gebhart/patrepeval huggingface dataset:
Acid-cleavable thiomaleamic acid linker for homogeneous antibody–drug conjugation (2013)

In this communication we describe a novel acid-cleavable linker strategy for antibody-drug conjugation. Functional disulfide bridging of the single interchain disulfide bond of a trastuzumab Fab fragment yields a homogeneous antibody-drug conjugate bearing a thiomaleamic acid linker. This linker is stable at physiological pH and temperature, but quantitatively cleaves at lysosomal pH to release the drug payload.
Subject-specific profiles of QT/RR hysteresis (2008)

The time lag of the QT interval adaptation to heart rate changes (QT/RR hysteresis) was studied in 40 healthy subjects (18 females; mean age, 30.4+/-8.1 yr) with 3 separate daytime (>13 h) 12-lead electrocardiograms (ECG) in each subject. In each recording, 330 individual 10-s ECG segments were measured, including 100 segments preceded by 2 min of heart rate varying greater than +/-2 beats/min. Other segments were preceded by a stable heart rate. In segments preceded by variable rate, QT/RR hysteresis was characterized by lambda parameters of the exponential decay models. The intrasubject SDs of lambda values were compared with the intersubject SD of the individual means. The lambda values were also correlated to individually optimized parameters of heart rate correction. Intrasubject SDs of lambda were substantially smaller than the population SD of individual means (0.390+/-0.197 vs. 0.711, P<0.0001). The lambda values were unrelated to the QT/RR correction parameters. When compared with the corrected QT (QTc) for averaged RR intervals in 10-s ECGs and with the averaged RR intervals in 2-min history, QTc for QT/RR hysteresis led to a substantially smaller SD of QTc values (11.4+/-2.00, 6.33+/-1.31, and 4.66+/-0.85 ms, respectively, P<0.0001). Thus the speed with which the QT interval adapts to heart rate changes is highly individual with intrasubject stability and intersubject variability. QT/RR hysteresis is independent of the static QT/RR relationship and should be considered as a separate physiological process. The combination of individual heart rate correction with individual hysteresis correction of the QT interval is likely to lead to substantial improvements of cardiac repolarization studies.
MD-2 Binds to Bacterial Lipopolysaccharide (2001)

The exact roles and abilities of the individual components of the lipopolysaccharide (LPS) receptor complex of proteins remain unclear. MD-2 is a molecule found in association with toll-like receptor 4. We produced recombinant human MD-2 to explore its LPS binding ability and role in the LPS receptor complex. MD-2 binds to highly purified rough LPS derived from Salmonella minnesota and Escherichia coli in five different assays; one assay yielded an apparent KD of 65 nm. MD-2 binding to LPS did not require LPS-binding proteins LBP and CD14; in fact LBP competed with MD-2 for LPS. MD-2 enhanced the biological activity of LPS in toll-like receptor 4-transfected Chinese hamster ovary cells but inhibited LPS activation of U373 astrocytoma cells and of monocytes in human whole blood. These data indicate that MD-2 is a genuine LPS-binding protein and strongly suggest that MD-2 could play a role in regulation of cellular activation by LPS depending on its local availability.
Minimum rate sampling and reconstruction of signals with arbitrary frequency support (1999)

We examine the question of reconstruction of signals from periodic nonuniform samples. This involves discarding samples from a uniformly sampled signal in some periodic fashion. We give a characterization of the signals that can be reconstructed at exactly the minimum rate once a nonuniform sampling pattern has been fixed. We give an implicit characterization of the reconstruction system, and a design method by which the ideal reconstruction filters may be approximated. We demonstrate that for certain spectral supports the minimum rate can be approached or achieved using reconstruction schemes of much lower complexity than those arrived at by using spectral slicing, as in earlier work. Previous work on multiband signals have typically been those for which restrictive assumptions on the sizes and positions of the bands have been made, or where the minimum rate was approached asymptotically. We show that the class of multiband signals which can be reconstructed exactly is shown to be far larger than previously considered. When approaching the minimum rate, this freedom allows us, in certain cases to have a far less complex reconstruction system.
The Nuclear Export Signal within the E4orf6 Protein of Adenovirus Type 5 Supports Virus Replication and Cytoplasmic Accumulation of Viral mRNA (2000)

