gebhart/patrepeval huggingface dataset:
The Human IL-23 Receptor rs11209026 A Allele Promotes the Expression of a Soluble IL-23R–Encoding mRNA Species (2015)

The human IL23R gene single nucleotide polymorphism rs11209026 A allele confers protection against inflammatory diseases. However, although this difference has been associated with reductions in IL-23-induced IL-17A production and STAT3 phosphorylation, the molecular mechanism underlying these changes remains undefined. Th17 cell maturation depends on IL-23 signaling. Multiple splice forms of the human IL23R transcript exist, and one, Δ9, encodes a soluble form of the receptor. In this study, we asked whether this protective allele was associated with mRNA splicing. Using mini-gene constructs and competitive oligonucleotide binding, we showed that the A allele alters IL-23R α-chain mRNA splicing and favors exon 9 skipping by reducing the binding of the splicing enhancer SF2. This enhances expression of the Δ9 mRNA and consequently diminishes IL-23 signaling. Thus, the presence of the A allele increases expression of the soluble form of IL23R mRNA (which then functions as a decoy receptor) and lowers the ability to develop a Th17 phenotype upon IL-23 stimulation. We further showed that antisense oligonucleotides targeting the SF2 binding site could efficiently induce exon 9 skipping in the presence of the G allele, and thereby replicate the effect of the A allele. Antisense oligonucleotide treatment caused dose-responsive induction of the IL23RΔ9 mRNA and interfered with in vitro differentiation of human Th17 cells, reducing their expression of the signature Th17 cytokines IL-17A and IL-17F. This may represent a novel approach to therapy of Th17-mediated diseases by elevating soluble IL-23R while simultaneously reducing the remaining cell surface receptor density.
All-optical light modulation in bacteriorhodopsin films (1995)

We report a convenient method to obtain all-optical light modulation in bacteriorhodopsin films using a degenerate four-wave mixing geometry. Chemically stabilized films of bacteriorhodopsin in a polymer matrix for which the lifetime of the excited M state is tens of seconds were used to demonstrate all-optical light intensity modulation. The films are observed to be stable over a period of 4 years. Due to the sensitivity of the films, small intensities of order microwatt/ cm2 are required in the modulation experiments. Furthermore the fast photochemical transition from M to B permit reasonably fast modulation speeds independent of the slow thermal M and B relaxation time. The experimental system also acts as an all-optical switch where a low power blue pulse turns on a signal red beam.
Inhibition of Activated Protein C Anticoagulant Activity by Prothrombin (1999)

In this study, we test the hypothesis that prothrombin levels may modulate activated protein C (APC) anticoagulant activity. Prothrombin in purified systems or plasma dramatically inhibited the ability of APC to inactivate factor Va and to anticoagulate plasma. This was not due solely to competition for binding to the membrane surface, as prothrombin also inhibited factor Va inactivation by APC in the absence of a membrane surface. Compared with normal factor Va, inactivation of factor Va Leiden by APC was much less sensitive to prothrombin inhibition. This may account for the observation that the Leiden mutation has less of an effect on plasma-based clotting assays than would be predicted from the purified system. Reduction of protein C levels to 20% of normal constitutes a significant risk of thrombosis, yet these levels are observed in neonates and patients on oral anticoagulant therapy. In both situations, the correspondingly low prothrombin levels would result in an increased effectiveness of the remaining functional APC of approximately 5-fold. Thus, while the protein C activation system is impaired by the reduction in protein C levels, the APC that is formed is a more effective anticoagulant, allowing protein C levels to be reduced without significant thrombotic risk. In situations where prothrombin is high and protein C levels are low, as in early stages of oral anticoagulant therapy, the reduction in protein C would result only in impaired function of the anticoagulant system, possibly explaining the tendency for warfarin-induced skin necrosis.
Long-range alpha detector (LRAD) sensitivity to beta contamination and soil moisture (1994)

