gebhart/patrepeval huggingface dataset:
Potent, Broad-Spectrum Inhibition of Human Immunodeficiency Virus Type 1 by the CCR5 Monoclonal Antibody PRO 140 (2001)

CCR5 serves as a requisite fusion coreceptor for clinically relevant strains of human immunodeficiency virus type 1 (HIV-1) and provides a promising target for antiviral therapy. However, no study to date has examined whether monoclonal antibodies, small molecules, or other nonchemokine agents possess broad-spectrum activity against the major genetic subtypes of HIV-1. PRO 140 (PA14) is an anti-CCR5 monoclonal antibody that potently inhibits HIV-1 entry at concentrations that do not affect CCR5's chemokine receptor activity. In this study, PRO 140 was tested against a panel of primary HIV-1 isolates selected for their genotypic and geographic diversity. In quantitative assays of viral infectivity, PRO 140 was compared with RANTES, a natural CCR5 ligand that can inhibit HIV-1 entry by receptor downregulation as well as receptor blockade. Despite their divergent mechanisms of action and binding epitopes on CCR5, low nanomolar concentrations of both PRO 140 and RANTES inhibited infection of primary peripheral blood mononuclear cells (PBMC) by all CCR5-using (R5) viruses tested. This is consistent with there being a highly restricted pattern of CCR5 usage by R5 viruses. In addition, a panel of 25 subtype C South African R5 viruses were broadly inhibited by PRO 140, RANTES, and TAK-779, although approximately 30-fold-higher concentrations of the last compound were required. Interestingly, significant inhibition of a dualtropic subtype C virus was also observed. Whereas PRO 140 potently inhibited HIV-1 replication in both PBMC and primary macrophages, RANTES exhibited limited antiviral activity in macrophage cultures. Thus CCR5-targeting agents such as PRO 140 can demonstrate potent and genetic-subtype-independent anti-HIV-1 activity.
Clinical activity of pertuzumab (rhuMab 2C4) in advanced, refractory or recurrent ovarian cancer (OC), and the role of HER2 activation status (2005)

5051 Background: Pertuzumab (P), a humanized HER2 antibody, represents a new class of targeted agents called HER dimerization inhibitors (HDIs) that inhibit dimerization of HER2 with EGFR, HER3 and HER4, and inhibit signaling through MAP and PI3 kinases. A phase I trial has demonstrated safety and activity in several tumors including ovarian cancer (OC). Interim data from a phase II trial with P in OC is presented. Methods: 65 pts with relapsed OC were enrolled with 61 receiving therapy with P. P was administered intravenously with a loading of 840mg followed by 420mg every 3 weeks. Tumor assessments were obtained after 2, 4, 6, 8, 12 and 16 cycles. Response rate (RR) by RECIST was the primary endpoint. Fresh tumor biopsies were mandatory in order to assay for HER2 phosphorylation (pHER2) status. Results: Median age was 59 years (range 35–78) and median ECOG PS was 1 (range 0–3). The median number of prior chemotherapy regimens was 5. 60 pts were evaluable for response. There were 2 objective partial responses (PRs) (RR=3%) and 24 (40%) of pts had stable disease (SD) per RECIST. CA125 RR of >50% reduction was 12%. 11 pts (15%) had SD for >18 weeks (range 18–36 weeks), with 4 pts >32 weeks. Of the 65 tumor biopsies, 31 were evaluable and 8 (26%) were positive for pHER2 by ELISA. Overall median time to progression (TTP) was 6.6 weeks (n=54); TTP for pHER2+ pts was 20.9 weeks (n=8), compared to 5.7 weeks for pHER2- (n=20), and 9.4 weeks for unknown pHER2 status (n=26). P was well tolerated with diarrhea in 57% of pts (grade 1–3). 1 pt had a drop in ejection fraction to < 50% (45%). Conclusions: As a single agent P is well tolerated. Clinical activity was demonstrated by PR’s and CA125 responses in 15%, and SD for > 4 months in 18% of pts with heavily pretreated OC. This study suggests P may be active in OC. Preliminary analysis suggests pHER2 status may be important for P activity. An update on this trial, as well as a 2nd cohort of pts treated with 1050mg single agent P will be reported. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech, Inc. for accrual patient costs only, Genentech
MeshGit: Diffing and Merging Polygonal Meshes (2012)

