Miracle-dz/UniFAR-FTUs huggingface dataset:
A Hybrid Task Graph Scheduler for High Performance Image Processing Workflows

Designing applications for scalability is key to improving their performance in hybrid and cluster computing. Scheduling code to utilize parallelism is difficult, particularly when dealing with data dependencies, memory management, data motion, and processor occupancy. The Hybrid Task Graph Scheduler (HTGS) improves programmer productivity when implementing hybrid workflows for multi-core and multi-GPU systems. The Hybrid Task Graph Scheduler (HTGS) is an abstract execution model, framework, and API that increases programmer productivity when implementing hybrid workflows for such systems. HTGS manages dependencies between tasks, represents CPU and GPU memories independently, overlaps computations with disk I/O and memory transfers, keeps multiple GPUs occupied, and uses all available compute resources. Through these abstractions, data motion and memory are explicit; this makes data locality decisions more accessible. To demonstrate the HTGS application program interface (API), we present implementations of two example algorithms: (1) a matrix multiplication that shows how easily task graphs can be used; and (2) a hybrid implementation of microscopy image stitching that reduces code size by ≈ 43% compared to a manually coded hybrid workflow implementation and showcases the minimal overhead of task graphs in HTGS. Both of the HTGS-based implementations show good performance. In image stitching the HTGS implementation achieves similar performance to the hybrid workflow implementation. Matrix multiplication with HTGS achieves 1.3x and 1.8x speedup over the multi-threaded OpenBLAS library for 16k × 16k and 32k × 32k size matrices, respectively.
Recombinant fungal lectin as a new tool to investigate O-GlcNAcylation processes

Glycosylation is a group of post-translational modifications that displays a large variety of structures and are implicated in a plethora of biological processes. Therefore, studying glycosylation requires different technical approaches and reliable tools, lectins being part of them. Here, we describe the use of the recombinant mushroom lectin PVL to discriminate O-GlcNAcylation, a modification consisting in the attachment of a single N-acetylglucosamine residue to proteins confined within the cytosolic, nuclear and mitochondrial compartments. Recombinant PVL (Psathyrella velutina lectin) (rPVL) displays significantly stronger affinity for GlcNAc over Neu5Ac residues as verified by thermal shift assays and surface plasmon resonance experiments, being therefore an excellent alternative to WGA (wheat germ agglutinin). Labeling of rPVL with biotin or HRP (horseradish peroxidase) allows its useful and efficient utilization by western blot. The staining of whole cell lysates with labeled-rPVL was dramatically decreased in response to O-GlcNAc transferase knockdown and seen to increase after pharmacological blockade of O-GlcNAcase. Also, HRP-rPVL seemed to be more sensitive than the anti-O-GlcNAc antibody RL2. Thus, rPVL is a potent new tool to selectively detect O-GlcNAcylated proteins.
Expression of Oncogenic Alleles Induces Multiple Blocks to Human Cytomegalovirus Infection

ABSTRACT In contrast to many viruses, human cytomegalovirus (HCMV) is unable to productively infect most cancer-derived cell lines. The mechanisms of this restriction are unclear. To explore this issue, we tested whether defined oncogenic alleles, including the simian virus 40 (SV40) T antigen (TAg) and oncogenic H-Ras, inhibit HCMV infection. We found that expression of SV40 TAg blocks HCMV infection in human fibroblasts, whereas the replication of a related herpesvirus, herpes simplex virus 1 (HSV-1), was not impacted. The earliest restriction of HCMV infection involves a block of viral entry, as TAg expression prevented the nuclear delivery of viral DNA and pp65. Subsequently, we found that TAg expression reduces the abundance of platelet-derived growth factor receptor α (PDGFRα), a host protein important for HCMV entry. Viral entry into TAg-immortalized fibroblasts could largely be rescued by PDGFRα overexpression. Similarly, PDGFRα overexpression in HeLa cells markedly increased the levels of HCMV gene expression and DNA replication. However, the robust production of viral progeny was not restored by PDGFRα overexpression in either HeLa cells or TAg-immortalized fibroblasts, suggesting additional restrictions associated with transformation and TAg expression. In TAg-expressing fibroblasts, expression of the immediate early 2 (IE2) protein was not rescued to the same extent as that of the immediate early 1 (IE1) protein, suggesting that TAg expression impacts the accumulation of major immediate early (MIE) transcripts. Transduction of IE2 largely rescued HCMV gene expression in TAg-expressing fibroblasts but did not rescue the production of infectious virions. Collectively, our data indicate that oncogenic alleles induce multiple restrictions to HCMV replication. IMPORTANCE HCMV cannot replicate in most cancerous cells, yet the causes of this restriction are not clear. The mechanisms that restrict viral replication in cancerous cells represent viral vulnerabilities that can potentially be exploited therapeutically in other contexts. Here we found that SV40 T antigen-mediated transformation inhibits HCMV infection at multiple points in the viral life cycle, including through inhibition of proper viral entry, normal expression of immediate early genes, and viral DNA replication. Our results suggest that the SV40 T antigen could be a valuable tool to dissect cellular activities that are important for successful infection, thereby potentially informing novel antiviral development strategies. This is an important consideration, given that HCMV is a leading cause of birth defects and causes severe infection in immunocompromised individuals.
Improving Baculovirus Infectivity by Efficiently Embedding Enhancing Factors into Occlusion Bodies

