Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Macroautophagy Triggers Apoptosis

ABSTRACT Mammalian cells were observed to die under conditions in which nutrients were depleted and, simultaneously, macroautophagy was inhibited either genetically (by a small interfering RNA targeting Atg5, Atg6/Beclin 1-1, Atg10, or Atg12) or pharmacologically (by 3-methyladenine, hydroxychloroquine, bafilomycin A1, or monensin). Cell death occurred through apoptosis (type 1 cell death), since it was reduced by stabilization of mitochondrial membranes (with Bcl-2 or vMIA, a cytomegalovirus-derived gene) or by caspase inhibition. Under conditions in which the fusion between lysosomes and autophagosomes was inhibited, the formation of autophagic vacuoles was enhanced at a preapoptotic stage, as indicated by accumulation of LC3-II protein, ultrastructural studies, and an increase in the acidic vacuolar compartment. Cells exhibiting a morphology reminiscent of (autophagic) type 2 cell death, however, recovered, and only cells with a disrupted mitochondrial transmembrane potential were beyond the point of no return and inexorably died even under optimal culture conditions. All together, these data indicate that autophagy may be cytoprotective, at least under conditions of nutrient depletion, and point to an important cross talk between type 1 and type 2 cell death pathways.
Bradykinin Regulates Osteoblast Differentiation by Akt/ERK/NFκB Signaling Axis

Bradykinin (BK), a well known mediator of pain and inflammation, is also known to be involved in the process of bone resorption. The present study therefore evaluated the role of BK in osteoblast lineage commitment. Our data showed that BK inhibits the migration of bone marrow mesenchymal stem cells, but does not affect their viability. Moreover, BK also inhibits osteoblastic differentiation by significantly downregulating the levels of mRNAs for osteopontin, runX2, col24, osterix, osteocalcin genes and bone mineralization (P < 0.05). Further, BK was found to elicit the BK receptors (BDKR1 and BDKR2) mediated activation of ERK1/2 and Akt pathways, which finally led to the activation of NFκB. BK also promoted the osteoclast differentiation of bone marrow derived preosteoclast cells by upregulating the expression of c‐fos, NFATC1, TRAP, clcn7, cathK, and OSCAR genes and increasing TRAP activity through NFκB pathway. In conclusion, our data suggest that BK decreases the differentiation of osteoblasts with concomitant increase in osteoclast formation and thus provides new insight into the mechanism of action of BK in modulating bone resorption. J. Cell. Physiol. 229: 2088–2105, 2014. © 2014 Wiley Periodicals, Inc.
Influence of crystallographic structure on polarization reversal in polycrystalline ferroelectric/ferroelastic materials

Polarization reversal is the most fundamental physical process in ferroelectrics and directly or indirectly influences all functional properties of these materials. While this process is influenced by various intrinsic material’s properties and external boundary conditions, arguably one of the most dominant parameters is the material’s crystallographic structure. In this work, the influence of the crystallographic structure on the polarization reversal was investigated on the model ferroelectric system Pb(Zr,Ti)O3 using simultaneous time-dependent polarization and strain measurements. This method enabled one to extend the understanding beyond the widely investigated relationship between the structure and coercive fields. Polarization reversal was described by three regimes, which represent a sequence of well-defined non-180° and 180° switching events. The crystallographic structure was found to largely influence the mobility of the non-180° domain walls during the first switching regime, the amplitude of negative strain, and the broadness of the transition between the first and the second switching regimes, as well as the speed of the second (main) switching regime. The observed changes could be related to the amount of possible polarization directions, distribution of the local electric fields, and strain mismatch at domain wall junctions influenced by the lattice distortion. Moreover, activation fields for the first and the second regimes were experimentally determined for the investigated series of Pb(Zr,Ti)O3 samples. Besides providing insight into fundamental mechanisms of polarization reversal, these results can also be used as input parameters for micromechanical or stochastic models.Polarization reversal is the most fundamental physical process in ferroelectrics and directly or indirectly influences all functional properties of these materials. While this process is influenced by various intrinsic material’s properties and external boundary conditions, arguably one of the most dominant parameters is the material’s crystallographic structure. In this work, the influence of the crystallographic structure on the polarization reversal was investigated on the model ferroelectric system Pb(Zr,Ti)O3 using simultaneous time-dependent polarization and strain measurements. This method enabled one to extend the understanding beyond the widely investigated relationship between the structure and coercive fields. Polarization reversal was described by three regimes, which represent a sequence of well-defined non-180° and 180° switching events. The crystallographic structure was found to largely influence the mobility of the non-180° domain walls during the first switching regime, the amplitude of .
Protein kinase C‐mediated phosphorylation of the human multidrug resistance P‐glycoprotein regulates cell volume‐activated chloride channels.

