Miracle-dz/UniFAR-FTUs huggingface dataset:
Prion-like proteins sequester and suppress the toxicity of huntingtin exon 1

Significance Expansion of polyglutamine tracts in at least nine proteins causes neurodegeneration. Although the pathology caused by each protein is different, there must be common features of the polyglutamine expansion that contribute to toxicity. We modeled polyglutamine toxicity in yeast by expressing a 103-glutamine expanded fragment of huntingtin (Htt103Q) and screened the yeast genome to identify proteins that alter this toxicity. Surprisingly, our suppressors were proteins containing glutamine- and asparagine-rich segments typical of prion proteins. When we expressed just these segments with Htt103Q, the two proteins formed large, coaggregated particles, and smaller, more toxic aggregated forms were absent. Proteins with such segments may interact with polyQ-expanded proteins and thereby modulate their toxicity. These interaction partners provide targets for therapeutic intervention. Expansions of preexisting polyglutamine (polyQ) tracts in at least nine different proteins cause devastating neurodegenerative diseases. There are many unique features to these pathologies, but there must also be unifying mechanisms underlying polyQ toxicity. Using a polyQ-expanded fragment of huntingtin exon-1 (Htt103Q), the causal protein in Huntington disease, we and others have created tractable models for investigating polyQ toxicity in yeast cells. These models recapitulate key pathological features of human diseases and provide access to an unrivalled genetic toolbox. To identify toxicity modifiers, we performed an unbiased overexpression screen of virtually every protein encoded by the yeast genome. Surprisingly, there was no overlap between our modifiers and those from a conceptually identical screen reported recently, a discrepancy we attribute to an artifact of their overexpression plasmid. The suppressors of Htt103Q toxicity recovered in our screen were strongly enriched for glutamine- and asparagine-rich prion-like proteins. Separated from the rest of the protein, the prion-like sequences of these proteins were themselves potent suppressors of polyQ-expanded huntingtin exon-1 toxicity, in both yeast and human cells. Replacing the glutamines in these sequences with asparagines abolished suppression and converted them to enhancers of toxicity. Replacing asparagines with glutamines created stronger suppressors. The suppressors (but not the enhancers) coaggregated with Htt103Q, forming large foci at the insoluble protein deposit in which proteins were highly immobile. Cells possessing foci had fewer (if any) small diffusible oligomers of Htt103Q. Until such foci were lost, cells were protected from death. We discuss the therapeutic implications of these findings.
OPTIMAL COORDINATED MANEUVERS FOR THREE DIMENSIONAL AIRCRAFT CONFLICT RESOLUTION

In this paper, we study the problem of designing optimal coordinated maneuvers for multiple aircraft conflict resolution. We propose an energy function to select among all the conflict-free maneuvers the optimal one. The introduced cost function incorporates a priority mechanism that favors those maneuvers where aircraft with lower priority assume more responsibility in resolving the predicted conflicts. The energy-minimizing resolution maneuvers may involve changes of heading and speed, as well as of altitude. However, vertical maneuvers are penalized with respect to horizontal ones for the sake of passenger comfort. A geometric construction and a numerical algorithm for computing the optimal resolution maneuvers are given in the two aircraft case. As for the multiaircraft case, an approximation scheme is proposed to compute a suboptimal two-legged solution. Extensive examples are presented to illustrate the effectiveness of the proposed algorithms.
Akathisia: Prevalence and Associated Dysphoria in an In-patient Population with Chronic Schizophrenia

In a sample of 120 long-stay in-patients who fulfilled DSM–III–R criteria for schizophrenia, chronic akathisia and pseudoakathisia were relatively common, with prevalence figures of 24% and 18%, respectively. Compared with patients without evidence of chronic akathisia, those patients with the condition were significantly younger, were receiving significantly higher doses of antipsychotic medication, and were more likely to be receiving a depot antipsychotic. Patients who experienced the characteristic inner restlessness and compulsion to move of akathisia also reported marked symptoms of dysphoria, namely tension, panic, irritability and impatience. The findings support the suggestion that dysphoric mood is an important feature of akathisia. Male patients appeared to be at an increased risk of pseudoakathisia. No significant relation was found between chronic akathisia and tardive dyskinesia, although there was a trend for trunk and limb dyskinesia to be commonest in patients with chronic akathisia while orofacial dyskinesia was most frequently observed in those with pseudoakathisia. Akathisia may mask the movements of tardive dyskinesia in the lower limb. There was no evidence that akathisia was associated with positive or negative symptoms of schizophrenia nor with depression.
Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease

