Miracle-dz/UniFAR-FTUs huggingface dataset:
Disparate Proteome Responses of Pathogenic and Nonpathogenic Aspergilli to Human Serum Measured by Activity-Based Protein Profiling (ABPP)*

Aspergillus fumigatus is the primary pathogen causing the devastating pulmonary disease Invasive Aspergillosis in immunocompromised individuals. There is high genomic synteny between A. fumigatus and closely related rarely pathogenic Neosartorya fischeri and Aspergillus clavatus genomes. We applied activity-based protein profiling to compare unique or overexpressed activity-based probe-reactive proteins of all three fungi over time in minimal media growth and in response to human serum. We found 360 probe-reactive proteins exclusive to A. fumigatus, including known virulence associated proteins, and 13 proteins associated with stress response exclusive to A. fumigatus culture in serum. Though the fungi are highly orthologous, A. fumigatus has a significantly greater number of ABP-reactive proteins across varied biological process. Only 50% of expected orthologs of measured A. fumigatus reactive proteins were observed in N. fischeri and A. clavatus. Activity-based protein profiling identified a number of processes that were induced by human serum in A. fumigatus relative to N. fischeri and A. clavatus. These included actin organization and assembly, transport, and fatty acid, cell membrane, and cell wall synthesis. Additionally, signaling proteins regulating vegetative growth, conidiation, and cell wall integrity, required for appropriate cellular response to external stimuli, had higher activity-based probe-protein reaction over time in A. fumigatus and N. fisheri, but not in A. clavatus. Together, we show that measured proteins and physiological processes identified solely or significantly over-represented in A. fumigatus reveal a unique adaptive response to human protein not found in closely related, but rarely pathogenic aspergilli. These unique activity-based probe-protein responses to culture condition may reveal how A. fumigatus initiates pulmonary invasion leading to Invasive Aspergillosis.
Coverage, Adherence and Costs of Intermittent Preventive Treatment of Malaria in Children Employing Different Delivery Strategies in Jasikan, Ghana

Background Intermittent preventive treatment of malaria in children (IPTc) involves the administration of a course of anti-malarial drugs at specified time intervals to children at risk of malaria regardless of whether or not they are known to be infected. IPTc provides a high level of protection against uncomplicated and severe malaria, with monthly sulphadoxine-pyrimethamine plus amodiaquine (SP&AQ) and sulphadoxine-pyrimethamine plus piperaquine being the most efficacious regimens. A key challenge is the identification of a cost-effective delivery strategy. Methods A community randomized trial was undertaken in Jasikan district, Ghana to assess IPTc effectiveness and costs using SP&AQ delivered in three different ways. Twelve villages were randomly selected to receive IPTc from village health workers (VHWs) or facility-based nurses working at health centres' outpatient departments (OPD) or EPI outreach clinics. Children aged 3 to 59 months-old received one IPT course (three doses) in May, June, September and October. Effectiveness was measured in terms of children covered and adherent to a course and delivery costs were calculated in financial and economic terms using an ingredient approach from the provider perspective. Results The economic cost per child receiving at least the first dose of all 4 courses was US$4.58 when IPTc was delivered by VHWs, US$4.93 by OPD nurses and US$ 5.65 by EPI nurses. The unit economic cost of receiving all 3 doses of all 4 courses was US$7.56 and US$8.51 when IPTc was delivered by VHWs or facility-based nurses respectively. The main cost driver for the VHW delivery was supervision, reflecting resources used for travelling to more remote communities rather than more intense supervision, and for OPD and EPI delivery, it was the opportunity cost of the time spent by nurses in dispensing IPTc. Conclusions VHWs achieve higher IPTc coverage and adherence at lower costs than facility-based nurses in Jasikan district, Ghana. Trial Registration ClinicalTrials.gov NCT00119132.
Privileged Structures Revisited

