gebhart/patrepeval huggingface dataset:
High transcytosis of melanotransferrin (P97) across the blood–brain barrier (2002)

The blood-brain barrier (BBB) performs a neuroprotective function by tightly controlling access to the brain; consequently it also impedes access of proteins as well as pharmacological agents to cerebral tissues. We demonstrate here that recombinant human melanotransferrin (P97) is highly accumulated into the mouse brain following intravenous injection and in situ brain perfusion. Moreover, P97 transcytosis across bovine brain capillary endothelial cell (BBCEC) monolayers is at least 14-fold higher than that of holo-transferrin, with no apparent intra-endothelial degradation. This high transcytosis of P97 was not related to changes in the BBCEC monolayer integrity. In addition, the transendothelial transport of P97 was sensitive to temperature and was both concentration- and conformation-dependent, suggesting that the transport of P97 is due to receptor-mediated endocytosis. In spite of the high degree of sequence identity between P97 and transferrin, a different receptor than the one for transferrin is involved in P97 transendothelial transport. A member of the low-density lipoprotein receptor protein family, likely LRP, seems to be involved in P97 transendothelial transport. The brain accumulation, high rate of P97 transcytosis and its very low level in the blood suggest that P97 could be advantageously employed as a new delivery system to target drugs directly to the brain.
Identification of intermediates in the pathway of protein import into chloroplasts and their localization to envelope contact sites. (1993)

We have used a hybrid precursor protein to study the pathway of protein import into chloroplasts. This hybrid (pS/protA) consists of the precursor to the small subunit of Rubisco (pS) fused to the IgG binding domains of staphylococcal protein A. The pS/protA is efficiently imported into isolated chloroplasts and is processed to its mature form (S/protA). In addition to the mature stromal form, two intermediates in the pathway of pS/protA import were identified at early time points in the import reaction. The first intermediate represents unprocessed pS/protA bound to the outer surface of the chloroplast envelope and is analogous to a previously characterized form of pS that is specifically bound to the chloroplast surface and can be subsequently translocated in the stroma (Cline, K., M. Werner-Washburne, T. H. Lubben, and K. Keegstra. 1985. J. Biol. Chem. 260:3691-3696.) The second intermediate represents a partially translocated form of the precursor that remains associated with the envelope membrane. This form is processed to mature S/protA, but remains susceptible to exogenously added protease in intact chloroplasts. We conclude that the envelope associated S/protA is spanning both the outer and inner chloroplast membranes en route to the stroma. Biochemical and immunochemical localization of the two translocation intermediates indicates that both forms are exposed at the surface of the outer membrane at sites where the outer and inner membrane are closely apposed. These contact zones appear to be organized in a reticular network on the outer envelope. We propose a model for protein import into chloroplasts that has as its central features two distinct protein conducting channels in the outer and inner envelope membranes, each gated open by a distinct subdomain of the pS signal sequence.
Influence of global ischemia on intracellular sodium in the perfused rat heart (1990)

Intracellular [Na+], [H+], and [ATP] and mechanical performance were measured in the isovolumic perfused rat heart during ischemia. The concentration of intracellular sodium, [Na+]i, was determined by atomic absorption spectroscopy under control conditions, and [Na+]i was monitored by 23Na NMR spectroscopy at 1-min intervals under control conditions and during global ischemia. [ATP], [H+], and [Pi] were measured by 31P NMR in a separate group under identical conditions. The control [Na+]i measured by atomic absorption was 30.7 +/- 3.3 mM (mean +/- SD, n = 6), and [Na+]i measured by NMR was 6.2 +/- 0.5 mM (n = 3). Brief ischemia (10 min) was associated with a 54% increase in [Na+]i which reversed completely with reperfusion. Developed pressure also returned to control values upon reperfusion. Prolonged ischemia (30 min) produced continuous further accumulation of sodium (0.53 mM/min, r2 = 0.99). [H+] also increased approximately linearly early in ischemia (0.084 microM/min, r2 = 0.97). The rate of increase in [Na+]i was more than 4000 times greater than the increase in [H+] on a molar basis. Nevertheless, [H+]/[Na+]i increased early in ischemia because the proportional change in [H+] was greater than that in [Na+]i. These results indicate that (1) intracellular sodium measured by NMR in the functioning heart is about 20% of total intracellular sodium; (2) intracellular acidosis and accumulation of sodium develop simultaneously during global ischemia; (3) increased intracellular sodium content is not in itself an indicator of irreversible injury; and (4) recovery of mechanical performance is associated with return of [Na+]i (measured by NMR) to baseline after brief ischemia. The mechanism of the increase in sodium content detected by NMR is unknown.
Draft Amendment to IEEE Standard for Local and Metropolitan Area Networks - Part 16: Air Interface for Fixed Broadband Wireless Access Systems - Management Information Base (2005)

