gebhart/patrepeval huggingface dataset:
Transfer of Genes to Chondrocytic Cells of the Lumbar Spine (1997)

The introduction of exogenous therapeutic genes into cells from the intervertebral end plate opens the possibility for a local gene-based treatment of intervertebral disc degeneration. This approach avoids some of the shortcomings of conventional drug- and surgery-based treatments and has the potential to be specific, effective, and appropriate to the chronicity of the disease.
Optimal wavelength for ultrahigh-resolution optical coherence tomography (2003)

The influence of depth dependent dispersion by the main component of biological tissues, water, on the resolution of OCT was studied. Investigations showed that it was possible to eliminate the influence of depth dependent dispersion by water in tissue by choosing a light source with a center wavelength near 1.0 microm. Ultrahigh resolution ophthalmic imaging was performed at this wavelength range with a microstructure fiber light source.
Generation and analysis of random point mutations in an antibody CDR2 sequence: many mutated antibodies lose their ability to bind antigen. (1992)

We have investigated the impact of mutations on the binding functions of the phosphocholine (PC)-specific T15 antibody in the absence of antigen selection pressure. The H chain complementarity determining region 2 (CDR2) sequence of T15 antibody was saturated with point mutations by in vitro random mutagenesis. From the mutant library, 289 clones were screened by direct DNA sequencing. The point mutations generated by this method were randomly distributed throughout the CDR2 region and included all kinds of substitutions. 46 unique mutant antibodies, containing one to four point mutations each, were expressed in SP2/0 myeloma cells. Functional analysis on these antibodies has provided insights into several aspects of somatic mutation. (a) The majority (26/46) of mutant antibodies either lost (20/46) or had reduced (6/46) ability to bind PC-protein conjugates or R36a, a PC-expressing strain of Streptococcus pneumoniae. In contrast, none of the mutant antibodies displayed increased binding for these PC antigens. Taken together with calculations of destructive mutations elsewhere in the V region, the data suggest that somatic mutation may cause extensive wastage among B cells during clonal expansion after antigen stimulation. (b) The frequency of binding-loss mutants increased sharply when a second mutation was introduced into the CDR2 sequence; it appears that, in some cases, two or more mutations are needed to destroy binding. (c) The mutant antibodies were tested for their reactivity to 11 non-PC antigens as well as to three PC analogues. None of the mutants gained new reactivity or changed their ability to discriminate structural analogues, supporting the notion that the major role of somatic mutation is to increase or decrease affinity rather than to create new specificities. (d) Mutations in at least five different positions in CDR2 were deleterious, suggesting that these residues may be essential for antigen binding. Three of these positions are novel in that they had not been identified to be important for binding PC by previous crystallographic analysis. (e) Introduction of mutations into two highly conserved residues in CDR2 did not alter the overall conformation of the V region as judged by antiidiotypic analysis, and, in some cases, did not affect the antigen binding function. The results thus indicate that even nonconservative substitutions of invariant residues need not be deleterious, suggesting that their conservation may be due to reasons other than maintaining antibody structure or specificity.
Isolation and properties of minB, a complex genetic locus involved in correct placement of the division site in Escherichia coli (1988)

Mutation of Escherichia coli minicell locus (minB) results in aberrant placement of the division septum. In this paper we report the isolation and characterization of the minB locus. Replacement of the chromosomal minB+ allele by cloned minB sequences containing transposon insertions resulted in the minicell phenotype, indicating that minB+ function is required to maintain the normal division pattern. Paradoxically, overexpression of the locus also resulted in the minicell phenotype. The locus codes for several peptides whose expression is coordinately affected by transposon mutations that also eliminate minB+ function. A subset of the minB peptides is sufficient to prevent minicell formation in minB1 mutants or to induce minicell formation when overproduced in wild-type strains, implicating these peptides in the normal process of localization of the division site. The results indicate that minB is a complex locus whose expression must be maintained within certain limits to maintain the normal pattern of localization of the division septum.
45 Mbps cat's eye modulating retro-reflector link over 7 Km (2006)

