Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflammatory Bowel Disease Alters Intestinal Bile Acid Transporter Expression s

The enterohepatic circulation of bile acids (BAs) critically depends on absorption of BA in the terminal ileum and colon, which can be affected by inflammatory bowel disease (IBD). Diarrhea in IBD is believed to result in part from BA malabsorption (BAM). We explored whether IBD alters mRNA expression of key intestinal BA transporters, BA detoxifying systems, and nuclear receptors that regulate BA transport and detoxification. Using real-time polymerase chain reaction, mucosal biopsy specimens from the terminal ileum in Crohn ’ s disease (CD) patients and from the descending colon in ulcerative colitis (UC) patients were assessed for mRNA expression. Levels were compared with healthy controls. The main ileal BA uptake transporter, the apical sodium dependent bile acid transporter, was downregulated in active CD and UC and in CD in remission. Other significant changes such as repression of breast cancer – related protein and sulphotransferase 2A1 were seen only during active disease. In UC, pancolitis (but not exclusively left-sided colitis) was associated with altered expression of major BA transporters [multidrug resistance – associated protein 3 (MRP3), MRP4, multidrug resistance gene 1, organic solute transporter a / b ] and nuclear receptors (pregnane X receptor, vitamin D receptor) in the descending colon. UC pancolitis leads to broad changes and CD ileitis to selective changes in intestinal BA transporter expression. Early medical manipulation of intestinal BA transporters may help prevent BAM.
Validation Study of Genes with Hypermethylated Promoter Regions Associated with Prostate Cancer Recurrence

Background: One challenge in prostate cancer is distinguishing indolent from aggressive disease at diagnosis. DNA promoter hypermethylation is a frequent epigenetic event in prostate cancer, but few studies of DNA methylation in relation to features of more aggressive tumors or prostate cancer recurrence have been completed. Methods: We used the Infinium HumanMethylation450 BeadChip to assess DNA methylation in tumor tissue from 407 patients with clinically localized prostate cancer who underwent radical prostatectomy. Recurrence status was determined by follow-up patient surveys, medical record review, and linkage with the Surveillance, Epidemiology, and End Results (SEER) registry. The methylation status of 14 genes for which promoter hypermethylation was previously correlated with advanced disease or biochemical recurrence was evaluated. Average methylation level for promoter region CpGs in patients who recurred compared with those with no evidence of recurrence was analyzed. For two genes with differential methylation, time to recurrence was examined. Results: During an average follow-up of 11.7 years, 104 (26%) patients recurred. Significant promoter hypermethylation in at least 50% of CpG sites in two genes, ABHD9 and HOXD3, was found in tumors from patients who recurred compared with those without recurrence. Evidence was strongest for HOXD3 (lowest P = 9.46 × 10−6), with higher average methylation across promoter region CpGs associated with reduced recurrence-free survival (P = 2 × 10−4). DNA methylation profiles did not differ by recurrence status for the other genes. Conclusions: These results validate the association between promoter hypermethylation of ADHB9 and HOXD3 and prostate cancer recurrence. Impact: Tumor DNA methylation profiling may help to distinguish patients with prostate cancer at higher risk for disease recurrence. Cancer Epidemiol Biomarkers Prev; 23(7); 1331–9. ©2014 AACR.
Amyloplasts and Vacuolar Membrane Dynamics in the Living Graviperceptive Cell of the Arabidopsis Inflorescence Stemw⃞

We developed an adequate method for the in vivo analysis of organelle dynamics in the gravity-perceptive cell (endodermis) of the Arabidopsis thaliana inflorescence stem, revealing behavior of amyloplasts and vacuolar membranes in those cells. Amyloplasts in the endodermis showed saltatory movements even before gravistimulation by reorientation, and these movements were confirmed as microfilament dependent. From our quantitative analysis in the wild type, the gravity-oriented movement of amyloplasts mainly occurred during 0 to 3 min after gravistimulation by reorientation, supporting findings from our previous physiological study. Even after microfilament disruption, the gravity-oriented movement of amyloplasts remained. By contrast, in zig/sgr4 mutants, where a SNARE molecule functioning in vacuole biogenesis has been disrupted, the movement of amyloplasts in the endodermis is severely restricted both before and after gravistimulation by reorientation. Here, we describe vacuolar membrane behavior in these cells in the wild-type, actin filament–disrupted, and zig/sgr4 mutants and discuss its putatively important features for the perception of gravity. We also discuss the data on the two kinds of movements of amyloplasts that may play an important role in gravitropism: (1) the leading edge amyloplasts and (2) the en mass movement of amyloplasts.
Sorting of membrane components from endosomes and subsequent recycling to the cell surface occurs by a bulk flow process

