gebhart/patrepeval huggingface dataset:
Semisynthetic Nanoreactor for Reversible Single-Molecule Covalent Chemistry (2016)

Protein engineering has been used to remodel pores for applications in biotechnology. For example, the heptameric α-hemolysin pore (αHL) has been engineered to form a nanoreactor to study covalent chemistry at the single-molecule level. Previous work has been confined largely to the chemistry of cysteine side chains or, in one instance, to an irreversible reaction of an unnatural amino acid side chain bearing a terminal alkyne. Here, we present four different αHL pores obtained by coupling either two or three fragments by native chemical ligation (NCL). The synthetic αHL monomers were folded and incorporated into heptameric pores. The functionality of the pores was validated by hemolysis assays and by single-channel current recording. By using NCL to introduce a ketone amino acid, the nanoreactor approach was extended to an investigation of reversible covalent chemistry on an unnatural side chain at the single-molecule level.
Intracellular processing and presentation of T cell epitopes, expressed by recombinant Escherichia coli and Salmonella typhimurium, to human T cells (1995)

Vaccines based on recombinant attenuated bacteria represent a potentially safe and effective immunization strategy. A carrier system was developed to analyze in vitro whether foreign T cell epitopes, inserted in the outer membrane protein PhoE of Escherichia coli and expressed by recombinant bacteria, are efficiently processed and presented via human leukocyte antigen (HLA) class I and II molecules by bacterial infected human macrophages. A well-defined HLA-B27-restricted cytotoxic T cell (CTL) epitope and an HLA-DR53 restricted T helper (Th) epitope of the fusion protein of measles virus were genetically inserted in a surface-exposed region of PhoE, and the chimeric proteins were expressed in E. coli and Salmonella typhimurium. Macrophages infected with both recombinant bacteria presented the Th epitope to the specific CD4+ T cell clone, but failed to present the CTL epitope to the specific CD8+ T cell clone. Presentation of the Th epitope by the infected macrophages was inhibited by cytochalasin D, indicating that phagocytic processing of intact bacteria within infected macrophages was essential for antigen presentation via HLA class II. Presentation of the Th epitope to the CD4+ T cell clone by infected macrophages was blocked by brefeldin A and cycloheximide, indicating the requirement of nascent HLA class II molecules for presentation. The efficiency of macrophages to process and present the inserted Th epitope was similar for both the recombinant E. coli and S. typhimurium strains.
Molecular Diagnosis of Familial Adenomatous Polyposis (1993)

The protein and allele-specific--expression assays provide a practical and sensitive method for molecular diagnosis of familial adenomatous polyposis. This approach will facilitate care, allowing routine testing of subjects at risk and genetic confirmation of spontaneous mutations.
Inverted-repeat DMA: a new gene-silencing tool for seed lipid modification (2000)

Post-transcriptional gene silencing (PTGS) has been successfully used to modify seed lipids in oilseed crops like soybean, canola and sunflower. Conventionally, PTGS has been induced by transforming the plants with either antisense or co-suppression constructs targeted against key seed lipid biosynthesis genes. A major drawback of this approach has been the recovery of only a modest proportion of silenced individuals from large populations of transgenic plants. In this report we show that inverted-repeat DNA constructs containing an intron encoding RNA with a hairpin structure can induce PTGS with very high frequency.
Deletion of the carboxyl-terminal exons of K-sam/FGFR2 by short homology-mediated recombination, generating preferential expression of specific messenger RNAs. (1999)

The K-sam gene was first identified as an amplified gene from human gastric cancer cell line KATOIII, and its product is identical to fibroblast growth factor receptor 2. The K-sam gene is located on human chromosome 10q26 and is preferentially amplified in the poorly differentiated types, especially in the scirrhous type, of gastric cancers. During the course of studies on the structural characterization of the amplification units, we found that the carboxyl-terminal exons of K-sam were deleted in three of four of the scirrhous type of gastric cancer cell lines. These deletions generate preferential expression of mRNAs encoding K-sam proteins lacking the carboxyl-terminal region containing the tyrosine residues at positions 780, 784, and 813. The carboxyl-terminal region has been reported to have a sequence required for the inhibition of NIH3T3 transformation, indicating that cells with amplification of the truncated K-sam gene have a growth advantage during the carcinogenic process for the scirrhous type of gastric cancers. This is the first report showing the deletion of the carboxyl-terminal exons of the receptor-type of the protein tyrosine kinase gene. Sequence analysis of the DNA sequences surrounding the deletion junctions shows the presence of unique sequences and indicates the involvement of short homology-mediated recombination in the generation of these deletions.
Living carbocationic polymerization. XXX. One‐pot synthesis of allyl‐terminated linear and tri‐arm star polyisobutylenes, and epoxy‐ and hydroxy‐telechelics therefrom (1990)

