Miracle-dz/UniFAR-FTUs huggingface dataset:
Bile acids directly augment caudal related homeobox gene Cdx2 expression in oesophageal keratinocytes in Barrett’s epithelium

Background and aims: The mechanism of transformation to intestinal metaplasia in Barrett’s oesophagus has not been clarified. We investigated the effects of various bile acids on expression of the caudal related homeobox gene Cdx2 in cultured oesophageal squamous epithelial cells. In addition, morphological and histochemical changes in squamous cells to intestinal epithelial cells were studied in response to bile acid induced expression of Cdx2. Methods: A rat model of Barrett’s oesophagus was created by anastomosing the oesophagus and jejunum, and Cdx2 expression was investigated by immunohistochemistry. Also, the response of various bile acids on Cdx2 gene expression was studied in the human colon epithelial cell lines Caco-2 and HT-29, as well as in cultured rat oesophageal squamous epithelial cells using a Cdx2 promoter luciferase assay. In addition, primary cultured oesophageal squamous epithelial cells were transfected with Cdx2 expression vectors and their possible transformation to intestinal-type epithelial cells was investigated. Results: Oesophagojejunal anastomoses formed intestinal goblet cell metaplasia in rat oesophagus specimens and metaplastic epithelia strongly expressed Cdx2. When the effects of 11 types of bile acids on Cdx2 gene expression were examined, only cholic acid (CA) and dehydrocholic acid dose dependently increased Cdx2 promoter activity and Cdx2 protein production in Caco-2 and HT-29 cells, and cultured rat oesophageal keratinocytes. Results from mutation analysis of Cdx2 promoter suggested that two nuclear factor κB (NFκB) binding sites were responsible for the bile acid induced activation of the Cdx2 promoter. When bile acids were measured in oesophageal refluxate of rats with experimental Barrett’s oesophagus, the concentration of CA was found to be consistent with the experimental dose that augmented Cdx2 expression in vitro. Furthermore, transfection of the Cdx2 expression vector in cultured rat oesophageal keratinocytes induced production of intestinal-type mucin, MUC2, in cells that expressed Cdx2. Conclusions: We found that CA activates Cdx2 promoter via NFκB and stimulates production of Cdx2 protein in oesophageal keratinocytes with production of intestinal-type mucin. This may be one of the mechanisms of metaplasia in Barrett’s oesophagus.
Successful Aging at Work: The Active Role of Employees

Since workforces are aging, governments, organizations, and researchers are increasingly interested in the topic of successful aging at work. In this article, I viewed successful aging at work from a sustainability perspective, and argued that a continuous person–job fit between the changing person and changing work is required for employees to be able to maintain their health, motivation, and work ability, and thus age successfully at work. Since one important way to achieve current and future fit is by engaging in proactive behaviors, I aimed to extend and specify the proactive behaviors proposed in lifespan psychology literature (e.g., selection) with proactive behaviors proposed in organizational psychology literature (e.g., job change negotiation) to identify proactive behaviors for successful aging at work. For example, job crafting can help aging workers to adjust their job to changing goals and motives, improving current person–job fit, and proactive career planning can help aging workers to set new career goals, improving future person–job fit.
Entrainment to an Auditory Signal: Is Attention Involved?

Many natural auditory signals, including music and language, change periodically. The effect of such auditory rhythms on the brain is unclear however. One widely held view, dynamic attending theory, proposes that the attentional system entrains to the rhythm and increases attention at moments of rhythmic salience. In support, 2 experiments reported here show reduced response times to visual letter strings shown at auditory rhythm peaks, compared with rhythm troughs. However, we argue that an account invoking the entrainment of general attention should further predict rhythm entrainment to also influence memory for visual stimuli. In 2 pseudoword memory experiments we find evidence against this prediction. Whether a pseudoword is shown during an auditory rhythm peak or not is irrelevant for its later recognition memory in silence. Other attention manipulations, dividing attention and focusing attention, did result in a memory effect. This raises doubts about the suggested attentional nature of rhythm entrainment. We interpret our findings as support for auditory rhythm perception being based on auditory-motor entrainment, not general attention entrainment.
Source Retrieval for Web-Scale Text Reuse Detection

