gebhart/patrepeval huggingface dataset:
Immune Ablation with Stem-Cell Rescue: A Possible Cure for Systemic Lupus Erythematosus? (1993)

The impressive prolongation of survival has been the most important progress made in clinical systemic lupus erythematosus (SLE). Quality of life has also greatly improved, including pregnancy. However, persisting disease and therapy-related morbidity outcomes justify new approaches, different from the usual long-term palliative immunosuppression. Haematopoietic stem cells (HSCs) from healthy histocompatible mice are capable of curing murine SLE after eradication of the original HSCs with total body irradiation. Syngeneic and even autologous HSCs are also capable of curing induced experimental autoimmune diseases such as adjuvant arthritis and experimental allergic encephalomyelitis. In man allogeneic bone-marrow transplantation (BMT) is becoming progressively safer, but cannot yet be offered to SLE patients. However, syngeneic transplants from twins non-concordant for the disease would be justified. Conditioning with high-dose cyclophosphamide followed by autologous HSC rescue, from the marrow and/or from the peripheral blood, may already be regarded as a powerful immunosuppressive procedure for selected cases of SLE and other severe autoimmune diseases. Autologous transplant procedures are not saddled with the immunologic problems of allo-BMT. Although eradication of SLE may not be achieved by auto-BMT, minimal residual immunologic disease can be suppressed or controlled, and long-term self-maintained remissions may be expected.
AspEm: Embedding Learning by Aspects in Heterogeneous Information Networks (2018)

Heterogeneous information networks (HINs) are ubiquitous in real-world applications. Due to the heterogeneity in HINs, the typed edges may not fully align with each other. In order to capture the semantic subtlety, we propose the concept of aspects with each aspect being a unit representing one underlying semantic facet. Meanwhile, network embedding has emerged as a powerful method for learning network representation, where the learned embedding can be used as features in various downstream applications. Therefore, we are motivated to propose a novel embedding learning framework---AspEm---to preserve the semantic information in HINs based on multiple aspects. Instead of preserving information of the network in one semantic space, AspEm encapsulates information regarding each aspect individually. In order to select aspects for embedding purpose, we further devise a solution for AspEm based on dataset-wide statistics. To corroborate the efficacy of AspEm, we conducted experiments on two real-words datasets with two types of applications---classification and link prediction. Experiment results demonstrate that AspEm can outperform baseline network embedding learning methods by considering multiple aspects, where the aspects can be selected from the given HIN in an unsupervised manner.
Endocytic pathway from the basal plasma membrane to the ruffled border membrane in bone-resorbing osteoclasts (1997)

We have characterized the convoluted ruffled border (RB) membrane that an activated osteoclast maintains against the bone matrix. The bulk of both lgp110 and rab7, a small GTP-binding protein participating in vesicle fusion to late endosomes, was localized to the RB. This indicates that the membrane has some characteristics of late endosomal membranes in other cells. Furthermore, the bulk of membrane-bound rab7 on the RB suggests that endocytic membrane transport is oriented towards the RB in resorbing osteoclasts. Consistently, both lumenal horseradish peroxidase and receptor-bound transferrin, a marker of the early endosomal recycling pathway, were efficiently endocytosed from the basal plasma membrane and delivered to the RB. Delivery of membrane-associated transferrin to the RB further indicates that the RB is compositionally different from lysosomes and suggests that the endocytic pathway contributes to the maintenance of functional RB. In addition to transporting receptor-bound cargo to the RB, the endocytic pathway could act in balancing the membrane traffic associated with transcytosis from the RB to the basal plasma membrane. Endocytic processes (retrieval of mannose 6-phosphate receptors) in osteoclasts appeared to be fairly sensitive to bafilomycin A1, a specific inhibitor of vacuolar-type proton ATPases. Thus blocking the endocytic membrane traffic towards the RB could explain the inactivation of cells by low concentrations of the drug.
Diels–Alder Reaction for Tumor Pretargeting: In Vivo Chemistry Can Boost Tumor Radiation Dose Compared with Directly Labeled Antibody (2013)