Antibody therapies to prevent or limit filovirus infections have received modest interest in recent years, in part because of early negative experimental evidence. We have overcome the limitations of this approach, leveraging the use of antibody from nonhuman primates (NHPs) that survived challenge to filoviruses under controlled conditions. By using concentrated, polyclonal IgG antibody from these survivors, we treated filovirus-infected NHPs with multiple doses administered over the clinical phase of disease. In the first study, Marburg virus (MARV)-infected NHPs were treated 15 to 30 min postexposure with virus-specific IgG, with additional treatments on days 4 and 8 postexposure. The postexposure IgG treatment was completely protective, with no signs of disease or detectable viremia. MARV-specific IgM antibody responses were generated, and all macaques survived rechallenge with MARV, suggesting that they generated an immune response to virus replication. In the next set of studies, NHPs were infected with MARV or Ebola virus (EBOV), and treatments were delayed 48 h, with additional treatments on days 4 and 8 postexposure. The delayed treatments protected both MARV- and EBOV-challenged NHPs. In both studies, two of the three IgG-treated NHPs had no clinical signs of illness, with the third NHP developing mild and delayed signs of disease followed by full recovery. These studies clearly demonstrate that postexposure antibody treatments can protect NHPs and open avenues for filovirus therapies for human use using established Food and Drug Administration-approved polyclonal or monoclonal antibody technologies.
Ser-634 and Ser-636 of Kaposi’s Sarcoma-Associated Herpesvirus RTA are Involved in Transactivation and are Potential Cdk9 Phosphorylation Sites

The replication and transcription activator (RTA) of Kaposi’s sarcoma-associated herpesvirus (KSHV), K-RTA, is a lytic switch protein that moderates the reactivation process of KSHV latency. By mass spectrometric analysis of affinity purified K-RTA, we showed that Thr-513 or Thr-514 was the primary in vivo phosphorylation site. Thr-513 and Thr-514 are proximal to the nuclear localization signal (527KKRK530) and were previously hypothesized to be target sites of Ser/Thr kinase hKFC. However, substitutions of Thr with Ala at 513 and 514 had no effect on K-RTA subcellular localization or transactivation activity. By contrast, replacement of Ser with Ala at Ser-634 and Ser-636 located in a Ser/Pro-rich region of K-RTA, designated as S634A/S636A, produced a polypeptide with ∼10 kDa shorter in molecular weight and reduced transactivation in a luciferase reporter assay relative to the wild type. In contrast to prediction, the decrease in molecular weight was not due to lack of phosphorylation because the overall Ser and Thr phosphorylation state in K-RTA and S634A/S636A were similar, excluding that Ser-634 or Ser-636 motif served as docking sites for consecutive phosphorylation. Interestingly, S634A/S636A lost ∼30% immuno-reactivity to MPM2, an antibody specific to pSer/pThr-Pro motif, indicating that 634SPSP637 motif was in vivo phosphorylated. By in vitro kinase assay, we showed that K-RTA is a substrate of CDK9, a Pro-directed Ser/Thr kinase central to transcriptional regulation. Importantly, the capability of K-RTA in associating with endogenous CDK9 was reduced in S634A/S636A, which suggested that Ser-634 and Ser-636 may be involved in CDK9 recruitment. In agreement, S634A/S636A mutant exhibited ∼25% reduction in KSHV lytic cycle reactivation relative to that by the wild type K-RTA. Taken together, our data propose that Ser-634 and Ser-636 of K-RTA are phosphorylated by host transcriptional kinase CDK9 and such a process contributes to a full transcriptional potency of K-RTA.
Resilient principals in challenging schools: the courage and costs of conviction