original derivative derivative a merged original derivative b Figure 1: Example of diffing and merging polygonal meshes done automatically by MeshGit. We determine mesh differences by computing the minimal set of operations needed to change one mesh into another. Left: Visual difference of two versions of a model in a series. We visualize mesh differences by showing the models side-by-side. On the original, we highlight in red faces that are either deleted or have changed. On the derivative, we highlight in green faces that have been added or have changed, and color face vertices in blue if they have moved. Right: MeshGit can automatically merge edits from different derivatives or detect if edits are conflicting. Here we visualize a three-way diff between two derivates and an original, and the merged mesh. Darker and lighter colors indicate from which derivative edits come. This paper presents MeshGit, a practical algorithm for diffing and merging polygonal meshes. Inspired by version control for text editing, we introduce the mesh edit distance as a measure of the dissimilarity between meshes. This distance is defined as the min-imum cost of matching the vertices and faces of one mesh to those of another. We propose an iterative greedy algorithm to approxi-mate the mesh edit distance, which scales well with model com-plexity, providing a practical solution to our problem. We translate the mesh correspondence into a set of mesh editing operations that transforms the first mesh into the second. The editing operations can be displayed directly to provide a meaningful visual difference between meshes. For merging, we compute the difference between two versions and their common ancestor, as sets of editing opera-tions. We robustly detect conflicting operations, automatically ap-ply non-conflicting edits, and allow the user to choose how to merge the conflicting edits. We evaluate MeshGit by diffing and merging a variety of meshes and find it to work well for all. 1
Three‐dimensional spiral MR imaging: Application to renal multiphase contrast‐enhanced angiography (2002)

A fast MR pulse sequence with spiral in-plane readout and conventional 3D partition encoding was developed for multiphase contrast-enhanced magnetic resonance angiography (CE-MRA) of the renal vasculature. Compared to a standard multiphase 3D CE-MRA with FLASH readout, an isotropic in-plane spatial resolution of 1.4 x 1.4 mm(2) over 2.0 x 1.4 mm(2) could be achieved with a temporal resolution of 6 sec. The theoretical gain of spatial resolution by using the spiral pulse sequence and the performance in the presence of turbulent flow was evaluated in phantom measurements. Multiphase 3D CE-MRA of the renal arteries was performed in five healthy volunteers using both techniques. A deblurring technique was used to correct the spiral raw data. Thereby, the off-resonance frequencies were determined by minimizing the imaginary part of the data in image space. The chosen correction algorithm was able to reduce image blurring substantially in all MRA phases. The image quality of the spiral CE-MRA pulse sequence was comparable to that of the FLASH CE-MRA with increased spatial resolution and a 25% reduced contrast-to-noise ratio. Additionally, artifacts specific to spiral MRI could be observed which had no impact on the assessment of the renal arteries.
Nucleosides. 114. 5'-O-Glucuronides of 5-fluorouridine and 5-fluorocytidine. Masked precursors of anticancer nucleosides (1981)

5'-O-Glucuronides of anticancer nucleosides, 5-fluorouridine and 5-fluorocytidine, were synthesized by three different methods. The best preparative procedure was the one starting from benzyl 5-O-(methyl 2', 3', 4'-tri-O-acetyl-beta-D-glucopyranosyluronate)-2,3-O-isopropylidene-beta-D-ribof uranoside (15) that was obtained almost quantitatively by condensation of benzyl 2,3-O-isopropylidene-beta-D-ribofuranoside (8) with methyl (2,3,4-tri-O-acetyl-alpha-D-glucopyranosyl bromide)uronate (2). After de-O-isopropylidenation of 15, the crystalline product, benzyl 5-O-(methyl 2', 3', 4'-tri-O-acetyl-beta-D-glucopyranosyluronate)-beta-D-ribofuranoside (16), was de-O-benzylated catalytically to 5-O-(methyl 2', 3', 4'-tri-O-acetyl-beta-glucopyranosyluronate)-D-ribofuranose (17). Compound 17 was acetylated to crystalline 5-O-(methyl 2',3',4'-tri-O-acteyl-beta-D-glucopyranosyluronate)-1,2,3-tri-O-acetyl-beta-D-ribofuranose (18) and condensed with trimethylsilylated 5-fluorouracil of 5-fluorocytosine in the presence of SnCl4 to afford the corresponding protected nucleosides 5 and 19 in good yields. Saponification of these compounds gave 5'-O-beta-D-glucuronides of 5-fluorouridine and 5-fluorocytidine (20 and 21) isolated as their crystalline N salts. These glucuronides were substrates of both bacterial and bovine beta-glucuronidase. They were, as expected, much less toxic against several leukemia cell lines in tissue culture.
The immunohistological demonstration of carcinoembryonic antigen in intra‐epithelial and invasive squamous carcinoma of the cervix (1983)

