Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuropilin-2/Semaphorin-3F-mediated repulsion promotes inner hair cell innervation by spiral ganglion neurons

Auditory function is dependent on the formation of specific innervation patterns between mechanosensory hair cells (HCs) and afferent spiral ganglion neurons (SGNs). In particular, type I SGNs must precisely connect with inner HCs (IHCs) while avoiding connections with nearby outer HCs (OHCs). The factors that mediate these patterning events are largely unknown. Using sparse-labeling and time-lapse imaging, we visualized for the first time the behaviors of developing SGNs including active retraction of processes from OHCs, suggesting that some type I SGNs contact OHCs before forming synapses with IHCs. In addition, we demonstrate that expression of Semaphorin-3F in the OHC region inhibits type I SGN process extension by activating Neuropilin-2 receptors expressed on SGNs. These results suggest a model in which cochlear innervation patterns by type I SGNs are determined, at least in part, through a Semaphorin-3F-mediated inhibitory signal that impedes processes from extending beyond the IHC region. DOI: http://dx.doi. org/10.7554/eLife.07830. 001
Costs of crowding for the transmission of malaria parasites

The utility of using evolutionary and ecological frameworks to understand the dynamics of infectious diseases is gaining increasing recognition. However, integrating evolutionary ecology and infectious disease epidemiology is challenging because within‐host dynamics can have counterintuitive consequences for between‐host transmission, especially for vector‐borne parasites. A major obstacle to linking within‐ and between‐host processes is that the drivers of the relationships between the density, virulence, and fitness of parasites are poorly understood. By experimentally manipulating the intensity of rodent malaria (Plasmodium berghei) infections in Anopheles stephensi mosquitoes under different environmental conditions, we show that parasites experience substantial density‐dependent fitness costs because crowding reduces both parasite proliferation and vector survival. We then use our data to predict how interactions between parasite density and vector environmental conditions shape within‐vector processes and onward disease transmission. Our model predicts that density‐dependent processes can have substantial and unexpected effects on the transmission potential of vector‐borne disease, which should be considered in the development and evaluation of transmission‐blocking interventions.
Placental Toll-Like Receptor 3 and Toll-Like Receptor 7/8 Activation Contributes to Preeclampsia in Humans and Mice

Preeclampsia (PE) is a pregnancy-specific hypertensive syndrome characterized by excessive maternal immune system activation, inflammation, and endothelial dysfunction. Toll-like receptor (TLR) 3 activation by double-stranded RNA (dsRNA) and TLR7/8 activation by single-stranded RNA (ssRNA) expressed by viruses and/or released from necrotic cells initiates a pro-inflammatory immune response; however it is unknown whether viral/endogenous RNA is a key initiating signal that contributes to the development of PE. We hypothesized that TLR3/7/8 activation will be evident in placentas of women with PE, and sufficient to induce PE-like symptoms in mice. Placental immunoreactivity and mRNA levels of TLR3, TLR7, and TLR8 were increased significantly in women with PE compared to normotensive women. Treatment of human trophoblasts with the TLR3 agonist polyinosine-polycytidylic acid (poly I:C), the TLR7-specific agonist imiquimod (R-837), or the TLR7/8 agonist CLO97 significantly increased TLR3/7/8 levels. Treatment of mice with poly I:C, R-837, or CLO97 caused pregnancy-dependent hypertension, endothelial dysfunction, splenomegaly, and placental inflammation. These data demonstrate that RNA-mediated activation of TLR3 and TLR7/8 plays a key role in the development of PE.
Local variations of bulk hydrogen and chlorine‐equivalent neutron absorption content measured at the contact between the Sheepbed and Gillespie Lake units in Yellowknife Bay, Gale Crater, using the DAN instrument onboard Curiosity

