Miracle-dz/UniFAR-FTUs huggingface dataset:
Mouse early extra-embryonic lineages activate compensatory endocytosis in response to poor maternal nutrition

Mammalian extra-embryonic lineages perform the crucial role of nutrient provision during gestation to support embryonic and fetal growth. These lineages derive from outer trophectoderm (TE) and internal primitive endoderm (PE) in the blastocyst and subsequently give rise to chorio-allantoic and visceral yolk sac placentae, respectively. We have shown maternal low protein diet exclusively during mouse preimplantation development (Emb-LPD) is sufficient to cause a compensatory increase in fetal and perinatal growth that correlates positively with increased adult-onset cardiovascular, metabolic and behavioural disease. Here, to investigate early mechanisms of compensatory nutrient provision, we assessed the influence of maternal Emb-LPD on endocytosis within extra-embryonic lineages using quantitative imaging and expression of markers and proteins involved. Blastocysts collected from Emb-LPD mothers within standard culture medium displayed enhanced TE endocytosis compared with embryos from control mothers with respect to the number and collective volume per cell of vesicles with endocytosed ligand and fluid and lysosomes, plus protein expression of megalin (Lrp2) LDL-family receptor. Endocytosis was also stimulated using similar criteria in the outer PE-like lineage of embryoid bodies formed from embryonic stem cell lines generated from Emb-LPD blastocysts. Using an in vitro model replicating the depleted amino acid (AA) composition found within the Emb-LPD uterine luminal fluid, we show TE endocytosis response is activated through reduced branched-chain AAs (leucine, isoleucine, valine). Moreover, activation appears mediated through RhoA GTPase signalling. Our data indicate early embryos regulate and stabilise endocytosis as a mechanism to compensate for poor maternal nutrient provision.
Network Meta-Analysis of Randomized Controlled Trials: Efficacy and Safety of UDCA-Based Therapies in Primary Biliary Cirrhosis

AbstractMajor ursodeoxycholic acid (UDCA)-based therapies for primary biliary cirrhosis (PBC) include UDCA only, or combined with either methotrexate (MTX), corticosteroids (COT), colchicine (COC), or bezafibrate (BEF). As the optimum treatment regimen is unclear and warrants exploration, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse events (AE). PubMed, the Cochrane Library, and Scopus were searched for randomized controlled trials up to August 31, 2014. We estimated the hazard ratios (HRs) for MOLT and odds ratios (ORs) for AE. A sensitivity analysis based on the dose of UDCA was also executed.Thirty-one eligible articles were included. Compared with COT plus UDCA, UDCA (HR 0.38, 95% confidence interval [CI] 0.09–1.39), BEF plus UDCA (HR 0.29, 95% CI 0.02–4.83), COC plus UDCA (HR 0.39, 95% CI 0.07–2.25), MTX plus UDCA (HR 0.28, 95% CI 0.05–1.63), or OBS (HR 0.49, 95% CI 0.11–2.01) all provided an increased risk of MOLT. With respect to drug AE profile, although not differing appreciably, BEF plus UDCA was associated with more AEs compared with UDCA (OR 3.16, 95% CI 0.59–20.67), COT plus UDCA (OR 2.27, 95% CI 0.15–33.36), COC plus UDCA (OR 1.00, 95% CI 0.09–12.16), MTX plus UDCA (OR 2.03, 95% CI 0.23–17.82), or OBS (OR 3.00, 95% CI 0.53–20.75). The results of sensitivity analyses were highly consistent with previous analyses.COT plus UDCA was the optimal UDCA-based regimen for both MOLT and AEs. BEF plus UDCA was most likely to cause AEs, whereas monotherapy with UDCA and coadministriation of COT plus UDCA appeared to be associated with the fewest AEs for PBC treatment.
On the optimal approximation of queries using tractable propositional languages

This paper investigates the problem of approximating conjunctive queries without self-joins on probabilistic databases by lower and upper bounds that can be computed more efficiently. We study this problem via an indirection: Given a propositional formula &phis;, find formulas in a more restricted language that are greatest lower bound and least upper bound, respectively, of &phis;. We study bounds in the languages of read-once formulas, where every variable occurs at most once, and of read-once formulas in disjunctive normal form. We show equivalences of syntactic and model-theoretic characterisations of optimal bounds for unate formulas, and present algorithms that can enumerate them with polynomial delay. Such bounds can be computed by queries expressed using first-order queries extended with transitive closure and a special choice construct. Besides probabilistic databases, these results can also benefit the problem of approximate query evaluation in relational databases, since the bounds expressed by queries can be computed in polynomial combined complexity.
Cognitive Distortions in Sexual Offenders: Should They All Be Treatment Targets?

