Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphorylation of Synapsin I by Cyclin-Dependent Kinase-5 Sets the Ratio between the Resting and Recycling Pools of Synaptic Vesicles at Hippocampal Synapses

Cyclin-dependent kinase-5 (Cdk5) was reported to downscale neurotransmission by sequestering synaptic vesicles (SVs) in the release-reluctant resting pool, but the molecular targets mediating this activity remain unknown. Synapsin I (SynI), a major SV phosphoprotein involved in the regulation of SV trafficking and neurotransmitter release, is one of the presynaptic substrates of Cdk5, which phosphorylates it in its C-terminal region at Ser549 (site 6) and Ser551 (site 7). Here we demonstrate that Cdk5 phosphorylation of SynI fine tunes the recruitment of SVs to the active recycling pool and contributes to the Cdk5-mediated homeostatic responses. Phosphorylation of SynI by Cdk5 is physiologically regulated and enhances its binding to F-actin. The effects of Cdk5 inhibition on the size and depletion kinetics of the recycling pool, as well as on SV distribution within the nerve terminal, are virtually abolished in mouse SynI knock-out (KO) neurons or in KO neurons expressing the dephosphomimetic SynI mutants at sites 6,7 or site 7 only. The observation that the single site-7 mutant phenocopies the effects of the deletion of SynI identifies this site as the central switch in mediating the synaptic effects of Cdk5 and demonstrates that SynI is necessary and sufficient for achieving the effects of the kinase on SV trafficking. The phosphorylation state of SynI by Cdk5 at site 7 is regulated during chronic modification of neuronal activity and is an essential downstream effector for the Cdk5-mediated homeostatic scaling.
45-fs Diode-Pumped Passively Mode-Locked Yb:NaY(WO4)2 Soliton Laser

We experimentally demonstrated 45-fs soliton pulses from a diode-pumped passively mode-locked Yb:NaY(WO4)2 laser with a semiconductor saturable absorber mirror. The soliton pulses are centered at 1042 nm and have a repetition rate of ~113 MHz. To the best of our knowledge, this is the first demonstration of sub-50-fs soliton pulse generation from the Yb:NaY(WO4)2 lasers, and it is also the shortest pulses ever obtained from the Yb-doped tetragonal double tungstate crystal family until now.
A COMPARISON OF THE EFFECTS OF HIGH AND LOW VISCOSITY GELATINS AFTER THEIR INTRAVENOUS INJECTION IN MAN.

The need for a substitute for plasma in the treatment of shock in the past few years has resulted in renewed interest in the use of gelatin solutions for intravenous injection. Many investigators have shown that intravenous injections of specially prepared gelatin solutions are well tolerated by man (1 to 6). Gelatin is not a well defined chemical substance and its properties depend both upon the source material and the degree of molecular degradation during preparation. Studies at the Department of Physical Chemistry, Harvard Medical School, under the direction of Dr. E. J. Cohn (7) show that different lots of gelatin are best characterized by oncotic pressure, viscosity, and sedimentation pattern in the ultracentrifuge. In general, the least degraded products show the highest viscosity and the sharpest sedimentation pattern. The purpose of the present study was to compare the effects produced in man by the intravenous injection of two gelatin solutions that differed greatly in their physical properties. Each patient received at different times comparable amounts of a high viscosity and a low viscosity gelatin preparation.
First XMM-Newton observations of an isolated neutron star: RX J0720.4-3125

We present the high resolution spectrum of the isolated neutron star RX J0720.4-3125, obtained with the Reflection Grating Spectrometer on XMM-Newton , complemented with the broad band spectrum observed with the EPIC PN camera. The spectrum appears smooth, with no evidence for strong photospheric absorption or emission features. We briefly discuss the implications of our failure to detect structure in the spectrum.
Role of FKS Mutations in Candida glabrata: MIC Values, Echinocandin Resistance, and Multidrug Resistance

