Miracle-dz/UniFAR-FTUs huggingface dataset:
Causal sets from computations : the case of Turing machines

Causality among events is widely recognized as a most fundamental structure of spacetime, and causal sets have been proposed as discrete models of the latter in the context of quantum gravity theories, notably in the Causal Set Programme. In the rather different context of what might be called the 'Computational Universe Programme' -one which associates the complexity of physical phenomena to the emergent features of models such as cellular automata -a choice problem arises with respect to the variety of formal systems that, in virtue of their computational universality (Turing-completeness), qualify as equally good candidates for a computational, unified theory of physics. This paper proposes Causal Sets as the only objects of physical significance and relevance to be considered under the 'computational universe' perspective, and as the appropriate abstraction for shielding the unessential details of the many different computationally universal candidate models. At the same time, we propose a fully deterministic, radical alternative to the probabilistic techniques currently considered in the Causal Set Programme for growing discrete spacetimes. We investigate a number of computation models by grouping them into two broad classes, based on the support on which they operate; in one case this is linear, like a tape or a string of symbols; in the other, it is a two-dimensional grid or a planar graph. For each model we identify the causality relation among computation events, implement it, and conduct a possibly exhaustive exploration of the associated causal set space, while examining quantitative and qualitative features such as dimensionality, curvature, planarity, emergence of pseudo-randomness, causal set substructures and particles.
Entry Glycoproteins HSVKinetics of Cell-Cell Fusion Induced by Virus ( HSV ) Glycoprotein gB Alter the Reveals that Mutations to Herpes Simplex Dual Split Protein-Based Fusion Assay

Published Ahead of Print 14 August 2013. 2013, 87(21):11332. DOI: 10.1128/JVI.01700-13. J. Virol. and Roselyn J. Eisenberg Cohen Hannah, Zene Matsuda, J. Charles Whitbeck, Gary H. Doina Atanasiu, Wan Ting Saw, John R. Gallagher, Brian P. Entry Glycoproteins HSV Kinetics of Cell-Cell Fusion Induced by Virus (HSV) Glycoprotein gB Alter the Reveals that Mutations to Herpes Simplex Dual Split Protein-Based Fusion Assay
Rapid analysis of inflammatory cytokines in cerebrospinal fluid using chip‐based immunoaffinity electrophoresis

A chip‐based capillary electrophoresis system has been designed for rapidly measuring the concentrations of inflammatory cytokines in the cerebrospinal fluid of patients with head trauma. Isolation of the reactive cytokines was achieved by immunoaffinity capture using a panel of six immobilized antibodies, directly attached to the injection port of the chip. The captured cytokines were labeled in situ with a red light‐emitting laser dye and electroeluted into the separation channel. Separation of the isolated cytokines was achieved by electrophoresis in under 2 min with quantification of the resolved peaks being achieved by on‐line laser‐induced fluorescence and integration of each peak area. Comparison of the results to commercially available high‐sensitivity immunoassays demonstrates that the chip‐based assay provides a fast, accurate procedure for studying the concentrations of these analytes in complex biological materials. The degree of accuracy and precision achieved by the chip‐based CE is comparable to conventional immunoassays, the system being able to analyze between 10–12 samples per hour. With the ever‐expanding array of antibodies that are commercially available, this chip‐based system can be applied to a wide variety of different analyses.
Pheochromocytoma associated with pregnancy: unexpected favourable outcome in patients diagnosed after delivery