Abstract Mono‐ and di‐ended linear and three‐arm star allyl‐telechelic polyisobutylenes, PIBA, APIBA and (where A = CH 2 CHCH 2 ) have been prepared by a rapid economical one‐pot polymerization‐functionalization process. The process involves the living polymerization of isobutylene (IB) by mono‐, di‐, or tri‐functional initiating systems, specifically by allphatic and aromatic tert ‐ester and ‐ether/TiCl 4 combinations, followed by electrophilic functionalization of the living sites with allyl‐trimethylsilane (ATMS). Structural characterization by 1 H‐NMR spectroscopy and end group titration with m ‐chloroperbenzoic acid ( m ‐CPBA) indicate quantitative end allylation even with relatively slowly initiating systems like DiOAcTMH 7 /TiCl 4 . Detailed kinetic analysis of the latter system indicates, unexpetedly, cationation to be rate determining. Quantitative derivatizations of the allyl termini have yielded mono‐, di‐, and tri‐epoxy‐ and ‐hydroxy‐telechelic PIBs. Strong rubbery networks have been made by curing the epoxy‐telechelic PIBs with triethylene tetramine and by reacting the hydroxy‐telechelic PIBs with MDI.
RheoSorb: A Specific Adsorber for Fibrinogen Elimination in Clinical Situations with Impaired Rheology (2002)

A functional microcirculation is crucial for the normal function of an organism. In many physiopathological situations, impaired microcirculation may contribute to the development or progress of diseases. Microcirculation is closely interrelated with blood and especially plasma rheology. Thus, improvement of plasma viscosity has beneficial effects on rheology, microcirculation, and the related tissue microenvironment. However, at best tools that only have a minor influence on plasma viscosity exist so far. Fibrinogen is known to be the major contributor to plasma viscosity, making it an interesting target for therapeutic intervention. An adsorber specific for fibrinogen was developed on the basis of the TheraSorb technology. The TheraSorb technology (PlasmaSelect AG, Teterow, Germany) allows the selective removal of components from human blood plasma by means of an affinity chromatography column. A ligand specific for a defined plasma component is coupled to a solid matrix (sepharose) thus binding and eliminating the target molecule from plasma. Using a fibrinogen specific pentapeptide as ligand, selective removal of fibrinogen, fibrin, and degradation products, containing the target sequence of these molecules, can be obtained. The LIFE-18, a state-of-the-art integrated plasma therapy instrument, is used to perform the treatment. The procedure improves plasma and whole blood viscosity in a dose dependent manner as shown in Phase 1 and 2 clinical trials. This article describes the first clinical experience in patients with diabetic foot syndrome and provides an outlook for further clinical and scientific investigations related to this promising new procedure.
The Influence of HLA-DRB1 Genes on Disease Severity in Rheumatoid Arthritis (1992)

Genotyping patients with rheumatoid arthritis for both HLA-DRB1 alleles identifies clinical subsets with distinct profiles of disease manifestations.
Microsurgical Anastomosis of Rat Carotid Arteries with the CO2 Laser (1986)

