gebhart/patrepeval huggingface dataset:
Optimizing the Generation of Recombinant Single-Chain Antibodies Against Placental Alkaline Phosphatase (2006)

Recombinant technologies to engineer ordinary hybridoma monoclonal antibodies (MAbs) to single-chain fragment variable (scFv) may cause loss of antibody affinity, increased tendency to aggregate, increased temperature sensitivity, and low yield of active protein. In the present investigation, the well-characterized MAb H7 against placental alkaline phosphatase (PLAP), used as a model antibody, was engineered to improve solubility and stability of scFv with retained high affinity. The original procedure to generate single-chain antibodies with a 10-amino acid linker between VH and VL yielded an almost insoluble product. By site-directed mutagenesis, four selective sequence substitutions were made in the VL fragment and one in the VH fragment to improve solubility. The importance of the linker length was investigated, and a 25/30 amino acid linker was found to improve solubility. In order to further increase the stability of the single-chain antibody, an additional covalent -S-S- bond was introduced between amino acid 100 in the VL fragment and amino acid 44 in the VH region, to make a single-chain disulphide stabilized variable fragment (scdsFv). Altogether five different antibody constructs were produced and compared in terms of solubility, stability, affinity, and production properties. Immunospecificity was tested by enzyme-linked immunosorbent assay (ELISA) against the target antigen, temperature sensitivity by exposing the purified scFv to higher temperatures. All the new constructs retained almost equal activity and high affinity for their target antigen, placental alkaline phosphatase (PLAP), compared to the intact MAb H7, up to +42 degrees C as evaluated by ELISA. The overall affinity K(A) > 10(9) (M(1)) of the new antibodies could be maintained in the same order of magnitude as the original one (H7), when evaluated by Biacore technology. The best final single-chain antibody was obtained by performing the specific site-directed mutations and introducing a linker of 30 amino acids, but not by additional stabilizing disulphide bonds. The yield of the final antibody was improved approximately 10-fold by the modifications. This antibody could easily be expressed in a bacterial system using the PET-32a TrxA vector and the Escherichia coli strain BL21 Origami B (DE3). Purified antibody, which could be kept at concentrations up to 0.8 mg/mL, was obtained, which is sufficient for clinical testing of therapeutic applications.
Immunostimulatory CpG-oligonucleotides cause proliferation, cytokine production, and an immunogenic phenotype in chronic lymphocytic leukemia B cells (2000)

Bacterial DNA and synthetic CpG-oligodeoxynucleotides (ODNs) derived thereof have attracted attention because they activate cells of the immune system in a sequence-dependent manner. Here we investigated the potential of CpG-ODNs to cause proliferation, cytokine production, and regulation of surface molecules in human B-chronic lymphocytic leukemia (CLL) cells. CpG-ODN induced proliferation in both B-CLL cells and normal B cells; however, only B-CLL cells increased proliferative responses when CpG-ODN was added to co-cultures of CD40-ligand transfected mouse fibroblasts (CD40LF) and B cells. Production of interleukin-6 and tumor necrosis factor alpha was detectable at borderline levels, using CpG-ODN as the only stimulus. In contrast, when CpG-ODN was added to co-cultures of B cells and CD40LF, a strong increase in cytokine production occurred in B-CLL cells as well as in normal B cells. The surface molecules CD40, CD58, CD80, CD86, CD54, and MHC class I molecules were up-regulated in B-CLL cells, whereas CD95 expression was not influenced by CpG-ODN stimulation. The same pattern of surface molecule regulation was observed in normal B cells, but up-regulation of CD40 was significantly stronger in B-CLL cells. Costimulation with CpG-ODN and CD40LF resulted in further up-regulation of CD58, CD80, CD86, and MHC class I molecules. In contrast, CD95 expression induced by CD40-ligation was inhibited by CpG-ODN. CpG-ODN activated B-CLL cells acquired a strong stimulatory capacity toward T cells in allogeneic mixed lymphocyte reaction. This effect was completely inhibited by a combination of anti-CD80 and anti-CD86 monoclonal antibody. Taken together, these findings suggest the possible use of CpG-ODN for immunotherapeutic strategies in patients with B-CLL.
Occurrence Of Human Immunodeficiency Virus Type I (HIV-I)-Specific Cytolytic T Cell Activity In Apparently Uninfected Children Born To HIV-1-Infected Mothers (1994)

Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocyte (CTL) activity against different viral antigens, including env, gag/pol, and nef, was detected in peripheral blood lymphocytes of as many as 25% of uninfected children born to HIV-1-infected mothers. The relatively high frequency of this finding in uninfected, exposed children suggests that CTL-mediated immunity may play a key role in the control or even elimination of the virus. Further characterization of this natural model of potentially protective immunity could provide new insight and suggest further strategies for the development of HIV-1 vaccines.
Germ-line mutations of the macrophage scavenger receptor 1 gene: association with prostate cancer risk in African-American men. (2003)

