Miracle-dz/UniFAR-FTUs huggingface dataset:
Requirement of a Macromolecular Signaling Complex for β Adrenergic Receptor Modulation of the KCNQ1-KCNE1 Potassium Channel

Sympathetic nervous system (SNS) regulation of cardiac action potential duration (APD) is mediated by β adrenergic receptor (βAR) activation, which increases the slow outward potassium ion current (I KS). Mutations in two humanI KS channel subunits, hKCNQ1 and hKCNE1, prolong APD and cause inherited cardiac arrhythmias known as LQTS (long QT syndrome). We show that βAR modulation of I KSrequires targeting of adenosine 3′,5′-monophosphate (cAMP)–dependent protein kinase (PKA) and protein phosphatase 1 (PP1) to hKCNQ1 through the targeting protein yotiao. Yotiao binds to hKCNQ1 by a leucine zipper motif, which is disrupted by an LQTS mutation (hKCNQ1-G589D). Identification of the hKCNQ1 macromolecular complex provides a mechanism for SNS modulation of cardiac APD throughI KS.
Functional Mechanisms Encoding Others' Direction of Gaze in the Human Nervous System

The direction of others' gaze is a strong social signal to their intentions and future behavior. Pioneering electrophysiological research identified cell populations in the primate visual cortex that are tuned to specific directions of observed gaze, but the functional architecture of this system is yet to be precisely specified. Here, we develop a computational model of how others' gaze direction is flexibly encoded across sensory channels within the gaze system. We incorporate the divisive normalization of sensory responses—a computational mechanism that is thought to be widespread in sensory systems but has not been examined in the context of social vision. We demonstrate that the operation of divisive normalization in the gaze system predicts a surprising and distinctive pattern of perceptual changes after sensory adaptation to gaze stimuli and find that these predictions closely match the psychophysical effects of adaptation in human observers. We also find that opponent coding, broadband multichannel, and narrowband multichannel models of sensory coding make distinct predictions regarding the effects of adaptation in a normalization framework and find evidence in favor of broadband multichannel coding of gaze. These results reveal the functional principles that govern the neural encoding of gaze direction and support the notion that divisive normalization is a canonical feature of nervous system function. Moreover, this research provides a strong foundation for testing recent computational theories of neuropsychiatric conditions in which gaze processing is compromised, such as autism and schizophrenia.
Spatial Relationships between GABAergic and Glutamatergic Synapses on the Dendrites of Distinct Types of Mouse Retinal Ganglion Cells across Development

Neuronal output requires a concerted balance between excitatory and inhibitory (I/E) input. Like other circuits, inhibitory synaptogenesis in the retina precedes excitatory synaptogenesis. How then do neurons attain their mature balance of I/E ratios despite temporal offset in synaptogenesis? To directly compare the development of glutamatergic and GABAergic synapses onto the same cell, we biolistically transfected retinal ganglion cells (RGCs) with PSD95CFP, a marker of glutamatergic postsynaptic sites, in transgenic Thy1YFPγ2 mice in which GABAA receptors are fluorescently tagged. We mapped YFPγ2 and PSD95CFP puncta distributions on three RGC types at postnatal day P12, shortly before eye opening, and at P21 when robust light responses in RGCs are present. The mature IGABA/E ratios varied among ON-Sustained (S) A-type, OFF-S A-type, and bistratified direction selective (DS) RGCs. These ratios were attained at different rates, before eye-opening for ON-S and OFF-S A-type, and after eye-opening for DS RGCs. At both ages examined, the IGABA/E ratio was uniform across the arbors of the three RGC types. Furthermore, measurements of the distances between neighboring PSD95CFP and YFPγ2 puncta on RGC dendrites indicate that their local relationship is established early in development, and cannot be predicted by random organization. These close spatial associations between glutamatergic and GABAergic postsynaptic sites appear to represent local synaptic arrangements revealed by correlative light and EM reconstructions of a single RGC's dendrites. Thus, although RGC types have different IGABA/E ratios and establish these ratios at separate rates, the local relationship between excitatory and inhibitory inputs appear similarly constrained across the RGC types studied.
CLINICAL PREDICTION OF RATE OF RESPONSE OF ENDOGENOUS DEPRESSION TO ELECTROCONVULSIVE THERAPY

