Miracle-dz/UniFAR-FTUs huggingface dataset:
Perirhinal Cortex Lesions in Rats: Novelty Detection and Sensitivity to Interference

Rats with perirhinal cortex lesions received multiple object recognition trials within a continuous session to examine whether they show false memories. Experiment 1 focused on exploration patterns during the first object recognition test postsurgery, in which each trial contained 1 novel and 1 familiar object. The perirhinal cortex lesions reduced time spent exploring novel objects, but did not affect overall time spent exploring the test objects (novel plus familiar). Replications with subsequent cohorts of rats (Experiments 2, 3, 4.1) repeated this pattern of results. When all recognition memory data were combined (Experiments 1–4), giving totals of 44 perirhinal lesion rats and 40 surgical sham controls, the perirhinal cortex lesions caused a marginal reduction in total exploration time. That decrease in time with novel objects was often compensated by increased exploration of familiar objects. Experiment 4 also assessed the impact of proactive interference on recognition memory. Evidence emerged that prior object experience could additionally impair recognition performance in rats with perirhinal cortex lesions. Experiment 5 examined exploration levels when rats were just given pairs of novel objects to explore. Despite their perirhinal cortex lesions, exploration levels were comparable with those of control rats. While the results of Experiment 4 support the notion that perirhinal lesions can increase sensitivity to proactive interference, the overall findings question whether rats lacking a perirhinal cortex typically behave as if novel objects are familiar, that is, show false recognition. Rather, the rats retain a signal of novelty but struggle to discriminate the identity of that signal.
Empirics for Economic Growth and Convergence Empirics for Economic Growth and Convergence

The convergence hypothesis has generated a huge empirical literature: this paper critically reviews some of the earlier key ndings, clari es their implications, and relates them to more recent results. Particular attention is devoted to interpreting convergence empirics. The main ndings are: (1) The much-heralded uniform 2% rate of convergence could arise for reasons unrelated to the dynamics of economic growth. (2) Usual empirical analyses|cross-section (conditional) convergence regressions, time series modelling, panel data analysis|can be misleading for understanding convergence; a model of polarization in economic growth clari es those di culties. (3) The data, more revealingly modelled, show persistence and immobility across countries: some evidence supports Baumol's idea of \convergence clubs"; some evidence shows the poor getting poorer, and the rich richer, with the middle class vanishing. (4) Convergence, unambiguous up to sampling error, is observed across US states.
Quantification of mitochondrial DNA mutation load

Mitochondrial DNA (mtDNA) mutations are an important cause of genetic disease and have been proposed to play a role in the ageing process. Quantification of total mtDNA mutation load in ageing tissues is difficult as mutational events are rare in a background of wild‐type molecules, and detection of individual mutated molecules is beyond the sensitivity of most sequencing based techniques. The methods currently most commonly used to document the incidence of mtDNA point mutations in ageing include post‐PCR cloning, single‐molecule PCR and the random mutation capture assay. The mtDNA mutation load obtained by these different techniques varies by orders of magnitude, but direct comparison of the three techniques on the same ageing human tissue has not been performed. We assess the procedures and practicalities involved in each of these three assays and discuss the results obtained by investigation of mutation loads in colonic mucosal biopsies from ten human subjects.
Genomics Perspectives on Metabolism, Survival Strategies, and Biotechnological Applications of Brettanomyces bruxellensis LAMAP2480

Wine production is an important commercial issue for the liquor industry. The global production was estimated at 275.7 million hectoliters in 2015. The loss of wine production due to Brettanomyces bruxellensis contamination is currently a problem. This yeast causes a “horse sweat” flavor in wine, which is an undesired organoleptic attribute. To date, 6 B. bruxellensis annotated genome sequences are available (LAMAP2480, AWRI1499, AWRI1608, AWRI1613, ST05.12/22, and CBS2499), and whole genome comparisons between strains are limited. In this article, we reassembled and reannotated the genome of B. bruxellensis LAMAP2480, obtaining a 27-Mb assembly with 5.5 kb of N50. In addition, the genome of B. bruxellensis LAMAP2480 was analyzed in the context of spoilage yeast and potential as a biotechnological tool. In addition, we carried out an exploratory transcriptomic analysis of this strain grown in synthetic wine. Several genes related to stress tolerance, micronutrient acquisition, ethanol production, and lignocellulose assimilation were found. In conclusion, the analysis of the genome of B. bruxellensis LAMAP2480 reaffirms the biotechnological potential of this strain. This research represents an interesting platform for the study of the spoilage yeast B. bruxellensis.
Blocking Central Opiate Function Modulates Hedonic Impact and Anterior Cingulate Response to Rewards and Losses

