gebhart/patrepeval huggingface dataset:
Hepatitis B virus nucleocapsid assembly: primary structure requirements in the core protein (1990)

As a step toward understanding the assembly of the hepatitis B virus (HBV) nucleocapsid at a molecular level, we sought to define the primary sequence requirements for assembly of the HBV core protein. This protein can self assemble upon expression in Escherichia coli. Applying this system to a series of C-terminally truncated core protein variants, we mapped the C-terminal limit for assembly to the region between amino acid residues 139 and 144. The size of this domain agrees well with the minimum length of RNA virus capsid proteins that fold into an eight-stranded beta-barrel structure. The entire Arg-rich C-terminal domain of the HBV core protein is not necessary for assembly. However, the nucleic acid content of particles formed by assembly-competent core protein variants correlates with the presence or absence of this region, as does particle stability. The nucleic acid found in the particles is RNA, between about 100 to some 3,000 nucleotides in length. In particles formed by the full-length protein, the core protein mRNA appears to be enriched over other, cellular RNAs. These data indicate that protein-protein interactions provided by the core protein domain from the N terminus to the region around amino acid 144 are the major factor in HBV capsid assembly, which proceeds without the need for substantial amounts of nucleic acid. The presence of the basic C terminus, however, greatly enhances encapsidation of nucleic acid and appears to make an important contribution to capsid stability via protein-nucleic acid interactions. The observation of low but detectable levels of nucleic acid in particles formed by core protein variants lacking the Arg-rich C terminus suggests the presence of a second nucleic acid-binding motif in the first 144 amino acids of the core protein. Based on these findings, the potential importance of the C-terminal core protein region during assembly in vivo into authentic, replication-competent nucleocapsids is discussed.
Identification of an IL-7-Associated Pre-Pro-B Cell Growth-Stimulating Factor (PPBSF). II. PPBSF Is a Covalently Linked Heterodimer of IL-7 and a M r 30,000 Cofactor (1998)

Evidence is provided in a companion paper for an IL-7-associated molecular complex that selectively stimulates the proliferation and presumptive differentiation of pre-pro-B cells in our long-term bone marrow culture system and "primes" them to proliferate in response to monomeric IL-7. Here, Western immunoblot analysis reveals that this pre-pro-B cell growth-stimulating factor (PPBSF) is a self-assembling heterodimer of IL-7 and a cofactor with a M(r) of 30,000. Thus, when developed with anti-IL-7 mAb, PPBSF migrates electrophoretically as a covalently bound approximately 55-kDa molecule under nonreducing conditions but dissociates under reducing conditions. Furthermore, the addition of rIL-7 or native IL-7 to medium conditioned by stromal cells from IL-7 gene-deleted (-/-) mice results in the formation of active 45-kDa and 55-kDa molecular complexes, respectively. Antiserum prepared in IL-7(-/-) mice against affinity-purified PPBSF contained separable reactivities for IL-7 and the non-IL-7 component of PPBSF. The PPBSF cofactor detected by this antiserum migrates as an approximately 30-kDa molecule and is able to maintain the viability, but not the proliferation, of pre-pro-B cells. Furthermore, the cofactor is produced constitutively by IL-7(-/-) and IL-7(+/+) bone marrow stromal cells under pro-B- but not pre-B-type culture conditions. Consequently, IL-7 appears to exist almost entirely as a heterodimer (i.e., PPBSF) in pro-B-type cultures, whereas it exists almost entirely as a monomer in pre-B-type cultures. Although the identity of the PPBSF cofactor remains to be determined, it does not appear to be stem cell factor, insulin-like growth factor-1, thymic stromal-derived lymphopoietin, flt3, stromal cell-derived factor-1, or IL-7R.
Intrinsic stress in sputter-deposited thin films (1992)

