gebhart/patrepeval huggingface dataset:
712. Improved Reduction in GM2 Ganglioside Accumulation in Tay-Sachs Mice Using a New Hexosaminidase Variant (2015)

GM2 gangliosidosis is a family of three genetic neurodegenerative disorders caused by the accumulation of GM2 gangliosides (GM2). Two of these are due to the deficiency of one of 2 similar but non-identical subunits that comprise heterodimeric β-hexosaminidase A (HexA) which hydrolyzes GM2. Mutations in the α-subunit (encoded by HEXA) of the enzyme HexA lead to Tay-Sachs disease (TSD), wherein mutations in the β-subunit (encoded by HEXB) lead to Sandhoff disease (SD). In their acute infantile forms, both rapidly progress with fatal neurological deterioration during childhood. The most significant pathological feature of TSD and SD is GM2 accumulation in neurons. Since functional HexA is a heterodimer of the α- and β-subunits, the efficacy of overexpressing only the deficient subunit in a gene therapy approach is limited by the levels of the endogenous subunit. An effective approach to treat either TSD or SD would be to express the α- and β-subunits at equimolar ratios from the same vector, which for AAV has been limited by size restrictions. The present study used a new variant of the Hex α-subunit, containing critical sequences from the β-subunit that can form a stable homodimer (HexM) capable of hydrolyzing GM2. A self-complementary (sc) AAV genome was designed with a synthetic promoter to allow packaging of HEXM. To test the efficacy of HEXM compared to that of the unmodified HEXA, these were packaged into scAAV9 vectors and injected stereotaxically into 4 or 15 month old TSD mice along with an identical titer of scAAV9/GFP vector to track vector spread. The mice were euthanized after 4 weeks and brain sections were subjected to IHC analysis against GFP and GM2. The HexA-like activity was assessed by clearance of GM2 within the injected region, compared to the contralateral brain hemisphere. Qualitatively, a marked reduction of GM2 was apparent in the areas of highest GFP expression. The various Hex vectors showed a clear difference in their ability to degrade GM2. As predicted, human HEXM was more capable of clearing GM2 aggregates than human HEXA at either 4 or 15 months of age. Interestingly, mouse HEXA was more effective than human HEXA, indicating a species-incompatibility, presumably in the formation of a human α- and murine β-subunit heterodimer. This incompatibility further reinforces the utility of HexM to form a functional homodimer independent of the endogenous α- and β-subunit, which should be effective in treating both TSD and SD. In conclusion, modified HEXM can form a functional homodimer capable of clearing GM2 aggregates. It can be packaged in a scAAV9 vector, which is amenable for strategies directed at widespread CNS gene transfer. These technological advances overcome previous barriers and provide pivotal reagents to develop a translatable gene therapy for TSD and SD.
A Conjugate Vaccine Using Enantiopure Hapten Imparts Superior Nicotine-Binding Capacity (2014)

A leading nicotine conjugate vaccine was only efficacious for one-third of clinical trial participants, likely due in part to its use of racemic nicotine hapten, (±)-3'-AmNic. Immunization of male Wistar rats with (+)-, (-)-, or (±)-3'-AmNicSucTT and subsequent antibody immunoassays suggest that a vaccine using enantiopure (-)-3'-AmNic hapten imparts superior capacity to bind (-)-nicotine. Future nicotine vaccine clinical candidates must incorporate this design consideration (i.e., hapten enantiopurity) in order to maximize efficacy.
Water drop corona effects on full-scale 500 kV non-ceramic insulators (1999)

It is shown that certain regions of commercially available 500 kV non-ceramic insulators have surface electric fields that are above the threshold for water drop corona. Observations made in a full scale accelerated aging chamber, and in service, demonstrate that water drop corona occurs on such insulators. A correlation between the magnitude of the surface electric fields and the condition of the silicone rubber non-ceramic insulator surfaces due to water drop corona is illustrated for two different insulator types in an accelerated aging chamber. Other examples of degradation of nonceramic insulators due to water drop corona are illustrated.
A novel APD-based detector module for multi-modality PET/SPECT/CT scanners (2002)

