Miracle-dz/UniFAR-FTUs huggingface dataset:
A High Throughput Assay to Identify Small Molecule Modulators of Prostatic Acid Phosphatase

Prostatic acid phosphatase (PAP) is expressed in nociceptive neurons and functions as an ectonucleotidase. Injection of the secretory isoform of PAP has potent antinociceptive effects in mouse models of chronic pain. These data suggested that a small molecule activator of PAP may have utility as a novel therapeutic for chronic pain, while inhibitors could be used to acutely inhibit PAP in vitro and in vivo. To identify small molecule modulators of PAP activity, we validated a high throughput, fluorescence-based biochemical assay and then used this assay to screen a compound library. We decreased the frequency of false positive activators by subtracting compound fluorescence from the final assay fluorescence. This approach significantly reduced the number of false positive activators found in the screen. While no activators were confirmed, seven novel inhibitors of PAP were identified. Our results suggest this high throughput assay could be used to identify small molecule modulators of PAP activity.
Confronting model predictions of carbon fluxes with measurements of Amazon forests subjected to experimental drought.

Considerable uncertainty surrounds the fate of Amazon rainforests in response to climate change. Here, carbon (C) flux predictions of five terrestrial biosphere models (Community Land Model version 3.5 (CLM3.5), Ecosystem Demography model version 2.1 (ED2), Integrated BIosphere Simulator version 2.6. 4 (IBIS), Joint UK Land Environment Simulator version 2.1 (JULES) and Simple Biosphere model version 3 (SiB3)) and a hydrodynamic terrestrial ecosystem model (the Soil-Plant-Atmosphere (SPA) model) were evaluated against measurements from two large-scale Amazon drought experiments. Model predictions agreed with the observed C fluxes in the control plots of both experiments, but poorly replicated the responses to the drought treatments. Most notably, with the exception of ED2, the models predicted negligible reductions in aboveground biomass in response to the drought treatments, which was in contrast to an observed c. 20% reduction at both sites. For ED2, the timing of the decline in aboveground biomass was accurate, but the magnitude was too high for one site and too low for the other. Three key findings indicate critical areas for future research and model development. First, the models predicted declines in autotrophic respiration under prolonged drought in contrast to measured increases at one of the sites. Secondly, models lacking a phenological response to drought introduced bias in the sensitivity of canopy productivity and respiration to drought. Thirdly, the phenomenological water-stress functions used by the terrestrial biosphere models to represent the effects of soil moisture on stomatal conductance yielded unrealistic diurnal and seasonal responses to drought.
Improving Parallel System Performance with a NUMA-aware Load Balancer

Multi-core nodes with Non-Uniform Memory Access (NUMA) are now a common architecture for high performance computing. On such NUMA nodes, the shared memory is physically distributed into memory banks connected by a network. Owing to this, memory access costs may vary depending on the distance between the processing unit and the memory bank. Therefore, a key element in improving the performance on these machines is dealing with memory affinity. We propose a NUMA-aware load balancer that combines the information about the NUMA topology with the statistics captured by the Charm++ runtime system. We present speedups of up to 1.8 for synthetic benchmarks running on different NUMA platforms. We also show improvements over existing load balancing strategies both in benchmark performance and in the time for load balancing. In addition, by avoiding unnecessary migrations, our algorithm incurs up to seven times smaller overheads in migration, than the other strategies.
Silica-based post-wall waveguide with high-performance input and output transitions for E-band passive front-end

We proposed silica-based post-wall waveguides (PWWs) with input and output (I/O) transitions from microstrip line for 71-76 GHz and 81-86 GHz, respectively. The PWWs were designed so that their reflection keeps lower than ™20 dB at the aimed frequencies. They were fabricated in silica substrates and the performance was measured. Realization of the bandwidth of 23.6% was confirmed at the lower band. The transmission loss of the sole PWW was 0.0326 dB/mm and the insertion loss of the transition was 0.25 dB, both at 85 GHz. The silica-based PWWs can offer a practical platform for passive front-end including antenna feeds in E-band.
A Statistical View of the Transient Signals That Support a Wireless Call

A wireless call in a cellular network requires the cooperation of a wireless enabled device such as a cell phone and a dynamic set of base stations, antennas, and other network elements, with control of the call changing in response to changes in signal strength and the location of the mobile. The signaling between the network and mobile needed to manage the call generates a huge amount of signal strength data, some of which is seen only by the mobile placing the call and some of which is seen only by the network. This article describes some of the complexities of the signal strength data and provides a statistical model of the signals from the network to the wireless device that takes the time-dependent, spatial, and multivariate nature of the call into account. An approach to estimating the model parameters online as network data are collected, which would be useful for network monitoring, is also described and applied to a set of call data obtained from an active commercial CDMA (code division multiple access) network.
Effect of a multifactorial intervention on mortality in type 2 diabetes.