Both rare germ-line mutations and common sequence variants of the macrophage scavenger receptor 1 (MSR1) gene have recently been implicated as potential prostate cancer susceptibility factors. However, existing studies are limited by the referral-based nature of samples and a paucity of African-American participants. In this context, we evaluated the association of germ-line mutations and common MSR1 sequence variants with prostate cancer risk in a case control study of a community-based sample of 134 African-American men with prostate cancer and 340 unaffected controls. In our sample, the rare Asp174Tyr missense change was identified nearly twice as frequently in men with prostate cancer (6.8%) compared with unaffected controls (3.6%; P = 0.14). Moreover, significantly different allele frequencies between cases and controls were observed for one of the sequence variants, IVS5-59 (P = 0.02). Taken together, our results provide some additional support for the hypothesis that selected, rare MSR1 mutations are associated with increased prostate cancer susceptibility among African-American men.
Auditory Steady-State Response Audiometry in Profound SNHL: The Impact of Abnormal Middle Ear Function (2005)

Auditory steady-state response (ASSR) audiometry is a commercially available tool that is used to predict behavioral auditory threshold levels. Its particular value stems from the technology's ability to measure frequency-specific responses in the background electroencephalogram to auditory stimuli presented across a broad range of frequencies and sound pressure levels. It is clearly of benefit when used to assess threshold levels in infants and children with severe-to-profound hearing impairment (i.e., cochlear implant candidates). Although numerous authors have provided evidence of the usefulness of ASSR testing, their reports have concerned patients whose middle ear impedance measures were normal. We report the cases of 2 patients who, following improvement of abnormal middle ear impedance values, experienced a marked improvement in measurable thresholds by ASSR testing.
Practical challenges for digital watermarking applications (2002)

The field of digital watermarking has recently seen numerous articles covering novel techniques, theoretical studies, attacks and analysis. We focus on practical challenges for digital watermarking applications. Challenges include design considerations, requirements analysis, choice of watermarking techniques, speed, robustness and the tradeoffs involved. We describe common attributes of watermarking systems and discuss the challenges in developing real world applications. We present, as a case study, a hypothetical application that captures important aspects of watermarking systems and illustrates some of the issues faced.
Platelet-mediated clumping of Plasmodium falciparum -infected erythrocytes is a common adhesive phenotype and is associated with severe malaria (2001)

Sequestration of malaria-infected erythrocytes in the peripheral circulation has been associated with the virulence of Plasmodium falciparum. Defining the adhesive phenotypes of infected erythrocytes may therefore help us to understand how severe disease is caused and how to prevent or treat it. We have previously shown that malaria-infected erythrocytes may form apparent autoagglutinates of infected erythrocytes. Here we show that such autoagglutination of a laboratory line of P. falciparum is mediated by platelets and that the formation of clumps of infected erythrocytes and platelets requires expression of the platelet surface glycoprotein CD36. Platelet-dependent clumping is a distinct adhesive phenotype, expressed by some but not all CD36-binding parasite lines, and is common in field isolates of P. falciparum. Finally, we have established that platelet-mediated clumping is strongly associated with severe malaria. Precise definition of the molecular basis of this intriguing adhesive phenotype may help to elucidate the complex pathophysiology of malaria.
A Branch and Bound Clustering Algorithm (1975)

The problem of clustering N objects into M classes may be viewed as a combinatorial optimization algorithm. In the literature on clustering, iterative hill-climbing techniques are used to find a locally optimum classification. In this paper, we develop a clustering algorithm based on the branch and bound method of combinatorial optimization. This algorithm determines the globally optimum classification and is computationally efficient
PHYSIOLOGY OF PLANTS UNDER STRESS, ABIOTIC FACTORS (1996)

Introductory Comments. The Physiological Basis of Growth. Plant Membranes as Envionmental Sensors. Phytohormone and Plant Response to Stress. Stable Isotopes and Plant Stress Physiology. Plant Carbon Balance. Water Dynamics in Plants. Water Limitation. Flooding. Irradiance. High Temperature and Energy Balance. Temperature: Chilling and Freezing. Multiple Stress Interactions. Biotechnology and Envionmental Stress. Generalities, Trends, and Future Directions. Appendices. Index.
A Review of Prognostic Pathologic Features and Algorithms for Patients Treated Surgically for Renal Cell Carcinoma (2005)