During the late phase of adenovirus infection, viral mRNA is efficiently transported from the nucleus to the cytoplasm while most cellular mRNA species are retained in the nucleus. Two viral proteins, E1B-55 kDa and E4orf6, are both necessary for these effects. The E4orf6 protein of adenovirus type 5 binds and relocalizes E1B-55 kDa, and the complex of the two proteins was previously shown to shuttle continuously between the nucleus and cytoplasm. Nucleocytoplasmic transport of the complex is achieved by a nuclear export signal (NES) within E4orf6. Mutation of this signal sequence severely reduces the ability of the E1B-55 kDa-E4orf6 complex to leave the nucleus. Here, we examined the role of functional domains within E4orf6 during virus infection. E4orf6 or mutants derived from it were transiently expressed, followed by infection with recombinant adenovirus lacking the E4 region and determination of virus yield. An arginine-rich putative alpha helix near the carboxy terminus of E4orf6 contributes to E1B-55 kDa binding and relocalization as well as to the synthesis of viral DNA, mRNA, and proteins. Further mutational analysis revealed that mutation of the NES within E4orf6 considerably reduces its ability to support virus production. The same effect was observed when nuclear export was blocked with a competitor. Further, a functional NES within E4orf6 contributed to the efficiency of late virus protein synthesis and viral DNA replication, as well as total and cytoplasmic accumulation of viral late mRNA. Our data support the view that NES-mediated nucleocytoplasmic shuttling strongly enhances most, if not all, intracellular activities of E4orf6 during the late phase of adenovirus infection.
Long-term Hardware-related Complications of Deep Brain Stimulation (2002)

Long-term follow-up reveals that hardware-related complications occur in a significant number of patients. Factors that lead to such complications must be identified and addressed to maximize the important benefits of DBS therapy.
Majorana Bound States without Vortices in Topological Superconductors with Electrostatic Defects (2010)

Vortices in two-dimensional superconductors with broken time-reversal and spin-rotation symmetry can bind states at zero excitation energy. These so-called Majorana bound states transform a thermal insulator into a thermal metal and may be used to encode topologically protected qubits. We identify an alternative mechanism for the formation of Majorana bound states, akin to the way in which Shockley states are formed on metal surfaces: An electrostatic line defect can have a pair of Majorana bound states at the end points. The Shockley mechanism explains the appearance of a thermal metal in vortex-free lattice models of chiral p-wave superconductors and (unlike the vortex mechanism) is also operative in the topologically trivial phase.
Activities of HIV-RNA targeted ribozymes transcribed from a 'shot-gun' type ribozyme-trimming plasmid. (1992)

We have constructed a "shot-gun" type ribozyme-trimming system. By concatenating several units, each consisting of a trans-acting ribozyme (targeted to HIV-RNA) and cis-acting ribozymes (trimming 5'- and 3'-ends of the trans-acting ribozyme), several kinds of trans-acting ribozymes can be liberated upon transcription and self-cleavage. Since each liberated HIV-RNA-targeted ribozymes can work independently, they can simultaneously cleave HIV-RNA at several different sites. Ribozymes were targeted at relatively conserved GUC-containing sites at LTR, gag and tat regions.
ENGRAFTMENT OF HUMAN KIDNEY TISSUE IN RAT RADIATION CHIMERA (1997)

Our model should be useful for the study of human fetal renal development and the human alloresponse against fetal tissue.
Microarray-Based Identification of Tenascin C and Tenascin XB , Genes Possibly Involved in Tumorigenesis Associated with Neurofibromatosis Type 1 (2007)

TNXB and TNC may be involved in the malignant transformation of plexiform neurofibromas. Anti-TNC antibodies, already used successfully in clinical trials to treat malignant human gliomas, may be an appropriate new therapeutic strategy for NF1.
Conservation of residual hearing with cochlear implantation. (1997)

Conservation of hearing occurred in approximately half of the subjects reviewed. There is no indication of what factors contributed to the preservation of hearing in those with postsurgical residual hearing or if that hearing is usable. The study does suggest that a larger multicenter longitudinal study would be of value of determine what factors may be related to conserved hearing in implanted patients.
Hemoglobin function in stored blood (1969)