The multidrug resistance P‐glycoprotein (P‐gp), which transports hydrophobic drugs out of cells, is also associated with volume‐activated chloride currents. It is not yet clear whether P‐gp is a channel itself, or whether it is a channel regulator. Activation of chloride currents by hypotonicity in cells expressing P‐gp was shown to be regulated by protein kinase C (PKC). HeLa cells exhibited volume‐activated chloride currents indistinguishable from those obtained in P‐gp‐expressing cells except that they were insensitive to PKC. HeLa cells did not express detectable P‐gp but, following transient transfection with cDNA encoding P‐gp, the volume‐activated channels acquired PKC regulation. PKC regulation was abolished when serine/threonine residues in the consensus phosphorylation sites of the linker region of P‐gp were replaced with alanine. Replacement of these residues with glutamate, in order to mimic the charge of the phosphorylated protein, also mimicked the effects of PKC on channel activation. These data demonstrate that PKC‐mediated phosphorylation of P‐gp regulates the activity of an endogenous chloride channel and thus indicate that P‐gp is a channel regulator.
Strengthening governance and accountability: putting Africans at the center of social services

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Query Understanding for Search on All Devices at WSDM 2016

It is our great pleasure to welcome you to the QRUMS 2016, the workshop on Query Understanding for Search on All Devices, held as part of the WSDM 2016 conference in San Francisco, USA. Theme and Purpose of the workshop: Query understanding has become a crucial component for today’s search engines. It is important to improve query understanding as query formulation is the way through which users express their search intent to a search engine. With the ubiquitousness of mobile devices, it is even more important to better understand user intent as typing on mobile is hard and time consuming. This workshop focuses on query understanding for mobile search with a motivation of reducing user efforts in formulating queries and getting their expected search results quickly. One of the most important problem in query understanding is Query auto-completion (QAC). QAC is the first service through which users interact with a search engine to input their search intent. QAC has to provide and update their suggestion lists based on each new character typed by the user in the search box. Returned suggestion lists are ranked based on different relevance models, such as most popular completion (based on historical frequency counts from query logs) [1], time-based (giving more weight to breaking news or recent popular queries) [10, 12, 11], location-based [9], context-sensitive (based on user’s context) [1, 5], personalized (based on user’s profile) [9], click modeling (based on user’s past clicks) [6], user-QAC interactions [8, 4], adaptive query auto-completion [13]. QAC becomes even more important as the focus shifts from desktop search to mobile search. On mobile, due to small typing keyboard, it is even more important to exploit all user and its context information available on mobile to provide the user better search suggestions. On query understanding and QAC: there is also a need of personalized and context models, especially for name queries. For example, a user may talk to his smart phone, “forward an email to Bill”. This implicitly triggers the query understanding engine to map “Bill” to a specific person in
Salary Dispersion for Lower Stratum Employees as a Predictor of Oligarchic Salary Practices

Company salary practices vary in terms of the average rate differential between upper- and lower stratum employees. Those companies with high interstrata rate multiples—typically run by a small, oligarchic leadership—are likely to evoke perceptions of vertical inequities among employees paid below the top echelon. This is especially a concern for small companies where all employees may work in close proximity. To mitigate the risk of dysfunctional behavior (e.g., turnover) stemming from interstrata rate disparities, companies with more oligarchic practices are predicted to engender greater salary dispersion within the lower stratum of employees, relative to those with more egalitarian practices, to “camouflage” the phenomenon. This article presents the results of an archival study that lends support for this prediction.
Thermal Modeling of Inductor and Transformer Windings Including Litz Wire