The first step of text reuse detection addresses the source retrieval problem: given a suspicious document, a set of candidate sources from which text might have been reused have to be retrieved by querying a search engine. Afterwards, in a second step, the retrieved candidates run through a text alignment with the suspicious document in order to identify reused passages. Obviously, any true source of text reuse that is not retrieved during the source retrieval step reduces the overall recall of a reuse detector. Hence, source retrieval is a recall-oriented task, a fact ignored even by experts: Only 3 of 20 teams participating in a respective task at PAN 2012-2016 managed to find more than half of the sources, the best one achieving a recall of only~0.59. We propose a new approach that reaches a recall of~0.89---a performance gain of~51%.
L2 experience and non-native vowel categorization of L1-Mandarin speakers

This study investigates the effect of L2-English experience on the perception of the English tense-lax high vowel contrast. Experienced L1-Mandarin, inexperienced L1-Mandarin and L1-English listeners identified and discriminated synthetic heed - hid and who’d - hood continua varying in five steps of F1, F2, and F3 variations and seven steps of duration variations. The results show a strong reliance on formant variations by L1-English listeners; reliance on duration variations by the inexperienced L1-Mandarin listeners, and a more dominant reliance on formant cues than on duration cues by the experienced L1-Mandarin listeners.
Effects of Candesartan on Cardiovascular Outcomes in Japanese Hypertensive Patients

In recent years, angiotensin receptor blockers (ARBs) have begun to represent a markedly larger percentage of the antihypertensive agents used in Japan. However, it remains uncertain whether ARBs are effective for protecting against hypertension-related organ damage in the general Japanese population. In the present report, we describe the results of a single blind, randomized, prospective study conducted in 1999–2002 and employing a total of 2,048 essential hypertensive subjects (sitting blood pressure 140–180/90–110 mmHg) aged 35–79 years. Subjects were randomly assigned to receive the ARB candesartan, 2 to 12 mg daily, or conventional antihypertensive drugs other than angiotensin converting enzyme inhibitors or ARBs. We used Cox regression analysis to compare the two regimens. The primary outcome was assessed by hospitalization due to stroke, myocardial infarction, and congestive heart failure. Blood pressure was reduced from 162.1/91.1 to 140.1/78.9 mmHg in the candesartan group and from 165.9/95.9 to 138.4/81.1 mmHg in the conventional therapy group. The main outcomes were as follows: there was a 39% reduction in hospitalization for stroke (5.8 vs. 9.4 cases: relative risk [RR]: 0.61; 95% confidence interval [CI]: 0.41–0.84; p<0.05) and a 57% reduction in hospitalization for myocardial infarction (RR: 0.44; CI: 0.21–0.84; p<0.05) with the candesartan-based treatment compared with the conventional treatment. In spite of a significant difference in the total incidence of both stroke and myocardial infarction, there was no significant reduction in the incidence of congestive heart failure (15% reduction: 4.3 vs. 5.0; RR: 0.85; CI: 0.57–1.26). Further analysis in stratifying the subjects with or without a past history of cardiovascular diseases including stroke and myocardial infarction revealed that candesartan reduced the incidence of stroke (61% reduction; RR: 0.39; CI: 0.15–0.43; p<0.01) and congestive heart failure (49% reduction; RR: 0.51; CI: 0.23–0.92; p<0.05) but not myocardial infarction (RR: 0.74; CI: 0.36–1.48; p=0.1) in hypertensive patients with a past history. However, conventional treatment was superior to candesartan-based treatment in reducing the incidence of stroke in the patients without a past history of cardiovascular diseases (66% reduction; RR: 0.34; CI: 0.16–0.69; p<0.05). This is the first demonstration that an ARB-based antihypertensive treatment was superior to the conventional treatment for reducing the risk of stroke and myocardial infarction in Japanese hypertensive patients, especially in the patients with a past history of cardiovascular diseases.
Reduced sTWEAK and Increased sCD163 Levels in HIV-Infected Patients: Modulation by Antiretroviral Treatment, HIV Replication and HCV Co-Infection