The lack of anatomical information in SPECT and PET images is one of the major factors limiting the ability to localize and accurately quantify radionuclide uptake in small regions of interest, This problem could be resolved by using multi-modality scanners having the capability to acquire anatomical and functional images simultaneously. The feasibility of a novel detector suitable for detecting high-energy annihilation radiation in PET, medium-energy /spl gamma/-rays in SPECT and low-energy X-rays in transmission CT is demonstrated and its performance is evaluated for potential use in multi-modality PET/SPECT/CT imaging. The proposed detector consists of a thin CsI(Tl) scintillator sitting on top of a deep GSO/LSO pair read out by an avalanche photodiode. The GSO/LSO pair provides depth-of-interaction information for 511 keV detection in PET, while the thin CsI(Tl) that is essentially transparent to annihilation radiation is used for detecting lower energy X- and /spl gamma/-rays. The detector performance is compared to that of an LSO/YSO phoswich. Although the implementation of the proposed GSO/LSO/CsI(Tl) detector raises special problems that increase complexity, it generally outperforms the LSO/YSO phoswich for simultaneous PET, SPECT and CT imaging.
Achromatic metasurfaces enable multi-wavelength flat optical components: demonstration of a dispersion-less beam deflector (2015)

Achromatic metasurfaces are introduced for multiwavelength light control. A wavelength-dependent phase response preserves the functionality within a certain bandwidth. Scattering properties of dielectric resonators are explored to demonstrate a dispersion-free beam deflector and an achromatic lens
Electronic Nose With Detection Method for Alcohol, Acetone, and Carbon Monoxide in Coronavirus Disease 2019 Breath Simulation Model (2021)

Electronic nose technology may have the potential to substantially slow the spread of contagious diseases with rapid signal indication. As our understanding of infectious diseases such as Corona Virus Disease 2019 improves, we expect electronic nose technology to detect changes associated with pathogenesis of the disease such as biomarkers of immune response for respiratory symptoms, central nervous system injury, and/or peripheral nervous system injury in the breath and/or odor of an individual. In this paper, a design of an electronic nose was configured to detect the concentration of a COVID-19 breath simulation sample of alcohol, acetone, and carbon monoxide mixture. After preheating for 24 hours, the sample was carried into an internal bladder of the collection vessel for analysis and data was collected from three sensors to determine suitability of these sensors for the application of exhaled breath analysis. Test results show a detection range in parts-per-million within the sensor detection range of at least 10-300 ppm. The output response of an MQ-2 and an MQ-135 sensor to a diverse environment of target gasses show the MQ-2 taking a greater length of time to normalize baseline drift compared to an MQ-135 sensor due to cross interferences with other gasses. The COVID-19 breath simulation sample was established and validated based on preliminary data obtained from parallel COVID-19 breath studies based in Edinburgh and Dortmund. This detection method provides a non-invasive, rapid, and selective detection of gasses in a variety of applications in virus detection as well as agricultural and homeland security.
Design and Semantics of a Decentralized Authorization Language (2007)

We present a declarative authorization language that strikes a careful balance between syntactic and semantic simplicity, policy expressiveness, and execution efficiency. The syntax is close to natural language, and the semantics consists of just three deduction rules. The language can express many common policy idioms using constraints, controlled delegation, recursive predicates, and negated queries. We describe an execution strategy based on translation to datalog with constraints, and table-based resolution. We show that this execution strategy is sound, complete, and always terminates, despite recursion and negation, as long as simple syntactic conditions are met.
Distributed Access Control For XML Document Centric Collaborations (2008)

This paper introduces a distributed and fine grained access control mechanism based on encryption for XML document centric collaborative applications. This mechanism also makes it possible to simultaneously protect the confidentiality of a document and to verify its authenticity and integrity, as well to trace its updates. The enforcement of access control is distributed to participants and does not rely on a central authority. Novel aspects of the proposed framework include the adoption of a decentralized key management scheme to support the client-based enforcement of the access control policy. This scheme is driven by the expression of access patterns of interest of the participants over document parts to determine the keys required. A lazy rekeying protocol is also defined to accommodate the delegation of access control decisions that in particular reduces rekeying latency when faced with the addition and removal of participants.
Predictive analogue generator excitation controller (1997)