The in vivo performance of chemical pretargeting falls within the range of results obtained for the clinically validated pretargeting approaches in mice, with the advantage of potentially allowing for fractionated radiotherapy as a result of a lower likelihood of immunogenicity. These findings demonstrate that biologic pretargeting concepts can be translated to rapid bioorthogonal chemical approaches with retained potential.
Synthesis, Characterization and Pharmacodynamics of Vitamin‐B12‐Conjugated Glucagon‐Like Peptide‐1 (2012)

Clearing the way: Glucagon-like peptide-1 (GLP-1) receptor agonists are proving a potent weapon in the treatment of type II diabetes. A new vitamin B(12)-GLP-1 conjugate is investigated and shown to have insulinotropic properties similar to the unmodified peptide. These results are critical to the exploitation of the vitamin B(12) oral uptake pathway for peptide delivery.
DNA polymerase beta can substitute for DNA polymerase I in the initiation of plasmid DNA replication (1995)

We previously demonstrated that mammalian DNA polymerase beta can substitute for DNA polymerase I of Escherichia coli in DNA replication and in base excision repair. We have now obtained genetic evidence suggesting that DNA polymerase beta can substitute for E. coli DNA polymerase I in the initiation of replication of a plasmid containing a pMB1 origin of DNA replication. Specifically, we demonstrate that a plasmid with a pMB1 origin of replication can be maintained in an E. coli polA mutant in the presence of mammalian DNA polymerase beta. Our results suggest that mammalian DNA polymerase beta can substitute for E. coli DNA polymerase I by initiating DNA replication of this plasmid from the 3' OH terminus of the RNA-DNA hybrid at the origin of replication.
PPARG Genotype Accounts for Part of Individual Variation in Body Weight Reduction in Response to Calorie Restriction (2009)

Several studies indicate that expression of the peroxisome proliferator-activated receptor gamma (PPARG) gene is influenced by calorie restriction. The aim of this study was to investigate whether PPARG gene variations are associated with weight reduction and changes in coronary heart disease (CHD) risk factors in response to a 14-week calorie restriction. In total, 95 middle-aged, Japanese women (BMI>or=25 kg/m2) enrolled as subjects for 14 weeks and attended weekly dietary lectures instructing them on how to consume a nutritionally balanced diet of 1,200 kcal/day. Eight single-nucleotide polymorphisms (SNPs) in the PPARG gene (rs1801282 (Pro/Ala), rs2292101, rs2959272, rs1386835, rs709158, rs1175540, rs1175544, and rs1797912) were analyzed. Body weight decreased significantly (-7.7+/-3.1 kg; -11.3+/-4.4%) during the intervention. Six PPARG SNPs (rs2959272, rs1386835, rs709158, rs1175540, rs1175544, and rs1797912) were significantly associated with the weight reduction, with rs1175544 having the strongest association (P=0.004). No differences across the rs1175544 genotypes were observed in any of the blood analyses or in blood pressure. In a multiple regression analysis, the rs1175544 genotypes accounted for 7% of the total weight reduction variance. These data suggest that one SNP of the PPARG genotype accounted for a significant portion of the total body weight reduction variance in response to a short-term intervention consisting of calorie restriction; however, no relationship was found between these SNPs and the changes in CHD risk factors which accompanied weight loss.
Analysis of Network Processing Workloads (2005)

Network processing is becoming an increasingly important paradigm as the Internet moves towards an architecture with more complex functionality inside the network. Modern routers not only forward packets, but also process headers and payloads to implement a variety of functions related to security, performance, and customization. It is important to get a detailed understanding of the workloads associated with this processing in order to be able to develop efficient network processing engines. We present a tool called PacketBench, which provides a framework for implementing network processing applications and obtaining an extensive set of workload characteristics. PacketBench provides the support functions to handle various packet traces and manage packet memory. For statistics collection, PacketBench provides the ability to derive a number of microarchitectural and networking related metrics. The understanding of workload details of network processing has many practical applications. As network processing systems move towards highly parallel embedded systems, it is becoming increasingly important to explore the processing requirements of individual packets rather than averaged statistics. We show a range of workload results that focus on individual packets and the variation between them
Construction of an Infectious Rhesus Rhadinovirus Bacterial Artificial Chromosome for the Analysis of Kaposi's Sarcoma-Associated Herpesvirus-Related Disease Development (2007)