Objective: The objective of this study is to present the clinical findings and outcome of a large cohort of pregnant women with pheochromocytoma (PHEO) with the aim to contribute to the better recognition, detection and management of pregnancy-related PHEO in the population of pregnant patients with hypertension. Methods: This is a longitudinal follow-up of a single cohort of 15 patients aged 19–40 years with PHEO associated with pregnancy. Urinary catecholamines and vanillylmandelic acid (VMA) were analysed. Ret proto-oncogene, SDHB and VHL mutations were determined in germline DNA from seven women using PCR followed by direct sequencing. Results: During pregnancy, all women presented typical features of catecholamines excess. Nevertheless, biochemical diagnosis was performed only in four out of 15 cases during pregnancy and postpartum in the remaining 11. Paroxysmal hypertension was the predominant pattern. Urinary catecholamines and/or VMA were increased in all patients. Tumours were adrenal in 13 patients and extraadrenal in two. Mutations in the Ret proto-oncogene were found in four patients, in the VHL gene in one and in the SDHB gene in one. Antihypertensive treatment resulted in effective control of blood pressure and all women survived. In the group of women diagnosed postpartum, one foetus demised. Newborns from mothers receiving adequate treatment survived. One woman left the hospital after caesarean section but before PHEO surgery became pregnant again and this gestation ended with maternal-foetal dead. Conclusion: A high index of suspicion in all pregnant women presenting hypertension mainly paroxystic during any gestational phase and/or a history of familial PHEO are the keys to disclose this important diagnosis.
Role of Adipokines in the Association between Thyroid Hormone and Components of the Metabolic Syndrome

Metabolic syndrome (MS) increases cardiovascular risk. The role of thyroid hormone on components of MS is unclear. We analyzed a sample of 4733 euthyroid subjects from SardiNIA study. In female thyrotropin (TSH) was significantly and positively associated with triglycerides (Standardized regression coefficients (β) = 0.081, p < 0.001). Free thyroxine (FT4) was positively associated with HDL (β = 0.056, p < 0.01), systolic blood pressure (SBP) (β = 0.059, p < 0.001), diastolic blood pressure (DBP) (β = 0.044, p < 0.01), and fasting glucose (β = 0.046, p < 0.01). Conversely, FT4 showed a negative association with waist circumference (β = −0.052, p < 0.001). In TSH was positively associated with triglycerides (β = 0.111, p < 0.001) and FT4 showed a positive association with DBP (β = 0.51, p < 0.01). The addition of leptin and adiponectin to the regression models did not substantially change the impact of thyroid hormones on components of MS. Our data suggest that, even within the euthyroid range, excess of truncal adipose tissue is associated with variations in FT4. Leptin and adiponectin exert an additive effect rather than a causal effect. Additional studies should be performed to determine the clinical significance of this finding.
University of Birmingham Investigation of the effect of the water to powder ratio on hydraulic cement properties

Objectives. The use of rheological properties to determine the optimal water: powder ratio of tricalcium silicate-based prototype materials incorporating alternative radiopacifiers and fillers. Determination of how the proportion of water incorporated affected the physicochemical behaviour of the materials. Methods. Endodontic cements replaced with 30% radio-opacifier, and additions of calcium phosphate and micro-silica were tested. The unmodified cements were mixed with a 0.35 water: powder ratio which served as control. At this water: powder ratio, the paste had an adequate clinical consistency and furthermore these pastes have been well characterized. Assessment of material rheological properties enabled adjustment of the water: powder ratio in each material to provide comparable viscosity values to those of the controls. The flowability, phase analysis and calcium release were measured for both viscosity-matched and the standard 0.35 water: powder ratio blends. The prototype materials with the adjusted water ratio were also characterized by scanning electron microscopy, energy-dispersive spectroscopy and evaluated for radio-opacity. Results. The use of the 0.35 water: powder ratio is not appropriate when changing the radiopacifier and incorporating additives. Zirconium oxide did not vary the water: powder ratio but tantalum oxide and calcium tungstate resulted in an increase and decrease in water demand respectively. Using the standard 0.35 ratio when the mixture had a low water demand resulted in higher flowability values and calcium release in solution. Micro-silica and calcium phosphate altered the hydration of the materials. All materials were adequately radiopaque. Significance. Rheological assessment is an easy reproducible way to determine the water: powder ratios of materials with varying amounts of additives and radiopacifiers during development. Modifications to the water: powder ratio affects material properties.
High α B-crystallin and p53 co-expression is associated with poor prognosis in ovarian cancer

