gebhart/patrepeval huggingface dataset:
Engineering and Structural Characterization of a Linear Polyubiquitin-Specific Antibody (2011)

Polyubiquitination is an essential posttranslational modification that plays critical roles in cellular signaling. PolyUb (polyubiquitin) chains are formed by linking the carboxyl-terminus of one Ub (ubiquitin) subunit to either a lysine residue or the amino-terminus of an adjacent Ub. Linkage through the amino-terminus results in linear polyubiquitination that has recently been demonstrated to be a key step in nuclear factor κB activation; however, tools to study linear chains have been lacking. We therefore engineered a linear-linkage-specific antibody that is functional in Western blot, immunoprecipitation, and immunofluorescence applications. A crystal structure of the linear-linkage-specific antibody Fab fragment in complex with linear diubiquitin provides molecular insight into the nature of linear chain specificity. We use the antibody to demonstrate that linear polyUb is up-regulated upon tumor necrosis factor α stimulation of cells, consistent with a critical role in nuclear factor κB signaling. This antibody provides an essential tool for further investigation of the function of linear chains.
Biomimetic Design of Affinity Peptide Ligand for Capsomere of Virus-Like Particle (2014)

Virus-like particle (VLP) of murine polyomavirus (MPV) is a T = 7d icosahedral capsid that self-assembles from 72 capsomeres (Caps), each of which is a pentamer of major coat protein VP1. VLP has great potential in vaccinology, gene therapy, drug delivery, and materials science. However, its application is hindered by high cost downstream processes, leading to an urgent demand of a highly efficient affinity ligand for the separation and purification of Cap by affinity chromatography. Herein a biomimetic design strategy of an affinity peptide ligand of Cap has been developed on the basis of the binding structure of the C-terminus of minor coat protein (VP2-C) on the inner surface of Cap. The molecular interactions between VP2-C and Cap were first examined using all-atom molecular dynamics (MD) simulations coupled with the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) method, where V283, P285, D286, W287, L289, and Y296 of VP2-C were identified as the hot spots. An affinity peptide library (DWXLXLXY, X denotes arbitrary amino acids except cysteine) was then constructed for virtual screening sequently by docking with AUTODOCK VINA, binding structure comparison, and final docking with ROSETTA FlexPepDock. Ten peptide candidates were selected and further confirmed by MD simulations and MM/PBSA, where DWDLRLLY was found to have the highest affinity to Cap. In DWDLRLLY, six residues are favorable for the binding, including W2, L4, L6 and Y8 inheriting from VP2-C, and R5 and L7 selected in the virtual screening. This confirms the high efficiency and accuracy of the biomimetic design strategy. DWDLRLLY was then experimentally validated by a one-step purification of Cap from crude cell lysate using affinity chromatography with the octapeptide immobilized on Sepharose gel. The purified Caps were observed to self-assemble into VLP with consistent structure of authentic MPV.
Automatic pre-tessellation culling (2009)

Graphics processing units supporting tessellation of curved surfaces with displacement mapping exist today. Still, to our knowledge, culling only occurs after tessellation, that is, after the base primitives have been tessellated into triangles. We introduce an algorithm for automatically computing tight positional and normal bounds on the fly for a base primitive. These bounds are derived from an arbitrary vertex shader program, which may include a curved surface evaluation and different types of displacements, for example. The obtained bounds are used for backface, view frustum, and occlusion culling before tessellation. For highly tessellated scenes, we show that up to 80% of the vertex shader instructions can be avoided, which implies an “instruction speedup” of 5×. Our technique can also be used for offline software rendering.
The Pink Bollworm (Lepidoptera: Gelechiidae): Alteration of Male Response to Gossyplure by Release of Its Component Z,Z- Isomer (1984)

