gebhart/patrepeval huggingface dataset:
Characterization of elk, a brain-specific receptor tyrosine kinase. (1991)

The elk gene encodes a novel receptorlike protein-tyrosine kinase, which belongs to the eph subfamily. We have previously identified a partial cDNA encompassing the elk catalytic domain (K. Letwin, S.-P. Yee, and T. Pawson, Oncogene 3:621-678, 1988). Using this cDNA as a probe, we have isolated cDNAs spanning the entire rat elk coding sequence. The predicted Elk protein contains all the hallmarks of a receptor tyrosine kinase, including an N-terminal signal sequence, a cysteine-rich extracellular domain, a membrane-spanning segment, a cytoplasmic tyrosine kinase domain, and a C-terminal tail. In both amino acid sequence and overall structure, Elk is most similar to the Eph and Eck protein-tyrosine kinases, suggesting that the eph, elk, and eck genes encode members of a new subfamily of receptorlike tyrosine kinases. Among rat tissues, elk expression appears restricted to brain and testes, with the brain having higher levels of both elk RNA and protein. Elk protein immunoprecipitated from a rat brain lysate becomes phosphorylated on tyrosine in an in vitro kinase reaction, consistent with the prediction that the mammalian elk gene encodes a tyrosine kinase capable of autophosphorylation. The characteristics of the Elk tyrosine kinase suggest that it may be involved in cell-cell interactions in the nervous system.
Angular dependence of polarizing beam-splitter cubes (1994)

The field-of-view dependence of polarizing beam-splitter cubes has been studied to characterize their behavior in imaging systems such as optical computers and optical correlators and in other applications that involve noncollimated light. Significant polarization aberration is present in polarizing beamsplitter cubes for two reasons: (1) the s- and p-component orientations, which define the polarizing axes, at the beam-splitting interface vary with the direction of propagation, and (2) the performance of the coating is a function of the angle of incidence. We describe the polarization aberration of a polarizing beam-splitter cube in terms of its diattenuation (polarizing efficiency). We use an imaging polarimeter to measure six figures of merit for three polarizing beam-splitter cubes demonstrating typical polarization aberrations. Finally, we derive the Mueller matrix for a polarizing beam-splitter cube in terms of the s and p transmittance and reflectance and the phase retardances, the parameters generally calculated with thin-film analysis programs.
Fragment size analysis of free fetal DNA in maternal plasma using Y-STR loci and SRY gene amplification. (2011)

Free fetal DNA (ffDNA) in maternal plasma has now become a valuable source for noninvasive prenatal diagnosis. Being able to accurately identify the size of ffDNA in maternal plasma is essential for a noninvasive prenatal diagnosis. Furthermore, it is important to investigate the molecular characteristics related to apoptosis which gives rise to ffDNA. We investigated the fragment size of ffDNA in each sample more precisely, using both Y-STR and SRY primers, in 20 maternal plasma samples from the 17th to 39th weeks of gestation. PCR was conducted with Y-STR and SRY primers which can be used to amplify 100-524 bp fragments. In samples from 10 pregnant women carrying male fetuses, the maximum fragment size detected by Y-STR and SRY primers ranged from 219 to 313 bp. As a result, the mean average maximum fragment size of free fetal DNA detected by Y-STR and SRY primers was 286 +/- 28 bp. The Y-STR alleles detected in each maternal plasma DNA sample were all in agreement with the results of their cord blood samples. We concluded that the fragment size of ffDNA comprises 2 nucleosomal complexes or less, but not exceeding 3.
The metabolites of Trichodermalongibrachiatum. Part 1. Isolation of the metabolites and the structure of trichodimerol (1992)

Trichodermalongibrachiatum Rifai aggr. is a fungus reported to be antagonistic to the fungus Mycenacitricolor, the causative agent of the American leaf spot disease of coffee. We have investigated the metabolites produced when T. longibrachiatum is grown in liquid culture and have isolated the known compounds sorbicillin (2), bisvertinol (3), and bisvertinolone (4) as well as several new compounds including trichodimerol (1), an interesting new natural product possessing a proper axis of symmetry. The structure of trichodimerol (1) was determined by a combination of spectroscopic techniques, including 1 H and 13 C nuclear magnetic resonance, infrared, ultraviolet, circular dichroism, optical rotatory dispersion, and mass spectrometry, and by transformation to octahydrotrichodimerol (6) and symmetrical and unsymmetrical derivatives thereof. The relative stereochemistry of bisvertinol (3) and bisvertinolone (4) has been revised. The metabolites described are not biologically active against Mycenacitricolor.
NASA's flight-technology development program: a 650-Mbit/s laser communications testbed (1991)