Abstract A review of the sputtered film stress literature shows that the intrinsic stress can be tensile or compressive depending on the energetics of the deposition process. Modeling studies of film growth and extensive experimental evidence show a direct link between the energetics of the deposition process and film microstructure, which in turn determines the nature and magnitude of the stress. The fundamental quantities are the particle flux and energy striking the condensing film, which are a function of many process parameters such as pressure (discharge voltage), target/sputtering gas mass ratio, cathode shape, bias voltage, and substrate orientation. Tensile stress is generally observed in zone 1-type, porous films and is explained in terms of the grain boundary relaxation model, whereas compressive stress, observed in zone T-type, dense films, is interpreted in terms of the atomic peening mechanism. Modeling of the atomic peening mechanism and experimental data indicate that the normalized momentum may be the appropriate stress scaling factor in the compressive stress regime. An idealized stress momentum curve is constructed depicting the three characteristic stress regions. The rapid tensile-to-compressive stress transition often observed in sputtered films may be associated with a threshold phenomenon, occurring at approximately the atomic displacement energy. Furthermore, data indicate that the inverse relationship between intrinsic stress and deposition temperature is a general phenomenon, independent of the nature of the stress, material, or method of deposition.
The Conversion of Testosterone to 17β-Hydroxy-5α-androstan-3-one (Dihydrotestosterone) by Human Hair Follicles (1972)

We demonstrated the conversion of testosterone-4-14C to dihydrotestosterone (17β-Phydroxy-5α-androstan-17-one), the tissue-active androgen, with 50–200 μg of freeze-dried human hair follicles plucked from various regions. All of the hair follicles thus far tested contained the 5α-reductase activity. Under optimal conditions, the 5α-reductase activity in growing hair follicles ranged from 10–20 nmoles/100 mg dry wt/hr. In the scalp, the growing follicles showed 3–8 times higher values than the resting. In other regions such as the beard, axilla, chest, pubis, arms and legs, the growing follicles showed nearly the same activities as those of the scalp or even higher, whereas the activities of the resting follicles varied considerably.
Experimental silicosis: morphologic and biochemical abnormalities produced by intratracheal instillation of quartz into guinea pig lungs. (1980)

Six months after intratracheal instillation of silica, histologic, ultrastructural, cytologic, and biochemical studies were performed on the lungs of guinea pigs. The tissue response consisted of both diffuse alveolar septal infiltration with interstitial fibrosis and granulomatous infiltration with nodular fibrosis. Ultrastructural studies confirmed the presence of a mixed inflammatory exudate in the alveolar interstitium (histiocytes, neutrophils, eosinophils, and lymphocytes) and the Type II lining of cell hyperplasia. The number of lung cells recovered by lavage and the proportions of neutrophils and multinucleated cells in bronchoalveolar cells were significantly greater in experimental animals (P < .05) than in controls (intratracheal saline). Total lung collagen and collagen synthesis by cultured lung tissue were also increased in the experimental animals. Since the response of guinea pig lung to intratracheal silica included pathologic features common to human silicosis and idiopathic pulmonary fibrosis, this model has the potential for improving our understanding of both of these important clinical disorders.
Regulation of autoproteolysis of the HIV-1 and HIV-2 proteases with engineered amino acid substitutions (1993)

Autoproteolysis of the retroviral aspartyl proteases is a major obstacle to purification and analysis of these enzymes. A mutagenic approach to rendering autolytic cleavage sites less labile was applied to the primary cleavage site between Leu5 and Trp6 in human immunodeficiency virus-1 (HIV-1) protease. From predictions based on known substrates it was concluded that amino acids Lys or Ser in place of Gln at position 7 would prevent cleavage at the Leu5-Trp6 peptide bond, therefore stabilizing the protein. Autoproteolytic stability was enhanced at least 100-fold by these mutations. At longer time points the protease was degraded at secondary sites which contained adequate substrate sequences but were conformationally restricted. Conversely, a mutation in HIV-2 protease which changed Lys7 to Gln rendered the protein 3-fold less stable and shifted the position of the initial autoproteolytic cleavage from Phe3-Ser4 to Leu5-Trp6. The effects of these mutations demonstrate that small changes in protein sequence can have a major impact on their autoproteolytic stability. The work described here suggests a general method for stabilizing proteases and perhaps other recombinantly produced proteins to autolysis.
Exosome-Bound WD Repeat Protein Monad Inhibits Breast Cancer Cell Invasion by Degrading Amphiregulin mRNA (2013)

