gebhart/patrepeval huggingface dataset:
Generation of anti-NZB red blood cell antibody-forming plasma cells from bone marrow cultures of syngeneic and allogeneic mice: functional modulation of helper T-cell subsets in autosensitization. (1983)

An in vitro anti-NZB red blood cell (RBC) autoantibody-forming system was developed by culturing young (antiglobulin negative) or old (antiglobulin positive) NZB mouse bone marrow cells in the presence of young or old NZB thymocyte homogenates (or RNA thymus extracts) and young NZB-RBC. Using young NZB bone marrow cells, the greatest number of autoantibody forming cells were seen following stimulation with a mixture of young and old thymocyte homogenates (TH). A higher response was seen with old NZB bone marrow cells stimulated by old NZB thymocyte homogenates and RBC. Phenol-extracted thymic RNA retained activity when added to bone marrow culture containing NZB-RBC. Thymus RNA from 9 to 10 days old NZB mice had no activity although their bone marrow cells responded well to stimulation by young and old thymic RNA together with RBC. By analysing results obtained using T-cells enriched for helper and suppressor activities, we have concluded that abrogation of self-tolerance in mice is due to the appearance of functionally modulated helper T-cell subsets and to imbalance between helper and suppressor T cells.
Mass selective axial ion ejection from a linear quadrupole ion trap (2003)

The electric fields responsible for mass-selective axial ejection (MSAE) of ions trapped in a linear quadrupole ion trap have been studied using a combination of analytic theory and computer modeling. Axial ejection occurs as a consequence of the trapped ions' radial motion, which is characterized by extrema that are phase-synchronous with the local RF potential. As a result, the net axial electric field experienced by ions in the fringe region, over one RF cycle, is positive. This axial field depends strongly on both the axial and radial ion coordinates. The superposition of a repulsive potential applied to an exit lens with the diminishing quadrupole potential in the fringing region near the end of a quadrupole rod array can give rise to an approximately conical surface on which the net axial force experienced by an ion, averaged over one RF cycle, is zero. This conical surface has been named the cone of reflection because it divides the regions of ion reflection and ion ejection. Once an ion penetrates this surface, it feels a strong net positive axial force and is accelerated toward the exit lens. As a consequence of the strong dependence of the axial field on radial displacement, trapped thermalized ions can be ejected axially from a linear ion trap in a mass-selective way when their radial amplitude is increased through a resonant response to an auxiliary signal.
Enabling Autologous Human Liver Regeneration with Differentiated Adipocyte Stem Cells (2013)

We developed a novel method for differentiating adipocyte-derived stem cells (ASCs) into hepatocyte-like cells (iHeps). ASCs are cultured as spherical cellular aggregates and are then induced by culture in chemically defined media for a short time period to differentiate into spherical culture iHeps (SCi-Heps). SCi-Heps have many of the in vitro functional properties of mature hepatocytes, and they can stably reconstitute functioning human liver in vivo in a murine model system. Implantation studies demonstrate that SCi-Heps have a very low malignant potential. All human liver regenerative procedures, including ultrasound-guided direct liver implantation, are scalable and appropriate for human clinical use. These methods can be used to achieve the major promise of regenerative medicine. It may now be possible to regenerate human liver using autologous stem cells obtained from a readily accessible tissue.
Heavy water delays growth of human carcinoma in nude mice. (1988)