A 650 Mbps laser communications testbed under construction for the development of flight qualifiable hardware suitable for near-term operation on geosynchronous-to-geosynchronous crosslink missions is presented. The program''s primary purpose is to develop and optimize laser communications unique subsystems. Requirements for the testbed experiments are to optimize the acquisition processes, to fully simulate the long range (up to 21,000 km) and the fine tracking characteristics of two narrow-beam laser communications terminals, and to fully test communications performance which will include average and burst bit error rates, effects of laser diode coalignment, degradation due to internal and external stray light, and the impact of drifts in the optical components.
A heterozygous female with Fabry disease due to a novel α-galactosidase A mutation exhibits a unique synaptopodin distribution in vacuolated podocytes (2014)

We report the case of a 42-yearold woman diagnosed with heterozygous Fabry disease (FD) due to a novel α-galactosidase A Pro210Ser mutation and exhibiting a unique distribution of synaptopodin within podocytes. The patient was referred to our hospital with moderate proteinuria, and a renal biopsy was performed. Light microscopic examination of the specimen revealed diffuse global enlargement of podocytes, which also showed foamy changes. Electron microscopy revealed abundant myeloid bodies in podocytes and focal mitochondrial abnormalities within the tubules. The patient exhibited none of the characteristic symptoms of FD except hypohidrosis and had no obvious family history. Genetic analysis revealed a novel missense mutation (Pro210Ser) in the α-galactosidase A gene. She was ultimately diagnosed with FD based on immunohistochemical staining indicating large amounts of accumulated globotriaosylceramide in her podocytes, detection of urinary globotriaosylceramide secretion using high-performance thin-layer chromatography/ immunostaining, and structural modeling of the mutated α-galactosidase A (Pro210Ser). Immunostaining of the swollen and foamy podocytes using podocyte-associated antibodies (against podocalyxin, Wilms tumor-1, vimentin, and synaptopodin) revealed a unique distribution of synaptopodin surrounding globotriaosylceramide. To our knowledge, this is the first report of immunohistologically detected synaptopodin upregulation in foamy podocytes in a patient with FD.
Cyclo-Oxygenase 2 Function Is Essential for Bone Fracture Healing (2002)

Despite the molecular and histological similarities between fetal bone development and fracture healing, inflammation is an early phase of fracture healing that does not occur during development. Cyclo-oxygenase 2 (COX-2) is induced at inflammation sites and produces proinflammatory prostaglandins. To determine if COX-2 functions in fracture healing, rats were treated with COX-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs) to stop COX-2-dependent prostaglandin production. Radiographic, histological, and mechanical testing determined that fracture healing failed in rats treated with COX-2-selective NSAIDs (celecoxib and rofecoxib). Normal fracture healing also failed in mice homozygous for a null mutation in the COX-2 gene. This shows that COX-2 activity is necessary for normal fracture healing and confirms that the effects of COX-2-selective NSAIDs on fracture healing is caused by inhibition of COX-2 activity and not from a drug side effect. Histological observations suggest that COX-2 is required for normal endochondral ossification during fracture healing. Because mice lacking Cox2 form normal skeletons, our observations indicate that fetal bone development and fracture healing are different and that COX-2 function is specifically essential for fracture healing.
Removal of MAP4 from microtubules in vivo produces no observable phenotype at the cellular level. (1996)

