Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and biochemical characterization of the SLC9A7 interactome

Organellar and cytosolic pH homeostasis is central to most cellular processes, including vesicular trafficking, post-translational modification/processing of proteins, and receptor-ligand interactions. SLC9A7 (NHE7) was identified as a unique (Na+, K+)/H+ exchanger that dynamically cycles between the trans-Golgi network (TGN), endosomes and the plasma membrane. Here we have used mass spectrometry to explore the affinity-captured interactome of NHE7, leading to the identification of cytoskeletal proteins, cell adhesion molecules, membrane transporters, and signaling molecules. Among these binding proteins, calcium-calmodulin, but not apo-calmodulin, binds to NHE7 and regulates the organellar transporter activity. Vimentin was co-immunoprecipitated with endogenous NHE7 protein in human breast cancer MDA-MB-231 cells. A sizable population of NHE7 relocalized to focal complexes in migrating cells and showed colocalization with vimentin and actin in focal complexes. Among the NHE7-binding proteins identified, CD44, a cell surface glycoprotein receptor for hyaluronate and other ligands, showed regulated interaction with NHE7. Pretreatment of the cells with phorbol ester facilitated the NHE7-CD44 interaction and the lipid raft association of CD44. When lipid rafts were chemically disrupted, the NHE7-CD44 interaction was markedly reduced. These results suggest potential dual roles of NHE7 in intracellular compartments and subdomains of cell-surface membranes.
Extracellular Matrix Composition and Remodeling in Human Abdominal Aortic Aneurysms: A Proteomics Approach*

Abdominal aortic aneurysms (AAA) are characterized by pathological remodeling of the aortic extracellular matrix (ECM). However, besides the well-characterized elastolysis and collagenolysis little is known about changes in other ECM proteins. Previous proteomics studies on AAA focused on cellular changes without emphasis on the ECM. In the present study, ECM proteins and their degradation products were selectively extracted from aneurysmal and control aortas using a solubility-based subfractionation methodology and analyzed by gel-liquid chromatography-tandem MS and label-free quantitation. The proteomics analysis revealed novel changes in the ECM of AAA, including increased expression as well as degradation of collagen XII, thrombospondin 2, aortic carboxypeptidase-like protein, periostin, fibronectin and tenascin. Proteomics also confirmed the accumulation of macrophage metalloelastase (MMP-12). Incubation of control aortic tissue with recombinant MMP-12 resulted in the extensive fragmentation of these glycoproteins, most of which are novel substrates of MMP-12. In conclusion, our proteomics methodology allowed the first detailed analysis of the ECM in AAA and identified markers of pathological ECM remodeling related to MMP-12 activity.
IGF-I Influences Everolimus Activity in Medullary Thyroid Carcinoma

Context Medullary thyroid carcinoma (MTC) is a rare tumor originating from thyroid parafollicular C cells. It has been previously demonstrated that insulin-like growth factor I (IGF-I) protects MTC from the effects of antiproliferative drugs. Everolimus, an mTOR inhibitor, has shown potent antiproliferative effects in a human MTC cell line, TT, and in two human MTC primary cultures. Objective To verify whether IGF-I may influence the effects of everolimus in a group of human MTC primary cultures. Design We collected 18 MTCs that were dispersed in primary cultures, treated without or with 10 nM–1 μM everolimus and/or 50 nM IGF-I. Cell viability was evaluated after 48 h, and calcitonin (CT) secretion was assessed after a 6 h incubation. IGF-I receptor downstream signaling protein expression profile was also investigated. Results Everolimus significantly reduced cell viability in eight MTC [by ~20%; P < 0.01 vs. control; everolimus-responders (E-R) MTCs], while cell viability did not change in 10 MTCs [everolimus-non-responders (E-NR) MTCs]. In E-R MTCs, IGF-I blocked the antiproliferative effects of everolimus that did not affect CT secretion, but blocked the stimulatory effects of IGF-I on this parameter. IGF-I receptor downstream signaling proteins were expressed at higher levels in E-NR MTC as compared to E-R MTCs. Conclusion IGF-I protects a subset of MTC primary cultures from the antiproliferative effects of everolimus and stimulates CT secretion by an mTOR mediated pathway that, in turn, may represent a therapeutic target in the treatment of aggressive MTCs.
Distinctive properties of CXC chemokine receptor 4‐expressing Cajal–Retzius cells versus GABAergic interneurons of the postnatal hippocampus