Increased stabilization of mRNA coding for key cancer genes can contribute to invasiveness. This is achieved by down-regulation of exosome cofactors, which bind to 3'-UTR in cancer-related genes. Here, we identified amphiregulin, an EGFR ligand, as a target of WD repeat protein Monad, a component of R2TP/prefoldin-like complex, in MDA-MB-231 breast cancer cells. Monad specifically interacted with both the 3'-UTR of amphiregulin mRNA and the RNA degrading exosome, and enhanced decay of amphiregulin transcripts. Knockdown of Monad increased invasion and this effect was abolished with anti-amphiregulin neutralizing antibody. These results suggest that Monad could prevent amphiregulin-mediated invasion by degrading amphiregulin mRNA.
ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells (2018)

Chimeric antigen receptor (CAR) T cell therapy is rapidly emerging as one of the most promising therapies for hematologic malignancies. Two CAR T products were recently approved in the United States and Europe for the treatment ofpatients up to age 25years with relapsed or refractory B cell acute lymphoblastic leukemia and/or adults with large B cell lymphoma. Many more CAR T products, as well as other immunotherapies, including various immune cell- and bi-specific antibody-based approaches that function by activation of immune effector cells, are in clinical development for both hematologic and solid tumor malignancies. These therapies are associated with unique toxicities of cytokine release syndrome (CRS) and neurologic toxicity. The assessment and grading of these toxicities vary considerably across clinical trials and across institutions, making it difficult to compare the safety of different products and hindering the ability to develop optimal strategies for management of these toxicities. Moreover, some aspects of these grading systems can be challenging to implement across centers. Therefore, in an effort to harmonize the definitions and grading systems for CRS and neurotoxicity, experts from all aspects of the field met on June 20 and 21, 2018, at a meeting supported by the American Society for Transplantation and Cellular Therapy (ASTCT; formerly American Society for Blood and Marrow Transplantation, ASBMT) in Arlington, VA. Here we report the consensus recommendations of that group and propose new definitions and grading for CRS and neurotoxicity that are objective, easy to apply, and ultimately more accurately categorize the severity of these toxicities. The goal is to provide a uniform consensus grading system for CRS and neurotoxicity associated with immune effector cell therapies, for use across clinical trials and in the postapproval clinical setting.
The story of the serpin plasminogen activator inhibitor 1: is there any need for another mutant? (2004)

The importance of obtaining insight in the structure/function relationship in the serpin plasminogen activator inhibitor type-1 can be understood from the major role PAI-1 plays in different (patho)physiological processes, mainly because of its involvement in the plasminogen/plasmin system. Moreover, during the past years, studies indicated a contribution of PAI-1 to the development of cardiovascular disease in common syndromes such as atherosclerosis, diabetes and hypertension. Furthermore, PAI-1 also inhibits u-PA, attributing a role in phenomena such as cell migration and tissue remodelling. Considering the role of PAI-1 in such various pathogenic path-ways, detailed insight into the structure/function relationship in PAI-1 might provide a means of interfering with a given pathological situation without disturbing other physiological processes. Therefore, since the discovery of PAI-1 and the cloning of its cDNA 20 years ago, over 600 PAI-1 variants have been constructed, elucidating the most important structural features of PAI-1. This review gives an overview of the contribution of the different PAI-1 variants to the understanding of the structure/function relationship in PAI-1, based on the different functional features of PAI-1.
Description of Staphylococcus Serine Protease ( ssp ) Operon in Staphylococcus aureus and Nonpolar Inactivation of sspA -Encoded Serine Protease (2001)

Signature tagged mutagenesis has recently revealed that the Ssp serine protease (V8 protease) contributes to in vivo growth and survival of Staphylococcus aureus in different infection models, and our previous work indicated that Ssp could play a role in controlling microbial adhesion. In this study, we describe an operon structure within the ssp locus of S. aureus RN6390. The ssp gene encoding V8 protease is designated as sspA, and is followed by sspB, which encodes a 40.6-kDa cysteine protease, and sspC, which encodes a 12.9-kDa protein of unknown function. S. aureus SP6391 is an isogenic derivative of RN6390, in which specific loss of SspA function was achieved through a nonpolar allelic replacement mutation. In addition to losing SspA, the culture supernatant of SP6391 showed a loss of 22- to 23-kDa proteins and the appearance of a 40-kDa protein corresponding to SspB. Although the 40-kDa SspB protein could degrade denatured collagen, our data establish that this is a precursor form which is normally processed by SspA to form a mature cysteine protease. Culture supernatant of SP6391 also showed a new 42-kDa glucosaminidase and enhanced glucosaminidase activity in the 29 to 32 kDa range. Although nonpolar inactivation of sspA exerted a pleiotropic effect, S. aureus SP6391 exhibited enhanced virulence in a tissue abscess infection model relative to RN6390. Therefore, we conclude that SspA is required for maturation of SspB and plays a role in controlling autolytic activity but does not by itself exert a significant contribution to the development of tissue abscess infections.
Residue Lys57 in the Collagen-Like Region of Human L-Ficolin and Its Counterpart Lys47 in H-Ficolin Play a Key Role in the Interaction with the Mannan-Binding Lectin-Associated Serine Proteases and the Collectin Receptor Calreticulin (2009)