The work of leaders in schools takes place in shifting and sometimes conflicting reform contexts which tend to increase and intensify their professional work and personal lives as they seek to influence a range of stakeholder groups and individuals in processes of school improvement. Such diverse and sometimes competing demands of policy, local context and educational values not only challenge the breadth of qualities, knowledge and skills possessed by leaders, but also test their adaptivity, flexibility and intellectual, and emotional energy on an everyday basis. Although much of the literature on resilience suggests that it is a necessary quality in extreme adverse circumstances – for example, physical or emotional trauma as a result of conflict – it seems obvious that everyday resilience will be an essential quality and a necessary capacity for leaders to lead to their best. However, this may be sorely tested as the range of their roles and responsibilities expands and their space to exercise ‘responsible agency’ at work shrinks, together with personal space outside the workplace – traditionally viewed as a time to reflect, recover and renew. A recent survey showed that, in England, for example, only 7% of secondary heads perceived that they had any time to engage in interests outside their work; it is unlikely that much will have changed in the years since then, as more recent root-and-branch reforms in the governance and curricula of schools in England and Wales demonstrate. How leaders of schools, which serve high-challenge communities of socio-economic disadvantage, sustain their resilience and the costs of doing so in raising and sustaining their levels of success has received only scant attention in the research literature. This paper reports the outcomes of research into the work of 12 successful principals who work in schools in challenging environments in different countries and were asked to talk about their contexts and the challenges which they had overcome in order to achieve their success. It uses one of these as an illustration of the role courage and conviction plays in all their lives.
Amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group.

CONTEXT Smaller hippocampal volumes are well established in posttraumatic stress disorder (PTSD), but the relatively few studies of amygdala volume in PTSD have produced equivocal results. OBJECTIVE To assess a large cohort of recent military veterans with PTSD and trauma-exposed control subjects, with sufficient power to perform a definitive assessment of the effect of PTSD on volumetric changes in the amygdala and hippocampus and of the contribution of illness duration, trauma load, and depressive symptoms. DESIGN Case-controlled design with structural magnetic resonance imaging and clinical diagnostic assessments. We controlled statistically for the important potential confounds of alcohol use, depression, and medication use. SETTING Durham Veterans Affairs Medical Center, which is located in proximity to major military bases. PATIENTS Ambulatory patients (n = 200) recruited from a registry of military service members and veterans serving after September 11, 2001, including a group with current PTSD (n = 99) and a trauma-exposed comparison group without PTSD (n = 101). MAIN OUTCOME MEASURE Amygdala and hippocampal volumes computed from automated segmentation of high-resolution structural 3-T magnetic resonance imaging. RESULTS Smaller volume was demonstrated in the PTSD group compared with the non-PTSD group for the left amygdala (P = .002), right amygdala (P = .01), and left hippocampus (P = .02) but not for the right hippocampus (P = .25). Amygdala volumes were not associated with PTSD chronicity, trauma load, or severity of depressive symptoms. CONCLUSIONS These results provide clear evidence of an association between a smaller amygdala volume and PTSD. The lack of correlation between trauma load or illness chronicity and amygdala volume suggests that a smaller amygdala represents a vulnerability to developing PTSD or the lack of a dose-response relationship with amygdala volume. Our results may trigger a renewed impetus for investigating structural differences in the amygdala, its genetic determinants, its environmental modulators, and the possibility that it reflects an intrinsic vulnerability to PTSD.
Investigations of electrical trees in the inner layer of XLPE cable insulation using computer-aided image recording monitoring