Deuterium-enriched water has an antiproliferative effect on transplantable mouse tumors without toxic side effects. Since the response to treatment of human carcinomas growing in nude mice is deemed to be a good indicator of the potential clinical behavior of these tumors, we studied the influence of this stable isotope of hydrogen on the growth of xenotransplanted human carcinomas of various histologic types, grades, and primary sites. Seven-week-old Balb/c-nu/nu mice were inoculated subcutaneously, either with oropharyngeal squamous cell carcinomas or with carcinomas of the large intestine. After tumor inoculation, the mice were given drinking water containing 30 atom% D2O. Heavy water effectively retarded the growth of the human carcinomas. At the end of the experiment, the weight of the tumors was reduced to values ranging from 22% to 65% of the control values. The reproducible antiproliferative effect was more conspicuous in poorly differentiated carcinomas than in moderately well-differentiated variants. Since animals in both groups, kept under identical conditions, drank the same amount of water and had similar body weights, the difference in tumor growth can be attributed to the moderate deuteration of the hosts.
Structural Basis for Ribosome Recruitment and Manipulation by a Viral IRES RNA (2006)

Canonical cap-dependent translation initiation requires a large number of protein factors that act in a stepwise assembly process. In contrast, internal ribosomal entry sites (IRESs) are cis-acting RNAs that in some cases completely supplant these factors by recruiting and activating the ribosome using a single structured RNA. Here we present the crystal structures of the ribosome-binding domain from a Dicistroviridae intergenic region IRES at 3.1 angstrom resolution, providing a view of the prefolded architecture of an all-RNA translation initiation apparatus. Docking of the structure into cryo-electron microscopy reconstructions of an IRES-ribosome complex suggests a model for ribosome manipulation by a dynamic IRES RNA.
Comparative genomic hybridization (CGH): ten years of substantial progress in human solid tumor molecular cytogenetics (2004)

Data from ten years of research using comparative genomic hybridization (CGH) for the detection of chromosomal alterations in human solid tumors are concisely reviewed. By use of a basic methodology with some variations more or less specific patterns of genomic imbalances were found in a large number of tumors of various entities. Specific gains and losses of genomic material have not only opened the way to the detection of a series of cancer-related genes but also to clinical implications. Not only several areas of basic oncogenetic research, but also differential diagnosis, prognosis of disease progression, and therapeutic decisions have profited by CGH.
How future tumor necrosis factor antagonists and other compounds will meet the remaining challenges in Crohn's disease. (2004)

The chimeric monoclonal antibody to tumor necrosis factor (TNF), infliximab, is an effective therapy for Crohn's disease. However, the formation of human anti-chimeric antibodies to infliximab (immunogenicity) can lead to loss of efficacy as well as acute infusion reactions and delayed hypersensitivity reactions. The fully human monoclonal antibody adalimumab and the pegylated humanized monoclonal antibody fragment CDP870 are biologic therapies against TNF that might be effective for Crohn's disease and less immunogenic than infliximab. Other potential alternatives to infliximab for Crohn's disease include the humanized anti-adhesion molecule antibodies natalizumab and MLN-02, the humanized anti-interleukin 12 antibody ABT-874, the humanized anti-interferon g antibody fontolizumab, the humanized anti-interleukin 6 receptor antibody MRA, and human recombinant granulocyte macrophage colony stimulating factor (sargramostim). Some, or all, of these therapies will likely represent important treatments for Crohn's disease in the future.
Gene therapy for metachromatic leukodystrophy (2016)

Leukodystrophies (LDs) are rare, often devastating genetic disorders with neurologic symptoms. There are currently no disease-specific therapeutic approaches for these diseases. In this review we use metachromatic leukodystrophy as an example to outline in the brief the therapeutic approaches to MLD that have been tested in animal models and in clinical trials, such as enzyme-replacement therapy, bone marrow/umbilical cord blood transplants, ex vivo transplantation of genetically modified hematopoietic stem cells, and gene therapy. These studies suggest that to be successful the ideal therapy for MLD must provide persistent and high level expression of the deficient gene, arylsulfatase A in the CNS. Gene therapy using adeno-associated viruses is therefore the ideal choice for clinical development as it provides the best balance of potential for efficacy with reduced safety risk. Here we have summarized the published preclinical data from our group and from others that support the use of a gene therapy with AAVrh.10 serotype for clinical development as a treatment for MLD, and as an example of the potential of gene therapy for LDs especially for Krabbe disease, which is the focus of this special issue. © 2016 Wiley Periodicals, Inc.
High-affinity antibodies to ssDNA are produced by CD-B cells in systemic lupus erythematosus patients. (1989)