Design optimization of magnetic components, which considers both electrical and thermal performance, can help in designing power converters with a high power density. This paper proposes an approximate analytical model for thermal resistance of inductor and transformer windings, including litz wire, which only requires knowledge of thermal properties of constituent materials and geometric dimensions. The model is based on regular square and hexagonal packing of insulated wires and is derived by integration of infinitesimal thermal resistances along a specified heat flow path. The model closely agrees with finite-element analysis (FEA) and can be used in place of time-consuming FEA as part of larger thermal network models for magnetic components. The model is also experimentally validated using a toroidal inductor with a litz-wire winding; the model has less than 12% error compared to the experimental measurement. Application of the model for practical windings, including litz-wire windings, is also discussed. The model can be used during the design process of magnetic components of a switching power converter to evaluate the temperature and potential hot spots. The model provides closed-form results, hence fast computation times, and so can be used in design optimization procedures.
Determinants of the shoulder pain and disability index in patients with subacromial shoulder pain.

OBJECTIVE To examine the influence of determinants on the Shoulder Pain and Disability Index. DESIGN A cross-sectional study. Baseline registrations were applied. PATIENTS Two hundred patients with subacromial shoulder pain lasting at least 3 months. METHODS A questionnaire consisting of possible determinants, 2 independent variables regarding pain and 2 regarding function, and the outcome measurement. Two multiple regression models (one with and one without the independent variables of pain and function) for the Shoulder Pain and Disability Index, the 2 subscales, and the determinants, were performed. RESULTS The included determinants explained 29% of the variance of the Shoulder Pain and Disability Index (25% for pain and 33% for disability subscale) with pain medication, emotional distress, flexion, and the hand-behind-back range accounting for 26%. When pain and function were included, the final model explained 65% of the variance, with gender, education and range of flexion showing significance. CONCLUSION The determinants explained 26% of the variance of the Shoulder Pain and Disability Index, but explained only a minor proportion when pain and function were included. This supports the Shoulder Pain and Disability Index as a shoulder pain and disability questionnaire.
Characterization of the Mitogen-activated Protein Kinase Kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 Pathways Regulated by MEK Kinases 2 and 3

We previously reported the isolation of cDNAs encoding two mammalian mitogen-activated protein kinase (MAPK)/extracellular-regulated kinase (ERK)kinase kinases, designated MEKK2 and MEKK3 (Blank, J.L., Gerwins, P., Elliott, E.M., Sather, S. and Johnson, G.L. (1996) J. Biol. Chem. 271, 5361–5368). In the present study, cotransfection experiments were used to examine the regulation by MEKK2 and MEKK3 of the dual specificityMAP kinase kinases, MKK3 and MKK4. MKK3 specifically phosphorylates and activates p38, whereas MKK4 phosphorylates and activates both p38 and JNK. Coexpression of MEKK2 or MEKK3 with MKK4 in COS-7 cells resulted in activation of MKK4, as assessed by enhanced autophosphorylation and by its ability to phosphorylate and activate recombinant JNK1 or p38 in vitro. MKK3 autophosphorylation and activation of p38 was also observed following coexpression of MKK3 with MEKK3, but not with MEKK2. Consistent with these observations, immunoprecipitated MEKK2 directly activated recombinant MKK4 in vitro but failed to activate MKK3. The sites of activating phosphorylation in MKK3 and MKK4 were identified within kinase subdomains VII and VIII. Replacement of Ser189 or Thr193 in MKK3 with Ala abolished autophosphorylation and activation of MKK3 by MEKK3. Analogous mutations in MKK4 indicated that Ser221 and, to a lesser extent, Thr225 were necessary for MKK4 activation by MEKK2 and MEKK3. These data indicate that MKK3 is preferentially activated by MEKK3, whereas MKK4 is activated both by MEKK2 and MEKK3. Consistent with these observations, MEKK2 and MEKK3 also activated JNK1 in vivo. However, MEKK3 failed to activate p38 when coexpressed in either the absence or presence of MKK3, indicating that MEKK3 is not coupled to p38 activation in vivo. These observations suggest that regulation of p38 and JNK1 pathways by MEKK3 may involve distinct mechanisms to prevent p38 activation but to allow JNK1 activation.
Modeling of Load Demand Due to EV Battery Charging in Distribution Systems

