gebhart/patrepeval huggingface dataset:
Arg1098 Is Critical for the Chloride Dependence of Human Angiotensin I-converting Enzyme C-domain Catalytic Activity (2001)

Angiotensin (Ang) I-converting enzyme (ACE) is a Zn(2+) metalloprotease with two homologous catalytic domains. Both the N- and C-terminal domains are peptidyl dipeptidases. Hydrolysis by ACE of its decapeptide substrate Ang I is increased by Cl(-), but the molecular mechanism of this regulation is unclear. A search for single substitutions to Gln among all conserved basic residues (Lys/Arg) in human ACE C-domain identified R1098Q as the sole mutant that lacked Cl(-) dependence. Cl(-) dependence is also lost when the equivalent Arg in the N-domain, Arg(500), is substituted with Gln. The Arg(1098) to Lys substitution reduced Cl(-) binding affinity by approximately 100-fold. In the absence of Cl(-), substrate binding affinity (1/K(m)) of and catalytic efficiency (k(cat)/K(m)) for Ang I hydrolysis are increased 6.9- and 32-fold, respectively, by the Arg(1098) to Gln substitution, and are similar (<2-fold difference) to the respective wild-type C-domain catalytic constants in the presence of optimal [Cl(-)]. The Arg(1098) to Gln substitution also eliminates Cl(-) dependence for hydrolysis of tetrapeptide substrates, but activity toward these substrates is similar to that of the wild-type C-domain in the absence of Cl(-). These findings indicate that: 1) Arg(1098) is a critical residue of the C-domain Cl(-)-binding site and 2) a basic side chain is necessary for Cl(-) dependence. For tetrapeptide substrates, the inability of R1098Q to recreate the high affinity state generated by the Cl(-)-C-domain interaction suggests that substrate interactions with the enzyme-bound Cl(-) are much more important for the hydrolysis of short substrates than for Ang I. Since Cl(-) concentrations are saturating under physiological conditions and Arg(1098) is not critical for Ang I hydrolysis, we speculate that the evolutionary pressure for the maintenance of the Cl(-)-binding site is its ability to allow cleavage of short cognate peptide substrates at high catalytic efficiencies.
WT1 and BCR-ABL specific small interfering RNA have additive effects in the induction of apoptosis in leukemic cells. (2005)

In conclusion, WT1 might be a suitable target for new therapeutic strategies using siRNAs in leukemic cells.
The Interdigestive Motor Complex of Normal Subjects and Patients with Bacterial Overgrowth of the Small Intestine (1977)

Intraluminal pressures were measured in the gastric antrum and at different levels of the upper small intestine in 18 normal subjects to investigate whether or not the interdigestive motor complex, identified in several animal species, occurs in man and, if so, to determine its characteristics. In all normal subjects, the activity front of the interdigestive motor complex was readily identified as an uninterrupted burst of rhythmic contraction waves that progressed down the intestine and that was followed by a period of quiescence. Quantitative analysis of various parameters of the complex and simultaneous radiological and manometrical observations revealed that it resembled closely the canine interdigestive motor complex. To test the hypothesis that disorders of this motor complex may lead to bacterial overgrowth in the small intestine, similar studies were performed in 18 patients with a positive (14)CO(2) bile acid breath test and in an additional control group of 9 patients with a normal (14)CO(2) breath test. All but five patients had normal interdigestive motor complexes. The five patients in whom the motor complex was absent or greatly disordered had bacterial overgrowth as evidenced by (14)CO(2) bile acid breath tests before and after antibiotics. These studies establish the presence and define the characteristics of the normal interdigestive motor complex in man. They also suggest that bacterial overgrowth may be due to a specific motility disorder i.e., complete or almost complete absence of the interdigestive motor complex.
Geometry-dependent functional changes in iPSC-derived cardiomyocytes probed by functional imaging and RNA sequencing (2017)

