gebhart/patrepeval huggingface dataset:
Mechanistically distinct cancer-associated mTOR activation clusters predict sensitivity to rapamycin (2016)

Genomic studies have linked mTORC1 pathway-activating mutations with exceptional response to treatment with allosteric inhibitors of mTORC1 called rapalogs. Rapalogs are approved for selected cancer types, including kidney and breast cancers. Here, we used sequencing data from 22 human kidney cancer cases to identify the activating mechanisms conferred by mTOR mutations observed in human cancers and advance precision therapeutics. mTOR mutations that clustered in focal adhesion kinase targeting domain (FAT) and kinase domains enhanced mTORC1 kinase activity, decreased nutrient reliance, and increased cell size. We identified 3 distinct mechanisms of hyperactivation, including reduced binding to DEP domain-containing MTOR-interacting protein (DEPTOR), resistance to regulatory associated protein of mTOR-mediated (RAPTOR-mediated) suppression, and altered kinase kinetics. Of the 28 mTOR double mutants, activating mutations could be divided into 6 complementation groups, resulting in synergistic Rag- and Ras homolog enriched in brain-independent (RHEB-independent) mTORC1 activation. mTOR mutants were resistant to DNA damage-inducible transcript 1-mediated (REDD1-mediated) inhibition, confirming that activating mutations can bypass the negative feedback pathway formed between HIF1 and mTORC1 in the absence of von Hippel-Lindau (VHL) tumor suppressor expression. Moreover, VHL-deficient cells that expressed activating mTOR mutants grew tumors that were sensitive to rapamycin treatment. These data may explain the high incidence of mTOR mutations observed in clear cell kidney cancer, where VHL loss and HIF activation is pathognomonic. Our study provides mechanistic and therapeutic insights concerning mTOR mutations in human diseases.
Artificial palate for use in dynamic palatographical speech researches and improvements and methods of fabricating the same (1984)

First Page
Eculizumab, a terminal complement inhibitor, improves anaemia in patients with paroxysmal nocturnal haemoglobinuria (2008)

In paroxysmal nocturnal haemoglobinuria (PNH), chronic destruction of PNH red blood cells (RBCs) by complement leads to anaemia and other serious morbidities. Eculizumab inhibits terminal complement-mediated PNH RBC destruction by targeting C5. In the phase III, double-blind, placebo-controlled, TRIUMPH study, eculizumab reduced haemolysis, stabilized haemoglobin levels, reduced transfusion requirements and improved fatigue in patients with PNH. Herein, we explored the effects of eculizumab on measures of anaemia in patients from the TRIUMPH study and the open-label SHEPHERD study, a more heterogeneous population. Eculizumab reduced haemolysis regardless of pretreatment transfusion requirements and regardless of whether or not patients became transfusion-dependent during treatment (P < 0.001). Reduction in haemolysis was associated with increased PNH RBC counts (P < 0.001) while reticulocyte counts remained elevated. Eculizumab-treated patients demonstrated significantly higher levels of haemoglobin as compared with placebo in TRIUMPH and relative to baseline levels in SHEPHERD (P < 0.001 for each study). Eculizumab lowered transfusion requirement across multiple pretreatment transfusion strata and eliminated transfusion support in a majority of both TRIUMPH and SHEPHERD patients (P < 0.001). Patients who required some transfusion support during treatment with eculizumab showed a reduction in haemolysis and transfusion requirements and an improvement in fatigue. Eculizumab reduces haemolysis and improves anaemia and fatigue, regardless of transfusion requirements.
Dehydration of sorbitol to isosorbide over H-beta zeolites with high Si/Al ratios (2015)

H-beta zeolite with a Si/Al ratio of 75 uniquely shows high catalytic activity for the dehydration of sorbitol, giving a 76% yield of isosorbide at 400 K over 2 h.
Short-Term MPEG-4 AVC Bandwidth Prediction for Broadband Cable Networks (2008)