Serial oxygen dissociation curves were performed on blood units preserved in acid-citrate-dextrose (ACD), ACD-adenine, and ACD-adenine-inosine. Dividing blood from a single donor into two or more bags allowed direct comparison between preservatives. During the 1st wk of storage in ACD, a progressive increase in oxygen affinity was observed. Thereafter, little further change was noted. Oxygen affinity increased even more rapidly during initial storage in ACD-adenine. However, with the inclusion of inosine as a preservative, oxygen affinity remained unaltered during the first 2 wk. Increases in oxygen affinity correlated well with falling levels of red cell 2,3-diphosphoglycerate (2,3-DPG) during storage. No significant changes in glutathione, reduced form (GSH), or A3 (A(I)) hemoglobin levels were noted during the first 3 wk of storage. No significant accumulation of ferrihemoglobin was detected. When blood stored 20 days in ACD or ACD-adenine was incubated with inosine for 60 min at 37 degrees C, 2,3-DPG and adenosine triphosphate (ATP) were resynthesized, and oxygen affinity was decreased. The distribution of 2,3-DPG in fresh and stored red cells appeared to influence experimental values for Hill's n, a measure of heme-heme interaction.
Loading databases using dataflow parallelism (1994)

This paper describes a parallel database load prototype for Digital's Rdb database product. The prototype takes a dataflow approach to database parallelism. It includes an explorer that discovers and records the cluster configuration in a database, a client CUI interface that gathers the load job description from the user and from the Rdb catalogs, and an optimizer that picks the best parallel execution plan and records it in a web data structure. The web describes the data operators , the dataflow rivers among them, the binding of operators to processes, processes to processors, and files to discs and tapes. This paper describes the optimizer's cost-based hierarchical optimization strategy in some detail. The prototype executes the web's plan by spawning a web manager process at each node of the cluster. The managers create the local executor processes, and orchestrate startup, phasing, checkpoint, and shutdown. The execution processes perform one or more operators. Data flows among the operators are via memory-to-memory streams within a node, and via web-manager multiplexed tcp/ip streams among nodes. The design of the transaction and checkpoint/restart mechanisms are also described. Preliminary measurements indicate that this design will give excellent scaleups.
Treatment of ethylene glycol poisoning with ethyl alcohol (1965)

In the course of phylogenetic evolution, the substrate specificity of alcohol dehydrogenase, the enzyme which detoxicates ethyl alcohol, has apparently broadened. Thus, while the enzyme from yeast oxidizes ethyl alcohol and only a few other alcohols,<sup>1</sup>the enzyme of the horse liver is capable of oxidizing a range of other alcohols.<sup>1,2</sup>The human enzyme has an even wider range,<sup>3</sup>since contrary to the horse enzyme it oxidizes both ethyl alcohol and ethylene glycol. While chemically ethylene glycol is very similar to ethyl alcohol, both these compounds are toxic to man. Detailed studies of the enzymatic oxidation of ethylene glycol demonstrate that ethyl alcohol, the natural substrate, is a potent competitive inhibitor of the oxidation of ethylene glycol.<sup>3</sup>Hence, low concentrations of ethyl alcohol prevent the oxidation of large concentrations of ethylene glycol. These biochemical features of the catalytic behavior of human-liver alcohol dehydrogenase have served as
Expression of hepatitis B virus S gene by herpes simplex virus type 1 vectors carrying alpha- and beta-regulated gene chimeras. (1984)