ABSTRACT The relatively low infectivity of baculoviruses to their host larvae limits their use as insecticidal agents on a larger scale. In the present study, a novel strategy was developed to efficiently embed foreign proteins into Autographa californica multiple nucleopolyhedrovirus (AcMNPV) occlusion bodies (OBs) to achieve stable expression of foreign proteins and to improve viral infectivity. A recombinant AcMNPV bacmid was constructed by expressing the 150-amino-acid (aa) N-terminal segment of polyhedrin under the control of the p10 promoter and the remaining C-terminal 95-aa segment under the control of the polyhedrin promoter. The recombinant virus formed OBs in Spodoptera frugiperda 9 cells, in which the occlusion-derived viruses were embedded in a manner similar to that for wild-type AcMNPV. Next, the 95-aa polyhedrin C terminus was fused to enhanced green fluorescent protein, and the recombinant AcMNPV formed fluorescent green OBs and was stably passaged in vitro and in vivo. The AcMNPV recombinants were further modified by fusing truncated Agrotis segetum granulovirus enhancin or truncated Cydia pomonella granulovirus ORF13 (GP37) to the C-terminal 95 aa of polyhedrin, and both recombinants were able to form normal OBs. Bioactivity assays indicated that the median lethal concentrations of these two AcMNPV recombinants were 3- to 5-fold lower than that of the control virus. These results suggest that embedding enhancing factors in baculovirus OBs by use of this novel technique may promote efficient and stable foreign protein expression and significantly improve baculovirus infectivity. IMPORTANCE Baculoviruses have been used as bioinsecticides for over 40 years, but their relatively low infectivity to their host larvae limits their use on a larger scale. It has been reported that it is possible to improve baculovirus infectivity by packaging enhancing factors within baculovirus occlusion bodies (OBs); however, so far, the packaging efficiency has been low. In this article, we describe a novel strategy for efficiently embedding foreign proteins into AcMNPV OBs by expressing N- and C-terminal (dimidiate) polyhedrin fragments (150 and 95 amino acids, respectively) as fusions to foreign proteins under the control of the p10 and polyhedrin promoters, respectively. When this strategy was used to embed an enhancing factor (enhancin or GP37) into the baculovirus OBs, 3- to 5-fold increases in baculoviral infectivity were observed. This novel strategy has the potential to create an efficient protein expression system and a highly efficient virus-based system for insecticide production in the future.
Posterior parietal cortex contains a command apparatus for hand movements