Rhesus rhadinovirus (RRV) is closely related to Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) and causes KSHV-like diseases in immunocompromised rhesus macaques (RM) that resemble KSHV-associated diseases including multicentric Castleman's disease and non-Hodgkin's lymphoma. RRV retains a majority of open reading frames (ORFs) postulated to be involved in the pathogenesis of KSHV and is the closest available animal model to KSHV infection in humans. Here we describe the generation of a recombinant clone of RRV strain 17577 (RRV(17577)) utilizing bacterial artificial chromosome (BAC) technology. Characterization of the RRV BAC demonstrated that it is a pathogenic molecular clone of RRV(17577), producing virus that behaves like wild-type RRV both in vitro and in vivo. Specifically, BAC-derived RRV displays wild-type growth properties in vitro and readily infects simian immunodeficiency virus-infected RM, inducing B cell hyperplasia, persistent lymphadenopathy, and persistent infection in these animals. This RRV BAC will allow for rapid genetic manipulation of the RRV genome, facilitating the creation of recombinant versions of RRV that harbor specific alterations and/or deletions of viral ORFs. This system will provide insights into the roles of specific RRV genes in various aspects of the viral life cycle and the RRV-associated pathogenesis in vivo in an RM model of infection. Furthermore, the generation of chimeric versions of RRV containing KSHV genes will allow analysis of the function and contributions of KSHV genes to viral pathogenesis by using a relevant primate model system.
Physical and chemical methods for enhancing rapid detection of viruses and other agents (1993)

Viral replication events can be enhanced by physical, chemical, or heat treatment of cells. The centrifugation of cells can stimulate them to proliferate, reduce their generation times, and activate gene expression. Human endothelial cells can be activated to release cyclo-oxygenase metabolites after rocking for 5 min, and mechanical stress can stimulate endothelial cells to proliferate. Centrifugation of virus-infected cultures can increase cytopathic effects (CPE), enhance the number of infected cells, increase viral yields, and reduce viral detection times and may increase viral isolation rates. The rolling of virus-infected cells also has an effect similar to that of centrifugation. The continuous rolling of virus-infected cultures at < or = 2.0 rpm can enhance enterovirus, rhinovirus, reovirus, rotavirus, paramyxovirus, herpesvirus, and vaccinia virus CPE or yields or both. For some viruses, the continuous rolling of infected cell cultures at 96 rpm (1.9 x g) is superior to rolling at 2.0 rpm for viral replication or CPE production. In addition to centrifugation and rolling, the treatment of cells with chemicals or heat can also enhance viral yields or CPE. For example, the treatment of virus-infected cells with dimethyl sulfoxide can enhance viral transformation, increase plaque numbers and plaque size, increase the number of cells producing antigens, and increase viral yields. The infectivity of fowl plague virus is increased by 80-fold when 4% dimethyl sulfoxide is added to culture medium immediately after infection. The heat shocking of virus-infected cells also has been shown to have a stimulatory effect on the replication events of cytomegalovirus, Epstein-Barr virus, and human immunodeficiency virus. The effects of motion, chemicals, or heat treatments on viral replication are not well understood. These treatments apparently activate cells to make them more permissive to viral infection and viral replication. Perhaps heat shock proteins or stress proteins are a common factor for this enhancement phenomenon. The utility of these treatments alone or in combination with other methods for enhancing viral isolation and replication in a diagnostic setting needs further investigation.
Effect of Hypotonic 0.4% Hyaluronic Acid Drops in Dry Eye Patients: A Cross-Over Study (2008)