OBJECTIVES The present study investigated the correlation between α B-crystallin (CRYAB, HSPB5) and p53 expression in ovarian cancer and further analyzed the relationship between their expression and clinicopathology and the prognostic value of their co-expression in ovarian cancer. METHODS CRYAB and p53 expression was assessed using immunohistochemistry on ovarian cancer tumor tissues from 103 cases and validated in an independent group of 103 ovarian cancer patients. RESULTS High CRYAB and p53 expression rates in ovarian cancer tissues were 61.17% (63/103) and 57.28% (59/103), respectively, and their expression was positively correlated (r = 0.525, P=0.000). High CRYAB expression was significantly correlated with tumor size (P=0.028), lymph node metastasis (P=0.000), distant metastasis (P=0.005), tumor node metastasis (TNM) stage (P=0.002), and survival (P=0.000), while high p53 expression was significantly correlated with tumor size (P=0.006), pathological grade (P=0.023), lymph node metastasis (P=0.001), and survival (P=0.000). Further studies found that the high CRYAB and p53 co-expression was also significantly correlated with pathological grade (P=0.024), lymph node metastasis (P=0.000), Distant metastasis (P=0.015), TNM stage (P=0.013), and survival (P=0.000). High expression of either CRYAB or p53 and high co-expression of CRYAB and p53 were significantly correlated with poor disease-free survival (DFS) and overall survival (OS), respectively (P<0.05). Patients with high CRYAB and p53 co-expression had the worst prognoses among the groups. In addition, multivariate Cox regression models showed that high expression of either CRYAB or p53 and high co-expression of CRYAB and p53 were independent prognostic factors for DFS and OS (P<0.05). Moreover, the positive correlation and prognostic value of CRYAB and p53 expression were verified in another independent dataset. CONCLUSIONS We demonstrated that patients with high CRYAB and p53 co-expression in ovarian cancer have significantly increased risks of recurrence, metastasis, and death compared with other patients. Therefore, more frequent follow-up of patients with high CRYAB and p53 co-expression is required. Our results also suggest that combination therapy with CRYAB inhibitors and p53 blockers may benefit future treatment of ovarian cancer patients with high co-expression of CRYAB and p53.
A Mobile Phone App for the Self-Management of Pediatric Concussion: Development and Usability Testing

Background Concussion is a common injury among Canadian children and adolescents that leads to a range of neurobehavioral deficits. However, noticeable gaps continue to exist in the management of pediatric concussion, with poor health outcomes associated with the inadequate application of best practice guidelines. Objective The aim of this study was to describe the development and assess the usability of a mobile phone app to aid youth in the self-management of concussion. A secondary objective was to assess the usefulness of the app. Methods An agile user-centered design approach was used to develop the technology, followed by a formative lab-based usability study for assessment and improvement proposals. Youths aged 10 to 18 years with a history of concussion and health care professionals involved in concussion management were recruited. This study included participants performing 12 tasks with the mobile phone app while using the think aloud protocol and the administration of the System Usability Scale (SUS), posttest questionnaire, and a semistructured interview. Results A mobile phone app prototype called NeuroCare, an easily accessible pediatric concussion management intervention that provides easy access to expert-informed concussion management strategies and helps guide youth in self-managing and tracking their concussion recovery, was developed. A total of 7 youths aged between 10 and 18 years with a history of concussion and 7 health care professionals were recruited. The mean SUS score was 81.9, mean task success rates were greater than 90% for 92% (11/12) of the tasks, 92% (11/12) of tasks had a total error frequency of less than 11 errors, and mean task completion times were less than 2 min for 100% of the tasks. Conclusions Results suggest that participants rated this app as highly usable, acceptable to users, and that it may be useful in helping youth self-manage concussion.
Ageing and muscular dystrophy differentially affect murine pharyngeal muscles in a region‐dependent manner

Millions of elderly individuals have dysphagia, a debilitating and life‐threatening condition in which the ability to swallow is impaired. Several muscles surround the three regions of the pharynx, which are essential for proper swallowing, yet the effects of ageing and disease on these muscles are not well understood. We demonstrate that the fibre size of murine pharyngeal muscles is differentially affected by ageing and muscular dystrophy depending on their location within the pharynx. Using a mouse model of an age‐associated dysphagic disease (oculopharyngeal muscular dystrophy), we show that overexpression of wild‐type polyadenylate binding nuclear protein 1 in muscle tissue prevents age‐related dysphagia and age‐related muscle atrophy of laryngopharyngeal muscles. These results demonstrate that mice are an excellent model for studying mechanisms of ageing and disease on pharyngeal muscle physiology, and such studies could lead to new therapies for individuals with dysphagia.
Adolescents' Engagement with Crisis Hotline Risk-management Services: A Report from the Emergency Department Screen for Teen Suicide Risk (ED-STARS) Study.

