gebhart/patrepeval huggingface dataset:
Altering APP Proteolysis: Increasing sAPPalpha Production by Targeting Dimerization of the APP Ectodomain (2012)

One of the events associated with Alzheimer's disease is the dysregulation of α- versus β-cleavage of the amyloid precursor protein (APP). The product of α-cleavage (sAPPα) has neuroprotective properties, while Aβ1-42 peptide, a product of β-cleavage, is neurotoxic. Dimerization of APP has been shown to influence the relative rate of α- and β- cleavage of APP. Thus finding compounds that interfere with dimerization of the APP ectodomain and increase the α-cleavage of APP could lead to the development of new therapies for Alzheimer's disease. Examining the intrinsic fluorescence of a fragment of the ectodomain of APP, which dimerizes through the E2 and Aβ-cognate domains, revealed significant changes in the fluorescence of the fragment upon binding of Aβ oligomers--which bind to dimers of the ectodomain--and Aβ fragments--which destabilize dimers of the ectodomain. This technique was extended to show that RERMS-containing peptides (APP(695) 328-332), disulfiram, and sulfiram also inhibit dimerization of the ectodomain fragment. This activity was confirmed with small angle x-ray scattering. Analysis of the activity of disulfiram and sulfiram in an AlphaLISA assay indicated that both compounds significantly enhance the production of sAPPα by 7W-CHO and B103 neuroblastoma cells. These observations demonstrate that there is a class of compounds that modulates the conformation of the APP ectodomain and influences the ratio of α- to β-cleavage of APP. These compounds provide a rationale for the development of a new class of therapeutics for Alzheimer's disease.
Maxikdiol: a novel dihydroxyisoprimane as an agonist of Maxi-K channels (1994)

Maxi-K (large-conductance calcium-activated potassium)channels are a family of proteins which are thought to play an important role in controlling the contractility of airway smooth muscle. Maxikdiol is a novel, 1,5-dihydroxyisoprimane, diterpenoid which acts as an agonist of the channel. The isolation, structure elucidation and biological activity of maxikdiol are described.
Targeted therapy for glioblastoma multiforme neoplastic meningitis with intrathecal delivery of an oncolytic recombinant poliovirus. (2006)

These results suggest that intrathecal treatment with PVS-RIPO may be useful for treatment of neoplastic meningitis in patients with glioblastoma multiforme and provides a rationale for clinical trials in this area.
Direct phenotypic conversion of human fibroblasts into functional osteoblasts triggered by a blockade of the transforming growth factor-β signal (2018)

A procedure to generate functional osteoblasts from human somatic cells may pave the way to a novel and effective transplantation therapy in bone disorders. Here, we report that human fibroblasts were induced to show osteoblast phenotypes by culturing with ALK5 i II, which is a specific inhibitor for activin-like kinase 5 (ALK5) (tumor growth factor-β receptor 1 (TGF-β R1)). Cells cultured with ALK5 i II expressed osteoblast-specific genes and massively produced calcified bone matrix, similar to the osteoblasts induced from mesenchymal stem cells (MSC-OBs). Treatment with vitamin D3 in addition to ALK5 i II induced more osteoblast-like characters, and the efficiency of the conversion reached approximately 90%. The chemical compound-mediated directly converted osteoblasts (cOBs) were similar to human primary osteoblasts in terms of expression profiles of osteoblast-related genes. The cOBs abundantly produced bone matrix in vivo and facilitated bone healing after they were transplanted into immunodeficient mice at an artificially induced defect lesion in femoral bone. The present procedure realizes a highly efficient direct conversion of human fibroblasts into transgene-free and highly functional osteoblasts, which might be applied in a novel strategy of bone regeneration therapy in bone diseases.
A Biodegradable and Proteolipid Bone Repair Composite (1983)