By reducing the osmolarity of tear film, the hypotonic solution not only improves the characteristics of tear film and the vitality of the epithelial cells of the cornea and conjunctiva but also proves to be effective in reducing dry eye symptoms.
Peak-to-average power ratio reduction of an OFDM signal by signal set expansion (2004)

A major drawback of orthogonal frequency division multiplexing (OFDM) is the high peak-to-average power ratio (PAPR) of the transmitted signal. In this paper, we propose a novel technique to reduce PAPR in an OFDM signal. Proposed technique is based on signal set expansion. Each point in the original signal set is associated with two or more points in the expanded signal set. Each symbol in an OFDM data block is mapped into a point among associated points in the expanded signal set so as to achieve PAPR reduction. The proposed technique is very simple and does not require any side information to be transmitted from the transmitter to the receiver.
Evidence for an additional ligand, distinct from B7, for the CTLA-4 receptor. (1993)

Activation of T lymphocytes requires the recognition of peptide-major histocompatibility complex complexes and costimulatory signals provided by antigen-presenting cells (APCs). The best-characterized costimulatory molecule to date is the B7 antigen, a member of the immunoglobulin family that binds two receptors, CD28 and CTLA-4, expressed on the T-cell surface. Using the anti-mouse B7 (mB7) monoclonal antibody (mAb) 16-10A1, which we recently developed, we found that mB7 is indeed an important costimulatory ligand for the antigen-specific activation of murine T cells by B lymphocytes. Three lines of evidence suggest, however, the existence of at least one additional ligand for the CTLA-4 receptor. First, a soluble fusion protein of human CTLA-4 and the IgG1 Fc region, termed CTLA4Ig, blocks better than the anti-mB7 mAb the allogeneic stimulation of T cells by unfractionated splenic APCs. Second, saturating amounts of anti-mB7 mAb do not significantly block binding of fluorescein isothiocyanate-conjugated CTLA4Ig to activated splenic APCs. Furthermore, CTLA4Ig but not the anti-mB7 mAb reacts with the M12 and M12.C3 cell lines. The identification of an additional ligand for CTLA-4 may have applications to the treatment of autoimmune disease and transplant-associated disorders.
Molecular Phenotyping of Human Endometrium Distinguishes Menstrual Cycle Phases and Underlying Biological Processes in Normo-Ovulatory Women (2005)

Histological evaluation of endometrium has been the gold standard for clinical diagnosis and management of women with endometrial disorders. However, several recent studies have questioned the accuracy and utility of such evaluation, mainly because of significant intra- and interobserver variations in histological interpretation. To examine the possibility that biochemical or molecular signatures of endometrium may prove to be more useful, we have investigated whole-genome molecular phenotyping (54,600 genes and expressed sequence tags) of this tissue sampled across the cycle in 28 normo-ovulatory women, using high-density oligonucleotide microarrays. Unsupervised principal component analysis of all samples revealed that samples self-cluster into four groups consistent with histological phenotypes of proliferative (PE), early-secretory (ESE), mid-secretory (MSE), and late-secretory (LSE) endometrium. Independent hierarchical clustering analysis revealed equivalent results, with two major dendrogram branches corresponding to PE/ESE and MSE/LSE and sub-branching into the four respective phases with heterogeneity among samples within each sub-branch. K-means clustering of genes revealed four major patterns of gene expression (high in PE, high in ESE, high in MSE, and high in LSE), and gene ontology analysis of these clusters demonstrated cycle-phase-specific biological processes and molecular functions. Six samples with ambiguous histology were identically assignable to a cycle phase by both principal component analysis and hierarchical clustering. Additionally, pairwise comparisons of relative gene expression across the cycle revealed genes/families that clearly distinguish the transitions of PE-->ESE, ESE-->MSE, and MSE-->LSE, including receptomes and signaling pathways. Select genes were validated by quantitative RT-PCR. Overall, the results demonstrate that endometrial samples obtained by two different sampling techniques (biopsy and curetting hysterectomy specimens) from subjects who are as normal as possible in a human study and including those with unknown histology, can be classified by their molecular signatures and correspond to known phases of the menstrual cycle with identical results using two independent analytical methods. Also, the results enable global identification of biological processes and molecular mechanisms that occur dynamically in the endometrium in the changing steroid hormone milieu across the menstrual cycle in normo-ovulatory women. The results underscore the potential of gene expression profiling for developing molecular diagnostics of endometrial normalcy and abnormalities and identifying molecular targets for therapeutic purposes in endometrial disorders.
Effect of dietary fibers on rat large bowel mucosal growth and cell proliferation (1984)