It was previously shown that human CD5+B cells are committed to the production of polyreactive "autoantibodies" that bind different self-Ag, including ssDNA, IgG Fc fragment, thyroglobulin, and insulin, as well as exogenous Ag, e.g., tetanus toxoid and other bacterial components. To define the contribution of the CD5+B cell subset to the production of antibodies to ssDNA in SLE, we quantitated, purified, and functionally characterized circulating CD5+ and CD5-B cells in patients and in healthy subjects. We found that in SLE patients circulating CD5+B cells were not increased in number, and both CD5+ and C5-B cells spontaneously secreted antibodies to ssDNA. Studies of the mAb we generated using CD5+ and CD5-B cells revealed that two types of antibody to ssDNA are produced in SLE. The first type, of the IgM class, is produced mainly by CD5+B cells and displays a moderate affinity for ssDNA (Kd, 10(-6) to 10(-7) mol/liter) and is polyreactive, not dissimilar to the autoantibodies inducible in the normal human B cell repertoire by polyclonal activation. The second type, mostly of the IgG and IgA class, is produced mainly by CD5-B cells and displays a higher affinity (Kd, 10(-8) mol/liter) for and reacts only with ssDNA. The functional features of the high affinity anti-ssDNA antibodies and the phenotype of their producing B cells mimic those characteristic of a "mature" Ag-driven response, such as that to tetanus toxoid in tetanus toxoid-vaccinated subjects.
A Novel mRNA of the A4 Amyloid Precursor Gene Coding for a Possibly Secreted Protein (1989)

The gene, encoding the A4 peptide found in the amyloid core of senile plaques isolated from the cerebral cortex of patients with Alzheimer's disease, produces at least three precursors that resemble cell surface receptors. A clone isolated from a human brain complementary DNA library contained the structural sequence for an A4 amyloid peptide precursor with a serine protease inhibitor domain in which 208 amino acids at the carboxyl terminal are replaced by 20 amino acids derived from nucleotide sequences with homology to the Alu repeat family. This protein devoid of the transmembrane domain most likely represents a secreted form of the A4 amyloid peptide precursor.
Structural elucidation of a capsular polysaccharide from a clinical isolate of Bacteroides vulgatus from a patient with Crohn’s disease (2001)

The structure of a capsular polysaccharide (CPS) from a clinical isolate of Bacteroides vulgatus was elucidated. B. vulgatus IMCJ 1204 was isolated from feces of a patient with Crohn's disease. CPS was prepared by phenol/water extraction of the bacterial cells followed by hydrophobic interaction chromatography and then gel filtration chromatography of the extract. The structure of CPS was determined by chemical analysis and NMR spectroscopy including DQF-COSY, TOCSY, ROESY, HSQC-TOCSY, HMQC and HMBC to be a polysaccharide composed of the following repeating unit: -->3)beta-D-Glcp(1-->6)[alpha-D-GalpNAc(1-->2)beta-D-Galp(1-->4)]beta-D-GlcpNAc(1-->3)alpha-D-Galp(1-->4)beta-D-Manp(1-->.
Engineered Trehalose Permeable to Mammalian Cells (2015)