Modulating retro-reflectors (MRR) allow free space optical links with no need for pointing, tracking or a laser on one end of the link. They work by coupling a passive optical retro-reflector with an optical modulator. The most common kind of MRR uses a corner cube retro-reflector. These devices must have a modulator whose active area is as large as the area of the corner cube. This limits the ability to close longer range high speed links because the large aperture need to return sufficient light implies a large modulator capacitance. To overcome this limitation we developed the concept of a cat's eye MRR. Cat's eye MRRs place the modulator in the focal plane of a lens system designed to passively retro-reflect light. Because the light focuses onto the modulator, a small, low capacitance, modulator can be used with a large optical aperture. However, the position of the focal spot varies with the angle of incidence so an array of modulators must be placed in the focal plane, In addition, to avoid having to drive all the modulator pixels, an angle of arrival sensor must be used. We discuss several cat's eye MRR systems with near diffraction limited performance and bandwidths of 45 Mbps. We also discuss a link to a cat's eye MRR over a 7 Km range.
Improvement of the corrosion resistance on Nd-Fe-B magnet with nickel plating (1989)

Three kinds of corrosion tests, a humidity test (80 degrees C, 90% RH), an autoclave test (120 degrees C, 2 atm saturated with water vapor), and a salt spray test (35 degrees C, 5% NaCl), were performed on a sintered magnet treated with nickel plating. For comparison, samples with epoxy resin coating, Al ion plating, and without coating were also exposed to the corrosion test. After specified periods of corrosion testing, the permanent flux loss of the remagnetized sample was measured. Changes in appearance were also observed. It was found that the epoxy resin coating could not prevent the penetration of moisture in the humidity and autoclave tests because of its hygroscopic properties. The nickel plating and Al ion plating withstood the humidity and autoclave tests reasonably well, but they suffered slight corrosion in the salt spray test. It is concluded that the use of nickel plating can provide high corrosion resistance and low cost of production.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Role of ICOS versus CD28 in antiviral immunity (2002)

The costimulatory protein ICOS is inducibly expressed on activated T cells. Previous results have shown that ICOS–/– mice are defective in germinal center formation, antibody (Ab) production and class switch as well as Th1 and Th2 cytokine production in response to protein or parasite antigens. However, ICOS-Ig failed to block antiviral Ab responses. To date the immune response to viruses has not been examined in ICOS–/– mice. In this report we compared antiviral Ab responses to LCMV, VSV and influenza virus in ICOS–/– versus wild-type mice. Our results show that ICOS is important in the Ab response to all three viruses, with greater effects on primary as compared to secondary responses. Although ICOS–/– mice are impaired in some immune responses following influenza infection, the effects were less severe than for CD28–/– mice. There was no defect in initial influenza-specific CD8 T cell expansion in ICOS–/– mice or in cytotoxic effector function. However, ICOS was important in maintaining CD4 cytokine production and CD8 T cell numbers late in the primary response. Upon secondary infection, ICOS–/– mice show wild-type levels of influenza-specific CD8 T cells, whereas CD28–/– mice show greatly impaired secondary CD8 T cell expansion. Overall, our results show that ICOS plays a clear role in the primary response to viruses at the level of Ab production, germinal center formation and Th cytokine production, but has diminished effects following secondary viral challenge.
ISOLATION AND PARTIAL CHARACTERIZATION OF A MAJOR INOSITOL-CONTAINING LIPID IN BAKER'S YEAST, MANNOSYL-DIINOSITOL, DIPHOSPHORYL-CERAMIDE (1969)

A polar lipid containing about 20 per cent of the lipid soluble inositol has been purified from cells of Saccharomyces cerevisiae. This compound labeled with (3)H-inositol, (32)P(i), or (14)C glucose was isolated from aqueous pyridine extracts by means of paper chromatography. Unlabeled compound was obtained by a differential solubility scheme. Analytical and degradation studies suggest that this compound can be formulated as a mannosyl-diinositol, diphosphoryl-ceramide. It can be converted by treatment with base or acid into a mannosylmonoinositol phosphoryl-ceramide, a composition which relates it to the basic structure of the phytoglycolipids.
Hepatic encephalopathy: A review (2003)

