Miracle-dz/UniFAR-FTUs huggingface dataset:
Piccolo Promotes Vesicle Replenishment at a Fast Central Auditory Synapse

Piccolo and Bassoon are the two largest cytomatrix of the active zone (CAZ) proteins involved in scaffolding and regulating neurotransmitter release at presynaptic active zones (AZs), but have long been discussed as being functionally redundant. We employed genetic manipulation to bring forth and segregate the role of Piccolo from that of Bassoon at central auditory synapses of the cochlear nucleus—the endbulbs of Held. These synapses specialize in high frequency synaptic transmission, ideally poised to reveal even subtle deficits in the regulation of neurotransmitter release upon molecular perturbation. Combining semi-quantitative immunohistochemistry, electron microscopy, and in vitro and in vivo electrophysiology we first studied signal transmission in Piccolo-deficient mice. Our analysis was not confounded by a cochlear deficit, as a short isoform of Piccolo (“Piccolino”) present at the upstream ribbon synapses of cochlear inner hair cells (IHC), is unaffected by the mutation. Disruption of Piccolo increased the abundance of Bassoon at the AZs of endbulbs, while that of RIM1 was reduced and other CAZ proteins remained unaltered. Presynaptic fiber stimulation revealed smaller amplitude of the evoked excitatory postsynaptic currents (eEPSC), while eEPSC kinetics as well as miniature EPSCs (mEPSCs) remained unchanged. Cumulative analysis of eEPSC trains indicated that the reduced eEPSC amplitude of Piccolo-deficient endbulb synapses is primarily due to a reduced readily releasable pool (RRP) of synaptic vesicles (SV), as was corroborated by a reduction of vesicles at the AZ found on an ultrastructural level. Release probability seemed largely unaltered. Recovery from short-term depression was slowed. We then performed a physiological analysis of endbulb synapses from mice which, in addition to Piccolo deficiency, lacked one functional allele of the Bassoon gene. Analysis of the double-mutant endbulbs revealed an increase in release probability, while the synapses still exhibited the reduced RRP, and the impairment in SV replenishment was exacerbated. We propose additive roles of Piccolo and Bassoon in SV replenishment which in turn influences the organization and size of the RRP, and an additional role of Bassoon in regulation of release probability.
Integrating Acoustic, Prosodic and Phonotactic Features for Spoken Language Identification

The fundamental issue of the automatic language identification is to explore the effective discriminative cues for languages. This paper studies the fusion of five features at different level of abstraction for language identification, including spectrum, duration, pitch, n-gram phonotactic, and bag-of-sounds features. We build a system and report test results on NIST 1996 and 2003 LRE datasets. The system is also built to participate in NIST 2005 LRE. The experiment results show that different levels of information provide complementary language cues. The prosodic features are more effective for shorter utterances while the phonotactic features work better for longer utterances. For the task of 12 languages, the system with fusion of five features achieved 2.38% EER for 30-sec speech segments on NIST 1996 dataset
Identification of Osteoporosis-Associated Protein Biomarkers from Ovariectomized Rat Urine

Objective: Osteoporotic fracture is one of the most common health risks and aggravates the quality of life among postmenopausal women worldwide. In this study, osteoporosis-associated protein biomarkers were identified from urine of osteoporotic female Sprague-Dawley rats developed by ovariectomy. Method: Four months after the operation, the bone mineral density of the femur of ovariectomized rats was significantly lowered in comparison with that of the sham operated rats. The protein profiles of the urine samples collected from the sham, ovariectomized (OVX) and 2 month-old non-operated (Young) rats were compared by 2-D gel and MS spectrometry. Results: Proteins consistently expressed between Young and sham but differentially expressed in OVX rats were selected and identified. One down-regulated 21 kDa protein, superoxide dismutase (SOD), and 1 up-regulated 53-54 kDa protein, alph-1-antitrypsin (A1AT), were selected from urine of the ovariectomized rats by 2-D gel analysis. Further, a total of 30 with 19 up-regulated and 11-down-regulated proteins were selected by LC-MS analysis with more than 2-fold differences in spectral counts. The fact that SOD and A1AT are also listed in the 30 differential proteins suggests that our biomarker isolation procedure suitably represents osteoporosis-associated proteins in urine. Conclusion: Supporting the facts, the differential expressions of SOD and A1AT in urine could be validated by Western blotting. These urinary osteoporosis-associated proteins have high potentials to become candidates for non-invasive diagnosis of osteoporosis from urine.
Stable stochastic receding horizon control of linear systems with bounded control inputs