The domain of the hepatitis B virus (HBV) S gene specifying the HBV surface antigen (HBsAg) and comprising 25 base pairs of the 5'-transcribed noncoding region, the structural gene sequences, and the 3'-noncoding gene sequences including the polyadenylylation site was fused to the promoter-regulatory regions of the beta-thymidine kinase and of the alpha 4 gene of herpes simplex virus type 1 (HSV-1). The chimeric constructs were then inserted into the HSV-1 genome and specifically into the thymidine kinase gene by homologous recombination through flanking sequences. Cells infected with recombinants carrying the chimeric genes produced and excreted the HBsAg into the extracellular medium for at least 12 hr concurrently with the multiplication of the HSV-1 vector. The temporal patterns of expression and the observation that HBV S gene linked to the HSV-1 alpha promoter-regulatory region was regulated as an HSV-1 alpha gene indicate that the HBsAg gene chimeras inserted into the virus were regulated as viral genes. The HBsAg banded in isopycnic CsCl density gradients at a density of 1.17 g/cm3. Electron microscopic studies revealed that HBsAg harvested from the extracellular medium and banded in CsCl density gradients contained spherical particles 15-22 nm in diameter, characteristic of empty HBV envelopes. The results indicate that HSV-1 is a suitable vector for the expression of foreign genes placed under the control of HSV promoter-regulatory regions.
Resazurin Microtiter Assay Plate Testing of Mycobacterium tuberculosis Susceptibilities to Second-Line Drugs: Rapid, Simple, and Inexpensive Method (2003)

The emergence of multidrug-resistant tuberculosis calls for new, rapid drug susceptibility tests. We have tested 150 Mycobacterium tuberculosis isolates against the second-line drugs ethionamide, kanamycin, capreomycin, ofloxacin, and para-aminosalicylic acid by the colorimetric resazurin microtiter assay and the proportion method. By visual reading, MICs were obtained after 8 days. A very good correlation between results by the colorimetric resazurin microtiter assay and the proportion method was obtained. The colorimetric resazurin microtiter assay is inexpensive, rapid, and simple to perform, and implementation of the assay is feasible for low-resource countries.
A Critical Role for CD48 Antigen in Regulating Alloengraftment and Lymphohematopoietic Recovery After Bone Marrow Transplantation (1998)

The binding of CD2, present on T cells, to its counterreceptor CD48 facilitates adhesion, signaling, alloantigen-induced cytokine production, and cytotoxic T-lymphocyte responses. Because these T-cell functions have been implicated in graft-versus-host disease (GVHD) pathogenesis, we have analyzed the effects of the CD2:CD48 pathway on GVHD mediated by CD4(+) and CD8(+) T cells infused into sublethally irradiated recipients. CD4(+) T-cell-mediated, and to a lesser extent, CD8(+) T-cell-mediated GVHD was inhibited by CD2 + 48 monoclonal antibody (MoAb) infusion. To assess the effects of combined MoAb infusion on alloengraftment, two different alloengraftment bone marrow transplantation (BMT) models were used. In both, MoAb infusion markedly inhibited alloengraftment and hematopoietic recovery post-BMT. To determine if the adverse effects on lymphohematopoiesis in the allogeneic BMT recipients were caused by an immune or nonimmune mechanism, studies were performed in congenic BMT recipients to preclude an immune mechanism as the cause for delayed recovery post-BMT. MoAb infusion resulted in impaired lymphohematopoietic recovery in congenic BMT recipients and markedly reduced day 12 colony-forming unit-spleen formation in syngeneic BMT recipients, consistent with a nonimmune mediated mechanism. Because the spleen is a site of early hematopoietic recovery post-BMT, studies were performed using adult splenectomized syngeneic BMT recipients. MoAb infusion delayed recovery in both nonsplenectomized and splenectomized recipients post-BMT, indicating that the delayed hematopoietic recovery was not the consequence of an abnormal homing pattern of hematopoietic progenitors to the spleen early post-BMT. CD48 MoAb was necessary and sufficient for the inhibition of GVHD lethality and delayed lymphohematopoietic effects of the combined MoAb regimen. CD48 MoAb was found to induce a profound modulation of CD48 antigen expression on BM cells, suggesting that the CD48 antigen may have an important function in hematopoiesis in the BM compartment. Taken together, these data provide evidence that the CD48 antigen plays a critical role in regulating hematopoiesis in post-BMT.
Isolation of a recombinant copy of the gene encoding C/EBP. (1988)