This paper presents a methodology for modeling and analyzing the load demand in a distribution system due to electric vehicle (EV) battery charging. Following a brief introduction to the common types of EV batteries and their charging characteristics, an analytical solution for predicting the EV charging load is developed. The method is stochastically formulated so as to account for the stochastic nature of the start time of individual battery charging and the initial battery state-of-charge. A comparative study is carried out by simulating four EV charging scenarios, i.e., uncontrolled domestic charging, uncontrolled off-peak domestic charging, “smart” domestic charging and uncontrolled public charging-commuters capable of recharging at the workplace. The proposed four EVs charging scenarios take into account the expected future changes to the electricity tariffs in the electricity market place and appropriate regulation of EVs battery charging loads. A typical U.K. distribution system is adopted as an example. The time-series data of EV charging loads is taken from two commercially available EV batteries: lead-acid and lithium-ion. Results show that a 10% market penetration of EVs in the studied system would result in an increase in daily peak demand by up to 17.9%, while a 20% level of EV penetration would lead to a 35.8% increase in peak load, for the scenario of uncontrolled domestic charging-the “worst-case” scenario.
Money Growth and Inflation in the Euro Area: A Time‐Frequency View

This article provides new insights on the relationship between money growth and inflation in the euro area over the last 40 years. This highly relevant link for the European Central Bank monetary policy strategy is assessed using wavelet analysis. The findings indicate a stronger link between inflation and money growth at low frequencies over the whole sample period. At the typical business cycle frequency range the link is only present until the beginning of the 1980s. Moreover, there seems to be a recent deterioration of the leading properties of money growth with respect to inflation in the euro area.
The effectiveness of child restraint systems for children aged 3 years or younger during motor vehicle collisions: 1996 to 2005.

OBJECTIVES We estimated the effectiveness of child restraints in preventing death during motor vehicle collisions among children 3 years or younger. METHODS We conducted a matched cohort study using Fatality Analysis Reporting System data from 1996 to 2005. We estimated death risk ratios using conditional Poisson regression, bootstrapping, multiple imputation, and a sensitivity analysis of misclassification bias. We examined possible effect modification by selected factors. RESULTS The estimated death risk ratios comparing child safety seats with no restraint were 0.27 (95% confidence interval [CI] = 0.21, 0.34) for infants, 0.24 (95% CI = 0.19, 0.30) for children aged 1 year, 0.40 (95% CI = 0.32, 0.51) for those aged 2 years, and 0.41 (95% CI = 0.33, 0.52) for those aged 3 years. Estimated safety seat effectiveness was greater during rollover collisions, in rural environments, and in light trucks. We estimated seat belts to be as effective as safety seats in preventing death for children aged 2 and 3 years. CONCLUSIONS Child safety seats are highly effective in reducing the risk of death during severe traffic collisions and generally outperform seat belts. Parents should be encouraged to use child safety seats in favor of seat belts.
The mosquitoes of Yellowstone National Park (Diptera:Culicidae).

Twenty-nine species belonging to 4 genera of mosquitoes are reported for Yellowstone National Park. W.Y. (USA). Phenology, local distribution, and ecology of each species are addressed along with taxonomic notes on certain species. Merinithid (nematode) parasitism of some of the park's Aedes species is also discussed.
Versatile use of Schizosaccharomyces pombe plasmids in Saccharomyces cerevisiae.