Microtubule-associated protein 4 (MAP4) promotes MT assembly in vitro and is localized along MTs in vivo. These results and the fact that MAP4 is the major MAP in nonneuronal cells suggest that MAP4's normal functions may include the stabilization of MTs in situ. To understand MAP4 function in vivo, we produced a blocking antibody (Ab) to prevent MAP4 binding to MTs. The COOH-terminal MT binding domain of MAP4 was expressed in Escherichia coli as a glutathione transferase fusion protein and was injected into rabbits to produce an antiserum that was then affinity purified and shown to be monospecific for MAP4. This Ab blocked > 95% of MAP4 binding to MTs in an in vitro assay. Microinjection of the affinity purified Ab into human fibroblasts and monkey epithelial cells abolished MAP4 binding to MTs as assayed with a rat polyclonal antibody against the NH2-terminal projection domain of MAP4. The removal of MAP4 from MTs was accompanied by its sequestration into visible MAP4-Ab immunocomplexes. However, the MT network appeared normal. Tubulin photoactivation and nocodazole sensitivity assays indicated that MT dynamics were not altered detectably by the removal of MAP4 from the MTs. Cells progressed to mitosis with morphologically normal spindles in the absence of MAP4 binding to MTs. Depleting MAP4 from MTs also did not affect the state of posttranslational modifications of tubulin subunits. Further, no perturbations of MT-dependent organelle distribution were detected. We conclude that the association of MAP4 with MTs is not essential for MT assembly or for the MT-based functions in cultured cells that we could assay. A significant role for MAP4 is not excluded by these results, however, as MAP4 may be a component of a functionally redundant system.
The similarity between N-terminal targeting signals for protein import into different organelles and its evolutionary relevance (2015)

The proper distribution of proteins between the cytosol and various membrane-bound compartments is crucial for the functionality of eukaryotic cells. This requires the cooperation between protein transport machineries that translocate diverse proteins from the cytosol into these compartments and targeting signal(s) encoded within the primary sequence of these proteins that define their cellular destination. The mechanisms exerting protein translocation differ remarkably between the compartments, but the predominant targeting signals for mitochondria, chloroplasts and the ER share the N-terminal position, an α-helical structural element and the removal from the core protein by intraorganellar cleavage. Interestingly, similar properties have been described for the peroxisomal targeting signal type 2 mediating the import of a fraction of soluble peroxisomal proteins, whereas other peroxisomal matrix proteins encode the type 1 targeting signal residing at the extreme C-terminus. The structural similarity of N-terminal targeting signals poses a challenge to the specificity of protein transport, but allows the generation of ambiguous targeting signals that mediate dual targeting of proteins into different compartments. Dual targeting might represent an advantage for adaptation processes that involve a redistribution of proteins, because it circumvents the hierarchy of targeting signals. Thus, the co-existence of two equally functional import pathways into peroxisomes might reflect a balance between evolutionary constant and flexible transport routes.
Mitotic-specific methylation of histone H4 Lys 20 follows increased PR-Set7 expression and its localization to mitotic chromosomes (2002)

We describe distinct patterns of histone methylation during human cell cycle progression. Histone H4 methyltransferase activity was found to be cell cycle-regulated, consistent with increased H4 Lys 20 methylation at mitosis. This increase closely followed the cell cycle-regulated expression of the H4 Lys 20 methyltransferase, PR-Set7. Localization of PR-Set7 to mitotic chromosomes and subsequent increase in H4 Lys 20 methylation were inversely correlated to transient H4 Lys 16 acetylation in early S-phase. These data suggest that H4 Lys 20 methylation by PR-Set7 during mitosis acts to antagonize H4 Lys 16 acetylation and to establish a mechanism by which this mark is epigenetically transmitted.
Low Reynolds Number Micro-Fluidic Devices (1996)

The fluid dynamics in microfabricated fluidic devices is inherently in the low Reynolds number regime. By recognizing this, efficient micro-devices can be designed. Two such devices are described, a diffusion-based filter and a virtual valve. The diffusion-based filter differentially separates particles and molecules based on diffusion co efficient while diluting their concentration. Results and a simple anal ysis indicate that the dilution of the particles is exponentially related to the diffusion coefficient. The virtual valve functions as a switch, directing flow at the intersection of three channels by manipulating the pressure driving the flow. Switching times as fast as 100 ms are demonstrated. These devices are unique to the micro-scale-they would not work as well if scaled up.
Relationship between head circumference and height in normal adults and in the nevoid basal cell carcinoma syndrome and neurofibromatosis type I (1991)