This draft standard defines the wmanIfMib (Wireless MAN Interface MIB) to suport the management of Medium Access Control layer and Physical layer features as defined in IEEE 802.16- 2004.
Hepcidin and Its Role in Regulating Systemic Iron Metabolism (2006)

Maintenance of stable extracellular iron concentrations requires the coordinate regulation of iron transport into plasma from dietary sources in the duodenum, from recycled senescent red cells in macrophages and from storage in hepatocytes. Moreover, during fetal development, the iron requirements of the fetus must be matched by the transport of maternal iron across the placenta. Hepcidin is a 25-amino acid disulfide-rich peptide synthesized in the liver that acts as a systemic iron-regulatory hormone by regulating iron transport from iron-exporting tissues into plasma. Hepcidin inhibits the cellular efflux of iron by binding to, and inducing the degradation of, ferroportin, the sole iron exporter in iron-transporting cells. In turn, hepcidin synthesis is increased by iron loading and decreased by anemia and hypoxia. Additionally, hepcidin synthesis is greatly increased during inflammation, trapping iron in macrophages, decreasing plasma iron concentrations and causing iron-restricted erythropoiesis characteristic of anemia of inflammation (anemia of chronic disease). Recent studies indicate that hepcidin deficiency underlies most known forms of hereditary hemochromatosis. This implies that, with the exception of very rare mutations that affect the hepcidin gene itself or modify ferroportin to make it less responsive to hepcidin, hemochromatosis genes encode molecules that regulate hepcidin synthesis. The central involvement of hepcidin in iron regulation and its pathologies should make the eventual hepcidin assay useful for the diagnosis of iron disorders and the monitoring of their treatments. The development of hepcidin agonists and antagonists may provide useful therapeutics for the treatment of iron disorders.
The Human Gene for the β Subunit of Nerve Growth Factor Is Located on the Proximal Short Arm of Chromosome 1 (1983)

Fragments of the recently cloned human gene for the beta subunit of nerve growth factor (beta-NGF) were used as hybridization probes in analyzing two sets of rodent-human somatic cell hybrids for the presence of human beta-NGF sequences. Results from the first set of hybrids assigned the human beta-NGF gene to chromosome 1 and ruled out the presence of sequences of comparable homology on any other chromosome. With the second set of hybrids, which contained seven different, but overlapping, regions of chromosome 1, the NGF locus was mapped to band 1p22.
Nucleotide sequence of cDNA coding for rat liver pI 6.1 esterase (ES-10), a carboxylesterase located in the lumen of the endoplasmic reticulum (1990)

A commercial rat liver cDNA library in lambda gt11 was screened with a rabbit antiserum to native pI 6.1 esterase (ES-10). The inserts of the immunoreactive clones were short (0.9-1.1 kbp). One of these was used as a probe to rescreen the library, yielding 30 clones, two of which contained relatively long (approx. 1.9 kbp) and widely overlapping cDNA inserts. They did not contain the first two nucleotide residues of the initiator codon, nor the 5′-end untranslated portion of the mRNA. These were derived from a home-made rat liver cDNA library in lambda gt11, screened with an oligonucleotide corresponding to the 5′-end of the already known cDNA sequence. The nucleotide sequence consists of 48 bp of 5′-end non-coding region, 1695 bp of coding region and 212 bp of 3′-end non-coding region including a 20 bp poly(A) tail. The signal peptide and the mature protein subunit are 18 and 547 residues long respectively. Tyr is confirmed as N-terminal residue. The predicted amino acid sequence is highly similar to those of rabbit liver esterase forms 1 (77% identity) and 2 (56% identity), determined by protein sequencing [Korza &amp; Ozols (1988) J. Biol. Chem. 263, 3486-3495; Ozols (1989) J. Biol. Chem. 264, 12533-12545]. The three enzymes share the Ser and His residues presumed to be part of the active site, four Cys residues and a high proportion of charged side chains at their C-terminus. The C-terminal tetrapeptides of the three esterases (-HVEL, -HIEL and -HTEL for pI 6.1 and forms 1 and 2 esterases respectively) are reminiscent of, but not identical with, the localization signal identified in other proteins of the endoplasmic-reticulum lumen (-KDEL in animal cells [Munro &amp; Pelham (1987) Cell 48, 899-907]; -HDEL in yeast [Pelham, Hardwick &amp; Lewis (1988) EMBO J. 7, 1757-1762]). We still lack direct evidence to decide whether or not these C-terminal tetrapeptides commit esterases to reside in the endoplasmic reticulum. In that case the antepenultimate residue (D, V, I or T) would be only weakly stringent, and some sequences primed by H instead of K would be recognized in animal as well as in yeast cells.
Making sense of ambiguity: evaluation in internal reliability and face validity of the SF 36 questionnaire in women presenting with menorrhagia. (1996)