The two model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe appear to have diverged 1000 million years ago. Here, we describe that S. pombe vectors can be propagated efficiently in S. cerevisiae as pUR19 derivatives, and the pREP and pJR vector series carrying the S. cerevisiae LEU2 or the S. pombe ura4(+) selection marker are maintained in S. cerevisiae cells. In addition, genes transcribed from the S. pombe nmt1(+) promoter and derivatives are expressed in budding yeast. Thus, S. pombe vectors can be used as shuttle vectors in S. cerevisiae and S. pombe. Our finding greatly facilitates the testing for functional orthologs of protein families and simplifies the cloning of new S. pombe plasmids by using the highly efficient in vivo homologous recombination activity of S. cerevisiae.
Measurement of Serum d-Arabinitol/Creatinine Ratios for Initial Diagnosis and for Predicting Outcome in an Unselected, Population-Based Sample of Patients with Candida Fungemia

ABSTRACT d-Arabinitol (DA) is a useful diagnostic marker for candidiasis in patients with neutropenia and other high-risk groups, but its use in unselected patients with a broad range of underlying diseases and conditions has not been studied. We used an automated enzymatic fluorometric assay to measure serum DA/creatinine ratios (DA/cr's) in 30 healthy adults, 100 hospitalized controls without Candida fungemia, and 83 patients from a study of all Candida fungemias in Connecticut between October 1998 and September 1999. Sixty-three of 83 (76%) fungemic patients and 11 of 100 (11%) nonfungemic controls had serum DA/cr's ≥3.9 μM/mg/dl (mean + 3 standard deviations for 30 healthy adults). High serum DA/cr's were less frequent in patients with cancer or fungemia caused by the DA nonproducer Candida glabrata than in patients with cancer or fungemia caused by a DA producer, C. albicans, C. tropicalis, or C. parapsilosis. The serum DA/cr was first ≥3.9 μM/mg/dl before, on the same day as, or after the first positive blood culture was drawn for 30 (36%), 22 (27%), and 11 (13%) fungemia patients, respectively. Mortality did not differ significantly among the patients with high or normal initial or peak serum DA/cr's, but mortality was higher if any serum DA/cr value was ≥3.9 μM/mg/dl 3 or more days after the onset of fungemia (18/27 versus 4/24 patients, respectively; P < 0.001). We conclude that serum DA/cr's are useful both for the initial diagnosis of Candida fungemia and for prognostic purposes for unselected patients with a broad range of underlying diseases and conditions.
Focal-adhesion-independent integrin-αv regulation of FAK and c-Myc is necessary for 3D skin formation and tumor invasion

ABSTRACT Integrins play crucial roles in epithelial adhesion, proliferation, wound healing and cancer. In the epidermis, the roles of many integrin subunits are incompletely defined and mechanistic details regarding their functions are lacking. We performed a multiplexed small hairpin (sh)RNA screen to define roles for each subunit in human organotypic skin. We show that integrin-αv (also known as ITGAV) heterodimers are essential for epidermal generation, with integrin-αv loss driving a keratinocyte G1–S cell cycle block. Surprisingly, integrin αv is not localized within keratinocyte focal adhesions, and instead maintains proliferation by controlling cellular (c)-Myc translation through FAK, p38β and p90RSK1. These phenotypes depend only on the binding partners of integrin-αv – integrin β5 and integrin β6 (also known as ITGB5 and ITGB6, respectively). Through inducible depletion of integrin αv in both normal organotypic epidermis and Ras-driven invasive neoplasia, we show that integrin αv is required for de novo tissue generation and neoplastic invasion but that it is dispensable for epidermal maintenance. Heterodimers of integrin αv with integrin β5 (integrin αvβ5) or integrin β6 (integrin αvβ6) are required to similar extents for neoplastic invasion, thus identifying integrin αvβ5 and integrin αvβ6 heterodimers as potential therapeutic targets for epidermal squamous cell carcinoma. Summary: Integrin-αv plays a crucial role in regulating skin tissue generation and tumor invasion through a focal-adhesion-independent FAK–p38–p90RSK–c-Myc signaling axis.