Abstract : A synthetic proteolipid was combined with a biodegradable copolymer (50:50) poly(L)-lactide co-glycolide) and inserted into defects prepared in the tibias of rats. At 3, 7, 14, 21, 28, and 42 days, animals were sacrificed and the implant sites were prepared for histomorphometric evaluation. Control defects, defects filled with copolymer alone, and defects filled with copolymer combined with proteolipid were analyzed with a Zeiss Image Analysis System with Osteoplan version 4.1. A two-way analysis of variance revealed more reparative bony elements in the defects filled with copolymer-proteolipid at an earlier period of time than either the copolymer alone or control sites. The copolymer-proteolipid implant amy provide to be an alternative to the agents commonly used for osseous repair.
Demonstration of alternative splicing of a pre-mRNA expressed in the blood stage form of Plasmodium falciparum. (1991)

By screening of a lambda gt11 library from Plasmodium falciparum genomic DNA with an antiserum raised against a 41-kDa protein band, which was shown to confer protective immunity to monkeys, the phage clone 41-3 was identified. The entire 41-3 gene was isolated, and its coding regions were determined by amplification and sequencing of 41-3 specific mRNA fragments. The 41-3 gene has a complex structure consisting of nine exons, encoding 375 amino acids in total with a calculated molecular weight of 43,400. Provided that the N-terminal hydrophobic residues function as signal sequence which is cleaved off, the molecular weight of the 41-3 protein decreases to 41,200 and could therefore be considered to be a component of the protective Mr = 41,000 protein band. Indeed, a 41-kDa protein could be detected by Western blot analysis using antisera raised against different recombinant expression products of the 41-3 gene. We furthermore demonstrate an alternative splice process for the mRNA precursor transcribed from the 41-3 gene to yield at least three distinct mRNAs. The major splice product carries all exons E1 to E9, whereas at least two minor 41-3 mRNA species can be identified which show deletions in the region between exons E5 and E7. The possible role of this differential splice process for the parasite is discussed.
Performance of a Micro-Optical Wall Shear Stress Sensor Based on Whispering Gallery Mode Resonators (2009)

In this paper, we discuss the dynamic performance of a novel wall shear stress sensor concept based on whispering gallery mode (WGM) shifts of a dielectric microsphere resonator. In the shear stress sensor model, the wall shear stress acting on a sensing element, typically 125 m in diameter, is transmitted mechanically to the microsphere and the transmitted force leads to shifts in the WGMs of the microsphere. By monitoring these WGM shifts, the magnitude as well as the direction of the wall shear stress can be measured. The measurement principle was demonstrated in a previous paper which presented static shear stress results. The sensor used in the present study is a dielectric microsphere made of Polydimethylsyloxane (PDMS), and is tested for loading for dynamic measurements, An electronic circuit is developed to track the fast moving optical resonances (WGM) under dynamic loading.
Nanoporous graphene by quantum dots removal from graphene and its conversion to a potential oxygen reduction electrocatalyst via nitrogen doping (2013)

