Miracle-dz/UniFAR-FTUs huggingface dataset:
PINK1 cleavage at position A103 by the mitochondrial protease PARL

Mutations in PTEN-induced kinase 1 (PINK1) cause early onset autosomal recessive Parkinson's disease (PD). PINK1 is a 63 kDa protein kinase, which exerts a neuroprotective function and is known to localize to mitochondria. Upon entry into the organelle, PINK1 is cleaved to produce a ∼53 kDa protein (ΔN-PINK1). In this paper, we show that PINK1 is cleaved between amino acids Ala-103 and Phe-104 to generate ΔN-PINK1. We demonstrate that a reduced ability to cleave PINK1, and the consequent accumulation of full-length protein, results in mitochondrial abnormalities reminiscent of those observed in PINK1 knockout cells, including disruption of the mitochondrial network and a reduction in mitochondrial mass. Notably, we assessed three N-terminal PD-associated PINK1 mutations located close to the cleavage site and, while these do not prevent PINK1 cleavage, they alter the ratio of full-length to ΔN-PINK1 protein in cells, resulting in an altered mitochondrial phenotype. Finally, we show that PINK1 interacts with the mitochondrial protease presenilin-associated rhomboid-like protein (PARL) and that loss of PARL results in aberrant PINK1 cleavage in mammalian cells. These combined results suggest that PINK1 cleavage is important for basal mitochondrial health and that PARL cleaves PINK1 to produce the ΔN-PINK1 fragment.
Early Presynaptic and Late Postsynaptic Components Contribute Independently to Brain-Derived Neurotrophic Factor-Induced Synaptic Plasticity

Trophin-induced synaptic plasticity consists of both presynaptic and postsynaptic processes. The potential interdependence of these mechanisms and their temporal relationships are undefined. The synaptic vesicle protein Rab3A is required for the early, initial 10 min phase but not for the later phase of BDNF-enhanced transmission. We now examine the temporal distinction and mechanistic relationships between these phases of BDNF action. Rab3A mutant cells did not exhibit increased miniature EPSC frequency in response to BDNF in cell culture, indicating an absence of the presynaptic component. In contrast, BDNF enhanced postsynaptic glutamate-induced current in the mutant neurons as in the wild type, indicating that the postsynaptic component of the response was intact. Finally, the postsynaptic NMDA receptor subunit NR2B was phosphorylated at Tyr1472 by BDNF in Rab3A knock-outs, as shown previously in wild type. Our results are the first to demonstrate that presynaptic and postsynaptic components of BDNF-enhanced synaptic activity are independent and temporally distinct.
Discovery of a Luminous, Variable, Off-Center Source in the Nucleus of M82 with the Chandra High-Resolution Camera

We present results from observations of the most famous starburst galaxy M82 with the High-Resolution Camera on board the Chandra X-Ray Observatory. We found nine sources in the central 1′ × 1′ region, but no source was detected at the galactic center. Comparing the observations on 1999 October 28 and on 2000 January 20, we found that four of the nine sources showed significant time variability. In particular, CXOM82 J095550.2+694047, which is 9'' away from the galactic center, showed extremely large time variability. We conclude that this source is the origin of the hard X-ray time variability of M82 detected with ASCA. Assuming a spectral shape obtained by the ASCA observation, its luminosity in the 0.5-10 keV band changed from 1.2 × 1040 ergs s-1 on 1999 October 28 to 8.7 × 1040 ergs s-1 on 2000 January 20.
Quantum Hadrodynamics: Evolution and Revolution

The underlying philosophy and motivation for quantum hadrodynamics (QHD), namely, relativistic field theories of nuclear phenomena featuring manifest covariance, have evolved over the last quarter century in response to successes, failures, and sharp criticisms. A recent revolution in QHD, based on modern effective field theory and density functional theory perspectives, explains the successes, provides antidotes to the failures, rebuts the criticisms, and focuses the arguments in favor of a covariant representation.
Towards Predicting the Effectiveness of Partial Evaluation