Abstract Privileged structures inspire compound library design in medicinal chemistry. We performed a comprehensive analysis of 1.4 million bioactive compounds, with the aim of assessing the prevalence of certain molecular frameworks. We used the Shannon entropy formalism to quantify the promiscuity of the most frequently observed atom scaffolds across the annotated target families. This analysis revealed an apparent inverse relationship between hydrogen‐bond‐acceptor count of a scaffold and its potential promiscuity. The results further suggest that chemically easily accessible scaffolds can serve as templates for the generation of bespoke compound libraries with differing degrees of multiple target engagement, and heterocyclic, sp3‐rich frameworks are particularly suited for target‐focused library design. The outcome of our study enables us to place some of the many narratives surrounding the concept of privileged structures into a critical context.
Assay for evaluation of rotavirus-cell interactions: identification of an enterocyte ganglioside fraction that mediates group A porcine rotavirus recognition

A virus-host cell-binding assay was developed and used to investigate specific binding between group A porcine rotavirus and MA-104 cells or porcine enterocytes. A variety of glycoconjugates and cellular components were screened for their ability to block rotavirus binding to cells. During these experiments a crude ganglioside mixture was observed to specifically block rotavirus binding. On the basis of these results, enterocytes were harvested from susceptible piglets and a polar lipid fraction was isolated by solvent extraction and partitioning. Throughout subsequent purification of this fraction by Sephadex partition, ion-exchange, silicic acid, and thin-layer chromatography, blocking activity behaved as a monosialoganglioside (GMX) that displayed a thin-layer chromatographic mobility between those of GM2 and GM3. The blocking activity of GMX was inhibited by treatment with neuraminidase and ceramide glycanase but not by treatment with protease or heat (100 degrees C). Further purification of GMX by high-pressure liquid chromatography resulted in the resolution of two monosialogangliosides, GMX and a band which comigrated with GM1 on thin-layer chromatography. These data suggest that a cell surface monosialoganglioside or family of monosialogangliosides may function as an in vivo relevant receptor for group A porcine rotavirus and that sialic acid is a required epitope for virus-binding activity.
An Optical Catalog of the Chandra Large Area Synoptic X-Ray Survey Sources

We present photometric and spectroscopic observations of the X-ray sources detected in the wide-area, moderately deep Chandra Large Area Synoptic X-ray Survey (CLASXS) of the Lockman Hole-Northwest field. We have B, V, R, I, and z′ photometry for 521 (99%) of the 525 sources in the X-ray catalog and spectroscopic redshifts for 271 (52%), including 20 stars. We do not find evidence for redshift groupings of the X-ray sources, like those found in the Chandra Deep Field surveys, because of the larger solid angle covered by this survey. We separate the X-ray sources by optical spectral type and examine the colors, apparent and absolute magnitudes, and redshift distributions for the broad-line and non–broad-line active galactic nuclei. Combining our wide-area survey with other Chandra and XMM-Newton hard X-ray surveys, we find a definite lack of luminous, high accretion rate sources at z < 1, consistent with previous observations that showed that supermassive black hole growth is dominated at low redshifts by sources with low accretion rates.
Effect of disodium cromoglycate on antigen-evoked histamine release from human skin.

The effect of disodium cromoglycate (DSCG) on antigen-evoked histamine release from IgE-sensitized human skin in vitro has been studied using breast skin from six donors. Concentrations of DSCG ranging from 10–200 μM did not produce any consistent effect on histamine release, the results ranging from moderate inhibition to moderate enhancement. With higher concentrations of DSCG (400–500 μM) enhancement of release occurred in nearly all experiments. Variation of antigen concentration did not modify the response to DSCG. These results do not support the possibility that DSCG may be effective in the treatment of immediate hypersensitivity reactions in human skin.
Physician over‐recommendation of mammography for terminally ill women

There has been recent, sometimes intense, debate about when to begin screening and how often to screen women for breast cancer with mammography. However, there should be no controversy regarding screening women who are unlikely to benefit from the procedure, such as those with a serious, life‐limiting illness who would not live long enough to benefit from the potential detection and treatment of breast cancer. Identifying characteristics of physicians who recommend mammography for terminally ill women can help guide efforts to minimize patient risks and make better use of health care resources.
16.4-Tflops Direct Numerical Simulation of Turbulence by a Fourier Spectral Method on the Earth Simulator

