gebhart/patrepeval huggingface dataset:
Endoplasmic reticulum stress leads to the selective transcriptional downregulation of the glucoamylase gene in Aspergillus niger (2004)

We describe a new endoplasmic reticulum (ER)-associated stress response in the filamentous fungus Aspergillus niger. The inhibition of protein folding within the ER leads to cellular responses known collectively as the unfolded protein response (UPR) and we show that the selective transcriptional downregulation of the gene encoding glucoamylase, a major secreted protein, but not two non-secreted proteins, is an additional consequence of ER stress. The transcriptional downregulation effect is shown by nuclear run-on studies to be at the level of transcription, rather than mRNA stability, and is found to be mediated through the promoter of glaA in a region more than 1 kb upstream of the translational start. The inhibition of protein folding in the ER can be induced in a variety of ways. We examined the effects of dithiothreitol (DTT), a reducing agent that causes the formation of unfolded proteins. Although a general downregulation of transcription was seen with DTT treatment, we show that selective downregulation was observed with the glaA gene compared with genes encoding the non-secreted proteins gamma-actin and glyceraldehyde 3'-phosphate dehydrogenase. The DTT-treated fungal cells also showed evidence for the induction of the UPR because expression of bipA and pdiA, encoding an ER-resident chaperone and foldase, respectively, are upregulated and splicing of hacA, the gene encoding the transcription factor responsible for induction of the UPR, occurs allowing the production of an active HacA protein. As a preliminary attempt to investigate if the transcriptional downregulation effect was mediated through HacA (i.e. part of the UPR), we examined ER stress induced through antisense technology to lower the level of PDI in the ER of A. niger. Although the transcription of glaA was attenuated in that strain of A. niger, UPR was not evident, suggesting that the transcriptional downregulation mechanism is controlled differently from the UPR.
An All-COTS High Sampling Frequency Pulse-Doppler Imaging Radar (2020)

This paper presents a high sampling frequency pulse-Doppler radar that was constructed using commercially available components. The system architecture is explained with emphasis placed on the digital transceiver subsystem. A calibration technique is presented to mitigate range ambiguity due to digital latency variation between resets of the system. The pulse-Doppler operation of the system is then evaluated through the range-Doppler mapping of moving and stationary targets, confirming the radar's potential for synthetic aperture radar imaging.
MEMS Tunable antennas to address LTE 600 MHz-bands (2015)

The broadcast television spectrum around 600 MHz has been freed in the united states and will be put for auction to wireless carriers in 2015. The newest generation of mobile communication standards will be deployed on these newly available bands, to provide mobile device users with an enhanced connectivity. This paper proposes a novel antenna design that overcomes the bandwidth challenge of such low operating frequencies on handsets.
Fabrication of Precursor by Consolidating Aluminum Alloy Powder Using Friction Stir Welding and Its Foaming (2022)

In this study, we fabricated a precursor by FSW using ADC12 (Al-Si-Cu alloy) powder and foamed the obtained precursor by optical heating to fabricate the porous aluminum (Al). If ADC12 powder can be used for fabricating the precursor, it is expected that Al waste materials from the manufacturing of industrial products, such as Al cutting scraps, can be used as recycled Al chips, with which the cost of porous Al manufacturing can be reduced. The results demonstrated that ADC12 powder can be consolidated as well as the blowing agent (titanium hydride) and stabilization agent (alumina) powders can be mixed into the consolidated ADC12 by FSW to fabricate precursors at the tool traversing speed v = 10–50 mm/min. In addition, the obtained precursor can be foamed by optical heating. It was also found that the precursor with fewer cracks and defects can be obtained at v = 10, 20, and 30 mm/min versus at v = 40 and 50 mm/min. As a result, porous Al with relatively good pore structures was obtained at v = 10–30 mm/min.
Androgen receptor activation in HER2-negative breast cancer liver metastases. (2016)