Ratios (1:0, 9:1, 3:1, 1:1, 1:3, 1:9, and 0:1) of Z,Z- to Z,E- isomers of 7,11- hexadecadienyl acetate (7,11-16:Ac) were tested as trap baits for capture of male pink bollworm moths, Pectinophora gossypiella (Saunders), in fields treated with either Z,Z-7,11-16:Ac or gossyplure (1:1 ratio of Z,Z- to Z,E-7,11-16:Ac, the sex pheromone of the pink bollworm), or left untreated. Males were captured primarily in traps baited with gossyplure in gossyplure-treated fields (78%of total catch) and in untreated fields (66%of total catch). However, in fields treated with Z,Z-7,11-16:Ac, 69% of the males were captured in traps containing the 9:1 ratio and 3% in traps baited with gossyplure, an induced shift in the response of males. The observed shift in male response suggests the possibility of male annihilation using traps of insecticide-treated sources (9:1 ratio, for example) in fields treated with Z,Z-7,11-16:Ac. Unlike males in fields treated with gossyplure, males in fields treated with Z,Z-7,11-16:Ac are not responsive to sources emitting gossyplure. The induced shift in male response to isomer ratios is attributed to selective adaptation of Z,Z- receptor sites on the antennae of males leading to the perception of the 9:1 ratio as ca. 1:1.
ARAKNES haptic interface: user-centered design approach (2010)

Minimally Invasive Surgery (MIS) methods have revolutionized surgical care, considerably improving the results of many surgical procedures. Technological advances, in particular in robotic surgical systems, have reduced the complexity of this surgical method enhancing a surgeon's dexterity, precision and visualization. Despite all these advantages, the progress in this field is constrained by an unsolved issue: the introduction of MIS has eliminated the possibility of direct organ manipulation and palpation. Nowadays, the majority of the robotic surgical systems do not provide suitable haptic feedback integrating both kinaesthetic (force and position) and tactile information. Although, haptics is a very active field of research due to its potential application in robotic surgical systems, most of the commercially available devices provide only kinesthetic feedback. Within ARAKNES project, we are developing a bimanual haptic workstation to teleoperate surgical micro-robots located in the abdominal cavity of the patient. Our final goal is to develop a haptic interface that provides to the surgeon the kinesthetic and tactile feedback that he/she is missing because of the indirect manipulation of the distal organs. In this abstract, we described the user-centered design approach chosen for the compilation of both the functional and ergonomic specifications of the device. Two examples of design iteration are presented to illustrate the proposed.
Total Synthesis and Selective Activity of a New Class of Conformationally Restrained Epothilones (2007)

Stereoselective total syntheses of two novel conformationally restrained epothilone analogues are described. Evans asymmetric alkylation, Brown allylation, and a diastereoselective aldol reaction served as the key steps in the stereoselective synthesis of one of the two key fragments of the convergent synthetic approach. Enzyme resolution was employed to obtain the second fragment as a single enantiomer. The molecules were assembled by esterification, followed by ring-closing metathesis. In preliminary cytotoxicity studies, one of the analogues showed strong and selective growth inhibitory activity against two leukemia cell lines over solid human tumor cell lines. The precise biological mechanism of action and high degree of selectivity of this analogue remain to be examined.
Automated Quantitation of Hemoglobin-Based Blood Substitutes in Whole Blood Samples (2001)

It is necessary to develop methods for accurate monitoring of cell-free hemoglobin in circulation. Routine monitoring of circulating cell-free hemoglobin will be useful for evaluating the efficacy of blood substitute administration andfor determining the clearance rates of the blood substitute from circulation. In addition, discriminating between cell-free hemoglobin and cell-associated hemoglobin will enable accurate determination of RBC indices, mean cell hemoglobin and mean corpuscular hemoglobin concentration, in individuals receiving hemoglobin-based blood substitutes. As colorimetric methods used by hematology analyzers to quantitate the hemoglobin value of a blood sample cannot distinguish between cell-associated and cell-free hemoglobin, it is currently not feasible to quantitate the levels of hemoglobin substitutes in circulation. The advent of a technology that measures volume and hemoglobin concentration of individual RBCs provides an alternative strategy for quantitating the cell-associated hemoglobin in a blood sample. We document that the combined use of cell-based and colorimetric hemoglobin measurements provides accurate discrimination between cell-associated and cell-free hemoglobin over a wide range of hemoglobin levels. This strategy should enable rapid and accurate monitoring of the levels of cell-free hemoglobin substitutes in the circulation of recipients of these blood substitutes.
Discovering outlier filtering rules from unlabeled data (2001)