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising platform for cardiac studies in vitro, and possibly for tissue repair in humans. However, hiPSC-CM cells tend to retain morphology, metabolism, patterns of gene expression, and electrophysiology similar to that of embryonic cardiomyocytes. We grew hiPSC-CM in patterned islands of different sizes and shapes, and measured the effect of island geometry on action potential waveform and calcium dynamics using optical recordings of voltage and calcium from 970 islands of different sizes. hiPSC-CM in larger islands showed electrical and calcium dynamics indicative of greater functional maturity. We then compared transcriptional signatures of the small and large islands against a developmental time course of cardiac differentiation. Although island size had little effect on expression of most genes whose levels differed between hiPSC-CM and adult primary CM, we identified a subset of genes for which island size drove the majority (58%) of the changes associated with functional maturation. Finally, we patterned hiPSC-CM on islands with a variety of shapes to probe the relative contributions of soluble factors, electrical coupling, and direct cell-cell contacts to the functional maturation. Collectively, our data show that optical electrophysiology is a powerful tool for assaying hiPSC-CM maturation, and that island size powerfully drives activation of a subset of genes involved in cardiac maturation.
Surfactant Protein D Enhances Clearance of Influenza A Virus from the Lung In Vivo (2001)

Mice lacking surfactant protein surfactant protein D (SP-D(-/-)) and wild-type mice (SP-D(+/+)) were infected with influenza A virus (IAV) by intranasal instillation. IAV infection increased the endogenous SP-D concentration in wild-type mice. SP-D-deficient mice showed decreased viral clearance of the Phil/82 strain of IAV and increased production of inflammatory cytokines in response to viral challenge. However, the less glycosylated strain of IAV, Mem/71, which is relatively resistant to SP-D in vitro, was cleared efficiently from the lungs of SP-D(-/-) mice. Viral clearance of the Phil/82 strain of IAV and the cytokine response were both normalized by the coadministration of recombinant SP-D. Since the airway is the usual portal of entry for influenza A virus and other respiratory pathogens, SP-D is likely to play an important role in innate defense responses to IAV.
APP processing is regulated by cytoplasmic phosphorylation (2003)

Amyloid-beta peptide (Abeta) aggregate in senile plaque is a key characteristic of Alzheimer's disease (AD). Here, we show that phosphorylation of amyloid precursor protein (APP) on threonine 668 (P-APP) may play a role in APP metabolism. In AD brains, P-APP accumulates in large vesicular structures in afflicted hippocampal pyramidal neurons that costain with antibodies against endosome markers and the beta-secretase, BACE1. Western blot analysis reveals increased levels of T668-phosphorylated APP COOH-terminal fragments in hippocampal lysates from many AD but not control subjects. Importantly, P-APP cofractionates with endosome markers and BACE1 in an iodixanol gradient and displays extensive colocalization with BACE1 in rat primary cortical neurons. Furthermore, APP COOH-terminal fragments generated by BACE1 are preferentially phosphorylated on T668 verses those produced by alpha-secretase. The production of Abeta is significantly reduced when phosphorylation of T668 is either abolished by mutation or inhibited by T668 kinase inhibitors. Together, these results suggest that T668 phosphorylation may facilitate the BACE1 cleavage of APP to increase Abeta generation.
Evaluating Neutralizing Antibodies Against HIV, SIV, and SHIV in Luciferase Reporter Gene Assays (2004)

Neutralizing antibody assays are powerful tools for assessing humoral immunity in AIDS virus infection and vaccine development. Although many different assays have been described, all are based on the same principle, measuring reductions in virus infectivity. This unit describes two assays utilizing a genetically engineered cell lines that are susceptible to infection by most strains of HIV-1, SIV, and SHIV. One assay is designed for optimal performance with uncloned viruses produced in either PBMC or CD4+ T cell lines. A second assay is designed for single-cycle infection with molecularly cloned pseudoviruses produced by transfection in 293T cells. Both assays are performed in a 96-well format and use tat-responsive luciferase reporter gene expression as readout.
Research on the Journal Work Research Based on Content Analysis (2010)

By using content analysis method,this paper makes a statistical analysis on 1 418 papers published in 17 core journals of library and information science from 2000 to 2008,inspects the research progress of China's journal work research,probes into the recent emphases and hot spots of journal work research,and looks forward to the development trends of the research.
N-(2-chloroethyl)-N-nitrosoureas covalently bound to nonionic and monocationic lexitropsin dipeptides. Synthesis, DNA affinity binding characteristics, and reactions with phosphorus-32-end-labeled DNA (1990)