The high-resolution direct numerical simulations (DNSs) of incompressible turbulence with numbers of grid points up to 40963 have been executed on the Earth Simulator (ES). The DNSs are based on the Fourier spectral method, so that the equation for mass conservation is accurately solved. In DNS based on the spectral method, most of the computation time is consumed in calculating the three-dimensional (3D) Fast Fourier Transform (FFT), which requires huge-scale global data transfer and has been the major stumbling block that has prevented truly high-performance computing. By implementing new methods to efficiently perform the 3D-FFT on the ES, we have achieved DNS at 16.4 Tflops on 20483 grid points. The DNS yields an energy spectrum exhibiting a wide inertial subrange, in contrast to previous DNSs with lower resolutions, and therefore provides valuable data for the study of the universal features of turbulence at large Reynolds number.
Imaging of myocardial infarction using ultrasmall superparamagnetic iron oxide nanoparticles: a human study using a multi-parametric cardiovascular magnetic resonance imaging approach.

AIMS The purpose of this clinical trial was to investigate whether cardiovascular magnetic resonance imaging (CMR) using ferumoxytol (Feraheme™, FH), an ultrasmall superparamagnetic iron oxide nanoparticle (USPIO), allows more detailed characterization of infarct pathology compared with conventional gadolinium-based necrosis/fibrosis imaging in patients with acute myocardial infarction. METHODS AND RESULTS Fourteen patients who had experienced an acute ST-elevation myocardial infarction were included in this study. Following coronary angiography, a first baseline study (pre-FH) was performed followed by subsequent CMR studies (post-FH) 48 h after intravenous ferumoxytol administration. The CMR studies comprised cine-CMR, T(2)-weighted short tau inversion recovery spin echo imaging, T(2)-mapping, and T(1)-weighted late gadolinium enhancement (LGE) imaging. The median extent of short-axis in-plane LGE was 30% [inter-quartile range (IQR) 26-40%]. The median in-plane extent of T(2)-weighted 'hypoenhancement' in the region of myocardial infarction, which was not present prior to ferumoxytol administration in any patient, was 19% (IQR 14-22%; P < 0.001 compared with the extent of LGE). The median in-plane extent of areas showing signal void in T(2)-mapping images post-FH in the region of myocardial infarction was 16% (IQR 12-18%; P < 0.001 compared with the extent of LGE; P = 0.34 compared with the extent of T(2)-weighted hypoenhancement). A substantial drop in absolute T(2)-values was observed not only in the infarct core and peri-infarct zone, but also in the remote 'healthy' myocardium, although there was only a minor change in the skeletal muscle. Substantial ferumoxytol uptake was detected only in cultured macrophages, but not in peripheral blood monocytes from study patients. CONCLUSION We could demonstrate in humans that USPIO-based contrast agents enable a more detailed characterization of myocardial infarct pathology mainly by detecting infiltrating macrophages. Considering the multi-functionality of USPIO-based particles and their superior safety profile compared with gadolinium-based compounds, these observations open up new vistas for the clinical application of USPIO.
GEMM-based level 3 BLAS: high-performance model implementations and performance evaluation benchmark

The level 3 Basic Linear Algebra Subprograms (BLAS) are designed to perform various matrix multiply and triangular system solving computations. Due to the complex hardware organization of advanced computer architectures the development of optimal level 3 BLAS code is costly and time consuming. However, it is possible to develop a portable and high-performance level 3 BLAS library mainly relying on a highly optimized GEMM, the routine for the general matrix multiply and add operation. With suitable partitioning, all the other level 3 BLAS can be defined in terms of GEMM and a small amount of level 1 and level 2 computations. Our contribution is twofold. First, the model implementations in Fortran 77 of the GEMM-based level 3 BLAS are structured to reduced effectively data traffic in a memory hierarchy. Second, the GEMM-based level 3 BLAS performance evaluation benchmark is a tool for evaluating and comparing different implementations of the level 3 BLAS with the GEMM-based model implementations.
Distributed admission control