Some questions on the SF 36 questionnaire were difficult to answer for this group of patients. Such problems can adversely effect the validity of the measure. It is suggested that comments of patients upon measures such as the SF 36 questionnaire could both determine the appropriateness of such measures for given studies and influence questionnaire design.
Reexamination of the Protective Role of the Capsular Polysaccharide (Vi antigen) of Salmonella typhi (1984)

The role of the Vi antigen, the capsular polysaccharide of &lt;it&gt;Salmonella typhi&lt;/it&gt;, in the pathogenesis of and immunity to typhoid fever remains the subject of controversy. Vipositive &lt;it&gt;S. typhi&lt;/it&gt; resist phagocytosis and the action of serum complement, both of which actions are initiated by antibodies to Vi antigen. Both the laboratory potency in mice and the clinical effectiveness of whole-cell vaccines were related to their content of immunogenic Vi antigen. A Vi polysaccharide used for immunizing humans against experimental challenge with &lt;it&gt;S. typhi&lt;/it&gt; failed to prevent typhoid fever; experimental conditions used to prepare this ineffective Vi antigen were shown to denature it and to reduce its immunogenicity. Assay of serum antibodies to Vi antigen with purified Vi antigen is a reliable method for diagnosis of typhoid fever and asymptomatic carriage of &lt;it&gt;S. typhi&lt;/it&gt;. Vi polysaccharides prepared by modern techniques passed the requirements for meningococcal polysaccharide vaccines and had approximately 13 times the protective activity in the mouse potency assay as did the US Standard 6A whole-cell typhoid vaccine.
The picture tells the story: Using surface morphology to probe chemical etching reactions (2001)

Highly anisotropic etchants, which only attack specific crystallographic planes of a material, are prized by industry, but the inherent defect selectivity of these etchants has stymied investigations into their chemical mechanism. Because of their chemical specificity, these etchants produce characteristic nanoscale morphological features, such as triangular etch pits and jagged atomic steps, which reflect the site-specific chemical reactions that control the etching. Using a combination of scanning tunnelling microscopy and kinetic Monte Carlo simulations, these site-specific rates can be directly quantified. By correlating these measurements with the structure of the etched sites, information on the reaction mechanism can be obtained. These techniques are illustrated with examples drawn from aqueous silicon etching reactions. For example, the production of atomically flat Si(111) surfaces by NH 4 F etching can be explained by the existence of a pentacoordinate transition state to OH - attack. Sites held in a rigid tetrahedral geometry, such as the Si(111) terrace site, are relatively resistant to attack, while defect sites, such as steps and kinks, are rapidly etched.
Enhancement of DNA vaccine potency by linkage of antigen gene to a gene encoding the extracellular domain of Fms-like tyrosine kinase 3-ligand. (2001)