This paper is concerned with the problem of detecting outliers from unlabeled data. In prior work we have developed SmartSifter, which is an on-line outlier detection algorithm based on unsupervised learning from data. On the basis of SmartSifter this paper yields a new framework for outlier filtering using both supervised and unsupervised learning techniques iteratively in order to make the detection process more effective and more understandable. The outline of the framework is as follows: In the first round, for an initial dataset, we run SmartSifter to give each data a score, with a high score indicating a high possibility of being an outlier. Next, giving positive labels to a number of higher scored data and negative labels to a number of lower scored data, we create labeled examples. Then we construct an outlier filtering rule by supervised learning from them. Here the rule is generated based on the principle of minimizing extended stochastic complexity. In the second round, for a new dataset, we filter the data using the constructed rule, then among the filtered data, we run SmartSifter again to evaluate the data in order to update the filtering rule. Applying of our framework to the network intrusion detection, we demonstrate that 1) it can significantly improve the accuracy of SmartSifter, and 2) outlier filtering rules can help the user to discover a general pattern of an outlier group.
Framing Mobile Information Needs (2016)

When using search engines, people often issue multiple related queries to accomplish a complex search task. A simple query-task structure may not fully capture the complexity of query relations since people may divide a task into multiple subtasks. As a result, this paper applies a three-level hierarchical structure with query, goal and mission - a mission includes several goals, and a goal consists of multiple queries. Particularly, we focus on analyzing query-goal-mission structure for mobile web search because of its increasing popularity and lack of investigation in the literature. This study has three main contributions: (1) we study the query-goal-mission structure for mobile web search, which was not studied before. (2) We identify several differences between mobile and desktop search patterns in terms of goal/mission length, duration and interleaving. (3) We demonstrate that the query-goal-mission structure can be applied to design better user satisfaction metrics. Specifically, goal-based search success rate and mission-based abandonment rate are better aligned with users' long-term engagement than query and session based metrics.
Control Aspects of the Tacoma Superconducting Magnetic Energy Storage Project (1987)

On February 16, 1983, a 10 MW/30 MJ superconducting magnetic energy storage unit was energized at the Bonneville Power Administration (BPA) substation in Tacoma, Washington. The unit was retired a year later, after extensive tests directed toward its experimental use as a small-signal stabilizer for the Pacific AC Intertie. This paper addresses the control aspects of the project. These include the response characteristics of the unit, a-priori modeling of power system response, tradeoffs in control-law design, measured power system dynamics, and projection of unit effectiveness as a stabilizer.
Novel Methylated Biomarkers and a Robust Assay to Detect Circulating Tumor DNA in Metastatic Breast Cancer (2014)

The ability to consistently detect cell-free tumor-specific DNA in peripheral blood of patients with metastatic breast cancer provides the opportunity to detect changes in tumor burden and to monitor response to treatment. We developed cMethDNA, a quantitative multiplexed methylation-specific PCR assay for a panel of ten genes, consisting of novel and known breast cancer hypermethylated markers identified by mining our previously reported study of DNA methylation patterns in breast tissue (103 cancer, 21 normal on the Illumina HumanMethylation27 Beadchip) and then validating the 10-gene panel in The Cancer Genome Atlas project breast cancer methylome database. For cMethDNA, a fixed physiologic level (50 copies) of artificially constructed, standard nonhuman reference DNA specific for each gene is introduced in a constant volume of serum (300 μL) before purification of the DNA, facilitating a sensitive, specific, robust, and quantitative assay of tumor DNA, with broad dynamic range. Cancer-specific methylated DNA was detected in training (28 normal, 24 cancer) and test (27 normal, 33 cancer) sets of recurrent stage IV patient sera with a sensitivity of 91% and a specificity of 96% in the test set. In a pilot study, cMethDNA assay faithfully reflected patient response to chemotherapy (N = 29). A core methylation signature present in the primary breast cancer was retained in serum and metastatic tissues collected at autopsy two to 11 years after diagnosis of the disease. Together, our data suggest that the cMethDNA assay can detect advanced breast cancer, and monitor tumor burden and treatment response in women with metastatic breast cancer.
Experimental evaluation of regression model-based walking speed estimation using lower body-mounted IMU (2016)