A simple way to produce an efficient metal-free oxygen reduction electrocatalyst from graphene by generating nanopores in the matrix and subsequently establishing nitrogen-doped active sites along the pore openings is demonstrated. Well-structured nanoporous graphene (pGr) and photoluminescent graphene quantum dots (GQDs) could be simultaneously generated by a chemically assisted oxidative treatment of graphene. The process helped to knock out small pieces of Gr through epoxide formation, which subsequently resulted in the generation of GQD and pGr simultaneously. A longer oxidation time increased the quantity of GQDs and also resulted in a higher photoluminescent (PL) quantum yield. The PL quantum yield of GQD formed after 72 h of the oxidative treatment (GQD-72) was 15.8%, which is greater than the previous reported values. The TEM images showed matching sizes for GQDs and the pores present in pGr, implying that the pores are generated by the removal of GQDs from graphene during the oxidative treatment. Since pore openings are expected to give higher levels of unsaturation and defect sites in the system and are thus being treated as fertile regions for heteroatom doping, pGr-72 was further subjected to nitrogen (NpGr-72). NpGr-72 displayed excellent activity towards the electrochemical oxygen reduction reaction (ORR) compared to nitrogen-doped non-porous graphene (NGr) and many other reported nitrogen-doped carbon materials. A distinct 50 mV gain in the overpotential and 2.5 times increment in the kinetic current density (jk) have been achieved in the case of NpGr-72 compared to NGr. Interestingly, unlike NGr, NpGr-72 effectively reduced the oxygen molecule with a greater involvement of the preferred four-electron pathway. Additionally, the overpotential difference of NpGr-72 with respect to 20 wt% Pt/C is only 60 mV. Additionally, in a single cell evaluation under anion exchange membrane fuel cell (AEMFC) conditions, NpGr-72 exhibited a maximum power density of 27 mW cm−2, which is significantly higher than the corresponding value of 10 mW cm−2 obtained for NGr. Thus, the overall enhancement in the performance characteristics of NpGr-72 is attributed to the higher content of nitrogen (7.8 wt%) and its large proportion of desired chemical environment, which could be established by utilizing the high level of carbon unsaturation around the pore openings.
Collective robot reinforcement learning with distributed asynchronous guided policy search (2017)

Policy search methods and, more broadly, reinforcement learning can enable robots to learn highly complex and general skills that may allow them to function amid the complexity and diversity of the real world. However, training a policy that generalizes well across a wide range of real-world conditions requires far greater quantity and diversity of experience than is practical to collect with a single robot. Fortunately, it is possible for multiple robots to share their experience with one another, and thereby, learn a policy collectively. In this work, we explore distributed and asynchronous policy learning as a means to achieve generalization and improved training times on challenging, real-world manipulation tasks. We propose a distributed and asynchronous version of guided policy search and use it to demonstrate collective policy learning on a vision-based door opening task using four robots. We describe how both policy learning and data collection can be conducted in parallel across multiple robots, and present a detailed empirical evaluation of our system. Our results indicate that distributed learning significantly improves training time, and that parallelizing policy learning and data collection substantially improves utilization. We also demonstrate that we can achieve substantial generalization on a challenging real-world door opening task.
Effect of filtering upon morphological methods for arrhythmia detection in implantable devices (2002)

Morphological analysis of intracardiac electrograms (ICEs) has been proposed as a complementary method for discrimination of monomorphic ventricular tachycardia from sinus rhythm by implantable pacemaker-cardioverter-defibrillators. This study compared the impact of filtering on two previously proposed time-domain methods: (1) correlation waveform analysis (CWA-independent of both amplitude fluctuation and ICE baseline) and (2) difference of area (DOA-dependent on amplitude fluctuation and ICE baseline). Using a statistical validation method for nonparametric distributions requiring 75% separation with 95% confidence interval, it was found that with CWA a bandwidth of 10-80 Hz gave results equivalent to that in wideband recordings, and in DOA a bandwidth of 20-80 Hz retained equivalent discriminatory power. A further increase in the lower passband limit (20-80 Hz for CWA and 30-80 Hz for DOA) reduced effectiveness of the methods.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Channel allocation tiering (CHAT): taking GSM/EDGE networks beyond one-reuse (2002)

A number of techniques to enhance the spectral efficiency of GSM/EDGE networks are currently being developed to meet the rapid growth in the use of mobile communications. Adoption of such features could render even one-reuse configurations blocking limited. To allow future networks to maximize spectral efficiency by remaining interference limited, the channel allocation tiering (CHAT) concept has been devised. With CHAT, methods to create and manage intracell interference are introduced. The CHAT concept is presented and its components evaluated by means of link and system simulations. Introduction of a CHAT configuration in a simulated GSM full-rate speech network is shown to lead to a 4-fold increase in downlink capacity and the effects of intracell interference are strongly mitigated.
Selective area nucleation for metal chemical vapor deposition using focused ion beams (1988)