Significance The primate hand has evolved into a specialized sensorimotor device that can grasp, explore, and manipulate objects with extraordinary skill. The frontal lobe is generally thought to be the exclusive source of descending commands to the spinal cord to control hand movements. Here, we identify a region within the parietal lobe that could also contribute commands to control hand movements directly at spinal levels. Intracortical stimulation in a lateral region in area 5 of posterior parietal cortex reliably evokes hand movements. Corticospinal neurons in this region make disynaptic connections with hand motoneurons. These observations suggest that a region within lateral area 5 contains a unique command apparatus that could assist in generating dexterous finger movements required during haptic behavior. Mountcastle and colleagues proposed that the posterior parietal cortex contains a “command apparatus” for the operation of the hand in immediate extrapersonal space [Mountcastle et al. (1975) J Neurophysiol 38(4):871–908]. Here we provide three lines of converging evidence that a lateral region within area 5 has corticospinal neurons that are directly linked to the control of hand movements. First, electrical stimulation in a lateral region of area 5 evokes finger and wrist movements. Second, corticospinal neurons in the same region of area 5 terminate at spinal locations that contain last-order interneurons that innervate hand motoneurons. Third, this lateral region of area 5 contains many neurons that make disynaptic connections with hand motoneurons. The disynaptic input to motoneurons from this portion of area 5 is as direct and prominent as that from any of the premotor areas in the frontal lobe. Thus, our results establish that a region within area 5 contains a motor area with corticospinal neurons that could function as a command apparatus for operation of the hand.
Effect of Irvingia gabonensis on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion.

The aim of this study was to evaluate the effect of Irvingia gabonensis on metabolic syndrome (MetS), insulin sensitivity, and insulin secretion. A randomized, double-blind, placebo-controlled clinical trial was performed in 24 patients with MetS in accordance with the International Diabetes Federation criteria. Twelve patients received I. gabonensis (150 mg) twice a day during 90 days, and 12 patients received placebo. Glucose and insulin concentrations were measured during a 2-h oral glucose tolerance test. Also, lipid profile, creatinine, uric acid, and hepatic enzymes were determined. The area under the curve (AUC) of glucose and insulin, total insulin secretion, first phase of insulin secretion, and insulin sensitivity were calculated. Data were tested using non-parametric tests. The Ethics Committee approved the protocol. After I. gabonensis administration, significant decreases in waist circumference (WC) (94.0 ± 8.0 vs. 91.0 ± 8.2 cm, P < .01), glucose 90' (10.0 ± 2.5 vs. 8.6 ± 2.7 mmol/L, P < .05), glucose 120' (8.8 ± 2.4 vs. 7.6 ± 2.7 mmol/L, P < .05), triglycerides (2.5 ± 1.2 vs. 2.0 ± 1.1 mmol/L, P < .05), very low-density lipoproteins (VLDL) (0.5 ± 0.2 vs. 0.4 ± 0.2 mmol/L, P < .05), and AUC of glucose (694 ± 142 vs. 629 ± 172 mmol/L/min, P < .05) were found. Seven patients (58.3%) of the I. gabonensis group showed remission of MetS and two patients (16.7%) of the placebo group (P = .045). I. gabonensis lead to remission of MetS in 58.3% of the patients and significantly decreased WC, glucose 90', glucose 120', triglycerides, VLDL, and AUC of glucose.
The fungal natural product azaphilone-9 binds to HuR and inhibits HuR-RNA interaction in vitro

The RNA-binding protein Hu antigen R (HuR) binds to AU-rich elements (ARE) in the 3’-untranslated region (UTR) of target mRNAs. The HuR-ARE interactions stabilize many oncogenic mRNAs that play important roles in tumorigenesis. Thus, small molecules that interfere with the HuR-ARE interaction could potentially inhibit cancer cell growth and progression. Using a fluorescence polarization (FP) competition assay, we identified the compound azaphilone-9 (AZA-9) derived from the fungal natural product asperbenzaldehyde, binds to HuR and inhibits HuR-ARE interaction (IC50 ~1.2 μM). Results from surface plasmon resonance (SPR) verified the direct binding of AZA-9 to HuR. NMR methods mapped the RNA-binding interface of HuR and identified the involvement of critical RNA-binding residues in binding of AZA-9. Computational docking was then used to propose a likely binding site for AZA-9 in the RNA-binding cleft of HuR. Our results show that AZA-9 blocks key RNA-binding residues of HuR and disrupts HuR-RNA interactions in vitro. This knowledge is needed in developing more potent AZA-9 derivatives that could lead to new cancer therapy.
Virulence Gene-Associated Mutant Bacterial Colonies Generate Differentiating Two-Dimensional Laser Scatter Fingerprints