Trehalose is a naturally occurring disaccharide which is associated with extraordinary stress-tolerance capacity in certain species of unicellular and multicellular organisms. In mammalian cells, presence of intra-and extracellular trehalose has been shown to confer improved tolerance against freezing and desiccation. Since mammalian cells do not synthesize nor import trehalose, the development of novel methods for efficient intracellular delivery of trehalose has been an ongoing investigation. Herein, we studied the membrane permeability of engineered lipophilic derivatives of trehalose. Trehalose conjugated with 6 acetyl groups (trehalose hexaacetate or 6-O-Ac-Tre) demonstrated superior permeability in rat hepatocytes compared with regular trehalose, trehalose diacetate (2-O-Ac-Tre) and trehalose tetraacetate (4-O-Ac-Tre). Once in the cell, intracellular esterases hydrolyzed the 6-O-Ac-Tre molecules, releasing free trehalose into the cytoplasm. The total concentration of intracellular trehalose (plus acetylated variants) reached as high as 10 fold the extracellular concentration of 6-O-Ac-Tre, attaining concentrations suitable for applications in biopreservation. To describe this accumulation phenomenon, a diffusion-reaction model was proposed and the permeability and reaction kinetics of 6-O-Ac-Tre were determined by fitting to experimental data. Further studies suggested that the impact of the loading and the presence of intracellular trehalose on cellular viability and function were negligible. Engineering of trehalose chemical structure rather than manipulating the cell, is an innocuous, cellfriendly method for trehalose delivery, with demonstrated potential for trehalose loading in different types of cells and cell lines, and can facilitate the wide-spread application of trehalose as an intracellular protective agent in biopreservation studies.
Apolar surface area determines the efficiency of translocon-mediated membrane-protein integration into the endoplasmic reticulum (2011)

Integral membrane proteins are integrated cotranslationally into the membrane of the endoplasmic reticulum in a process mediated by the Sec61 translocon. Transmembrane α-helices in a translocating polypeptide chain gain access to the surrounding membrane through a lateral gate in the wall of the translocon channel [van den Berg B, et al. (2004) Nature 427:36-44; Zimmer J, et al. (2008) Nature 455:936-943; Egea PF, Stroud RM (2010) Proc Natl Acad Sci USA 107:17182-17187]. To clarify the nature of the membrane-integration process, we have measured the insertion efficiency into the endoplasmic reticulum membrane of model hydrophobic segments containing nonproteinogenic aliphatic and aromatic amino acids. We find that an amino acid's contribution to the apparent free energy of membrane-insertion is directly proportional to the nonpolar accessible surface area of its side chain, as expected for thermodynamic partitioning between aqueous and nonpolar phases. But unlike bulk-phase partitioning, characterized by a nonpolar solvation parameter of 23 cal/(mol · Å(2)), the solvation parameter for transfer from translocon to bilayer is 6-10 cal/(mol · Å(2)), pointing to important differences between translocon-guided partitioning and simple water-to-membrane partitioning. Our results provide compelling evidence for a thermodynamic partitioning model and insights into the physical properties of the translocon.
A capability representation with embedded address and nearly-exact object bounds (2000)

We present a capability format which improves upon prior capability formats by simultaneously providing four key features. First, address and bounds information are embedded directly in the capability representation. Second, a capability may point to an arbitrary word in its segment. Third, internal fragmentation due to segment/object size mismatch is less than 6%; with a simple, high-locality allocation scheme, total fragmentation is less than 12%. Fourth, objects of 32 or fewer words, e.g. most class instances in object-oriented systems, may be allocated with no fragmentation and will thus have precise hardware bounds-checking. These features make it entirely practical to use a capability-guarded segment per allocated object, thus ensuring robust inter- and intra-program memory protection. Additionally, we describe the implementation and application of increment-only pointers which enable precise hardware-only bounds-checking for Javastyle objects/arrays. Finally, we also demonstrate how to generate capabilities for sub-segments from which the enclosing segment can be recovered by system routines.
Cationic RuII Complexes with N‐Heterocyclic Carbene Ligands for UV‐Induced Ring‐Opening Metathesis Polymerization (2008)