Recent approaches to partial evaluation—a well-known technique for program specialization—include a so called size-change analysis for ensuring the termination of the process. This paper presents a novel application of size-change analysis for predicting the effectiveness of partial evaluation. Size-change analysis is based on computing an approximation of the program loops. Here, we present an automatic transformation that takes the output of the size-change analysis and produces an approximation of the loops in the specialized program. This information can be used for determining—before performing the actual specialization process—when partial evaluation may produce a significant improvement and when it would be useless. An experimental evaluation demonstrates the usefulness of our approach.
The use of a linguistically motivated language model in conversational speech recognition

Structured language models have recently been shown to give significant improvements in large-vocabulary recognition relative to traditional word N-gram models, but typically imply a heavy computational burden and have not been applied to large training sets or complex recognition systems. Previously, we developed a linguistically motivated and computationally efficient almost-parsing language model, using a data structure derived from constraint dependency grammar parsing, that tightly integrates knowledge of words, lexical features, and syntactic constraints. We show that such a model can be used effectively and efficiently in all stages of a complex, multi-pass conversational telephone speech recognition system. Compared to a state-of-the-art 4-gram interpolated word- and class-based language model, we obtained a 6.2% relative word error reduction (a 1.6% absolute reduction) on a recent NIST evaluation set.
Very fast ellipse detection for embedded vision applications

Real-time ellipse detection is an important yet challenging task, since the estimation of the five parameters of an ellipse requires heavy computation. This task is even more challenging when the processing must be done on a mobile device with limited computational power. The typical trade-off between accuracy, efficiency and limited resources of embedded vision programming must be accounted. In this paper we present a novel strategy for edge point selection, which allows to drastically reduce the number of edge points to be evaluated for parameters estimation, making embedded mobile vision applications feasible. Extensive results show the increased efficiency of the proposed method over state-of-the-art ellipse detectors, in synthetic and challenging real images, and in a live mobile application.
Characterization of a Highly pH Stable Chi-Class Glutathione S-Transferase from Synechocystis PCC 6803

Glutathione S-transferases (GSTs) are multifunctional enzymes present in virtually all organisms. Besides having an essential role in cellular detoxification, they also perform various other functions, including responses in stress conditions and signaling. GSTs are highly studied in plants and animals; however, the knowledge regarding GSTs in cyanobacteria seems rudimentary. In this study, we report the characterization of a highly pH stable GST from the model cyanobacterium- Synechocystis PCC 6803. The gene sll0067 was expressed in Escherichia coli (E. coli), and the protein was purified to homogeneity. The expressed protein exists as a homo-dimer, which is composed of about 20 kDa subunit. The results of the steady-state enzyme kinetics displayed protein’s glutathione conjugation activity towards its class specific substrate- isothiocyanate, having the maximal activity with phenethyl isothiocyanate. Contrary to the poor catalytic activity and low specificity towards standard GST substrates such as 1-chloro-2,4-dinitrobenzene by bacterial GSTs, PmGST B1-1 from Proteus mirabilis, and E. coli GST, sll0067 has broad substrate degradation capability like most of the mammalian GST. Moreover, we have shown that cyanobacterial GST sll0067 is catalytically efficient compared to the best mammalian enzymes. The structural stability of GST was studied as a function of pH. The fluorescence and CD spectroscopy in combination with size exclusion chromatography showed a highly stable nature of the protein over a broad pH range from 2.0 to 11.0. To the best of our knowledge, this is the first GST with such a wide range of pH related structural stability. Furthermore, the presence of conserved Proline-53, structural motifs such as N-capping box and hydrophobic staple further aid in the stability and proper folding of cyanobacterial GST- sll0067.
Weight Gain in the First Two Years of Life Is an Important Predictor of Schooling Outcomes in Pooled Analyses from Five Birth Cohorts from Low- and Middle-Income Countries12

