gebhart/patrepeval huggingface dataset:
Dynamics of Hepatitis B Virus Capsid Protein Dimer Regulate Assembly through an Allosteric Network (2020)

While there is an effective vaccine for Human Hepatitis B Virus (HBV), 257 million people have chronic infections for which there is no cure. The assembly process for the viral capsid is a potential therapeutic target. In order to understand the capsid assembly process, we investigated the dimeric building blocks of the capsid. To understand what blocks assembly, we took advantage of an assembly incompetent mutant dimer, Cp149-Y132A, located in the interdimer interface. This mutation leads to changes in protein dynamics throughout the structure of the dimer as measured by hydrogen-deuterium exchange mass spectrometry (HDX-MS). To further understand how the HBV capsid assembles, the homologue woodchuck HBV (WHV) capsid protein dimer (Cp) was used. WHV is more stable than HBV in HDX-MS and native mass spectrometry experiments. Because the WHV Cp assembles more rapidly into viral capsids than HBV, it was suspected that an increase in stability of the intradimer interface and/or in the contact region leads to increased assembly rates. The differences in dynamics when comparing HBV and human Cp149-Y132A as well as the differences in dynamics when comparing the HBV and WHV Cps allowed us to map an allosteric network within the HBV dimer. Through a careful comparison of structure, stability, and dynamics using four different capsid protein dimers, we conclude that protein subunit dynamics regulate HBV capsid assembly.
A phase I dose escalation trial of vaccine replicon particles (VRP) expressing prostate-specific membrane antigen (PSMA) in patients (pts) with castration-resistant prostate cancer (CRPC): Preliminary results. (2011)

140 Background: Prostate-specific membrane antigen (PSMA), a type II transmembrane protein overexpressed in prostate cells as they emerge into the androgen-independent state, remains a target to which vaccines with novel adjuvants or naked DNA has been directed. The PSMA-Viral Replicon Package (VRP) is a propagation-defective vector system from an attentuated strain of an alpha virus (VEE) encoding PSMA for use as a vaccine in prostate cancer. The PSMA gene is encoded by a subgenomic messenger RNA (mRNA), leading to high level expression of PSMA protein and presentation to the immune system.. We report preliminary results of a first in human trial using PSMA VRP to elicit immune responses targeting PSMA. Methods: Up to 18 pts with chemotherapy naïve CRPC metastatic to bone or soft tissue were permitted with 12 pts enrolled with ECOG status of 0 or 1. PSMA VRP was administered SC doses of either 0.9×10 7 IU or 0.36×10 8 IU for a total of 5 doses given on weeks 1, 4, 7, 10 and 18. Adverse events, PSA, circulating tumor cells, and clinical disease progression were assessed. Immune assessment was performed on patients' sera by ELISA and flow cytometry of serum binding to PSMA expressing tumor cells (3T3) and cellular (IFN-g EliSpot) components. Patients underwent imaging with bone and CAT scans every 3 months. Results: Three pts received 0.9×10 7 IU and 9 received 0.36×10 8 IU. Of these, 8 pts received all 5 vaccines. Four pts were taken off study for disease progression. One pt at the 0.36×10 8 continues on study and will be receiving his seventh vaccine. The demographic featuresof the 12 subjects enrolled were similar (mean age 69±11 yrs). No significant adverse events were noted; no aberrant laboratory abnormalities were associated with treatment. Weak humoral responses were observed in 1 patient in the 0.9×10 7 IU group and in 3 treated at 0.36×10 8 . Conclusions: In this first-in-man evaluation, vaccination with PSMA VRP appeared to be well-tolerated but does not appear to show impact on disease progression. Further studies are ongoing to assess immune responses and identify potential pathways for enhancement of the PSMA VRP approach. [Table: see text]
Public data multi-service interface interworking using ATM (balancing connectivity, efficiency and performance) (2002)