ABSTRACT In this study, we investigated whether a laser scatterometer designated BARDOT (bacterial rapid detection using optical scattering technology) could be used to directly screen colonies of Listeria monocytogenes, a model pathogen, with mutations in several known virulence genes, including the genes encoding Listeria adhesion protein (LAP; lap mutant), internalin A (ΔinlA strain), and an accessory secretory protein (ΔsecA2 strain). Here we show that the scatter patterns of lap mutant, ΔinlA, and ΔsecA2 colonies were markedly different from that of the wild type (WT), with >95% positive predictive values (PPVs), whereas for the complemented mutant strains, scatter patterns were restored to that of the WT. The scatter image library successfully distinguished the lap mutant and ΔinlA mutant strains from the WT in mixed-culture experiments, including a coinfection study using the Caco-2 cell line. Among the biophysical parameters examined, the colony height and optical density did not reveal any discernible differences between the mutant and WT strains. We also found that differential LAP expression in L. monocytogenes serotype 4b strains also affected the scatter patterns of the colonies. The results from this study suggest that BARDOT can be used to screen and enumerate mutant strains separately from the WT based on differential colony scatter patterns. IMPORTANCE In studies of microbial pathogenesis, virulence-encoding genes are routinely disrupted by deletion or insertion to create mutant strains. Screening of mutant strains is an arduous process involving plating on selective growth media, replica plating, colony hybridization, DNA isolation, and PCR or immunoassays. We applied a noninvasive laser scatterometer to differentiate mutant bacterial colonies from WT colonies based on forward optical scatter patterns. This study demonstrates that BARDOT can be used as a novel, label-free, real-time tool to aid researchers in screening virulence gene-associated mutant colonies during microbial pathogenesis, coinfection, and genetic manipulation studies.
THERMAL BEHAVIOR OF COMPOSITE BRIDGES - INSULATED AND UNINSULATED

REPORTED ARE THEORIES AND EXPERIMENTAL DATA PERTAINING TO VARIOUS THERMAL ASPECTS OF COMPOSITE BRIDGE STRUCTURES WITH STEEL BEAMS AND CONCRETE DECKS OR PRESTRESSED CONCRETE BEAMS AND CONCRETE DECKS, SOME OF WHICH ARE INSULATED ON THE UNDERSIDE WITH URETHANE FOAM. HEAT CONDUCTION BEHAVIOR AS WELL AS INDUCED THERMOELASTIC STRESSES AND DEFORMATIONS ARE DISCUSSED IN REGARD TO THESE BRIDGE TYPES. CERTAIN LIMITED CONCLUSIONS ARE DRAWN AS AFFECTING CURRENT DESIGN PROCEDURES . /AUTHOR/
Effect of Heat Treatment on Microstructures and Mechanical Properties of Spring Steel

Oil quench and temper process offer enormous advantages to the heavy duty spring production because its treatment results can reveal optimum combination of toughness and ductility, and also improves fatigue life. The material used in this study was a commercial grade of heavy duty spring steel. Quench and temper process were used as a major heat treatment method. The resultant microstructures after quenching process are observed as martensite with small amount of retained austainite. After the tempering process, the resulting optimum mechanical properties are found at bainitic structure. In the hardening process, selective alloy was heated up to its austenitizing temperature, 870°C, and quenched in oil. After that, tempering was done at 450°C increased by 50°C to 550°C for each tempering time (1 hr, 2 hr, and 3 hr) interval. In this research work, microstructural examination, hardness, tensile and fatigue tests were done before and after tempering condition at room temperature. The experimental results revealed that mechanical properties of selective alloy were significantly changed by temper treatment. By increasing the tempering time and temperature, hardness and ultimate tensile strength are gradually decreased and ductility was improved. Moreover, rather interesting condition is observed in elastic properties and endurance limit at 450°C and one hour tempering condition, and this state is the optimum condition for spring production.
An anatomical study of plate‐rod fixation in feline tibiae