A central question in the endocytic process concerns the mechanism for sorting of recycling components (such as transferrin or low density lipoprotein receptors) from lysosomally directed components; membrane- associated molecules including receptors are generally directed towards the recycling pathway while the luminal content of sorting endosomes, consisting of the acid-released ligands, are lysosomally targeted. However, it is not known whether recycling membrane receptors follow bulk membrane flow or if these proteins are actively sorted from lysosomally directed material because of specific protein sequences and/or structural features. Using quantitative fluorescence microscopy we have determined the endocytic route and kinetics of traffic of the bulk carrier, membrane lipids, to address this issue directly. We show that N-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl)-epsilon-aminohexanoyl]- sphingosylphosphorylcholine (C6-NBD-SM) in endocytosed as bulk membrane, and it transits the endocytic system kinetically and morphologically identically to fluorescently labeled transferrin in a CHO cell line. With indistinguishable kinetics, the two labeled markers sort from lysosomally destined molecules in peripherally located sorting endosomes, accumulate in a peri-centriolar recycling compartment, and finally exit the cell. Other fluorescently labeled lipids, C6-NBD-phosphatidylcholine and galactosylceramide also traverse the same pathway. The constitutive nature of sorting of bulk membrane towards the recycling pathway and the lysosomal direction of fluid phase implies a geometric basis of sorting.
Steady-State Motion Visual Evoked Potentials Produced by Oscillating Newton's Rings: Implications for Brain-Computer Interfaces

In this study, we utilize a special visual stimulation protocol, called motion reversal, to present a novel steady-state motion visual evoked potential (SSMVEP)-based BCI paradigm that relied on human perception of motions oscillated in two opposite directions. Four Newton's rings with the oscillating expansion and contraction motions served as visual stimulators to elicit subjects' SSMVEPs. And four motion reversal frequencies of 8.1, 9.8, 12.25 and 14 Hz were tested. According to Canonical Correlation Analysis (CCA), the offline accuracy and ITR (mean ± standard deviation) over six healthy subjects were 86.56±9.63% and 15.93±3.83 bits/min, respectively. All subjects except one exceeded the level of 80% mean accuracy. Circular Hotelling's T-Squared test () also demonstrated that most subjects exhibited significantly strong stimulus-locked SSMVEP responses. The results of declining exponential fittings exhibited low-adaptation characteristics over the 100-s stimulation sequences in most experimental conditions. Taken together, these results suggest that the proposed paradigm can provide comparable performance with low-adaptation characteristic and less visual discomfort for BCI applications.
Role of the vascular endothelium in O2 extraction during progressive ischemia in canine skeletal muscle.

O2 extraction during progressive ischemia in canine skeletal muscle, J. Appl. Physiol. 79(4): 1351-1360, 1995. --O2 uptake (VO2) is defended during decreased O2 delivery (QO2) by an increase in the O2 extraction ratio (O2ER, VO2/QO2), presumably by recruitment of capillaries. This study tested the hypothesis that activity of the microvascular endothelium plays a necessary role in achievement of maximal O2ER. We pump perfused the vascularly isolated hindlimbs of 24 anesthetized and paralyzed dogs at progressively lower flows over a 90-min period. In eight dogs, hindlimb vascular endothelium was removed by injection of deoxycholate (DOC) into the perfusing artery before the ischemic challenge. DOC treatment resulted in loss of normal in vivo and in vitro endothelium-dependent dilatory responses to acetylcholine, but endothelium-independent vascular smooth muscle responses were intact. Eight other dogs were pretreated with nitro-L-arginine methyl ester plus indomethacin (L+I group) to block the synthesis of the vasodilators nitric oxide and prostacyclin. L+I and DOC treatment were associated with increases in hindlimb vascular resistance of 168 +/- 17 and 63 +/- 12%, respectively. O2ER at critical QO2 (QO2 at which VO2 begins to decrease) was 81 +/- 2% in eight control dogs, 66 +/- 6% in L+I, and 42 +/- 4% in DOC, indicating a significant O2 extraction defect in the two treatment groups. These data suggest that products of the vascular endothelium play an important role in the matching of O2 supply to demand during supply limitation in skeletal muscle.
Autologous stem cell transplantation in the treatment of systemic sclerosis: report from the EBMT/EULAR Registry

