Miracle-dz/UniFAR-FTUs huggingface dataset:
Gut-brain peptides in corticostriatal-limbic circuitry and alcohol use disorders

Peptides synthesized in endocrine cells in the gastrointestinal tract and neurons are traditionally considered regulators of metabolism, energy intake, and appetite. However, recent work has demonstrated that many of these peptides act on corticostriatal-limbic circuitry and, in turn, regulate addictive behaviors. Given that alcohol is a source of energy and an addictive substance, it is not surprising that increasing evidence supports a role for gut-brain peptides specifically in alcohol use disorders (AUD). In this review, we discuss the effects of several gut-brain peptides on alcohol-related behaviors and the potential mechanisms by which these gut-brain peptides may interfere with alcohol-induced changes in corticostriatal-limbic circuitry. This review provides a summary of current knowledge on gut-brain peptides focusing on five peptides: neurotensin, glucagon-like peptide 1, ghrelin, substance P, and neuropeptide Y. Our review will be helpful to develop novel therapeutic targets for AUD.
A similarity-based method for the generalization of face recognition over pose and expression

Human observers are capable of recognizing a face seen only once before when confronted with it subsequently under different viewing conditions. We constructed a working computational model of such generalization from a single view, and tested it on a homogeneous database of face images obtained under tightly controlled viewing conditions. The model effectively constructs a view space for novel faces by interpolating view spaces of familiar ones. Its performance /spl sim/30% error rate in one out of 18 recognition, and 8% in one out of three discrimination-is encouraging, given that it reflects generalization from a single view/expression to a range of /spl plusmn/34/spl deg/ rotation in depth and to two additional expressions. For comparison, human subjects in the one out of three task involving only viewpoint changes exhibit a 3% error rate.
Narrow Networks on the Health Insurance Exchanges: What Do They Look Like and How Do They Affect Pricing? A Case Study of Texas.

The Affordable Care Act has engendered significant changes in the design of health insurance products. We examine the "narrowness" of hospital networks affiliated with plans offered in the first year of the marketplaces. Using data from Texas, we find limited evidence of a tight link between pricing and a simple measure of network breadth, or a more complex measure of network value derived from a logit model of hospital choice. The state's largest insurer priced its narrow networks at a fairly constant discount relative to its broad networks, notwithstanding significant variation in its broad-narrow gap across geographic markets in Texas.
Formalising argumentative story-based analysis of evidence

In the present paper, we provide a formalised version of a merged argumentative and story-based approach towards the analysis of evidence. As an application, we are able to show how our approach sheds new light on inference to the best explanation with case evidence. More specifically, it will be clarified how the events in a case story that are considered to be proven abductively explain the otherwise unproven events of the case story. We compare our approach with existing AI work on modelling legal reasoning with evidence.
A scalable architecture for providing deterministic guarantees

The Internet community has proposed the integrated services architecture (Intserv) and the signaling protocol RSVP to provide deterministic guarantees (bandwidth, delay and jitter) to individual flows. However, experience with practical systems has revealed the severe scalability problems of the Intserv model due to the amount of routing and reservation state that is required to he maintained in the routers. A natural approach to improving scalability of the Intserv architecture is through a reduction of the number of states in the routers by using aggregated flow state instead of per-flow state. We present a novel architecture that uses very few states in the routers, while still providing the deterministic guarantees of the Intserv model.
Clinical Significance of Epidermal Growth Factor Receptor Protein Overexpression and Gene Copy Number Gains in Prostate Cancer