SUMMARY In depression, the identification of predictors of fast response is necessary to improve patient selection for ECT. In a double-blind, prospective study of 32 endogenously depressed patients treated with ECT, we attempted to identify the clinical characteristics of ECT responders which predicted fast (requiring ≤ 5 treatments to produce maximum recovery) and slow (requiring ≥ 6 treatments to produce maximum recovery) response to ECT. Of the 22 ECT responders in the study, 13 were fast and 9 were slow responders. We found that male sex, and greater age associated with lesser initial severity of depression were significantly associated with fast recovery. Surprisingly, factors suggested or expected to predict good outcome with ECT failed to predict fast outcome. Finally, the treatment variables of mean seizure duration and stimulus waveform were found to be unrelated to recovery rate. The findings are briefly discussed.
Fear of movement in cancer survivors: validation of the Modified Tampa Scale of Kinesiophobia—Fatigue

Objective: To date, there is no validated questionnaire to assess fear of movement in cancer survivors. We aim to validate the Modified Tampa Scale of Kinesiophobia‐Fatigue (TSK‐F) in Dutch cancer survivors participating in a rehabilitation programme. We first select the optimal model for cancer survivors. Subsequently, stability, internal consistency, and construct validity of the optimal model is tested.
Statistical Mechanics: J Theory and Experiment Universality of rain event size distributions

We compare rain event size distributions derived from measurements in climatically diﬀerent regions, which we ﬁnd to be well approximated by power laws of similar exponents over broad ranges. Diﬀerences can be seen in the large-scale cutoﬀs of the distributions. Event duration distributions suggest that the scale-free aspects are related to the absence of characteristic scales in the meteorological mesoscale.
Predisposing Factors Associated With Chronic and Recurrent Rhinosinusitis in Childhood

Purpose There is currently no information regarding predisposing factors for chronic and recurrent rhinosinusitis (RS), although these are considered to be multifactorial in origin, and allergic diseases contribute to their pathogenesis. We evaluated the predisposing factors that may be associated with chronic and recurrent RS. Methods In this prospective study, we examined patients with RS younger than 13 years of age, diagnosed with RS at six tertiary referral hospitals in Korea between October and December, 2006. Demographic and clinical data related to RS were recorded and analyzed. Results In total, 296 patients were recruited. Acute RS was the most frequent type: 56.4% of the patients had acute RS. The prevalences of other types of RS, in descending order, were chronic RS (18.9%), subacute RS (13.2%), and recurrent RS (11.5%). Factors associated with recurrent RS were similar to those of chronic RS. Patients with chronic and recurrent RS were significantly older than those with acute and subacute RS. The prevalences of allergic rhinitis, atopy, and asthma were significantly higher in patients with chronic and recurrent RS than those with acute and subacute RS. Conclusions An association between atopy and chronic/recurrent RS, compared to acute and subacute RS, suggests a possible causal link.
Ownership Consolidation and Product Quality : A Study of the U . S . Daily Newspaper Market

I develop a structural model of newspaper markets to analyze the effects of ownership consolidation. In the model, firms choose both price and quality including the amount of nonadvertising space, the number of reporters, and the number of opinion section staff. I estimate the model using a new data set on newspaper prices and characteristics. I then simulate the effect of a merger in the Minneapolis newspaper market. I also study how welfare effects of mergers vary with market characteristics. I find that ignoring adjustments of product characteristics causes substantial differences in estimated effects of mergers.
Prospective Effectiveness of Stapes Surgery for Otosclerosis in a Multicenter Audit Setting: Feasibility of the Common Otology Database as a Benchmark Database