Schooling predicts better reproductive outcomes, better long-term health, and increased lifetime earnings. We used data from 5 cohorts (Brazil, Guatemala, India, the Philippines, and South Africa) to explore the relative importance of birthweight and postnatal weight gain for schooling in pooled analyses (n = 7945) that used appropriate statistical methods [conditional weight (CW) gain measures that are uncorrelated with prior weights] and controlled for confounding. One SD increase in birthweight, ∼0.5 kg, was associated with 0.21 y more schooling and 8% decreased risk of grade failure. One SD increase in CW gain between 0 and 2 y, ∼0.7 kg, was associated with higher estimates, 0.43 y more schooling, and 12% decreased risk of failure. One SD increase of CW gain between 2 and 4 y, ∼0.9 kg, was associated with only 0.07 y more schooling but not with failure. Also, in children born in the lowest tertile of birthweight, 1 SD increase of CW between 0 and 2 y was associated with 0.52 y more schooling compared with 0.30 y in those in the upper tertile. Relationships with age at school entry were inconsistent. In conclusion, weight gain during the first 2 y of life had the strongest associations with schooling followed by birthweight; weight gain between 2 and 4 y had little relationship to schooling. Catch-up growth in smaller babies benefited schooling. Nutrition interventions aimed at women and children under 2 y are among the key strategies for achieving the millennium development goal of universal primary education by 2015.
Dynamic Risk Stratification in Patients with Differentiated Thyroid Cancer Treated Without Radioactive Iodine.

CONTEXT Although response to therapy assessment is a validated tool for dynamic risk stratification in patients with differentiated thyroid cancer (DTC) treated with total thyroidectomy (TT) and radioactive iodine therapy (RAI), it has not been well studied in patients treated with lobectomy or TT without RAI. Because these responses to therapy definitions are heavily dependent on serum thyroglobulin (Tg) levels, modifications of the original definitions were needed to appropriately classify patients treated without RAI. OBJECTIVE This study aimed to validate the response to therapy assessment in patients with DTC treated with lobectomy or TT without RAI. DESIGN AND SETTING This was a retrospective study, which took place at a referral center. PATIENTS A total of 507 adults with DTC were treated with lobectomy (n = 187) or TT (n = 320) without RAI. They had a median age of 43.7 y, 88% were female, 85.4% had low risk, and 14.6% intermediate risk. MAIN OUTCOME MEASURE Main outcome measured was recurrent/persistent structural evidence of disease (SED) during a median followup period of 100.5 months (24-510). RESULTS Recurrent/persistent SED was observed in 0% of the patients with excellent response to therapy (nonstimulated Tg for TT < 0.2 ng/mL and for lobectomy < 30 ng/mL, undetectable Tg antibodies [TgAb] and negative imaging; n = 326); 1.3% with indeterminate response (nonstimulated Tg for TT 0.2-5 ng/mL, stable or declining TgAb and/or nonspecific imaging findings; n = 2/152); 31.6% of the patients with biochemical incomplete response (nonstimulated Tg for TT > 5 ng/mL and for lobectomy > 30 ng/mL and/or increasing Tg with similar TSH levels and/or increasing TgAb and negative imaging; n = 6/19) and all (100%) patients with structural incomplete response (n = 10/10) (P < .0001). Initial American Thyroid Association risk estimates were significantly modified based on response to therapy assessment. CONCLUSIONS Our data validate the newly proposed response to therapy assessment in patients with DTC treated with lobectomy or TT without RAI as an effective tool to modify initial risk estimates of recurrent/persistent SED and better tailor followup and future therapeutic approaches. This study provides further evidence to support a selective use of RAI in DTC.
Redox Homeostasis in Pancreatic β Cells