We address stability of receding horizon control for stochastic linear systems with additive noise and bounded control authority. We construct tractable and recursively feasible receding horizon control policies that ensure a mean-square bounded system in closed-loop if the noise has bounded forthorder moment, the unexcited system is stabilizable, the system matrix A is Lyapunov stable, and there is large enough control authority.
Participation in recreational activities in school age children with high functioning autism and their peers

The patterns of recreational engagement and health related quality of life (HRQL) of school-aged children with High Functioning Autism (HFA) are not well understood. The objectives of this study of children with HFA and their typically developing peers were to: compare their recreational profiles; identify child-based factors related to recreational participation; and, estimate their HRQL in relation to recreational engagement. Additionally, the psychometric properties of the Children’s Assessment of Participation and Enjoyment/ Preference for Activities of Children (CAPE/PAC) for this population were estimated. A cross sectional study of a volunteer sample of children with HFA (n=30) and peers (n=31) recruited through multiple Vermont sources was conducted. Data collection took place during 2-3 home visits. Standardized and psychometrically sound tools were used to independently confirm diagnosis and ascertain children’s characteristics. The CAPE/PAC and Pediatric Quality of Life 4.0 were the primary outcome measures. The groups were similar on key characteristics except those related to the HFA attributes. Children with HFA differed from peers in terms of diversity (p=.002), social aspects (p=.006) and locations (p<.001) of recreational participation. The two groups were not statistically different in personal intensity (p=.684), enjoyment (p=.239) or preferences (p=.788) of recreation. Children with HFA had significantly poorer HRQL whether reported by themselves (p<.001) or their parents (p<.001), although disagreement (ICC=-.075) between children and parental scores suggested that they had different viewpoints about children’s HRQL. The study results have value for parents, clinicians, teachers and administrators in understanding and supporting the recreational engagement of children with HFA.
Isotope Coded Protein Labeling Coupled Immunoprecipitation (ICPL-IP): A Novel Approach for Quantitative Protein Complex Analysis From Native Tissue*

High confidence definition of protein interactions is an important objective toward the understanding of biological systems. Isotope labeling in combination with affinity-based isolation of protein complexes has increased in accuracy and reproducibility, yet, larger organisms—including humans—are hardly accessible to metabolic labeling and thus, a major limitation has been its restriction to small animals, cell lines, and yeast. As composition as well as the stoichiometry of protein complexes can significantly differ in primary tissues, there is a great demand for methods capable to combine the selectivity of affinity-based isolation as well as the accuracy and reproducibility of isotope-based labeling with its application toward analysis of protein interactions from intact tissue. Toward this goal, we combined isotope coded protein labeling (ICPL)1 with immunoprecipitation (IP) and quantitative mass spectrometry (MS). ICPL-IP allows sensitive and accurate analysis of protein interactions from primary tissue. We applied ICPL-IP to immuno-isolate protein complexes from bovine retinal tissue. Protein complexes of immunoprecipitated β-tubulin, a highly abundant protein with known interactors as well as the lowly expressed small GTPase RhoA were analyzed. The results of both analyses demonstrate sensitive and selective identification of known as well as new protein interactions by our method.
Suppressor of Cytokine Signaling 1 Regulates IL-15 Receptor Signaling in CD8+CD44high Memory T Lymphocytes 1