In this paper we consider two sets of so-called 'cognitive distortions': those that have been shown to be unrelated to reoffending (i.e., noncriminogenic factors) and those that have been demonstrated to predict recidivism (i.e., criminogenic factors). While most sexual offender programs target the modification of all these distortions, we argue that treatment should only address the criminogenic attitudes and beliefs. Dissimulation characterises human responses to personal bad behaviour where the person attempts to present themselves as not having behaved in a harmful way and sexual offenders are no exception. As it turns out excuse-making is healthful and results in a reduction in reoffending. It may, therefore, not only be counter to accepted principles of offender treatment to attempt to change noncriminogenic distortions, it may result in increased rates of reoffending. However, those distortions that are criminogenic must be targeted in treatment if we are to reduce reoffending.
Pitch Syntax Violations Are Linked to Greater Skin Conductance Changes, Relative to Timbral Violations – The Predictive Role of the Reward System in Perspective of Cortico–subcortical Loops

According to contemporary opinion emotional reactions to syntactic violations are due to surprise as a result of the general mechanism of prediction. The classic view is that, the processing of musical syntax can be explained by activity of the cerebral cortex. However, some recent studies have indicated that subcortical brain structures, including those related to the processing of emotions, are also important during the processing of syntax. In order to check whether emotional reactions play a role in the processing of pitch syntax or are only the result of the general mechanism of prediction, the comparison of skin conductance levels reacting to three types of melodies were recorded. In this study, 28 subjects listened to three types of short melodies prepared in Musical Instrument Digital Interface Standard files (MIDI) – tonally correct, tonally violated (with one out-of-key – i.e., of high information content), and tonally correct but with one note played in a different timbre. The BioSemi ActiveTwo with two passive Nihon Kohden electrodes was used. Skin conductance levels were positively correlated with the presented stimuli (timbral changes and tonal violations). Although changes in skin conductance levels were also observed in response to the change in timbre, the reactions to tonal violations were significantly stronger. Therefore, despite the fact that timbral change is at least as equally unexpected as an out-of-key note, the processing of pitch syntax mainly generates increased activation of the sympathetic part of the autonomic nervous system. These results suggest that the cortico–subcortical loops (especially the anterior cingulate – limbic loop) may play an important role in the processing of musical syntax.
The Prefrontal Cortex and Hierarchical Behavior

Every day, often without thinking about it, you create and achieve goals. These goals range in complexity from brushing your teeth in the morning, to avoiding traffic on your way to school, to figuring out how you're ever going to graduate from Berkeley. The intricate workings of your prefrontal cortex enable the planning and execution of such behaviors. For years, scientists have studied the mechanisms of simple choice behavior and learning in the form of stimulus- and action-outcome associations but the question of how increasingly complex and temporally-extended learning arises remains largely unknown. Informed by converging work from the fields of psychology and computer science, we set out to understand the computations performed at the level of single cells that may contribute to the ideation, mental maintenance, and stringing together of actions to perform a hierarchical gambling task. We recorded extracellular activity from two subjects as they performed an n¬-armed bandit task and compared and contrasted the information processed simultaneously in three distinct brain areas: the lateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex. While our data do not support the preferential processing of superordinate versus subordinate goals in prefrontal cortex, we did find many signals that may underlie hierarchical behavior. These include value and action encoding that depended on the hierarchical level, as well as encoding of past choices that could be used to chunk actions at the same level of the hierarchy. Understanding these mechanisms could help elucidate how the complex behavioral repertoire of the primate is implemented.
Infections with FK 506 immunosuppression: preliminary results with primary therapy.