OBJECTIVE This study examines the feasibility of a risk-management protocol for adolescent research participants at risk for suicide that relies on engagement with telephone crisis counselors. The study also examines whether engagement is moderated by adolescent demographics and clinical characteristics. METHOD Participants were 234 adolescents (83% female; 63% White) ages 12-18 (M = 15.3 years) drawn from the national study, Emergency Department Screen for Teens at Risk for Suicide (ED-STARS) Study One sample of adolescents randomized for 3-month telephone follow-up (n = 2,850). This study's sample was comprised of adolescents who completed the follow-up (69% retention), met study risk criteria, and were transferred to a crisis hotline for risk management. Engagement with a counselor was assessed by successful call connection, call duration, and information sharing. RESULTS Ninety-four percent of calls resulted in a successful call transfer, and the majority of youth (84%) shared information with counselor about one or more coping strategies. Average call length was 12.6 min (SD = 9.9). Engagement did not vary by gender, race, age, ethnicity, or clinical characteristics. CONCLUSIONS Adolescents' engagement with telephone risk-management services was strong, suggesting that this strategy can address safety. Further, findings suggest telephone risk-management services effectively engage youth across demographic and clinical subgroups.
Clinical Improvements in Comorbid Gambling/Cocaine Use Disorder (GD/CUD) Patients Undergoing Repetitive Transcranial Magnetic Stimulation (rTMS)

(1) Background: Pathological gambling behaviors may coexist with cocaine use disorder (CUD), underlying common pathogenic mechanisms. Repetitive transcranial magnetic stimulation (rTMS) has shown promise as a therapeutic intervention for CUD. In this case series, we evaluated the clinical effects of rTMS protocol stimulating the left dorsolateral prefrontal cortex (DLPFC) on the pattern of gambling and cocaine use. (2) Methods: Gambling severity, craving for cocaine, sleep, and other negative affect symptoms were recorded in seven patients with a diagnosis of gambling disorder (South Oaks Gambling Screen (SOGS) >5), in comorbidity with CUD, using the following scales: Gambling-Symptom Assessment Scale (G-SAS), Cocaine Craving Questionnaire (CCQ), Beck Depression Inventory-II (BDI-II), Self-rating Anxiety Scale (SAS), and Symptoms checklist-90 (SCL-90). The measures were assessed before the rTMS treatment and after 5, 30, and 60 days of treatment. Patterns of gambling and cocaine use were assessed by self-report and regular urine screens. (3) Results: Gambling severity at baseline ranged from mild to severe (mean ± Standard Error of the Mean (SEM), G-SAS score baseline: 24.42 ± 2.79). G-SAS scores significantly improved after treatment (G-SAS score Day 60: 2.66 ± 1.08). Compared to baseline, consistent improvements were significantly seen in craving for cocaine and in negative-affect symptoms. (4) Conclusions: The present findings provide unprecedent insights into the potential role of rTMS as a therapeutic intervention for reducing both gambling and cocaine use in patients with a dual diagnosis.
EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS) is a recessive disorder typified by bone marrow failure and predisposition to hematological malignancies. SDS is predominantly caused by deficiency of the allosteric regulator SBDS that cooperates with the GTPase EFL1 to catalyze release of the ribosome anti-association factor eIF6 and activate translation. Here, we report biallelic mutations in EFL1 in three unrelated individuals with clinical features of SDS. Cellular defects in these individuals include impaired ribosomal subunit joining and attenuated global protein translation as a consequence of defective eIF6 eviction. In mice, Efl1 deficiency recapitulates key aspects of the SDS phenotype. By identifying biallelic EFL1 mutations in SDS, we define this leukemia predisposition disorder as a ribosomopathy that is caused by corruption of a fundamental, conserved mechanism, which licenses entry of the large ribosomal subunit into translation.
Hostile attribution bias and angry rumination: A longitudinal study of undergraduate students