In order to further evaluate the role of lasers in microvascular tissue closure, we modified an existing CO2 surgical laser (Xanar XA-20) by adding a partially reflecting mirror to attenuate the beam. This allowed the laser to operate at an output of approximately 100 mW, which was appropriate to achieve microvascular closures. In each of 43 rats, one carotid artery was transected and then anastomosed with standard suture technique with 10 to 12 simple interrupted sutures of size 10-0 Ethilon nylon suture (Ethicon, Inc.). The opposite carotid in each rat was anastomosed by the placement of three stay sutures followed by the application of laser irradiation to the tissue between the stay sutures at 90 to 100 mW, spot size of 0.2 mm, pulse duration 0.2 seconds, approximately 20 to 30 pulses per anastomosis. In vivo test periods were 1 hour, 1 day, 3 days, 7 days, 10 days, 14 days, 28 days, 91 days, and 180 days. All anastomoses were evaluated for patency, and selected samples were utilized for light microscopy, and mechanical testing (intraluminal pressure raised to 300 mmHg). It was determined that similar patency rates and slightly faster time to perform the same procedure could be achieved with the use of the low-powered CO2 laser. However, histologic evidence of significant medial damage raises concern about the long-term risk of a higher aneurysm rate. Vessel damage and the lack of simple intraoperative methods to verify the quality of the laser technique restrict these authors from advocating the clinical introduction of the procedure until further advances are made.(ABSTRACT TRUNCATED AT 250 WORDS)
Blockade of the B7-H1/PD-1 pathway for cancer immunotherapy. (2011)

The aim of cancer immunotherapy is to treat malignant disease by inducing or enhancing cancer specific immune responses. With the identification of tumor-associated antigens (TAAs) in the 1990s, cancer immunotherapy research largely focused on inducing immune responses against TAAs but achieved limited success. More recently, the underlying mechanisms and molecular pathways that cancers manipulate to subvert immune-mediated destruction have been identified, including a set of molecules with potent coinhibitory functions. Coinhibitory molecules are expressed on the surface of immune cells, cancer cells, and stromal cells and negatively regulate immune responses to cancer. In particular, one of these ligand-receptor coinhibitory interactions, B7-H1/PD-1, is critical for modulating immune responses to cancer. This knowledge led to the design of revolutionary new immunotherapeutics based on the manipulation of these molecular pathways. Monoclonal antibodies (mAbs) are the primary immunotherapeutic modality used to promote immune function via antagonism or agonism of inhibitory or stimulatory molecular pathways, respectively. Here, we review current knowledge on the function of the B7-H1/PD-1 pathway in mice and humans, its role in the subversion of immune responses in cancer, and clinical evidence that mAb targeting of this pathway results in profound immune anti-cancer effects.
cDNA cloning and expression of platelet p24/CD9. Evidence for a new family of multiple membrane-spanning proteins (1991)

This study was designed to clone, sequence, and express the full-length cDNA for the human platelet p24/CD9 antigen. A 1.3-kilobase cDNA clone was identified that has an open reading frame encoding a mature protein of 228 amino acids (approximately 25,400 Da) containing 10 cysteine residues and four putative transmembrane domains. The identity of the clone was confirmed by: (i) its predicted size, (ii) identity to four peptide sequences from the isolated protein including the NH2 terminus, and (iii) expression of the isolated clone in Xenopus oocytes and Chinese hamster ovary cells. p24/CD9 has sequence identity (24-34%) to four other cell-surface proteins: ME491, a melanoma antigen; CO-029, a carcinoma antigen; CD37, a leukocyte antigen; and SM23, an antigen of the parasitic helminth Schistosoma mansoni. The five proteins have a similar number of amino acids and are characterized by the presence of four putative transmembrane domains. These data indicate the presence of a new family of surface antigens that may function in cellular activation and differentiation.
DNA ligands that bind tightly and selectively to cellobiose (1998)

Cell surface oligosaccharides have been shown to play essential biological roles in such diverse biological phenomena as cellular adhesion, molecular recognition, and inflammatory response. The development of high-affinity ligands capable of selectively recognizing a variety of small motifs in different oligosaccharides would be of significant interest as experimental and diagnostic tools. As a step toward this goal we have developed DNA ligands that recognize the disaccharide cellobiose, whether in soluble form or as the repeating unit of the polymer, cellulose. These DNA "aptamers" bind with high selectivity to cellobiose with little or no affinity for the related disaccharides lactose, maltose, and gentiobiose. Thus, the DNA ligands can discriminate sugar epimers, anomers, and disaccharide linkages.
A Molecular Platform in Neurons Regulates Inflammation after Spinal Cord Injury (2008)