Long-range alpha detector (LRAD) systems are designed to monitor alpha contamination by measuring the ionization in air formed by the alphas. Recent tests have been performed to determine the sensitivity of LRAD systems to beta contamination and soil moisture levels. These results and the general technology are discussed in this paper.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
ABE: an environment for engineering intelligent systems (1988)

The ABE multilevel architecture for developing intelligent systems addresses the key problems of intelligent systems engineering: large-scale applications and the reuse and integration of software components. ABE defines a virtual machine for module-oriented programming and a cooperative operating system that provides access to the capabilities of that virtual machine. On top of the virtual machine, ABE provides a number of system design and development frameworks, which embody such programming metaphors as control flow, blackboards, and dataflow. These frameworks support the construction of capabilities, including knowledge processing tools, which span a range from primitive modules to skeletal systems. Finally, applications can be built on skeletal systems. In addition, ABE supports the importation of existing software, including both conventional and knowledge processing tools.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Movable-mask reactive ion etch process for thickness control in devices (1996)

By moving the substrate relative to a shadow mask in a reactive ion etching system, we are able to precisely tailor the thickness of critical layers. To minimize disturbing the plasma, all the mechanical components are kept below the anode. The system is highly reproducible, and can be programmed to yield arbitrary vertical profiles along one horizontal axis. Using silicon-on-insulator substrates, the resonance wavelength was modified as a function of position with better than 1 nm control in the vertical dimension. This technique should prove useful for optical devices where the thickness of the layers controls the device characteristics.
Application of Mass Spectrometry Technology to Early Diagnosis of Invasive Fungal Infections (2016)

We recently developed a mass spectrometry (MS) procedure based on the detection of a serum disaccharide (MS-DS) in patients with invasive candidiasis (IC). Here, we compare the performance of MS-DS for the diagnosis of IC, invasive aspergillosis (IA), and mucormycosis (MM) with those of commercially available antigen detection tests. This retrospective study included 48 patients (23 IC patients [74 serum samples], 15 IA patients [40 serum samples], and 10 MM patients [15 serum samples]) and 49 appropriate controls (102 serum samples). MS-DS, mannan (Mnn), galactomannan (GM), and (1,3)-β-d-glucan (BDG) were detected by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) MS, Platelia, and Fungitell assays, respectively. For IC, the sensitivity and specificity of the MS-DS index, BDG detection, and Mnn detection were 62% and 84%, 82% and 60%, and 33% and 94% per serum sample and 83% and 69%, 96% and 31%, and 39% and 86% per patient, respectively. For IA, the corresponding values in comparison to BDG and GM detection were 83% and 81%, 62% and 95%, and 62% and 100% per serum sample and 93% and 76%, 87% and 90%, and 93% and 100% per patient, respectively. Nine of the 10 MM patients had a positive MS-DS result. MS-DS gave an early diagnosis in IC (73% positivity before blood culture), IA (positive before GM detection in six patients), and MM (positivity mainly preceded the date of diagnosis) patients. For IC, persisting MS-DS was associated with a poor prognosis. The different biomarkers were rarely detected simultaneously, suggesting different kinetics of release and clearance. For IA, MS-DS provided better complementation to GM monitoring than BDG monitoring. MS-DS detects panfungal molecules circulating during invasive fungal infections. The performance of MS-DS compared favorably with those of biological tests currently recommended for monitoring at-risk patients. Further validation of this test in multicenter studies is required.
Tailored Glycopolymers as Anticoagulant Heparin Mimetics (2013)

Gerinnungshemmer: Heparin und seine niedermolekularen Derivate werden zur Vorbeugung und klinischen Behandlung von Blutgerinnseln verwendet. Als potenziell sicherere Heparinmimetika wurden nun Heparin-basierte Glycopolymere synthetisiert, die gegen Proteasen (FXa und FIIa) in der Koagulationskaskade wirken und die Gerinnungszeit in humanem Blutplasma ähnlich effizient verlängern wie klinische Antikoagulantien. ATIII=Antithrombin III. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
A bicomponent <i>Plasmodium falciparum</i> investigational vaccine composed of protein-peptide conjugates (2009)