Using the sensitive peroxidase, anti-peroxidase immunohistological technique, carcinoembryonic antigen (CEA) was studied in formalin-fixed, paraffin-embedded cervical specimens from 225 patients. CEA was demonstrated in 33% of moderate dysplasia, 78.5% of severe dysplasia, 79% of in-situ carcinoma and 78% of invasive carcinoma. CEA was not demonstrated in normal squamous epithelium, squamous metaplasia, reserve cell hyperplasia nor in mild dysplasia.
Developmental changes in distribution of death-associated protein kinase mRNAs (1999)

Death-associated protein kinase (DAP-kinase) is Ca(2+)/calmodulin-dependent serine/threonine kinase that contains ankyrin repeats and the death domain. It has been isolated as a positive mediator of interferon-gamma-induced apoptotic cell death of HeLa cells. In order to reveal the physiological role of DAP-kinase, the tissue distribution and developmental changes in mRNA expression of DAP-kinase were investigated by Northern blot and in situ hybridization analyses. DAP-kinase mRNA was predominantly expressed in brain and lung. In brain, DAP-kinase mRNA had already appeared at embryonic day 13 (E13) and was, thereafter, detected throughout the entire embryonic period. High levels of expression were detected in proliferative and postmitotic regions within cerebral cortex, hippocampus, and cerebellar Purkinje cells. These findings suggest that DAP-kinase may play an important role in neurogenesis where a physiological type of cell death takes place. The overall expression of DAP-kinase mRNA in the brain gradually declined at postnatal stages, and the expression became restricted to hippocampus, in which different expression patterns were observed among rostral, central, and caudal coronal sections, suggesting that DAP-kinase may be implicated in some neuronal functions. Furthermore, it was found that the expression of DAP-kinase mRNA was increased prior to a certain cell death induced by transient forebrain ischemia, indicating a possible relationship between DAP-kinase and neuronal cell death.
Reactivities of serotyping monoclonal antibodies with culture-adapted human rotaviruses (1991)

Rotaviruses collected in Bangladesh during 1985 to 1986 were culture adapted and used in a comparative serotyping study with three groups of monoclonal antibodies, all of which reacted with the major neutralization protein (VP7) of serotype 1, 2, 3, or 4. The goals were to determine which monoclonal antibodies most accurately predicted the serotype and why large variations in serotyping efficiencies have occurred with these monoclonal antibodies in previous studies. The 143 rotavirus isolates used in this study belonged to 69 different electropherotypes; and 44, 23, 21, and 55 isolates were identified as serotype 1 through 4, respectively, by neutralization with serotype-specific hyperimmune antisera. Serotyping specificity by enzyme-linked immunosorbent assay with monoclonal antibodies was 100% consistent with results found by neutralization with polyclonal antisera, but large differences were observed in the sensitivities of the different monoclonal antibodies. Monoclonal antibodies 5E8 (serotype 1), 1C10 (serotype 2), 159 (serotype 3), RV3:1 (serotype 3), ST-3:1 (serotype 4), and ST-2G7 (serotype 4) reacted with all the isolates of the corresponding serotype for which there were sufficient infectious particles. Monoclonal antibody 2F1 (serotype 2) was much less sensitive and reacted with only five serotype 2 isolates, but these were among those with the highest titers. Monoclonal antibodies RV4:2 (serotype 1), KU6BG (serotype 1), RV5:3 (serotype 2), and S2-2G10 (serotype 2), on the other hand, failed to react with between one and three isolates of the corresponding serotypes which had high titers, apparently because of epitope changes in these isolates. Effects of epitope variation were, however, most apparent with monoclonal antibodies 2C9 (serotype 1) and YO-1E2 (serotype 3), which reacted with one and no isolates of the corresponding serotypes, respectively. Cross-neutralization of escape mutants indicated that the serotype 1 monoclonal antibodies 5E8, 2C9, and RV4:2 reacted with different but probably overlapping epitopes, as did serotype 2 monoclonal antibodies 2F1, 1C10, and RV5:3, finding that were consistent with the enzyme-linked immunosorbent assay data. Because of epitope variations between rotavirus strains, serotyping with several monoclonal antibodies directed at different epitopes may increase the sensitivity of the method.
Is Genetic Vaccination against Allergy Possible? (2006)