The CXC chemokine receptor 4 (CXCR4) for the chemokine (C‐X‐C motif) ligand 12/stromal cell‐derived factor‐1 α (CXCL12/SDF‐1 α) is highly expressed in the postnatal CA1 stratum lacunosum‐moleculare. However, both the network events triggered by SDF‐1 α in this microcircuit and the cellular targets of this chemokine remain virtually unexplored. Here, we have studied SDF‐1 α‐mediated neuromodulation of the stratum lacunosum‐moleculare by directly comparing the properties of CXCR4‐expressing Cajal–Retzius cells vs. CXCR4‐non‐expressing interneurons, and by recording the electrophysiological effects caused by application of SDF‐1 α on either cell type. We demonstrate that SDF‐1 α dramatically reduces spontaneous firing in Cajal–Retzius cells via hyerpolarization, and that cessation of firing is prevented by the CXCR4‐specific antagonist AMD3100. In contrast, no effects on the excitability of interneurons of the same layer were observed following exposure to the chemokine. We also provide evidence that, despite the expression of functional glutamate receptors, Cajal–Retzius cells are integrated in the synaptic network of the stratum lacunosum‐moleculare via excitatory GABAergic input. Furthermore, we show that the axons of Cajal–Retzius cells target specifically the stratum lacunosum‐moleculare and the dentate gyrus, but lack postsynaptic specializations opposite to their axonal varicosities. These results, taken together with our observation that SDF‐1 α reduces evoked field responses at the entorhinal cortex–CA1 synapse, suggest that Cajal–Retzius cells produce a diffuse output that may impact information processing of stratum lacunosum‐moleculare. We propose that pathological alterations of local levels of SDF‐1 α or CXCR4 expression may affect the functions of an important hippocampal microcircuit.
A facile method to observe graphene growth on copper foil

A novel scanning electron microscope (SEM) method is presented for high contrast identification of each layer of pyramidal graphene domains grown on copper. We obtained SEM images by combining the advantages of the high resolution property of the secondary electron signal and the elemental sensitivity of the backscattering electron signal. Through this method, we investigated the difference in the growth mechanisms of mono-layer and few-layer graphene. Due to different lattice mismatches, both the surface adsorption process and the epitaxial growth process existed under the atmospheric growth conditions. Moreover, the copper oxidation process can be easily discovered. It is obvious from the SEM images that the graphene greatly delayed the oxidation process of the copper surface. Finally, the nucleation and growth speed of graphene domains was found to depend on the linear array distribution of surface ledges and terraces of annealed rolled copper foil. This result explains the linear rows of graphene during the growth process and accords with theoretical results.
Classical Neurotransmitters and Neuropeptides Involved in Major Depression: a Review

ABSTRACT We propose several pathways that could be involved in major depression. According to our proposal, noradrenaline hypoactivity could occur through a strong presynaptic GABAergic inhibition, via GABAB receptors, and serotonin hypoactivity through a strong glutaminergic inhibition via subreceptor 5 of the metabotropic glutaminergic receptor. In this sense, it is important to know whether the antagonists of such receptors might be able to improve the symptoms observed in major depression. Some neuropeptides are also altered in such states (corticotropin-releasing hormone, neuropeptide Y, galanin). It is also important to know whether in addition to current antidepressants the administration of neuropeptides and their agonists/antagonists could ameliorate depressive symptoms.
Punitive parenting practices of contemporary young parents.