ABSTRACT Candida glabrata is the second leading cause of candidemia in U.S. hospitals. Current guidelines suggest that an echinocandin be used as the primary therapy for the treatment of C. glabrata disease due to the high rate of resistance to fluconazole. Recent case reports indicate that C. glabrata resistance to echinocandins may be increasing. We performed susceptibility testing on 1,380 isolates of C. glabrata collected between 2008 and 2013 from four U.S. cities, Atlanta, Baltimore, Knoxville, and Portland. Our analysis showed that 3.1%, 3.3%, and 3.6% of the isolates were resistant to anidulafungin, caspofungin, and micafungin, respectively. We screened 1,032 of these isolates, including all 77 that had either a resistant or intermediate MIC value with respect to at least one echinocandin, for mutations in the hot spot regions of FKS1 and FKS2, the major mechanism of echinocandin resistance. Fifty-one isolates were identified with hot spot mutations, 16 in FKS1 and 35 in FKS2. All of the isolates with an FKS mutation except one were resistant to at least one echinocandin by susceptibility testing. Of the isolates resistant to at least one echinocandin, 36% were also resistant to fluconazole. Echinocandin resistance among U.S. C. glabrata isolates is a concern, especially in light of the fact that one-third of those isolates may be multidrug resistant. Further monitoring of U.S. C. glabrata isolates for echinocandin resistance is warranted.
Exploring personality and motivational characteristics of student pre-drinkers

The purpose of this research was to investigate pre-drinking motivations and behaviour within the theoretical framework of reversal theory and the consideration of future consequences. This study assessed the Prepartying Motivations Inventory (PMI) and examined novel motivations identified through a thematic analysis. Pre-drinking was studied in relation to reversal theory as well as the consideration of future and immediate consequences. A sample of 248 undergraduate students completed an online survey consisting of open-ended questions, drinking and pre-drinking questions, a metamotivational state measure, the Motivational Style Profile, the Consideration of Future Consequences scale, the PMI, and a brief demographic questionnaire. It was demonstrated that pre-drinking motivations may be a function of metamotivational dominance, and that consideration of immediate consequences, telic dominance, negativism dominance, and arousal seeking, were significantly related to pre-drinking behaviour. Findings are discussed in terms of practical implications as well as suggestions for future research directions.
State-space analysis on time-varying correlations in parallel spike sequences

A state-space method for simultaneously estimating time-dependent rate and higher-order correlation underlying parallel spike sequences is proposed. Discretized parallel spike sequences are modeled by a conditionally independent multivariate Bernoulli process using a log-linear link function, which contains a state of higher-order interaction factors. A nonlinear recursive filtering formula is derived from a log-quadratic approximation to the posterior distribution of the state. Together with a fixed-interval smoothing algorithm, time-dependent log-linear parameters are estimated. The smoothed estimates are optimized via EM-algorithm such that their prior covariance matrix maximizes the expected complete data log-likelihood. In addition, we perform model selection on the hierarchical log-linear state-space models to avoid over-fitting. Application of the method to simultaneously recorded neuronal spike sequences is expected to contribute to uncover dynamic cooperative activities of neurons in relation to behavior.
Long-Term Treatment with High-Dose Thiamine in Parkinson Disease: An Open-Label Pilot Study.

