gebhart/patrepeval huggingface dataset:
Hypermutation is observed only in antibody H chain V region transgenes that have recombined with endogenous immunoglobulin H DNA: implications for the location of cis-acting elements required for somatic mutation. (1993)

Mice with transgenes containing an antibody H chain V region (VHDJH) gene were used in an analysis of the cis-acting elements required for hypermutation of immunoglobulin (Ig) V genes. These transgenes can somatically recombine with endogenous IgH DNA, leading to the formation of functional heavy (H) chains partially encoded by the transgenic VHDJH. The transgenomes in the five different lines of mice analyzed contain as little as 150 bp, and as much as 2.8 kb of natural DNA flanking the 5' side of the VH and either 1.5 or 2.3 kb (including the intronic enhancer and 5' matrix attachment region [MAR]) flanking the 3' side of VH. Hybridomas were constructed from immunized transgenic mice, and transgenes present in these hybridomas that had or had not recombined to form functional H chain loci were sequenced. The data obtained show that: (a) the recombined transgenes contain hypermutated VH genes; and (b) among such transgenes, even those containing only 150 bp of natural VH 5' flanking sequence and several kilobases of 5' plasmid vector sequence display a frequency, distribution, and type of mutation characteristic of conventional IgH loci. The data also indicate that transgenic VHDJH genes that have not recombined with endogenous IgH DNA are not substrates for hypermutation, even if they are flanked by 2.8 kb of natural 5' DNA, and 2.3 kb of natural 3' DNA, including the JH2-JH4 region, a MAR, and the intronic enhancer. Collectively, the data suggest that sequences 5' of the VH promoter are dispensable, a VH promoter and the intronic IgH enhancer region are not sufficient, and a region(s) within or 3' of the IgH constant region locus is requisite, for hypermutation of Ig VH transgenes.
Homozygous Mutation of P450 Side-Chain Cleavage Enzyme Gene (CYP11A1) in 46, XY Patient with Adrenal Insufficiency, Complete Sex Reversal, and Agenesis of Corpus Callosum (2006)

This report of a homozygous mutation in CYP11A1 gene in a child with agenesis of corpus callosum shows that homozygous mutations in CYP11A1 gene can be compatible with term pregnancy and delayed presentation.
Dynamic range of an electro-optic field sensor and its imaging applications (1996)

We report the measurement of the dynamics of free-space electro-optic field sensors for pulsed electromagnetic wave radiation. With an optical probe power spanning six decades of linearity and excellent signal-to-noise ratio (SNR), it is feasible to convert a far-infrared 2D image into an optical 2D image. A simple estimation indicates that 100 mW of optical probe power can achieve an image of 256×256 pixels with a 50 pA signal current per pixel and a SNR ≳200. We also present a comparison measurement of an ultrafast photoconductive antenna and an electro-optic sensor crystal.
Lung Cancer Screening (2014)

The United States Preventive Services Task Force recommends lung cancer screening with low-dose computed tomography (LDCT) in adults of age 55 to 80 years who have a 30 pack-year smoking history and are currently smoking or have quit within the past 15 years. This recommendation is largely based on the findings of the National Lung Screening Trial. Both policy-level and clinical decision-making about LDCT screening must consider the potential benefits of screening (reduced mortality from lung cancer) and possible harms. Effective screening requires an appreciation that screening should be limited to individuals at high risk of death from lung cancer, and that the risk of harm related to false positive findings, overdiagnosis, and unnecessary invasive testing is real. A comprehensive understanding of these aspects of screening will inform appropriate implementation, with the objective that an evidence-based and systematic approach to screening will help to reduce the enormous mortality burden of lung cancer.
Epidermal Growth Factor Receptor Dependence in Human Tumors: More Than Just Expression? (2002)