A generator excitation control scheme is introduced which is capable of providing good and consistent voltage control performance, despite wide variations in the system operating conditions. The control scheme is organised so that it comprises a main forward loop, based on a standard voltage error signal, as in a conventional AVR, supplemented by an auxiliary loop incorporating direct axis voltage and current signals. The former loop serves to provide the voltage regulation requirements while the latter serves to compensate for the influence of generator load current on dynamic behaviour.
The melA gene is essential for melanin biosynthesis in the marine bacterium Shewanella colwelliana (1993)

The surface-adhering, Gram-negative marine bacterium Shewanella colwelliana synthesizes a red-brow melanin in the late stage of exponential growth in laboratory culture. Previous studies identified a single gene, melA, from S. colwelliana that could impart the ability to produce melanin to an E. coli host. However, these studies did not demonstrate a requirement for melA during melanization in S. colwelliana. In this paper, genetic analyses, using a broad host range conjugation system to generate specific lesions, reveal that melA null mutants fail to synthesize pigment. The wild-type melA gene provided in trans on a low copy number plasmid complemented these null mutations, as well as a spontaneous pigment variant, to wild-type melanin synthesis. Polyclonal antibodies, raised against a MelA-LacZ fusion protein, were used to confirm the presence of the melA gene product in wild-type S. colwelliana and verify its absence in the non-pigmented mutants. In addition, detection of the MelA protein over the course of growth in batch culture revealed a constant steady-state level of MelA protein, suggesting that the timing of melanization and the quantity of melanin synthesized is not controlled at the level of melA expression.
DIFMOS&#8212;A floating-gate electrically erasable nonvolatile semiconductor memory technology (1977)

Electrically alterable read-only memories (EAROM's) or reprogrammable read-only memories (RPROM's) can be fabricated using a single-level metal-gate p-channel MOS technology with all conventional processing steps. Given the acronym DIFMOS for dual-injector floating-gate MOS, this technology utilizes the floating-gate technique for nonvolatile storage of data. Avalanche injection of hot electrons through gate oxide from a special injector diode in each bit is used to charge the floating gates. A second injector structure included in each bit permits discharge of the floating gate by avalanche injection of holes through gate oxide. The overall design of the DIFMOS bit is dictated by the physical considerations required for each of the avalanche injector types. The end result is a circuit technology which can provide fully decoded bit-erasable EAROM-type circuits using conventional manufacturing techniques.
A Technique for Building Representation in Oblique View Maps of Modern Urban Areas (2009)

This paper presents a technique for creating oblique view maps of urban areas. We identify and apply cartographic and cognitive principles to develop a solution in the context of state-of-art geographic information systems. The gap in the ability of these systems to render three-dimensional buildings into maps is addressed. At the core of our solution is a building facade modelling approach that supports varying degrees of abstraction. This is achieved by introducing a concept of 'facade waveforms' and representing building facades as combinations of these waveforms. A Fourier series approximation of the waveforms is used during the rendering processes resulting in an elegant solution to anti-aliasing. The formulation retains the semantic information in the representation that enables meaningful extensions like night time facade generation. The solution is implemented as a pixel shader and therefore leads to a large reduction in texture memory requirement compared with existing building rendering techniques. Additionally, in the case of web based systems, there is significant reduction in bandwidth requirement. We highlight the features of the proposed solution by generating demonstrative maps and images.
<title>70-J repped pulse (0.5 Hz) closed-cycle photolytic atomic iodine laser at 1.315 microns with excellent BQ, coherence length, and reliable operation</title> (1992)