In two previous studies we described the properties of a heat-stable DNA-binding protein present in rat liver nuclei. This protein, hereafter termed C/EBP, is capable of selective binding to the CCAAT homology of several viral promoters (Graves et al. 1986), as well as the core homology common to many viral enhancers (Johnson et al. 1987). We now report the isolation of a recombinant clone of the gene that encodes C/EBP. Expression of the clone in bacterial cells yields a protein that binds in vitro to both the CCAAT homology and the enhancer core homology, providing conclusive evidence that a single gene product accounts for both binding activities. By examining the properties of protease-derived fragments of C/EBP, we have localized its DNA-binding domain to a 14-kD fragment. A 60-amino-acid segment located within the DNA-binding domain of C/EBP bears sequence similarity to the products of the myc and fos oncogenes.
Enhanced activity of a hydrogen sulphide‐releasing derivative of mesalamine (ATB‐429) in a mouse model of colitis (2007)

ATB-429 exhibits a marked increase in anti-inflammatory activity and potency in a murine model of colitis, as compared to mesalamine. These results are consistent with recently described anti-inflammatory effects of H(2)S. ATB-429 may represent an attractive alternative to mesalamine for the treatment of inflammatory bowel disease.
Fast Learning in Networks of Locally-Tuned Processing Units (1989)

We propose a network architecture which uses a single internal layer of locally-tuned processing units to learn both classification tasks and real-valued function approximations (Moody and Darken 1988). We consider training such networks in a completely supervised manner, but abandon this approach in favor of a more computationally efficient hybrid learning method which combines self-organized and supervised learning. Our networks learn faster than backpropagation for two reasons: the local representations ensure that only a few units respond to any given input, thus reducing computational overhead, and the hybrid learning rules are linear rather than nonlinear, thus leading to faster convergence. Unlike many existing methods for data analysis, our network architecture and learning rules are truly adaptive and are thus appropriate for real-time use.
Synthesis and characterization of sulfone containing main chain oligobenzoxazine precursors (2011)

Abstract The preparation of soluble and processable polybenzoxazine precursors capable of forming high performance networks is an important field of research with a broad spectrum of application. This study demonstrates an approach that utilizes aromatic sulfonediamine, bisphenol‐A, and formaldehyde in Mannich‐type polycondesation to prepare polybenzoxazine precursor. The structure of the oligomeric precursor ( M n = 2600) was confirmed by FTIR and 1 H NMR spectral analysis. The precursor contained both sulfone and benzoxazine ring structures in the backbone. It was shown that small amount of ring‐opened phenolic groups were also present. Thermally activated self‐curing behavior of precursor in the absence of catalyst was studied by differential scanning calorimetry. Thermal properties of the cured polymers were also investigated by thermo gravimetric analysis. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
The Direct Pathway of Human T‐Cell Allorecognition is not Tolerized by Stimulation with Allogeneic Peripheral Blood Mononuclear Cells Irradiated with High‐Dose Ultraviolet Ba (2006)

Transfusions of high-dose (> or =10,000 Joule/m(2)) ultraviolet-B (UVB)-irradiated allogeneic leukocytes in rodent models have been shown to induce immunologic tolerance that is mediated by allospecific regulatory CD4(+) T cells. Whether these regulatory T cells recognize alloantigens through the direct or indirect pathway of allorecognition is controversial. Here, we demonstrate that the proliferative response obtained in standard primary mixed leukocyte reactions (MLRs) with human peripheral blood mononuclear cells (PBMCs) reflected a CD4(+) T-cell-dependent direct pathway of allorecognition and that high-dose UVB irradiation of PBMCs totally inhibited their capacity to induce a proliferative alloresponse. Re-stimulation with gamma-irradiated PBMCs from the same allogeneic donor (secondary MLR) elicited a proliferative and Th1-deviated response that was similar to the response induced in unprimed PBMCs. Finally, high-dose UVB was found to induce a rapid and massive apoptosis of irradiated PBMCs. Collectively, these data indicate that leukocytes irradiated with high-dose UVB are unable to prime for unresponsiveness or immune deviation in T cells directly recognizing allogeneic major histocompatibility complex molecules. Because it is well-established that antigens within transfused apoptotic cells are captured by resident tolerogenic spleen dendritic cells, we propose that tolerance induced by transfusions of high-dose UVB-irradiated leukocytes primarily involve T cells indirectly recognizing alloantigens.