Objective: To analyse the durability of the responses after haematopoietic stem cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine whether the high transplant related mortality (TRM) improved with experience. This EBMT/EULAR report describes the longer outcome of patients originally described in addition to newly recruited cases. Methods: Only patients with SSc, treated by HSCT in European phase I–II studies from 1996 up to 2002, with more than 6 months of follow up were included. Transplant regimens were according to the international consensus statements. Repeated evaluations analysed complete, partial, or non-response and the probability of disease progression and survival after HSCT (Kaplan-Meier). Results: Given as median (range). Among 57 patients aged 40 (9.1–68.7) years the skin scores improved at 6 (n = 37 patients), 12 (n = 30), 24 (n = 19), and 36 (n = 10) months after HSCT (p<0.005). After 22.9 (4.5–81.1) months, partial (n = 32) or complete response (n = 14) was seen in 92% and non-response in 8% (n = 4) of 50 observed cases. 35% of the patients with initial partial (n = 13/32) or complete response (n = 3/14) relapsed within 10 (2.2–48.7) months after HSCT. The TRM was 8.7% (n = 5/57). Deaths related to progression accounted for 14% (n = 8/57) of the 23% (n = 13/57) total mortality rate. At 5 years, progression probability was 48% (95% CI 28 to 68) and the projected survival was 72% (95% CI 59 to 75). Conclusion: This EBMT/EULAR report showed that response in two thirds of the patients after HSCT was durable with an acceptable TRM. Based on these results prospective, randomised trials are proceeding.
Evaluating the molecule-based prediction of clinical drug responses in cancer

MOTIVATION Molecule-based prediction of drug response is one major task of precision oncology. Recently, large-scale cancer genomic studies, such as The Cancer Genome Atlas (TCGA), provide the opportunity to evaluate the predictive utility of molecular data for clinical drug responses in multiple cancer types. RESULTS Here, we first curated the drug treatment information from TCGA. Four chemotherapeutic drugs had more than 180 clinical response records. Then, we developed a computational framework to evaluate the molecule based predictions of clinical responses of the four drugs and to identify the corresponding molecular signatures. Results show that mRNA or miRNA expressions can predict drug responses significantly better than random classifiers in specific cancer types. A few signature genes are involved in drug response related pathways, such as DDB1 in DNA repair pathway and DLL4 in Notch signaling pathway. Finally, we applied the framework to predict responses across multiple cancer types and found that the prediction performances get improved for cisplatin based on miRNA expressions. Integrative analysis of clinical drug response data and molecular data offers opportunities for discovering predictive markers in cancer. This study provides a starting point to objectively evaluate the molecule-based predictions of clinical drug responses. CONTACT jgu@tsinghua.edu. cn SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Towards Provably-Secure Remote Memory Attestation

We initiate the study of provably secure remote memory attestation. We present two protocols offering various efficiency and security trade-offs that detect the presence of injected malicious code in remotelystored heap memory. While our solutions offer protection only against a specific class of attacks, our novel formal security definitions are general enough to cover a wide range of attacks and settings, and should be useful for further research on the subject.
Risk-Based Generalizations of f-divergences

We derive a generalized notion of f-divergences, called (f, l)-divergences. We show that this generalization enjoys many of the nice properties of f-divergences, although it is a richer family. It also provides alternative definitions of standard divergences in terms of surrogate risks. As a first practical application of this theory, we derive a new estimator for the Kulback-Leibler divergence that we use for clustering sets of vectors.
Diurnal changes in postural control in normal children: Computerized static and dynamic assessments