Hepatic encephalopathy (HE) is a complication that presents in as many as 28% of patients with cirrhosis, and reported up to ten years after the diagnosis of cirrhosis. Commonly, it is observed in patients with severe hepatic failure and is characterized by neuropsychiatric manifestations that can range in severity from a mild alteration in mental state to a coma; additionally, some neuromuscular symptoms can be observed. This complication of either acute or chronic hepatic disease is the result of a diminished hepatic reservoir and inability to detoxify some toxins that originate in the bowel. Today, the role of astrocytes, specifically the Alzheimer type II cells, is known to be very important in the pathogenesis of the hepatic encephalopathy, and will be reviewed later. In conclusion, the objectives of this review are: To understand the pathogenesis of hepatic encephalopathy, To recognize the precipitating factors, as well as preventive measures for the development of the hepatic encephalopathy, To describe the new classification of hepatic encephalopathy and its clinical implications, To recognize the clinical manifestations and stages of the disease, To understand the main diagnostic tests used to detect the hepatic encephalopathy, To describe the main therapeutic treatments of hepatic encephalopathy.
Adenovirus DNA. I. Molecular weight and conformation. (1967)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Proteomics and Bioinformatics Approaches for Identification of Serum Biomarkers to Detect Breast Cancer (2002)

Proteomics approaches such as SELDI mass spectrometry, in conjunction with bioinformatics tools, could greatly facilitate the discovery of new and better biomarkers. The high sensitivity and specificity achieved by the combined use of the selected biomarkers show great potential for the early detection of breast cancer.
Single‐cell analysis of siRNA‐mediated gene silencing using multiparameter flow cytometry (2006)

Multiparameter flow cytometry is a powerful technique for the quantitative analysis of siRNA-mediated protein knockdown in complex hard-to-transfect cell populations.
Single-chain Fv multimers of the anti-neuraminidase antibody NC10: the residue at position 15 in the VL domain of the scFv-0 (VL−VH) molecule is primarily responsible for formation of a tetramer–trimer equilibrium (2003)

Single-chain variable fragment of the murine monoclonal antibody NC10 specific to influenza virus N9 neuraminidase, joined directly in the V(L) to V(H) orientation (scFv-0), forms an equilibrium mixture of tetramer and trimer with the tetramer as the preferred multimeric species. In contrast, the V(H)-V(L) isomer was previously shown to exist exclusively as a trimer. Computer-generated trimeric and tetrameric scFv models, based on the refined crystal structure for NC10 Fv domain, were constructed and used to evaluate factors influencing the transition between V(L)-V(H) trimer and tetramer. These model structures indicated that steric restrictions between loops spanning amino acid residues L55-L59 and L13-L17 from the two adjacent V(L) domains within the V(L)-V(H) trimer were responsible for four scFv-0 molecules assembling to form a tetramer. In particular, leucine at position L15 and glutamate at position L57 appeared to interfere significantly with each other. To minimize this steric interference, the site-directed mutagenesis technique was used to construct several NC10 scFv-0 clones with mutations at these positions. Size-exclusion chromatographic analyses revealed that several of these mutations resulted in the production of NC10 scFv-0 proteins with significantly altered tetramer-trimer equilibrium ratios. In particular, introduction of a polar residue, such as asparagine or threonine, at position L15 generated a highly stable NC10 scFv-0 trimer.
Structure Based Drug Design of Crizotinib (PF-02341066), a Potent and Selective Dual Inhibitor of Mesenchymal–Epithelial Transition Factor (c-MET) Kinase and Anaplastic Lymphoma Kinase (ALK) (2011)

Because of the critical roles of aberrant signaling in cancer, both c-MET and ALK receptor tyrosine kinases are attractive oncology targets for therapeutic intervention. The cocrystal structure of 3 (PHA-665752), bound to c-MET kinase domain, revealed a novel ATP site environment, which served as the target to guide parallel, multiattribute drug design. A novel 2-amino-5-aryl-3-benzyloxypyridine series was created to more effectively make the key interactions achieved with 3. In the novel series, the 2-aminopyridine core allowed a 3-benzyloxy group to reach into the same pocket as the 2,6-dichlorophenyl group of 3 via a more direct vector and thus with a better ligand efficiency (LE). Further optimization of the lead series generated the clinical candidate crizotinib (PF-02341066), which demonstrated potent in vitro and in vivo c-MET kinase and ALK inhibition, effective tumor growth inhibition, and good pharmaceutical properties.
Role of chemokines and chemokine receptors in the gastrointestinal tract (2002)

