Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Vitamin A Metabolome in Human Livers With and Without Nonalcoholic Fatty Liver Disease

Retinoids are essential endogenous compounds involved in regulation of critical biologic processes, including maintenance of metabolic homeostasis in the liver. Much of the knowledge of altered retinoid homeostasis in human disease states is derived from changes in indirect markers such as mRNA expression of retinoid-related genes and circulating concentrations of retinol or its binding protein RBP4. We hypothesized that in the human liver, concentrations of the active retinoid all-trans-retinoic acid (atRA) correlate with the concentrations of retinyl palmitate (RP), the storage form of atRA, retinol, the inactive vitamin A, and the mRNA expression of retinoid-related genes. On the basis of existing knowledge of altered vitamin A homeostasis in metabolic syndrome, we also predicted that in human livers with nonalcoholic fatty liver disease (NAFLD) retinoid concentrations would be decreased. Using novel liquid chromatography–tandem mass spectrometry methods, the hepatic vitamin A metabolome was quantified in normal human livers (n = 50) and 22 livers from donors with NAFLD. The hepatic concentrations of RP, atRA, 13-cisRA, and 4-oxo-atRA were significantly decreased in NAFLD samples in comparison with normal liver samples, whereas retinol levels remained unchanged. The concentrations of atRA were positively correlated with RP and 13-cisRA but not with retinol or the relative mRNA expression of LRAT, ALDH1A1, CYP26A1, RARα, and RARβ. An active metabolite of atRA, 4-oxo-atRA was, for the first time, detected in human tissues at comparable concentration with RA isomers, suggesting this retinoid may contribute to retinoid signaling in humans. Significance Statement This study shows that in NAFLD liver vitamin A homeostasis is disrupted potentially contributing to disease progression. The results show that interpretation of retinoid homeostasis on the basis of indirect markers such as retinol concentrations or mRNA data is probably misleading when evaluating human disease processes, and analysis of the broader retinoid metabolome is needed to characterize disease effects on retinoid signaling.
A Comprehensive Structure to Understand Outward Mobility - Reflections for University International Offices

This article was published in May 2016 (online), full version available at https://www.handbook-internationalisation.com/en/handbuch/gliederung/#/Beitragsdetailansicht/173/425/A-Comprehensive-Structure-to-Understand-Outward-Mobility---Reflections-for-University-International-Offices
RADIOGRAPHIC PROGRESSION IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background: Antibody against cyclic citrullinated proteins (ACPA) is counted as one of the most important biomarkers in diagnosis, classification, and prognosis of rheumatoid arthritis (RA). The clinical implications of change in ACPA level over time remain undetermined. Objectives: We examined the evolution of ACPA during disease course and assess predictive value of time-weighted cumulative ACPA titer on radiographic progression in patients with RA. Methods: A group of 734 patients with RA was followed longitudinally over 2 years, with annual measurements of IgM rheumatoid factor (RF) and ACPA. Radiographs of the hands were scored with the modified Sharp score (SHS). Cumulative ACPA antibody titers were calculated using the trapezoidal rule. Results: The patients with radiographic progression had a higher SHS at baseline; and smoking status, diabetes, RF positivity, and use of biologic DMARDs were independently associated with radiographic progression (all P <0.05). As for ACPA, reversion happened more commonly in men and was associated with younger onset age and lower titer at baseline, but it had no direct relevance to radiographic outcome. In multivariable regression analysis, only high cumulative or baseline titer of ACPA had a predictive power for rapid radiographic progression (all P <0.05), and cumulative ACPA titer was superior in terms of statistical significance (Cohen ’ s d, 0.637 versus 0.583). Conclusion: High cumulative ACPA titer was an independent predictor for accelerated radiographic progression, especially with initiation of joint damage. Serial measurement of ACPA titer can provide information about its dynamics over the clinical course and can facilitate an additional assessment of radiographic progression. Acknowledgement: Nothing specified. Disclosure of Interests:
NATTACK: Learning the Distributions of Adversarial Examples for an Improved Black-Box Attack on Deep Neural Networks