OBJECTIVES To investigate the potential clinical, restorative, and neuroprotective effects of long-term treatment with thiamine in Parkinson disease (PD). DESIGN Observational open-label pilot study. SETTING Outpatient neurologic rehabilitation clinic. PATIENTS AND METHODS Starting in June 2012, we have recruited 50 patients with PD (33 men and 17 women; mean age, 70.4 ± 12.9 years; mean disease duration, 7.3 ± 6.7 years). All the patients were assessed at baseline with the Unified Parkinson's Disease Rating Scale (UPDRS) and the Fatigue Severity Scale (FSS) and began treatment with 100 mg of thiamine administered intramuscularly twice a week, without any change to personal therapy. All the patients were re-evaluated after 1 month and then every 3 months during treatment. RESULTS Thiamine treatment led to significant improvement of motor and nonmotor symptoms: mean UPDRS scores (parts I-IV) improved from 38.55 ± 15.24 to 18.16 ± 15.08 (p = 2.4 × 10(-14), t test for paired data) within 3 months and remained stable over time; motor UPDRS part III score improved from 22.01 ± 8.57 to 9.92 ± 8.66 (p = 3.1 × 10(-22)). Some patients with a milder phenotype had complete clinical recovery. FSS scores, in six patients who had fatigue, improved from 53.00 ± 8.17 to 23.60 ± 7.77 (p < 0.0001, t test for paired data). Follow-up duration ranged from 95 to 831 days (mean, 291.6 ± 207.2 days). CONCLUSIONS Administration of parenteral high-dose thiamine was effective in reversing PD motor and nonmotor symptoms. The clinical improvement was stable over time in all the patients. From our clinical evidence, we hypothesize that a dysfunction of thiamine-dependent metabolic processes could cause selective neural damage in the centers typically affected by this disease and might be a fundamental molecular event provoking neurodegeneration. Thiamine could have both restorative and neuroprotective action in PD.
Should You Stay Home with Your Baby

immediate family member. As a person who has specialized in the study of child development for more than twenty years, I am very disturbed by this situation. I'm worried most about the effects on children, but I'm also worried about the pressure being put on women who don't want to join in the trend. I'm also saddened by the thought that many adults stand to miss some of life's sweetest pleasures. I do not pretend to be expert in all aspects of family life. Rather, I present myself as someone with knowledge of the educational needs of young children. This message then will focus on the impact of various forms of childrearing on the development of the child. I am writing not only because I feel qualified to do so, but also because, in spite of the many privately expressed concerns, few of my colleagues have spoken out on this topic. I would like to state my position at the outset. Given the current incomplete state of knowledge about children's needs and substitute care, I firmly believe that most children will get off to a better start in life when they spend the majority of their waking hours being cared for by their parents and other family members rather than in any form of substitute care. The needs of infants and toddlers In the eyes of most students of human development, the first three years of life are extremely important and like no other. Clearly, the emotional development of babies is what most worries parents and experts. Few would debate the almost mystical significance of the mother-infant bond. Research from many fields, including psychiatry, child psychology and studies of other animal species, has confirmed a respect of the mother-infant bond and also has pointed to the first two years of life as the particular time in life when that bond forms (Scott, 1963; Bowlby, 1958). For obvious reasons, experiments have not been performed with babies to see how far childrearing practices can deviate from the ordinary before that bond is harmfully affected. However, information about major and lesser deviations from the normal has been gained from a few unusual kinds of circumstances. During this century, many studies have been performed involving physically normal babies reared in institutions (Bowlby, 1951; Yarrow, 1961). In most such instances, no single adult has had the primary responsibility for a baby. These studies have almost always indicated that the absence of a primary caretaker during a child's first few years produces serious emotional and psychological debilitation. Observing an "unattached" toddler is a chilling experience for most adults, and not many would advocate such institutional childrearing. What effects do lesser deviations from the usual have on
Lineup Construction and Lineup Fairness 2 2

1. Introduction. Police lineups come from English criminal law and procedure. According to Devlin (1976), lineups were instituted through a Middlesex magistrate's order in the mid 19 th century. They were intended as a 'fair' replacement for the practices of courtroom identification, and showups, which were widely used in 19 th century England, but widely recognized as potentially unfair to the defendant. Their origin indicates that the notion of 'fairness' is their raison d'etre. They are intended to secure an identification that can potentially incriminate someone, but also is fair to those who are subjected to it, particularly those who are innocent of the crime. Study of the case law in many countries, as well as recent DNA-based exonerations in the U.S., indicates that lineups are not invariably fair – many innocent people are convicted after identification from a lineup by an eyewitness. The problem is significant because eyewitness evidence is cited as the most significant source of wrongful conviction (Scheck, Neufeld, & Dwyer, 2001). The DNA exoneration cases where the false conviction is established with near certainty show that eyewitness evidence has been largely responsible for false conviction in more than 70% of cases (www.innocenceproj.org). Wrongful identifications result from a number of failures of police procedure, however many of these are minimized when the lineups presented to witnesses are fair. If witnesses are induced to make a lineup identification, a fair lineup will expose the innocent suspect to an identification risk of 1/the number of persons in the lineup. A lineup biased against the
The C-Terminal Dilysine Motif Confers Endoplasmic Reticulum Localization to Type I Membrane Proteins in Plants