Infectious complications following orthotopic liver transplantation (OLT) remain the major cause of patient mortality and morbidity. Despite advances in technical and preservation management, these complications have not decreased significantly with present immunosuppression regimens. We have initiated the first human clinical trials of OLT under FK 506 immunosuppression, and report the infectious disease profile in this early experience.
Statistical Evidence and Inference

Understanding the methods used by economists requires some basic terminology regarding the distribution of random variables. The mean of a distribution is simply the arithmetic average of all of the observations. The median is the observation that falls in the middle; half of the observations have values below the median and half are above. Both the mean and the median are measures of the center of the distribution, but the median is less sensitive to extreme observations. The variance is the average squared deviation from the mean for all of the observations, and is a measure of the spread of the distribution around the mean. The standard deviation is the square root of the variance. The standard tool of economic data analysis is regression, which is a form of curve tting. The most common method of regression used is Ordinary Least Squares (OLS). OLS can be used to t any linear model of the form y = a+bx+e, where a is a constant and b is the coe¢ cient that describes how y changes with changes in x. Because the relationship between x and y is not expected to hold exactly for every individual, there is an error term, e. For example, the relationship between age and hours worked (Figure 24) can be described as hours = a+ b age+ e, and OLS used to obtain estimates of the parameters a and b.
The Reflective Learning Continuum: Reflecting on Reflection

The importance of reflection to marketing educators is increasingly recognized. However, there is a lack of empirical research that considers reflection within the context of both the marketing and general business education literature. This article describes the use of an instrument that can be used to measure four identified levels of a reflection hierarchy: habitual action, understanding, reflection, and intensive reflection and two conditions for reflection: instructor-to-student interaction and student-to-student interaction. The authors also demonstrate the importance of reflective learning in predicting Graduates' perception of program quality. Although the focus was on assessment of MBA-level curricula, the findings have great importance to marketing education and educators.
Impact of Albuminuria on Early Neurological Deterioration and Lesion Volume Expansion in Lenticulostriate Small Infarcts

Background and Purpose— Albuminuria, a marker of chronic kidney disease, is associated with an increased risk of incident stroke and unfavorable long-term outcomes. However, the association of albuminuria with short-term outcomes and change in infarct volume in patients with acute small subcortical infarction remains unknown. Methods— We retrospectively reviewed 85 consecutive patients with acute small subcortical infarcts in the lenticulostriate artery territory who were admitted to our stroke center within 24 hours of symptom onset and underwent serial diffusion-weighted imaging (DWI). Albuminuria was determined based on the urinary albumin-to-creatinine ratio obtained from a first morning spot urine after admission. Infarct volume was measured on axial sections of the initial and follow-up DWI. Early neurological deterioration (END) was defined as an increase of ≥2 points in the National Institutes of Health Stroke Scale score during the first 5 days after admission. Results— Albuminuria (UACR ≥30 mg/g creatinine) was observed in 14 of 18 patients with END (77.8%) and in 25 of 67 patients without END (37.3%), P=0.002. Multivariate logistic regression analysis revealed that albuminuria was associated with END after adjustment for age, low estimated glomerular filtration rate (<60 mL/min per 1.73 m2), and infarct volume on initial DWI (odds ratio, 6.64; 95% confidence interval, 1.62–27.21; P=0.009). In addition, albuminuria was an independent predictor of increase in infarct volume using multivariate linear regression analysis (&bgr; coefficient=0.217; P=0.038). Conclusions— Our findings suggest that albuminuria is associated with END and infarct volume expansion in patients with small subcortical infarcts in the lenticulostriate artery territory.
Ritual and rationality: some problems of interpretation in European archaeology