Purpose: The epidermal growth factor receptor (EGFR) is a protein involved in the tumor progression of many cancer types and is an important therapeutic target. To determine its role in prostate cancer, we analyzed 2,497 prostate cancers on the DNA and protein level. Experimental Design: Tissue samples from each tumor were brought into a tissue microarray and analyzed by immunohistochemistry and fluorescence in situ hybridization. A subset of cancers was also sequenced for EGFR exon 18 to 21 mutations. Results: Detectable EGFR expression was found in 18% of cancers and was significantly associated with high grade, advanced stage, and high risk for prostate-specific antigen recurrence in univariate analysis (P < 0.0001, each). Fluorescence in situ hybridization analysis with a dual-labeling probe for centromere 7 and EGFR showed increased EGFR copy number in 3.3% of cases. EGFR copy number gains were mostly due to an overrepresentation of the entire chromosome and were associated with EGFR protein expression (P < 0.0001), high grade (P < 0.0001), and advanced stage (P = 0.0056). Only one cancer had a high-level amplification (>20 EGFR gene copies per cell). This amplification was heterogeneous, involving only ∼30% of the cancer volume. EGFR mutations were not found in 35 of the cases analyzed. Conclusion: Increased EGFR expression is often seen in prostate cancer and is associated with poor prognosis. The significant association of EGFR copy number gains with protein expression argues for the significant role of minimal gene copy number changes for protein expression. Although EGFR expression was not an independent prognostic variable, the potential utility of anti-EGFR medications might be worth further investigation in EGFR-expressing prostate cancer.
A model for Ti–6Al–4V microstructure evolution for arbitrary temperature changes

This paper presents a microstructure model for the titanium alloy Ti–6Al–4V designed to be used in coupled thermo-metallurgical-mechanical simulations of, e.g., welding processes. The microstructure evolution is increasingly taken into consideration in analyses of manufacturing processes since it directly affects the mechanical properties. Thermally driven phase evolutions are accounted for in the model. A state variable approach is adopted to represent the microstructure with the objective to integrate the microstructure changes with a thermo-mechanical model of manufacturing process simulation such as welding. The model is calibrated using the literature data and also validated against a cyclic temperature history during multi-pass welding.
Hydroxyurea Therapy Mobilises Arachidonic Acid from Inner Cell Membrane Aminophospholipids in Patients with Homozygous Sickle Cell Disease

The cytotoxic compound hydroxyurea (HU) is effective therapy for sickle cell disease. However, its effect on unsaturated membrane lipids is unknown. Red cell fatty acids were investigated in HU-treated (n = 19) and HU-untreated (n = 17) sickle cell patients and controls (n = 20). The HU-treated compared with the HU-untreated patients had lower arachidonic (AA) acid level in ethanolamine, physphoglycerids (EPG) (22.9 ± 1.2 versus 24.0 ± 1.1%, P < 0.05) serine SPG (22.13 ± 2.2 versus 24.9 ± 2.3%, P < 0.01) phosphoglycerides. The treated patients and controls had comparable levels of docosahexaenoic (DHA) and total n-3 fatty acids in EPG and choline phosphoglycerides (CPG). In contrast, the untreated group had significantly (P < 0.05) lower DHA and total n-3 compared with the controls in EPG (2.7 ± 0.4 versus 3.2 ± 0.6% and 4.6 ± 0.5 versus 5.2 ± 0.7%) and CPG (0.7 ± 0.2 versus 1.0 ± 0.2% and 1.2 ± 0.2 versus 1.4 ± 0.3). HU is known to activate cytosolic phospholipase A2 and cyclooxygenase 2, and from this study, it appears to induce mobilisation of AA from the inner cell membrane EPG and SPG. Hence, eicosanoids generated from the released AA may play a role in clinical improvements which occur in HU-treated patients.
Detection of snRNP assembly intermediates in Cajal bodies by fluorescence resonance energy transfer