Background Patients infected with the human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily. Circulating levels of sTWEAK and sCD163 have been previously associated with cardiovascular disease, but no previous studies have fully analyzed their association with HIV. Objective The aim of this study was to analyze circulating levels of sTWEAK and sCD163 as well as other known markers of inflammation (hsCRP, IL-6 and sTNFRII) and endothelial dysfunction (sVCAM-1 and ADMA) in 26 patients with HIV before and after 48 weeks of antiretroviral treatment (ART) and 23 healthy subjects. Results Patients with HIV had reduced sTWEAK levels and increased sCD163, sVCAM-1, ADMA, hsCRP, IL-6 and sTNFRII plasma concentrations, as well as increased sCD163/sTWEAK ratio, compared with healthy subjects. Antiretroviral treatment significantly reduced the concentrations of sCD163, sVCAM-1, hsCRP and sTNFRII, although they remained elevated when compared with healthy subjects. Antiretroviral treatment had no effect on the concentrations of ADMA and sTWEAK, biomarkers associated with endothelial function. The use of protease inhibitors as part of antiretroviral therapy and the presence of HCV-HIV co-infection and/or active HIV replication attenuated the ART-mediated decrease in sCD163 plasma concentrations. Conclusion HIV-infected patients showed a proatherogenic profile characterized by increased inflammatory, immune-activation and endothelial-dysfunction biomarkers that partially improved after ART. HCV-HIV co-infection and/or active HIV replication enhanced immune activation despite ART.
Group Faultlines

Organizations have been searching for ways to harness the benefits of groups while simultaneously reducing process losses associated with groups. The focus on group composition and individual attribute alignment has led to an interest in the topic of faultlines. Faultlines are hypothetical dividing lines that split a group into two or more subgroups based on the alignment of one or more individual attributes and have been found to influence group processes, performance outcomes, and affective outcomes. Using 59 published articles, the authors summarize the current state of the faultlines literature with respect to the following themes: theoretical foundations, faultline measurement, empirical findings, and the contingent role of context. A quantitative aggregation of 34 published empirical articles is used to summarize identified relationships in the literature and shows that the faultlines construct explains variance above and beyond the effect of team diversity measures on group outcomes. The authors provide guidance for future research that should be of interest to scholars in the areas of diversity, teams, power, alliances, subgroups, social networks, intergroup behavior, conflict, learning, and decision making. Future research directions build off the extant findings, such as extending conceptualizations of faultlines and refining the measurement of faultlines. The authors further propose the application of faultlines to the areas of leadership, international studies, and strategic management.
Arctic greening from warming promotes declines in caribou populations

A greener Arctic does not benefit caribou; the shift in tundra vegetation due to warming is associated with declining caribou herds. The migratory tundra caribou herds in North America follow decadal population cycles, and browsing from abundant caribou could be expected to counteract the current climate-driven expansion of shrubs in the circumpolar tundra biome. We demonstrate that the sea ice cover in the Arctic Ocean has provided a strong signal for climate-induced changes on the adjacent caribou summer ranges, outperforming other climate indices in explaining the caribou-plant dynamics. We found no evidence of a negative effect of caribou abundance on vegetation biomass. On the contrary, we found a strong bottom-up effect in which a warmer climate related to diminishing sea ice has increased the plant biomass on the summer pastures, along with a paradoxical decline in caribou populations. This result suggests that this climate-induced greening has been accompanied by a deterioration of pasture quality. The shrub expansion in Arctic North America involves plant species with strong antibrowsing defenses. Our results might therefore be an early signal of a climate-driven shift in the caribou-plant interaction from a system with low plant biomass modulated by cyclic caribou populations to a system dominated by nonedible shrubs and diminishing herds of migratory caribou.
Intractable: species in New Zealand that continue to decline despite conservation efforts