Introduction: The Common Otology Database (COD) is a joint effort by an international group of otologists to organize audit with a standardized reporting method in middle ear surgery. The first results on hearing outcome of the COD are presented in this article. Objective: The primary objective was to confirm the validity of the benchmark group by comparing hearing outcome results with previously reported results. The secondary objective was to describe the population, technical aspects, and hearing outcomes of stapes surgery. Study Design: Nonrandomized prospective multicenter audit. Setting: Twenty tertiary-referral otologic centers. Patients and Intervention: Primary and revision stapes operations in patients with otosclerosis. Main Outcome Measures: Air-bone gap (ABG), bone-conduction (BC) thresholds, and air-conduction (AC) thresholds were evaluated at 3 and 12 months according to the guidelines of the Committee on Hearing and Equilibrium for the evaluation of conductive hearing loss. Raw data were displayed in an Amsterdam Hearing Evaluation Plot. Results: In primary stapes surgeries, the postoperative ABG was closed to 10 dB or less in 63.6% and to 20 dB or less in 92.6% (median, 8.75 dB). In revision stapes surgeries, the postoperative ABG was closed to 10 dB in 41.2% and to 20 dB in 76.5% of cases (median, 11.25 dB). The overall mean postoperative ABG at 12 months was 10.38 dB compared with 28.75 dB preoperatively. Using laser to perform the fenestration results in a less pronounced BC improvement when compared with procedures without laser assistance. No statistically significant difference in ABG pure-tone average at 3 months could be demonstrated between the different prosthesis types. Conclusion: Results of hearing outcome are similar to previous, primarily retrospective, single-center studies. Our data confirm the effectiveness of stapes surgery in patients with otosclerosis.
The Role of Interplanetary Scattering in Western Hemisphere Large Solar Energetic Particle Events

Using high-sensitivity instruments on the ACE spacecraft, we have examined the intensities of O and Fe in 14 large solar energetic particle events whose parent activity was in the solar western hemisphere. Sampling the intensities at low (~273 keV nucleon-1) and high (~12 MeV nucleon-1) energies, we find that at the same kinetic energy per nucleon, the Fe/O ratio decreases with time, as has been reported previously. This behavior is seen in more than 70% of the cases during the rise to maximum intensity and continues in most cases into the decay phase. We find that for most events if we compare the Fe intensity with the O intensity at a higher kinetic energy per nucleon, the two time-intensity profiles are strikingly similar. Examining alternate scenarios that could produce this behavior, we conclude that for events showing this behavior the most likely explanation is that the Fe and O share similar injection profiles near the Sun, and that scattering in the interplanetary medium dominates the profiles observed at 1 AU.
Sprobes: Enforcing Kernel Code Integrity on the TrustZone Architecture

Many smartphones now deploy conventional operating systems, so the rootkit attacks so prevalent on desktop and server systems are now a threat to smartphones. While researchers have advocated using virtualization to detect and prevent attacks on operating systems (e.g., VM introspection and trusted virtual domains), virtualization is not practical on smartphone systems due to the lack of virtualization support and/or the expense of virtualization. Current smartphone processors do have hardware support for running a protected environment, such as the ARM TrustZone extensions, but such hardware does not control the operating system operations sufficiently to enable VM introspection. In particular, a conventional operating system running with TrustZone still retains full control of memory management, which a rootkit can use to prevent traps on sensitive instructions or memory accesses necessary for effective introspection. In this paper, we present SPROBES, a novel primitive that enables introspection of operating systems running on ARM TrustZone hardware. Using SPROBES, an introspection mechanism protected by TrustZone can instrument individual operating system instructions of its choice, receiving an unforgeable trap whenever any SPROBE is executed. The key challenge in designing SPROBES is preventing the rootkit from removing them, but we identify a set of five invariants whose enforcement is sufficient to restrict rootkits to execute only approved, SPROBE-injected kernel code. We implemented a proof-of-concept version of SPROBES for the ARM Fast Models emulator, demonstrating that in Linux kernel 2.6. 38, only 12 SPROBES are sufficient to enforce all five of these invariants. With SPROBES we show that it is possible to leverage the limited TrustZone extensions to limit conventional kernel execution to approved code comprehensively.
Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease

BACKGROUND Measurement of 6-thioguanine nucleotide concentrations may be useful for optimising treatment with azathioprine and 6-mercaptopurine. METHODS We conducted a study of 170 patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine to determine the relationship between 6-thioguanine nucleotide concentrations and both disease activity, as measured by the inflammatory bowel disease questionnaire (active disease <170, remission ⩾170) and leucopenia. Blood was submitted for whole blood 6-thioguanine nucleotide concentration and leucocyte count. RESULTS Mean (SD) inflammatory bowel disease questionnaire score was 176 (32). There was no correlation between inflammatory bowel disease questionnaire scores and 6-thioguanine nucleotide concentrations (r s=−0.09, p=0.24). Median 6-thioguanine nucleotide concentrations in 56 patients with active disease and 114 patients in remission were similar (139v 131 pmol/8×108 red blood cells; p=0.26). There was no correlation between 6-thioguanine nucleotide concentrations and leucocyte counts. CONCLUSIONS In patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine, 6-thioguanine nucleotide concentrations did not correlate with disease activity, as measured by the inflammatory bowel disease questionnaire, or leucocyte count. These findings are discrepant with most previous studies, possibly due to selection of responding patients who tolerated the medications. A prospective, randomised, dose optimisation trial using 6-thioguanine nucleotide concentrations is warranted.
Which factors hinder the adoption of open innovation in SMEs?

ABSTRACT The literature on open innovation (OI) is characterised by studies based both on large companies and small and medium-sized enterprises (SMEs). Among all, one of the less explored issues in SMEs is what impedes them to adopt OI. Thus, this paper has the threefold objective to identify which factors hinder the adoption of OI in SMEs, to investigate if different behaviours exist among SMEs in relation to these factors, and to understand if the same factors effectively influence the level of adoption of OI. Based on a survey on 157 Italian SMEs, we identified four main barriers (namely, ‘knowledge’, ‘collaboration’, ‘organisational’, and ‘financial and strategic’) and three profiles of firms, different in terms of innovativeness of the industries they belong to (knowledge intensive, medium-innovative, and less innovative) and hampering factors perceived (‘knowledge’, ‘financial and strategic’, and ‘collaboration’ and ‘organisational’ barriers). Moreover, we found that some of these factors effectively impede the adoption of the paradigm.
Interleukin‐8 modulates growth and invasiveness of estrogen receptor‐negative breast cancer cells

Breast cancer, especially estrogen receptor (ER)‐negative breast cancer, remains hard to treat despite major advances in surgery and adjuvant therapies. The deletion of ER has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis. Among other differences in biological features, ER‐negative breast cancers express high levels of interleukin‐8 (IL‐8), whereas their ER‐positive counterparts do not. IL‐8 is a multi‐functional cytokine with many important biological functions in tumor formation and development. We aimed to study the role(s) of IL‐8 in ER‐negative breast cancer progression by using RNA interference to specifically knockdown IL‐8 expression in ER‐negative breast cancer cell lines MDA‐MB‐231 and MDA‐MB‐468. In vitro, suppression of IL‐8 led to significant reductions in cell invasion (p < 0.001), but had no effects on cell proliferation or cell cycle. In vivo, suppression of IL‐8 significantly reduced the microvessel density (p < 0.05), and markedly reduced neutrophil infiltration into the tumors (p < 0.05). In contrast to in vitro observations, suppression of IL‐8 promoted tumor growth in nude mice (p < 0.05). Our results imply that the complex roles of IL‐8 in the regulation of ER‐negative breast cancer progression may in part be related to its potent chemotactic effects on neutrophils, which in turn mediates many of the biological functions of IL‐8. © 2007 Wiley‐Liss, Inc.
Structure of BipA in GTP form bound to the ratcheted ribosome