T lymphocyte survival, proliferation, and death in the periphery are dependent on several cytokines. Many of these cytokines induce the expression of suppressor of cytokine signaling-1 (SOCS1), a feedback inhibitor of JAK kinases. However, it is unclear whether the cytokines that regulate T lymphocyte homeostasis are critically regulated by SOCS1 in vivo. Using SOCS1−/−IFN-γ−/− mice we show that SOCS1 deficiency causes a lymphoproliferative disorder characterized by decreased CD4/CD8 ratio due to chronic accumulation of CD8+CD44high memory phenotype T cells. SOCS1-deficient CD8+ T cells express elevated levels of IL-2Rβ, show increased proliferative response to IL-15 and IL-2 in vitro, and undergo increased bystander proliferation and vigorous homeostatic expansion in vivo. Sorted CD8+CD44high T cells from SOCS1−/−IFN-γ−/− mice respond 5 times more strongly than control cells, indicating that SOCS1 is a critical regulator of IL-15R signaling. Consistent with this idea, IL-15 stimulates sustained STAT5 phosphorylation in SOCS1-deficient CD8+ T cells. IL-15 strongly induces TNF-α production in SOCS1-deficient CD8+ T cells, indicating that SOCS1 is also a critical regulator of CD8+ T cell activation by IL-15. However, IL-15 and IL-2 induce comparable levels of Bcl-2 and Bcl-xL in SOCS1-deficient and SOCS1-sufficient CD8+ T cells, suggesting that cytokine receptor signals required for inducing proliferation and cell survival signals are not identical. These results show that SOCS1 differentially regulates common γ-chain cytokine signaling in CD8+ T cells and suggest that CD8+ T cell homeostasis is maintained by distinct mechanisms that control cytokine-mediated survival and proliferation signals.
Kepler Eclipsing Binary Stars. V. Identification of 31 Candidate Eclipsing Binaries in the K2 Engineering Dataset

Over 2500 eclipsing binaries were identified and characterized from the ultraprecise photometric data provided by the Kepler space telescope. Kepler is now beginning its second mission, K2, which is proving to again provide ultraprecise photometry for a large sample of eclipsing binary stars. In the 1951 light curves covering 12 days in the K2 engineering dataset, we have identified and determined the ephemerides for 31 candidate eclipsing binaries that demonstrate the capabilities for eclipsing binary science in the upcoming campaigns in K2. Of those, 20 are new discoveries. We describe both manual and automated approaches to harvesting the complete set of eclipsing binaries in the K2 data, provide identifications and details for the full set of candidate eclipsing binaries present in the engineering dataset, and discuss the prospects for application of eclipsing binary searches in the K2 mission.
Testing for Group Effect in a 2 × k Heteroscedastic ANOVA Model

It is natural to want to relax the assumption of homoscedasticity and Gaussian error in ANOVA models. For a two‐way ANOVA model with 2 × k cells, one can derive tests of main effect for the factor with two levels (referred to as group) without assuming homoscedasticity or Gaussian error. Empirical likelihood can be used to derive testing procedures. An approximate empirical likelihood ratio test (AELRT) is derived for the test of group main effect. To approximate the distributions of the test statistics under the null hypothesis, simulation from the approximate empirical maximum likelihood estimate (AEMLE) restricted by the null hypothesis is used. The homoscedastic ANOVA F ‐test and a Box‐type approximation to the distribution of the heteroscedastic ANOVA F ‐test are compared to the AELRT in level and power. The AELRT procedure is shown by simulation to have appropriate type I error control (although possibly conservative) when the distribution of the test statistics are approximated by simulation from the constrained AEMLE. The methodology is motivated and illustrated by an analysis of folate levels in the blood among two alcohol intake groups while accounting for gender. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dimensionality and the category of major depressive episode

Major depressive episode (MDE) is a chronic disease typified by episodes that remit and recur. It is a major contributor to the burden of disease. The diagnosis of a disorder is an expert opinion that the disorder is present. The nine symptoms of MDE exist on dimensions of greater or lesser intensity, persistence over time, change in usual state, distress and impairment. It is the clinician's task to judge whether the elicited symptoms warrant the diagnosis. The surprise is that trained clinicians can do this reliably and that diagnostic interviews and questionnaires can emulate this process.
Linear Modeling and Regulation Quality Analysis for Hydro-Turbine Governing System with an Open Tailrace Channel