Angry rumination and hostile attribution bias are important cognitive factors of aggression. Although prior theoretical models of aggression suggest that aggressive cognitive factors may influence each other, there are no studies examining the longitudinal relationship between angry rumination and hostile attribution bias. The present study used cross-lagged structural equation modeling to explore the longitudinal mutual relationship between hostile attribution bias and angry rumination; 941 undergraduate students (38.5% male) completed questionnaires assessing the variables at two time points. The results indicate that hostile attribution bias showed a small but statistically significant effect on angry rumination 6 months later, and angry rumination showed a quite small but marginally significant effect on hostile attribution bias across time. The present study supports the idea that hostile attribution bias influences angry rumination, and argue that the relationship between angry rumination and hostile attribution bias may be mutual. Additionally, the results suggest that there may be a causal relation of different aggression-related cognitive factors.
Golgi-resident TRIO regulates membrane trafficking during neurite outgrowth

Neurite outgrowth requires coordinated cytoskeletal rearrangements in the growth cone and directional membrane delivery from the neuronal soma. As an essential Rho guanine nucleotide exchange factor (GEF), TRIO is necessary for cytoskeletal dynamics during neurite outgrowth, but its participation in the membrane delivery is unclear. Using co-localization studies, live-cell imaging, and fluorescence recovery after photobleaching analysis, along with neurite outgrowth assay and various biochemical approaches, we here report that in mouse cerebellar granule neurons, TRIO protein pools at the Golgi and regulates membrane trafficking by controlling the directional maintenance of both RAB8 (member RAS oncogene family 8)– and RAB10-positive membrane vesicles. We found that the spectrin repeats in Golgi-resident TRIO confer RAB8 and RAB10 activation by interacting with and activating the RAB GEF RABIN8. Constitutively active RAB8 or RAB10 could partially restore the neurite outgrowth of TRIO-deficient cerebellar granule neurons, suggesting that TRIO-regulated membrane trafficking has an important functional role in neurite outgrowth. Our results also suggest cross-talk between Rho GEF and Rab GEF in controlling both cytoskeletal dynamics and membrane trafficking during neuronal development. They further highlight how protein pools localized to specific organelles regulate crucial cellular activities and functions. In conclusion, our findings indicate that TRIO regulates membrane trafficking during neurite outgrowth in coordination with its GEF-dependent function in controlling cytoskeletal dynamics via Rho GTPases.
Musashi interaction with poly(A)-binding protein is required for activation of target mRNA translation

The Musashi family of mRNA translational regulators controls both physiological and pathological stem cell self-renewal primarily by repressing target mRNAs that promote differentiation. In response to differentiation cues, Musashi can switch from a repressor to an activator of target mRNA translation. However, the molecular events that distinguish Musashi-mediated translational activation from repression are not understood. We have previously reported that Musashi function is required for the maturation of Xenopus oocytes and specifically for translational activation of specific dormant maternal mRNAs. Here, we employed MS to identify cellular factors necessary for Musashi-dependent mRNA translational activation. We report that Musashi1 needs to associate with the embryonic poly(A)-binding protein (ePABP) or the canonical somatic cell poly(A)-binding protein PABPC1 for activation of Musashi target mRNA translation. Co-immunoprecipitation studies demonstrated an increased Musashi1 interaction with ePABP during oocyte maturation. Attenuation of endogenous ePABP activity severely compromised Musashi function, preventing downstream signaling and blocking oocyte maturation. Ectopic expression of either ePABP or PABPC1 restored Musashi-dependent mRNA translational activation and maturation of ePABP-attenuated oocytes. Consistent with these Xenopus findings, PABPC1 remained associated with Musashi under conditions of Musashi target mRNA de-repression and translation during mammalian stem cell differentiation. Because association of Musashi1 with poly(A)-binding proteins has previously been implicated only in repression of Musashi target mRNAs, our findings reveal novel context-dependent roles for the interaction of Musashi with poly(A)-binding protein family members in response to extracellular cues that control cell fate.