Mild traumatic brain injury (mTBI) causes postural control deficits and accordingly comparison of aberrant postural control against normal postural control may help diagnose mTBI. However, in the current literature, little is known regarding the normal pattern of postural control in young children. This study was therefore conducted as an effort to fill this knowledge gap. Eight normal school-aged children participated. Posture assessment was conducted before (7–8 a.m. in the morning) and after (4–7 p.m. in the afternoon) school on regular school days using the Balance Master® evaluation system composed of 3 static tests and 2 dynamic balance tests. A significant difference in the weight-bearing squats was detected between morning hours and afternoon hours (P < 0.05). By end of afternoon, the body weight was borne mainly on the left side with the knee fully extended and at various degrees of knee flexion. A significantly better directional control of the lateral rhythmic weight shifts was observed at the end of the afternoon than at morning hours (P < 0.05). In summary, most of our findings are inconsistent with results from previous studies in adults, suggesting age-related differences in posture control in humans. On a regular school day, the capacity of postural control and laterality or medio-lateral balance in children varies between morning and afternoon hours. We suggest that posturographic assessment in children, either in normal (e.g., physical education and sports training) or in abnormal conditions (e.g., mTBI-associated balance disorders), be better performed late in the afternoon.
Drug Treatment in Older People before and after the Transition to a Multi-Dose Drug Dispensing System–A Longitudinal Analysis

Background An association has been found between multi-dose drug dispensing (MDD) and use of many drugs. The aim of this study was to investigate the nature of this association, by performing a longitudinal analysis of the drug treatment before and after the transition to MDD. Methods Inclusion critera in this register-based study were inhabitants in Region Västra Götaland, Sweden, who, at ≥65 years of age and between 1st July 2006 and 30th June 2010, filled their first MDD prescription. For each individual, prescribed drugs were estimated at three month intervals before and after (maximum 3 years, respectively) the first date of filling an MDD prescription (index date). Results A total of 30,922 individuals matched the inclusion criteria (mean age: 83.2 years; 59.9% female). There was a temporal association between the transition to MDD and an increased number of drugs: 5.4±3.9 and 7.5±3.8 unique drugs three months before and after the index date, respectively, as well as worse outcomes on several indicators of prescribing quality. When either data before or after the index date were used, a multi-level regression analysis predicted the number of drugs at the index date at 5.76 (95% confidence limits: 5.71; 5.80) and 7.15 (7.10; 7.19), respectively, for an average female individual (83.2 years, 10.8 unique diagnoses, 2.4 healthcare contacts/three months). The predicted change in the number of drugs, from three months before the index date to the index date, was greater when data before this date was used as compared with data after this date: 0.12 (0.09; 0.14) versus 0.02 (−0.01; 0.05). Conclusions After the patients entered the MDD system, they had an increased number of drugs, more often potentially harmful drug treatment, and fewer changes in drug treatment. These findings support a causal relationship between such a system and safety concerns as regards prescribing practices.
Human Neuroscience

The present paper focuses on task-related deactivations in areas collectively referred to as the default mode network. The default network is an organized network of brain sites that are engaged when the brain is in a resting state (Raichle et al., 2001), and is isolated in fMRI studies by examining interconnectivity among sites with subjects at rest or by contrasting baseline neural activity (e.g., staring at a fi xation point) in a cognitive study with neural activations that occur under cognitive challenge (Shulman et al., 1997; Raichle and Snyder, 2007). The default network encompasses a range of neural sites including the medial frontal cortex, medial and lateral parietal cortex, and anterior and posterior cingulate, as well as medial temporal areas. Default activity does not represent a state of " no cognitive activity, " but rather is characteristic of thought that is not goal-directed and may involve day dreaming , self-referential processing, or the simulation of future events 1. It is clear that when young adults are faced with a cognitive challenge , the activity in the default sites is suppressed, and areas that
Light Propagation in Inhomogeneous Universes. V. Gravitational Lensing of Distant Supernovae