There is yet no licensed vaccine against malaria, a serious human disease affecting mostly children, with an annual death rate of about one million. Plasmodia, the malaria-causing parasites, have two obligatory hosts: mammals or birds, in which they multiply asexually, and mosquitoes with sexual multiplication. The most common and serious type of malaria is caused by Plasmodium falciparum. The circumsporozoite protein (CSP), a major surface antigen of sporozoites, is a protective antigen. A unique feature of P. falciparum CSP is its large central domain composed of over 30 tetrapeptide repeats of Asn-Ala-Asn-Pro (NANP). Several NANP peptide-protein conjugates were tested clinically but elicited a low level of CSP antibodies for a short duration. To provide a CSP-based candidate vaccine, we investigated recombinant CSP and NANP conjugates of various peptide lengths, with different N-terminal amino acids, bound at different ratios to various carrier proteins. Injected into mice, CSP alone and CSP or NANP conjugates induced antibodies with booster responses and were positive by the sporozoite immunofluorescent assay. The use of the mosquito stage P. falciparum ookinete surface protein, Pfs25, cross-linked onto itself as a carrier for NANP, induced in mice high levels of uniquely long-lasting antibodies to both vaccine components with secondary biological activities, that will provide immunity to liver infection by sporozoites and block transmission by mosquitoes.
Efficient Cloud-based Secret Shuffling via Homomorphic Encryption (2020)

When working with joint collections of confidential data from multiple sources, e.g., in cloud-based multi-party computation scenarios, the ownership relation between data providers and their inputs itself is confidential information. Protecting data providers’ privacy desires a function for secretly shuffling the data collection. We present the first efficient secure multi-party computation protocol for secret shuffling in scenarios with a central server. Based on a novel approach to random index distribution, our solution enables the randomization of the order of a sequence of encrypted data such that no observer can map between elements of the original sequence and the shuffled sequence with probability better than guessing. It allows for shuffling data encrypted under an additively homomorphic cryptosystem with constant round complexity and linear computational complexity. Being a general-purpose protocol, it is of relevance for a variety of practical use cases.
Employing an Amphipathic Viral Peptide to Create a Lipid Bilayer on Au and TiO<sub>2</sub> (2007)

Supported lipid bilayers formed by the fusion of small unilamellar vesicles onto SiO2 or organic film-modified surfaces serve as model membranes in both scientific research and practical applications. Here, we describe the use of an amphipathic α-helical viral peptide derived from the hepatitis C virus NS5A protein (AH peptide) to destabilize the vesicles leading to lipid bilayer formation on gold and TiO2 solid substrates. Whereas previous researchers have been limited in their selection of surface materials for lipid biomembranes, the use of such peptides as destabilizing agents will allow the freedom to choose a broader variety of solid substrates to support planar bilayers. In particular, the favorable electrical properties of gold and the beneficial biocompatibility of TiO2 make these substrates attractive. The formation of model lipid bilayers supported on gold and TiO2 substrates can be utilized in many membrane-associated biological, physiological, or electrochemical applications with the advantages provided by both of these supporting solid surfaces.
An olfactory virtual reality system for mice (2018)

All motile organisms use spatially distributed chemical features of their surroundings to guide their behaviors, but the neural mechanisms underlying such behaviors in mammals have been difficult to study, largely due to the technical challenges of controlling chemical concentrations in space and time during behavioral experiments. To overcome these challenges, we introduce a system to control and maintain an olfactory virtual landscape. This system uses rapid flow controllers and an online predictive algorithm to deliver precise odorant distributions to head-fixed mice as they explore a virtual environment. We establish an odor-guided virtual navigation behavior that engages hippocampal CA1 "place cells" that exhibit similar properties to those previously reported for real and visual virtual environments, demonstrating that navigation based on different sensory modalities recruits a similar cognitive map. This method opens new possibilities for studying the neural mechanisms of olfactory-driven behaviors, multisensory integration, innate valence, and low-dimensional sensory-spatial processing.
Codebook-based quantized MIMO feedback for closed-loop transmit precoding (2009)