Powerful adversarial attack methods are vital for understanding how to construct robust deep neural networks (DNNs) and for thoroughly testing defense techniques. In this paper, we propose a black-box adversarial attack algorithm that can defeat both vanilla DNNs and those generated by various defense techniques developed recently. Instead of searching for an "optimal" adversarial example for a benign input to a targeted DNN, our algorithm finds a probability density distribution over a small region centered around the input, such that a sample drawn from this distribution is likely an adversarial example, without the need of accessing the DNN's internal layers or weights. Our approach is universal as it can successfully attack different neural networks by a single algorithm. It is also strong; according to the testing against 2 vanilla DNNs and 13 defended ones, it outperforms state-of-the-art black-box or white-box attack methods for most test cases. Additionally, our results reveal that adversarial training remains one of the best defense techniques, and the adversarial examples are not as transferable across defended DNNs as them across vanilla DNNs.
A Novel Nuclear Interactor of ARF and MDM2 (NIAM) That Maintains Chromosomal Stability*

The ARF tumor suppressor signals through p53 and other poorly defined anti-proliferative pathways to block carcinogenesis. In a search for new regulators of ARF signaling, we discovered a novel nuclear protein that we named NIAM (nuclear interactor of ARF and MDM2) for its ability to bind both ARF and the p53 antagonist MDM2. NIAM protein is normally expressed at low to undetectable levels in cells because of, at least in part, MDM2-mediated ubiquitination and proteasomal degradation. When reintroduced into cells, NIAM activated p53, caused a G1 phase cell cycle arrest, and collaborated with ARF in an additive fashion to suppress proliferation. Notably, NIAM retains growth inhibitory activity in cells lacking ARF and/or p53, and knockdown experiments revealed that it is not essential for ARF-mediated growth inhibition. Thus, NIAM and ARF act in separate anti-proliferative pathways that intersect mechanistically and suppress growth more effectively when jointly activated. Intriguingly, silencing of NIAM accelerated chromosomal instability, and microarray analyses showed reduced NIAM mRNA expression in numerous primary human tumors. This study identifies a novel protein with tumor suppressor-like behaviors and functional links to ARF-MDM2-p53 signaling.
Recombinator-k-means: Enhancing k-means++ by seeding from pools of previous runs

We present a heuristic algorithm, called recombinator-k-means, that can substantially improve the results of k-means optimization. Instead of using simple independent restarts and returning the best result, our scheme performs restarts in batches, using the results of a previous batch as a reservoir of candidates for the new initial starting values (seeds), exploiting the popular k-means++ seeding algorithm to piece them together into new promising initial configurations. Our scheme is general (it only affects the seeding part of the optimization, thus it could be applied even to k-medians or k-medoids, for example), it has no additional costs and it is trivially parallelizable across the restarts of each batch. In some circumstances, it can systematically find better configurations than the best one obtained after 10^4 restarts of a standard scheme. Our implementation is publicly available at this https URL.
Deformed Intersecting D6-Brane GUTS I

By employing D6-branes intersecting at angles in D = 4 toroidal orientifolded type IIA strings, we construct four stack string GUT models (PS-I class), that contain at low energy exactly the three generation Standard model with no extra matter and/or extra gauge group factors. These classes of models are based on the Pati-Salam (PS) gauge group SU(4)C × SU(2)L × SU(2)R. They represent deformations around the quark and lepton basic intersection number structure. The models possess the same phenomenological characteristics of some recently discussed examples (PS-A class) of four stack PS GUTS. Namely, there are no colour triplet couplings to mediate proton decay and proton is stable as baryon number is a gauged symmetry. Neutrinos get masses of the correct sizes. Also the mass relation me = md at the GUT scale is recovered. Moreover, we clarify the novel role of extra branes, the latter having non-trivial intersection numbers with quarks and leptons and creating scalar singlets, needed for the satisfaction of RR tadpole cancellation conditions. The presence of N = 1 supersymmetry in sectors involving the extra branes is equivalent to the, model dependent, orthogonality conditions of the U(1)'s surviving massless the generalized Green-Schwarz mechanism. The use of extra branes creates mass couplings that predict the appearance of light fermion doublets up to the scale of electroweak scale symmetry breaking.
Limit theorems for weighted samples with applications to sequential Monte Carlo methods