OBJECTIVE To investigate the feasibility of placing bi-cortical cortex (B-cort) or mono-cortical locking screws (M-lock) in a plate-rod construct applied to the feline tibia in combination with different intramedullary (IM) pins. METHODS Twenty-four feline tibiae of cats were divided into 4 groups, corresponding to IM pin sizes filling approximately 30% (1.0 mm), 40% (1.4 mm), 45% (1.6 mm), and 50% (1.8 mm) of the medullary canal. Computed tomography (CT) was performed to trace potential screw trajectories in each group. A 12-hole, 2.4 mm locking compression plate was then applied on the medial aspect of the tibia. M-lock and B-cort screws were inserted subsequently in each plate hole. Success rates of screw insertion based on CT analysis and cadaveric simulation were compared with screw type, IM pin diameter, and anatomic location as variables. RESULTS Screw insertion rates were underestimated on CT compared to cadaveric specimens. During cadaveric simulation, B-cort screws could be inserted in all specimens in the 3 most proximal plate holes and in at least 1 of the 3 distal plate holes. The smallest pin size (30%) allowed placement of a greater number of B-cort screws (P < .05) compared to other pins. Fewer B-cort screws could be inserted in the distal diaphyseal region (P < .05) compared to other regions. A total of 99.3% of M-lock screws could be inserted regardless of IMP size. CLINICAL SIGNIFICANCE Plate rod constructs can include bicortical screws in the proximal and distal metaphysis, and monocortical screws in the diaphysis, combined with an IM pin filling up to 50% of the medullary canal.
Stress affects expression of the clock gene Bmal1 in the suprachiasmatic nucleus of neonatal rats via glucocorticoid‐dependent mechanism

The reactivity of the circadian clock in the suprachiasmatic nuclei (SCN) to stressful stimuli has been controversial but most studies have confirmed the resilience of the SCN to stress. We tested the hypothesis that during a critical period shortly after birth, the developing SCN clock is affected by glucocorticoids.
Beta-Barrel Detection for Medium Resolution Cryo-Electron Microscopy Density Maps Using Genetic Algorithms and Ray Tracing

Cryo-electron microscopy (cryo-EM) is a technique that produces three-dimensional density maps of large protein complexes. This allows for the study of the structure of these proteins. Identifying the secondary structures within proteins is vital to understanding the overall structure and function of the protein. The [Formula: see text]-barrel is one such secondary structure, commonly found in lipocalins and membrane proteins. In this article, we present a novel approach that utilizes genetic algorithms, kd-trees, and ray tracing to automatically detect and extract [Formula: see text]-barrels from cryo-EM density maps. This approach was tested on simulated and experimental density maps with zero, one, or multiple barrels in the density map. The results suggest that the proposed approach is capable of performing automatic detection of [Formula: see text]-barrels from medium resolution cryo-EM density maps.
Chronic Verubecestat Treatment Suppresses Amyloid Accumulation in Advanced Aged Tg2576-AβPPswe Mice Without Inducing Microhemorrhage

Verubecestat is a potent BACE1 enzyme inhibitor currently being investigated in Phase III trials for the treatment of mild-to-moderate and prodromal Alzheimer’s disease. Multiple anti-amyloid immunotherapies have been dose-limited by adverse amyloid related imaging abnormalities such as vasogenic edema (ARIA-E) and microhemorrhage (ARIA-H) observed in human trials and mice. Verubecestat was tested in a 12-week nonclinical study for the potential to exacerbate microhemorrhage (ARIA-H) profiles in 18-22-month-old post-plaque Tg2576-AβPPswe mice. Animals were treated with verubecestat or controls including the anti-Aβ antibody analog of bapineuzumab (3D6) as a positive control for ARIA induction. ARIA-H was measured using in-life longitudinal T2*-MRI and Prussian blue histochemistry at study end. Verubecestat reduced plasma and cerebrospinal fluid Aβ40 and Aβ42 by >90% and 62% to 68%, respectively. The ARIA-H profile of verubecestat-treated mice was not significantly different than controls. Anti-Aβ treatment significantly increased ARIA-H detected by Prussian blue staining; however, anti-Aβ antibody treatment did not impact plaque status. Verubecestat treatment significantly suppressed the accumulation of total levels of brain Aβ40 and Aβ42 and Thioflavin S positive plaque load. Stereological analysis of cortex and hippocampus plaque load similarly revealed significantly reduced area of Aβ immunoreactivity and reduced plaque number in verubecestat-treated animals compared to controls. The absence of elevated ARIA events in verubecestat-treated mice was associated with a significant reduction in the level of accumulated CNS amyloid pathology and brain Aβ peptides; effects consistent with the desired therapeutic mechanism of verubecestat in AD patients. These data will be compared with longitudinal MRI profiles from ongoing clinical trials.