We reviewed mechanisms that determine reactive oxygen species (redox) homeostasis, redox information signaling and metabolic/regulatory function of autocrine insulin signaling in pancreatic β cells, and consequences of oxidative stress and dysregulation of redox/information signaling for their dysfunction. We emphasize the role of mitochondrion in β cell molecular physiology and pathology, including the antioxidant role of mitochondrial uncoupling protein UCP2. Since in pancreatic β cells pyruvate cannot be easily diverted towards lactate dehydrogenase for lactate formation, the respiration and oxidative phosphorylation intensity are governed by the availability of glucose, leading to a certain ATP/ADP ratio, whereas in other cell types, cell demand dictates respiration/metabolism rates. Moreover, we examine the possibility that type 2 diabetes mellitus might be considered as an inevitable result of progressive self-accelerating oxidative stress and concomitantly dysregulated information signaling in peripheral tissues as well as in pancreatic β cells. It is because the redox signaling is inherent to the insulin receptor signaling mechanism and its impairment leads to the oxidative and nitrosative stress. Also emerging concepts, admiting participation of redox signaling even in glucose sensing and insulin release in pancreatic β cells, fit in this view. For example, NADPH has been firmly established to be a modulator of glucose-stimulated insulin release.
Movement-Related Changes in Local and Long-Range Synchronization in Parkinson's Disease Revealed by Simultaneous Magnetoencephalography and Intracranial Recordings

Functional neurosurgery has afforded the opportunity to assess interactions between populations of neurons in the human cerebral cortex and basal ganglia in patients with Parkinson's disease (PD). Interactions occur over a wide range of frequencies, and the functional significance of those >30 Hz is particularly unclear. Do they improve movement, and, if so, in what way? We acquired simultaneously magnetoencephalography and direct recordings from the subthalamic nucleus (STN) in 17 PD patients. We examined the effect of synchronous and sequential finger movements and of the dopamine prodrug levodopa on induced power in the contralateral primary motor cortex (M1) and STN and on the coherence between the two structures. We observed discrete peaks in M1 and STN power at 60–90 Hz and at 300–400 Hz. All these power peaks increased with movement and levodopa treatment. Only STN activity at 60–90 Hz was coherent with activity in M1. Directionality analysis showed that STN gamma activity at 60–90 Hz tended to drive gamma activity in M1. The effects of levodopa on both local and distant synchronization at 60–90 Hz correlated with the degree of improvement in bradykinesia-rigidity as did local STN activity at 300–400 Hz. Despite this, there were no effects of movement type, nor interactions between movement type and levodopa in the STN, nor in the coherence between STN and M1. We conclude that synchronization at 60–90 Hz in the basal ganglia cortical network is prokinetic but likely through a modulatory effect rather than any involvement in explicit motor processing.
Development of the Questionnaire for Teenagers' Future Orientation

Based on literature review,interview and open questionnaire,the authors conducted these major dimensions of the future orientation questionnaire,and implemented pretest and test among junior high students,senior high students and college students.Applying exploratory factor analysis and confirmatory analysis methods,we constructed the future orientation questionnaire for young children.This questionnaire includes three dimensions and six factors,namely future cognition(extensive and destiny),future emotion(optimism and anxiety) and future will action(planning and enforceability). The reliability and validity of the scale are relatively good and meet the requirement of psychometrics.
Estimating simple functions on the union of data streams

Massive data sets often arise as physically distributed, parallel data streams. We present algorithms for estimating simple functions on the union of such data streams, while using only logarithmic space per stream. Each processor observes only its own stream, and communicates with the other processors only after observing its entire stream. This models the set-up in current network monitoring products. Our algorithms employ a novel coordinated sampling technique to extract a sample of the union; this sample can be used to estimate aggregate functions on the union. The technique can also be used to estimate aggregate functions over the distinct “labels” in one or more data streams, e.g., to determine the zeroth frequency moment (i.e., the number of distinct labels) in one or more data streams. Our space and time bounds are the best known for these problems, and our logarithmic space bounds for coordinated sampling contrast with polynomial lower bounds for independent sampling. We relate our distributed streams model to previously studied non-distributed (i.e., merged) streams models, presenting tight bounds on the gap between the distributed and merged models for deterministic algorithms.
Examining the relationship between emotion regulation deficits and borderline personality disorder features: A daily diary study