In the last decade, sequential Monte-Carlo methods (SMC) emerged as a key tool in computational statistics (see for instance [Doucet, De Freitas and Gordon,Sequential Monte Carlo Methods in Practice. Springer, New York, 2001], [Liu. Monte Carlo Strategies in Scientific Computing. Springer, New York, 2001], [Kunsch. Complex Stochastic Systems , 109-173, CRC Publisher, Boca raton, 2001]). These algorithms approximate a sequence of distributions by a sequence of weighted empirical measures associated to a weighted population of particles, which are generated recursively. Despite many theoretical advances (see for instance [Gilks and Berzuini. J. Roy. Statist. Soc. Ser. B , 63(1) , 127-146, 2001], [Kunsch. Ann. Statist. , 33(5) , 1983-2021, 2005], [Del Moral. Feynman-Kac Formulae. Genealogical and Interacting Particle Systems with Applications , Springer, 2004], [Chopin. Ann. Statist. , 32(6) , 2385-2411, 2004]), the asymptotic property of these approximations remains a question of central interest. In this paper, we analyze sequential Monte Carlo (SMC) methods from an asymptotic perspective, that is, we establish law of large numbers and invariance principle as the number of particles gets large. We introduce the concepts of weighted sample consistency and asymptotic normality, and derive conditions under which the transformations of the weighted sample used in the SMC algorithm preserve these properties. To illustrate our findings, we analyze SMC algorithms to approximate the filtering distribution in state-space models. We show how our techniques allow to relax restrictive technical conditions used in previously reported works and provide grounds to analyze more sophisticated sequential sampling strategies, including branching, selection at randomly selected times, etc.
Clinical and diagnostic outcomes in arthroscopic treatment for posterolateral plicae impingement within the radiocapitellar joint

Abstract Synovial plica is rarely diagnosed as cause of elbow pain. Impingemnt of posterolateral plicae in the radiocapitellar joint tends to be usually overlooked. The purpose of this study was to present outcomes of arthroscopic treatment in relatively large number of cases and propose reliable diagnostic test for posterolateral plicae of the radiocapitellar joint. From January 2000 to December 2010, 24 cases diagnosed with pathologic posterolateral radiocapitellar plica on arthroscopic finding were retrospectively reviewed. Magnetic resonance imaging (MRI) evaluation and preoperative physical examination were performed. The posterolateral radiocapitellar plica test newly proposed by the present study was also conducted. To measure postoperative clinical outcomes, the disabilities of the arm, shoulder, and hand (DASH) score and Mayo elbow performance score (MEPS) were employed. Minimum duration of follow up was 24 months. According to the preoperative MRI, pathologic radiocapitellar plica was identified in 17 cases (70.8%). Preoperatively, maximal tender point was present on the radiocapitellar joint line in 20 cases (83.3%) and mechanical symptoms were observed in 9 cases (37.5%). 6 cases (25%) demonstrated pain at terminal extension and limitation of extension. 20 (83.3%) cases tested positive for posterolateral radiocapitellar plica test. The sensitivity and specificity of the posterolateral radiocapitellar plica test were 83.3% and 87.5%, respectively. The accuracy value was 86.3%. Arthroscopic debridement of pathologic plica in the radiocapitellar joint demonstrated clinical improvements: DASH score was from 36.6 to 8.9 and MEPS was from 56.9 to 95.6 at the latest follow-up. Symptomatic impingement by the pathologic posterolateral plica of the radiocapitellar joint should be considered when posterolateral elbow pain which is refractory to conservative treatment, and other prevalent diseases are excluded. The posterolateral radiocapitellar plica test and radiocapitellar joint line tenderness could be recommended as reliable examination maneuvers to obtain accurate diagnosis. Arthroscopic debridement was an effective method for treating symptomatic plicae.
CO(2) Exchange and Dinitrogen Fixation of Subterranean Clover in Response to Light Level.

