gebhart/patrepeval huggingface dataset:
Mouse Polyomavirus Enters Early Endosomes, Requires Their Acidic pH for Productive Infection, and Meets Transferrin Cargo in Rab11-Positive Endosomes (2006)

Mouse polyomavirus (PyV) virions enter cells by internalization into smooth monopinocytic vesicles, which fuse under the cell membrane with larger endosomes. Caveolin-1 was detected on monopinocytic vesicles carrying PyV particles in mouse fibroblasts and epithelial cells (33). Here, we show that PyV can be efficiently internalized by Jurkat cells, which do not express caveolin-1 and lack caveolae, and that overexpression of a caveolin-1 dominant-negative mutant in mouse epithelial cells does not prevent their productive infection. Strong colocalization of VP1 with early endosome antigen 1 (EEA1) and of EEA1 with caveolin-1 in mouse fibroblasts and epithelial cells suggests that the monopinocytic vesicles carrying the virus (and vesicles containing caveolin-1) fuse with EEA1-positive early endosomes. In contrast to SV40, PyV infection is dependent on the acidic pH of endosomes. Bafilomycin A1 abolished PyV infection, and an increase in endosomal pH by NH4Cl markedly reduced its efficiency when drugs were applied during virion transport towards the cell nucleus. The block of acidification resulted in the retention of a fraction of virions in early endosomes. To monitor further trafficking of PyV, we used fluorescent resonance energy transfer (FRET) to determine mutual localization of PyV VP1 with transferrin and Rab11 GTPase at a 2- to 10-nm resolution. Positive FRET between PyV VP1 and transferrin cargo and between PyV VP1 and Rab11 suggests that during later times postinfection (1.5 to 3 h), the virus meets up with transferrin in the Rab11-positive recycling endosome. These results point to a convergence of the virus and the cargo internalized by different pathways in common transitional compartments.
Odiparcil, a potential glycosaminoglycans clearance therapy in mucopolysaccharidosis VI—Evidence from in vitro and in vivo models (2020)

Mucopolysaccharidoses are a class of lysosomal storage diseases, characterized by enzymatic deficiency in the degradation of specific glycosaminoglycans (GAG). Pathological accumulation of excess GAG leads to multiple clinical symptoms with systemic character, most severely affecting bones, muscles and connective tissues. Current therapies include periodic intravenous infusion of supplementary recombinant enzyme (Enzyme Replacement Therapy-ERT) or bone marrow transplantation. However, ERT has limited efficacy due to poor penetration in some organs and tissues. Here, we investigated the potential of the β-D-xyloside derivative odiparcil as an oral GAG clearance therapy for Maroteaux-Lamy syndrome (Mucopolysaccharidosis type VI, MPS VI). In vitro, in bovine aortic endothelial cells, odiparcil stimulated the secretion of sulphated GAG into culture media, mainly of chondroitin sulphate (CS) /dermatan sulphate (DS) type. Efficacy of odiparcil in reducing intracellular GAG content was investigated in skin fibroblasts from MPS VI patients where odiparcil was shown to reduce efficiently the accumulation of intracellular CS with an EC50 in the range of 1 μM. In vivo, in wild type rats, after oral administrations, odiparcil was well distributed, achieving μM concentrations in MPS VI disease-relevant tissues and organs (bone, cartilage, heart and cornea). In MPS VI Arylsulphatase B deficient mice (Arsb-), after chronic oral administration, odiparcil consistently stimulated the urinary excretion of sulphated GAG throughout the treatment period and significantly reduced tissue GAG accumulation in liver and kidney. Furthermore, odiparcil diminished the pathological cartilage thickening observed in trachea and femoral growth plates of MPS VI mice. The therapeutic efficacy of odiparcil was similar in models of early (treatment starting in juvenile, 4 weeks old mice) or established disease (treatment starting in adult, 3 months old mice). Our data demonstrate that odiparcil effectively diverts the synthesis of cellular glycosaminoglycans into secreted soluble species and this effect can be used for reducing cellular and tissue GAG accumulation in MPS VI models. Therefore, our data reveal the potential of odiparcil as an oral GAG clearance therapy for MPS VI patients.
Murine cerebral organoids develop network of functional neurons and hippocampal brain region identity (2021)