This study provides a concurrent comparison of regression model-based walking speed estimation accuracy using lower body mounted inertial sensors. The comparison is based on different sets of variables, features, mounting locations and regression methods. An experimental evaluation was performed on 15 healthy subjects during free walking trials. Our results show better accuracy of Gaussian process regression compared to least square regression using Lasso. Among the variables, external acceleration tends to provide improved accuracy. By using both time-domain and frequency-domain features, waist and ankle-mounted sensors result in similar accuracies: 4.5% for the waist and 4.9% for the ankle. When using only frequency-domain features, estimation accuracy based on a waist-mounted sensor suffers more compared to the one from ankle.
NADA: A Unified Congestion Control Scheme for Real-Time Media (2019)

This document describes NADA (network-assisted dynamic adaptation), a
novel congestion control scheme for interactive real-time media
applications, such as video conferencing. In the proposed scheme, the
sender regulates its sending rate based on either implicit or explicit
congestion signaling, in a unified approach. The scheme can benefit
from explicit congestion notification (ECN) markings from network
nodes. It also maintains consistent sender behavior in the absence of
such markings, by reacting to queuing delays and packet losses
instead.
Intrinsic detection of motion in segmented sequences (2010)

While many motion correction techniques for MRI have been proposed, their use is often limited by increased patient preparation, decreased patient comfort, additional scan time, or the use of specialized sequences not available on many commercial scanners. For this reason, we propose a simple self-navigating technique designed to detect motion in segmented sequences. We demonstrate that comparing two segments containing adjacent sets of k-space lines results in an aliased error function. A global shift of the aliased error function indicates the presence of in-plane rigid-body translation, while other types of motion are evident in the dispersion or breadth of the error function. Since segmented sequences commonly acquire data in sets of adjacent k-space lines, this method provides these sequences with an inherent method of detecting object motion. Motion corrupted data can then be reacquired proactively or in some cases corrected or removed retrospectively.
P3‐314: Prevention of amyloid β‐peptide fibrillation by the BRICHOS domain (2011)

Amyloid diseases are associated with a specific form of protein misfolding, in which the protein aggregates into oligomers and fibrils of ß-sheet structure. More than 27 amyloid diseases are known today, and among them Alzheimer's disease (AD), which is a progressive neurodegenerative disorder. The senile plaques found in brain of AD patients contain amyloid fibrils formed by amyloid ß-peptide (Aß), mainly consisting of 40-42 residues. The BRICHOS domain contains ∼100 residues and is found in a diverse set of human membrane proteins associated with degenerative and proliferative disease, including lung fibrosis (surfactant protein C precursor; proSP-C) and familial dementia (Bri2). Bri2 is expressed in neurons, and mutations in the Bri2 gene are linked to familial British and Danish dementia. These mutations lead to extensions of the proprotein and generation of extended peptides (ABri or ADan) that form amyloid. 3D crystal structure determination and homology modeling. Aggregation kinetics were studied by recording the ThT fluorescence intensity as a function of time and circular dichroism measurements. The crystal structure of proSP-C-BRICHOS, determined at 2.0 Å, shows a homotrimer with a novel subunit fold composed of a five-stranded ß-sheet flanked by a-helices and loops. A homology model for Bri2-BRICHOS was built using the X-ray structure of proSP-C BRICHOS as a template. Mapping sequence differences between the two BRICHOS domains to the structure reveals a number of changes from hydrophobic residues in proSP-C BRICHOS to charged residues in Bri2-BRICHOS. We have found that the Brichos domains from both proSP-C and Bri2 prevent fibril formation of both Aß40 and Aß42, well below stoichiometric amounts and that the inhibition is concentration dependent. Kinetic experiments show a prolonged lag phase for Aß fibril formation in the presence of BRICHOS proteins and circular dichroism experiments imply that Aß40 is kept in a mainly unstructured state in the presence of BRICHOS. Our results suggest that BRICHOS binds oligomeric aggregates of Aß and destabilizes the oligomer, whereby unstructured monomers are released. We are presently investigating the anti-amyloidogenic potential of the BRICHOS domain in vivo, in a fly model of AD.
Isolation and expression of the Pneumocystis carinii thymidylate synthase gene. (1989)