The effects of three different fibers on large intestinal mucosal mass per unit length, crypt morphometrics, and cytokinetics were compared by feeding fiber supplements to 40 rats for 4 wk. A control group of rats was fed a fiber-free diet and the experimental groups received the same diet, uniformly diluted by the addition (wt/wt) of 20% oat bran, 10% pectin, or 10% guar. All groups of rats exhibited equal caloric intakes and weight gains. Guar consistently produced an increase in cecal and colonic mucosal wet weight, DNA, and RNA when compared with the control group (P less than 0.05). DNA levels were increased in the cecum and proximal colon of the pectin group but remained unaltered in those rats fed oat bran. Autoradiographic measurements demonstrated that epithelial cell turnover time was longer in the distal colon of the guar and pectin groups (P less than 0.001), but shorter in the proximal colon of the oat bran group, when compared with the controls (P less than 0.01). This comparative study provides further insight into the possible mechanisms by which specific dietary fibers elicit a hyperproliferative response in the large bowel.
Tight Junctions: A Barrier to the Initiation and Progression of Breast Cancer? (2010)

Breast cancer is a complex and heterogeneous disease that arises from epithelial cells lining the breast ducts and lobules. Correct adhesion between adjacent epithelial cells is important in determining the normal structure and function of epithelial tissues, and there is accumulating evidence that dysregulated cell-cell adhesion is associated with many cancers. This review will focus on one cell-cell adhesion complex, the tight junction (TJ), and summarize recent evidence that TJs may participate in breast cancer development or progression. We will first outline the protein composition of TJs and discuss the functions of the TJ complex. Secondly we will examine how alterations in these functions might facilitate breast cancer initiation or progression; by focussing on the regulatory influence of TJs on cell polarity, cell fate and cell migration. Finally we will outline how pharmacological targeting of TJ proteins may be useful in limiting breast cancer progression. Overall we hope to illustrate that the relationship between TJ alterations and breast cancer is a complex one; but that this area offers promise in uncovering fundamental mechanisms linked to breast cancer progression.
The Crystal Structure of Human Cyclin B (2007)

Cyclin B is the key regulatory protein controlling mitosis in all eukaryotes, where it binds cyclin-dependent kinase, cdk1, forming a complex which initiates the mitotic program through phosphorylation of select proteins. Cyclin B regulates the activation, subcellular localization, and substrate specificity of cdk1, and destruction of cyclin B is necessary for mitotic exit. Overexpression of human cyclin B1 has been found in numerous cancers and has been associated with tumor aggressiveness. Here we report the crystal structure of human cyclin B1 to 2.9 A. Comparison of the structure with cyclin A and cyclin E reveals remarkably similar N-terminal cyclin box motifs but significant differences among the C-terminal cyclin box lobes. Divergence in sequence gives rise to unique interaction surfaces at the proposed cyclin B/cdk1 interface as well as the 'RxL' motif substrate binding site on cyclin B. Examination of the structure provides insight into the molecular basis for differential affinities of protein based cyclin/cdk inhibitors such as p27, substrate recognition, and cdk interaction.
Is exocrine pancreatic insufficiency in adult coeliac disease a cause of persisting symptoms? (2007)

Low faecal elastase is common in patients with coeliac disease and chronic diarrhoea, suggesting exocrine pancreatic insufficiency. In this group of patients, pancreatic enzyme supplementation may provide symptomatic benefit.