Spliceosomal small nuclear ribonucleoprotein particles (snRNPs) are required for pre-mRNA splicing throughout the nucleoplasm, yet snRNPs also concentrate in Cajal bodies (CBs). To address a proposed role of CBs in snRNP assembly, we have used fluorescence resonance energy transfer (FRET) microscopy to investigate the subnuclear distribution of specific snRNP intermediates. Two distinct complexes containing the protein SART3 (p110), required for U4/U6 snRNP assembly, were localized: SART3•U6 snRNP and SART3•U4/U6 snRNP. These complexes segregated to different nuclear compartments, with SART3•U6 snRNPs exclusively in the nucleoplasm and SART3•U4/U6 snRNPs preferentially in CBs. Mutant cells lacking the CB-specific protein coilin and consequently lacking CBs exhibited increased nucleoplasmic levels of SART3•U4/U6 snRNP complexes. Reconstitution of CBs in these cells by expression of exogenous coilin restored accumulation of SART3•U4/U6 snRNP in CBs. Thus, while some U4/U6 snRNP assembly can occur in the nucleoplasm, these data provide evidence that SART3•U6 snRNPs form in the nucleoplasm and translocate to CBs where U4/U6 snRNP assembly occurs.
The (neuro)cognitive mechanisms behind attention bias modification in anxiety: proposals based on theoretical accounts of attentional bias

Recently, researchers have investigated the causal nature of attentional bias for threat (AB) in the maintenance of anxiety disorders by experimentally manipulating it. They found that training anxious individuals to attend to non-threat stimuli reduces AB, which, in turn, reduces anxiety. This effect supports the hypothesis that AB can causally impact the maintenance of anxiety. At a fundamental level, however, uncertainty still abounds regarding the nature of the processes that mediate this effect. In the present paper, we propose that two contrasting approaches may be derived from theoretical accounts of AB. According to a first class of models, called the “valence-specific bias” models, modifying AB requires the modification of valence-specific attentional selectivity. According to a second class of models, called the “attention control models,” modifying AB requires the modification of attention control, driven by the recruitment of the dorsolateral prefrontal cortex. We formulate a series of specific predictions, to provide suggestions to trial these two approaches one against the other. This knowledge is critical for understanding the mechanisms of AB in anxiety disorders, which bares important clinical implications.
Towards Trace Based Model Synthesis for Program Understanding and Test Automation

Effective maintenance and evolution of complex, software intensive systems requires understanding how the system works and having tests available to verify the effects of changes. Understanding complex systems is difficult, and testability of these systems is often low due to design constraints, system complexity and long- term evolution. Thus understanding the system and adding new tests is difficult. Yet, especially in these cases, the understanding and tests are important to verify the system correctness over long-term evolution. This paper discusses synthesizing models from system traces and using these models to facilitate program understanding and test automation. Basing the models on execution traces allows generation of automated tests even for low testability systems. Generating and visualizing abstracted models facilitates program understanding, which helps in system maintenance.
Impairment of Health‐Related Quality of Life in Patients With Inflammatory Bowel Disease: a Spanish Multicenter Study

Background: Inflammatory bowel disease impairs patients' perception of health and has a negative impact on health‐related quality of life (HRQOL). Most studies include patients from a single hospital. This may bias limit results through the use of small patient samples and/or samples within a restricted disease spectrum. Methods: HRQOL was measured in patients with ulcerative colitis (UC) and Crohn's disease (CD) from 9 hospitals located in different geographical areas in Spain using 2 questionnaires: the Spanish version of the Inflammatory Bowel Disease Questionnaire (IBDQ) and the EuroQol. Results are expressed as medians. Results: The study included 1156 patients (528 patients with UC and 628 with CD; median age, 35 yr; slight predominance of women, 617 versus 539). HRQOL worsened in parallel with disease severity to a similar extent in both UC (IBDQ scores of 6.1, 4.7, and 4.0 for the 3 disease severity groups, respectively) and CD (IBDQ scores of 6.1, 5.0, and 4.1, respectively). A similar inverse relation between clinical activity and quality of life was observed when EuroQol preference values were used. All 5 dimensions of the IBDQ showed significantly lower scores in patients with active UC and CD than in patients in remission. The pattern of scores by IBDQ dimensions differed between patients in relapse (who scored worse on the digestive symptoms dimension) and patients in remission. Variables related with disease activity, time of evolution since diagnosis and female sex, were significantly associated with having a worse perception of HRQOL. The type of disease or geographical area of residence did not influence results on the IBDQ. Conclusions: UC and CD impair patients' HRQOL, and the degree of impairment depends on disease activity but is independent of the type of disease and place of residence.
Running stability is enhanced by a proximo-distal gradient in joint neuromechanical control