11527 Background: The androgen receptor (AR) is expressed in the majority of breast cancers (BC) and its signaling may contribute to the development of BC metastases. The expression pattern of AR, its phosphorylated (p) form, and correlations with other BC growth and survival pathways was evaluated by protein pathway activation mapping in primary and metastatic (met) BC tissues. Methods: Group 1: 72 human BC primary and metastatic tissues underwent phosphoproteomic analysis using the TheraLink Assay, a reverse phase protein array (RPPA)-based method at a CLIA-certified laboratory (Theranostics Health). Immunostaining with 24 antibodies was directed against AR, pAR, pMet, and total and pHER1/2/3 pathway proteins. Spearman correlation was performed. Group 2: 25 met BC tissues from the SideOut Foundation-sponsored clinical trial (#NCT01919749) were analyzed by RPPA at GMU. Results: Group 1: 34 were primary BCs (55%); 38 were mets (45%). Sites of mets: liver (n = 24); lung (n = 7); chest wall (n = 7). AR expression was increased in chest wall (1.7-fold) and liver (1.3-fold) compared to primary BCs. pAR was increased in liver (2.3-fold) and chest wall (1.8-fold) compared to primary BCs. Liver mets showed a negative correlation between pAR and HER2 (p = 0.014), pAR and pHER2 (p = 0.001), and pAR and pmTOR (p = 0.046); this was observed in the 17 liver mets that were HER2–. A strong positive correlation was seen in these HER2– liver mets between total AR and pAKT (p = 0.012), pAR and p4EBP1 (p = 0.029), pAR and pMek1/2 (p = 0.006), pAR and pMet (p = 0.005), and pMet and pHER3 (p = 0.071). Group 2: Sites of mets: liver (n = 10), skin/chest wall (n = 7), lymph node (n = 3), intra-abdominal masses (n = 3), lung (n = 2). High expression levels of pAR were seen in 4/10 (40%) of the liver mets whereas 2/15 (13%) of the other mets had any measurable pAR. Conclusions: 2 independent sets of HER2 metBC tissues showed strong liver-specific activation of AR along with activation of cMet/HER3 signaling. These results suggest a possible role of AR in the growth of HER2 liver mets. Clinical trials inhibiting AR as well as HER3 or cMet kinase activity in patients with liver mets would be of interest.
Explanation of the Charge Trapping Properties of Silicon Nitride Storage Layers for NVMs—Part II: Atomistic and Electrical Modeling (2011)

Based on the material analysis of the SiN layers presented in part I of this paper, we develop accurate atomistic and electrical models for the silicon nitride (SiN)-based nonvolatile memory devices, taking into account the candidate SiN defects responsible for the memory effect. Our analysis points out the role of the hydrogen atoms and Si dangling bonds in the trapping properties of SiN films with different stoichiometries. The atomistic models provide a comprehensive picture describing the energy level and the occupation number of the different defects in the SiN. The electrical model coupled with the atomistic results, for the first time, demonstrates the ability to describe the program/erase curves of charge-trap memory cells with SiN storage layers with diversified composition. Good agreement between simulations and experimental results coming from the material analysis and the electrical characterization of thin (type-B device) and thick (type-A device) tunnel oxide memory cells is shown.
Detection of Amyloid Plaques Targeted by Bifunctional USPIO in Alzheimer’s Disease Transgenic Mice Using Magnetic Resonance Microimaging (2013)

Amyloid plaques are a key pathological hallmark of Alzheimer's disease (AD). The detection of amyloid plaques in the brain is important for the diagnosis of AD, as well as for following potential amyloid targeting therapeutic interventions. Our group has developed several contrast agents to detect amyloid plaques in vivo using magnetic resonance microimaging (µMRI) in AD transgenic mice, where we used mannitol to enhance blood brain barrier (BBB) permeability. In the present study, we used bifunctional ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, chemically coupled with Aβ1-42 peptide to image amyloid plaque deposition in the mouse brain. We coupled the nanoparticles to polyethylene glycol (PEG) in order to improve BBB permeability. These USPIO-PEG-Aβ1-42 nanoparticles were injected intravenously in AD model transgenic mice followed by initial in vivo and subsequent ex vivo μMRI. A 3D gradient multi-echo sequence was used for imaging with a 100 µm isotropic resolution. The amyloid plaques detected by T2*-weighted μMRI were confirmed with matched histological sections. The region of interest-based quantitative measurement of T2* values obtained from the in vivo μMRI showed contrast injected AD Tg mice had significantly reduced T2* values compared to wild-type mice. In addition, the ex vivo scans were examined with voxel-based analysis (VBA) using statistical parametric mapping (SPM) for comparison of USPIO-PEG-Aβ1-42 injected AD transgenic and USPIO alone injected AD transgenic mice. The regional differences seen by VBA in the USPIO-PEG-Aβ1-42 injected AD transgenic correlated with the amyloid plaque distribution histologically. Our results indicate that USPIO-PEG-Aβ1-42 can be used for amyloid plaque detection in vivo by intravenous injection without the need to co-inject an agent which increases permeability of the BBB. This technique could aid the development of novel amyloid targeting drugs by allowing therapeutic effects to be followed longitudinally in model AD mice.
Back to the Future: The TIA Alliance as a Student Recruitment Tool (2019)