ATM is an emerging, high speed, flexible set of data communications protocols that are based upon a solidifying set of standards and specifications. Data networking is primarily the domain of large enterprises today, with typical networks having only a few locations that can justify the speeds of ATM, with connectivity required to many more locations that have lower speed requirements. Furthermore, many users will want to utilize existing, or less expensive equipment at the smaller locations. A technological answer to these seemingly divergent requirements is that of interworking between other lower speed public data service interfaces and ATM. This paper first details the above market and service requirements as motivation. As background a high-level overview of each of the major, emerging public data network services is then given. Next, an overview of several newly defined service interface interworking protocols is given. Finally, critical success factors for public data service interface interworking with ATM in order to support an economically viable evolution to ATM/BISDN are identified.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A green-light inducible lytic system for cyanobacterial cells (2014)

A green-light inducible lytic system was constructed in Synechocystis sp. PCC 6803. The engineered lytic cyanobacterial cells should be beneficial for the recovery of biofuels and related compounds from cells with minimal effort and energy, due to the fragile nature of the induced cells. Furthermore, the use of light-sensing two-component systems to regulate the expression of exogenous genes in cyanobacteria promises to replace conventional chemical inducers in many bioprocess applications, impacting the limiting water management issues.
FlowSense: A Natural Language Interface for Visual Data Exploration within a Dataflow System (2019)

Dataflow visualization systems enable flexible visual data exploration by allowing the user to construct a dataflow diagram that composes query and visualization modules to specify system functionality. However learning dataflow diagram usage presents overhead that often discourages the user. In this work we design FlowSense, a natural language interface for dataflow visualization systems that utilizes state-of-the-art natural language processing techniques to assist dataflow diagram construction. FlowSense employs a semantic parser with special utterance tagging and special utterance placeholders to generalize to different datasets and dataflow diagrams. It explicitly presents recognized dataset and diagram special utterances to the user for dataflow context awareness. With FlowSense the user can expand and adjust dataflow diagrams more conveniently via plain English. We apply FlowSense to the VisFlow subset-flow visualization system to enhance its usability. We evaluate FlowSense by one case study with domain experts on a real-world data analysis problem and a formal user study.
A 1-MHz-Bandwidth Continuous-Time Delta-Sigma ADC Achieving >90dB SFDR and >80dB Antialiasing Using Reference-Switched Resistive Feedback DACs (2023)

Continuous-time delta-sigma (CT DSM) ADCs offer implicit antialiasing and a resistive input impedance. This allows a dramatic relaxation of the ADC’s antialiasing filter requirement and a drastic simplification of its driver’s design. This has proved transformative in the particular case of integrated narrowband direct conversion receivers (RXs) where, following the mixer, a simple T1A with a firstorder roll-off is sufficient to drive the ADC (Fig. 1). The ADC, however, must be easy to integrate, have no signal transfer function (STF) peaking, and satisfy the stringent requirements of >90dB SFDR with >80dB antialiasing and an NSD <-150dBFS/Hz over lMHz bandwidth with low power dissipation. The resistive feedback DAC (RDAC) has been critical to achieving a low-NSD CT DSM with low power. However, reference-switched RDACs (Fig. 2) suffer from higher sensitivity to reference impedance [1]. The virtual-ground-switched RDAC[I] is less sensitive to this, but sampling of the virtual ground node by the RDAC switches severely degrades the ADC’s antialiasing; e.g., it is only 50dB in [1] [2]. Further, prior RDAC work relies on off-chip references [1] –[4], a major limitation for an ADC that is part of a production-level integrated RX due to associated overheads such as extra 1/O pins and need for external decoupling.
Assignment of Effective Network Chains in Cured Rubbers Derived from Chemical Crosslinking, Entanglements, Polymer End Linking to Carbon Black and Filler Interaction: VII. Tensile Retraction Measurements (2006)