The performance of a repetitively pulsed, high energy, closed cycle photolytic atomic iodine lasers at 1.315 microns is presented. Using an I<SUB>2</SUB> removal system for the photolyzed C<SUB>3</SUB>F<SUB>7</SUB>I laser fuel, more than 70 joules/pulse was acquired in the fundamental mode from a M equals 3 confocal unstable resonator at a 0.5 Hz repetition rate. The closed cycle chemical scrubber system consisted of a condensative-evaporative section, two Cu wool I<SUB>2</SUB> reactor sections, and an internal turbo-blower. This closed cycle system provided C<SUB>2</SUB>F<SUB>7</SUB>I gas at 10 - 60 torr absent of I<SUB>2</SUB>. The turbo-blower produced longitudinal flow velocities greater than 10 m/s through the 150 cm long by 7.5 X 7.5 cm<SUP>2</SUP> cross sectional photolytic iodine gain region. In addition to the high energy output, the resulting 10 - 12 microsecond(s) ec laser had a beam quality of less than 1.5 times diffraction limited with a coherence length greater than 45 meters, and a polarization extinction ratio better than 100:1. Projections from this pulsed photolytic atomic iodine laser technology to larger energies, high repetition rates, and variable pulsewidths are discussed. In addition, the performance of cw photolytically excited atomic iodine laser at 1.315 micrometers is reported which has excellent scaling potential. Volumetric extractable cw powers of 55 watts/liter are reported with a small signal gain coefficient of 2%/cm. The potential of enhancing the cw powers to kilowatt levels plus producing variable pulsewidth, repetition rate iodine laser using an internal electro-optical modulator are also discussed.
Mono-grooved circular waveguide polarizers (2003)

This paper presents a unique type of polarizer that is composed of a circular waveguide with an only groove. The presented polarizer is suitable for realizing compact size and reducing degradation in performance due to manufacturing inaccuracy. An accurate design of the polarizer is performed using mode-matching techniques. A W-band polarizer has, been designed, and the results of error analysis have verified the high efficiency of the presented polarizer.
Microstructure-property relationships in discontinuous fiber reinforced thermoplastic composites (1996)

A novel Aligned Discontinuous Fiber (ADF) composite process has been developed to optimize performance and processability of discontinuous fiber thermoplastic composites. The principle feature of this process is the alignment of the fibers using electric fields in air. The successful control of the orientation state of the fibers using the ADF process led to the fabrication of micro-structure controlled discontinuous fiber composites and the subsequent investigation into the microstructure-property relationships of these materials.
Urinary hyperglycosylated hCG in first trimester screening for chromosomal abnormalities (2000)

Hyperglycosylated human chorionic gonadotrophin (H-hCG), also known as Invasive Trophoblast Antigen or ITA, is a unique metabolic variant of hCG with more complex oligosaccharide side chains. Concentrations are independent of regular hCG. Urine H-hCG has recently proved to be a highly sensitive marker for Down syndrome screening in the second trimester of pregnancy. We evaluated H-hCG as a potential marker in the first trimester of pregnancy. Maternal urine samples were collected from 10(+0) to 11(+6) weeks of gestation prior to genetic analysis and stored in frozen form. Samples from eight cases of Down syndrome, two cases of trisomy 13, one case of trisomy 18, and 55 control pregnancies were hand-carried frozen to the USA and tested blindly. Samples were tested in a specific H-hCG immunoassay and values were normalized to creatinine concentration. Values were plotted against gestational age, and multiples of control pregnancy median (MoM) calculated. The median level of the MoMs of the eight Down syndrome cases was 3.6 MoM. Five of the eight Down syndrome cases exceeded the 90th centile of the 55 unaffected cases. The MoMs of the trisomy 13 and 18 pregnancies were 0.2, 0.2 and 0.3. All three cases were under the 10th centile of unaffected pregnancies. The results of this study indicate that H-hCG testing may be useful in screening for Down syndrome in the first trimester of pregnancy. Further studies are needed to assess the potential screening values of urine H-hCG and the combination of this test with free beta-subunit, PAPP-A and other markers for Down syndrome in the first trimester of pregnancy.
An adaptive optical equalizer concept for single channel distortion compensation (2002)