The tomato Cf-9 disease resistance gene encodes a type I membrane protein carrying a cytosolic dilysine motif. In mammals and yeast, this motif promotes the retrieval of type I membrane proteins from the Golgi apparatus to the endoplasmic reticulum (ER). To test whether the C-terminal KKXX signal of Cf-9 is functional as a retrieval motif and to investigate its role in plants, green fluorescent protein (GFP) was fused to the transmembrane domain of Cf-9 and expressed in yeast, Arabidopsis, and tobacco cells. The fusion protein was targeted to the ER in each of these expression systems, and mutation of the KKXX motif to NNXX led to secretion of the fusion protein. In yeast, the mutant protein reached the vacuole, but plants secreted it as a soluble protein after proteolytic removal of the transmembrane domain. Triple hemagglutinin (HA)–tagged full-length Cf-9 was also targeted to the ER in tobacco cells, and cleavage was also observed for the NNXX mutant protein, suggesting an endoprotease recognition site located within the Cf-9 lumenal sequence common to both the GFP- and the HA-tagged fusions. Our results indicate that the KKXX motif confers ER localization in plants as well as mammals and yeast and that Cf-9 is a resident protein of the ER.
The Dialectics of Childhood Diarrhea Mortality

As in European countries a century ago, diarrhea is a major cause of child mortality in poor countries today. In Stockholm at the turn of the 19th century, political commitment, infrastructural investments in water and sanitation, and enforcement of sanitary improvements by a strong implementing organization helped eliminate diarrhea as a principal cause of death among children. These interventions also had an equitable impact on social class differences in diarrhea mortality, but not on overall mortality; overall mortality declined, but class differences remained. General infrastructural improvement and health education coupled with targeted interventions to vulnerable children may be successful in improving child health and reducing social differentials in mortality. Specific health care interventions may need to be complemented by infrastructural investments to improve water and sanitation if diarrhea mortality is to be further reduced in poor countries today.
CFD Modelling of Abdominal Aortic Aneurysm on Hemodynamic Loads Using a Realistic Geometry with CT

The objective of this study is to find a correlation between the abdominal aortic aneurysm (AAA) geometric parameters, wall stress shear (WSS), abdominal flow patterns, intraluminal thrombus (ILT), and AAA arterial wall rupture using computational fluid dynamics (CFD). Real AAA 3D models were created by three-dimensional (3D) reconstruction of in vivo acquired computed tomography (CT) images from 5 patients. Based on 3D AAA models, high quality volume meshes were created using an optimal tetrahedral aspect ratio for the whole domain. In order to quantify the WSS and the recirculation inside the AAA, a 3D CFD using finite elements analysis was used. The CFD computation was performed assuming that the arterial wall is rigid and the blood is considered a homogeneous Newtonian fluid with a density of 1050 kg/m3 and a kinematic viscosity of 4 × 10−3 Pa·s. Parallelization procedures were used in order to increase the performance of the CFD calculations. A relation between AAA geometric parameters (asymmetry index (β), saccular index (γ), deformation diameter ratio (χ), and tortuosity index (ε)) and hemodynamic loads was observed, and it could be used as a potential predictor of AAA arterial wall rupture and potential ILT formation.
Preclinical Evaluation of Liposomal C8 Ceramide as a Potent anti-Hepatocellular Carcinoma Agent