Using a computer-aided image recording monitoring system, extensive measurements have been performed in the inner layer of 66 kV cross-linked polyethylene (XLPE) cables. It has been found that there are three kinds of electrical trees in the samples, the branch-like tree, the bush-like tree and the mixed tree that is a mixture of the above two kinds. When the applied voltage frequency is less than or equal to 250 Hz, only the mixed tree appears in XLPE samples, when the frequency is greater than or equal to 500 Hz, only the dense branch-like tree develops, both of which are attributed to the coexistence of non-uniform crystallization and internal residual stress in semicrystalline XLPE cables during the process of manufacturing. Through the fractal analyses of these electrical trees, it has been found that both the propagation and structure characteristics can be described by fractal dimension directly or indirectly. It is suggested that the propagation and structural characteristics of electrical trees are closely related to the morphology and the residual stress in material at low frequency, i.e., the propagation characteristics of electrical trees depends upon not only the boundaries between big spherulites and amorphous region, but also the impurity, micropore concentration and the relative position of needle electrode tip with respect to spherulites or amorphous region in the low frequency range. However, at high frequency, it has nothing to do with the morphology of material. It is suggested that the injection and extraction process of charge from and to dielectrics via the needle electrode are more intense at high frequency than in low frequency. Thus, it can form relatively uniform dielectric weak region in front of needle electrode, which leads to similar initiation and propagation characteristics of electrical trees at high frequency.
Fast and efficient automatic memory management for GPUs using compiler-assisted runtime coherence scheme

Exploiting the performance potential of GPUs requires managing the data transfers to and from them efficiently which is an error-prone and tedious task. In this paper, we develop a software coherence mechanism to fully automate all data transfers between the CPU and GPU without any assistance from the programmer. Our mechanism uses compiler analysis to identify potential stale accesses and uses a runtime to initiate transfers as necessary. This allows us to avoid redundant transfers that are exhibited by all other existing automatic memory management proposals. We integrate our automatic memory manager into the X10 compiler and runtime, and find that it not only results in smaller and simpler programs, but also eliminates redundant memory transfers. Tested on eight programs ported from the Rodinia benchmark suite it achieves (i) a 1.06× speedup over hand-tuned manual memory management, and (ii) a 1.29× speedup over another recently proposed compiler-runtime automatic memory management system. Compared to other existing runtime-only and compiler-only proposals, it also transfers 2.2× to 13.3× less data on average.
Differences in GFR and Tissue Oxygenation, and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular Disease.

BACKGROUND AND OBJECTIVES Atherosclerotic renal artery stenosis (ARAS) can reduce renal blood flow, tissue oxygenation, and GFR. In this study, we sought to examine associations between renal hemodynamics and tissue oxygenation with single-kidney function, pressor hormones, and inflammatory biomarkers in patients with unilateral ARAS undergoing medical therapy alone or stent revascularization. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Nonrandomized inpatient studies were performed in patients with unilateral ARAS (>60% occlusion) before and 3 months after revascularization (n=10) or medical therapy (n=20) or patients with essential hypertension (n=32) under identical conditions. The primary study outcome was change in single-kidney GFR. Individual kidney hemodynamics and volume were measured using multidetector computed tomography. Tissue oxygenation (using R(2)* as a measure of deoxyhemoglobin) was determined by blood oxygen level-dependent magnetic resonance imaging at 3 T. Renal vein neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), and plasma renin activity were measured. RESULTS Total GFR did not change over 3 months in either group, but the stenotic kidney (STK) GFR rose over time in the stent compared with the medical group (+2.2[-1.8 to 10.5] versus -5.3[-7.3 to -0.3] ml/min; P=0.03). Contralateral kidney (CLK) GFR declined in the stent group (43.6±19.7 to 36.6±19.5 ml/min; P=0.03). Fractional tissue hypoxia fell in the STK (fraction R(2)* >30/s: 22.1%±20% versus 14.9%±18.3%; P<0.01) after stenting. Renal vein biomarkers correlated with the degree of hypoxia in the STK: NGAL(r=0.3; P=0.01) and MCP-1(r=0.3; P=0.02; more so after stenting). Renal vein NGAL was inversely related to renal blood flow in the STK (r=-0.65; P<0.001). Biomarkers were highly correlated between STK and CLK, NGAL (r=0.94; P<0.001), and MCP-1 (r=0.96; P<0.001). CONCLUSIONS These results showed changes over time in single-kidney GFR that were not evident in parameters of total GFR. Furthermore, they delineate the relationship of measurable tissue hypoxia within the STK and markers of inflammation in human ARAS. Renal vein NGAL and MCP-1 indicated persistent interactions between the ischemic kidney and both CLK and systemic levels of inflammatory cytokines.
The Development of Numerical Estimation