Abstract The individual contributions to effective network chains from chemical cross-links and from trapped polymer chain entanglements were estimated for gum rubber compounds using Tensile Retraction (TR). In addition, the influences of carbon black and of polymers with functional end-groups, on the character of the polymer network in filled compounds were explored. The effective network chain contributions were established for gum vulcanizates through an entanglement model and an independent estimate of the polymer molecular weight between entanglements, M e . It was found that M e was related closely to the extrapolated γ intercepts obtained from the TR of cured gums. The gum compounds were used to further estimate the effects of fillers and functional end-groups on the total number of effective network chains. Comparing an α,ω-difunctional SBR with its non-functional counterpart enabled the assessment of the effects of functional end-groups. The comparison allowed for the determination of the probability, π, that a functional end group reacts with carbon black. The π was seen to increase as the volume fraction of filler increased, and π 2 provided an estimate of the fraction of functional polymer chains that react with carbon black at both ends.
Attosecond energy transfer dynamics in band-gap materials (Conference Presentation) (2018)

If the energy of a photon exceeds the band-gap of a material, an electron can be promoted from the valence into the conduction band with a probability described by the linear absorption coefficient. For photons with energies below the bandgap, the medium is transparent. However, even large band-gap materials that are transparent for visible light in the linear regime can become absorptive in the presence of strong electric fields either through multi-photon, or via tunneling transitions. To study the intricate dynamics of these excitation pathways we developed Attosecond Polarization Sampling (APS). This method resolves the light-matter energy transfer dynamics with attosecond temporal resolution and allows real-time recording of the evolution of both the linear and nonlinear polarization wave driven by the external electric field inside a material. In APS, the laser electric field E(t) is recorded after passage through the sample in two different settings: First, we attenuate the laser pulses before sending them through the material (here: 10 μm fused silica (SiO2)), ensuring only linear effects occur. In the second step, we use intensities close to the damage threshold of SiO2 so that both linear and non-linear interaction occurs. Comparison of the two electric fields yields slight differences in the instantaneous temporal phase of the pulse carrying information about the time evolution of the induced nonlinear polarization wave. The observed phase shifts record the field amplitude dependency of the nonlinear refractive index due to the Kerr-effect including its response time and can be directly related to the degree of light-field induced conduction band population. Consequently, these measurements, as shown in Fig. 1, allow to determine the amount of energy exchanged between light-field and sample with sub-optical-cycle time resolution. In the case of strong-field illumination of SiO2 we find that the nonlinear energy transfer has a strong reversible component occurring only during short time intervals around the field crests of the strong laser field and corresponding to the non-permanent transfer of electrons into conduction band-states. Build-up and immediate decay of this transient conduction band population are the result of a bi-directional energy transfer between field and matter and conform to the assumption of energy absorption from the field during the first half of the laser pulse and re-emission of energy into the same field within the duration of the few-cycle laser pulses. Most interestingly, we find settings where the transient energy exchange yields a significant modification of the optical and electronic material properties for femtosecond time intervals but no lasting energy transfer (i.e. residual conduction band population) is observable. This ultrafast, dissipation free switching of material properties might turn useful for a future all-optical, ultrafast and loss-free signal metrology.
DNA-PK triggers histone ubiquitination and signaling in response to DNA double-strand breaks produced during the repair of transcription-blocking topoisomerase I lesions (2015)

Although defective repair of DNA double-strand breaks (DSBs) leads to neurodegenerative diseases, the processes underlying their production and signaling in non-replicating cells are largely unknown. Stabilized topoisomerase I cleavage complexes (Top1cc) by natural compounds or common DNA alterations are transcription-blocking lesions whose repair depends primarily on Top1 proteolysis and excision by tyrosyl-DNA phosphodiesterase-1 (TDP1). We previously reported that stabilized Top1cc produce transcription-dependent DSBs that activate ATM in neurons. Here, we use camptothecin (CPT)-treated serum-starved quiescent cells to induce transcription-blocking Top1cc and show that those DSBs are generated during Top1cc repair from Top1 peptide-linked DNA single-strand breaks generated after Top1 proteolysis and before excision by TDP1. Following DSB induction, ATM activates DNA-PK whose inhibition suppresses H2AX and H2A ubiquitination and the later assembly of activated ATM into nuclear foci. Inhibition of DNA-PK also reduces Top1 ubiquitination and proteolysis as well as resumption of RNA synthesis suggesting that DSB signaling further enhances Top1cc repair. Finally, we show that co-transcriptional DSBs kill quiescent cells. Together, these new findings reveal that DSB production and signaling by transcription-blocking Top1 lesions impact on non-replicating cell fate and provide insights on the molecular pathogenesis of neurodegenerative diseases such as SCAN1 and AT syndromes, which are caused by TDP1 and ATM deficiency, respectively.
A history of Water distribution (2006)