AbstractThis paper argues that the conception of ritual employed in both archaeology and anthropology is a product of post-Enlightenment rationalism. Because it does not meet modern western criteria for practical action, ritual is frequently described as non-functional and irrational; furthermore, this designation is employed as the primary way of identifying ritual archaeologically. However, this evaluation of ritual action must be questioned. Contemporary modes of categorizing human practice are not untainted by socio-political interest but enable the reproduction of certain forms of power. It is argued that many other societies do not distinguish ritual from secular action. In fact, what anthropologists identify as ritual is generally considered practical and effective action by its practitioners. This is because different conceptions of instrumentality and causation inform such activities. For archaeologists, use of the concept of ritual has resulted in a serious misapprehension of prehistoric rationa.
Risk of Prostate Cancer in a Randomized Clinical Trial of Calcium Supplementation

Background: In some studies, high calcium intake has been associated with an increased risk of prostate cancer, but no randomized studies have investigated this issue. Methods: We randomly assigned 672 men to receive either 3 g of calcium carbonate (1,200 mg of calcium), or placebo, daily for 4 years in a colorectal adenoma chemoprevention trial. Participants were followed for up to 12 years and asked periodically to report new cancer diagnoses. Subject reports were verified by medical record review. Serum samples, collected at randomization and after 4 years, were analyzed for 1,25-(OH)2 vitamin D, 25-(OH) vitamin D, and prostate-specific antigen (PSA). We used life table and Cox proportional hazard models to compute rate ratios for prostate cancer incidence and generalized linear models to assess the relative risk of increases in PSA levels. Results: After a mean follow-up of 10.3 years, there were 33 prostate cancer cases in the calcium-treated group and 37 in the placebo-treated group [unadjusted rate ratio, 0.83; 95% confidence interval (95% CI), 0.52-1.32]. Most cases were not advanced; the mean Gleason's score was 6.2. During the first 6 years (until 2 years post-treatment), there were significantly fewer cases in the calcium group (unadjusted rate ratio, 0.52; 95% CI, 0.28-0.98). The calcium risk ratio for conversion to PSA >4.0 ng/mL was 0.63 (95% CI, 0.33-1.21). Baseline dietary calcium intake, plasma 1,25-(OH)2 vitamin D and 25-(OH) vitamin D levels were not materially associated with risk. Conclusion: In this randomized controlled clinical trial, there was no increase in prostate cancer risk associated with calcium supplementation and some suggestion of a protective effect.
Bioactive Silica Nanoparticles Promote Osteoblast Differentiation through Stimulation of Autophagy and Direct Association with LC3 and p62

We recently identified an engineered bioactive silica-based nanoparticle formulation (designated herein as NP1) that stimulates in vitro differentiation and mineralization of osteoblasts, the cells responsible for bone formation, and increases bone mineral density in young mice in vivo. The results demonstrate that these nanoparticles have intrinsic biological activity; however, the intracellular fate and a complete understanding of the mechanism(s) involved remains to be elucidated. Here we investigated the cellular mechanism(s) by which NP1 stimulates differentiation and mineralization of osteoblasts. We show that NP1 enters the cells through a caveolae-mediated endocytosis followed by stimulation of the mitogen activated protein kinase ERK1/2 (p44/p42). Our findings further revealed that NP1 stimulates autophagy including the processing of LC3β-I to LC3β-II, a key protein involved in autophagosome formation, which is dependent on ERK1/2 signaling. Using a variant of NP1 with cobalt ferrite magnetic metal core (NP1-MNP) to pull down associated proteins, we found direct binding of LC3β and p62, two key proteins involved in autophagosome formation, with silica nanoparticles. Interestingly, NP1 specifically interacts with the active and autophagosome associated form of LC3β (LC3β-II). Taken together, the stimulation of autophagy and associated signaling suggests a cellular mechanism for the stimulatory effects of silica nanoparticles on osteoblast differentiation and mineralization.
Metformin increases degradation of phospholamban via autophagy in cardiomyocytes