Reward processing is linked to specific neuromodulatory systems with a dopaminergic contribution to reward learning and motivational drive being well established. Neuromodulatory influences on hedonic responses to actual receipt of reward, or punishment, referred to as experienced utility are less well characterized, although a link to the endogenous opioid system is suggested. Here, in a combined functional magnetic resonance imaging–psychopharmacological investigation, we used naloxone to block central opioid function while subjects performed a gambling task associated with rewards and losses of different magnitudes, in which the mean expected value was always zero. A graded influence of naloxone on reward outcome was evident in an attenuation of pleasure ratings for larger reward outcomes, an effect mirrored in attenuation of brain activity to increasing reward magnitude in rostral anterior cingulate cortex. A more striking effect was seen for losses such that under naloxone all levels of negative outcome were rated as more unpleasant. This hedonic effect was associated with enhanced activity in anterior insula and caudal anterior cingulate cortex, areas implicated in aversive processing. Our data indicate that a central opioid system contributes to both reward and loss processing in humans and directly modulates the hedonic experience of outcomes.
Structural Plasticity of the Semliki Forest Virus Glycome upon Interspecies Transmission

Cross-species viral transmission subjects parent and progeny alphaviruses to differential post-translational processing of viral envelope glycoproteins. Alphavirus biogenesis has been extensively studied, and the Semliki Forest virus E1 and E2 glycoproteins have been shown to exhibit differing degrees of processing of N-linked glycans. However the composition of these glycans, including that arising from different host cells, has not been determined. Here we determined the chemical composition of the glycans from the prototypic alphavirus, Semliki Forest virus, propagated in both arthropod and rodent cell lines, by using ion-mobility mass spectrometry and collision-induced dissociation analysis. We observe that both the membrane-proximal E1 fusion glycoprotein and the protruding E2 attachment glycoprotein display heterogeneous glycosylation that contains N-linked glycans exhibiting both limited and extensive processing. However, E1 contained predominantly highly processed glycans dependent on the host cell, with rodent and mosquito-derived E1 exhibiting complex-type and paucimannose-type glycosylation, respectively. In contrast, the protruding E2 attachment glycoprotein primarily contained conserved under-processed oligomannose-type structures when produced in both rodent and mosquito cell lines. It is likely that glycan processing of E2 is structurally restricted by steric-hindrance imposed by local viral protein structure. This contrasts E1, which presents glycans characteristic of the host cell and is accessible to enzymes. We integrated our findings with previous cryo-electron microscopy and crystallographic analyses to produce a detailed model of the glycosylated mature virion surface. Taken together, these data reveal the degree to which virally encoded protein structure and cellular processing enzymes shape the virion glycome during interspecies transmission of Semliki Forest virus.
Automatic Chord Recognition from Audio Using Enhanced Pitch Class Profile

In this paper, a feature vector called the Enhanced Pitch Class Profile (EPCP) is introduced for automatic chord recognition from the raw audio. To this end, the Harmonic Product Spectrum is first obtained from the DFT of the input signal, and then an algorithm for computing a 12-dimensional pitch class profile is applied to it to give the EPCP feature vector. The EPCP vector is correlated with the pre-defined templates for 24 major/minor triads, and the template yielding maximum correlation is identified as the chord of the input signal. The experimental results show the EPCP yields less errors than the conventional PCP in frame-rate chord recognition.
Role of the Barhl2 homeobox gene in the specification of glycinergic amacrine cells

The mammalian retina contains numerous morphological and physiological subtypes of amacrine cells necessary for integrating and modulating visual signals presented to the output neurons. Among subtypes of amacrine cells grouped by neurotransmitter phenotypes, the glycinergic andγ -aminobutyric acid (GABA)ergic amacrine cells constitute two major subpopulations. To date, the molecular mechanisms governing the specification of subtype identity of amacrine cells remain elusive. We report here that during mouse development, the Barhl2 homeobox gene displays an expression pattern in the nervous system that is distinct from that of its homologue Barhl1. In the developing retina, Barhl2 expression is found in postmitotic amacrine, horizontal and ganglion cells, while Barhl1 expression is absent. Forced expression of Barhl2 in retinal progenitors promotes the differentiation of glycinergic amacrine cells, whereas a dominant-negative form of Barhl2 has the opposite effect. By contrast, they exert no effect on the formation of GABAergic neurons. Moreover, misexpressed Barhl2 inhibits the formation of bipolar and Müller glial cells, indicating that Barhl2 is able to function both as a positive and negative regulator, depending on different types of cells. Taken together, our data suggest that Barhl2 may function to specify the identity of glycinergic amacrine cells from competent progenitors during retinogenesis.
Coordinated Selfish Distributed Caching for Peering Content-Centric Networks