Open sesame: Novel cationic RuII complexes with N-heterocyclic carbene ligands (see structure) have been prepared and used as UV-triggerable photoinitiators for ring-opening metathesis polymerization. They may be used for the high-yield synthesis of bulk polymers as well as for surface functionalization. Laser pulse radiolysis and NMR spectroscopy experiments supported by quantum chemical calculations give insight into the initiation mechanism.
9-cis-Retinoic Acid (9cRA), a Retinoid X Receptor (RXR) Ligand, Exerts Immunosuppressive Effects on Dendritic Cells by RXR-Dependent Activation: Inhibition of Peroxisome Proliferator-Activated Receptor γ Blocks Some of the 9cRA Activities, and Precludes Them to Mature Phenotype Development (2007)

At nanomolar range, 9-cis-retinoic acid (9cRA) was able to interfere in the normal differentiation process from human monocyte to immature dendritic cell (DC) and produced a switch in mature DCs to a less stimulatory mode than untreated cells. 9cRA-treated mature DCs secreted high levels of IL-10 with an IL-12 reduced production. The phenotypic alterations unleashed by 9cRA were similar but not identical to other specific retinoid X receptor (RXR) agonists and to those already reported for rosiglitazone, a PPARgamma activator, on DCs. The simultaneous addition of 9cRA and rosiglitazone on DCs displayed additive effects. Moreover, addition to cultures of GW9662, a specific inhibitor of PPARgamma, or the RXR pan-antagonist HX603, blocked these changes. All these results suggest an activation of PPARgamma-RXR and other RXR containing dimers by 9cRA in DCs. Finally, both GW9662 and HX603 by themselves altered the maturation process unleashed by TNFalpha, poly(I:C) or LPS on human DCs further suggesting that the heterodimer PPARgamma-RXR must fulfill a significant role in the physiological maturation process of these cells in addition to the repressing effects reported till now for this nuclear receptor.
Latent reservoirs of HIV: Obstacles to the eradication of virus (1999)

The use of highly active antiretroviral therapy (HAART) in the treatment of HIV-1-infected individuals has provided a considerable amount of information regarding the dynamics of viral replication and has resulted in enormous advances in HIV therapeutics. The profound suppression of plasma viremia in HIV-infected individuals receiving HAART has resulted in a highly beneficial clinical effect and a dramatic decrease in the death rate attributable to AIDS. Nonetheless, the persistance of reservoirs of HIV, including latently infected, resting CD4+ T cells that can give rise to infectious HIV upon stimulation in vitro, has posed a sobering challenge to the long-term control or eradication of HIV in infected individuals receiving HAART. Although a recent study has demonstrated th at the size of the pool of latently infected, resting CD4+ T cells can be markedly diminished with intermittent interleukin (IL-2) and continuous HAART, complete eradication of HiV in infected individuals remains extremely problematic. Here we discuss recent developments in studies of the latent reservoir of HIV in patients receiving HAART and implications for the long-term treatment of infected individuals and eradication of the infection.
A second envelope glycoprotein mediates neutralization of a pestivirus, hog cholera virus (1992)

Several monoclonal antibodies (MAbs) raised against hog cholera virus (HCV) reacted with the HCV structural glycoprotein gp44/48 and neutralized the virus. The presence of HCV gp44/48 on the viral surface was directly demonstrated by immunogold electron microscopy. Eight anti-HCV gp44/48 MAbs were tested by immunoperoxidase assay against a panel of pestivirus strains. Each MAb showed a distinct pattern of reactivity with HCV strains. It is suggested that the MAbs are well suited for epidemiological investigations of HCV outbreaks.
Automated surface mounting of miniaturized optical elements (2002)

An automated surface mounting assembly procedure has been developed for mounting miniaturized optical elements. It is based on a low cost universal holding device, free space optical interconnection, and on-line adjustment of the elements. It is characterized by submicron mounting precision and excellent mechanical properties. Flexibility in the layout, simple handling, high packaging density render this technique suitable to low cost prototyping and mass production of optoelectronic devices. The possibility of mass production will allow a new class of optical systems to be conceived for the customer market.