SUMMARY We currently know little about how animals achieve dynamic stability when running over uneven and unpredictable terrain, often characteristic of their natural environment. Here we investigate how limb and joint mechanics of an avian biped, the helmeted guinea fowl Numida meleagris, respond to an unexpected drop in terrain during running. In particular, we address how joint mechanics are coordinated to achieve whole limb dynamics. Based on muscle–tendon architecture and previous studies of steady and incline locomotion, we hypothesize a proximo-distal gradient in joint neuromechanical control. In this motor control strategy, (1) proximal muscles at the hip and knee joints are controlled primarily in a feedforward manner and exhibit load-insensitive mechanical performance, and (2) distal muscles at the ankle and tarsometatarso-phalangeal (TMP) joints are highly load-sensitive, due to intrinsic mechanical effects and rapid, higher gain proprioceptive feedback. Limb kinematics and kinetics during the unexpected perturbation reveal that limb retraction, controlled largely by the hip, remains similar to level running throughout the perturbed step, despite altered limb loading. Individual joints produce or absorb energy during both level and perturbed running steps, such that the net limb work depends on the balance of energy among the joints. The hip maintains the same mechanical role regardless of limb loading, whereas the ankle and TMP switch between spring-like or damping function depending on limb posture at ground contact. Initial knee angle sets limb posture and alters the balance of work among the joints, although the knee contributes little work itself. This distribution of joint function results in posture-dependent changes in work performance of the limb, which allow guinea fowl to rapidly produce or absorb energy in response to the perturbation. The results support the hypothesis that a proximo-distal gradient exists in limb neuromuscular performance and motor control. This control strategy allows limb cycling to remain constant, whereas limb posture, loading and energy performance are interdependent. We propose that this control strategy provides simple, rapid mechanisms for managing energy and controlling velocity when running over rough terrain.
Toward First-Principle Simulations of Galaxy Formation: I. How Should We Choose Star-Formation Criteria in High-Resolution Simulations of Disk Galaxies?

We performed three-dimensional N -body/SPH simulations to study how mass resolution and other model param- eters, such as the star-formation efficiency parameter, Cand the threshold density for star formation, nth affect structures of the galactic gaseous/stellar disk. We employed 10 6 -10 7 particles to resolve a cold ( T 100 cm � 3 ) phase as well as diffuse, hot phases. We found that structures of the interstellar medium (ISM) and the distribution of young stars were sensitive to the assumed values of nth. High-nth models with nth = 100 cm � 3 yielded clumpy multi-phase features in the ISM. Young stars were distributed in a thin disk, of which the half-mass scale height was 10-30 pc. In low-nth models with nth = 0.1 cm � 3 , which is usually employed in cosmological galaxy-formation simulations, the gas disk appears to be smoother and the stellar disk is found to be several-times thicker than the high-nth models. A high-resolution simulation with high-nth is necessary to reproduce the complex structure of the gas disk. The global star-formation properties of galaxies, such as the star-formation history, in low-nth models are similar to those in high-nth models when we tune the value of Cso that they repro- duce the observed relation between the surface gas density and the surface star-formation rate density. We however emphasize that high-nth models automatically reproduce the relation, regardless of the values of C� . T he ISM structure, phase distribution and distributions of young star-forming regions are quite similar in runs with different values of C� . We found that the timescale of the flow from the reservoir (nH � 1c m � 3 ) to the star-forming regions (nH & 100cm � 3 ) is about five-times as long as the local dynamical time, and this evolution timescale is independent
Cognitive Impairments in Schizophrenia and Schizoaffective Disorder: Relationship With Clinical Characteristics