AIMS To describe the punitive parenting practices of a cohort of young (<25 years) New Zealand parents and to examine the life course risk factors that placed these parents at increased risk of severe child physical punishment/abuse. METHODS The data were gathered as part of the Christchurch Health and Development Study. At age 25, all respondents who had become a parent were interviewed about their parenting practices and family circumstances, including an assessment of child physical punishment/abuse using the Parent-Child Conflict Tactics Scale. The present analysis was confined to those young parents (n=155) who were living full-time with their children at the time of assessment. RESULTS Amongst this high-risk group of young parents, 77% reported having physically punished a child and almost 12% reported having severely physically assaulted a child in the past year. Although higher rates of child physical punishment were reported for parents of older children, a substantial proportion of parents reported having physically disciplined an infant (37%) or preschooler (84%) in their care. Risks of severe physical punishment/abuse were greatest amongst those young parents from lower socioeconomic status family backgrounds whose own parents were controlling, restrictive, and over-protective, and who (as young adult parents) were responsible for the care of larger numbers of children under conditions of socioeconomic and family functioning stress. CONCLUSIONS The use of physical punishment and more severe forms of physical assault/abuse are relatively common amongst contemporary young parents. Implications of study findings for social policy aimed at reducing levels of family violence in New Zealand are considered.
Multithreaded pipeline synthesis for data-parallel kernels

Pipelining is an important technique in high-level synthesis, which overlaps the execution of successive loop iterations or threads to achieve high throughput for loop/function kernels. Since existing pipelining techniques typically enforce in-order thread execution, a variable-latency operation in one thread would block all subsequent threads, resulting in considerable performance degradation. In this paper, we propose a multithreaded pipelining approach that enables context switching to allow out-of-order thread execution for data-parallel kernels. To ensure that the synthesized pipeline is complexity effective, we further propose efficient scheduling algorithms for minimizing the hardware overhead associated with context management. Experimental results show that our proposed techniques can significantly improve the effective pipeline throughput over conventional approaches while conserving hardware resources.
Explicit beat structure modeling for non-negative matrix factorization-based multipitch analysis

This paper proposes model-based non-negative matrix factorization (NMF) for estimating basis spectra and activations, detecting note onsets and offsets, and determining beat locations, simultaneously. Multipitch analysis is a process of detecting the pitch and onset of each note from a musical signal. Conventional NMF-based approaches often lead to unsatisfactory results very possibly due to the lack of musically meaningful constraints. As music is highly structured in terms of the temporal regularity underlying the onset occurrences of notes, we use this rhythmic structure to constrain NMF by parametrically modeling each note activation with a Gaussian mixture and derive an algorithm for iteratively updating model parameters. It is experimentally shown that the proposed model outperforms the standard NMF algorithms as regards onset detection rate.
Increased Cytoplasmic Localization of p27kip1 and Its Modulation of RhoA Activity during Progression of Chronic Myeloid Leukemia

The role of p27kip1 in Chronic Myeloid Leukemia (CML) has been well studied in relation to its function as a cell cycle inhibitor. However, its cytoplasmic function especially in CML remains to be seen. We studied the localization of p27kip1 and its function during the progression of CML from chronic to blast phase. Our investigations revealed an increased localization of p27kip1 in the cytoplasm of CD34+ cells in the blast phase compared to chronic phase. Cytoplasmic p27kip1 was found to modulate RhoA activity in CD34+ stem and progenitor cells. Further, RhoA activity was shown to be dependent on cytoplasmic p27kip1 which in turn was dependent on p210Bcr-Abl kinase activity. Interestingly, RhoA activity was observed to affect cell survival in the presence of imatinib through the SAPK/JNK pathway. Accordingly, inhibition of SAPK/JNK pathway using SP600125 increased apoptosis of K562 cells in presence of imatinib. Our results, for the first time, thus reveal a crucial link between cytoplasmic p27kip1, RhoA activity and SAPK/JNK signalling. To this effect we observed a correlation between increased cytoplasmic p27kip1, increased RhoA protein levels, decreased RhoA-GTP levels and increased SAPK/JNK phosphorylation in blast phase CD34+ cells compared to chronic phase CD34+ cells.
Universal Rendering Sequences for Transparent Vertex Caching of Progressive Meshes