This article discusses the advances in science and technology that made our modern water distribution systems possible. The article begins with a brief history of early distribution systems, and chronicles the transition to modern day distribution systems. The science of hydraulics, piping, pumps, fire protection, metering, storage tanks, water quality considerations, hydraulic analysis, and computer applications are all discussed.
Interplay among Subunit Identity, Subunit Proportion, Chain Length, and Stereochemistry in the Activity Profile of Sequence-Random Peptide Mixtures (2013)

Fmoc-based solid-phase synthesis methodology was used to prepare peptide mixtures containing one type of hydrophobic residue and one type of cationic residue. Each mixture was random in terms of sequence but highly controlled in terms of length. Analysis of the antibacterial and hemolytic properties of these mixtures revealed that selective antibacterial activity can be achieved with heterochiral binary mixtures but not homochiral binary mixture, if the proper amino acid residues are used.
The accessible chromatin landscape of the murine hippocampus at single-cell resolution (2019)

Here we present a comprehensive map of the accessible chromatin landscape of the mouse hippocampus at single-cell resolution. Substantial advances of this work include the optimization of a single-cell combinatorial indexing assay for transposase accessible chromatin (sci-ATAC-seq); a software suite, <i>scitools</i>, for the rapid processing and visualization of single-cell combinatorial indexing data sets; and a valuable resource of hippocampal regulatory networks at single-cell resolution. We used sci-ATAC-seq to produce 2346 high-quality single-cell chromatin accessibility maps with a mean unique read count per cell of 29,201 from both fresh and frozen hippocampi, observing little difference in accessibility patterns between the preparations. By using this data set, we identified eight distinct major clusters of cells representing both neuronal and nonneuronal cell types and characterized the driving regulatory factors and differentially accessible loci that define each cluster. Within pyramidal neurons, we identified four major clusters, including CA1 and CA3 neurons, and three additional subclusters. We then applied a recently described coaccessibility framework, Cicero, which identified 146,818 links between promoters and putative distal regulatory DNA. Identified coaccessibility networks showed cell-type specificity, shedding light on key dynamic loci that reconfigure to specify hippocampal cell lineages. Lastly, we performed an additional sci-ATAC-seq preparation from cultured hippocampal neurons (899 high-quality cells, 43,532 mean unique reads) that revealed substantial alterations in their epigenetic landscape compared with nuclei from hippocampal tissue. This data set and accompanying analysis tools provide a new resource that can guide subsequent studies of the hippocampus.
Identification of sources of low frequency variability of arterial blood pressure: Cardiac output acts as a buffer and not as a source (2010)

Arterial blood pressure (ABP) short term variability is due to beat-by-beat fluctuations in cardiac output (CO) and total peripheral resistance (TPR), which have distinct effects at low and high frequencies. In particular, it was shown that CO is able to buffer TPR slow oscillations in the LF band, but it has not been addressed if CO can contribute to oscillations of ABP in this band. In this paper, we propose a model for the identification of ABP variability sources, in order to show evidence that CO fluctuations are not a source of ABP LF oscillations, but they only buffer ABP variability of vasomotor origin.
Crowdsourcing for Robustness in Web Search. (2013)