BACKGROUND Intensified multifactorial intervention - with tight glucose regulation and the use of renin-angiotensin system blockers, aspirin, and lipid-lowering agents - has been shown to reduce the risk of nonfatal cardiovascular disease among patients with type 2 diabetes mellitus and microalbuminuria. We evaluated whether this approach would have an effect on the rates of death from any cause and from cardiovascular causes. METHODS In the Steno-2 Study, we randomly assigned 160 patients with type 2 diabetes and persistent microalbuminuria to receive either intensive therapy or conventional therapy; the mean treatment period was 7.8 years. Patients were subsequently followed observationally for a mean of 5.5 years, until December 31, 2006. The primary end point at 13.3 years of follow-up was the time to death from any cause. RESULTS Twenty-four patients in the intensive-therapy group died, as compared with 40 in the conventional-therapy group (hazard ratio, 0.54; 95% confidence interval [CI], 0.32 to 0.89; P=0.02). Intensive therapy was associated with a lower risk of death from cardiovascular causes (hazard ratio, 0.43; 95% CI, 0.19 to 0.94; P=0.04) and of cardiovascular events (hazard ratio, 0.41; 95% CI, 0.25 to 0.67; P<0.001). One patient in the intensive-therapy group had progression to end-stage renal disease, as compared with six patients in the conventional-therapy group (P=0.04). Fewer patients in the intensive-therapy group required retinal photocoagulation (relative risk, 0.45; 95% CI, 0.23 to 0.86; P=0.02). Few major side effects were reported. CONCLUSIONS In at-risk patients with type 2 diabetes, intensive intervention with multiple drug combinations and behavior modification had sustained beneficial effects with respect to vascular complications and on rates of death from any cause and from cardiovascular causes. (ClinicalTrials.gov number, NCT00320008.)
Brucellosis.

It seems particularly appropriate for doctors of veterinary and of human medicine to exchange ideas and to. work together in the study and control of brucellosis, a widespread infection of man and animals. That some of the most important contributions to the knowledge of the subject have been made by doctors of veterinary medicine is too well known to require documentation but too important to fail to acknowledge. The interdependence of the two disciplines is so great as to make desirable an even greater degree of collaboration. Brucellosis of animals and of man presents an almost unique twofold problem. It is one of the most difficult of all diseases to diagnose, particularly in the chronic illness. When a diagnosis has been arrived at, the problems of treatment are manifold. DIAGNOSIS Importance of Early Diagnosis. — Brucellosis must be considered in the diagnosis of any obscure illness. Early diagnosis is difficult with
Regulation of Ras Localization by Acylation Enables a Mode of Intracellular Signal Propagation

Active Ras is relayed between subcellular compartments by the acylation cycle. Ras Radio Waves The Ras family of small guanosine triphosphatases (GTPases) has roles in cellular proliferation and is frequently mutated in tumors. Stimulation of cells with epidermal growth factor leads to the transient activation of H-Ras at the plasma membrane, followed by an echo of this activity at the Golgi. This distinct spatiotemporal activity profile suggests that the Golgi is a passive receiver of Ras signals from the plasma membrane. Lorentzen et al. performed quantitative imaging and mathematical modeling of cells in which binding of H-Ras to GDP or GTP was decoupled from the acylation cycle that maintains its spatial organization. Regulation of H-Ras binding to GDP or GTP occurred only at the plasma membrane and not at the Golgi. Furthermore, the acylation cycle delivered active H-Ras from the plasma membrane to the Golgi, as well as from the endoplasmic reticulum to the Golgi; this latter delivery route enabled sustained H-Ras activity at the Golgi after the initial activation echo. Thus, the amount of active Ras at the Golgi is determined by activation of Ras at the plasma membrane and the endoplasmic reticulum, and the acylation cycle serves to relay activated Ras between subcellular compartments. Growth factor stimulation generates transient H-Ras activity at the plasma membrane but sustained activity at the Golgi. Two overlapping regulatory networks control compartmentalized H-Ras activity: the guanosine diphosphate–guanosine triphosphate cycle and the acylation cycle, which constitutively traffics Ras isoforms that can be palmitoylated between intracellular membrane compartments. Quantitative imaging of H-Ras activity after decoupling of these networks revealed regulation of H-Ras activity at the plasma membrane but not at the Golgi. Nevertheless, upon stimulation with epidermal growth factor, Ras activity at the Golgi displayed a pulse-like profile similar to that at the plasma membrane but also remained high after the initial stimulus. A compartmental model that included the acylation cycle and H-Ras regulation at the plasma membrane accounted for the pulse-like profile of H-Ras activity at the Golgi but implied that sustained H-Ras activity at the Golgi required H-Ras activation at an additional compartment, which we experimentally determined to be the endoplasmic reticulum. Thus, in addition to maintaining the localization of Ras, the acylation cycle underlies a previously unknown form of signal propagation similar to radio transmission in its generation of a constitutive Ras “carrier wave” that transmits Ras activity between subcellular compartments.
Ubicación óptima de PMU considerando restricciones de contingencias N-1 en sistemas eléctricos de potencia