Occipitofrontal circumference (OFC) was strongly correlated with height in 72 normal Caucasian men (r = 0.28, P = 0.018) and 78 women (r = 0.53, P less than 0.0001). OFC:height ratios were approximately normally distributed in each sex with a mean of 0.326 (standard deviation [sd] = 0.0139) in males and 0.335 (sd = 0.0177) in females. Relative macrocephaly (an OFC greater than the 95th centile for height) was seen in seven of nine probands with the nevoid basal cell carcinoma syndrome (NBCC), eight of 32 non-probands with NBCC, three of four neurofibromatosis type 1 (NF1) probands, and six of nine non-probands with NF1. Thirty-one percent of the non-proband NBCC cases had OFC less than the 50th centile for height, while none of the NF1 cases had this finding. Head size appears to be related to proband status in NBCC, while the evidence suggests that NF1 is a true macrocephaly syndrome. Objective detection of relative abnormalities in head size may aid in syndrome delineation and diagnosis.
Integrating a personal-computer local-area network with a radiology information system: value as a tool for clinical research. (1994)

Integrating a personal-computer local-area network with a radiology information system: value as a tool for clinical research.M S Frank, R Berge, E J Stern and J A JohnsonAudio Available | Share
Generation of protein-reactive antibodies by short peptides is an event of high frequency: implications for the structural basis of immune recognition. (1983)

Recent studies have shown that chemically synthesized small peptides can induce antibodies that often react with intact proteins regardless of their position in the folded molecule. These findings are difficult to explain in view of the experimental and theoretical data which suggest that in the absence of forces provided by the folded protein, small peptides in aqueous solution do not readily adopt stable structures. In order to rationalize the two findings, there has been general acceptance of a stochastic model which suggests that the multiple conformers of a peptide in solution induce sets of antibodies with a small percentage reactive with conformations shared by the folded protein. This stochastic model has become less tenable as the success rate for the generation of protein-reactive anti-peptide antibodies has grown. To test the stochastic model, we have used monoclonal anti-peptide antibodies as a way of estimating the frequency with which small peptides induce antibodies that react with folded proteins. We have made monoclonal antibodies to six chemically synthesized peptides from three proteins. The frequency with which the peptides induce protein-reactive antibodies is at least 4 orders of magnitude greater than expected from previous experimental work and vastly different from what would be predicted by calculating the possible number of peptide conformers in solution. These findings make the stochastic model less likely and lead to consideration of other models. Aside from their practical significance for generation of highly specific reagents, these findings may have important implications for the protein folding problem.
Identification by representational difference analysis of a homozygous deletion in pancreatic carcinoma that lies within the BRCA2 region. (1995)

Homozygous deletions have been central to the discovery of several tumor-suppressor genes, but their finding has often been either serendipitous or the result of a directed search. A recently described technique [Lisitsyn, N., Lisitsyn, N. & Wigler, M. (1993) Science 259, 946-951] held out the potential to efficiently discover such events in an unbiased manner. Here we present the application of the representational difference analysis (RDA) to the study of cancer. We cloned two DNA fragments that identified a homozygous deletion in a human pancreatic adenocarcinoma, mapping to a 1-centimorgan region at chromosome 13q12.3 flanked by the markers D13S171 and D13S260. Interestingly, this lies within the 6-centimorgan region recently identified as the BRCA2 locus of heritable breast cancer susceptibility. This suggests that the same gene may be involved in multiple tumor types and that its function is that of a tumor suppressor rather than that of a dominant oncogene.
Heparin and glutathione: Physiological decondensing agents of human sperm nuclei (1989)

It has been proposed that reduced glutathione (GSH) or other thiol reagents may participate in the basic mechanism by which sperm-decondensing activity is accomplished. However, in vitro, these reagents seem to be inactive and require the presence of other chemicals, usually detergents. Heparin binds specifically to the sperm membrane and provokes the decondensation of human sperm and the activation of DNA transcription and synthesis. However, the concentrations at which these effects occur seem to be higher than those expected under physiological conditions. In the present study, thiol reagents at 10 mM concentration, either alone or combined, were completely ineffective in inducing any significant nuclear decondensation after prolonged exposures (24 hr) of incubation. Heparin, 153.8 microM, was capable of inducing only a small increase in nuclear swelling. However, GSH at concentrations as low as 0.1 mM in combination with heparin induces decondensation of human sperm nuclei in vitro. When GSH concentration was kept constant at 5 mM, nuclear decondensation was induced with heparin at concentrations as low as 11.6 microM, and a maximal decondensation (90%) was obtained with only 21.6 microM of heparin. The latter is more than ten times less than the minimal active concentration of heparin used alone.
Expression of human apolipoprotein E reduces amyloid-β deposition in a mouse model of Alzheimer's disease (1999)