In this paper, we propose and evaluate the accuracy of a new traffic model that predicts, in the short term, the size of the B-frames of MPEG-4 AVC compressed video. To quantify the prediction accuracy, a model for the prediction error is also proposed. In a broadband cable network, the prediction model can be employed by a cable headend to provision video bandwidth efficiently or more importantly, reduce bit rate variability and bandwidth requirements via selective B-frame dropping, thereby minimizing buffering requirements and packet losses at the set top box. It will be shown that the model provides highly accurate prediction for a wide variety of video types, in particular, high action and regular movies encoded in high quality resolution. This is an important benefit since high motion MPEG videos demand the highest bandwidth and generate the widest range of bit rate requirements. Although the prediction model is very simple to implement, this paper also proposes two methods to simplify its operation further without sacrificing prediction accuracy.
Self‐Healing Supramolecular Polymers In Action (2011)

Abstract Sophisticated polymeric materials with “responsive” properties, such as self‐healing, are beginning to reach the market. Supramolecular polymers, i.e., polymers that owe their mechanical properties primarily to the reversible, non‐covalent interactions, such as hydrogen bonding interactions, between the macromolecules, have frequently been employed as self‐healing materials. The quadruple hydrogen bonding ureidopyrimidinone (UPy) unit is a particularly effective and versatile design motif, since it forms very strong but reversible linkages, and can be incorporated into virtually any type of polymer backbone, leading to materials with increased mechanical properties. Supramolecular polymers are presented, with an emphasis on those based on the UPy‐unit, and their use in self‐healing applications is highlighted and discussed.
An integrated framework of vision-based vehicle detection with knowledge fusion (2005)

This paper describes an integrated framework of on-road vehicle detection through knowledge fusion. In contrast to appearance-based detectors that make instant decisions, the proposed detection framework fuses appearance, geometry and motion information over multiple image frames. The knowledge of vehicle/non-vehicle appearance, scene geometry and vehicle motion is utilized through prior models obtained by learning, modeling and estimation algorithms. It is shown that knowledge fusion largely improves the robustness and reliability of the detection system.
Electron beam-positive polyimides. Technical report (1989)

Polyimides from cyclobutane dianhydrides were prepared and shown to be sensitive to electron beams as well as to deep UV irradiation. Synthesis, thermal properties and sensitivity data are presented.
Mining and Visualizing Associations of Concepts on a Large-Scale Unstructured Data (2016)

We investigate the problem of finding unknown associations between 'concepts' in a given text corpus. A 'concept' is an entity, which is referred to by a phrase or multiple phrases (in case an entity has several names or synonyms, e.g. "illness", "disease"), while an 'association' is a relationship defined in a particular domain. The pairwise associations computation poses major challenges when the size of concepts to be investigated is large. In this paper, we propose a new framework for computing and visualizing the association between concepts using the generic association measures and the public knowledge available in data sources such as Wikipedia. Core to our methodology are the pruning techniques employed to filter the pairs of concepts which are very unlikely to be associated. Moreover, we study the performance of different correlation measures in finding both 'direct' and 'indirect' associations between concepts. The indirect association analysis extends the utility of the proposed framework to a broader class of association mining applications including the interesting area of new hypothesis generation. The extracted associations in our framework are demonstrated using the Neo4J graph database, which not only provides a user-friendly visualization interface for observing the associations between concepts in a big graph, but also supports more advanced analytics such as 'community detection', 'centrality analysis', and SQL-like querying of the concept graph. We evaluate the performance of our proposed methodology on two datasets, including a 'gene-disease' association dataset from the DisGeNET public database, and 'disease-symptom-treatment' associations extracted manually from the "MedicineNet.net" website. Our results show that the proposed association measure is capable of finding 80% of true gene-disease associations with a false positive rate of 15%.
CVD Synthesis of Graphene Nanomesh on Ge(001) (2022)