Vigorous immune responses are induced in the immune privileged CNS by injury and disease, but the molecular mechanisms regulating innate immunity in the CNS are poorly defined. The inflammatory response initiated by spinal cord injury (SCI) involves activation of interleukin-1beta (IL-1beta) that contributes to secondary cell death. In the peripheral immune response, the inflammasome activates caspase-1 to process proinflammatory cytokines, but the regulation of trauma-induced inflammation in the CNS is not clearly understood. Here we show that a molecular platform [NALP1 (NAcht leucine-rich-repeat protein 1) inflammasome] consisting of caspase-1, caspase-11, ASC (apoptosis-associated speck-like protein containing a caspase-activating recruitment domain), and NALP1 is expressed in neurons of the normal rat spinal cord and forms a protein assembly with the X-linked inhibitor of apoptosis protein (XIAP). Moderate cervical contusive SCI induced processing of IL-1beta, IL-18, activation of caspase-1, cleavage of XIAP, and promoted assembly of the multiprotein complex. Anti-ASC neutralizing antibodies administered to injured rats entered spinal cord neurons via a mechanism that was sensitive to carbenoxolone. Therapeutic neutralization of ASC reduced caspase-1 activation, XIAP cleavage, and interleukin processing, resulting in significant tissue sparing and functional improvement. Thus, rat spinal cord neurons contain a caspase-1, pro-ILbeta, and pro-IL-18 activating complex different from the human NALP1 inflammasome that constitutes an important arm of the innate CNS inflammatory response after SCI.
Association of Polymorphisms in Genes Regulating the Corticotropin-Releasing Factor System With Antidepressant Treatment Response (2010)

These data indicate that a genetic variant within the CRHBP locus affects response to citalopram in African American and Hispanic patients, suggesting a role for this gene and for the CRF system in antidepressant treatment response.
Degradation of Starch–Poly(β-Hydroxybutyrate-Co-β-Hydroxyvalerate) Bioplastic in Tropical Coastal Waters (1999)

Extruded bioplastic was prepared from cornstarch or poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate) (PHBV) or blends of cornstarch and PHBV. The blended formulations contained 30 or 50% starch in the presence or absence of polyethylene oxide (PEO), which enhances adherence of starch granules to PHBV. Degradation of these formulations was monitored for 1 year at four stations in coastal water southwest of Puerto Rico. Two stations were within a mangrove stand. The other two were offshore; one of these stations was on a shallow shoulder of a reef, and the other was at a location in deeper water. Microbial enumeration at the four stations revealed considerable flux in the populations over the course of the year. However, in general, the overall population densities were 1 order of magnitude less at the deeper-water station than at the other stations. Starch degraders were 10- to 50-fold more prevalent than PHBV degraders at all of the stations. Accordingly, degradation of the bioplastic, as determined by weight loss and deterioration of tensile properties, correlated with the amount of starch present (100% starch >50% starch > 30% starch > 100% PHBV). Incorporation of PEO into blends slightly retarded the rate of degradation. The rate of loss of starch from the 100% starch samples was about 2%/day, while the rate of loss of PHBV from the 100% PHBV samples was about 0.1%/day. Biphasic weight loss was observed for the starch-PHBV blends at all of the stations. A predictive mathematical model for loss of individual polymers from a 30% starch-70% PHBV formulation was developed and experimentally validated. The model showed that PHBV degradation was delayed 50 days until more than 80% of the starch was consumed and predicted that starch and PHBV in the blend had half-lives of 19 and 158 days, respectively. Consistent with the relatively low microbial populations, bioplastic degradation at the deeper-water station exhibited an initial lag period, after which degradation rates comparable to the degradation rates at the other stations were observed. Presumably, significant biodegradation occurred only after colonization of the plastic, a parameter that was dependent on the resident microbial populations. Therefore, it can be reasonably inferred that extended degradation lags would occur in open ocean water where microbes are sparse.
Involvement of the Ubiquitin/Proteasome System in Sorting of the Interleukin 2 Receptor β Chain to Late Endocytic Compartments (2001)