ABSTRACT Global biodiversity loss is accelerating at an alarming rate. While considerable effort and resources have gone into conservation management for many threatened species in New Zealand (NZ), some species are still ‘losing the battle’ despite much effort, and others have been ignored altogether. Here, we present seven case studies to illustrate the breadth of complex, often ambiguous, threats faced by taxa in NZ. These threats originate from the effects of agriculture and harvesting, irreversible habitat modification and loss, impediments to connectivity, disruption of parasite–host relationships, introduced species and susceptibility to disease, and are further exacerbated by complexities of political and legal inertia, low prioritisation and limited conservation funding. We outline the conservation challenges and identify advances needed to meet NZ's long-term conservation goals. The next 30 years of conservation require new tools in order to protect especially those ‘intractable’ species that have thus far defied efforts to ensure their survival.
Rapid and Efficient Filtration-Based Procedure for Separation and Safe Analysis of CBRN Mixed Samples

Separating CBRN mixed samples that contain both chemical and biological warfare agents (CB mixed sample) in liquid and solid matrices remains a very challenging issue. Parameters were set up to assess the performance of a simple filtration-based method first optimized on separate C- and B-agents, and then assessed on a model of CB mixed sample. In this model, MS2 bacteriophage, Autographa californica nuclear polyhedrosis baculovirus (AcNPV), Bacillus atrophaeus and Bacillus subtilis spores were used as biological agent simulants whereas ethyl methylphosphonic acid (EMPA) and pinacolyl methylphophonic acid (PMPA) were used as VX and soman (GD) nerve agent surrogates, respectively. Nanoseparation centrifugal devices with various pore size cut-off (30 kD up to 0.45 µm) and three RNA extraction methods (Invisorb, EZ1 and Nuclisens) were compared. RNA (MS2) and DNA (AcNPV) quantification was carried out by means of specific and sensitive quantitative real-time PCRs (qPCR). Liquid chromatography coupled to time-of-flight mass spectrometry (LC/TOFMS) methods was used for quantifying EMPA and PMPA. Culture methods and qPCR demonstrated that membranes with a 30 kD cut-off retain more than 99.99% of biological agents (MS2, AcNPV, Bacillus Atrophaeus and Bacillus subtilis spores) tested separately. A rapid and reliable separation of CB mixed sample models (MS2/PEG-400 and MS2/EMPA/PMPA) contained in simple liquid or complex matrices such as sand and soil was also successfully achieved on a 30 kD filter with more than 99.99% retention of MS2 on the filter membrane, and up to 99% of PEG-400, EMPA and PMPA recovery in the filtrate. The whole separation process turnaround-time (TAT) was less than 10 minutes. The filtration method appears to be rapid, versatile and extremely efficient. The separation method developed in this work constitutes therefore a useful model for further evaluating and comparing additional separation alternative procedures for a safe handling and preparation of CB mixed samples.
BOUNDED AREA THEOREMS FOR HIGHER-GENUS BLACK HOLES

By a simple modification of Hawking's well known topology theorems for black hole horizons, we find lower bounds for the areas of smooth apparent horizons and smooth cross sections of stationary black hole event horizons of genus g>1 in four dimensions. For a negatively curved Einstein space, the bound is 4(g-1)/(-) where is the cosmological constant of the spacetime. This is complementary to the known upper bound on the area of g = 0 black holes in de Sitter spacetime. It also emerges that g>1 quite generally requires a mean negative energy density on the horizon. The bound is sharp; we show that it is saturated by certain extreme, asymptotically locally anti-de Sitter spacetimes. Our results generalize a recent result of Gibbons.
The Lamin B receptor is essential for cholesterol synthesis and perturbed by disease-causing mutations