Genetic immunization has proven a powerful method to induce antiallergic immune responses. The underlying functional principle has been described to be based on the recruitment of allergen-specific Th1 cells, CD8+ cells and the establishment of a Th1 cytokine milieu, which prevent the development of a Th2-biased response in a protective setup and can balance an ongoing Th2-type response in a therapeutic situation. Genetic immunization with plasmid DNA offers innovative solutions to the major problems associated with protein immunization, such as crosslinking of pre-existing immunoglobulin E on mast cells/basophils or induction of de novo synthesis of immunoglobulin E by the protein immunization itself. It easily enables the routine production of hypoallergenic vaccines, which do not translate native allergens, thus avoiding potential anaphylactic side effects. DNA vaccines can also be applied as mixtures of single vaccines, making them interesting candidates for treatment based on component-resolved diagnosis, followed by an individualized therapy with the relevant allergens. In addition to the description of up-to-date allergen gene vaccine approaches, this review gives an overview of animal studies dealing with the following topics: danger signals as the inherent adjuvant properties, methods to optimize the vaccine immunogenicity, modulation of the immune response, nonparenteral applications and low-dose vaccination strategies.
Techniques for the analysis of protein-protein interactions in vivo (2016)

Identifying key players and their interactions is fundamental for understanding biochemical mechanisms at the molecular level. The ever-increasing number of alternative ways to detect protein-protein interactions (PPIs) speaks volumes about the creativity of scientists in hunting for the optimal technique. PPIs derived from single experiments or high-throughput screens enable the decoding of binary interactions, the building of large-scale interaction maps of single organisms, and the establishment of cross-species networks. This review provides a historical view of the development of PPI technology over the past three decades, particularly focusing on in vivo PPI techniques that are inexpensive to perform and/or easy to implement in a state-of-the-art molecular biology laboratory. Special emphasis is given to their feasibility and application for plant biology as well as recent improvements or additions to these established techniques. The biology behind each method and its advantages and disadvantages are discussed in detail, as are the design, execution, and evaluation of PPI analysis. We also aim to raise awareness about the technological considerations and the inherent flaws of these methods, which may have an impact on the biological interpretation of PPIs. Ultimately, we hope this review serves as a useful reference when choosing the most suitable PPI technique.
Managing DICOM images: Tips and tricks for the radiologist (2012)

All modalities in radiology practice have become digital, and therefore deal with DICOM images. Image files that are compliant with part 10 of the DICOM standard are generally referred to as "DICOM format files" or simply "DICOM files" and are represented as ".dcm." DICOM differs from other image formats in that it groups information into data sets. A DICOM file consists of a header and image data sets packed into a single file. The information within the header is organized as a constant and standardized series of tags. By extracting data from these tags one can access important information regarding the patient demographics, study parameters, etc. In the interest of patient confidentiality, all information that can be used to identify the patient should be removed before DICOM images are transmitted over a network for educational or other purposes. In addition to the DICOM format, the radiologist routinely encounters images of several file formats such as JPEG, TIFF, GIF, and PNG. Each format has its own unique advantages and disadvantages, which must be taken into consideration when images are archived, used in teaching files, or submitted for publication. Knowledge about these formats and their attributes, such as image resolution, image compression, and image metadata, helps the radiologist in optimizing the archival, organization, and display of images. This article aims to increase the awareness among radiologists regarding DICOM and other image file formats encountered in clinical practice. It also suggests several tips and tricks that can be used by the radiologist so that the digital potential of these images can be fully utilized for maximization of workflow in the radiology practice.
The Impact of Recanalization on Ischemic Stroke Outcome (2007)

Formal meta-analysis confirms a strong correlation between recanalization and outcome in acute ischemic stroke. Recanalization is strongly associated with improved functional outcomes and reduced mortality. These findings suggest that recanalization is an appropriate biomarker of therapeutic activity in early phase trials of thrombolytic treatment in acute ischemic stroke.
Effect of Ta getter on the quality of MgO tunnel barrier in the polycrystalline CoFeB∕MgO∕CoFeB magnetic tunnel junction (2007)