Data gathered with the Dynamic Albedo of Neutron (DAN) instrument onboard rover Curiosity were analyzed for variations in subsurface neutron flux and tested for possible correlation with local geological context. A special DAN observation campaign was executed, in which 18 adjacent DAN active measurements were acquired every 0.75–1.0 m to search for the variations of subsurface hydrogen content along a 15 m traverse across geologic contacts between the Sheepbed and Gillespie Lake members of the Yellowknife Bay formation. It was found that several subunits in Sheepbed and Gillespie Lake could be characterized with different depth distributions of water‐equivalent hydrogen (WEH) and different chlorine‐equivalent abundance responsible for the distribution of neutron absorption elements. The variations of the average WEH at the top 60 cm of the subsurface are estimated at up to 2–3%. Chlorine‐equivalent neutron absorption abundances ranged within 0.8–1.5%. The largest difference in WEH and chlorine‐equivalent neutron absorption distribution is found between Sheepbed and Gillespie Lake.
Mutations in Proline 82 of p53 Impair Its Activation by Pin1 and Chk2 in Response to DNA Damage

ABSTRACT Tumor suppression by the p53 protein largely depends on the elimination of damaged cells by apoptosis. Mutations in the polyproline region (PPR) of p53 impair its apoptotic function. Deletion of the PPR renders p53 more sensitive to inhibition by Mdm2 via an unknown mechanism. We have explored the mechanism by which the PPR modulates the p53/Mdm2 loop. Proline 82 of p53 was identified to be essential for its interaction with the checkpoint kinase 2 (Chk2) and consequent phosphorylation of p53 on serine 20, following DNA damage. These physical and functional interactions are regulated by Pin1 through cis-trans isomerization of proline 82. Our study unravels the pathway by which Pin1 activates p53 in response to DNA damage and explains how Pin1 protects p53 from Mdm2. Further, we propose a role for Pin1-dependent induction of p53 conformational change as a mechanism responsible for the enhanced interaction between p53 and Chk2 following DNA damage. Importantly, our findings elucidate the selection for mutations in the Pin1 target Thr81/Pro82 motif within the PPR of p53 in human cancer.
Security of two signature schemes based on two hard problems

To provide more confidence to users of digital signatures, recently, Wei and Yuan et al. proposed two digital signature schemes respectively. They claimed that the security of their schemes is based on factoring and discrete logarithms simultaneously. Moreover, they thought that their schemes accomplish three merits proposed by Shao. In this paper, we show that the two schemes are not secure at all. We can forge signatures for arbitrary messages without any knowledge about the private keys.
AICRG, Part II: Crestal bone loss associated with the Ankylos implant: loading to 36 months.

PROBLEM The Ankylos endosseous dental implant is a new implant design that will be available in the United States in early 2004. It features an internal tapered abutment connection, a smooth polished collar without threads at the coronal part of the implant body, and a roughened surface with variable threads on the body of the implant fixture. A precise, tapered, conical abutment connection eliminates the microgap often found in 2-stage implant systems. This microgap may allow the accumulation of food debris and bacteria, as well as micromovement between the parts during clinical function, both of which can lead to a localized inflammation and crestal bone loss. PURPOSE The purpose of this section of the study was to assess any crestal bone loss associated with this new implant. METHOD The clinical performance of this new implant design was studied under well-controlled clinical conditions. Over 1500 implants were placed and restored. The vertical crestal bone loss was measured "directly" between the time of implant placement and uncovering, using a periodontal probe. Serial dental radiographs were taken between loading, and the 12-, 24-, and 36-month follow-up visits to determine "indirect" crestal bone loss within a specific period. RESULTS Bone loss varied among the participating centers from less than 0.5 mm to 2.0 mm. The largest amount of bone loss occurred between the time of placement and uncovering. Following loading, the mean bone loss for all implants for a period of 3 years was about 0.2 mm/y. CONCLUSIONS The extent of the crestal bone loss after loading was minimal for patients regardless of age, gender, prosthetic applications, bone density, and remote or crestal incisions, as well as for smokers or nonsmokers. Bone loss per year is well within the guidelines of 0.2 mm/y proposed by others.
An Analysis of Laplacian Methods for Value Function Approximation in MDPs

Recently, a method based on Laplacian eigenfunctions was proposed to automatically construct a basis for value function approximation in MDPs. We show that its success may be explained by drawing a connection between the spectrum of the Laplacian and the value function of the MDP. This explanation helps us to identify more precisely the conditions that this method requires to achieve good performance. Based on this, we propose a modification of the Laplacian method for which we derive an analytical bound on the approximation error. Further, we show that the method is related the augmented Krylov methods, commonly used to solve sparse linear systems. Finally, we empirically demonstrate that in basis construction the augmented Krylov methods may significantly outperform the Laplacian methods in terms of both speed and quality.
Reconstitution of native-type noncrystalline lens fiber gap junctions from isolated hemichannels