Bottom-up synthesis of functional graphene nanostructures on industry-compatible semiconductors such as Si and Ge is the key to unlocking the tremendous potential of graphene in electronic applications. Herein, we demonstrate the growth of graphene nanomesh on Ge using chemical vapor deposition – a technique used widely in the semiconductor industry. Graphene nanomesh is a promsing material in semiconductor electronics because of its ability to simultaneously achieve a large drive current and on/off ratio – one of the key challenges in graphene nanoribbon electronics[1]. However, in order to realize a nanomesh with desired and tunable electrical characteristics – an accurate control over the nanoribbon width, presence of atomically smooth edges, and nanoribbon placement is desired. In the literature, several techniques have been demonstrated to fabricate graphene nanomesh such as top-down lithography[2], bottom-up polymerization[3], and molecule-assisted CVD[4]; yet, a combination of accurate placement, tunable widths and atomically smooth edges has been challenging to achieve. We attempt to overcome this bottleneck by initiating CVD nanoribbon synthesis from deterministically placed arrays of graphene nanoseeds on Ge. We are able to tune the nanoribbon widths by changing the starting seed size and array pitch. The nanoribbons evolved from these nanoseeds fuse into each other when grown long enough – forming a nanomesh. These nanomeshes have atomically smooth edges and exhibit semiconducting characteristics. We also perform extensive simulations to identify the seed-sizes and pitches and demonstrate that this technique allows us to synthesize nanomeshes of desired architecture and electrical characteristics and thus can be used as channel materials in high performance / RF applications as well as BEOL interconnects. References Saraswat et al. ACS Nano , 15 ,3674-3708 (2021) Bai et al. Nature Nanotechnology , 5 , 190–194 (2010) Moreno et al. Science , 360 , 199-203 (2018) Kim et al. ACS Applied Materials & Interfaces , 13 , 28593-28599 (2021)
Anti-cancer efficacy including Rb-deficient tumors and VHL-independent HIF1α proteasomal destabilization by dual targeting of CDK1 or CDK4/6 and HSP90 (2021)

A prevalent characteristic of solid tumors is intra-tumoral hypoxia. Hypoxia-inducible factor 1α (HIF1α) predominantly mediates the adaptive response to O<sub>2</sub> oscillation and is linked to multiple malignant hallmarks. Here we describe a strategy to robustly target HIF1α by dual inhibition of CDK(s) and heat shock protein 90 (HSP90). We show that CDK1 may contribute to HSP90-mediated HIF1α stabilization. CDK1 knockdown enhances the decrease of HIF1α by HSP90 inhibition. Dual inhibition of CDK1 and HSP90 significantly increases apoptosis and synergistically inhibits cancer cell viability. Similarly, targeting CDK4/6 using FDA-approved inhibitors in combination with HSP90 inhibition shows a class effect on HIF1α inhibition and cancer cell viability suppression not only in colorectal but also in various other cancer types, including Rb-deficient cancer cells. Dual inhibition of CDK4/6 and HSP90 suppresses tumor growth in vivo. In summary, combined targeting of CDK(s) (CDK1 or CDK4/6) and HSP90 remarkably inhibits the expression level of HIF1α and shows promising anti-cancer efficacy with therapeutic potential.
Multi-carrier Differential Chaos Shift Keying Wireless Communication Based On Chaotic Shape-forming Filter (2019)

In recent years, chaotic communication has shown advantages, such as used the simplest matched filter to make signal-to-noise ratio (SNR) maximization and improve the resistance to multi-path interference. The chaotic shape-forming filter (CSF) has been proposed to generate the chaotic baseband signal in the wireless communication, the additional advantage of the chaotic shape-forming filter is able to generate the chaotic signal as spread sequence in Differential Chaotic Shift Key (DCSK), which encodes information in the sequence. In this paper, the chaotic signal generated by CSF is used in DCSK and combined with multi-carrier frequency to improve the bit transmission rate. Because of CSF used, it helps to improve both Bit Error Rate (BER) performance and provide an additional information flow in the spread sequence itself. Simulation results indicate that the proposed method is superior to other methods over the Addition White Gaussian Noise (AWGN) channel and wireless channel.
Signaling motifs in the IL-17 receptor (94.2) (2007)