Localized growth of metal lines on Si wafers has been demonstrated using a focused Ga+ beam to selectively enhance the nucleation site density during a thermal chemical vapor deposition process. Iron and aluminum lines with thicknesses up to 2 μm have been formed using ion line doses between 4×1010 and 4×1012 Ga+/cm. Thus, the sensitivity of this process can be several orders of magnitude greater than ion beam induced polymerization techniques performed at room temperature. Auger analysis indicated that the total impurity concentration deep within the metal lines was roughly 15%. No Ga was detected in the deposited films.
Engineering the Carrier Dynamics of InGaN Nanowire White Light-Emitting Diodes by Distributed p-AlGaN Electron Blocking Layers (2015)

We report on the demonstration of a new type of axial nanowire LED heterostructures, with the use of self-organized InGaN/AlGaN dot-in-a-wire core-shell nanowire arrays. The large bandgap AlGaN shell is spontaneously formed on the sidewall of the nanowire during the growth of AlGaN barrier of the quantum dot active region. As such, nonradiative surface recombination, that dominates the carrier dynamics of conventional axial nanowire LED structures, can be largely eliminated, leading to significantly increased carrier lifetime from ~0.3 ns to 4.5 ns. The luminescence emission is also enhanced by orders of magnitude. Moreover, the p-doped AlGaN barrier layers can function as distributed electron blocking layers (EBLs), which is found to be more effective in reducing electron overflow, compared to the conventional AlGaN EBL. The device displays strong white-light emission, with a color rendering index of ~95. An output power of >5 mW is measured for a 1 mm × 1 mm device, which is more than 500 times stronger than the conventional InGaN axial nanowire LEDs without AlGaN distributed EBLs.
Directed evolution of O6-alkylguanine-DNA alkyltransferase for applications in protein labeling (2006)

The specific reaction of O6-alkylguanine-DNA alkyltransferase (AGT) with O6-benzylguanine (BG) derivatives allows for a specific labeling of AGT fusion proteins with chemically diverse compounds in living cells and in vitro. The efficiency of the labeling depends on a number of factors, most importantly on the reactivity, selectivity and stability of AGT. Here, we report the use of directed evolution and two different selection systems to further increase the activity of AGT towards BG derivatives by a factor of 17 and demonstrate the advantages of this mutant for the specific labeling of AGT fusion proteins displayed on the surface of mammalian cells. The results furthermore identify two regions of the protein outside the active site that influence the activity of the protein towards BG derivatives.
Effective method to determine time‐delay stability margin and its application to power systems (2017)

In an interconnected bulk power system, wide‐area measurement system (WAMS) can provide abundant remote measurement for the coordinated control system. However, WAMS data have obvious time delays, which affect the performance of the control system and should be properly considered. Time‐delay stability margin (TDSM) is an index to reflect the maximum delay that a time‐delay system can sustain without losing its stability. To construct a coordinated control system based on WAMS data, it is crucial to accurately and rapidly determine the TDSM value. In this paper, a novel Jordan‐Taylor‐Schur (JTS) approach to determine the TDSM value of power system is proposed. It consists of three, Jordan standardization, Taylor separation and Schur simplification. With the three procedures of this method, the model dimension of time‐delay system can be reduced, and the stability criterion derivation can be rebuilt to omit some unnecessary variables so that both the computational efficiency and accuracy can be boosted. Further, it is worth highlighting that the proposed method can be applied to various Lyapunov‐based stability criteria to improve their efficiency with small errors. Finally, three power systems with time delays have been used to demonstrate the effectiveness of the proposed method.
A single-filament effusion cell with reduced thermal gradient for molecular-beam epitaxy (1989)