Lamin B receptor (LBR) is a polytopic membrane protein residing in the inner nuclear membrane in association with the nuclear lamina. We demonstrate that human LBR is essential for cholesterol synthesis. LBR mutant derivatives implicated in Greenberg skeletal dysplasia or Pelger-Huët anomaly fail to rescue the cholesterol auxotrophy of a LBR-deficient human cell line, consistent with a loss-of-function mechanism for these congenital disorders. These disease-causing variants fall into two classes: point mutations in the sterol reductase domain perturb enzymatic activity by reducing the affinity for the essential cofactor NADPH, while LBR truncations render the mutant protein metabolically unstable, leading to its rapid degradation at the inner nuclear membrane. Thus, metabolically unstable LBR variants may serve as long-sought-after model substrates enabling previously impossible investigations of poorly understood protein turnover mechanisms at the inner nuclear membrane of higher eukaryotes. DOI: http://dx.doi. org/10.7554/eLife.16011. 001
Reducing dropouts in outpatient care through an SMS-based system

The objective of this work is to reduce the number of outpatients dropouts, i.e. appointments that, unexpectedly, are not attended by the scheduled patients, thus causing disturbances to the regular ambulatory workflow, waste of resources, and, eventually, longer waiting lists for ambulatory care. A collateral, but not less important result is the improvement of the relationship between citizens and the public Hospital Company. The method proposed consists in sending short instant messages to remind the appointment. After the promising estimates obtained by a preliminary cost-benefit analysis, a commercial product was purchased for the communication infrastructure, while a software module has been developed for interacting with the legacy system, in order to retrieve the information necessary to compose the text of every sms and send it to the citizen. The system has been implemented since seven months, and its benefits have been measured. Dropouts trend, stable at 7-8% during last years, is clearly decreasing, while the number of citizens providing their mobile number to the healthcare booking facilities is constantly increasing. Our conclusion is that the cost of the system will be amortised in a very short time, leading to a significant cost saving and, hopefully, to shorter waiting lists.
Inter-Relationships of Cardinal Features and Outcomes of Symptomatic Pediatric Plasmodium falciparum Malaria in 1,933 Children in Kampala, Uganda

Malaria remains a challenging diagnosis with variable clinical presentation and a wide spectrum of disease severity. Using a structured case report form, we prospectively assessed 1,933 children at Mulago Hospital in Kampala, Uganda with acute Plasmodium falciparum malaria. Children with uncomplicated malaria significantly differed from those with severe disease for 17 features. Among 855 children with severe disease, the case-fatality rate increased as the number of severity features increased. Logistic regression identified five factors independently associated with death: cerebral malaria, hypoxia, severe thrombocytopenia, leukocytosis, and lactic acidosis. Cluster analysis identified two groups: one combining anemia, splenomegaly, and leukocytosis; and a second group centered on death, severe thrombocytopenia, and lactic acidosis, which included cerebral malaria, hypoxia, hypoglycemia, and hyper-parasitemia. Our report updates previous clinical descriptions of severe malaria, quantifies significant clinical and laboratory inter-relationships, and will assist clinicians treating malaria and those planning or assessing future research (NCT00707200) (www.clinicaltrials.gov).
Partial nitritation for subsequent Anammox to treat high-ammonium leachate

Nitrogen removal via autotrophic denitrification, an anaerobic ammonium oxidation (Anammox) process, requires an appropriate NO2-N/NH4-N ratio to provide nitrite as an intermediate. In this study, a laboratory-scale Hybrid Sequencing Batch Reactor (HSBR) was implemented for treating high-ammonium raw leachate to yield an appropriate NO2-N/NH4-N mixture as a pretreatment for subsequent Anammox. The optimal operating conditions were examined through the long-term operation of the HSBR. The experimental results showed that the prerequisite ratio of NO2-N/NH4-N was found with an initial ammonium concentration of 1200 mg/L, dissolved oxygen (DO) of 0.5–1.0 mg/L, sludge retention time (SRT) of 3 days and temperature of 31°C, which is essential for the subsequent Anammox process. Moreover, the inhibition of free ammonia (FA) and free nitrous acid (FNA) were also examined under a constant pH condition, and it was found that AOB (ammonium oxidation bacteria) had a great ability to adapt to a broad FA and FNA concentration, whereas NOB (nitrite-oxidizing bacteria) were inhibited by either FA or FNA concentration to a certain extent. It appears that partial nitritation could be implemented by facilitating FA and/or suppressing FNA concentration.