Small swards of nodulated subterranean clover plants were grown in pots to a common dry weight under controlled conditions. The rooting medium was a porous calcined clay. All mineral nutrients except nitrogen were supplied daily in solution. Pots then were placed in an assimilation chamber for 3 days for the measurement of net CO(2) exchange at light levels ranging from 0.1 to 2.0 millieinsteins per square meter per second. N(2)-fixation (acetylene reduction) of each pot was measured subsequently. H(2)-evolution and N(2)-fixation were measured for similar treatments in separate experiments using smaller pots.CO(2)-assimilation rate and N(2)-fixation rate responded similarly to increase in light level so that N(2)-fixation was found to be a linear function of both the daily (12-hour) net CO(2)-uptake and of the growth rate (24 hours) of the sward over a wide range. N-concentration of the plants was independent of the light level under which they were grown. The rate of N(2)-fixation per unit weight of nodule varied over a wide range depending on the number of nodules present and on the demand for nitrogen as determined by the growth rate of the sward. It is concluded that the amount of assimilate available to the whole plant is a major factor determining the rate of N(2)-fixation by the whole plant, although it may not be important in determining specific rates of nodule activity. N(2)-fixation per unit weight of nodule therefore is considered to have limited utility for comparative purposes.The relative efficiency of N(2)-fixation was found to be about 0.7 and independent of the level of the incident light after growth at two contrasting light levels, 0.4 and 1.0 millieinsteins per square meter per second.
Cobalt Chloride Treatment Used to Ablate the Lateral Line System Also Impairs the Olfactory System in Three Freshwater Fishes

Fishes use multimodal signals during both inter- and intra-sexual displays to convey information about their sex, reproductive state, and social status. These complex behavioral displays can include visual, auditory, olfactory, tactile, and hydrodynamic signals, and the relative role of each sensory channel in these complex multi-sensory interactions is a common focus of neuroethology. The mechanosensory lateral line system of fishes detects near-body water movements and is implicated in a variety of behaviors including schooling, rheotaxis, social communication, and prey detection. Cobalt chloride is commonly used to chemically ablate lateral line neuromasts, thereby eliminating water-movement cues to test for mechanosensory-mediated behavioral functions. However, cobalt acts as a nonspecific calcium channel antagonist and could potentially disrupt function of all superficially located sensory receptor cells, including those for chemosensing. Here, we examined whether CoCl2 treatment used to ablate the lateral line system also impairs olfaction in three freshwater fishes, the African cichlid fish Astatotilapia burtoni, goldfish Carassius auratus, and the Mexican blind cavefish Astyanax mexicanus. To examine the impact of CoCl2 on the activity of peripheral receptors, we quantified DASPEI fluorescence intensity of the olfactory epithelium from fish exposed to control and CoCl2 solutions. In addition, we examined brain activation in olfactory processing regions of A. burtoni immersed in either control or cobalt solutions. All three species exposed to CoCl2 had decreased DASPEI staining of the olfactory epithelium, and in A. burtoni, cobalt treatment caused reduced neural activation in olfactory processing regions of the brain. To our knowledge this is the first empirical evidence demonstrating that the same CoCl2 treatment used to ablate the lateral line system also impairs olfactory function. These data have important implications for the use of CoCl2 in future research and suggest that previous studies using CoCl2 should be reinterpreted in the context of both impaired mechanoreception and olfaction.
Treatment of vascular risk factors is associated with slower decline in Alzheimer disease

Background: There is growing evidence that vascular risk factors (VRF) contribute to cognitive decline. Whether their treatment can slow down the progression of Alzheimer disease (AD) remains unsettled. The aim of this observational study was to evaluate whether the treatment of VRF is associated with a slower cognitive decline in patients who have AD without cerebrovascular disease (CVD). Methods: We recruited 301 consecutive patients who had AD without CVD (mean age 71.7 years; 69.4% women; first Mini-Mental State Examination [MMSE] mean score 21.6; mean follow-up 2.3 years), who had attended a memory clinic between 1997 and 2003. VRF sought were high blood pressure, dyslipidemia, diabetes mellitus, tobacco smoking, and atherosclerotic disease. Only 21 patients (7.0%) had no VRF. Others were classified as having no VRF treated (n = 72; 25.7%), some VRF treated (n = 119; 42.5%), or all VRF treated (n = 89; 31.8%). We compared MMSE progression over time among these 3 groups using a mixed random effects regression model. Results: Baseline MMSE scores were similar in the 3 groups. With adjustment for confounding factors, MMSE progression over time differed significantly between groups (p = 0.002). Patients with all their VRF treated declined less than those with none of their VRF treated. Those with some VRF treated tended to have an intermediate decline. Conclusions: In patients who have Alzheimer disease without CVD, treatment of vascular risk factors (VRF) is associated with a slower decline in Mini-Mental State Examination score. Randomized controlled trials are needed to confirm this association, but our data suggest that dementia should not prevent treatment of VRF.
Seasonal Variation in Mortality, Medical Care Expenditure and Institutionalization in Older People: Evidence from a Dutch Cohort of Older Health Insurance Clients

