gebhart/patrepeval huggingface dataset:
The HCF repeat is an unusual proteolytic cleavage signal. (1995)

The herpes simplex virus VP16-associated protein HCF is a nuclear host-cell factor that exists as a family of polypeptides encoded by a single gene. The mature HCF polypeptides are amino- and carboxy-terminal fragments of a large approximately 300-kD precursor protein that arise through cleavage at one or more centrally located sites. The sites of cleavage are the HCF repeats, highly conserved 26-amino-acid sequences repeated six times in the HCF precursor protein. The HCF repeat alone is sufficient to induce cleavage of a heterologous protein, and cleavage occurs at a defined site--PPCE/THET--within the HCF repeat. Alanine-scan mutagenesis was used to identify a large 18-amino-acid segment of the HCF repeat that is important to induce cleavage of a heterologous protein. Even though HCF is cleaved, the majority of amino- and carboxy-terminal cleavage products remain tightly, albeit noncovalently, associated. Modulation of this noncovalent association may provide a mechanism for regulating HCF activity. For example, the cleaved products of an alternative mRNA splicing variant of HCF do not remain associated.
Octreotide: a therapeutic option for idiopathic intracranial hypertension. (2007)

Octreotide resulted in a significant and sustained improvement of IIH in our patients. These results suggest that it may be an effective alternative to existing treatments for IIH.
Developing New Isotope-Coded Mass Spectrometry-Cleavable Cross-Linkers for Elucidating Protein Structures (2014)

Structural characterization of protein complexes is essential for the understanding of their function and regulation. However, it remains challenging due to limitations in existing tools. With recent technological improvements, cross-linking mass spectrometry (XL-MS) has become a powerful strategy to define protein-protein interactions and elucidate structural topologies of protein complexes. To further advance XL-MS studies, we present here the development of new isotope-coded MS-cleavable homobifunctional cross-linkers: d0- and d10-labeled dimethyl disuccinimidyl sulfoxide (DMDSSO). Detailed characterization of DMDSSO cross-linked peptides further demonstrates that sulfoxide-containing MS-cleavable cross-linkers offer robust and predictable MS2 fragmentation of cross-linked peptides, permitting subsequent MS3 analysis for simplified, unambiguous identification. Concurrent usage of these reagents provides a characteristic doublet pattern of DMDSSO cross-linked peptides, thus aiding in the confidence of cross-link identification by MS(n) analysis. More importantly, the unique isotopic profile permits quantitative analysis of cross-linked peptides and therefore expands the capability of XL-MS strategies to analyze both static and dynamic protein interactions. Together, our work has established a new XL-MS workflow for future studies toward the understanding of structural dynamics of protein complexes.
A Framework for IP Based Virtual Private Networks (2000)

This document describes a framework for Virtual Private Networks (VPNs) running across IP backbones. It discusses the various different types of VPNs, their respective requirements, and proposes specific mechanisms that could be used to implement each type of VPN using existing or proposed specifications. The objective of this document is to serve as a framework for related protocol development in order to develop the full set of specifications required for widespread deployment of interoperable VPN solutions.
Development and survival of neurons in dissociated fetal mesencephalic serum-free cell cultures: I. Effects of cell density and of an adult mammalian striatal-derived neuronotrophic factor (SDNF) (1988)

The use of CNS cultures for detection and quantification of neuronotrophic activity in the CNS has been analyzed. In particular the development, i.e., neurotransmitter uptake characteristics, and survival of dopaminergic and GABAergic neurons in fetal mouse (E13)-dissociated mesencephalic cells cultured in serum-free, hormone-supplemented medium have been assessed as a function of culture time and cell density. At all times, more than 98% of the cells were classified as neurons on the basis of immunocytochemical criteria. Results indicate that the increase of cell density in vitro significantly enhances specific high-affinity dopamine uptake per dopaminergic cell and cell survival. This effect is not limited to the dopaminergic cells and suggests that the development of neurotransmitter-related traits and cell survival are influenced by cell density-derived trophic signals. The above-mentioned cultures and parameters have also been used to detect neuronotrophic activity in adult mammalian brain extracts or more purified preparations. In particular, bovine striatal extracts contain activity capable of increasing high-affinity neurotransmitter uptake parameters and cell survival of at least the dopaminergic and GABAergic neurons present in the culture system. The neuronotrophic activity from bovine striatum has been partially purified and is associated with a fraction whose main component is a basic protein of approximately 14 kDa.
Curbing activation: proprotein convertases in homeostasis and pathology (2003)