La evaluación de los parámetros eléctricos mediante unidades de medición fasorial en los sistemas de potencia es fundamental, ya que con los datos obtenidos se realiza la estimación del estado de la operación de los mismos. En la presente investigación se plantea el problema para el despliegue óptimo de unidades de medición fasorial respetando restricciones de observabilidad, redundancia y contingencias N-1. La minimización de unidades considera la salida de una línea de transmisión o la falla de una unidad de medición fasorial y garantiza el 100 % de observabilidad de sistema de potencia; para la optimización se utilizó programación lineal entera mixta. El algoritmo propuesto fue probado con los modelos de prueba del IEEE de 9, 14, 30 y 118 nodos.
The Role of BRCA1 Domains and Motifs in Tumor Suppression

Abstract : The purpose of this research is to classify BRCA1 variants for which cancer association is not known (called variants of uncertain significance or VUS). To approach this problem we hypothesized that poorly characterized but conserved domains in BRCA1 directly participate in its tumor suppression function. To test this hypothesis we set out to develop: 1. A system of functional assays to test the functions of domains anywhere in coding region of BRCA1. Our results indicate that the intra S phase checkpoint function of BRCA1 can be used for further classification of BRCA1 unclassified variants for their cancer association as well as for analyzing BRCA1 function. 2. We also studied the function of under explored but conserved small motifs in BRCA1. Using as bait in yeast two hybrid screening one of these motifs we identified the cytoskeletal protein Filamin A as a specific BRCA1 binding partner. Their interaction is abrogated by a mutation found in breast cancer families. We systematically evaluated DNA damage signaling after treatment with ionizing radiation in cells that lack Filamin A. We found that these cells have an impaired BRCA1 and Rad51 foci formation and accumulate single stranded DNA. Our data showed that lack of Filamin A leads to an impairment in both HR and NHEJ repair pathways.
Trends and burden of bronchiectasis-associated hospitalizations in the United States, 1993-2006.

BACKGROUND Current data on bronchiectasis prevalence, trends, and risk factors are lacking; such data are needed to estimate the burden of disease and for improved medical care and public health resource allocation. The objective of the present study was to estimate the trends and burden of bronchiectasis-associated hospitalizations in the United States. METHODS We extracted hospital discharge records containing International Classification of Diseases, 9th Revision, Clinical Modification codes for bronchiectasis (494, 494.0, and 494.1) as any discharge diagnosis from the State Inpatient Databases from the Agency for Healthcare Research and Quality. Discharge records were extracted for 12 states with complete and continuous reporting from 1993 to 2006. RESULTS The average annual age-adjusted hospitalization rate from 1993 to 2006 was 16.5 hospitalizations per 100,000 population. From 1993 to 2006, the age-adjusted rate increased significantly, with an average annual percentage increase of 2.4% among men and 3.0% among women. Women and persons aged > 60 years had the highest rate of bronchiectasis-associated hospitalizations. The median cost for inpatient care was 7,827 US dollars (USD) (range, 13-543,914 USD). CONCLUSIONS The average annual age-adjusted rate of bronchiectasis-associated hospitalizations increased from 1993 to 2006. This study furthers the understanding of the impact of bronchiectasis and demonstrates the need for further research to identify risk factors and reasons for the increasing burden.
Excitation of surface plasmons in metallic thin films using nanoparticle arrays

In this paper, a device for coupling light into symmetric and asymmetric surface plasmon modes in a metallic thin film is presented. This device consists of a two-dimensional periodic array of nanoparticles located above a silver thin film that supports surface plasmons. The nanoparticles and the metallic thin film are embedded in silica. By exciting local surface plasmons in these nanoparticles, light is coupled into the metallic thin film. The coupling process is simulated using finite integration technique. The effects of size of nanoparticles, their distance from the metallic film and the thickness of the metallic film on the coupling are investigated.
Odd correlation: Parkinson’s disease and melanoma. What is the possible link?