Brain organoids are <i>in vitro</i> three-dimensional (3D) self-organized neural structures, which can enable disease modeling and drug screening. However, their use for standardized large-scale drug screening studies is limited by their high batch-to-batch variability, long differentiation time (10-20 weeks), and high production costs. This is particularly relevant when brain organoids are obtained from human induced pluripotent stem cells (iPSCs). Here, we developed, for the first time, a highly standardized, reproducible, and fast (5 weeks) murine brain organoid model starting from embryonic neural stem cells. We obtained brain organoids, which progressively differentiated and self-organized into 3D networks of functional neurons with dorsal forebrain phenotype. Furthermore, by adding the morphogen WNT3a, we generated brain organoids with specific hippocampal region identity. Overall, our results showed the establishment of a fast, robust and reproducible murine 3D <i>in vitro</i> brain model that may represent a useful tool for high-throughput drug screening and disease modeling.
The Influence of Chemical Potential on Wellbore Stability (1993)

Summary An experimental investigation was begun to understand fundamental borehole stability mechanisms. This laboratory study was directed toward understanding why and how drilling-fluid chemistry affects borehole stability. The ability of drilling-fluid chemistry to alter shale mechanical behavior and the borehole stress state as a result of shale water content alteration was investigated. Experimental results demonstrate the influence of various drilling-fluid parameters (e.g., salt concentration, salt type, and diesel/water ratio) in oil-based drilling fluids on the water content, compressive strength, and mechanical properties of five shales. The influences of temperature and drilling-fluid exposure time on shale strength alteration also are addressed. The results are explained on the basis of chemical potential differences between oil-based drilling fluid and shale. The change in the shale water content caused by these differences is identified as the predominant factor leading to alteration of shale mechanical behavior and hence borehole stability.
CO Oxidation on Rutile‐Supported Au Nanoparticles (2005)

Wie aktiviert man Gold? Indem man die Struktur nanoskaliger Au-Partikel so beeinflusst, dass entweder viele Grenzflächenplätze oder viele niederkoordinierte Au-Atome vorliegen. Dieses Prinzip veranschaulichen Modellrechnungen für die Oxidation von CO an einem Au-Nanocluster auf einem Rutil-Träger, der am Übergangszustand nicht beteiligt ist (Au gelb, Ti hellgrau, C dunkelgrau, O rot).
Local Distortions and Dynamics in Hydrated Y-doped BaZrO3 (2020)

Y-doped BaZrO$_3$ is a promising proton conductor for intermediate temperature solid oxide fuel cells. In this work, a combination of static DFT calculations and DFT based molecular dynamics (DFT-MD) was used to study proton conduction in such a material. Geometry optimisations of 100 structures with a 12.5% dopant concentration allowed us to identify a clear correlation between the bending of the metal-oxygen-metal angle and the energies of the simulated cells. Depending on the type of bending, two configurations, designated as inwards bending and outwards bending, were defined. The results demonstrate that a larger bending decreases the energy and that the lowest energies are observed for structures combining inwards bending with protons being close to the dopant atoms. These lowest energy structures are the ones with the strongest hydrogen bonds. DFT-MD simulations in cells with different yttrium distributions provide complementary microscopic information on proton diffusion as they capture the dynamic distortions of the lattice caused by thermal motion. A careful analysis of the proton jumps between different environments confirmed that the inwards and outwards bending states are relevant for the understanding of proton diffusion. Indeed, intra-octahedral jumps were shown to only occur starting from an outwards configuration while the inwards configuration seems to favor rotations around the oxygen. On average, in the DFT-MD simulations, the hydrogen bond lengths are shorter for the outwards configuration which facilitates the intraoctahedral jumps. Diffusion coefficients and activation energies were also determined and compared to previous theoretical and experimental data showing a good agreement with previous data corresponding to local proton motion.
Immediate-Early Expression of the Herpes Simplex Virus Type 1 ICP27 Transcript Is Not Critical for Efficient Replication In Vitro or In Vivo (2004)