A future content-centric Internet would likely consist of autonomous systems (ASes) just like today's Internet. It would thus be a network of interacting cache networks, each of them optimized for local performance. To understand the influence of interactions between autonomous cache networks, in this paper, we consider ASes that maintain peering agreements with each other for mutual benefit and engage in content-level peering to leverage each others' cache contents. We propose a model of the interaction between the caches managed by peering ASes. We address whether stable and efficient content-level peering can be implemented without explicit coordination between the neighboring ASes. We show that content-level peering leads to stable cache configurations, both with and without coordination. However, peering Internet Service Providers (ISPs) that coordinate to avoid simultaneous updates converge to a stable configuration more efficiently. Furthermore, if the content popularity estimates are inaccurate, content-level peering is likely to lead to cost efficient cache allocations. We validate our analytical results using simulations on the measured peering topology of more than 600 ASes.
A Critical Role for Eosinophils in Allergic Airways Remodeling

Features of chronic asthma include airway hyperresponsiveness, inflammatory infiltrates, and structural changes in the airways, termed remodeling. The contribution of eosinophils, cells associated with asthma and allergy, remains to be established. We show that in mice with a total ablation of the eosinophil lineage, increases in airway hyperresponsiveness and mucus secretion were similar to those observed in wild-type mice, but eosinophil-deficient mice were significantly protected from peribronchiolar collagen deposition and increases in airway smooth muscle. These data suggest that eosinophils contribute substantially to airway remodeling but are not obligatory for allergen-induced lung dysfunction, and support an important role for eosinophil-targeted therapies in chronic asthma.
Quiescent Oct4+ Neural Stem Cells (NSCs) Repopulate Ablated Glial Fibrillary Acidic Protein+ NSCs in the Adult Mouse Brain

Adult primitive neural stem cells (pNSCs) are a rare population of glial fibrillary acidic protein (GFAP)– Oct4+ cells in the mouse forebrain subependymal zone bordering the lateral ventricles that give rise to clonal neurospheres in leukemia inhibitory factor in vitro. pNSC neurospheres can be passaged to self‐renew or give rise to GFAP+ NSCs that form neurospheres in epidermal growth factor and fibroblast growth factor 2, which we collectively refer to as definitive NSCs (dNSCs). Label retention experiments using doxycycline‐inducible histone‐2B (H2B)–green fluorescent protein (GFP) mice and several chase periods of up to 1 year quantified the adult pNSC cell cycle time as 3–5 months. We hypothesized that while pNSCs are not very proliferative at baseline, they may exist as a reserve pool of NSCs in case of injury. To test this function of pNSCs, we obtained conditional Oct4 knockout mice, Oct4fl/fl;Sox1Cre (Oct4CKO), which do not yield adult pNSC‐derived neurospheres. When we ablated the progeny of pNSCs, namely all GFAP+ dNSCs, in these Oct4CKO mice, we found that dNSCs did not recover as they do in wild‐type mice, suggesting that pNSCs are necessary for dNSC repopulation. Returning to the H2B‐GFP mice, we observed that the cytosine β‐d‐arabinofuranoside ablation of proliferating cells including dNSCs‐induced quiescent pNSCs to proliferate and significantly dilute their H2B‐GFP label. In conclusion, we demonstrate that pNSCs are the most quiescent stem cells in the adult brain reported to date and that their lineage position upstream of GFAP+ dNSCs allows them to repopulate a depleted neural lineage. Stem Cells 2017;35:2071–2082
Cerebellar Ataxia in Patients With Mitochondrial DNA Disease: A Molecular Clinicopathological Study

Abstract Cerebellar ataxia is a prominent clinical symptom in patients with mitochondrial DNA (mtDNA) disease. This is often progressive with onset in young adulthood. We performed a detailed neuropathologic investigation of the olivary-cerebellum in 14 genetically and clinically well-defined patients with mtDNA disease. Quantitative neuropathologic investigation showed varying levels of loss of Purkinje cells and neurons of the dentate nucleus and inferior olivary nuclei. Typically, focal Purkinje cell loss was present in patients with the m.3243A>G mutation caused by the presence of microinfarcts, with relative preservation of neuronal cell populations in the olivary and dentate nuclei. In contrast, patients with the m.8344A>G mutation orrecessive POLG mutations showed extensive and global neuronal cell loss in all 3 olivary-cerebellum areas examined. Molecular analysisof mutated mtDNA heteroplasmy levels revealed that neuronal cell loss occurred independently of the level of mutated mtDNA present within surviving neurons. High levels of neuronal respiratory chain deficiency, particularly of complex I, were detected in surviving cells; levels of deficiency were greater in regions with extensive cell loss. Wefound a relationship between respiratory deficiency and neuronal cell density, indicating that neuronal cell death correlates with respiratory deficiency. These findings highlight the vulnerability of the olivary-cerebellum to mtDNA defects.
Comparison of some mechanical models of larynx in the synthesis of voiced sounds