Significance Phospholamban (PLN) can regulate Ca2+ uptake rates in the sarcoplasmic reticulum in cardiomyocytes. However, the mechanisms that control PLN levels are not fully understood. This study shows that PLN degradation depends on ubiquitinylation of its lysine 3 residue and p62-mediated selective autophagy. Metformin was shown to accelerate autophagy and to induce PLN degradation, resulting in increased Ca2+ uptake. These results suggest that changes in PLN degradation could account for the cardiac inotropic effects of metformin. Phospholamban (PLN) is an effective inhibitor of the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA). Here, we examined PLN stability and degradation in primary cultured mouse neonatal cardiomyocytes (CMNCs) and mouse hearts using immunoblotting, molecular imaging, and [35S]methionine pulse-chase experiments, together with lysosome (chloroquine and bafilomycin A1) and autophagic (3-methyladenine and Atg5 siRNA) antagonists. Inhibiting lysosomal and autophagic activities promoted endogenous PLN accumulation, whereas accelerating autophagy with metformin enhanced PLN degradation in CMNCs. This reduction in PLN levels was functionally correlated with an increased rate of SERCA2a activity, accounting for an inotropic effect of metformin. Metabolic labeling reaffirmed that metformin promoted wild-type and R9C PLN degradation. Immunofluorescence showed that PLN and the autophagy marker, microtubule light chain 3, became increasingly colocalized in response to chloroquine and bafilomycin treatments. Mechanistically, pentameric PLN was polyubiquitinylated at the K3 residue and this modification was required for p62-mediated selective autophagy trafficking. Consistently, attenuated autophagic flux in HECT domain and ankyrin repeat-containing E3 ubiquitin protein ligase 1-null mouse hearts was associated with increased PLN levels determined by immunoblots and immunofluorescence. Our study identifies a biological mechanism that traffics PLN to the lysosomes for degradation in mouse hearts.
Regrets in the East and West: Role of intrapersonal versus interpersonal norms

Regrets are stronger following atypical than following normal behaviour. No studies have tested this effect for both intrapersonal normality (consistency within a person) and interpersonal normality (consistency between people) simultaneously. The present research examined whether the impact of violating the two kinds of normality on regret varies across cultures, using a manipulation of mutability crossed with that of norm violation. Among Korean participants (but not Americans) the impacts of mutability on regret were stronger when the intrapersonal rather than the interpersonal norm was violated, which was interpreted in terms of the greater collectivist emphasis in Korea than in the USA.
The development of children adopted following a socialemotional intervention in an institution

Worldwide, over 2 million children reside in institutional care; while family care is ideal, institutions will continue to exist for many years, and it is important to investigate ways to improve the care of children who reside in institutions. The current study is a post-adoption follow-up of an intervention in St. Petersburg, Russian Federation Baby Homes (BHs) wherein children received enhanced social-emotional care by regular BH caregivers. Children in this study previously resided in a St. Petersburg BH and received either No Intervention (CNoI), Training Only (TO), or Training and Structural Changes (T+SC). While children were in the institution, there were clear differences between groups in their physical, behavioral, and social-emotional development with T+SC faring the best, TO intermediate, and NoI having the poorest outcomes (St. Petersburg-USA Orphanage Research Team, 2008). This dissertation aimed to determine whether benefits of the intervention persisted up to 8 years after adoption. Parents completed measures including the 23-item Attachment Questionnaire, Indiscriminately Friendly Behavior Measure, BRIEF-P, CBQ (selected subtests), ITSEA, and CBCL 1½-5. Hierarchical regression analyses were conducted to examine the effect of Age at Adoption, Years in Adoptive Home, Intervention Group, and Age at Adoption x Intervention Group interactions on each outcome measure. Overall, while there are some residual effects of the intervention on children after adoption, graduates of each intervention group are functioning very well in early childhood. Graduates of intervention BHs tend to have better attachment security, lower levels of indiscriminately friendly behavior (T+SC only), fewer behavior problems (T+SC only), and lower levels of Internalizing problems (TO only) and Dysregulation (TO only) than CNoI. An older age at adoption or more time in the adoptive home were associated poorer outcomes in some domains. Children who had more exposure to intervention conditions (e.g., T+SC and TO adopted at older ages) had better attachment security (T+SC) fewer externalizing (TO only) and internalizing (TO only) problems, but poorer executive function and lower competence. Because all groups were, on average, functioning within the normal range of behavior, “poorer” outcomes are hypothesized to reflect the increased agency, creativity, and emotional expression of children from intervention BHs.