The proprotein convertases (PCs) are a seven-member family of endoproteases that activate proproteins by cleavage at basic motifs. Expression patterns for individual PCs vary widely, and all cells express several members. The list of substrates activated by PCs has grown to include neuropeptides, peptide hormones, growth and differentiation factors, receptors, enzymes, adhesion molecules, blood coagulation factors, plasma proteins, viral coat proteins, and bacterial toxins. It has become clear that the PC family plays a crucial role in a variety of physiological processes and is involved in the pathology of diseases such as cancer, viral infection, and Alzheimer's disease. Recent studies using PC inhibitors have demonstrated their potential as therapeutic targets. Despite the avalanche of in vitro data, the physiological role of individual PCs has remained largely elusive. Recently, however, knockout mouse models have been developed for furin, PC1, PC2, PC4, PC6B, LPC, and PACE4, and human patients with PC1 deficiency have been identified. The phenotypes range from undetectable to early embryonic lethality. The major lesson learned from these studies is that specific PC-substrate pairs do exist, but that there is substantial redundancy for the majority of substrates. To some extent, redundancy may be cell type and even species dependent.
Joint-sparing or Physeal-sparing Diaphyseal Resections: The Challenge of Holding Small Fragments (2010)

Weak plates such as reconstruction plates are best avoided for these reconstructions. Custom plates allow secure fixation with technical ease. CDIs allow immediate weightbearing and ability to lengthen with predictable good functional short-term outcome.
Myeloid cells in tumor inflammation (2012)

Bone marrow derived myeloid cells progressively accumulate in tumors, where they establish an inflammatory microenvironment that is favorable for tumor growth and spread. These cells are comprised primarily of monocytic and granulocytic myeloid derived suppressor cells (MDSCs) or tumor-associated macrophages (TAMs), which are generally associated with a poor clinical outcome. MDSCs and TAMs promote tumor progression by stimulating immunosuppression, neovascularization, metastasis and resistance to anti-cancer therapy. Strategies to target the tumor-promoting functions of myeloid cells could provide substantial therapeutic benefit to cancer patients.
Adaptable N-gram classification model for data leakage prevention (2013)

Data confidentiality, integrity and availability are the ultimate goals for all information security mechanisms. However, most of these mechanisms do not proactively protect sensitive data; rather, they work under predefined policies and conditions to protect data in general. Few systems such as anomaly-based intrusion detection systems (IDS) might work independently without much administrative interference, but with no dedication to sensitivity of data. New mechanisms called data leakage prevention systems (DLP) have been developed to mitigate the risk of sensitive data leakage. Current DLPs mostly use data fingerprinting and exact and partial document matching to classify sensitive data. These approaches can have a serious limitation because they are susceptible to data misidentification. In this paper, we investigate the use of N-grams statistical analysis for data classification purposes. Our method is based on using N-grams frequency to classify documents under distinct categories. We are using simple taxicap geometry to compute the similarity between documents and existing categories. Moreover, we examine the effect of removing the most common words and connecting phrases on the overall classification. We are aiming to compensate the limitations in current data classification approaches used in the field of data leakage prevention. We show that our method is capable of correctly classifying up to 90.5% of the tested documents.
Correction: Ecological Drivers of Biogeographic Patterns of Soil Archaeal Community (2013)