The epidermal growth factor receptor (EGFR) is a rational target for antitumor strategies. EGFR signaling causes increased proliferation, decreased apoptosis, and enhanced tumor cell motility and neo-angiogenesis. The EGFR is expressed or highly expressed in a variety of human tumors of epithelial origin. ZD1839 (Iressa) is an orally active, selective EGFR tyrosine kinase inhibitor, which blocks signal transduction pathways implicated in proliferation and survival of cancer cells. The lack of a consistent method of evaluating levels of EGFR has caused a disparity in reports of the EGFR as a prognostic factor; however, for some tumors, EGFR is a strong prognostic indicator associated with more aggressive disease and reduced survival. So far, no clear association between EGFR levels and response to EGFR-targeted agents has been found. Preclinical studies with ZD1839 have noted a relationship between the two in some cases, but not others. EGFR signaling may be increased by a number of mechanisms in addition to high expression levels of EGFR, including receptor mutations, heterodimerization with other members of this receptor family such as HER2 (erbB2), increased expression of (autocrine/ paracrine) ligands, and alterations in molecules that control receptor signaling output. Each of these components could be assessed to give an indication of the magnitude of EGFR signal amplification. Evaluation of signaling components downstream from EGFR should provide information on the activation of the EGFR pathway. Until EGFR-based assays predictive of a response to receptor-targeted therapies are available, there is no clear justification for stratifying patients by EGFR status or excluding patients with low EGFR levels from trials with ZD1839 or other EGFR inhibitors.
A retrovirus carrying an MDR1 cDNA confers multidrug resistance and polarized expression of P-glycoprotein in MDCK cells. (1988)

A full-length cDNA for the human multidrug resistance gene 1 (MDR1) has been inserted into a retroviral vector containing a murine Harvey sarcoma virus from which the viral oncogene was deleted. Ecotropic and amphotropic virus was produced after transfection of this vector into psi-2 and PA-12 packaging cell lines. This virus conferred the full phenotype of multidrug resistance on mouse and human cell lines. Viral titers of up to 2 X 10(5) drug-resistant colonies per ml were observed. Infected cells became resistant to colchicine, vinblastine, doxorubicin, VP16 (etoposide), and puromycin, but not cisplatin, indicating that the presence of the human MDR1 gene is sufficient to cause multidrug resistance. When the dog kidney cell line MDCK was infected with the MDR1 virus, P-glycoprotein was expressed in a polarized manner on the upper surface of the cells, showing that the cloned cDNA also encodes information for polarized expression of P-glycoprotein. The MDR1 virus should be useful for introducing this drug resistance gene into a variety of cell types for biological experiments in vitro and in vivo.
Preparation of Thiol-Reactive Cy5 Derivatives from Commercial Cy5 Succinimidyl Ester (2000)

The present study offers reliable protocols for the preparation of new thiol-reactive Cy5 derivatives which are urgently needed for single molecule fluorescence microscopy. In a systematic approach, two alternate strategies were found for the extension of commercial amine-reactive Cy5 with thiol-reactive end groups. In the two-step method, Cy5 succinimidyl ester was first reacted with ethylenediamine under conditions which gave approximately 99% asymmetric "Cy5-amine" and only approximately 1% symmetric product with two Cy5 residues. Subsequently, "Cy5-amine" was derivatized with commercial heterobifunctional cross-linkers to introduce thiol-reactive end groups (maleimide or pyridyldithio). Alternatively, commercial Cy5 succinimidyl ester was reacted with a primary amine (MTSEA, methanethiosulfonylethylamine, or PDEA, pyridyldithioethylamine) or a secondary amine (PEM, piperazinylethylmaleimide) to give the corresponding thiol-reactive derivatives in a single step. Results were good for MTSEA, moderate for PEM, and poor for PDEA. An additional drawback of the one-step method was the need for rigorous removal of unreacted Cy5 succinimidyl ester, which would label lysine residues on probe molecules. It is concluded that, except for the Cy5-MTSEA conjugate, the two-step method is much more general, reliable, and easier to follow by the typical biophysicist, biologist, etc., for whose benefit, these procedures are being published. All thiol-reactive Cy5 derivatives showed similar absorption and fluorescence properties as Cy5 succinimidyl ester, and fluorescence was fully retained after binding to thiols on proteins. The kinetics of protein labeling was also examined in order to get an idea of proper labeling conditions.
The Significance of Artificial Cerebrospinal Fluid as Perfusate and Endoneurosurgery (1996)