Advanced quantization schemes are proposed for closed-loop transmit precoding over correlated multiple-input multiple-output (MIMO) channels in this work. Unlike the conventional schemes that directly quantize the MIMO channel covariance matrix and feed back each quantized matrix element, the proposed schemes quantize the channel covariance matrix by exploiting the common rank-one codebook shared by mobile stations and base stations. Compared to the conventional quantization schemes, the proposed quantization schemes can achieve comparable throughput performance with more than 50% overhead reduction at the cost of affordable increase in computational complexity.
Near-Field Sub-Nyquist Source Localization via Uniform Linear Array (2019)

The important problem of source localization of multi-band signal sampled at sub-Nyquist rates is considered in this paper. We address this problem by considering uniform linear array under the condition of sources being present in the near-field (unlike the existing approaches which focus on far-field scenarios). Starting with an existing delay based sub-Nyquist receiver architecture, a new method to unambiguously estimate the triple- direction of arrival (DOA), range and carrier frequency is proposed. The approach has the capability to provide the appropriately paired DOA and the carrier frequency, thus overcoming the additional difficult step of pairing. Simulation results show unambiguous estimation of parameters and a significant reduction in the overall sampling rate with a minimal performance loss compared to classical Nyquist sampling.
Na-K-Cl cotransport in normal and glaucomatous human trabecular meshwork cells. (1999)

These findings indicate that Na-K-Cl cotransport function and regulation are altered in glaucomatous TM cells compared with that of normal TM cells. However, the observation that cell volume of glaucomatous TM cells is greater than that of normal TM cells, despite reduced Na-K-Cl cotransport activity, suggests that other volume-regulatory ion flux pathways may be involved in the reduced outflow of glaucoma.
A cDNA presumptively coding for the .alpha. subunit of the receptor with high affinity for immunoglobulin E (1987)

Rat mast cells and a neoplastic analogue such as rat basophilic leukemia (RBL) cells have receptors that have exceptionally high affinity for immunoglobulin E (IgE). When aggregated, these receptors induce cellular degranulation. The alpha chain of the receptor contains the binding site for IgE; the function(s) of the noncovalently associated beta and gamma chains is (are) still undefined. Using a cDNA library constructed from the mRNA of RBL cells, we have isolated a cDNA clone whose sequence predicts a putative 23-residue signal peptide, followed by a sequence that accurately predicts the amino acid composition, the peptide molecular weight, and six peptide sequences (encompassing 59 residues or 26% of the total number) determined for the alpha chain by direct analysis. These findings provide strong evidence that the cDNA codes for the alpha chain, even though expression has not been unambiguously achieved. The sequence suggests that the alpha chain contains a 180-residue extracellular portion with two homologous domains of approximately 35 residues, a 20-residue transmembrane segment containing an aspartic acid, and a 27-residue cytoplasmic portion containing 9 basic amino acids. The sequence shows no homology with the low-affinity receptor for IgE from lymphocytes but over 30% homology with an Fc gamma receptor.
Videorealistic talking faces: a morphing approach. (1997)

We present a method for the construction of a videorealistic text-to-audiovisual speech synthesizer. A visual corpus of a subject enunciating a set of key words is initially recorded. The key words are chosen so that they collectively contain most of the American English viseme images, which are subsequently identified and extracted from the data by hand. Next, using optical flow methods borrowed from the computer vision literature, we compute realistic transitions between every viseme to every other viseme. The images along these transition paths are generated using a morphing method. Finally, we exploit phoneme and timing information extracted from a text-tospeech synthesizer to determine which viseme transitions to use, and the rate at which the morphing process should occur. In this manner, we are able to synchronize the visual speech stream with the audio speech stream, and hence give the impression of a videorealistic talking face. 1 Introduction There has been an increased inte...
Efficient receiver algorithms for DFT-spread OFDM systems (2009)