Future natural resource management success depends on a workforce of well-trained, motivated, and relevant conservation professionals. Today’s high school students need to ‘rub elbows’ with inspirational natural resource managers doing field work culminating in meaningful experiences. Over the last six years, a James Madison High School club in Vienna, VA piloted a successful program. Urban students traveled to the Blue Ridge Mountains, conducted basic headwater drainage basin assessments and identified release sites for brook trout raised in Northern Virginia Classrooms. They were rewarded with fishing trips sponsored by a local Trout Unlimited (TU) chapter, potentially recruiting them as nontraditional anglers. In November 2018, TU joined the Izaak Walton League of America (IWLA) and the American Fisheries Society (AFS), creating the TIA Alliance, pledging to work together to expand the Madison club approach, potentially creating a nationwide program. One local area where this work may happen is the New River Valley, Virginia area, where the primary author is the Virginia Department of Game and Inland Fisheries fisheries biologist, an IWLA member and an active AFS member. Meaningful outdoor experiences will be enhanced by leaders providing quality mentorship to propel us ‘Back to the Future’ by creating new natural resource managers.
Modular Smart Molecules for PSMA-Targeted Chemotherapy (2022)

New targeted chemotherapeutics are urgently needed to minimize off-target toxicity and reduce the high-mortality rate associated with metastatic prostate cancer. Herein, we report on the modular synthesis, pharmacokinetics, and efficacy of two small-molecule-drug conjugates (SMDC) targeted to prostate-specific membrane antigen (PSMA) incorporating either: (i) a cathepsin-B-cleavable valine-citrulline (Val-Cit), or (ii) an acid-cleavable phosphoramidate linker. Crucial components used in the design of the conjugates include: (i) CTT1298, a nanomolar affinity ligand that binds irreversibly to PSMA and has proven in past studies to rapidly internalize and shuttle payloads into PSMA-expressing prostate cancer cells, (ii) MMAE, a known potent cytotoxic payload, and (iii) an albumin-binder, proven to improve residence time of drug conjugates. At dose of 0.8 mg/kg (∼250 nmol/kg), the two SMDCs showed significant efficacy in a PSMA(+) PC3-PIP mouse model of human prostate cancer compared with controls, without inducing systemic toxicity. Though localization of the SMDCs was observed in tissues apart from the tumor, release of MMAE was observed predominantly in tumor tissue, at levels that were 2-3 orders of magnitude higher than non-target tissues. Furthermore, SMDC2, which incorporated a novel pH-responsive phosporamidate linker, demonstrated significantly improved efficacy over SMDC1 that has a Val-Cit linker, with a 100% survival over 90 days and 4 out of 8 mice showing complete tumor growth inhibition after 6 weekly doses of 0.8 mg/kg (244 nmol/kg). Our findings demonstrate the potential of irreversible PSMA inhibitors combined with pH-responsive linkers as a way to specifically deliver chemotherapeutic drugs to prostate cancer tumors with minimal toxicity.
Influence Of Isolation On Interference In Bioelectric Recordings (2005)

Isolation in bioelectric recordings is not only of importance for the electrical safety of the patient, but is often supposed to be also beneficial for the suppression of interference. In this paper, the influence of isolation on the reduction of interference is treated. Its effect appears to depend on the isolation capacitance. Interference caused by the capacitances between the input cables and the interference source is not influenced by isolation. An often overlooked source of interference is the voltage across the isolation barrier. The feedthrough of this signal to the output is specified by the isolation mode rejection ratio (IMRR). Measures to reduce this type of interference are discussed.
Magnetorheological finishing and subaperture stitching interferometry of large and lightweight optics (2004)