To compare the benefits of physiological saline solution and artificial cerebrospinal fluid (CSF) as perfusates, we investigated 12 patients with presumed symptomatic aqueductal stenosis by clinical course and CSF analysis. In all patients, endoneurosurgical third ventriculostomy and cine magnetic resonance imaging confirmed the patency of ventriculostomy. After endoneurosurgery, patients who received the saline solution experienced high fever, headaches, and elevated cell count in lumbar CSF. Saline solution provoked a striking inflammatory reaction in the CSF. In contrast, the artificial CSF reduced these conditions to a minimum. Artificial CSF used as a physiological perfusate during endoneurosurgery can suppress host reactions within the CSF pathway and is also available for routine neurosurgical procedures.
Parallel Coiled-coil Association of the RhoA-binding Domain in Rho-kinase (2003)

Rho-kinase is a serine/threonine protein kinase that regulates cytoskeletal events in cells. The enzyme activity of Rho-kinase is auto-inhibited in the free state but is activated through direct binding to the small GTPase Rho in the GTP-bound form. The crystal structure of the Rho-binding domain (RhoBD) of Rho-kinase has been determined at 1.8-A resolution by the multi-wavelength anomalous dispersion technique. The structure shows that RhoBD dimerizes to form a parallel coiled-coil with long consecutive alpha-helices extended to approximately 97 A and suggests that free Rho-kinase can also form a dimer through parallel self-association. At the middle region of the coiled-coil, the polypeptide chains are flexible and display loose "knobs-into-holes" packing of the side chains from both chains. RhoBD residues that have been shown to be critical for Rho-binding are spread in the positively charged C-terminal region. The parallel coiled-coil structure of our Rho-kinase RhoBD in the free form is different from the anti-parallel coiled-coil structure of RhoBD of protein kinase N when complexed with RhoA. Implications derived from these structural studies in relation to the mechanism of Rho-kinase activation will be addressed with previously reported experimental data.
Immune T lymphocyte to tumor cell adhesion. Magnesium sufficient, calcium insufficient. (1980)

The prelytic adhesion of immune cytolytic thymus-derived lymphocytes to specific antigen-bearing ascites tumor target cells has been studied. A new assay was used in which adhesions are permitted to form for 2.5 min; the cells are then dispersed to prevent further adhesion, and the predispersion adhesions are quantitated by subsequent 51Cr release from the tumor cells as a result of cytolytic activity of the adhering lymphocytes. There were the following new findings: (a) magnesium is sufficient to support optimal adhesion formation even when EGTA is added to remove contaminating traces of calcium; (b) calcium supports no adhesion formation when traces of contaminating magnesium are removed by pretreating the medium with a chelating ion exchange resin; (c) calcium synergizes with suboptimal magnesium, increasing the apparent adhesion-supporting potency of magnesium 20-fold in the presence of 50 microM calcium; (d) in the presence of optimal magnesium (2--4 mM), calcium has not effect on the properties of the adhesion by any of six criteria; and (e) manganese supports adhesion better than magnesium, and strontium is ineffective. A survey of previous literature indicates that these results are remarkably similar to the predominant pattern for nonimmunologic cell adhesion (e.g., fibroblasts) involving cells from a variety of tissues in late embryonic and adult avians and mammals. This suggests that a "magnesium sufficient, calcium insufficient" mechanism may be found among the latter types of cell adhesions when appropriately examined. Moreover, it seems that the present lymphocyte-tumor cell adhesion, although evoked by specific receptor-antigen recognition, relies predominantly on mechanisms common to nonimmunologic intercellular adhesion processes.
The design and implementation of a service logic execution environment platform (2002)

The paper describes the design and implementation of the service logic execution environment platform of GTE's intelligent network (IN) testbed. The platform is a layer of software built on top of computer operating systems. Based on the primitive services provided by the underlying operating systems, the platform provides higher-level services to service logic programs (SLPs). SLPs, applications of the platform, provide the logic that implements IN services. The paper presents an overview of the abstraction and services presented to SLPs, and then discusses the server architecture which realizes that abstraction.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Prognostic significance of circulating microsatellite markers in the plasma of melanoma patients. (2001)