The process of voiced sounds production can be described as follows: air coming from the lungs is forced through the narrow space between the two vocal folds, which are set in motion in a frequency governed by the tension of their tissues. The vocal folds change the continuous flow that comes from the lungs into a series of pulses. Then, as the flow passes through the oral and nasal cavities it is amplified and changed until it is finally radiated from the mouth. This complex process can be modeled by a system of integral-differential equations. In spite of such complexity, this paper shows that it is possible to obtain synthetic voice sounds of satisfactory realism using simple mathematical models. The perception of a synthetic sound as natural is increased by choosing suitable waveforms for the time-varying subglottal pressure, rather than by augmenting the number of degrees of freedom of the mechanical model. This paper also shows possible ways to adapt the models to voices of men, women and children. Keywords : Voice production, articulatory synthesis, signal processing
JAG1 Mutation Spectrum and Origin in Chinese Children with Clinical Features of Alagille Syndrome

Alagille syndrome is an autosomal dominant disorder that results from defects in the Notch signaling pathway, which is most frequently due to JAG1 mutations. This study investigated the rate, spectrum, and origin of JAG1 mutations in 91 Chinese children presenting with at least two clinical features of Alagille syndrome (cholestasis, heart murmur, skeletal abnormalities, ocular abnormalities, characteristic facial features, and renal abnormalities). Direct sequencing and/or multiplex-ligation-dependent probe amplification were performed in these patients, and segregation analysis was performed using samples available from the parents. JAG1 disease-causing mutations were detected in 70/91 (76.9%) patients, including 29/70 (41.4%) small deletions, 6/70 (8.6%) small insertions, 16/70 (22.9%) nonsense mutations, 8/70 (11.4%) splice-site mutations, 6/70 (9.4%) missense mutations, and 5/70 (7.1%) gross deletions. Of the mutations detected, 45/62 (72.6%) were novel, and almost all were unique, with the exception of c.439C>T, c.439+1G>A, c.703C>T, c. 1382_1383delAC, c.2698C>T, and c.2990C>A, which were detected in two cases each; three cases exhibited entire gene deletions. A majority (69.2%) of the point and frameshift mutations could be detected by the sequencing of eleven exons (exons 3, 5, 6, 11, 14, 16, 18, 21, and 23–25). The mutation detection rate was 50.0% (10/20) in atypical cases that only presented with two or three clinical features of Alagille syndrome. Segregation analysis revealed that 81.1% (30/37) of these mutations were de novo. In conclusion, JAG1 mutations are present in the majority of Chinese pediatric patients with clinical features of Alagille syndrome, and the mutations concentrate on different exons from other reports. Genetic study is important for the diagnosis of atypical Alagille syndrome in Chinese patients.
Exploring the use of I/O nodes for computation in a MIMD multiprocessor

As parallel systems move into the production scientific-computing world, the emphasis will be on cost-effective solutions that provide high throughput for a mix of applications. Costeffective solutions demand that a system make effective use of all of its resources. Many MIMD multiprocessors today, however, distinguish between "compute" and "I/O" nodes, the latter having attached disks and being dedicated to running the file-system server. This static division of responsibilities simplifies system management but does not necessarily lead to the best performance in workloads that need a different balance of computation and I/O. Of course, computational processes sharing a node with a file-system service may receive less CPU time, network bandwidth, and memory bandwidth than they would on a computationonly node. In this paper we begin to examine this issue experimentally. We found that highperformance I/O does not necessarily require substantial CPU time, leaving plenty of time for application computation. There were some complex file-system requests, however, which left little CPU time available to the application. (The impact on network and memory bandwidth still needs to be determined.) For applications (or users) that cannot tolerate an occasional interruption, we recommend that they continue to use only compute nodes. For tolerant applications needing more cycles than those provided by the compute nodes, we recommend that they take full advantage of both compute and I/O nodes for computation, and that operating systems should make this possible.
Recommendations for the optimal care of patients with recent‐onset psychosis in the Asia‐Pacific region

Providing optimal care to patients with recent‐onset psychosis can improve outcomes and reduce relapse. However, there is a lack of consistency of the implementation of guidelines for such patients across the Asia‐Pacific region. We determined a pragmatic set of recommendations for use on a day‐to‐day basis to help provide optimal care at this crucial stage of illness. The recommendations were developed over a series of meetings by an international faculty of 15 experts from the Asia‐Pacific region, Europe, and South Africa. A structured search of the PubMed database was conducted. This was further developed based on the faculty's clinical experience and knowledge of the literature into 10 key aspects of optimal care for patients during the first five years of a diagnosis of a psychotic disorder, with particular relevance to the Asia‐Pacific region. Several common principles emerged: adherence to antipsychotic medications is crucial; substance abuse, psychiatric and medical comorbidities should be addressed; psychosocial interventions play a pivotal role; and family members can play a vital role in overall patient care. By following these recommendations, clinicians may improve outcomes for patients with recent‐onset psychosis.