Search systems are typically evaluated by averaging an effectiveness measure over a set of queries. However, this method does not capture the the robustness of the retrieval approach, as measured by its variability across queries. Robustness can be a critical retrieval property, especially in settings such as commercial search engines that must build user trust and maintain brand quality. This paper investigates two ways of integrating crowdsourcing into web search in order to increase robustness. First, we use crowd workers in query expansion; votes by crowd workers are used to determine candidate expansion terms that have broad coverage and high relatedness to query terms mitigating the risky nature of query expansion. Second, crowd workers are used to filter the top ranks of a ranked list in order to remove nonrelevant documents. We find that these methods increase robustness in search results. In addition, we discover that different evaluation measures lead to different optimal parameter settings when optimizing for robustness; precisionoriented metrics favor safer parameter settings while recalloriented metrics can handle riskier configurations that improve average performance.
Synthesis of Transportation Fuels from Biomass: Chemistry, Catalysts, and Engineering (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Test generation for fault isolation in analog circuits using behavioral models (2002)

Test generation techniques to isolate failures to different parts of an analog circuit, have relied on a list of failure modes being available for the circuit being tested. This may be difficult to obtain for general analog circuits. In this paper we propose a new methodology for isolation of parametric failures in analog circuits that (a) does not require a fully specified fault list, (b) is able to work with high-level behavioral descriptions of the various sub-modules of the CUT (c) is able to isolate faults caused by multiple parameter variations in the CUT and (d) is robust in the presence of measurement noise and manufacturing tolerances of analog components. Experimental results to demonstrate the effectiveness of the proposed technique are presented.
A multi-parametric particle-pairing algorithm for particle tracking in single and multiphase flows (2011)

Multiphase flows (MPFs) offer a rich area of fundamental study with many practical applications. Examples of such flows range from the ingestion of foreign particulates in gas turbines to transport of particles within the human body. Experimental investigation of MPFs, however, is challenging, and requires techniques that simultaneously resolve both the carrier and discrete phases present in the flowfield. This paper presents a new multi-parametric particle-pairing algorithm for particle tracking velocimetry (MP3-PTV) in MPFs. MP3-PTV improves upon previous particle tracking algorithms by employing a novel variable pair-matching algorithm which utilizes displacement preconditioning in combination with estimated particle size and intensity to more effectively and accurately match particle pairs between successive images. To improve the method's efficiency, a new particle identification and segmentation routine was also developed. Validation of the new method was initially performed on two artificial data sets: a traditional single-phase flow published by the Visualization Society of Japan (VSJ) and an in-house generated MPF data set having a bi-modal distribution of particles diameters. Metrics of the measurement yield, reliability and overall tracking efficiency were used for method comparison. On the VSJ data set, the newly presented segmentation routine delivered a twofold improvement in identifying particles when compared to other published methods. For the simulated MPF data set, measurement efficiency of the carrier phases improved from 9% to 41% for MP3-PTV as compared to a traditional hybrid PTV. When employed on experimental data of a gas–solid flow, the MP3-PTV effectively identified the two particle populations and reported a vector efficiency and velocity measurement error comparable to measurements for the single-phase flow images. Simultaneous measurement of the dispersed particle and the carrier flowfield velocities allowed for the calculation of instantaneous particle slip velocities, illustrating the algorithm's strength to robustly and accurately resolve polydispersed MPFs.
A Novel Antiprotozoal Aminosteroid from Saracha punctata (1998)

A new aminosteroid, 3beta-amino-22,26-epiminocholest-5-ene named sarachine (1), and two known flavonoids, eriodictyol (2) and 7-O-beta-D-glucopyranosyl-eriodictyol (3), were isolated from the leaves of Saracha punctata. The alkaloid was found to inhibit the growth of Leishmania braziliensis promastigotes (100% at 25 microM) and of Trypanosoma cruzi epimastigotes in culture (50% at 25 microM) and showed a strong in vitro antiplasmodial activity with an IC50 of 25 nM.
Alterations in adipocytokines and cGMP homeostasis in morbid obesity patients reverse after bariatric surgery (2013)

Altered cGMP homeostasis seems to contribute more than inflammation to changes in leptin and adiponectin in morbid obesity.