Accurate subtyping of RCC is critically important and should be considered in algorithms that are developed as prognostic tools for the patient and clinician. The TNM classification, already a powerful prognostic factor, will continue to evolve. The authors recommend that each component of the classification be assessed and reported during pathologic examination. This article also highlighted the importance of assigning a nuclear grade that is based on standardized and reproducible criteria that reflect the heterogeneity of nuclear and nucleolar features within RCC. Lastly, it is increasingly evident that coagulative tumor necrosis and sarcomatoid differentiation are compelling prognostic factors, on par with nuclear grade, and should be assessed routinely. To conclude, the complete list of pathologic features that are evaluated as part of the Mayo Clinic Nephrectomy Registry is presented. The features that are reported routinely in clinical practice also are indicated; this can serve as a guide for the reporting of results from the pathologic examination of RCC.
Dynamic floating body control SOI CMOS circuits for power managed multimedia ULSIs (2002)

A novel body potential controlling technique for floating SOI CMOS circuits is proposed and verified. High speed operation is realized with a small chip size by using body-floating SOI transistors. By using this technique, the threshold voltage of the body-floating transistors is varied transitionally. Therefore, the standby current of SOI CMOS logic is reduced less than 1/10th compared to the non-control operation of the body potential and operates at high speed during the active period. There is no access penalty for the recovery operation from the standby mode. This technique supports sub 1 V operation, which is required for future battery operated devices with wide range covering.
What’s new in human papillomavirus infection (2000)

Warts continue to be a therapeutic challenge, especially widespread warts on children. A single, most effective treatment has not been defined. Conventional methods attempt to nonspecifically destroy infected tissue. Most of these procedures are painful, poorly tolerated by children, and often require multiple treatments. The efficacy of destructive techniques is impossible to verify in controlled clinical trials. Uncontrolled success rates are suboptimal and often no better than that seen with placebos. Alternative pharmacologic approaches have been designed to stimulate immunologic responses or provide anti-viral activity. Further study is needed to establish efficacy of these treatments.
B-Spline Surfaces with Knot Segments (1994)

This report presents a generalization of tensor-product B-spline surfaces. The new scheme permits knots whose endpoints lie in the interior of the domain rectangle of a surface. This allows local refinement of the knot structure for approximation purposes as well as modeling surfaces with local tangent or curvature discontinuities. The surfaces are represented in terms of B-spline basis functions, ensuring affine invariance, local control, the convex hull property, and evaluation by de Boor's algorithm. A dimension formula for a class of generalized tensor-product spline spaces is developed.
Data mining techniques (1996)

Data mining, or knowledge discovery in databases, has been popularly recognized as an important research issue with broad applications. We provide a comprehensive survey, in database perspective, on the data mining techniques developed recently. Several major kinds of data mining methods, including generalization, characterization, classification, clustering, association, evolution, pattern matching, data visualization, and meta-rule guided mining, will be reviewed. Techniques for mining knowledge in different kinds of databases, including relational, transaction, object-oriented, spatial, and active databases, as well as global information systems, will be examined. Potential data mining applications and some research issues will also be discussed.
Effects of radiofrequency catheter ablation on regional myocardial blood flow. Possible mechanism for late electrophysiological outcome. (1994)

RF catheter ablation not only results in a marked reduction in blood flow within the acute pathological lesion but also causes reduced flow beyond the borders of the acute lesion because of microvascular endothelial cell injury. The progression or resolution of tissue injury within the region beyond the border of the pathological lesion may explain the late electrophysiological effects of RF ablation.
Electronic Structure of Gallium, Copper, and Nickel Complexes of Corrole. High-Valent Transition Metal Centers versus Noninnocent Ligands (2000)

Using regular nonlocal density functional theory (DFT) as well as combined DFT and configuration interaction calculations, we have carried out a first theoretical study of the electronic structure of metallocorroles. The valence orbital energy spectra and the calculated electronic absorption spectrum of (Cor)Ga (Cor3- = corrolato), a prototype non-transition-metal corrole, are qualitatively similar to those of a metalloporphyrin such as zinc porphyrin. The "four-orbital model" holds well for corroles. The a2 and b1 HOMOs of (Cor)Ga are crude analogues of the well-known a1u and a2u porphyrin HOMOs, respectively. Thus, as in the case of porphyrins, there are two nearly equienergetic π-cation radical states for corroles. DFT also appears to provide a good description of the stabilization of high-valent transition-metal centers and of ligand noninnocence, two intertwined and central themes in metallocorrole chemistry. The calculated ground state of (Cor)Cu is a diamagnetic d8 Cu(III) state, with Cu(II) π-cation radical states only slightly higher in energy, which faithfully mirrors the experimental scenario. In contrast, there are no known Cu(III) porphyrin complexes. For (Cor)Ni, low-spin Ni(II) π-cation radical states are significantly lower in energy than a Ni(III) state, again consistent with experiment, reflecting the favorable energetics of d8 square planar complexes. The various optimized geometries reveal significant, characteristic structural changes accompanying the formation of A2- and B1-type corrole π-cation radicals. We predict that the resonance Raman spectra of metallocorroles should reflect these structural features and, thereby, assist in the assignment of valence tautomeric states of transition-metal corrole complexes.
Indexing method for multidimensional vector data (2013)