On the basis of the state–space method (SSM), a novel linear mathematical model of the unsteady flow for the tailrace system with an open channel is proposed. This novel model is an elastic linearized model of water hammer. The validity of the model has been verified by several examples of numerical simulation, which are based on a finite difference technique. Then, the complete mathematical model for the hydro-turbine governing system of hydropower station with an open tailrace channel, which is used for simulating the transient process of the hydro-turbine governing system under load disturbance, is established by combining the models of hydro-turbine, generator, governor and open tailrace channel. Finally, according to the complete model, the regulation quality for hydro-turbine governing system with an open tailrace channel under load disturbance is studied, and the effects of open tailrace channel and tailrace surge tank on regulation quality are analyzed. The results indicate that: The open tailrace channel has a strong influence on the regulation quality by observing the water level fluctuations in tailrace surge tank. The surge shows a piecewise periodical change along with the variation in the length of an open channel. The open tailrace channel can be used to improve the regulation quality of hydro-turbine governing system.
PHOSPHORUS CYCLING AND ALGAL-BACTERIAL COMPETITION IN SANDSFJORD, WESTERN NORWAY

Microbial phosphorus-cycling, with particular emphasis on algal/bacterial competition, was studied in depth profiles through the halocline separating a brackish top layer, rich in nitrate and poor in phosphate, from the underlying coastal water, poor in both nitrate and phosphate, in the Sandsfjord area, western Norway. At 2 stations along the axis of natural freshwater outflow, physiological P-deficiency of algae and bacteria in the brackish layer was inferred from rapid luxury consumption of added PO43- by organisms in size fractions > 1 mum and 1-0.2 mum, respectively. In a branch of the fjord without natural freshwater outlets, luxury consumption in the brackish layer was less, and without a clear difference between the 2 water layers. High luxury consumption coincided with short ( 1 mum and 1-0.2 mum was found to depend on whether label was added as (gamma-AVP)-P-32 or as (PO43-)-P-32, indicating that coupling of uptake to hydrolysis by cell-bound enzymes could modify the outcome of algal-bacterial phosphorus competition. Disappearance rate of P-32 from the 1-0.2 mum size fraction following initial labeling and a subsequent cold chase with PO43- was used to estimate the flow-rate of phosphorus through the microbial food web. Combined with measured kinetic constants for PO43- uptake, alkaline phosphatases and 5'nucleotidases, a coherent flow-scheme could only be obtained assuming very low (< 1 nmol l-1) concentrations of PO43- and nucleotides. Chemically measured concentrations of dissolved organic phosphorus (DOP) more than 2 orders of magnitude above the estimated nucleotide level and with an estimated turnover time of ca 500 h, are consistent with the view that this large P-reservoir consists mainly of slowly hydrolyzable polymers.
Sucrose compared with artificial sweeteners: a clinical intervention study of effects on energy intake, appetite, and energy expenditure after 10 wk of supplementation in overweight subjects.

BACKGROUND There is a lack of appetite studies in free-living subjects supplying the habitual diet with either sucrose or artificially sweetened beverages and foods. Furthermore, the focus of artificial sweeteners has only been on the energy intake (EI) side of the energy-balance equation. The data are from a subgroup from a 10-wk study, which was previously published. OBJECTIVE The objective was to investigate changes in EI and energy expenditure (EE) as possible reasons for the changes in body weight during 10 wk of supplementation of either sucrose or artificial sweeteners in overweight subjects. DESIGN Supplements of sucrose-sweetened beverages and foods (2 g/kg body weight; n = 12) or similar amounts containing artificial sweeteners (n = 10) were given single-blind in a 10-wk parallel design. Beverages accounted for 80% and solid foods for 20% by weight of the supplements. The rest of the diet was free choice. Indirect 24-h whole-body calorimetry was performed at weeks 0 and 10. At week 0 the diet was a weight-maintaining standardized diet. At week 10 the diet consisted of the supplements and ad libitum choice of foods. Visual analog scales were used to record appetite. RESULTS Body weight increased in the sucrose group and decreased in the sweetener group during the intervention. The sucrose group had a 3.3-MJ higher EI but felt less full and had higher ratings of prospective food consumption than did the sweetener group at week 10. Basal metabolic rate was increased in the sucrose group, whereas 24-h EE was increased in both groups at week 10. Energy balance in the sucrose group was more positive than in the sweetener group at the stay at week 10. CONCLUSION The changes in body weight in the 2 groups during the 10-wk intervention seem to be attributable to changes in EI rather than to changes in EE.
Anabaena sp. strain PCC 7120 bifA gene encoding a sequence-specific DNA-binding protein cloned by in vivo transcriptional interference selection