The thymidylate synthase (TS) gene from Pneumocystis carinii has been isolated from complementary and genomic DNA libraries and expressed in Escherichia coli. The coding sequence of TS is 891 nucleotides, encoding a 297-amino acid protein of Mr 34,269. The deduced amino acid sequence is similar to TS from other organisms and is most closely related to the enzyme from Saccharomyces cerevisiae with 65% identity. TS is found on a 330-kilobase-pair chromosome in P. carinii. While TS and dihydrofolate reductase reside on a single polypeptide chain in all protozoa studied to date, TS is not linked to dihydrofolate reductase in P. carinii. The TS gene shows the presence of four small intervening sequences, some of which interrupt the coding sequence in highly ordered structural regions of the protein. Heterologous expression of P. carinii TS in E. coli was accomplished by cloning the coding sequence into plasmid vectors under control of the lac and tac promoters. These constructs direct the synthesis of catalytically active enzyme to the extent of 2% of total soluble protein.
TU‐D‐AUD C‐03: Liquid Scintillators for 2D Photon Dosimetry (2008)

Purpose: Liquid scintillators have the potential of providing real‐time dosimetric information in 2D and even possibly in 3D. The purpose of this work is to study the performance of a liquid scintillator (LS) detector system for photon beam dosimetry. Method and Materials: The detector system consisted of a lucite tank (7×7×16 cm 3 ), a camera objective and a cooled CCD type camera (Luca, Andor Technology, South Windsor, CT), which was shifted by 59 cm with respect to the center of the tank. The LS material BC‐531 (Saint‐Gobain, Newbury, OH) was used. The detector system was irradiated with 6‐MV photons on a Varian Clinac 21EX under standard conditions. Different field sizes, dose rates and camera light enhancement modes were measured and compared to the dose profiles of the treatment machine. Results: The light signal produced by the LS was slightly distorted by light scattering isotropically within the liquid and refraction at the tank interface. Taking into account this blurring we could reproduce the dose distribution. The LS material is nearly water equivalent. The detector system was also found to be dose rate independent. Using the electron magnification mode of the CCD camera we were also capable of measuring very low dose rates from an I‐125 seed. Conclusion: The present detector system is suitable for measuring 2D dose distributions under the conditions used in therapeutic photon treatments. Further investigations are underway to fully characterize this system to make it practical for routine clinical use. Supported by the NCI (1R01CA120198‐01A2).
Formation of Highly Dense Aligned Ribbons and Transparent Films of Single-Walled Carbon Nanotubes Directly from Carpets (2008)

Utilizing aligned carbon nanotube arrays grown from chemical vapor deposition, we present a highly scalable route toward the formation of ribbons and ultrathin transparent films directly from vertically aligned single-walled carbon nanotube arrays (SWNT carpets). To "lay-over" the aligned nanotubes to form a film, we use a roller which acts to compress the film and preserve the alignment of nanotubes within the film. As we demonstrate, we can control the nanotube-catalyst interaction, leading to highly efficient transfer of the film to virtually any host substrate by following growth with a controlled H(2)O vapor etch. In addition, we demonstrate our ability to grow carpets on patterned substrates leading to upright carpet lines, which can be rolled over to form transparent films composed of ultralong carbon nanotubes. This work demonstrates a highly scalable technique to form homogeneous, transparent films of aligned SWNTs that can be ultralong with absolutely no need for liquid phase SWNT processing.
Synthetic cephalosporins. VII. Synthesis and antibacterial activity of 7-((Z)-2-(2-aminothiazol-4-yl)-2-(3-(3-hydroxy-4-pyridon-1-yl)-3-carboxypropoxyimino)acetamido)-3-(1,2,3-thiadiazol-5-yl)-thiomethyl-3-cephem-4-carboxylic acid and its related compounds. (1990)

Synthesis and antibacterial activity of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(3-(3-hydroxy-4-pyridon-1-y l)-3- carboxypropoxyimino)acetamido]-3-(1,2,3-thiadiazol-5-yl)thio methyl-3-cephem-4-carboxylic acid (12a) and its related compounds are described. Compound 12a exhibited excellent antibacterial activity against gram-negative bacteria, including Pseudomonas aeruginosa.