This study used a six-day daily diary methodology to precisely specify the nature of emotion regulation deficits associated with borderline personality disorder (BPD) features. Three possibilities were explored: that BPD features are associated with (1) the overall underuse of emotion regulation strategies; (2) the overuse of dysfunctional and the underuse of functional strategies; and (3) the lower perceived effectiveness of emotion regulation strategies. One hundred and fifty-four undergraduate participants completed self-report measures of BPD feature severity, and then reported their daily negative emotional intensity, whether or not they used various emotion regulation strategies, and whether or not the strategies that they used were effective across a six-day period. Higher BPD features were associated with (a) higher total frequency use of emotion regulation strategies; (b) higher frequency use of dysfunctional and functional emotion regulation strategies; and (c) less self-reported effectiveness of functional strategies. BPD features may be characterized by increased attempts to regulate emotions, without corresponding increases in perceived effectiveness.
Fitness of Leishmania donovani Parasites Resistant to Drug Combinations

Drug resistance represents one of the main problems for the use of chemotherapy to treat leishmaniasis. Additionally, it could provide some advantages to Leishmania parasites, such as a higher capacity to survive in stress conditions. In this work, in mixed populations of Leishmania donovani parasites, we have analyzed whether experimentally resistant lines to one or two combined anti-leishmanial drugs better support the stress conditions than a susceptible line expressing luciferase (Luc line). In the absence of stress, none of the Leishmania lines showed growth advantage relative to the other when mixed at a 1:1 parasite ratio. However, when promastigotes from resistant lines and the Luc line were mixed and exposed to different stresses, we observed that the resistant lines are more tolerant of different stress conditions: nutrient starvation and heat shock-pH stress. Further to this, we observed that intracellular amastigotes from resistant lines present a higher capacity to survive inside the macrophages than those of the control line. These results suggest that resistant parasites acquire an overall fitness increase and that resistance to drug combinations presents significant differences in their fitness capacity versus single-drug resistant parasites, particularly in intracellular amastigotes. These results contribute to the assessment of the possible impact of drug resistance on leishmaniasis control programs.
The Frequency of Visually Induced Gamma-Band Oscillations Depends on the Size of Early Human Visual Cortex

The structural and functional architecture of the human brain is characterized by considerable variability, which has consequences for visual perception. However, the neurophysiological events mediating the relationship between interindividual differences in cortical surface area and visual perception have, until now, remained unknown. Here, we show that the retinotopically defined surface areas of central V1 and V2 are correlated with the peak frequency of visually induced oscillations in the gamma band, as measured with magnetoencephalography. Gamma-band oscillations are thought to play an important role in visual processing. We propose that individual differences in macroscopic gamma frequency may be attributed to interindividual variability in the microscopic architecture of visual cortex.
Neuroimaging endophenotypes in autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has a strong genetic basis, and is heterogeneous in its etiopathogenesis and clinical presentation. Neuroimaging studies, in concert with neuropathological and clinical research, have been instrumental in delineating trajectories of development in children with ASD. Structural neuroimaging has revealed ASD to be a disorder with general and regional brain enlargement, especially in the frontotemporal cortices, while functional neuroimaging studies have highlighted diminished connectivity, especially between frontal-posterior regions. The diverse and specific neuroimaging findings may represent potential neuroendophenotypes, and may offer opportunities to further understand the etiopathogenesis of ASD, predict treatment response, and lead to the development of new therapies.
Anti-superiority redux: A criticism of relational approach

I will show that anti-superiority effect can receive a more satisfactory account, given the asymmetric scope taking strategy of the two types of wh-words as claimed by Choi (2002). The relational approach by Watanabe (1992) and Saito (1994) as crucially based on the idea that wh-words in Korean type languages, being like quantifiers, should have their relation as established at some point maintained throughout the derivation is flawed, given that wh-words, unlike quantifiers, have the same scope in the same clause. It will be also shown that there are examples which violate relation preservation but are more or less acceptable, suggesting that the constraint of relation preservation cannot be part of the grammar.