Abstract IL-17 and its receptor IL-17RA have received much attention as the defining cytokine of a new class of T helper cells termed Th17. Mounting evidence suggests that IL-17 causes pathology in autoimmunity, but surprisingly little is known about mechanisms of IL-17 signal transduction. Although produced by T cells, IL-17 activates genes typical of innate immune cytokines such as TNFα and IL-1β, despite little sequence similarity in their respective receptors. A prior bioinformatics study predicted a subdomain in IL-17-family receptors with homology to a Toll/IL-1R (TIR) domain, termed “SEFIR.” However, the SEFIR domain lacks motifs critical for bona fide TIR domains, and its functionality has never been verified. Here, we used a reconstitution system in IL-17RA-null fibroblasts to map functional domains within IL-17RA. We demonstrate for the first time that the SEFIR domain mediates signaling, independently of TIR adaptors such as MyD88 and TRIF. Moreover, we identified a novel “TIR-like loop” (TILL) also required for activation of NF-κB, NF-κB-dependent genes and upregulation of C/EBPβ and C/EBPδ. We further identified a distinct domain required for activation of C/EBPβ and induction of a subset IL-17 target genes. This is the first structure-function analysis of any IL-17R superfamily receptor, and reveals unique structural and functional properties in IL-17 signaling.
Linearization of a harmonic radar transmitter by feed-forward filter reflection (2014)

In order to generate a detectable harmonic-radar response from an electronic device, the required power-on-target is comparable to that observed directly below a cellular base station. Also, the signal emitted from the target is often very weak. This weak signal must not be masked by harmonics generated by the radar itself. Thus, high transmit power must be provided with high linearity for detection of a nonlinear-radar target. In this paper, a technique is presented which achieves better than 135 dBc harmonic distortion at 7 W output power, at transmit frequencies between 800 MHz and 1 GHz.
Materials and design concepts for an intervertebral disc spacer. II. Multidurometer composite design (1995)

The main function of the intervertebral disc is to transmit and attenuate compressive and torsional forces, and stabilize the intervertebral joint. Unfortunately, the disc may be displaced or damaged due to trauma or disease causing the nucleus to herniate and protrude into the vertebral canal or intervertebral foramen. Pressure on the spinal nerve may cause pain or paralysis in the area of its distribution. At present, the surgical procedures used to alleviate this condition include disc excision, and/or spinal fusion. A more desirable situation would involve removing the nucleus pulposus and part or all of the annulus fibrosis and implanting a suitable biofunctional equivalent. Such a prosthesis should attenuate stresses and prevent abnormal stress at adjacent intervertebral joints. Maintenance of normal disc height would prevent impingement of the posterior facet joints and facet joint syndrome. In a previous companion paper (J. Applied Biomat. 5:125-132; 1994), the mechanical behavior of disc prostheses manufactured from fiber reinforced, elastomeric thermoset resins were examined. In order to develop devices which were more practical from a manufacturing standpoint and extremely reproducible, the fiber reinforced thermoset resins were replaced by multi-durometer thermoplastic elastomeric materials. In the present paper, the mechanical properties of thermoplastic multicomponent designs have been investigated.
Transcriptional activation of <i>Brassica napus</i> β‐ketoacyl‐ACP synthase II with an engineered zinc finger protein transcription factor (2012)

Targeted gene regulation via designed transcription factors has great potential for precise phenotypic modification and acceleration of novel crop trait development. Canola seed oil composition is dictated largely by the expression of genes encoding enzymes in the fatty acid biosynthetic pathway. In the present study, zinc finger proteins (ZFPs) were designed to bind DNA sequences common to two canola β-ketoacyl-ACP Synthase II (KASII) genes downstream of their transcription start site. Transcriptional activators (ZFP-TFs) were constructed by fusing these ZFP DNA-binding domains to the VP16 transcriptional activation domain. Following transformation using Agrobacterium, transgenic events expressing ZFP-TFs were generated and shown to have elevated KASII transcript levels in the leaves of transgenic T(0) plants when compared to 'selectable marker only' controls as well as of T(1) progeny plants when compared to null segregants. In addition, leaves of ZFP-TF-expressing T(1) plants contained statistically significant decreases in palmitic acid (consistent with increased KASII activity) and increased total C18. Similarly, T(2) seed displayed statistically significant decreases in palmitic acid, increased total C18 and reduced total saturated fatty acid contents. These results demonstrate that designed ZFP-TFs can be used to regulate the expression of endogenous genes to elicit specific phenotypic modifications of agronomically relevant traits in a crop species.
A novel active snubber for high-power boost converters (2000)