We constructed a promoter mutation altering the immediate-early expression of the herpes simplex virus type 1 (HSV-1) ICP27 transcript and its cognate wild-type rescue viruses in order to assess the role of the ICP27 protein in the earliest stages of viral infection by global transcriptional analysis with a DNA microarray. This mutant, ICP27/VP16, replaces the whole ICP27 promoter/enhancer with the VP16 promoter. It demonstrates loss of immediate-early expression of ICP27 according to the criteria expression in the absence of de novo protein synthesis and earliest expression in the kinetic cascade. Significant differences in relative transcript abundances between the mutant and wild-type rescue viruses were limited at the earliest times measured and not evident at all by 4 h after infection. Consistent with this observation, levels of some critical proteins were reduced in the mutant as compared to rescue virus infections at the earliest times tested, but were equivalent by 8 h postinfection. Further, both single and multistep levels of virus replication were equivalent with both mutant and rescue viruses. Thus, altering the immediate-early kinetics of ICP27 leads to a suboptimal quantitative lag phase in gene expression but without consequence for replication fitness in vitro. Infections in vivo also revealed equivalent ability of mutant and rescue viruses to invade the central nervous system of mice following footpad injections. Limitations to an immediate-early role of ICP27 in the biology of HSV are discussed in light of these observations.
Barriers of the peripheral nerve (2013)

This review introduces the traditionally defined anatomic compartments of the peripheral nerves based on light and electron microscopic topography and then explores the cellular and the most recent molecular basis of the different barrier functions operative in peripheral nerves. We also elucidate where, and how, the homeostasis of the normal human peripheral nerve is controlled in situ and how claudin-containing tight junctions contribute to the barriers of peripheral nerve. Also, the human timeline of the development of the barriers of the peripheral nerve is depicted. Finally, potential future therapeutic modalities interfering with the barriers of the peripheral nerve are discussed.
Harnessing RNA sequencing for global, unbiased evaluation of two new adjuvants for dendritic-cell immunotherapy (2017)

Effective stimulation of immune cells is crucial for the success of cancer immunotherapies. Current approaches to evaluate the efficiency of stimuli are mainly defined by known flow cytometry-based cell activation or cell maturation markers. This method however does not give a complete overview of the achieved activation state and may leave important side effects unnoticed. Here, we used an unbiased RNA sequencing (RNA-seq)-based approach to compare the capacity of four clinical-grade dendritic cell (DC) activation stimuli used to prepare DC-vaccines composed of various types of DC subsets; the already clinically applied GM-CSF and Frühsommer meningoencephalitis (FSME) prophylactic vaccine and the novel clinical grade adjuvants protamine-RNA complexes (pRNA) and CpG-P. We found that GM-CSF and pRNA had similar effects on their target cells, whereas pRNA and CpG-P induced stronger type I interferon (IFN) expression than FSME. In general, the pathways most affected by all stimuli were related to immune activity and cell migration. GM-CSF stimulation, however, also induced a significant increase of genes related to nonsense-mediated decay, indicating a possible deleterious effect of this stimulus. Taken together, the two novel stimuli appear to be promising alternatives. Our study demonstrates how RNA-seq based investigation of changes in a large number of genes and gene groups can be exploited for fast and unbiased, global evaluation of clinical-grade stimuli, as opposed to the general limited evaluation of a pre-specified set of genes, by which one might miss important biological effects that are detrimental for vaccine efficacy.
Synthesis and Performance Optimization of a Switching Nano-Crossbar Computer (2016)

Beyond CMOS, new technologies are emerging to extend electronic systems with features unavailable to silicon-based devices. Emerging technologies provide new logic and interconnection structures for computation, storage and communication that may require new design paradigms, and therefore trigger the development of a new generation of design automation tools. In the last decade, several emerging technologies have been proposed and the time has come for studying new ad-hoc techniques and tools for logic synthesis, physical design and testing. The main goal of this project is developing a complete synthesis and optimization methodology for switching nano-crossbar arrays that leads to the design and construction of an emerging nanocomputer. New models for diode, FET, and four-terminal switch based nanoarrays are developed. The proposed methodology implements both arithmetic and memory elements, necessitated by achieving a computer, by considering performance parameters such as area, delay, power dissipation, and reliability. With combination of arithmetic and memory elements a synchronous state machine (SSM), representation of a computer, is realized. The proposed methodology targets variety of emerging technologies including nanowire/nanotube crossbar arrays, magnetic switch-based structures, and crossbar memories. The results of this project will be a foundation of nano-crossbar based circuit design techniques and greatly contribute to the construction of emerging computers beyond CMOS. The topic of this project can be considered under the research area of "Emerging Computing Models" or "Computational Nanoelectronics", more specifically the design, modeling, and simulation of new nanoscale switches beyond CMOS.
The Platform as a service model for networking (2010)