The pathological association between leucocytes and gastrointestinal diseases has long been recognized. Chemokines are a large family of chemotactic cytokines whose fundamental role is the recruitment of leucocytes to tissues. Although chemokines and their receptors are considered to be mediators of inflammation and tissue injury in several inflammatory diseases, their precise role in the pathophysiology of gastrointestinal diseases remains incompletely understood. Nonetheless, by virtue of their expression and localization at sites of gastrointestinal tissue injury and inflammation, a number of investigators have suggested a vital role for chemokines and their receptors in the pathophysiology of gastrointestinal diseases. This short review examines the role of chemokines and their receptors in the gastrointestinal tract with an emphasis on their involvement in the regulation of intestinal and hepatic inflammation.
Protection against herpes simplex virus-induced eye disease after vaccination with seven individually expressed herpes simplex virus 1 glycoproteins. (1995)

These results suggest that when used as vaccines, different HSV-1 glycoproteins provide different levels of protection against HSV-1-induced eye disease. Based on comparison with the authors' previously published results, the ability of each glycoprotein to protect against eye disease correlated with the ability of the glycoprotein to induce high serum neutralizing antibody titers and killer cell activity. Results suggest that the effectiveness of these seven glycoproteins in protecting against eye disease can be ranked as follows: gD > gB > gI > (gC = gE) > gG > gH.
Synthesis of (3-hydroxy-2-phosphonylmethoxypropyl) derivatives of heterocyclic bases (1989)

Analogs of the antiviral 9-( S )-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA, I ), containing modified heterocyclic base, were prepared from racemic or ( S )-N-(2,3-dihydroxypropyl) derivatives II . Compounds II are heated with chloromethylphosphonyl dichloride ( XVII ), the formed chloromethylphosphonylester chlorides of compounds II react with water to give a mixture of 2'- and 3'-chloromethylphosphonyl derivatives XVIII and XIX , respectively, which on isomerization by boiling with water in the arising acidic medium affords predominantly the 3'-isomer XIX . Treatment of this isomeric mixture with aqueous sodium hydroxide yields a mixture of 2'-O-phosphonylmethyl ethers (predominating, XXI ) and 3'-O-phosphonylmethyl ethers of compounds II ( XX ). This approach has been applied to the synthesis of isomeric mixtures in the racemic as well as in the ( S )-series derived from C-2, C-8 and N-6 substituted derivatives of adenine, from hypoxanthine and additional 6-substituted derivatives of purine, from guanine, 3-deazaadenine and other modified purine bases, from uracil, cytosine, their 5-methyl derivatives and 5-fluorouracil. Regioselective synthesis of compounds XXI was performed for biologically active derivatives (derivative of 2-aminoadenine ( XXIe ), guanine ( XXIn ), 3-deazaadenine ( XXIp ) and cytosine ( XXIt )) as well as some other compounds (derivative of hypoxanthine ( XXIj ), uracil ( XXIr ), thymine ( XXIs ) and 5-methylcytosine ( XXIu )): the former were obtained either from 3'-O-chloromethylphosphonyl derivatives XIX , isolated from the above-mentioned mixtures by ion-exchanger chromatography or HPLC, or by regioselective substitution, whereas the latter compounds were prepared by deamination (compound XXIj from adenine derivative I or the uracil and thymine derivatives XXIr and XXIu from the cytosine derivatives XXIt and XXIu ). N-( S )-(3-Hydroxy-2-benzoyloxypropyl) derivative of N 4 -benzoylcytosine ( XXIX ) and N 2 -benzoylguanine ( XXIV ), obtained from compounds IIn and IIt by successive N-benzoylation, reaction with dimethoxytrityl chloride, benzoylation and mild acid treatment, were subjected to reaction with the chloride XVII and subsequent neutral and alkaline hydrolysis (compound XXIV ), or to reaction with sodium methoxide followed by treatment with bromotrimethylsilane (compound XXIX ), being thus converted into 1-( S )-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine ( XXIt , HPMPC) and 9-( S )-(3-hydroxy-2-phosphonylmethoxypropyl)guanine ( XXIn , HPMPG), respectively. The starting compounds ( S )- II were synthesized from sodium salt of the corresponding heterocyclic base by reaction with 1-O- p -toluenesulfonyl-2,3-O-isopropylidene-( R )-glycerol ( IIIa ) (the ( RS )-derivatives by reaction with 4-chloromethyl-2,2-dimethyl-1,3-dioxolane ( IIIb )), followed by acid hydrolysis.
Regulation of cell size in growth, development and human disease: PI3K, PKB and S6K (2002)