Significant challenges are faced in the manufacturing of the complex optics for the next generation of astronomical telescopes. Process improvements are required to establish cost effective techniques to finish the optics to the tight specification required in a timely manner. An added complication is realized when the optics are lightweight. The non-uniform support of the face-sheet in this case requires special efforts to avoid a print-through of the cell structure due to fabrication processes, gravity and/or cryogenic effects. Magnetorheological finishing (MRF) is a deterministic, sub-aperture polishing process that has been a revolutionary success in the fabrication of optics in the size range of 10-1000 mm. This production proven process is capable of polishing flats, spheres, aspheres and cylinders to a surface figure accuracy of better than 30 nm peak-to-valley (better than 5 nm rms), and microroughness better than 1 nm rms on a variety of glasses, glass ceramics and single crystal materials. Unique characteristics of MRF such as a high, stable removal rate, conformal nature of the sub-aperture tool and shear mode of material removal give it advantages in the finishing of large and lightweight optics. These qualities provide for a cost-effective process with a high rate of convergence that requires few iterations. Such a technology is ideally complemented by a system for the stitching of interferometric sub-aperture data. Stitching inherently enables the testing of larger apertures with higher resolution and, thanks to the built-in calibration, even to higher accuracy in many situations. While this approach enables the non-null testing of parts with greater aspheric departure and can lead to a significantly reduced non-common air path in the testing of long-radius concave parts, it is especially effective for convex optics. That is, stitching is particularly well suited to the testing of secondary mirrors and, alongside the testing of the off-axis primary segments.
A Systematic Granulized Piecewise Linear Approximation to the Jacobian Logarithm (2012)

A systematic, granulized piecewise linear approximation to the Jacobian logarithm is developed. This approximation reverts to the Jacobian approximation and the exact Jacobian logarithm at the far extremes. The utility of the derived approximation is demonstrated by applying it to the decoding of Turbo coded, MIMO/BICM-ID systems.
Neural networks for computing invariant clustering of a large open set of DNA-PCR-primers generated by a feature-knowledge based system (1990)

A neural network computing model for image sorting by means of invariant clustering is described. Such image sorting by clustering belongs to the class of inverse problems of image processing. One of the biomedical applications is to diagnose AIDS virus-mutated DNA by a powerful recombinant DNA technology, the polymerase chain reaction (PCR), based on judicious choice of oligonucleotide primers for the synthesis of an imprecisely known DNA sequence due to the unknown viral infections. Thus, a smaller set of primers among a larger open set, generated by a feature rule-based system, must be found. A neural network is needed to do nondestructive sorting and maintain the chemical bases (G, C, A, T) of the chosen primers. The problem is solved by an ART-1 neural network for feature extraction by clustering and an ART-4 (a hybrid ART-1) neural network for image sorting by clustering. The initial condition of ART-1 is precisely the complement of the initial condition of ART-4. The ART-1 whitens the cluster leader by the veto power of newcomers, while the ART-4 edifies and preserves the cluster leader by the consent of followers. A feature based expert system provides a powerful training environment for the ART-4 neural network to further discover new cluster rules
Analysis of the 1H NMR spectra of the carboxylic ionophore narasin A in its Apo and cation‐bound forms (1989)

Abstract As a first step in the conformational analysis of the cation‐binding reactions of the carboxylic ionophore narasin A, 1 H NMR spectra of narasin A in its apo and H + ‐, K + ‐ and Na + ‐bound forms in CD 3 OD were assigned. In addition, new assignments for the spectrum of H + ‐narasin A in CDCl 3 were obtained. Two dimensional 1 H− 1 H chemical shift correlation, one‐dimensional nuclear Overhauser effect and decoupling difference techniques were used to determine the chemical shifts and 1 H 1 H coupling constants.
Tracing indoor contaminant release location based on local mean residual-life-time of air (2020)