We present methods to generate rendering sequences for triangle meshes which preserve mesh locality as much as possible. This is useful for maximizing vertex reuse when rendering the mesh using a FIFO vertex buffer, such as those available in modern 3D graphics hardware. The sequences are universal in the sense that they perform well for all sizes of vertex buffers, and generalize to progressive meshes. This has been verified experimentally.
THE USE OF FINANCIAL RATIOS AS MEASURES OF RISK IN THE DETERMINATION OF THE BID-ASK SPREAD

The effect of financial reports on stock market behavior is a central issue of research in accounting and finance. A number of studies investigate how financial information becomes impounded in security prices and affects investment decisions. Prior studies on the determinants of the bid-ask spread investigate the effect of market risk measures, and provide evidence that the bid-ask spread is a positive function of risk. Other studies report on an association between market risk measures and accounting risk measures. The present study extends this line of research by examining the effect of risk, proxied by accounting risk measures, on the bid-ask spread. The results of ordinary least squares (OLS) regressions provide evidence of a statistically significant association between certain accounting ratios and the bid-ask spread, and indicate that accounting risk measures account for more variability in the bid-ask spread than market risk measures. Most notably, the results indicate that a model which includes both accounting risk measures and market risk measures is a better fitted model that one which includes either accounting risk measures or market risk measures alone.
Personalized Forecasting Student Performance

This work proposes a novel approach - personalized forecasting - to take into account the sequential effect in predicting student performance (PSP). Instead of using all historical data as other methods in PSP, the proposed methods only use the information of the individual students for forecasting his/her own performance. Moreover, these methods also encode the "student effect" (e.g. how good/clever a student is, in performing the tasks) and "task effect" (e.g. how difficult/easy the task is) into the models. Experimental results show that the proposed methods perform nicely and much faster than the other state-of-the-art methods in PSP.
Secondary Waste Form Down-Selection Data Package—DuraLith

This data package developed for the DuraLith wasteform includes information available in the open literature and from data obtained from testing currently underway. DuraLith is an alkali-activated geopolymer waste form developed by the Vitreous State Laboratory at The Catholic University of America (VSL-CUA) for encapsulating liquid radioactive waste. A DuraLith waste form developed for treating Hanford secondary waste liquids is prepared by alkali-activation of a mixture of ground blast furnace slag and metakaolinite with sand used as a filler material. Based on optimization tests, solid waste loading of {approx}7.5% and {approx}14.7 % has been achieved using the Hanford secondary waste S1 and S4 simulants, respectively. The Na loading in both cases is equivalent to {approx}6 M. Some of the critical parameters for the DuraLith process include, hydrogen generation and heat evolution during activator solution preparation using the waste simulant, heat evolution during and after mixing the activator solution with the dry ingredients, and a working window of {approx}20 minutes to complete the pouring of the DuraLith mixture into molds. Results of the most recent testing indicated that the working window can be extended to {approx}30 minutes if 75 wt% of the binder components, namely, blast furnace slag and metakaolin are replaced by Class F fly ash. A preliminary DuraLith process flow sheet developed by VSL-CUA for processing Hanford secondary waste indicated that 10 to 22 waste monoliths (each 48 ft3 in volume) can be produced per day. There are no current pilot-scale or full-scale DuraLith plants under construction or in operation; therefore, the cost of DuraLith production is unknown. The results of the non-regulatory leach tests, EPA Draft 1313 and 1316, Waste Simulant S1-optimized DuraLith specimens indicated that the concentrations of RCRA metals (Ag, Cd, Cr, Hg, and Pb) in the leachates were well below the Universal Treatment Standard limits in 40 CFR 268.48. The data from the EPA draft 1315 leach test showed that LI values for COCs, namely 99Tc and I, ranged from 8.2 to 11.4 and 4.3 to 7.5, respectively. These values indicate that 99Tc meets the WAC LI requirement of 9.0 whereas, the LI values for I does not meet the WAC requirement of 11.0. Results of Toxicity Characteristic Leaching Procedure (TCLP)(EPA Method 1311) conducted on Waste Simulant S1-optimized DuraLith specimens, indicated that the concentrations of RCRA metals (Ag, As, Cd, Cr, Hg, and Pb) in the leachates were well below the Universal Treatment Standard limits in 40 CFR 268.48. The data from the ANSI/ANS 16.1 leach test showed that LI values for COC, namely Re (as a Tc surrogate), ranged from 8.06 to 10.81. The LI value for another COC, namely I, was not measured in this test. The results of the compressive strength testing of Waste Simulant S1-optimized DuraLith specimens indicated that the monoliths were physically robust with compressive strengths ranging from 115.5 MPa (16757 psi) to 156.2 MPA (22667 psi).
Uptake of lamivudine by rat renal brush border membrane vesicles