This study provides evidence that blood testing for circulating tumor genetic markers may provide valuable prognostic information and guide future therapy.
The Prevention of Sub-surface Demineralization of Bovine Enamel and Change in Plaque Composition by Casein in an Intra-oral Model (1987)

The ability of bovine milk phosphoprotein (casein) to be incorporated into plaque, prevent enamel sub-surface demineralization, and affect bacterial composition was determined using a modified intra-oral caries model. The intra-oral model consisted of a removable appliance containing a left and right pair of bovine enamel slabs placed to simulate an approximal area. Supragingival plaque was collected and impacted into the left and right inter-enamel spaces. The left side of the appliance was exposed to various sugar and salt solutions, while the right side was exposed to sugar and casein solutions. Sodium caseinate, the major fraction alpha s1-casein, and a tryptic digest of alpha s1-casein (TD-casein) were studied. Sodium caseinate at a level of 2% w/v in a 3% sucrose-3% glucose-salt solution (pH 7.0) prevented sub-surface enamel demineralization over a ten-day period as shown by microradiography and microhardness. Two exposures of a 2% w/v sodium caseinate, alpha s1-casein, or TD-casein solution (pH 7.0) per day prevented sub-surface enamel demineralization caused by six exposures of a 3% sucrose-3% glucose-salt solution per day over a ten-day period. Intact alpha s1-casein and tryptic peptides were shown immunochemically to be incorporated into the inter-enamel plaque. The incorporation of casein and its breakdown in plaque did not produce a significant change in the amount or composition of plaque bacteria. The ability of casein and tryptic peptides to prevent enamel demineralization was related to their incorporation into plaque, thereby increasing plaque calcium phosphate and acid-buffering capacity by the phosphoseryl, histidyl, glutamyl, and aspartyl residues and indirectly through catabolism by plaque bacteria.
PbS in polymers. From molecules to bulk solids (1987)

The transition of PbS from molecular to bulk form has been observed in polymer films. As the particle size decreases the band gap shifts to the blue and eventually approaches the transition energy of the first allowed excited state, X→A, of a PbS molecule. Discrete absorption bands also appear. The electron-hole-in-a-box model with effective mass approximation cannot explain the observed size dependence. We have developed two theoretical models, both including the effect of band nonparabolicity, that successfully explain the observed size dependence down to about 25 Å.
Cloning of cDNAs encoding human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2. Comparison of their deduced amino acid sequences. (1988)

We have isolated and sequenced cDNA clones corresponding to the entire coding sequences of the human lysosomal membrane glycoproteins, lamp-1 and lamp-2 (h-lamp-1 and h-lamp-2). The deduced amino acid sequences indicate that h-lamp-1 and h-lamp-2 consist of 416 and 408 amino acid residues, respectively, and suggest that 27 and 28 NH2-terminal residues are cleavable signal peptides. The major portions of both h-lamp-1 and h-lamp-2 reside on the luminal side of the lysosome and are heavily glycosylated by N-glycans: h-lamp-1 and h-lamp-2 were found to contain 19 and 16 potential N-glycosylation sites, respectively. The findings are consistent with the results obtained by endo-beta-N-acetylglucosaminidase F treatment of h-lamp-1 and h-lamp-2 precursors, described in the preceding paper (Carlsson, S. R., Roth, J., Piller, F., and Fukuda, M. (1988) J. Biol. Chem. 263, 18911-18919). These N-glycosylation sites are clustered into two domains separated by a hinge-like structure enriched with proline and serine in h-lamp-1 or proline and threonine in h-lamp-2. The two domains of h-lamp-1 on each side of the hinge region are homologous to each other, whereas no such homology was detected between the two domains of h-lamp-2. Both proteins have one putative transmembrane domain consisting of 24 hydrophobic amino acids near the COOH terminus, and contain a short cytoplasmic segment composed of 11 amino acid residues at the COOH-terminal end. Comparison of h-lamp-1 and h-lamp-2 sequences reveal strong homology between the two molecules, particularly in the proximity to the COOH-terminal end. It is possible that this portion is important for targeting the molecules to lysosomes. These results also suggest that lamp-1 and lamp-2 are evolutionarily related. Comparison of known lamp-1 sequences among different species, on the other hand, show that human lamp-1 has more similarity to lamp-1 from other species than to human lamp-2. This fact, taken together with the finding that h-lamp-2 lacks repeating domains, suggests that lamp-1 and lamp-2 diverged from a putative ancestor gene in early stages of evolution. These results also suggest that lamp-1 and lamp-2 probably have distinctly separate functions despite the fact that they share many structural features.
Fine Mapping of a cis -Acting Sequence Element in Yellow Fever Virus RNA That Is Required for RNA Replication and Cyclization (2003)