Knowledge about the biogeography of organisms has long been a focus in ecological research, including the mechanisms that generate and maintain diversity. In this study, we targeted a microbial group relatively underrepresented in the microbial biogeographic literature, the soil Archaea. We surveyed the archaeal abundance and community composition using real-time quantitative PCR and T-RFLP approaches for 105 soil samples from 2 habitat types to identify the archaeal distribution patterns and factors driving these patterns. Results showed that the soil archaeal community was affected by spatial and environmental variables, and 79% and 51% of the community variation was explained in the non-flooded soil (NS) and flooded soil (FS) habitat, respectively, showing its possible biogeographic distribution. The diversity patterns of soil Archaea across the landscape were influenced by a combination of stochastic and deterministic processes. The contribution from neutral processes was higher than that from deterministic processes associated with environmental variables. The variables pH, sample depth and longitude played key roles in determining the archaeal distribution in the NS habitat, while sampling depth, longitude and NH 4 + -N were most important in the FS habitat. Overall, there might be similar ecological drivers in the soil archaeal community as in macroorganism communities.
On Time-Series Topological Data Analysis: New Data and Opportunities (2016)

This work introduces a new dataset and framework for the exploration of topological data analysis (TDA) techniques applied to time-series data. We examine the end-toend TDA processing pipeline for persistent homology applied to time-delay embeddings of time series – embeddings that capture the underlying system dynamics from which time series data is acquired. In particular, we consider stability with respect to time series length, the approximation accuracy of sparse filtration methods, and the discriminating ability of persistence diagrams as a feature for learning. We explore these properties across a wide range of time-series datasets spanning multiple domains for single source multi-segment signals as well as multi-source single segment signals. Our analysis and dataset captures the entire TDA processing pipeline and includes time-delay embeddings, persistence diagrams, topological distance measures, as well as kernels for similarity learning and classification tasks for a broad set of time-series data sources. We outline the TDA framework and rationale behind the dataset and provide insights into the role of TDA for time-series analysis as well as opportunities for new work.
Thalidomide — A Revival Story (1999)

One of the most devastating tragedies of modern medicine was set into motion by the over-the-counter marketing of thalidomide in Europe during the late 1950s for the treatment of morning sickness. The drug was withdrawn in the 1960s after the appearance of reports of teratogenicity and phocomelia associated with its use. The recent return of thalidomide stems from the broad spectrum of its pharmacologic and immunologic effects.1 Thalidomide has been approved by the Food and Drug Administration for the treatment of erythema nodosum leprosum, an inflammatory manifestation of leprosy,2 and potential therapeutic applications span a wide spectrum of other diseases. . . .
Sperm Transport and Motility in the Mouse Oviduct: Observations in Situ1 (1987)

Sperm transport and motility were studied through the transparent walls of the mouse oviduct by direct microscopic observation and videomicrography. Observations were made on excised female tracts 1-2 h post-coitus (pc) and 1-2 h before and after the approximate time of ovulation. Motile sperm were seen at the uterine entrance to the uterotubal junction (UTJ) in all females at 1-2 h pc, but in fewer females at later times. The intramural UTJ was usually constricted and held few sperm. The extramural UTJ and adjacent lower isthmus contained many motile sperm at 1-2 h pc. Apparently, the column of sperm moved upwards because in some females, sperm were found in the upper isthmus and not in the UTJ at the later time points. Few sperm were seen in the ampulla in the periovulatory period, and none at 1-2 h pc. There appeared to be two mechanisms retaining sperm in the lower oviduct: immobilization and adherence to the epithelium. Columns of immotile sperm were seen in the lower isthmus of some females. Motile sperm usually appeared to adhere by their heads to the oviductal epithelium, only occasionally breaking free to move vigorously about the lumen.
Characterization of a New Humanized Anti-CD20 Monoclonal Antibody, IMMU-106, and Its Use in Combination with the Humanized Anti-CD22 Antibody, Epratuzumab, for the Therapy of Non-Hodgkin’s Lymphoma (2004)

It is expected that in humans IMMU-106 should be at least as effective as rituximab and, due to its human framework construction, it may exhibit different pharmacokinetic, toxicity, and therapy profiles. In addition, it may be possible to enhance efficacy by combination therapy comprised of anti-CD20 and other B-cell lineage targeting MAbs, such as epratuzumab. The current results emphasize that in vitro as well as in vivo studies with many of the NHL cell lines were generally predictive of the known activity of anti-CD20 MAbs in NHL patients, as well as the enhanced efficacy of epratuzumab combined with rituximab observed in early clinical trials.
AIF and EndoG in noise-induced hearing loss. (2004)