We present a new adaptive optical equalizer concept for single-channel distortion compensation and analyze the performance of an adaptive optical FIR-filter in lattice structure (cascaded MZI) with respect to equalization of residual dispersion, self-phase modulation and polarization-mode dispersion.
Low-temperature pathways to Ge-rich Si1−xGex alloys via single-source hydride chemistry (2005)

We report rapid low-temperature (300–470°C) growth of Si0.50Ge0.50, Si0.33Ge0.67, Si0.25Ge0.75, and Si0.20Ge0.80 alloys on Si(100) using heavy single-source hydride molecular compounds (H3Ge)nSiH4−n (n=1–4). Incorporation of the entire SiGe, SiGe2, SiGe3, and SiGe4 framework of these precursors into the film provides precise control of morphology, composition, and strain. Low-energy electron microscopy analysis indicates that the (H3Ge)xSiH4−x (x=2–4) species are highly reactive, with H2 desorption characteristics comparable to those of Ge2H6, despite the presence of strong Si–H bonds in their molecular structure.
An orally available non-nucleotide STING agonist with antitumor activity (2020)

Pharmacological activation of the STING (stimulator of interferon genes)-controlled innate immune pathway is a promising therapeutic strategy for cancer. Here we report the identification of MSA-2, an orally available non-nucleotide human STING agonist. In syngeneic mouse tumor models, subcutaneous and oral MSA-2 regimens were well tolerated and stimulated interferon-β secretion in tumors, induced tumor regression with durable antitumor immunity, and synergized with anti-PD-1 therapy. Experimental and theoretical analyses showed that MSA-2 exists as interconverting monomers and dimers in solution, but only dimers bind and activate STING. This model was validated by using synthetic covalent MSA-2 dimers, which were potent agonists. Cellular potency of MSA-2 increased upon extracellular acidification, which mimics the tumor microenvironment. These properties appear to underpin the favorable activity and tolerability profiles of effective systemic administration of MSA-2.
Mixed α/β-Peptides as a Class of Short Amphipathic Peptide Hydrogelators with Enhanced Proteolytic Stability (2016)

Peptide hydrogels are a highly promising class of materials for biomedical application, albeit facing many challenges with regard to stability and tunability. Here, we report a new class of amphipathic peptide hydrogelators, namely mixed α/β-peptide hydrogelators. These mixed α/β-gelators possess good rheological properties (high storage moduli) and form transparent self-supporting gels with shear-thinning behavior. Infrared spectroscopy indicates the presence of β-sheets as the underlying secondary structure. Interestingly, self-assembled nanofibers of the mixed α/β-peptides display unique structural morphologies with alteration of the C-terminus (acid vs amide) playing a key role in the fiber formation and gelation properties of the resulting hydrogels. The incorporation of β3-homoamino acid residues within the mixed α/β-peptide gelators led to an increase in proteolytic stability of the peptides under nongelating conditions (in solution) as well as gelating conditions (as hydrogel). Under diluted conditions, degradation of mixed α/β-peptides in the presence of elastase was slowed down 120-fold compared to that of an α-peptide, thereby demonstrating beneficial enzymatic resistance for hydrogel applications in vivo. In addition, increased half-life values were obtained for the mixed α/β-peptides in human blood plasma, as compared to corresponding α-peptides. It was also found that the mixed α/β-peptides were amenable to injection via needles used for subcutaneous administrations. The preformed peptide gels could be sheared upon injection and were found to quickly reform to a state close to that of the original hydrogel. The shown properties of enhanced proteolytic stability and injectability hold great promise for the use of these novel mixed α/β-peptide hydrogels for applications in the areas of tissue engineering and drug delivery.
The utilization of two frequency‐shifted sinc pulses for performing volume‐selected <i>in vivo</i> NMR spectroscopy (1986)

A new approach to volume-selected in vivo NMR spectroscopy uses two frequency-shifted sinc pulses, in conjunction with pulsed field gradients, to destroy the coherence of the unwanted signals. A hard pi/2 pulse can then be used to read the z magnetization in the region of interest. This method is independent of T2, provides complete volume selection in a single acquisition, and can be readily implemented on most high-field commercial imaging/spectroscopy systems.