Significance The regulation of protein synthesis is a vital process in all cells. We have determined the structure of the BPI-inducible protein A (BipA), a GTPase involved in bacterial stress response, in various biologically relevant states, including bound to the ribosome in its active form. Our study provides the first structural basis to our knowedge for BipA working as a ribosome-dependent translational GTPase factor and serves as a crucial step for elucidating BipA functioning in vivo. Because no other stress response factor is known to interact with the A-site tRNA, our findings provide a novel mechanistic insight of translational regulation by BipA. Furthermore, the distinctive structural attributes of ribosome upon BipA binding can shed new light on the translational factor recruitment and GTPase activation mechanisms by the ribosome. BPI-inducible protein A (BipA) is a member of the family of ribosome-dependent translational GTPase (trGTPase) factors along with elongation factors G and 4 (EF-G and EF4). Despite being highly conserved in bacteria and playing a critical role in coordinating cellular responses to environmental changes, its structures (isolated and ribosome bound) remain elusive. Here, we present the crystal structures of apo form and GTP analog, GDP, and guanosine-3′,5′-bisdiphosphate (ppGpp)-bound BipA. In addition to having a distinctive domain arrangement, the C-terminal domain of BipA has a unique fold. Furthermore, we report the cryo-electron microscopy structure of BipA bound to the ribosome in its active GTP form and elucidate the unique structural attributes of BipA interactions with the ribosome and A-site tRNA in the light of its possible function in regulating translation.
Presence of Bartonella Species in Wild Carnivores of Northern Spain

ABSTRACT The genus Bartonella was detected by PCR in 5.7% (12/212) of wild carnivores from Northern Spain. Based on hybridization and sequence analyses, Bartonella henselae was identified in a wildcat (Felis silvestris), Bartonella rochalimae in a red fox (Vulpes vulpes) and in a wolf (Canis lupus), and Bartonella sp. in badgers (Meles meles).
Reducing Stress and Tension in the Classroom through the Use of Humor.

The purpose of this paper was threefold: (1) to review the literature; (2) to determine the effects of the use of humor upon stress within the classroom; and (3) to examine the extent to which students and teachers use humor as a coping mechanism to deal with stressful school situations. It was hypothesized that humor in the classroom is effective in reducing the stress and tension of both teachers and students and is, therefore, an important classroom management technique. Two groups of subjects participated in the study. One group was composed of 9to 11-year-old students (N=98). Twenty-three fifthand sixth-grade teachers comprised the second group. All subjects completed an adapted version of Martin & Lefcourt's (1983) Coping Humor Scale, a survey concerning the use of humor in coping with stressful school situations. According to the data analysis, results supported the hypothesis for both groups. However, a slightly greater use of humor as a coping mechanism was reported by teachers. A developmental sequence of humor behavior and a copy of the survey instrument are appended. Six tables depict the number and percentage of students/teachers who selected each response, the number and percentages of combined subjects who selected each response, and the total percentage of teachers versus students who selected each response. (Contains 27 references.) (Author/La *****************************************k***************************ir* Reproductions supplied by EDRS are the best that,can be made * from the original document. *********************************************************************** Reducing Stress and Tensiol
Dynamic predictor for linear time-delay systems with disturbances

A dynamic predictor is proposed for linear time invariant disturbed systems with delay in the control input. The proposed dynamic predictor has a structure similar to the Luenberger observer. It outperforms the current predictors because it does not need the full state, as long as the plant is observable, it only requires the output from the system. The controller is proposed making use of the state vector from the dynamic predictor. The full control scheme including predictor and control law is applied in simulation. The advantages of the proposed predictor include robustness against external disturbances, and also the fact that the controllers developed making use of predictor are capable of tracking time-variable signals.
Security analysis of logic obfuscation

Due to globalization of Integrated Circuit (IC) design flow, rogue elements in the supply chain can pirate ICs, overbuild ICs, and insert hardware trojans. EPIC [1] obfuscates the design by randomly inserting additional gates; only a correct key makes the design to produce correct outputs. We demonstrate that an attacker can decipher the obfuscated nctlist, in a time linear to the number of keys, by sensitizing the key values to the output. We then develop techniques to fix this vulnerability and make obfuscation truly exponential in the number of inserted keys.