Recently, Flt3 (Fms-like tyrosine kinase 3)-ligand has been identified as an important cytokine for the generation of professional antigen-presenting cells (APCs), particularly dendritic cells (DCs). A recombinant chimera of the extracellular domain of Flt3-ligand (FL) linked to a model antigen may potentially target the antigen to DCs and their precursor cells. Using human papillomavirus-16 E7 as a model antigen, we evaluated the effect of linkage to FL on the potency of antigen-specific immunity generated by naked DNA vaccines administered intradermally via gene gun. We found that vaccines containing chimeric FL-E7 fusion genes significantly increased the frequency of E7-specific CD8+ T cells relative to vaccines containing the wild-type E7 gene. In vitro studies indicated that cells transfected with FL-E7 DNA presented E7 antigen through the MHC class I pathway more efficiently than wild-type E7 DNA. Furthermore, bone marrow-derived DCs pulsed with cell lysates containing FL-E7 fusion protein presented E7 antigen through the MHC class I pathway more efficiently than DCs pulsed with cell lysates containing wild-type E7 protein. More importantly, this fusion converted a less effective vaccine into one with significant potency against established E7-expressing metastatic tumors. The FL-E7 fusion vaccine mainly targeted CD8+ T cells, and antitumor effects were completely CD4 independent. These results indicate that fusion of a gene encoding the extracellular domain of FL to an antigen gene may greatly enhance the potency of DNA vaccines via CD8-dependent pathways.
High-power laser light source for near-field optics and its application to high-density optical data storage (1999)

A laser light source for high-resolution near-field optics applications with an output power exceeding 1 mW (104 times the power from previous sources) and small (300 nm square to less than 50 nm square) output beam size is demonstrated. The very-small-aperture laser (VSAL) tremendously expands the range of applications possible with near-field optics and increases the signal-to-noise ratios and data rates obtained in existing applications. As an example, 250-nm-diam marks corresponding to 7.5 Gb/in.2 storage density have been recorded and read back in reflection and transmission on a rewritable phase-change disk at 24 Mb/s with a 250-nm-square aperture VSAL. VSALs potentially enable data storage densities of over 500 Gb/in.2 (up to 100 times today’s magnetic or optical storage densities).
Transcriptional Regulators and the Evolution of Plant Form (1998)

The modern or neo-Darwinian theory of evolution was formulated well over half a century ago at a time when genes were abstractions and development was understood only as the transition between a series of phenotypic states. Since that time, our knowledge of the gene, the diversity of types of genes
Evidence for N-terminal exposure of the protein IA subclass of Neisseria gonorrhoeae protein I (1986)

The JS3 and FA638 strains of Neisseria gonorrhoeae bear a protein IA subclass of protein I (P.I). The purified P.Is of surface-labeled strains JS3 and FA638 were cleaved with the N-terminal degradation enzyme leucine amino peptidase (LAP), and the resultant fragments were separated in sodium dodecyl sulfate-polyacrylamide gels. Autoradiography demonstrated that the surface radiolabel was absent in a LAP-generated P.I peptide that was about 1,900 daltons lower in apparent molecular mass than the native P.I in both strains. Moreover, the 4G5 monoclonal epitope, known to be located on the surface of the organism, was also absent in the LAP-generated P.I peptide that was about 1,900 daltons less in apparent molecular mass than the original P.I of strain FA638. These data strongly suggest that the N terminus of the P.IA subclass is exposed on the surface of the bacterium and that this region represents about 5%, or 15 to 20 amino acids, of the total protein.
The role of the Grb2–p38 MAPK signaling pathway in cardiac hypertrophy and fibrosis (2003)

Cardiac hypertrophy is a common response to pressure overload and is associated with increased mortality. Mechanical stress in the heart can result in the integrin-mediated activation of focal adhesion kinase and the subsequent recruitment of the Grb2 adapter molecule. Grb2, in turn, can activate MAPK cascades via an interaction with the Ras guanine nucleotide exchange factor SOS and with other signaling intermediates. We analyzed the role of the Grb2 adapter protein and p38 MAPK in cardiac hypertrophy. Mice with haploinsufficiency of the Grb2 gene (Grb2(+/-) mice) appear normal at birth but have defective T cell signaling. In response to pressure overload, cardiac p38 MAPK and JNK activation was inhibited and cardiac hypertrophy and fibrosis was blocked in Grb2(+/-) mice. Next, transgenic mice with cardiac-specific expression of dominant negative forms of p38alpha (DN-p38alpha) and p38beta (DN-p38beta) MAPK were examined. DN-p38alpha and DN-p38beta mice developed cardiac hypertrophy but were resistant to cardiac fibrosis in response to pressure overload. These results establish that Grb2 action is essential for cardiac hypertrophy and fibrosis in response to pressure overload, and that different signaling pathways downstream of Grb2 regulate fibrosis, fetal gene induction, and cardiomyocyte growth.
Mutagenic scan of the H-N-H motif of colicin E9: implications for the mechanistic enzymology of colicins, homing enzymes and apoptotic endonucleases (2002)