The epsilon4 allele of apolipoprotein E (apo E) is associated with an increased risk for developing Alzheimer's disease (AD). This may be due to interactions between apo E and the amyloid-beta protein (Abeta). To assess the effects of human apo E isoforms on Abeta deposition in vivo, we bred apo E3 and apo E4 hemizygous (+/-) transgenic mice expressing apo E by astrocytes to mice homozygous (+/+) for a mutant amyloid precursor protein (APPV717F) transgene that develop age-dependent AD neuropathology. All mice were on a mouse apo E null (-/-) background. By nine months of age, APPV717F+/-, apo E-/- mice had developed Abeta deposition, and, as reported previously, the quantity of Abeta deposits was significantly less than that seen in APPV717F+/- mice expressing mouse apo E. In contrast to effects of mouse apo E, similar levels of human apo E3 and apo E4 markedly suppressed early Abeta deposition at nine months of age in APPV717F+/- transgenic mice, even when compared with mice lacking apo E. These findings suggest that human apo E isoforms decrease Abeta aggregation or increase Abeta clearance relative to an environment in which mouse apo E or no apo E is present. The results may have important implications for understanding mechanisms underlying the link between apo E and AD.
Crystal and Molecular Structure of a Dimer Composed of the Variable Portions of the Bence-Jones Protein REI (1974)

The structure of the variable part of a χ-type Bence-Jones protein RE1 has been determined at a resolution of 0.28 nm. It forms a dimer in the crystal related by a local diad, held together by hydrogen bonding interactions of residues Tyr-36, Gln-38, Ala-43, Pro-44, Tyr-87, Gln-89 and Phe-98, which are largely conserved in light chains. The structure consists of two hydrogen-bonded sheets covering a hydrophobic interior made up of mostly conserved amino-acid side chains. Approximately 50% of the residues form β-pleated sheets. Several of the pleated sheet strands are connected by hair-pin bends, which contain glycine residues conserved in most light chains. The arrangement of the hypervariable segments especially in comparison with the Fab structure suggests that the V dimers form a primitive antibody. The folding of the poly-peptide chain and the spatial relationship of the two monomers appear to be the same as in the λ-type Bence-Jones protein dimer and the Fab fragment.
A role for PACE4 in the proteolytic activation of anthrax toxin protective antigen (1997)

Several bacterial protein toxins require activation by eukaryotic proteases. Previous studies have shown that anthrax toxin protective antigen (PA), Pseudomonas exotoxin A (PE), and diphtheria toxin (DT) are cleaved by furin C-terminal to the sequences RKKR, RQPR, and RVRR, respectively. Because furin-deficient cells retain some sensitivity to PA and DT, it is evident that other cellular proteases can activate these toxins. Whereas furin has been shown to require arginine residues at positions -1 and -4 for substrate recognition, another protease with an activity which could substitute for furin in toxin activation, the furin-related protease PACE4, requires basic residues in the -1, -2, and -4 positions of the substrate sequence. To examine the relative roles of furin and PACE4 in toxin activation, we used furin-deficient CHO cells (FD11 cells) transfected with either the furin (FD11/furin cells) or PACE4 (FD11/PACE4 cells) gene. Mutant PA proteins containing the cleavage sequence RAAR or KR were cytotoxic toward cells expressing only PACE4. In vitro cleavage data demonstrated that PACE4 can recognize RAAR and, to a much lesser extent, KR and RR. When extracts from PACE4-transfected cells were used as a source of proteases, PACE4 had minimal activity, indicating that it had been partially inactivated or did not remain associated with the cell membranes. Cleavage of iodinated PA containing the sequence RKKR or RAAR was detected on the surface of all cell types tested, but cleavage of a dibasic sequence was detected only intracellularly and only in cells that expressed furin or PACE4. The data provide evidence that PACE4 is present at the exterior of cells, that it plays a role in the proteolytic activation of anthrax toxin PA, and that PACE4 can activate substrates at the sequence RAAR or KR.