Gap junctions contain numerous channels that are clustered in apposed membrane patches of adjacent cells. These cell-to-cell channels are formed by pairing of two hemichannels or connexons, and are also referred to as connexon pairs. We have investigated various detergents for their ability to separately solubilize hemichannels or connexon pairs from isolated ovine lens fiber membranes. The solubilized preparations were reconstituted with lipids with the aim to reassemble native-type gap junctions and to provide a model system for the characterization of the molecular interactions involved in this process. While small gap junction structures were obtained under a variety of conditions, large native-type gap junctions were assembled using a novel two-step procedure: in the first step, hemichannels that had been solubilized with octylpolyoxyethylene formed connexon pairs by dialysis against n-decyl-beta-D-maltopyranoside. In the second step, connexon pairs were reconstituted with phosphatidylcholines by dialysis against buffer containing Mg2+. This way, double-layered gap junctions with diameter < or = 300 nm were obtained. Up to several hundred channels were packed in a noncrystalline arrangement, giving these reconstituted gap junctions an appearance that was indistinguishable from that of the gap junctions in the lens fiber membranes.
A systematic review of nursing research priorities on health system and services in the Americas.

OBJECTIVE To systematically review literature on priorities in nursing research on health systems and services in the Region of the Americas as a step toward developing a nursing research agenda that will advance the Regional Strategy for Universal Access to Health and Universal Health Coverage. METHOD This was a systematic review of the literature available from the following databases: Web of Science, PubMed, LILACS, and Google. Documents considered were published in 2008-2014; in English, Spanish, or Portuguese; and addressed the topic in the Region of the Americas. The documents selected had their priority-setting process evaluated according to the "nine common themes for good practice in health research priorities. " A content analysis collected all study questions and topics, and sorted them by category and subcategory. RESULTS Of 185 full-text articles/documents that were assessed for eligibility, 23 were selected: 12 were from peer-reviewed journals; 6 from nursing publications; 4 from Ministries of Health; and 1 from an international organization. Journal publications had stronger methodological rigor; the majority did not present a clear implementation or evaluation plan. After compiling the 444 documents' study questions and topics, the content analysis resulted in a document with 5 categories and 16 subcategories regarding nursing research priorities on health systems and services. CONCLUSIONS Research priority-setting is a highly important process for health services improvement and resources optimization, but implementation and evaluation plans are rarely included. The resulting document will serve as basis for the development of a new nursing research agenda focused on health systems and services, and shaped to advance universal health coverage and universal access to health.
Metabolic Stress Reversibly Activates the DrosophilaLight-Sensitive Channels TRP and TRPL In Vivo

Drosophila transient receptor potential (TRP) is a prototypical member of a novel family of channel proteins underlying phosphoinositide-mediated Ca2+ entry. Although the initial stages of this signaling cascade are well known, downstream events leading to the opening of the TRP channels are still obscure. In the present study we applied patch-clamp whole-cell recordings and measurements of Ca2+ concentration by ion-selective microelectrodes in eyes of normal and mutant Drosophilato isolate the TRP and TRP-like (TRPL)-dependent currents. We report that anoxia rapidly and reversibly depolarizes the photoreceptors and induces Ca2+ influx into these cells in the dark. We further show that openings of the light-sensitive channels, which mediate these effects, can be obtained by mitochondrial uncouplers or by depletion of ATP in photoreceptor cells, whereas the effects of illumination and all forms of metabolic stress were additive. Effects similar to those found in wild-type flies were also found in mutants with strong defects in rhodopsin, Gq-protein, or phospholipase C, thus indicating that the metabolic stress operates at a late stage of the phototransduction cascade. Genetic elimination of both TRP and TRPL channels prevented the effects of anoxia, mitochondrial uncouplers, and depletion of ATP, thus demonstrating that the TRP and TRPL channels are specific targets of metabolic stress. These results shed new light on the properties of the TRP and TRPL channels by showing that a constitutive ATP-dependent process is required to keep these channels closed in the dark, a requirement that would make them sensitive to metabolic stress.
Does the Timing of Preoperative Epidural Steroid Injection Affect Infection Risk After ACDF or Posterior Cervical Fusion?