The synthesis and characterization of a series of compounds that contain an N-alkyl-N-nitrosourea functionality linked to DNA minor groove binding bi- and tripeptides (lexitropsins or information-reading peptides) based on methylpyrrole-2-carboxamide subunits are described. The lexitropsins (lex) synthesized have either a 3-(dimethylamino)propyl or propyl substituent on the carboxyl terminus. The preferred DNA affinity binding sequences of these compounds were footprinted in 32P-end-labeled restriction fragments with methidiumpropyl-EDTA.Fe(II), and in common with other structural analogues, e.g., distamycin and netropsin, these nitrosoureas recognize A-T-rich runs. The affinity binding of the compound with the dimethylamino terminus, which is ionized at near-neutral pH, appeared stronger than that observed for the neutral dipeptide. The sequence specificity for DNA alkylation by (2-chloroethyl)nitrosourea-lex dipeptides (Cl-ENU-lex), with neutral and charged carboxyl termini, using 32P-end-labeled restriction fragments, was determined by the conversion of the adducted sites into single-strand breaks by sequential heating at neutral pH and exposure to base. The DNA cleavage sites were visualized by polyacrylamide gel electrophoresis and autoradiography. The alkylation of DNA by Cl-ENU-lex was compared to that by N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea (CCNU), which has no DNA affinity binding properties. While all the Cl-ENU compounds generate DNA breaks as a consequence of the formation of N7-alkyl-guanine, the Cl-ENU-lex compounds induced, in a time- and dose-dependent fashion, intense DNA cleavage bands at adenine, cytosine, and thymine residues associated with affinity binding sites. These non-G cleavages induced by Cl-ENU-lex were inhibited by the coaddition of distamycin at concentrations that did not affect G alkylation break sites. CCNU, even at much higher concentrations, does not generate any similar detectable lesions at non-G sites. Therefore, linking the Cl-ENU moiety to minor groove binders is a viable strategy to qualitatively and quantitatively control the delivery and release of the ultimate DNA alkylating agent in a sequence-dependent fashion.
Binding of membrane-anchored macrophage colony-stimulating factor (M- CSF) to its receptor mediates specific adhesion between stromal cells and M-CSF receptor-bearing hematopoietic cells (1993)

To explore the biologic significance of the membrane-anchored form of macrophage colony-stimulating factor (M-CSF), we examined whether interaction between membrane-bound M-CSF and its receptor mediates intercellular adhesion as well as cell proliferation and differentiation. Human M-CSF receptors were expressed on a murine interleukin-2 (IL-3)-dependent cell line, FDC-P2, by DNA transfection with the c-fms gene (FDC-P2-MCSFR). A human bone marrow-derived stromal cell line, KM102, was used in the cell adhesion assay. The expression of membrane-bound M-CSF on KM102 cells was demonstrated by flow cytometry and immunoblot analysis. After the incubation of parent and transformed FDC-P2 cells on confluent KM102 cells, nonadherent cells were removed and the cells attached to KM102 cells were examined microscopically. Almost all parent FDC-P2 cells were nonadherent, whereas a significant number of FDC-P2-MCSFR cells bound to KM102 cells. The addition of anti-M-CSF or anti-M-CSF receptor neutralizing antibodies dose-dependently inhibited the binding of [3H]-thymidine- labeled FDC-P2-MCSFR cells to KM102 cells. An excess amount of M-CSF also inhibited the binding. On the other hand, the addition of antibodies against some representative adhesion molecules (vitronectin receptor, Pgp-1/CD44, and VLA-4) did not inhibit the adhesion between FDC-P2-MCSFR cells and KM102 cells. These results support the idea that membrane-anchored M-CSF and its receptor may function as mediators of cell-cell adhesion.
Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal carcinomas (1999)

The MTA1 gene is a recently identified novel candidate breast cancer metastasis-associated gene which has been implicated in the signal transduction or regulation of gene expression. We examined the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in 47 surgically resected oesophageal squamous cell carcinomas by quantitative reverse transcription polymerase chain reaction. The relative overexpression of MTA1 mRNA (tumour/normal ratio > or = 2) was observed in 16 out of 47 (34.0%) oesophageal carcinomas. Oesophageal tumours overexpressing MTA1 mRNA (T/N ratio > or = 2) showed significantly higher frequencies of adventitial invasion (P < 0.05) and lymph node metastasis (P < 0.05), and tended to have a higher rate of lymphatic involvement than the remaining tumours. Thus, the data suggest that the MTA1 gene might play an important role in invasion and metastasis of oesophageal carcinomas.
A Modified Selective Mapping with PAPR Reduction and Error Correction in OFDM Systems (2007)