A technique which improves the performance of the boost converter by reducing the reverse-recovery-related losses in the boost switch and rectifier with an active snubber that is implemented with a minimum number of components is presented. This minimum-component-count snubber consists of a snubber inductor, an auxiliary switch, and a rectifier. The proposed technique reduces the reverse-recovery-related losses by controlling the turn-off di/dt rate of the rectifier current with the snubber inductor connected in series with the boost switch and rectifier. The voltage and current stresses of the components in the proposed active-snubber boost converter are similar to those in its conventional "hard-switched" counterpart.
Development of a hybrid alphavirus-SARS-CoV-2 pseudovirion for rapid quantification of neutralization antibodies and antiviral drugs (2022)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S)-pseudotyped viruses are commonly used for quantifying antiviral drugs and neutralizing antibodies. Here, we describe the development of a hybrid alphavirus-SARS-CoV-2 (Ha-CoV-2) pseudovirion, which is a non-replicating SARS-CoV-2 virus-like particle composed of viral structural proteins (S, M, N, and E) and an RNA genome derived from a fast-expressing alphaviral vector. We validated Ha-CoV-2 for rapid quantification of neutralization antibodies, antiviral drugs, and viral variants. In addition, as a proof of concept, we used Ha-CoV-2 to quantify the neutralizing antibodies from an infected and vaccinated individual and found that the one-dose vaccination with Moderna mRNA-1273 greatly increased the anti-serum titer by approximately 6-fold. The post-vaccination serum can neutralize all nine variants tested. These results demonstrate that Ha-CoV-2 can be used as a robust platform for the rapid quantification of neutralizing antibodies against SARS-CoV-2 and its emerging variants.
Engineering Yeast for Producing Human Glycoproteins: Where are We Now? (2015)

Yeast has advanced as an alternative for mammalian cell culture for the production of recombinant therapeutic glycoproteins. Engineered yeast strains not only allow to mimic the human N-glycosylation pathway but also specific types of human O-glycosylation. This is of great value for therapeutic protein production and indispensable to determine the structure-function relationships of glycans on recombinant proteins. However, as the technology matures, some limitations have come up that may hamper biomedical applications and must be considered to exploit the full potential of the unprecedented glycan homogeneity obtained on relevant biopharmaceuticals. In this special report, we focus on the recent developments in N- and O-glycosylation engineering in yeasts of industrial importance, to produce recombinant therapeutics with customized glycans.
Self-calibrated interferometric/intensity-based (SCIIB) optical fiber pressure sensor (1999)

A novel self-calibrated interferometer/industry-based (SCIIB) fiber optic sensor is described in this paper. The novel sensing scheme combines the advantages of both fiber interferometry senors and intensity-based sensors. The sensor operates on a single fiber Fabry-Perot interferometric cavity with a white light source. The interference signal of the sensor is coherent-sliced into two channels. Which allow fully real-time compensation for the source power drifting and fiber los variation. Temperature and pressure sensors with various dynamic ranges were designed and fabricated based on the SCIIB technology. Experimental result show that the SCIIB sensor scheme achieves excellent resolution and accuracy with the self- calibration function.
Two‐dimensional phase correction method for single and multi‐shot echo planar imaging (2011)

Ghost artifacts are a serious issue in single and multi-shot echo planar imaging. Because of these coherent artifacts, it is essential to consistently suppress the ghosts. In this article, we present a phase correction algorithm that achieves excellent ghost suppression for single and multi-shot echo planar imaging. The phase correction is performed along both the x (read) direction and y (phase) direction. To this end, we apply a double field of view prescan and compute the phase required for ghost suppression. This phase is fitted to a 2D polynomial. The fitted phase is used to correct the echo planar imaging images. The correction algorithm can be used with any readout gradient polarities and any number of shots. A flow chart of the correction method is provided to better clarify the full process. Finally, phantom and volunteer images demonstrate the improvement of artifact suppression obtained with this algorithm over conventional phase correction methods.
A Carbohydrate-Derived Splice Modulator (2016)

Small-molecule splice modulators have recently been recognized for their clinical potential for diverse cancers. This, combined with their use as tools to study the importance of splice-regulated events and their association with disease, continues to fuel the discovery of new splice modulators. One of the key challenges found in the current class of materials arises from their instability, where rapid metabolic degradation can lead to off-target responses. We now describe the preparation of bench-stable splice modulators by adapting carbohydrate motifs as a central scaffold to provide rapid access to potent splice modulators.