Apoptosis plays a critical role in neuronal cell death, including sensory cell death in noise-induced hearing loss. The purpose of this study is to investigate the role of a caspase-independent apoptotic pathway, involving apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in cell death in the inner ear after intense noise exposure (120 dB SPL, 4 kHz OBN, 5 h). EndoG was translocated to the nucleus after noise trauma, whereas immunostaining for AIF was expressed only in the cytosol. These findings indicate that EndoG is a factor in noise-induced caspase-independent apoptosis. In contrast, AIF may not be involved in cell death, but act as a redox factor in response to noise-induced oxidant stress.
Two recombinant human monoclonal antibodies that protect against lethal Andes hantavirus infection in vivo (2018)

Andes hantavirus (ANDV) is an etiologic agent of hantavirus cardiopulmonary syndrome (HCPS), a severe disease characterized by fever, headache, and gastrointestinal symptoms that may progress to hypotension, pulmonary failure, and cardiac shock that results in a 25 to 40% case-fatality rate. Currently, there is no specific treatment or vaccine; however, several studies have shown that the generation of neutralizing antibody (Ab) responses strongly correlates with survival from HCPS in humans. In this study, we screened 27 ANDV convalescent HCPS patient sera for their capacity to bind and neutralize ANDV in vitro. One patient who showed high neutralizing titer was selected to isolate ANDV-glycoprotein (GP) Abs. ANDV-GP-specific memory B cells were single cell sorted, and recombinant immunoglobulin G antibodies were cloned and produced. Two monoclonal Abs (mAbs), JL16 and MIB22, potently recognized ANDV-GPs and neutralized ANDV. We examined the post-exposure efficacy of these two mAbs as a monotherapy or in combination therapy in a Syrian hamster model of ANDV-induced HCPS, and both mAbs protected 100% of animals from a lethal challenge dose. These data suggest that monotherapy with mAb JL16 or MIB22, or a cocktail of both, could be an effective post-exposure treatment for patients infected with ANDV-induced HCPS.
Comparison of Cell Cycle Arrest, Transactivation, and Apoptosis Induced by the Simian Immunodeficiency Virus SIVagm and Human Immunodeficiency Virus Type 1vprGenes (2001)

All primate lentiviruses known to date contain one or two open reading frames with homology to the human immunodeficiency virus type 1 (HIV-1) vpr gene. HIV-1 vpr encodes a 96-amino-acid protein with multiple functions in the viral life cycle. These functions include modulation of the viral replication kinetics, transactivation of the long terminal repeat, participation in the nuclear import of preintegration complexes, induction of G2 arrest, and induction of apoptosis. The simian immunodeficiency virus (SIV) that infects African green monkeys (SIVagm) contains a vpr homologue, which encodes a 118-amino-acid protein. SIVagm vpr is structurally and functionally related to HIV-1 vpr. The present study focuses on how three specific functions (transactivation, induction of G2 arrest, and induction of apoptosis) are related to one another at a functional level, for HIV-1 and SIVagm vpr. While our study supports previous reports demonstrating a causal relationship between induction of G2 arrest and transactivation for HIV-1 vpr, we demonstrate that the same is not true for SIVagm vpr. Transactivation by SIVagm vpr is independent of cell cycle perturbation. In addition, we show that induction of G2 arrest is necessary for the induction of apoptosis by HIV-1 vpr but that the induction of apoptosis by SIVagm vpr is cell cycle independent. Finally, while SIVagm vpr retains its transactivation function in human cells, it is unable to induce G2 arrest or apoptosis in such cells, suggesting that the cytopathic effects of SIVagm vpr are species specific. Taken together, our results suggest that while the multiple functions of vpr are conserved between HIV-1 and SIVagm, the mechanisms leading to the execution of such functions are divergent.
Single-cell gene-expression profiling reveals qualitatively distinct CD8 T cells elicited by different gene-based vaccines (2011)