Hepatocellular carcinoma (HCC) remains a global health threat. The search for novel anti-HCC agents is urgent. In the current study, we synthesized a liposomal C8 ceramide, and analyzed its anti-tumor activity in pre-clinical HCC models. The liposomal C8 (ceramide) potently inhibited HCC cell (HepG2, SMMC-7721 and Huh-7 lines) survival and proliferation, more efficiently than free C8 ceramide. Yet, non-cancerous HL7702 human hepatocytes were resistant to the liposomal C8 treatment. Liposomal C8 activated caspase-dependent apoptosis in HCC cells, and HCC cytotoxicity by liposomal C8 was significantly attenuated with co-treatment of caspase inhibitors. At the molecular level, we showed that liposomal C8 activated ASK1 (apoptosis signal-regulating kinase 1)-JNK (Jun N-terminal protein kinase) signaling in HCC cells. On the other hand, JNK pharmacological inhibition or dominant negative mutation, as well as ASK1 shRNA-knockdown remarkably inhibited liposomal C8-induced apoptosis in HCC cells. Further studies showed that liposomal C8 inhibited AKT-mTOR (mammalian target of rapamycin) activation in HCC cells. Restoring AKT-mTOR activation by introducing a constitutively-active AKT alleviated HepG2 cytotoxicity by liposomal C8. In vivo, intravenous (i.v.) injection of liposomal C8 significantly inhibited HepG2 xenograft growth in severe combined immuno-deficient (SCID) mice, and mice survival was significantly improved. These preclinical results suggest that liposomal C8 could be further studied as a valuable anti-HCC agent.
A robust feature descriptor based on multiple gradient-related features

In this paper, we propose a robust descriptor named as multiple gradient-related features (MGRF) in virtue of local and overall order encoding. Specifically, three types of features are introduced, including multidirectional gradient, gradient orientation, and first derivative of gradient orientation, each of which represents different aspect of region of interest (ROI). To extract these features, we also propose a novel sampling pattern of tree structure. Furthermore, each gradient-related feature is encoded with both local and overall order information of ROI, and the encoding results are respectively called local and overall gradient order code (GOC). Finally, our descriptor is formed by concatenating the respective feature vector of each type of feature, which is computed as a 2-D joint histogram of GOC and ordinal bin. The experiments conducted on Oxford dataset demonstrate that the proposed descriptor significantly outperforms other state-of-the-art descriptors.
Forecast Timing and Reputational Concerns : Theory and Evidence

I develop a model in which analysts strategically time and exaggerate their forecasts to convince the public that they are skilled. The model’s key predictions are that an analyst will tend to forecast later if he has a better ex ante reputation, and he will tend to forecast earlier if the quality of public information is lower. Using a database of individual analysts’ earnings forecasts, I empirically test and find support for both of these predictions.
Processing Coordination Ambiguity

We examined temporarily ambiguous coordination structures such as put the butter in the bowl and the pan on the towel. Minimal Attachment predicts that the ambiguous noun phrase the pan will be interpreted as a noun-phrase coordination structure because it is syntactically simpler than clausal coordination. Constraint-based theories assume that interpretations are the result of a constraint-satisfaction process, which predicts that frequency or context can bias the parser to initially pursue a more complex interpretation. The results showed an initial preference for noun-phrase coordination, despite the fact that sentential coordination is more frequent in imperative structures. These data suggest that the parser uses a syntactic simplicity heuristic for building initial structural analyses.
The Evaluation of Training: An Organizational Culture Approach.

Recognizes the difficulties of evaluating training and argues that what is required to make it more effective is the adoption of an integrated approach to evaluation and, most significantly, the creation of an appropriate organizational culture, which promotes and recognizes the value of evaluation in general and training evaluation in particular. Discusses reasons for the absence of, or ineffective practice of, evaluation within so many organizations and these are shown to be related to organizational cultures which discourage training evaluation, especially organizational‐level evaluation. Discusses the nature and meaning of organizational culture from a practical point of view before providing advice to those responsible for training about how they can attempt to change an organization′s culture towards one which supports and values the evaluation of training.