L- and H-ficolins are serum oligomeric defense proteins consisting of a collagen-like region and a fibrinogen-like recognition domain that bind to pathogen- and apoptotic cell-associated molecular patterns. They share with mannan-binding lectin (MBL) the ability to associate with MBL-associated serine proteases (MASP)-1, -2, -3, and protein MAp19 and to trigger the lectin complement pathway through MASP-2 activation. Recent studies have revealed the essential role of Lys(55) in the collagenous region of MBL in the interaction with the MASPs and calreticulin (CRT). To test the possible involvement of the homologous residues Lys(57) of L-ficolin and Lys(47) of H-ficolin, point mutants of both proteins were produced in which these residues were mutated to Ala, Glu, or Arg. The resulting mutants exhibited oligomerization patterns and ligand binding properties similar to those of their wild-type counterparts. In contrast, all three mutations strongly inhibited the interaction of L- and H-ficolins with MAp19 and MASP-2 and impaired the ability of each ficolin to trigger the lectin pathway. In the case of MASP-1 and MASP-3, replacement of the target Lys residues by Ala or Glu abolished interaction, whereas the Lys to Arg mutations had only slight inhibitory effects. Likewise, binding of each ficolin to CRT was inhibited by mutation of Lys to Ala or Glu, but not to Arg. In conclusion, residues Lys(57) of L-ficolin and Lys(47) of H-ficolin are key components of the interaction with the MASPs and CRT, providing strong indication that MBL and the ficolins share homologous binding sites for both types of proteins.
Multichannel Sampling of Parametric Signals with a Successive Approximation Property (2006)

Recently the sampling theory for certain parametric signals based on rate of innovation has been extended to all sampling kernels that satisfy the Strang-Fix conditions, thus including many attractive choices with finite support. We propose a new sampling scheme in which samples are taken simultaneously at the outputs of multiple channels. This new scheme is closely related to previously known cases, but provides a successive approximation property that can be used for detecting undermodeling. We also draw connections to splines and multi-scale sampling of signals.
Modulation of DNA Vaccine-Elicited CD8 + T-Lymphocyte Epitope Immunodominance Hierarchies (2006)

Generating broad cellular immune responses against a diversity of viral epitopes is a major goal of current vaccine strategies for human immunodeficiency virus type 1 (HIV-1) and other pathogens. Virus-specific CD8(+) T-lymphocyte responses, however, are often highly focused on a very limited number of immunodominant epitopes. For an HIV-1 vaccine, the breadth of CD8(+) T-lymphocyte responses may prove to be critical as a result of the need to cover a wide diversity of viral isolates in the population and to limit viral escape from dominant epitope-specific T lymphocytes. Here we show that epitope modification strategies can alter CD8(+) T-lymphocyte epitope immunodominance hierarchies elicited by a DNA vaccine in mice. Mice immunized with a DNA vaccine expressing simian immunodeficiency virus Gag lacking the dominant D(b)-restricted AL11 epitope generated a marked and durable augmentation of responses specific for the subdominant D(b)-restricted KV9 epitope. Moreover, anatomic separation strategies and heterologous prime-boost regimens generated codominant responses against both epitopes. These data demonstrate that dominant epitopes can dramatically suppress the immunogenicity of subdominant epitopes in the context of gene-based vaccines and that epitope modification strategies can be utilized to enhance responses to subdominant epitopes.
Functional analysis of T lymphocyte subsets in antiviral host defense. (1987)