Parkinson’s disease (PD) is a neurodegenerative disorder, characterised by depletion of dopamine in the striatum and loss of melanin-positive, dopaminergic neurons in the substantia nigra. Melanoma is a skin neoplasm arising from epidermal melanocytes. The epidemiology of melanoma focuses on well-known risk factors such as light skin and hair colour, gender, eye pigmentation, and ultraviolet (UV) exposure. Many studies have suggested an association between Parkinson’s disease and melanoma. The mechanism underlying the possible connection between PD and melanoma is not clear and has aroused lots of interest. More interesting is that the link between these two diseases runs both ways. What is the underlying cause of this reciprocal association? Is it due to Parkinson’s treatment? Is levodopa the reason for increased incidence of melanoma in people with the neurodegenerative condition? Are there any genetic, immune system irregularities or environmental risk factors that serve as the common denominator between these two conditions? Should we consider melanoma comorbidity with Parkinson’s disease and vice versa? Some hypotheses include pigmentation changes in melanin and/or melanin synthesis enzyme like tyrosinase hydroxylase, autophagy deficits, disturbed form of metabolically controlled cell death, and changes of PD-related genes such as Parkin or a-synuclein. Learning more about the relationship between PD and melanoma may lead to a better understanding of each disease and contribute to more effective treatments of both.
Analysis of Cardiac Diffusion Tensor Magnetic Resonance Images Using Sparse Representation

In cardiac diffusion tensor magnetic resonance imaging (DT-MRI), low signal-to-noise ratio (SNR) inherently hampers the measurement accuracy of myocardium fiber structures. This paper presents a new method for filtering diffusion weighted (DW) images in cardiac DT-MRI. The method is based on sparse representation through using basis pursuit denoising (BPDN) algorithm allowing seeking overall sparest solution. It decomposes useful structures in DW images into sparsely representing atoms with Heaviside dictionary, while yielding nonsparse representation on noise, which leads to the separation of the noise from the image's useful structures. The proposed method is evaluated on both simulated and real cardiac DW images.
Conversational gaze in light and darkness

The way we use our gaze in face-to-face interaction is an important part of our social behavior. This exploratory study investigates the relationship between mutual gaze and joint silences and overlaps, where speaker changes and backchannels often occur. Seven dyadic conversations between two persons were recorded in a studio. Gaze patterns were annotated in ELAN to find instances of mutual gaze. Part of the study was conducted in total darkness as a way to observe what happens to our gaze-patterns when we cannot see our interlocutor, although the physical face-to-face condition is upheld. The results show a difference in the frequency of mutual gaze in conversation in light and darkness.
Extragenic Suppression of a Mutation in Herpes Simplex Virus 1 UL34 That Affects Lamina Disruption and Nuclear Egress

ABSTRACT Nuclear egress of herpesviruses is accompanied by changes in the architecture of the nuclear membrane and nuclear lamina that are thought to facilitate capsid access to the inner nuclear membrane (INM) and curvature of patches of the INM around the capsid during budding. Here we report the properties of a point mutant of pUL34 (Q163A) that fails to induce gross changes in nuclear architecture or redistribution of lamin A/C. The UL34(Q163A) mutant shows a roughly 100-fold defect in single-step growth, and it forms small plaques. This mutant has a defect in nuclear egress, and furthermore, it fails to disrupt nuclear shape or cause observable displacement of lamin A/C despite retaining the ability to recruit the pUS3 and PKC protein kinases and to mediate phosphorylation of emerin. Extragenic suppressors of the UL34(Q163A) phenotype were isolated, and all of them carry a single mutation of arginine 229 to leucine in UL31. Surprisingly, although this UL31 mutation largely restores virus replication, it does not correct the lamina disruption defect, suggesting that, in Vero cells, changes in nuclear shape and gross displacements of lamin A/C may facilitate but are unnecessary for nuclear egress. IMPORTANCE Herpesvirus nuclear egress is an essential and conserved process that requires close association of the viral capsid with the inner nuclear membrane and budding of the capsid into that membrane. Access to the nuclear membrane and tight curvature of that membrane are thought to require disruption of the nuclear lamina that underlies the inner nuclear membrane, and consistent with this idea, herpesvirus infection induces biochemical and architectural changes at the nuclear membrane. The significance of the nuclear membrane architectural changes is poorly characterized. The results presented here address that deficiency in our understanding and show that a combination of mutations in two of the viral nuclear egress factors results in a failure to accomplish at least two components of lamina disruption while still allowing relatively efficient viral replication, suggesting that changes in nuclear shape and displacement of lamins are not necessary for herpes simplex virus 1 (HSV-1) nuclear egress.
Conversationally Relevant Descriptions

Conversationally relevant descriptions are definite descriptions that are not merely tools for the identification of a referent, but are also crucial to the discourse in other respects. I analyse the uses of such descriptions in assertions as conveying a particular type of conversational implicatures. Such implicatures can be represented within the framework of possible world semantics. The analysis is extended to non-assertive illocutionary acts on the one hand, and to indefinite descriptions on the other.