Abstract The present study aimed to compare population-based familial samples of patients with schizophrenia (n = 218) and schizoaffective disorder (n = 62) and a healthy control group (n = 123). Patients with schizoaffective disorder outperformed patients with schizophrenia in verbal ability, processing speed, visual working memory, and verbal memory. When compared with controls, patients with schizoaffective disorder also had a generalized cognitive impairment. Adjusting for clinical characteristics removed significant differences between the patient groups. Irrespective of the diagnosis, patients with the most severe negative symptoms and highest dose of antipsychotics had the most severe cognitive impairments, whereas mood symptoms were not related to cognitive performance. In conclusion, people with schizoaffective disorder have severe cognitive impairments, but the impairments are milder than in schizophrenia. Mood symptoms may not explain the difference between the diagnostic groups in cognitive functions, but the difference may be related to differences in the severity of negative symptoms.
Lipoprotein Subfractions Highly Associated With Renal Damage in Familial Lecithin: Cholesterol Acyltransferase Deficiency

Objective— In familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD), deposition of abnormal lipoproteins in the renal stroma ultimately leads to renal failure. However, fish-eye disease (FED) does not lead to renal damage although the causative mutations for both FLD and FED lie within the same LCAT gene. This study was performed to identify the lipoproteins important for the development of renal failure in genetically diagnosed FLD in comparison with FED, using high-performance liquid chromatography with a gel filtration column. Approach and Results— Lipoprotein profiles of 9 patients with LCAT deficiency were examined. Four lipoprotein fractions specific to both FLD and FED were identified: (1) large lipoproteins (>80 nm), (2) lipoproteins corresponding to large low-density lipoprotein (LDL), (3) lipoproteins corresponding to small LDL to large high-density lipoprotein, and (4) to small high-density lipoprotein. Contents of cholesteryl ester and triglyceride of the large LDL in FLD (below detection limit and 45.8±3.8%) and FED (20.7±6.4% and 28.0±6.5%) were significantly different, respectively. On in vitro incubation with recombinant LCAT, content of cholesteryl ester in the large LDL in FLD, but not in FED, was significantly increased (to 4.2±1.4%), whereas dysfunctional high-density lipoprotein was diminished in both FLD and FED. Conclusions— Our novel analytic approach using high-performance liquid chromatography with a gel filtration column identified large LDL and high-density lipoprotein with a composition specific to FLD, but not to FED. The abnormal lipoproteins were sensitive to treatment with recombinant LCAT and thus may play a causal role in the renal pathology of FLD.
Deep X-ray survey of the young open cluster NGC 2516 with XMM-Newton

We report on a deep X-ray survey of the young (~ 140 Myr), rich open cluster NGC 2516 obtained with the EPIC camera on board the XMM-Newton satellite. By combining data from six observations, a high sensitivity, greater than a factor 5 with respect to recent Chandra observations, has been achieved. We detected 431 X-ray sources and 234 of them have as optical counterparts cluster stars spanning the entire NGC 2516 Main Sequence. The X-ray luminosities of cluster stars span the range log Lx (erg/s) = 28.4 - 30.8. The representative temperatures span the 0.3 - 0.6 keV (3.5 - 8 MK) range for the cool component and 1.0 - 2.0 keV (12 -- 23 MK) for the hot one; similar values are found in other young open clusters like the Pleiades, IC 2391, and Blanco 1. While no significant differences are found in X-ray spectra, NGC 2516 solar type stars are definitely less luminous in X-rays than the nearly coeval Pleiades. The comparison with a previous ROSAT survey evidence the lack of variability amplitudes larger than a factor 2 in solar type stars in a ~11 yr time scale of the cluster and thus activity cycles like in the Sun are probably absent or different by period and amplitude in young stars.