The role of different T cell subsets in antiviral host defense was investigated by treating thymectomized C57BL/6 and CBA/J mice with monoclonal rat anti-Lyt-2 or anti-L3/T4 IgG 2b antibodies 14 and 10 days before infection. This treatment depleted the respective T cell subsets to undetectable levels in peripheral blood when assayed by immunofluorescence. In mice treated with anti-Lyt-2, induction of cytotoxic T cells was reduced to less than 1 to 2% after intravenous infection with Armstrong strain of lymphocytic choriomeningitis virus (LCMV). In addition, no primary swelling of the footpad could be detected following local inoculation of the virus. In animals treated with anti-L3/T4, antiviral cytotoxic T lymphocyte responses were reduced by a factor of 10. These L3/T4+ cell-depleted mice showed delayed footpad swelling after local injection of LCMV Armstrong. After intracerebral infection with LCMV, anti-Lyt-2-treated mice were resistant and those injected with anti-L3/T4 were totally susceptible to LCMV Armstrong-triggered immunopathologic disease. Virus could be detected in the blood of antibody-treated mice 7 days after inoculation; however, no virus could be measured in the blood of surviving anti-Lyt-2-treated animals 15 days after intracerebral infection. Serum titers of interferon-alpha,beta induced by viral infection remained unaffected by depletion of T cell subsets. Anti-L3/T4 antibody-treated C57BL/6 mice failed to generate IgG antibodies against the New Jersey strain of vesicular stomatitis virus, whereas Lyt-2+ cell-depleted mice had normal antivesicular stomatitis virus (New Jersey strain) IgG antibody titers.
Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay. (1976)

Cytotoxic effector T cells of F1 (BALB/c X BALB.B) (H-2d/b) mice immunized against the minor histocompatibility differences of C57BL/10 (H-2b) can lyse targets from C57BL/10, but cannot lyse B10.D2 (H-2d) targets. Despite this lack of cross-reaction in the cytotoxic assay, C57BL/10 cells do prime F1 (BALB/c X BALB.B) mice for a secondary cytotoxic response to B10.D2. C57BL/10-primed, B10.D2-boosted cytotoxic cells lyse B10.D2 targets but not C57BL/10 targets. DBA/2 (H-2d) spleen cells or thymocytes prime F1 mice for a secondary response to DBA/2, B10.D2, and C57BL/10 cells, but DBA/2 mastocytes, P815, do not prime for a response to C57BL/10. Whether H-2 congenic lymphoid cells express minor histocompatibility determinants which cross-react at the cytotoxic T-cell level or the helper T-cell level is discussed.
Multifiber, multiwavelength, fiber optic fluorescence spectrophotometer (1992)

A fiberoptic spectrofluorimeter was constructed capable of remote operation of up to 18 biosensors under fully automated, multiplexed control. Excitation and emission wavelengths were separately adjustable, as were optical bandwidths, signal gain, phase, integration time, and illumination duty cycle. Synchronous demodulation was used to enhance signal-to-noise ratio and allow operation under ambient lighting conditions. Detection limit for aqueous sodium-fluorescein was below 1 ng/mL at greater than unity signal-to-noise ratio, with effective sampling volumes less than 0.02 microL. The fluorimeter showed characteristics fiberoptic sampling behavior with asymptotic nonzero signal magnitudes under increasing pathlength conditions.
Efficient Gene Transfer To Pancreatic Islets Mediated By Adenoviral Vectors (1995)

Csete, Marie E.; Benhamou, Pierre Y.; Drazan, Kenneth E.; Wu, Llily; McIntee, Diane F.; Afra, Robert; Mullen, Yoko; Busuttil, Ronald W.; Shaked, Abraham Author Information
Safety in numbers (2001)

A mandatory minimum nurse to patient ratio improves outcomes. Linda Aiken reports on her research
IVECS: An Interactive Virtual Environment for the Correction of .STL Files (1996)

Abstract The current trends towards fully integrated digital design processes depend on the use of physical mockups. Free Form Fabrication extracts data from Computer Aided Design software and transforms them into a tangible reality. Virtual Reality (VR) provides a remarkable complement to these techniques. The system presented responds to the needs to ensure accurate data and quick prototyping by providing visualization and edition of Computer Aided Design files in a Virtual Environment. This paper expands on the use of VR to virtually prototype artifacts represented by .STL files. It describes different techniques to interact with the object in the VE. Besides manipulating the object, various methods to display the triangles generated by tessellation are detailed and ways to correct the files are illustrated.