X-ray photoelectron spectroscopy and high-resolution Rutherford backscattering reveal that Ta getter presputtering enhances the stoichiometry and lowers the interstitial defect density of MgO barrier. This results in higher magnetoresistance ratio, 205%, of magnetic tunnel junction, compared to 46% for no Ta getter, at 1.2nm MgO thickness. Fitting yields the corresponding barrier height of the MgO of 3.0eV, which is higher compared to 2.3eV for without Ta getter. However, the tunnel junction prepared with Ta getter shows lower resistance-area product by an order of magnitude. Microstructure of MgO barrier and oxidation of bottom electrode can be attributed to the contradictory results.
Pancreatic lipase hydrolysis of triglycerides by a semimicro technique (1964)

Abstract Procedures are described for rapid lipase hydrolysis of triglycerides, isolation of the hydrolytic products by TLC and their conversion to methyl esters and fatty acid analysis by GLC. The techniques are applicable to a few mg of triglycerides or fats. Examples of data obtained with purified triglycerides indicate that the specific action of pancreatic lipase for the 1,3 ester groups is nearly absolute and the technique may be used as a criterion of purity of di‐ and tri‐acid triglycerides. Ca. 83% of the palmitic but only 10~12% of stearic and C 18 unsaturated acids of commercial lard occur in 2‐position.
Synthesis by AGET ATRP of Degradable Nanogel Precursors for In Situ Formation of Nanostructured Hyaluronic Acid Hydrogel (2009)

A nanostructured hyaluronic acid (HA) hydrogel was prepared by a combination of atom transfer radical polymerization (ATRP) and Michael-type addition reaction. Biodegradable POEO(300)MA-co-PHEMA nanogels with pendent hydroxy groups were prepared by activators generated by electron transfer ATRP in cyclohexane inverse miniemulsion in the presence of a hydrolytically labile cross-linker. The hydroxy groups were subsequently modified with acryloyl chloride to form reactive acrylated-nanogels (ACRL-nanogels). These nanogels degrade upon hydrolysis into polymeric sols enabling controlled release of entrapped fluorescently labeled biomolecules, such as rhodamine B isothiocyanate-dextran used as a drug model. Thiol-derivatized HA (HA-SH) was prepared by carbodiimide-mediated coupling reaction of HA with cysteamine hydrochloride. The nanostructured hydrogel was formed by mixing HA-SH with ACRL-nanogels under physiological conditions (pH = 7.4, 37 degrees C). Gelation occurred within a few minutes after mixing the precursor liquid solution via a Michael-type addition reaction between unsaturated acrylated moieties and nucleophilic thiols, leading to a chemically cross-linked network. Formation of the nanostructured HA hydrogel was visually observed with digital images after gelation and hydration. The gel was analyzed by scanning electron microscopy for morphological observation. Surface morphology demonstrates that the nanostructured gel was well-constructed with a porous three-dimensional structure and uniform distribution of nanogels. This novel biodegradable scaffold hybridized with nanogels offers the advantage of selective, fast, in situ polymerization and potential as an injectable biocompatible matrix for cell and protein encapsulation in both tissue engineering and drug delivery applications.
Compliant Control of Multicontact and Center-of-Mass Behaviors in Humanoid Robots (2010)

This paper presents a new methodology for the analysis and control of internal forces and center-of-mass (CoM) behavior, which are produced during multicontact interactions between humanoid robots and the environment. The approach leverages the virtual-linkage model that provides a physical representation of the internal and CoM resultant forces with respect to reaction forces on the supporting surfaces. A grasp/contact matrix describing the complex interactions between contact forces and CoM behavior is developed. Based on this model, a new torque-based approach for the control of internal forces is suggested and illustrated on the Asimo humanoid robot. The new controller is integrated into the framework for whole-body-prioritized multitasking, thus enabling the unified control of CoM maneuvers, operational tasks, and internal-force behavior. The grasp/contact matrix is also proposed to analyze and plan internal force and CoM control policies that comply with frictional properties of the links in contact.
Gene transfer into vascular cells using adeno-associated virus (AAV) vectors (1997)

AAV vectors can efficiently transduce rat VSMC in vitro. AAV-mediated ex vivo gene transfer into the normal aorta resulted in efficient gene transfer into endothelial and adventitial cells but not into medial VSMC. These findings suggest that AAV-based vectors are promising for use in cardiovascular gene therapy.
RNase P: Variations and Uses (2002)

This essay will bring to date a picture of the properties of RNase P from several organisms and a summary of how this enzyme can be used to decrease specific gene expression. Current details of how the enzyme works and other features governing its reaction are reviewed elsewhere (1-3).