For the 3GPP LTE uplink transmissions, the DFTspread OFDM technique has been adopted as the air interface in order to reduce the peak-to-average-power ratio (PAPR). In this scheme, each data symbol is spread over many tones by a discrete Fourier transform (DFT) operation at the transmitter before being sent to the orthogonal frequency division multiplexing (OFDM) modulator. Moreover, more than one user can be scheduled over the same frequency and time resource block (RB) via space-division multiple-access (SDMA). The conventional receiver technique for such DFT-spread OFDM systems involves tone-by-tone single-tap equalization followed by an inverse DFT operation. In this paper, we propose a more powerful receiver technique for DFT-spread OFDM systems that consists of an efficient linear pre-filter and a two-symbol soft output demodulator. The proposed method can be applied to both single-user per RB (DFT-S-OFDMA) and multiple users per RB (DFT-S-OFDMSDMA) systems and it offers significant performance gains over the conventional method, especially in the high-rate regime, with little attendant increase in computational complexity.
TRANSIENT RESPONSE OF A DISTRIBUTED RLC INTERCONNECT BASED ON DIRECT POLE EXTRACTION (2009)

With higher operating frequencies, transmission lines are required to model global on-chip interconnects. In this paper, an accurate and efficient solution for the transient response at the far end of a transmission line based on a direct pole extraction of the system is proposed. Closed form expressions of the poles are developed for two special interconnect systems: an RC interconnect and an RLC interconnect with zero driver resistance. By performing a system conversion, the poles of an interconnect system with general circuit parameters are solved. The Newton–Raphson method is used to further improve the accuracy of the poles. Based on these poles, closed form expressions for the step and ramp response are determined. Higher accuracy can be obtained with additional pairs of poles. The computational complexity of the model is proportional to the number of pole pairs. With two pairs of poles, the average error of the 50% delay is 1% as compared with Spectre simulations. With ten pairs of poles, the average error of the 10%-to-90% rise time and the overshoots is 2% and 1.9%, respectively. Frequency dependent effects are also successfully included in the proposed method and excellent match is observed between the proposed model and Spectre simulations.
Discovery of a dual-action small molecule that improves neuropathological features of Alzheimer’s disease mice (2022)

Alzheimer's disease (AD) is characterized by complex, multifactorial neuropathology, suggesting that small molecules targeting multiple neuropathological factors are likely required to successfully impact clinical progression. Acid sphingomyelinase (ASM) activation has been recognized as an important contributor to these neuropathological features in AD, leading to the concept of using ASM inhibitors for the treatment of this disorder. Here we report the identification of KARI 201, a direct ASM inhibitor evaluated for AD treatment. KARI 201 exhibits highly selective inhibition effects on ASM, with excellent pharmacokinetic properties, especially with regard to brain distribution. Unexpectedly, we found another role of KARI 201 as a ghrelin receptor agonist, which also has therapeutic potential for AD treatment. This dual role of KARI 201 in neurons efficiently rescued neuropathological features in AD mice, including amyloid beta deposition, autophagy dysfunction, neuroinflammation, synaptic loss, and decreased hippocampal neurogenesis and synaptic plasticity, leading to an improvement in memory function. Our data highlight the possibility of potential clinical application of KARI 201 as an innovative and multifaceted drug for AD treatment.
<title>Generalized pipeline for preview and rendering of synthetic holograms</title> (1997)

We describe a general pipeline for the computation and display of either fully-computed holograms or holographic stereograms using the same 3D database. A rendering previewer on a Silicon Graphics Onyx allows a user to specify viewing geometry, database transformations, and scene lighting. The previewer then generates one of two descriptions of the object--a series of perspective views or a polygonal model--which is then used by a fringe rendering engine to compute fringes specific to hologram type. The images are viewed on the second generation MIT Holographic Video System. This allows a viewer to compare holographic stereograms with fully-computed holograms originating from the same database and comes closer to the goal of a single pipeline being able to display the same data in different formats.