Efficient management of multidimensional data is a challenge when building modern database applications that involve many fold data such as temporal, spatial, data warehousing, bio-informatics, etc. This problem stems from the fact that multidimensional data has no order that preserves proximity. The majority of existing solutions to this problem cannot be easily integrated into the current relational database systems since they require modifications to the kernel. A prominent class of methods that can use existing access structures are ‘space filling curves’. In this work we describe a method that is also based on the space filling curve approach, but in contrast to earlier methods, it connects regions of various sizes rather than points in multidimensional space. Our approach allows efficient transformation of interval queries into regions of data which results in significant improvements when accessing the data. In detailed empirical study, we have demonstrated that the proposed method, which can be integrated within the commercial RDBMS, outperforms the best available off-the-shelf methods for accessing multidimensional point data.
Culture-Independent Analyses of Temporal Variation of the Dominant Fecal Microbiota and Targeted Bacterial Subgroups in Crohn's Disease (2006)

Gut microbiota shows host-specific diversity and temporal stability and significantly contributes to maintenance of a healthy gut. However, in inflammatory bowel disease, this microbiota has been implicated as a contributory factor to the illness. This study compared bacterial dynamics in Crohn's disease patients to those in a control group using a culture-independent method to assess the temporal stability, relative diversity, and similarity of the dominant fecal microbiota, Clostridium spp., Bacteroides spp., Bifidobacterium spp., and lactic acid bacteria spp. (LAB) for all individuals. Fecal samples were collected over several time points from individuals with Crohn's disease who were in remission (n = 11), from Crohn's disease patients who relapsed into an active Crohn's disease state (n = 5), and from a control group (n = 18). Denaturing gradient gel electrophoresis profiles were generated for the different microbial groups by specifically targeting different regions of the 16S rRNA gene and were compared on the basis of similarity and diversity. The temporal stability of dominant species for all Crohn's disease patients was significantly lower (P < 0.005) than that for the control group. Analysis of group-specific profiles for Bifidobacterium spp. found that they were similar in all samples, while the diversity of the LAB varied significantly between the groups, but temporal stability was not significantly altered. We observed significant changes in two functionally important mutualistic groups of bacteria, viz., Clostridium and Bacteroides spp., which may have implications for the host's gut health, since some genera are involved in production of short-chain fatty acid, e.g., butyrate.
Drug-Induced Prolongation of the QT Interval (2004)

The single most common cause of the withdrawal or restriction of the use of marketed drugs has been QT-interval prolongation associated with polymorphic ventricular tachycardia, or torsade de pointes, a condition that can be fatal. This review summarizes the current knowledge about molecular and clinical predictors of drug-induced QT-interval prolongation and torsade de pointes and discusses how new molecular predictors of drug action might be incorporated into drug-development programs and clinical practice. A general approach to drugs suspected of causing this problem is presented.
A primary role for RPE transplants in the inhibition and regression of neovascularization in the RCS rat. (1994)

These data provide still further evidence for the role of healthy RPE in maintaining the homeostasis of the normal retinal vasculature in the retina of the RCS rat. The relationships between the RPE and the retinal vasculature are important when considering that alterations in the vascularization of the retina play a major role in some of the most sight-debilitating diseases, such as the wet form of age-related macular degeneration and proliferative diabetic retinopathy.
Reversal of autoimmune diabetes by restoration of antigen-specific tolerance using genetically modified Lactococcus lactis in mice (2012)

Current interventions for arresting autoimmune diabetes have yet to strike the balance between sufficient efficacy, minimal side effects, and lack of generalized immunosuppression. Introduction of antigen via the gut represents an appealing method for induction of antigen-specific tolerance. Here, we developed a strategy for tolerance restoration using mucosal delivery in mice of biologically contained Lactococcus lactis genetically modified to secrete the whole proinsulin autoantigen along with the immunomodulatory cytokine IL-10. We show that combination therapy with low-dose systemic anti-CD3 stably reverted diabetes in NOD mice and increased frequencies of local Tregs, which not only accumulated in the pancreatic islets, but also suppressed immune response in an autoantigen-specific way. Cured mice remained responsive to disease-unrelated antigens, which argues against excessive immunosuppression. Application of this therapeutic tool achieved gut mucosal delivery of a diabetes-relevant autoantigen and a biologically active immunomodulatory cytokine, IL-10, and, when combined with a low dose of systemic anti-CD3, was well tolerated and induced autoantigen-specific long-term tolerance, allowing reversal of established autoimmune diabetes. Therefore, we believe this method could be an effective treatment strategy for type 1 diabetes in humans.