This paper describes a framework for admission control for a packet-based network where the decisions are taken by edge devices or end-systems, rather than resources within the network. The decisions are based on the results of probe packets that the end-systems send through the network, and require only that resources apply a mark to packets in a way that is load dependent. One application example is the Internet, where marking information is fed back via an ECN bit, and we show how this approach allows a rich QoS framework for flows or streams. Our approach allows networks to be explicitly analyzed, and consequently engineered.
Synergistic Potentiation of Cystic Fibrosis Transmembrane Conductance Regulator Gating by Two Chemically Distinct Potentiators, Ivacaftor (VX-770) and 5-Nitro-2-(3-Phenylpropylamino) Benzoate

Cystic fibrosis (CF) is caused by loss-of-function mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene encoding a phosphorylation-activated but ATP-gated chloride channel. Previous studies suggested that VX-770 [ivacaftor, N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide], a CFTR potentiator now used in clinics, increases the open probability of CFTR by shifting the gating conformational changes to favor the open channel configuration. Recently the chloride channel blocker and CFTR potentiator 5-nitro-2-(3-phenylpropylamino) benzoate (NPPB) has been reported to enhance CFTR activity by a mechanism that exploits the ATP hydrolysis-driven, nonequilibrium gating mechanism unique to CFTR. Surprisingly however, NPPB increased the activity of nonhydrolytic G551D-CFTR, the third most common disease-associated mutation. Here, we further investigated the mechanism of NPPB’s effects on CFTR gating by assessing its interaction with well-studied VX-770. Interestingly, once G551D-CFTR was maximally potentiated by VX-770, NPPB further increased its activity. However, quantitative analysis of this drug–drug interaction suggests that this pharmacologic synergism is not due to independent actions of NPPB and VX-770 on CFTR gating; instead, our data support a dependent mechanism involving two distinct binding sites. This latter idea is further supported by the observation that the locked-open time of a hydrolysis-deficient mutant K1250A was shortened by NPPB but prolonged by VX-770. In addition, the effectiveness of NPPB, but not of VX-770, was greatly diminished in a mutant whose second nucleotide-binding domain was completely removed. Interpreting these results under the framework of current understanding of CFTR gating not only reveals insights into the mechanism of action for different CFTR potentiators but also brings us one step forward to a more complete schematic for CFTR gating.
The Paradoxical Relationship Between Stallion Fertility and Oxidative Stress1

ABSTRACT The relationship between stallion fertility and oxidative stress remains poorly understood. The purpose of this study was to identify criteria for thoroughbred fertility assessment by performing a logistical regression analysis using “dismount” sperm parameters as predictors and weekly per-cycle conception rate as the dependent variable. Paradoxically, positive relationships between fertility and oxidative stress were revealed, such that samples that produced pregnancies exhibited higher rates of 8-hydroxy-2′-deoxyguanosine release (1490.2% vs. 705.5 pg/ml/24 h) and lower vitality (60.5% vs. 69.6%) and acrosome integrity (40.2% vs. 50.1%) than those that did not. We hypothesized that the most fertile spermatozoa exhibited the highest levels of oxidative phosphorylation (OXPHOS), with oxidative stress simply being a by-product of intense mitochondrial activity. Accordingly, an experiment to investigate the relationship between oxidative stress and motility was conducted and revealed positive correlations between mitochondrial ROS and total motility (R2 = 0.90), rapid motility (R2 = 0.89), average path velocity (VAP; R2 = 0.59), and curvilinear velocity (VCL; R2 = 0.66). Similarly, lipid peroxidation was positively correlated with total motility (R2 = 0.46), rapid motility (R2 = 0.51), average path velocity (R2 = 0.62), and VCL (R2 = 0.56), supporting the aforementioned hypothesis. The relative importance of OXPHOS in supporting the motility of equine spermatozoa was contrasted with human spermatozoa, which primarily utilize glycolysis. In this study, mitochondrial inhibition significantly reduced the velocity (P < 0.01) and ATP (P < 0.05) content of equine, but not human, spermatozoa, emphasizing the former's relative dependence on OXPHOS. The equine is the first mammal in which such a positive relationship between oxidative stress and functionality has been observed, with implications for the management of stallion fertility in vitro and in vivo.
Somatosensory-evoked Fields for Gingiva, Lip, and Tongue