Study Design. A retrospective database analysis. Objective. The aim of this study was to determine whether any association exists between preoperative cervical epidural steroid injections (CESIs) at various time intervals before anterior cervical discectomy and fusion (ACDF) or posterior cervical fusion (PCF) and the incidence of postoperative infection. Summary of Background Data. Although infectious complications following CESI are uncommon, the association between preoperative CESI and postoperative infection following ACDF or PCF has yet to be evaluated in the current literature. Methods. A national insurance database was utilized to compare postoperative infection rates within 90 days in patients who received a CESI before ACDF or PCF. Three cohorts were created for each procedure: PCF (n = 402) or ACDF (n = 4354) within 3 months, PCF (n = 586) or ACDF (n = 5183) between 3 and 6 months, and PCF (n = 629) or ACDF (3648) between 6 and 12 months following a CESI. These cohorts were compared with control cohorts who underwent PCF (n = 61,253) or ACDF (n = 241,678) without prior CESI. Postoperative infection rates within 90 days were assessed using International Classification of Disease, 9th Revision (ICD-9) and Current Procedural Terminology (CPT) codes. Odds ratios (ORs), 95% confidence intervals (95% CIs), and P values were then calculated using SPSS. A multivariate binomial logistic regression analysis was performed to determine the independent effect of preoperative injection on postoperative infection following ACDF or PCF controlling for known risk factors for infection, including age, gender, obesity, diabetes, and smoking. Results. Patients who underwent CESI within 3 months (OR 2.21, P < 0.0001) and within 3 to 6 months (OR 1.95, P = 0.0002) before PCF had significantly increased odds of developing a postoperative infection. Patients who underwent CESI within 3 months (OR 1.83, P < 0.0001) before ACDF had significantly increased odds of developing a postoperative infection. Conclusion. The present study demonstrates that cervical ESI within 6 months of PCF, and within 3 months of ACDF, is independently associated with significantly increased rates of postoperative infection. Level of Evidence: 3
The Practice of Carotid Endarterectomy In A Large Metropolitan Area

All carotid endarterectomies performed in the greater Cincinnati metropolitan area during 1980 were reviewed. For the 431 procedures performed in 16 hospitals, the operative stroke rate was 8.6% (37 of 431), and the operative mortality rate was 2.8% (12 of 431). The combined morbidity and mortality was 9.5% (41 of 431). Fifty percent of the procedures were done for asymptomatic carotid disease (216 of 431) and 50% were done for symptomatic carotid disease (215 of 431). The stroke rate was 5.6% for the asymptomatic patients and 11.6% for the symptomatic patients (difference significant, P < 0.05). Neuro- surgeons and vascular surgeons had similar surgical morbidity. All of the operative strokes involved the hemisphere ipsilateral to the endarterectomy. Fifty-seven percent of the operative strokes (21 of 37) occurred after a neurologicalty intact interval lasting hours to days. Four occurred following combined endarterectomy-coronary bypass surgery, and one was an intracerebral hemorrhage. The other late strokes (17) occurred without evidence for cardiac embolus or hemorrhage, consistent with a thrombogenic- embologenic operative site, and raising the question of need for adjunctive perioperative medical therapy. Stroke Vol 15, No 6, 1984
The reaction of thiol compounds and chloroacetamide. 2. The reaction between chloroacetamide and cysteine peptides.