Even in case ventilation system is operating in optimal fashion, indoor air quality could be varied depending on the indoor contaminant release occasions. Thus, accurate and rapid identification of contaminant source locations in indoor environment is critical for occupants’ health as well as building safety and integrity. This study presented a novel method to locate indoor contaminant source using local mean residual-life-time (LMR). Based on the theoretical definition of LMR, a characteristic quantitative relationship between the LMR at source location and the contaminant concentration profile of a room was derived and assessed through two stages of studies: experimental and numerical explorations. In the experiments, by changing contaminant release location under limited condition, the LMR at the source location and the contaminant concentration profile of a test chamber were measured. Then, the outcomes were examined to verify whether the derived equation was established in the chamber. Computational Fluid Dynamics (CFD) technique was also used to make up for the experimental limitations. CFD simulations were carried out to analyze the validity of the equation in response to different release locations of the contaminant in a more complex physical environment by obtaining high-resolution information. Both experimental and numerical results showed that the presented equation was well established and could be used to locate indoor contaminant source even in non-ideal situation or in complicated spaces.
Setting the Stage for New Catalytic Functions in Designed Proteins—Exploring the Imine Pathway in the Efficient Decarboxylation of Oxaloacetate by an Arg–Lys Site in a Four-Helix Bundle Protein Scaffold (2002)

Fourteen 42-residue polypeptides have been designed to identify reactive sites for the catalysis of the decarboxylation of oxaloacetate, a chemical transformation that proceeds through the formation of an imine intermediate. The sequences fold into helix-loop-helix motifs and dimerize to four-helix bundles. The catalytically active lysine residues were incorporated in several surface exposed positions, but also in positions characterised by hydrophobic properties to reduce their pKa values. The molecular environments of the Lys residues were systematically varied, to find which residues were able to stabilise and bind the imine intermediate in the decarboxylation reaction. A two-residue Arg-Lys site formed the main component of the reactive site of the helix-loop-helix dimer Decarb-K34_R33, which obeyed saturation kinetics in catalysing the reaction with a kcat/KM of 0.59 M-1S-1. The rate constant measured was nearly three orders of magnitude larger than the second-order rate constant of the butylamine-catalysed reaction (0.0011 M-1S-1), and four orders of magnitude larger than the pseudo first-order rate constant of the uncatalyzed reaction (1.3 x 10(-5) s(-1)). The sequence of Decarb-K34_R33 contained only a single lysine residue. It was flanked by an arginine in the preceding position in the sequence. A flanking Arg residue provided more efficient catalysis than a flanking Lys or Gln residue. Arginines in flanking positions in the helix, in positions four residues before or after the Lys in the sequence, are not as important in catalysis as the Arg of the Arg-Lys pair. The effect of pKa on the catalytic efficiency of the Lys residue in the decarboxylation reaction is well known. The identification of the role of the flanking Arg residue in catalysing decarboxylation, its optimal position, and the importance of conformational stability reported here sets the stage for developing a number of catalytic systems that depend on the formation of imine intermediates, but that lead to different reaction products.
Optimization of delivery time in broadcast with acknowledgement and partial retransmission (2016)

In this paper, we discuss a hybrid scheduling approach of content delivery for broadcast systems. TWo components are considered: the broadcast component and the unicast component. The broadcast component is used to deliver the content to part of the mobiles located in the cell. The remaining mobiles, that do not successfully receive the content because are in a deep fade or suffer from bad channel conditions, use retransmissions in order to improve the packet detection probability. We show that there is a compromise between the number of users that are allowed to use retransmissions and the data rate at which the broadcast content is transmitted. Unlike the pure broadcast approach where there is a race to the bottom in order to serve the weakest user in the cell, this approach frees up the scheduler from building on the worst channel quality in the cell by allowing a degree of retransmission for cell edge users.
Self-defocusing in ultrasonic hyperthermia: Experiment and simulation (1999)

During hyperthermia treatments with high intensity focused ultrasounds, the temperature elevation locally induces a change of sound speed which acts itself as an aberrator for the ultrasonic beam. Such a thermal lens effect may become noticeable as time increases and leads to significant effects like the self-defocusing of the beam. This letter presents an experimental evidence of this effect, and a finite difference simulation of the coupled wave and heat equations is presented that demonstrates similar phenomenon.