To localize the oral primary somatosensory cortex, we measured somatosensory-evoked fields for the lip, gingiva, and tongue in six healthy subjects. The latency of the first peak of the posterior-oriented current in the contralateral hemisphere was 50.9 ± 8.3 ms for the gingiva, significantly shorter than those for the lip and tongue peaks. The equivalent current dipole was localized on the central sulcus. The gingival dipole was localized significantly inferior to the lip dipole but not different from the tongue dipole. The moment of the gingival dipole was significantly smaller than that of the lip dipole but not different from that of the tongue dipole. Differences in the above parameters were negligible between the left and right, anterior and posterior, and upper and lower locations within the same organ, except that the dipole location for the anterior upper tongue was significantly inferior to that for the lower tongue.
DAMPING OF COHERENT OSCILLATIONS

Damping of coherent oscillations by feedback is straightforward in principle. It has been a vital ingredient for the safe operation of accelerators since a long time [1,2]. The increasing dimensions and beam intensities of the new generation of hadron colliders impose unprecedented demands on the performance of future systems. The arguments leading to the specification of a transverse feedback system for the CERN SPS in its role as LHC injector and the LHC collider itself are developed to illustrate this. The preservation of the transverse emittance is the guiding principle during this exercise keeping in mind the hostile environment which comprises: transverse impedance bent on developing coupled bunch instabilities, injection errors, unwanted transverse excitation, unavoidable tune spreads and noise in the damping loop.
Numerical simulation of transport and deposition of micro-particles in two-phase flow in a human upper airway model from CT images

In this paper the air flow for typical inhalation rates as well as transport and deposition of particles in a realistic human upper airway model were analysed using a validated ﬁnite-volume code with user-enhanced programmes. Most important parameters affecting deposition of particles are inlet flow rate, airway geometry and geometric and physical characteristics of particles. The tubular airway model in this study consists of upper trachea-bronchial airways starting from trachea (G0) to second generation of bifurcations (G2) reconstructed from computerised tomography (CT) data of a healthy human. The low Reynolds number (LRN) k-ω turbulence model was used to simulate the laminar to turbulent occurred airflow. The results show that deposition efficiencies (DE) are typically larger during high level breathing (Qin = 60 l/min) than low-level breathing (Qin = 15 l/min) and DE is significantly larger in the right bronchial airway to the left, mainly because of the slightly greater dimensions of the right bron.
Spatial-temporal analysis of passive TCP measurements

In this paper we look at TCP data which was passively collected from an edge ISP, and analyze it to obtain some new results and deeper understanding of TCP loss process. The focus of our study is to identify the 'root cause' links, i.e., the links that are responsible for the majority of the losses or reorders found on the end-to-end TCP connection. We suggest a new root cause criterion and a cost-effective algorithm to identify the root cause links. The algorithm incorporates a new out-of-sequence packet classification technique which is interesting by itself. We test our algorithm on the collected and simulated data and analytically justify its correctness. The simulation results show that the algorithm has a 95% detection rate with 10% false detection rate. We also analyze TCP temporal loss process, and found that the burst loss size is geometrically distributed. We analyze the TCP time-out loss indication under the Bernoulli loss model, which is the simplest model that can cause a geometric distribution, and show that the behavior of the TCP loss process is not different than when tail drop is assumed.
Incorporation of iron in rat incisor enamel.

– The electron microprobe technique was used to study the accumulation of iron in rat incisor ameloblasts as well as the subsequent release of iron from the cells and deposition into the outer layer of the enamel. Starting about 3 mm from the developing end, a gradual accumulation of iron occurred in the ameloblasts. At a stage where the iron content of the cells had reached a maximal level, and the calcium content of the adjacent hard tissue had reached the level of mature enamel, the initial incorporation of iron in the enamel was seen. In the iron incorporation zone the iron content of the enamel increased from less than 0.1 % to about 9 % and the iron content of the ameloblasts was gradually reduced. Concomitant with the increase of iron in the enamel, a decrease of the calcium content was observed in the same region, indicating a withdrawal of calcium from the enamel. Since the incorporation of iron occurs at a stage where the enamel is highly mineralized, the processes involved can hardly be explained as an interaction with the organic matrix. The key to the understanding of these processes should therefore be sought in the adjacent cell layer.