Colicin E9 is a microbial toxin that kills bacteria through random degradation of chromosomal DNA. Within the active site of the cytotoxic endonuclease domain of colicin E9 (the E9 DNase) is a 32 amino acid motif found in the H-N-H group of homing endonucleases. Crystal structures of the E9 DNase have implicated several conserved residues of the H-N-H motif in the mechanism of DNA hydrolysis. We have used mutagenesis to test the involvement of these key residues in colicin toxicity, metal ion binding and catalysis. Our data show, for the first time, that the H-N-H motif is the site of DNA binding and that Mg2+-dependent cleavage of double-stranded DNA is responsible for bacterial cell death. We demonstrate that more active site residues are required for catalysis in the presence of Mg2+ ions than transition metals, consistent with the recent hypothesis that the E9 DNase hydrolyses DNA by two distinct, cation-dependent catalytic mechanisms. The roles of individual amino acids within the H-N-H motif are discussed in the context of the available structural information on this and related DNases and we address the possible mechanistic similarities between caspase-activated DNases, responsible for the degradation of chromatin in eukaryotic apoptosis, and H-N-H DNases.
Transdermal Testosterone Treatment in Women With Impaired Sexual Function After Oophorectomy (2001)

Shifren, Jan L.; Braunstein, Glenn D.; Simon, James A.; Casson, Peter R.; Buster, John E.; Redmond, Geoffrey P.; Burki, Regula E.; Ginsburg, Elizabeth S.; Rosen, Raymond C.; Leiblum, Sandra R.; Caramelli, Kim E.; Mazer, Norman A.
Human TrkB gene: novel alternative transcripts, protein isoforms and expression pattern in the prefrontal cerebral cortex during postnatal development (2010)

Brain-derived neurotrophic factor and neurotrophin-4 high-affinity receptor tropomyosine related kinase (Trk) B is required for the differentiation and maintenance of specific neuron populations. Misregulation of TrkB has been reported in many human diseases, including cancer, obesity and neurological and psychiatric disorders. Alternative splicing that generates receptor isoforms with different functional properties also regulates TrkB function. Here, we describe numerous novel isoforms of TrkB proteins, including isoforms generated by alternative splicing of cassette exons in the regions encoding both the extracellular and intracellular domain and also N-terminally truncated isoforms encoded by novel 5' exon-containing transcripts. We also characterize the intracellular localization and phosphorylation potential of novel TrkB isoforms and find that these proteins have unique properties. In addition, we describe the expression profiles of all the known human TrkB transcripts in adult tissues and also during postnatal development in the human prefrontal cortex. We show that transcripts encoding the full-length TrkB receptor and the C-terminally truncated TrkB-T1 have different expression profiles as compared to the proteins they encode. Identification of 36 potential TrkB protein isoforms suggests high complexity in the synthesis, regulation and function of this important neurotrophin receptor emphasizing the need for further study of these novel TrkB variants.
Multipermutation Codes in the Ulam Metric for Nonvolatile Memories (2014)

We address the problem of multipermutation code design in the Ulam metric for novel storage applications. Multipermutation codes are suitable for flash memory where cell charges may share the same rank. Changes in the charges of cells manifest themselves as errors whose effects on the retrieved signal may be measured via the Ulam distance. As part of our analysis, we study multipermutation codes in the Hamming metric, known as constant composition codes. We then present bounds on the size of multipermutation codes and their capacity, for both the Ulam and the Hamming metrics. Finally, we present constructions and accompanying decoders for multipermutation codes in the Ulam metric.
Distributed interactive ray tracing of dynamic scenes (2004)

Recently developed interactive ray tracing systems combine the high performance of todays CPUs with new algorithms and implementations to achieve a flexible and high-performance rendering system offering high-quality, but nonetheless interactive 3D graphics. However, due to its history in offline rendering, interactive ray tracing is usually limited to static scenes and simple walkthroughs. In order to become truly interactive ray tracing must efficiently support dynamic scenes. We present a simple and practical method that allows to interactively ray trace dynamic scenes in a distributed PC cluster environment. Our method separates the scene into independent objects with common properties concerning dynamic updates - similar to OpenGL display lists and scene graph libraries. Three classes of objects are distinguished: static objects are treated as before, objects undergoing affine transformations are handled by transforming rays, and objects with unstructured motion are rebuilt whenever necessary. We present performance and scalability results of our system using a variety of test scenes stressing a wide range of dynamic behaviour.