This paper proposed a PAPR reduction method for BPSK OFDM systems and 16-QAM OFDM systems respectively. The strategy of the algorithms is to use a correction subcode for error control and a scrambling subcode for PAPR control. The transmitted OFDM sequence is selected with minimum PAPR from a number of candidates which form a coset of scrambling subcode for each codeword of correction subcode. In a BPSK OFDM system, the PAPR reduction is obtained by combining the SLM method with binary cyclic codes. In a 16-QAM OFDM system, the PAPR reduction is achieved by combining the SLM with block coded modulation. The received signal of the modified SLM can be decoded without the need of explicit side information and the proposed scheme achieves good PAPR reduction.
WormBase: a cross-species database for comparative genomics (2003)

WormBase (http://www.wormbase.org/) is a web-accessible central data repository for information about Caenorhabditis elegans and related nematodes. The past two years have seen a significant expansion in the biological scope of WormBase, including the integration of large-scale, genome-wide data sets, the inclusion of genome sequence and gene predictions from related species and active literature curation. This expansion of data has also driven the development and refinement of user interfaces and operability, including a new Genome Browser, new searches and facilities for data access and the inclusion of extensive documentation. These advances have expanded WormBase beyond the obvious target audience of C. elegans researchers, to include researchers wishing to explore problems in functional and comparative genomics within the context of a powerful genetic system.
Embolization of cranial/spinal tumours and vascular malformations with hydrogel microspheres. An experience of 69 cases (2002)

Objective: To evaluate polymethyl methacrylate hydrogel microspheres (HMs) as an embolization material in the management of hypervascular craniofacial and spinal lesions.



Material and Methods: Sixty-nine patients with vascular lesions of the craniofacial and spinal regions underwent embolization with HM. The pathologies included craniofacial tumours (n=38), cranial arteriovenous malformations (AVMs) (n=7), dural AVM (n=1), cavernous carotid fistula (n=1), spinal tumours (n=7), spinal AVMs (n=6), orbital lesions (n=4) and scalp AVMs (n=5). Surgery was done in 56 patients. The blood loss at surgery, tumour shrinkage, surgical cleavage and ease of removal of tumour was noted from the records. Histopathology was available in 39 patients. A follow-up of 3 months to 6 years was available in 13 patients in whom embolization was the sole treatment. Surgical and histopathological findings were correlated with angio-embolization findings.



Results: HMs were easy to inject through the microcatheter with good control. Good devascularization was obtained in 61 patients and partial in 8 patients. Two patients developed complications due to presence of anastomoses between intra- and extracranial circulation and 1 patient due to tumor swelling. Histopathology showed presence of HMs in all the lesions, with minimal inflammatory reaction in 2 patients. Patients with spinal lesions treated with embolization only stabilised in neurologic deficits.



Conclusion: HMs are highly suitable as embolization agents in the management of craniofacial and spinal hypervascular lesions.
Previous Exposure to Measles, Mumps, and Rubella—but Not Vaccination During Adolescence—Correlates to the Prevalence of Pancreatic and Thyroid Autoantibodies (1999)

Previous natural infection or vaccination against measles, mumps, or both seemed to have an inhibitory effect on the development of thyroid autoantibodies. In contrast, children with previous exposure to rubella had higher levels of ICA. No evidence was found that MMR vaccination during adolescence may trigger autoimmunity.
Invariant-based automatic testing of AJAX user interfaces (2009)

AJAX-based Web 2.0 applications rely on stateful asynchronous client/server communication, and client-side runtime manipulation of the DOM tree. This not only makes them fundamentally different from traditional web applications, but also more error-prone and harder to test. We propose a method for testing AJAX applications automatically, based on a crawler to infer a flow graph for all (client-side) user interface states. We identify AJAX-specific faults that can occur in such states (related to DOM validity, error messages, discoverability, back-button compatibility, etc.) as well as DOM-tree invariants that can serve as oracle to detect such faults. We implemented our approach in ATUSA, a tool offering generic invariant checking components, a plugin-mechanism to add application-specific state validators, and generation of a test suite covering the paths obtained during crawling. We describe two case studies evaluating the fault revealing capabilities, scalability, required manual effort and level of automation of our approach.
Visual navigation of large environments using textured clusters (1995)