Down-regulation of cell surface growth factor receptors plays a key role in the tight control of cellular responses. Recent reports suggest that the ubiquitin system, in addition to participating in degradation by the proteasome of cytosolic and nuclear proteins, might also be involved in the down-regulation of various membrane receptors. We have previously characterized a signal in the cytosolic part of the interleukin 2 receptor beta chain (IL2Rbeta) responsible for its targeting to late endosomes/lysosomes. In this report, the role of the ubiquitin/proteasome system on the intracellular fate of IL2Rbeta was investigated. Inactivation of the cellular ubiquitination machinery in ts20 cells, which express a thermolabile ubiquitin-activating enzyme E1, leads to a significant decrease in the degradation rate of IL2Rbeta, with little effect on its internalization. In addition, we show that a fraction of IL2Rbeta can be monoubiquitinated. Furthermore, mutation of the lysine residues of the cytosolic region of a chimeric receptor carrying the IL2Rbeta targeting signal resulted in a decreased degradation rate. When cells expressing IL2Rbeta were treated either by proteasome or lysosome inhibitors, a significant decrease in receptor degradation was observed. Our data show that ubiquitination is required for the sorting of IL2Rbeta toward degradation. They also indicate that impairment of proteasome function might more generally affect intracellular routing.
View Invariant Appearance-Based Person Reidentification Using Fast Online Feature Selection and Score Level Fusion (2012)

Fast and robust person reidentification is an important task in multi-camera surveillance and automated access control. We present an efficient appearance-based algorithm, able to reidentify a person regardless of occlusions, distance to the camera, and changes in view and lighting. The use of fast online feature selection techniques enables us to perform reidentification in hyper-real-time for a multi-camera system, by taking only 10 seconds for evaluating 100 minutes of HD-video data. We demonstrate, that our approach surpasses current appearance-based state-of-the-art in reidentification quality and computational speed and sets a new reference in non-biometric reidentification.
Time of commitment of inside cells isolated from preimplantation mouse embryos (1978)

ABSTRACT Groups of inside cells (ICs) and inner cell masses (ICMs) were isolated from individual mouse embryos between the late morula and day expanded blastocyst stages using a modified immunosurgical procedure, and their purity and developmental potential were assessed in vitro. Several different techniques failed to detect the presence of viable contaminating outside cells on ICs isolated from any of the stages studied. The numbers of inside cells isolated from the earlier stages, counted in air-dried preparations, were considerably higher than previous estimates from serial sections; whereas the numbers isolated from expanded blastocysts were in reasonable agreement. Thus the proportion of inside cells recovered by immunosurgery decreases over this period of development. In view of the evidence that inside cells divide at a faster rate than outside cells at these stages, it is argued that there may be an outward movement of inside cells capable of forming trophectoderm, during expansion of the blastocyst. ICs and ICMs in vitro were observed to develop in one of two distinct ways according to the stage at which they were isolated. ICs from late morulae and some early cavitating blastocysts formed blastocyst-like vesicles over a period of 24-36 h in culture. The presence of trophectoderm cells in these vesicles was confirmed by the persistence of giant cells after ectopic transfer. In contrast ICs from a minority of early cavitating blastocysts, and all ICMs from day expanded blastocysts did not form vesicles, but proliferated endodermlike cells. Thus at least some inside cells do not appear to lose the capacity to form trophectoderm and do not become committed to an ICM fate until after the initial formation of the blastocoel cavity.
Entanglement and bifurcations in Jahn-Teller models (2004)

We compare and contrast the entanglement in the ground state of two Jahn-Teller models. The $E\ensuremath{\bigotimes}\ensuremath{\beta}$ system models the coupling of a two-level electronic system, or qubit, to a single-oscillator mode, while the $E\ensuremath{\bigotimes}\ensuremath{\epsilon}$ models the qubit coupled to two independent, degenerate oscillator modes. In the absence of a transverse magnetic field applied to the qubit, both systems exhibit a degenerate ground state. Whereas there always exists a completely separable ground state in the $E\ensuremath{\bigotimes}\ensuremath{\beta}$ system, the ground states of the $E\ensuremath{\bigotimes}\ensuremath{\epsilon}$ model always exhibit entanglement. For the $E\ensuremath{\bigotimes}\ensuremath{\beta}$ case we aim to clarify results from previous work, alluding to a link between the ground-state entanglement characteristics and a bifurcation of a fixed point in the classical analog. In the $E\ensuremath{\bigotimes}\ensuremath{\epsilon}$ case we make use of an ansatz for the ground state. We compare this ansatz to exact numerical calculations and use it to investigate how the entanglement is shared between the three system degrees of freedom.