Lindley (1960) showed that the reaction between chloroacetamide and thiol compounds proceeds via the thiol anion RS-, and hence it was possible to show for cysteine and ,B-mercaptoethylamine that the two ionic species -S R -NH3+ and HS *R -NH2 occurred simultaneously in solution. The paper reports the results obtained in a similar investigation of the reaction between chloroacetamide and cysteine peptides which was undertaken to study the effect of increased separation of the charged groups and neighbouring side chains on thiol reactivity.
Timing and Grounding in Motor Skill Coaching Interaction: Consequences for the Information State

While tutorial dialogues have been wellstudied, the nature of dialogue in physical coaching scenarios is much less well understood. We present a corpus study on coaching interactions wherein a coach trains a trainee to improve a motor skill. We show how our findings put novel requirements on pedagogic dialogue act taxonomies, grounding criteria and information state update models of situated dialogue. One of these requirements is to distinguish between grounding in the traditional sense along an understanding dimension and grounding in terms of a motor program schema, the latter being due to the coach’s goal to transfer knowledge of a physical movement to the trainee. Another requirement is that a fine-grained notion of time, both in absolute and relative terms, must become a first class citizen of the dialogue state to be able to model motor skill coaching. A final requirement for an information state model is characterizing what is under discussion and in the established common ground– in these kind of domains this is generally not questions and propositions, but skills and their desired and observed parameters.
NCX1 Is a Novel Target Gene for Hypoxia-Inducible Factor-1 in Ischemic Brain Preconditioning

Background and Purpose— The sodium–calcium exchanger-1 (NCX1) represents a key mediator for maintaining [Na+]i and [Ca2+]i homeostasis. Although changes in NCX1 protein and transcript expression have been detected during stroke, its transcriptional regulation is still unknown. Thus far, however, there is evidence that hypoxia-inducible factor-1 (HIF-1) is a nuclear factor required for transcriptional activation of several genes implicated in stroke. The main objective of this study was to investigate whether NCX1 gene might be a novel target of HIF-1 in the brain. Methods and Results— Here we report that: (1) in neuronal cells, NCX1 increased expression after oxygen and glucose deprivation or cobalt-induced HIF-1 activation was prevented by silencing HIF-1; (2) the brain NCX1 promoter cloned upstream of the firefly-luciferase gene contained 2 regions of HIF-1 target genes called hypoxia-responsive elements that are sensitive to oxygen and glucose deprivation or cobalt chloride; (3) HIF-1 specifically bound hypoxia-responsive elements on brain NCX1, as demonstrated by band-shift and chromatin immunoprecipitation assays; (4) HIF-1&agr; silencing prevented NCX1 upregulation and neuroprotection induced by ischemic preconditioning; and (5) NCX1 silencing partially reverted the preconditioning-induced neuroprotection in rats. Conclusions— NCX1 gene is a novel HIF-1 target, and HIF-1 exerts its prosurvival role through NCX1 upregulation during brain preconditioning.
Which Way Social Justice in Mathematics Education

About the Authors List of Tables and Figures Preface by Series Editor Introduction by Leone Burton Setting the Scene What is a Gender-Sensitive Mathematics Classroom? by Helga Jungwirth Research on Equity in Mathematics Education: Progress and New Directions by Laurie E. Hart Teaching and Learning Mathematics: Can the Concept of Citizenship Be Reclaimed for Social Justice? by Hilary Povey Mothers Returning to Study Mathematics: The Development of Mathematical Authority through Evolving Relationships with their Children by Christine Brew What Does Social Justice Mean in Classrooms? Opportunity to Learn Mathematics Among Aymara-, Quechua-, and Spanish Speaking Rural and Urban, Fourth and Fifth Graders in Puno, Peru by Walter G. Secada, Santiago Cueto, and Fernando Andrade Teachers' Beliefs about Teaching Mathematics to Students from Socially Disadvantaged Backgrounds: Implications for Social Justice by Robyn Zevenbergen Gender-Related Differences in Working Style During Cooperative Learning in Secondary School Mathematics: A Malawian Case Study by Panji Catherine Chamdimba Choosing Maths/Doing Gender: A Look at Why There are More Boys than Girls in Advanced Mathematics Classes in England by Heather Mendick Constructing Difference: Assessment in Mathematics Education by Dylan Wiliam First Results of a Study on Different Mathematical Thinking Styles of German School Children by Rita Borromeo Ferri and Gabriele Kaiser Mathematics Participation, Achievement and Attitudes: What's New in Australia? by Helen J. Forgasz, Gilah C. Leder and Jan Thomas Computers and Mathematics Learning Toys for Boys by Leigh Wood, Dubravka Viskic and Peter Petocz Computers in Mathematics: A Super Highway to Social Justice by Colleen M. Vale