VF1 is a DNA-binding protein from the cyanobacterium Anabaena sp. strain PCC 7120. VF1 was originally identified on the basis of its binding affinity to the upstream region of xisA, which encodes a heterocyst-specific site-specific recombinase. VF1 also binds to the glnA, rbcL, and nifH promoters in vitro, suggesting that VF1 interacts with genes expressed in both vegetative cells and heterocysts. The role of VF1 in regulating gene expression in PCC 7120 is unknown. As a step towards the goal of understanding the role of VF1 in regulating gene expression, we have cloned the bifA gene by using a genetic selection strategy. bifA encodes a protein, BifA, that has chromatographic and DNA-binding properties indistinguishable from those of VF1. The cloning strategy was based on a transcriptional interference assay in which a strong synthetic promoter, conII, interferes with the expression of an aadA gene, which provides resistance to spectinomycin and streptomycin (S. J. Elledge, P. Sugiono, L. Guarente, and R. W. Davis, Proc. Natl. Acad. Sci. USA 86:3689-3693, 1989). A selection plasmid, pAM994, which has the conII promoter negatively regulated by a VF1-binding site, was used to enrich for VF1-producing clones from an expression library containing PCC 7120 DNA fragments. Mobility shift assays were used to identify a 672-bp open reading frame that encoded VF1-like binding activity. The deduced BifA amino acid sequence shows 77% identity to NtcA, which is a global regulator involved in nitrogen control in Synechococcus sp. strain PCC 7942. Both BifA and NtcA belong to the cyclic AMP receptor protein (CRP) family of prokaryotic regulatory proteins. Genes similar to envM, hisB, and ORF60-5 were found near the bifA gene.
Increasing access to specialty care: A pilot, randomized controlled trial of telemedicine for Parkinson's disease

We conducted a randomized, controlled pilot trial to evaluate the feasibility of providing subspecialty care via telemedicine for patients with Parkinson's disease residing in a remote community located ∼130 miles from an academic movement disorders clinic. Study participants were randomized to receive telemedicine care with a movement disorder specialist at the University of Rochester or to receive their usual care. Participants in the telemedicine group received three telemedicine visits over six months. Feasibility, as measured by the completion of telemedicine visits, was the primary outcome measure. Secondary measures were quality of life, patient satisfaction, and clinical outcomes. Ten participants residing in the community were randomized to receive telemedicine care (n = 6) or their usual care (n = 4). Four nursing home patients were assigned to telemedicine. Those receiving telemedicine completed 97% (29 of 30) of their telemedicine visits as scheduled. At the study's conclusion, 13 of 14 study participants opted to receive specialty care via telemedicine. Compared with usual care, those randomized to telemedicine had significant improvements in quality of life (3.4 point improvement vs. 10.3 point worsening on the Parkinson's Disease Questionnaire 39; P = 0.04) and motor performance (0.3 point improvement vs. 6.5 point worsening on the Unified Parkinson's Disease Rating Scale, motor subscale; P = 0.03). Relative to baseline, nursing home patients experienced trends toward improvement in quality of life and patient satisfaction. Providing subspecialty care via telemedicine for individuals with Parkinson's disease living remotely is feasible. © 2010 Movement Disorder Society
The effects of chelating agents on radical generation in alkaline peroxide systems, and the relevance to substrate damage

A spin-trapping EPR technique has been employed to explore the generation of hydroxyl radicals from reactions between a series of first row transition metal ions and aqueous hydrogen peroxide at pH 10, and with a range of chelating agents (EDTA, DTPMP and the readily biodegradable ligands S,S-EDDS and IDS). In the absence of these chelating agents only Cu(II) generates a significant level of hydroxyl radicals; in their presence with Cu(II) EDTA and IDS give similar behaviour whereas EDDS and DTPMP inhibit hydroxyl radical generation. For Fe(II), EDTA, DTPMP and IDS significantly enhance √OH production under these conditions whereas EDDS does not. Results from model cellulose damage experiments broadly confirm the findings for copper, though experiments with Fe(II) lead to somewhat contrasting results. Our findings are discussed in terms of binding constants and implications for alkaline peroxygen bleaching systems.