A molecular-beam source utilizing single-filament construction to generate a reproducible and uniform beam of elemental molecules is presented. The filament design is constructed to conform to the shape of pyrolytic boron nitride crucibles utilized in molecular-beam epitaxy (MBE) systems, and to minimize the thermal gradient between the crucible opening and the crucible bottom which is inherent in Knudsen cell technology. The design also improves heat transfer, efficiency, and flux response of the cell. We show that this cell exhibits a better flux response than typical commercially available effusion cells and successfully prevents source material redistribution, thus providing for long-term flux stability and reproducibility in certain materials used in MBE. No increase in background impurity concentration in epitaxial AlGaAs films was observed, when compared to films grown using a standard Varian effusion cell. This cell is currently installed and being used as an aluminum source in a Varian GEN II system.
Results of the first phase 1 clinical trial of the HER‐2/<i>neu</i> peptide (GP2) vaccine in disease‐free breast cancer patients (2009)

The GP2 peptide vaccine appears safe and well tolerated with minimal local/systemic toxicity. GP2 elicited HER-2/neu-specific immune responses, including epitope spreading, in high-risk, lymph node-negative breast cancer patients. These findings support further investigation of the GP2 vaccine for the prevention of breast cancer recurrence.
Development of a Multi-Fidelity Approach to Acoustic Liner Impedance Eduction (2017)

The use of acoustic liners has proven to be extremely effective in reducing aircraft engine fan noise transmission/radiation. However, the introduction of advanced fan designs and shorter engine nacelles has highlighted a need for novel acoustic liner designs that provide increased fan noise reduction over a broader frequency range. To achieve aggressive noise reduction goals, advanced broadband liner designs, such as zone liners and variable impedance liners, will likely depart from conventional uniform impedance configurations. Therefore, educing the impedance of these axial- and/or spanwise-variable impedance liners will require models that account for three-dimensional effects, thereby increasing computational expense. Thus, it would seem advantageous to investigate the use of multifidelity modeling approaches to impedance eduction for these advanced designs. This paper describes an extension of the use of the CDUCT-LaRC code to acoustic liner impedance eduction. The proposed approach is applied to a hardwall insert and conventional liner using simulated data. Educed values compare well with those educed using two extensively tested and validated approaches. The results are very promising and provide justification to further pursue the complementary use of CDUCT-LaRC with the currently used finite element codes to increase the efficiency of the eduction process for configurations involving three-dimensional effects.
Detailed Modeling of Injection and Production Induced Rock Displacements (2017)

Summary Reservoir injection and production leads to stress changes in the reservoir and the surrounding rock. For compacting reservoirs, these effects are particularly prominent. The associated rock displacements make infill drilling and optimization of performance and integrity challenging. Constant monitoring and prediction of the displacements of the rock is key to identify risks early. Once such risks are identified the production strategy can be adjusted to mitigate such risks and overall increase the recovery of hydrocarbons. This paper describes how displacement information obtained from time-lapse seismic data and estimates of rock material properties from well data or databases can be used in detailed modeling of geomechanical effects. The output of the geomechanical simulation is the stress change and the vertical and horizontal rock displacements. The displacements at the boundary of the model are imposed based on displacement estimates from the time-lapse seismic data, and together with the computed displacements in the interior of the model a complete description of the stress exchange can be obtained. An advantage of the method is, that no input from reservoir flow simulations coupled with potentially complex yield functions is required, and a detailed description truly consistent with the time-lapse seismic data can be obtained. As a starting point the displacement at top reservoir is estimated from the observed time-lapse time shift using an R-factor model for the time shift to depth shift conversion. Together with the locally dependent material parameters the boundary displacements are used as input to the geomechanical model. The displacements can then be simulated everywhere in the interior of the model. In a next step these displacements are compared to the displacements observed in the time-lapse seismic data. According to the mismatch, the accuracy of the current geomechanical model can be evaluated. To improve the match between simulated displacements and the displacements estimated from the time-lapse seismic data, the local material properties in the model and/or the depth shift estimates can be adjusted. The whole process improves the confidence in the proposed model parameters. Once the parameters are adjusted and the simulated displacements agree well with the seismic observations the resulting local stress conditions can be trusted. Knowledge of the local stress conditions is important in infill drilling and optimizing well performance and integrity.