We examined children's and adults' numerical estimation and the representations that gave rise to their estimates. The results were inconsistent with two prominent models of numerical representation: the logarithmic-ruler model, which proposes that people of all ages possess a single, logarithmically spaced representation of numbers, and the accumulator model, which proposes that people of all ages represent numbers as linearly increasing magnitudes with scalar variability. Instead, the data indicated that individual children possess multiple numerical representations; that with increasing age and numerical experience, they rely on appropriate representations increasingly often; and that the numerical context influences their choice of representation. The results, obtained with second graders, fourth graders, sixth graders, and adults who performed two estimation tasks in two numerical contexts, strongly suggest that one cause of children's difficulties with estimation is reliance on logarithmic representations of numerical magnitudes in situations in which accurate estimation requires reliance on linear representations.
Infant predictors of behavioural inhibition

Behavioural inhibition in the second year of life is a hypothesized predictor for shyness, social anxiety and depression in later childhood, adolescence and even adulthood. To search for the earliest indicators of this fundamental temperamental trait, this study examined whether behavioural characteristics in early infancy can predict behavioural inhibition, as previously postulated. The results show that infant crying to unfamiliar stimuli at 4 months of age is a significant predictor (p = .002) of behavioural inhibition in the second year of life. These data implicate the possibility of measuring a temperamental anxiety disposition at a very young age simply by assessing crying in the face of novel stimuli.
Transformer-coupled voltage controlled osillator

This paper presents transformer-coupled VCO using symmetric transformer. By adopting cross-coupled transistors at both side of transformer, phase noise performance is improved by 6 dB compared with conventional VCO. The proposed VCO has been fabricated in CMOS 0.13. m technology. Measured results show -108 dBc/Hz phase noise at 1 MHz offset and frequency range 6.54~6.86 GHz while dissipating 2.1 mA from a 0.6 V supply.
Eigenfunctions of Linear Systems 1 0.1 Eigenfunctions of Underspread Linear Systems: Theory and Applications to Digital Communi- Cations 0 0.1.1 Summary 0.1.2 Eigenfunctions of Time-varying Systems

The knowledge of the eigenfunctions of a linear system is a fundamental issue both from the theoretical as well as from the applications point of view. Nonetheless, no analytic solution is available for the eigenfunctions of a general linear system. There are two important classes of contributions suggesting analytic expressions for the eigenfunctions of slowly-varying operators: [5], and the references therein, where it was proved that the eigenfunctions of underspread operators can be approximated by signals whose time-frequency distribution (TFD) is well localized in the time-frequency plane, and [7] where a strict relationship between the instantaneous frequency of the channel eigenfunctions and the contour lines of the Wigner Transform of the operator kernel (or Weyl symbol) was derived for Hermi-tian slowly-varying operators. In this article, following an approach similar to [7], we will show that the eigenfunctions can be found exactly for systems whose spread function is concentrated along a straight line and they can be found in approximate sense for those systems whose spread function is maximally concentrated in regions of the Doppler-delay plane whose area is smaller than one. The input/output relationship of a continuous-time (CT) linear system is [3]: y(t) = ∞ −∞ h(t, τ)x(t − τ)dτ (0.1.1) where h(t, τ) is the system impulse response. Although throughout this section we will use the terminology commonly adopted in the transit of signals through time-varying channels, it is worth pointing out that the mathematical formulation is much more general. For example, (0.1.1) can be used to describe the propagation of waves through non homogeneous media and in such a case the independent variables t and τ are spatial coordinates. Following the same notation introduced by Bello [3], any linear time-varying (LTV) channel can be fully characterized by its impulse response h(t, τ), or equivalently by the delay-Doppler spread function (or simply spread function) S(ν, τ) := ∞ −∞ h(t, τ)e −j2πνt dt, or by the time-varying transfer function H(t, f) := ∞ −∞ h(t, τ)e −j2πf τ dτ. Since the kernels of LTV systems in general are not self-adjoint, it is not possible to dene the eigenfunctions of a linear system, but we can introduce the so called left and right singular functions (in the following we will use the term eigenfunction