Decoupling infrastructure management from service management can lead to innovation, new business models, and a reduction in the complexity of running services. It is happening in the world of computing, and is poised to happen in networking. While many have considered this in the context of network virtualization, they all focus on one model – overlaying a virtual network of multiple virtual routers on top of a shared physical infrastructure, each completely isolated from the others through the use of virtualization. In this paper we argue for a different approach, where those running the service are presented with the abstraction of a single router in order to enable them to focus solely on their service rather than worrying about managing a virtual network as well. We discuss the abstraction of a single router, and the challenges of mapping the collection of abstract routers (from different parties) to the distributed and shared physical infrastructure. 1
Modification of Porous Alumina Membranes Using Al2O3 Atomic Layer Controlled Deposition (1997)

Al2O3 films were deposited with atomic layer control inside the pores of Anodisc alumina membranes. To achieve this controlled deposition on a high aspect ratio structure, a binary reaction for Al2O3 chemical vapor deposition (2Al(CH3)3 + 3H2O → Al2O3 + 6CH4) was separated into two half-reactions: (A) AlOH* + Al(CH3)3 → Al-O-Al(CH3)2* + CH4 and (B) AlCH3* + H2O → AlOH* + CH4, where the asterisks designate the surface species. The trimethylaluminum [Al(CH3)3] (TMA) and H2O reactants were employed alternately in an ABAB... binary reaction sequence to deposit the Al2O3 film. Because each half-reaction is self-limiting, atomic layer controlled Al2O3 deposition was achieved on the surface of the high aspect ratio pores. To determine the necessary reaction conditions, surface species during each half-reaction were periodically monitored using in situ transmission FTIR spectroscopy. Ex situ gas flux and permporometry measurements were also performed to determine the effect of the binary reaction sequence on the pore diameter. Gas flux measurements for H2 and N2 were consistent with a progressive pore size reduction versus the number of AB reaction cycles. The permporometry measurements showed that the original pore diameter of ∼220 Å was reduced to ∼140 Å after 120 AB reaction cycles.
A Feasibility Analysis of Power Awareness in Commodity-Based High-Performance Clusters (2005)

We present a feasibility study of a power-reduction scheme that reduces the thermal power of processors by lowering frequency and voltage in the context of high-performance computing. The study revolves around a 16-processor Opteron-based Beowulf cluster, configured as four nodes of quad-processors, and shows that one can easily reduce a significant amount of CPU and system power dissipation and its associated energy costs while still maintaining high performance. Specifically, our study shows that a 5% performance slowdown can be traded off for an average of 19% system energy savings and 24% system power reduction. These preliminary empirical results, via real measurements, are encouraging because hardware failures often occur when the cluster is running hot, i.e, when the workload is heavy, and the new power-reduction scheme can effectively reduce a cluster's power demands during these busy periods
Capacitive Tilt Sensor Using Metallic Ball (2009)

A new capacitive type of tilt sensor using metallic ball is proposed primarily to get over the contact problem in measurement of tilt angle. Its structure and fabrication process are simpler than other previous sensors. Capacitive sensing type has many advantages such as simplicity, non-contact measurement of angle, long-throw linear displacement, and sub-micron plate spacing comparing to other types. The dimension of this prototype sensor is 20mm × 20mm and the diameter of the polystyrene tube is 5mm and the thickness of the tube is 0.15mm. The test result shows the linear relationship between tilt angles and capacitances.
THE COVID-19 PANDEMIC AND FACE SHIELDS: A REVIEW (2020)