Uptake of lamivudine, a nucleoside analogue antiviral agent, by brush border membrane vesicles (BBMV) prepared from rat renal cortex was investigated. Initial uptake of lamivudine by BBMV was stimulated in the presence of an outward pH gradient. Determination of the kinetic parameters of the initial uptake yielded apparent Km and Vmax values of 2.28 mM and 1.56 nmol (mg protein)−1 (20 s)−1, respectively. The pH‐driven uptake of lamivudine was inhibited by organic cations such as trimethoprim and cimetidine. The inhibitory effect of trimethoprim on lamivudine uptake was competitive, with an apparent Ki of 27.6 μM. The uptake of lamivudine was also inhibited by nitrobenzylthioinosine, a representative inhibitor of nucleoside transport, and by other nucleoside analogues, such as azidothymidine and dideoxycytidine, that are excreted by renal tubular secretion. These findings suggest that efflux of lamivudine at the brush border membrane of renal tubular epithelium is mediated by an H+/lamivudine antiport system, which may correspond to the H+/organic cation antiport system, and that this system is also involved in the renal secretion of other nucleoside analogues.
Estimation of variances due to direct and maternal effects for growth traits of Nelore cattle.

Estimates of (co)variance components and genetic parameters were obtained for birth, 205-d, and 365-d weight for Nelore cattle in Brazil, using single and multiple-trait animal models. Data were from the Brazilian Zebu Breeders Association (ABCZ). Records of 27,549 calves sired by 587 bulls and raised on pasture in 57 herds were analyzed by restricted maximum likelihood fitting an animal model including direct and maternal genetic and permanent environmental effects. Single and multiple-trait analyses were carried out. Heritability estimates for direct effects were lower than previous values reported for the Nelore breed. The estimates for maternal genetic effects showed that the contribution of this component to the phenotypic variance of birth and weaning weight is not very high but is still present at yearling weight. Correlations between direct and maternal additive genetic effects were negative for all traits analyzed except for yearling weight in the single-trait analysis where the sign was positive but the magnitude was small (+.09). Genetic correlations between weaning and yearling weights were . 74 (direct effect) and . 84 (maternal effect). Permanent environmental and residual correlations among traits were also obtained.
Selection and Peer-review under Responsibility of the Organizing Committee of Espera 2013 Selection and Peer-review under Responsibility of the Organizing Committee of Espera 2013

The public debt in Romania-factors of influence, scenarios for the future and a sustainability analysis considering both a finite and infinite time horizon Abstract This paper, starting from the public debt equations and the intertemporal budget constraint proposes an analysis of the evolution of public debt to GDP ratio in Romania during the 2002-2013 periods, identifying the main factors of influence and also performs a sustainability analysis on both a finite and infinite time horizon. Thus, the paper determines the gap to the level of primary balance consistent with debt sustainability under different scenarios and concludes that the current level of public indebtedness, alongside with the long term projections of the underlying factors of influence ensure the fulfillment of the obligations to the creditors.
ournal of Statistical Mechanics : J Theory and Experiment Towards a self-consistent description of irregular and asynchronous cortical activity

Experimental evidence shows that cortical activity exhibits correlated variability, often referred to as noise correlations. Reported correlation coefficients cover a wide range of values, from moderate to very small ones. There is an evident need of models and mathematical techniques with which to guide the interpretation of these results. However, the very existence of correlated variability is responsible for the technical difficulties that have prevented theory from making enough progress in determining how noise correlations are related to neuron and network properties. Here we review recent work that we have done to develop a program to study these issues. Given that noise correlations depend on the behavioral state, understanding how they are generated is a critical problem that has to be solved before biophysical models can be used to study behavioral tasks.