Background The mortality rates of older people changes with the seasons. However, it has not been properly investigated whether the seasons affect medical care expenditure (MCE) and institutionalization. Seasonal variation in MCE is plausible, as MCE rises exponentially before death. It is therefore important to investigate the impact of the seasons on MCE both mediated and unmediated by mortality. Methods Data on mortality, MCE and institutionalization from people aged 65 and older in a region in the Netherlands from July 2007 through 2010 were retrieved from a regional health care insurer and were linked with data from the Netherlands Institute for Social Research, and Statistics Netherlands (n = 61,495). The Seasonal and Trend decomposition using Loess (STL) method was used to divide mortality rates, MCE, and institutionalization rates into a long-term trend, seasonal variation, and remaining variation. For every season we calculated the 95% confidence interval compared to the long-term trend using Welch’s t-test. Results The mortality rates of older people differ significantly between the seasons, and are 21% higher in the winter compared to the summer. MCE rises with 13% from the summer to the winter; this seasonal difference is higher for the non-deceased than for the deceased group (14% vs. 6%). Seasonal variation in mortality is more pronounced in men and people in residential care. Seasonal variation in MCE is more pronounced in women. Institutionalization rates are significantly higher in the winter, but the other seasons show no significant impact. Conclusions Seasonal changes affect mortality and the level of MCE of older people; institutionalization rates peak in the winter. Seasonal variation in MCE exists independently from patterns in mortality. Seasonal variation in mortality is similar for both institutionalized and community-dwelling elderly. Policy-makers, epidemiologists and health economists are urged to acknowledge and include the impact of the seasons in future policy and research.
Some remarks on atypical intersections

We prove weak versions of the Zilber-Pink conjecture in the semi-abelian and modular settings. Given a "small" set $\Gamma$, which is a subgroup of finite rank in the semi-abelian case and a subset of $\mathbb{Q}^{alg}$ consisting of special points and Hecke orbits of finitely many non-special points in the modular case, we consider $\Gamma$-special subvarieties---weakly special subvarities containing a point of $\Gamma$ (or a tuple from $\Gamma$ in the modular case)---and show that every variety $V$ contains only finitely many maximal $\Gamma$-atypical subvarieties, i.e. atypical intersections of $V$ with $\Gamma$-special varieties the weakly special closures of which are $\Gamma$-special. The Mordell-Lang conjecture and its modular analogue (established by Habegger and Pila), as well as the Ax-Schanuel theorem in each setting, play a key role in our proofs.
A BAYESIAN CURE RATE MODEL FOR REPEATED MEASUREMENTS AND INTERVAL CENSORING

We extend a recently published multivariate Bayesian cure rate model to handle interval censoring and a varying number of measurements per individual. The model assumes an unknown number of latent causes of the event in question at each repeated measurement. This number is assumed to be distributed Poisson, with rate a function of covariates multiplied by a subject-specific frailty term. The observed event time is the minimum of the event times of the latent causes, and may only be recorded as contained within a given time interval. If the number of latent causes of the event is zero for an individual at a measurement, then that individual will not experience the event at that measurement. We present the model for a general frailty distribution and lifetime distribution. Our model formulation also allows covariates to describe the lifetime distribution. We illustrate the model using a data set from NASA’s Hypobaric Decompression Sickness Databank. We model the time to onset of grade IV venous gas emboli in hypobaric environment using both a gamma frailty distribution and an inverse Gaussian frailty distribution. We compare the two frailty models using the conditional predictive ordinate (CPO) statistic.