CD8 T cells play a key role in mediating protective immunity against selected pathogens after vaccination. Understanding the mechanism of this protection is dependent upon definition of the heterogeneity and complexity of cellular immune responses generated by different vaccines. Here, we identify previously unrecognized subsets of CD8 T cells based upon analysis of gene-expression patterns within single cells and show that they are differentially induced by different vaccines. Three prime-boost vector combinations encoding HIV Env stimulated antigen-specific CD8 T-cell populations of similar magnitude, phenotype, and functionality. Remarkably, however, analysis of single-cell gene-expression profiles enabled discrimination of a majority of central memory (CM) and effector memory (EM) CD8 T cells elicited by the three vaccines. Subsets of T cells could be defined based on their expression of Eomes, Cxcr3, and Ccr7, or Klrk1, Klrg1, and Ccr5 in CM and EM cells, respectively. Of CM cells elicited by DNA prime-recombinant adenoviral (rAd) boost vectors, 67% were Eomes(-) Ccr7(+) Cxcr3(-), in contrast to only 7% and 2% stimulated by rAd5-rAd5 or rAd-LCMV, respectively. Of EM cells elicited by DNA-rAd, 74% were Klrk1(-) Klrg1(-)Ccr5(-) compared with only 26% and 20% for rAd5-rAd5 or rAd5-LCMV. Definition by single-cell gene profiling of specific CM and EM CD8 T-cell subsets that are differentially induced by different gene-based vaccines will facilitate the design and evaluation of vaccines, as well as enable our understanding of mechanisms of protective immunity.
A Member of the Dendritic Cell Family That Enters B Cell Follicles and Stimulates Primary Antibody Responses Identified by a Mannose Receptor Fusion Protein (1999)

Dendritic cells (DCs) are known to activate naive T cells to become effective helper cells. In addition, recent evidence suggests that DCs may influence naive B cells during the initial priming of antibody responses. In this study, using three-color confocal microscopy and three-dimensional immunohistograms, we have observed that in the first few days after a primary immunization, cells with dendritic morphology progressively localize within primary B cell follicles. These cells were identified by their ability to bind a fusion protein consisting of the terminal cysteine-rich portion of the mouse mannose receptor and the Fc portion of human immunoglobulin (Ig)G1 (CR-Fc). In situ, these CR-Fc binding cells express major histocompatibility complex class II, sialoadhesin, and CD11c and are negative for other markers identifying the myeloid DC lineage, such as (CD11b), macrophages (F4/80), follicular DCs (FDC-M2), B cells (B220), and T cells (CD4). Using CR-Fc binding capacity and flow cytometry, the cells were purified from the draining lymph nodes of mice 24 h after immunization. When injected into naive mice, these cells were able to prime T cells as well as induce production of antigen-specific IgM and IgG1. Furthermore, they produced significantly more of the lymphocyte chemoattractant, macrophage inflammatory protein (MIP)-1alpha, than isolated interdigitating cells. Taken together, these results provide evidence that a subset of DCs enters primary follicles, armed with the capacity to attract and provide antigenic stimulation for T and B lymphocytes.
The interplay between registered and unregistered domestic partnerships under the Draft Domestic Patnerships Bill, 2008, and the potential role of the (contextualised) putative marriage doctrine (2011)

In 2008 the South African legislature published a draft Domestic Partnerships Bill aimed at regulating the position of persons who live together outside of a legal marriage or civil union. The Bill makes provision for both registered and unregistered domestic partnerships. While the former involves a formal registration procedure, the latter allows either partner to an unregistered partnership that satisfies certain threshold criteria to 'opt-in' to the protection provided by the Bill by approaching a competent court, after the termination of the union, for certain relief. This article considers the salient features of, and interplay between, the partnership options under the Bill with a view to ascertaining whether the common law putative marriage doctrine is capable of being extended in order to assist partners who are of the bona fide belief that their partnerships will be recognised and protected under the Bill, while this is in reality not the case. The conclusion is reached that while the doctrine may in principle be extended to invalid 'registered' domestic partnerships, a refusal to extend the doctrine to 'unregistered' domestic partnerships will pass constitutional muster. This notwithstanding, the doctrine as currently applied in the context of the law of marriage is in need of being developed in order to cater for polygamous civil 'marriages', and this has important implications for applying the doctrine to domestic partnerships. The article also concludes that the Bill itself requires certain amendments, and that the applicability of the putative marriage doctrine depends on whether or not these amendments are made.