We use a series of ray-tracing experiments to determine the magnification distribution of high-redshift sources by gravitational lensing. We determine empirically the relation between magnification and redshift, for various cosmological models. We then use this relation to estimate the effect of lensing on the determination of the cosmological parameters from observations of high-z supernovae. We found that, for supernovae at redshifts z < 1.8, the effect of lensing is negligible compared to the intrinsic uncertainty in the measurements. Using mock data in the range 1.8 < z < 8, we show that the effect of lensing can become significant. Hence, if a population of very high z supernovae was ever discovered, it would be crucial to fully understand the effect of lensing, before these SNe could be used to constrain cosmological models. We show that the distance moduli m − M for an open CDM universe and a ΛCDM universe are comparable at z > 2. Therefore, if supernovae up to these redshifts were ever discovered, it is still the ones in the range 0.3 < z < 1 that would distinguish these two models.
Comparison of intravascular ultrasound and angiography in the assessment of myocardial bridging.

BACKGROUND In autopsy, myocardial bridging is a common finding. With coronary angiography, a systolic compression, mainly of the left anterior descending coronary artery, is observed in 1% to 3% of the patients. Controversy exists concerning the functional importance of this finding. To obtain a functional insight into the myocardial bridging, intravascular ultrasound and intracoronary Doppler were performed. METHODS AND RESULTS Intracoronary ultrasound and Doppler were performed in 14 patients with angiographic evidence of systolic vessel compression ("milking effect") in the left anterior descending coronary artery. The 4.8F, 20-MHz ultrasound catheter could not be advanced through the entire myocardial bridge segment in 6 of the 14 patients studied because the lumen was < 1.6 mm. In these patients, only the proximal parts of the bridge segment were scanned. The changes in cross-sectional shape during the cardiac cycle were determined for both the normal proximal segment and the bridge segment by use of a semiautomatic computer program. Intracoronary Doppler (20 MHz) was performed in 7 patients with a 3F catheter. A highly characteristic systolic eccentric or concentric compression with delayed relaxation in diastole of the myocardial bridging segment was clearly visualized in all patients. The cross-sectional lumen area variation was 40 +/- 25% in the bridging segments and 9 +/- 7% in the normal segments (P < .01). No atherosclerotic lesions were detected in the bridge or the distal segment in the 8 patients in whom the IVUS catheter was successfully advanced through the entire myocardial bridge. However, atherosclerotic plaques were found in the segments proximal to the bridge in 12 of 14 patients (86%). The resting mean flow velocity was 6.4 +/- 1.2 cm/s; the maximal mean flow velocity after intracoronary administration of 10 mg papaverine was 14.1 +/- 3.4 cm/s. The coronary flow velocity reserve was 2.2 +/- 0.7. A highly characteristic pattern showing a prominent peak in coronary velocity in early diastole was observed in 86% of patients, and this pattern was enhanced after injection of intracoronary papaverine. CONCLUSION Intravascular ultrasound demonstrated a characteristic systolic compression of the bridge segments. The delayed compression release may explain the characteristic sharp early diastolic peak in coronary flow velocity found with intracoronary Doppler in vessels with myocardial bridging. Reduced coronary flow reserve may be related to this phenomenon, possibly explaining signs of ischemia detected in some of the patients, but may alternatively be a result of the presence of atherosclerosis in the segment proximal to the bridge in these patients.
Business Process and Business Rule Modeling: A Representational Analysis

Process modeling and rule modeling languages are both used to document organizational policies and procedures. However, little work has been done to understand their synergies and overlap. Understanding the relationship between the two modeling types would allow organizations to maximize synergies and reduce their modeling effort. In this paper we use the well-established Bunge-Wand-Weber (BWW) representation theory to compare the representation capabilities of both types of languages. We perform a representational analysis of two rule modeling languages, viz., SRML and SBVR. We compare their representation capabilities with those of four popular conceptual business process modeling languages, and focus on the aspects of maximum ontological completeness and minimum ontological overlap. The outcome of this study shows that no single language is internally complete with respect to the BWW representation model and that a combination of two languages, viz. SRML and BPMN, is better suited for process modeling than any single modeling language.