Introduction The coronavirus disease 2019 (COVID-19) pandemic has placed personal protective equipment (PPE) for healthcare workers (HCW) in the spotlight. HCW’s face has been reported to be the body part most commonly contaminated by body fluids. The aim of this narrative review to examine the current evidence on face shield as a PPE for droplet or aerosol prevention. Methods A literature search was conducted on the PubMed, MedLine, and Embase databases, with the keywords “face shield”, “visor”, and “droplet precaution”. Bibliographic search was also undertaken. Results Respiratory droplet is particle with diameter greater than 5µm, while aerosol are ≤5µm according to the World Health Organisation. However, infection is not neatly separated into the dichotomy of droplet versus airborne transmission route. Modelling and simulation have shown the importance of the conjunctival mucosa as a route of transmission of disease in blood splashes, droplets and aerosols containing virus. The limited reports from SARS, COVID-19 and influenza season supports its use. However, HCW do not routinely use face shield if they consider the procedures to be unlikely to be associated with potential contamination. They also erroneously believe that prescription glasses is adequate protection. The issues associated with eye shield use, may be less of a problem with face shield. Conclusion Transmission of viruses is multimodal, and the conjunctival mucosa presents a real risk for viral transmission. Eye and face protection is important to prevent transmission of COVID-19.
Facioscapulohumeral muscular dystrophy family studies of DUX4 expression: evidence for disease modifiers and a quantitative model of pathogenesis (2012)

Facioscapulohumeral muscular dystrophy (FSHD), the most prevalent myopathy afflicting both children and adults, is predominantly associated with contractions in the 4q35-localized macrosatellite D4Z4 repeat array. Recent studies have proposed that FSHD pathology is caused by the misexpression of the DUX4 (double homeobox 4) gene resulting in production of a pathogenic protein, DUX4-FL, which has been detected in FSHD, but not in unaffected control myogenic cells and muscle tissue. Here, we report the analysis of DUX4 mRNA and protein expression in a much larger collection of myogenic cells and muscle biopsies derived from biceps and deltoid muscles of FSHD affected subjects and their unaffected first-degree relatives. We confirmed that stable DUX4-fl mRNA and protein were expressed in myogenic cells and muscle tissues derived from FSHD affected subjects, including several genetically diagnosed adult FSHD subjects yet to show clinical manifestations of the disease in the assayed muscles. In addition, we report DUX4-fl mRNA and protein expression in muscle biopsies and myogenic cells from genetically unaffected relatives of the FSHD subjects, although at a significantly lower frequency. These results establish that DUX4-fl expression per se is not sufficient for FSHD muscle pathology and indicate that quantitative modifiers of DUX4-fl expression and/or function and family genetic background are determinants of FSHD muscle disease progression.
Comparing isogenic strains of Beijing genotype Mycobacterium tuberculosis after acquisition of Isoniazid resistance: A proteomics approach (2016)

We determined differences in the protein abundance among two isogenic strains of Mycobacterium tuberculosis (Mtb) with different Isoniazid (INH) susceptibility profiles. The strains were isolated from a pulmonary tuberculosis patient before and after drug treatment. LC-MS/MS analysis identified 46 Mtb proteins with altered abundance after INH resistance acquisition. Protein abundance comparisons were done evaluating the different bacterial cellular fractions (membrane, cytosol, cell wall and secreted proteins). MS data have been deposited to the ProteomeXchange with identifier PXD002986.
Tau binding protein CAPON induces tau aggregation and neurodegeneration (2019)

To understand the molecular processes that link Aβ amyloidosis, tauopathy and neurodegeneration, we screened for tau-interacting proteins by immunoprecipitation/LC-MS. We identified the carboxy-terminal PDZ ligand of nNOS (CAPON) as a novel tau-binding protein. CAPON is an adaptor protein of neuronal nitric oxide synthase (nNOS), and activated by the N-methyl-D-aspartate receptor. We observed accumulation of CAPON in the hippocampal pyramidal cell layer in the App<sup>NL-G-F</sup> -knock-in (KI) brain. To investigate the effect of CAPON accumulation on Alzheimer's disease (AD) pathogenesis, CAPON was overexpressed in the brain of App<sup>NL-G-F</sup> mice crossbred with MAPT (human tau)-KI mice. This produced significant hippocampal atrophy and caspase3-dependent neuronal cell death in the CAPON-expressing hippocampus, suggesting that CAPON accumulation increases neurodegeneration. CAPON expression also induced significantly higher levels of phosphorylated, oligomerized and insoluble tau. In contrast, CAPON deficiency ameliorated the AD-related pathological phenotypes in tauopathy model. These findings suggest that CAPON could be a druggable AD target.