We present fine mapping of a cis-acting nucleotide sequence found in the 5' region of yellow fever virus genomic RNA that is required for RNA replication. There is evidence that this sequence interacts with a complementary sequence in the 3' region of the genome to cyclize the RNA. Replicons were constructed that had various deletions in the 5' region encoding the capsid protein and were tested for their ability to replicate. We found that a sequence of 18 nucleotides (residues 146 to 163 of the yellow fever virus genome, which encode amino acids 9 to 14 of the capsid protein) is essential for replication of the yellow fever virus replicon and that a slightly longer sequence of 21 nucleotides (residues 146 to 166, encoding amino acids 9 to 15) is required for full replication. This region is larger than the core sequence of 8 nucleotides conserved among all mosquito-borne flaviviruses and contains instead the entire sequence previously proposed to be involved in cyclization of yellow fever virus RNA.
Secretory vesicles are the intracellular reservoir of complement receptor 1 in human neutrophils. (1994)

The subcellular localization of complement receptor 1 (CR1) was investigated in human neutrophils. CR1 was located exclusively in the light membrane fractions containing secretory vesicles and plasma membranes in Percoll density gradients of unperturbed neutrophils. Separation of plasma membranes from secretory vesicles by high-voltage free-flow electrophoresis of the light membranes from the Percoll gradient revealed that more than 80% of the CR1 was located intracellularly in secretory vesicles. After weak stimulation of neutrophils, the increase in CR1 surface expression closely paralleled both surface increase of known secretory vesicle membrane Ags and the release of matrix proteins from secretory vesicles. More potent stimulation of the neutrophils did not enhance CR1 surface expression further, in agreement with the lack of CR1 in granules as demonstrated on Percoll gradient. CR3 (Mac-1), which has been shown to be located both in secretory vesicles and in neutrophil granules, was up-regulated in parallel with CR1 after weak stimuli, whereas a profound increase of CR3 was observed after more potent stimuli in accordance with granule mobilization. These results identify secretory vesicles as the reservoir of CR1, which translocates to the plasma membrane after weak stimulation, and underscore the functional significance of this recently identified organelle.
Design, Synthesis, and Self-assembly of Oligothiophene Derivatives with a Diketopyrrolopyrrole Core (2008)

Oligothiophenes containing diketopyrrolopyrrole (DPP) cores were synthesized, and their electrochemistry, photophysics, and film morphology were studied. Density functional theory calculations indicate that the highest occupied molecular orbital and the lowest unoccupied molecular orbital can be tuned by changing the number of thiophene units. The compounds synthesized in this study had electrochemical gaps ranging from 1.80 to 2.25 V and intense absorption bands in the UV, assigned to the thiophene units, as well as bands in the visible part of the spectrum, attributed to charge-transfer transitions between the electron-rich thiophene moieties and the electron-withdrawing DPP core. All of the compounds were found to be luminescent in solution with emission wavelengths ranging from 562 to 682 nm. Atomic force microscopy studies show that the length and type of alkyl substitution on the DPP core affect the film morphology, and hence, the solid state photophysical and electronic properties. Long and straight alkyl chains lead to rod-like or needle-like structures, whereas compounds with branched alkyl chains do not show ordering in the solid state. The self-assembling process can also be manipulated by changing the number of thiophene units. Nanoscale fibrous structures were obtained when either two or four thiophene units were added to the initial bis-thiophenyl-DPP unit.