It has generally been observed that cells grow to a certain size before they divide. In the last few years, the PI3K signal transduction pathway has emerged as one of the main signaling routes utilized by cells to control their increase in size. Here we focus on two components of this pathway, PKB and S6K, and briefly review the experiments that initially uncovered their roles in cell size control. In addition, we discuss a number of recent observations suggesting that the generic models used to describe this pathway to date may have been oversimplified. Indeed, recent observations in Drosophila and mouse support a more complex interaction between these signaling components in development. Finally, we have utilized two contemporary studies involving PKB- and S6K-deficient mice as a paradigm to underscore the importance of cell size and to accurately delineate the connections between signaling pathways for human disease, such as diabetes mellitus.
A mouse/human-chimeric bispecific antibody reactive with human carcinoembryonic antigen-expressing cells and human T-lymphocytes. (1996)

A mouse/human-chimeric bispecific antibody, designated CBA-CEACD3, with dual specificities for carcinoembryonic antigen (CEA) and CD3, was generated by chemical cross-linking of a chimeric antibody specific for CEA to another chimeric antibody against CD3. Flow cytometric analysis showed that CBA-CEACD3 can bind specifically to cells expressing CEA and to normal human peripheral blood mononuclear cells (HPBMCs) bearing CD3, respectively. Furthermore, a cell to cell adhesion analysis by a colorimetric assay using the dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) demonstrated that CBA-CEACD3 is able to bind CEA-producing cells to CD3-expressing cells, suggesting that both arms of CBA-CEACD3 are simultaneously working and can retarget T-cells to the tumor. In an additional colorimetric assay using MTT, this antibody was shown to effectively mediate CEA-expressing tumor cell killing by freshly isolated HPBMCs. Together these results demonstrate that this chimeric bispecific antibody may serve as a potentially useful immunotherapeutic reagent for human CEA-producing cancers.
SSX: A multigene family with several members transcribed in normal testis and human cancer (1997)

Analysis of t(X;18) translocation in synovial sarcoma had previously led to the definition of the SSX2 gene, the fusion partner on chromosome X. Subsequent screening of testicular cDNA libraries identified 2 highly homologous genes, SSX1 and SSX3. Among these 3 genes, SSX2 has been found to be identical to HOM-MEL-40, which codes for an immunogenic tumor antigen expressed in various human cancers. SSX2 thus belongs to the family of cancer/testis (CT) antigens, i.e., immunogenic protein antigens with characteristic mRNA expression in normal testis and in cancer. To define additional CT antigens, we have immuno-screened a testicular cDNA expression library with an allogeneic serum from a melanoma patient, and both SSX2 and SSX3 were isolated. Further studies using testicular cDNA and SSX probes defined 2 new members of this gene family, SSX4 and SSX5, while a shorter cDNA variant of SSX4 was also identified. All 5 members of the SSX family shared strong sequence homology, with nucleotide homology ranging from 88 to 95% and amino acid homology ranging from 77 to 91%. Genomic cloning of a prototype SSX gene (SSX2) showed that its coding region is encoded by 6 exons, and the shortened form of SSX4 cDNA represents an alternatively spliced product lacking the 5th exon. Analysis of SSX mRNA expression by gene-specific RT-PCR confirmed that all 5 SSX genes are expressed in testis. In addition, analysis of a panel of 12 melanoma cell lines showed strong mRNA expression of either SSX1 (3/12), SSX2 (3/12), SSX4 (1/12), or SSX5 (1/12), indicating variable activation of the genes in malignant cells.