturated fat ingestion rapidly increases hepatic lipid storage, energy metabolism, and insulin resistance. This is accompanied by regulation of hepatic gene expression and signaling that may contribute to development of NAFLD. REGISTRATION. ClinicalTrials.gov NCT01736202. FUNDING. Germany: Ministry of Innovation, Science, and Research North Rhine–Westfalia, German Federal Ministry of Health, Federal Ministry of Education and Research, German Center for Diabetes Research, German Research Foundation, and German Diabetes Association. Portugal: Portuguese Foundation for Science and Technology, FEDER – European Regional Development Fund, Portuguese Foundation for Science and Technology, and Rede Nacional de Ressonância Magnética Nuclear.
Impact of Major RF Impairments on mm-Wave Communications Using OFDM Waveforms

In this paper, we study the joint impact of three major RF im-pairments, namely, oscillator phase noise, power amplifier non-linearity and I/Q imbalance on the performance of a mm-wave communication link based on OFDM modulation. General im-pairment models are first derived for describing the joint effects in each TX, each RX as well as a mm-wave communication link. Based on the obtained signal models and initial air interface de-sign from the mmMAGIC project, we numerically evaluate the impact of RF impairments on channel estimation in terms of channel-to-noise ratio (CNR) and also channel fluctuation due to common phase error (CPE) caused by phase noise within the channel coherence time. Then the impact on the link performance in terms of maximum sum rate is evaluated using extensive com-puter simulations. The simulation results show that the used air interface design is generally robust to the presence of RF impair-ments. With regard to the use of high order modulation alphabet and implementation of low-power and low-cost RF transceivers in mm-wave communication, special attention needs to be paid on phase noise where the inter-carrier-interference (ICI) can become a major limiting factor.