A visual navigation system is described which uses texture mapped primitives to represent clusters of objects to maintain high and approximately constant frame rates. In cases where there are more unoccluded primitives inside the viewing frustum than can be drawn in real-time on the workstation, this system ensures that each visible object, or a cluster that includes it, is drawn in each frame. The system supports the use of traditional “level-of-detail” representations for individual objects, and supports the automatic generation of a certain type of level-of-detail for objects and clusters of objects. The concept of choosing a representation from among those associated with an object that accounts for the direction from which the object is viewed is also supported. The level-of-detail concept is extended to the whole model and the entire scene is stored as a hierarchy of levels-of-detail that is traversed top-down to find a good representation for a given viewpoint. This system does not assume that visibility information can be extracted from the model and is thus especially suited for outdoor environments.
Novel Antibody Hinge Regions for Efficient Production of CH2 Domain-deleted Antibodies (2005)

HuCC49 deltaCH2 is a heavy chain constant domain 2 domain-deleted antibody under development as a radioimmunotherapeutic for treating carcinomas overexpressing the TAG-72 tumor antigen. Mammalian cell culture biosynthesis of HuCC49 deltaCH2 produces two isoforms (form A and form B) in an approximate 1:1 ratio, and consequently separation and purification of the desired form A isoform adversely impact process and yield. A protein engineering strategy was used to develop a panel of hinge-engineered HuCC49 deltaCH2 antibodies to identify hinge sequences to optimize production of the form A isoform. We found that adding a single proline residue at Kabat position 243, immediately adjacent to the carboxyl end of the core middle hinge CPPC domain, resulted in an increase from 39 to 51% form A isoform relative to the parent HuCC49 deltaCH2 antibody. Insertion of the amino acids proline-alanine-proline (PAP) at positions 243-245 enhanced production of the form A isoform to 72%. Insertion of a cysteine-rich 15-amino acid IgG3 hinge motif (CPEPKSCDTPPPCPR) in both of these mutant antibodies resulted in secretion of predominantly form A isoform with little or no detectable form B. Yields exceeding 98% of the form A isoform have been realized. Preliminary peptide mapping and mass spectrometry analysis suggest that at least two, and as many as five, inter-heavy chain disulfide linkages may be present.
bcl-2and Other Genomic Alterations in the Prognosis of Large-Cell Lymphoma (1989)

Approximately half the patients with diffuse or follicular large-cell or mixed large- and small-cell lymphoma enter a prolonged remission or are cured after receiving combined-drug therapy. It has been unclear, however, why the other half do not respond. We evaluated 54 previously untreated patients with diffuse lymphoma and 20 with follicular lymphoma, all of whom had a large-cell component and Stage II through IV disease, subsequently treated with combined chemotherapy. Different recurrent genomic defects were associated with differences in the response to treatment. Among the 54 patients with diffuse lymphoma, all 12 patients with a duplication of chromosome 3p had a complete clinical remission after a median follow-up of 39 months (11 patients survived). In contrast, all seven patients with a duplication of chromosome 2p had a partial response or no response to treatment and a median survival of six months (all died). Among the 20 patients with follicular lymphoma, all 5 patients with duplication 3p or +3 had a complete clinical remission (all survived), and 3 of 4 patients with duplication 2p or +2 had no response or a partial response to treatment and died. Twenty-three patients with B-cell non-immunoblastic lymphoma or follicular lymphoma who had a bcl-2 oncogene rearrangement had a poorer response to therapy (7 of 23 with complete remission) than the patients without bcl-2 rearrangement (21 of 26 with complete remission). We conclude that in large-cell or mixed-cell lymphoma, duplication of chromosome 3p is associated with a relatively good prognosis and duplication of chromosome 2p or bcl-2 oncogene rearrangement is associated with a relatively poor prognosis. Because such multiple recurrent genomic defects are also common in most other types of cancer, they may have general prognostic importance.