gebhart/patrepeval huggingface dataset:
The interaction of vincristine with calf brain tubulin. (1983)

The interaction of the antimitotic drug vincristine with tubulin has been investigated by the techniques of self-assembly, velocity sedimentation, fluorescence, circular dichroism, and differential spectroscopy. Vincristine has been shown to inhibit the self-assembly of tubulin into microtubules at substoichiometric concentrations. The sedimentation velocity patterns at low vincristine concentration (less than 1 X 10(-5) M to 7 X 10(-5) M) consist of a bimodal boundary with a 5.8 S peak and a fast moving peak, with a nominal S20,w value of 9 S. The data conform to the ligand-promoted self-association theory of Cann and Goad (Cann, J.R., and Goad, W.B. (1972) Arch. Biochem. Biophys. 153, 603-609). At higher vincristine concentrations (greater than 8 X 10(-5 M), most of the protein is polymerized and sediments as a hypersharp peak with a nominal S20,w value of approximately 20 S. The association constant for the binding of vincristine to tubulin, determined by spectrofluorometry, is 3.5 X 10(4) liters/mol at 25 degrees C. The binding of vincristine does not induce any significant conformational changes in tubulin; however, the difference spectral results indicate perturbation of both vincristine and protein chromophores.
Efficacy of an Influenza Hemagglutinin‐Diphtheria Toxoid Conjugate Vaccine in Elderly Nursing Home Subjects During an Influenza Outbreak (1994)

HA-D was more immunogenic in institutionalized elderly recipients and produced greater protection from influenza infection. Superior protection may be due to HA-D's ability to stimulate and recruit antigen-presenting cells, thus enabling the recipient to achieve and maintain functional antibody titers.
Immune responses and protection against infection and abortion in cattle experimentally vaccinated with mutant strains of Brucella abortus (1993)

Twenty-four 10-month-old Polled Hereford heifers were inoculated SC with live cells of one of the following strains of Brucella abortus: S19 delta 31K (n = 4), S19 delta SOD (n = 4), RB51 (n = 4), and strain 19 (n = 6); controls (n = 6) were given saline solution. Heifers given the deletion mutants S19 delta 31K and S19 delta SOD, and those given strain 19 developed antibody responses to B abortus and cutaneous reactions to brucellin. Heifers given strain RB51 did not develop antibodies that reacted in the standard tube agglutination test, but sera reacted in tests, using an antibody dot-blot assay containing RB51 antigen. The S19 delta 31K and S19 delta SOD strains of B abortus isolated from lymph node tissue after vaccination did not differ genetically from the master stock strain. All heifers were bred naturally at 16 to 17 months of age, and were challenge-exposed intraconjunctivally with virulent B abortus strain 2308 during the fifth month of pregnancy. All vaccinated heifers were protected (ie, none aborted and none had B abortus isolated from their tissues after parturition). Calves born from vaccinated dams were free of B abortus. Antibody responses in heifers after challenge exposure were an indicator of immunity. All 5 control heifers (nonvaccinated) developed serum antibodies after challenge exposure; 3 aborted, and 1 delivered a small, weak calf at 8.5 months of gestation. Thus live mutant strains of B abortus can induce protective immunity when given at 10 months of age, and strain RB51 is a strong candidate for further testing.
Optical isolation with epsilon-near-zero metamaterials (2013)

We suggest a principle for isolation of circularly polarized waves in magnetically active extreme-parameter metamaterials. Using theoretical analysis and numerical simulations, we show that metamaterials with extreme parameters, such as epsilon-near-zero materials (ENZ), when merged with magneto-optical materials, become transparent for forward circularly polarized waves of a given handedness and opaque for backward propagating waves of the same handedness. We theoretically study two possible implementations of such hybrid materials: (1) the case of metal-dielectric stacks; and (2) rectangular waveguide near its cut-off frequency. We prove that these structures can be utilized as compact isolators for circularly polarized waves.
The Gene Locus yijP Contributes to Escherichia coli K1 Invasion of Brain Microvascular Endothelial Cells (1999)

Most cases of Escherichia coli meningitis develop as a result of hematogenous spread, but it is not clear how circulating E. coli crosses the blood-brain barrier. A TnphoA mutant of E. coli K1 RS218 was shown to be significantly less invasive than its parent strain in bovine and human brain microvascular endothelial cells (BMEC), which constitute the blood-brain barrier. More importantly, traversal of the blood-brain barrier was significantly less with this mutant than with the parent strain in newborn rats with experimental hematogenous meningitis. A DNA segment containing the TnphoA insertion site was cloned from RS218, and the cloned DNA complemented the TnphoA mutant in invasion of BMEC. Nucleotide sequence revealed a near identity to that of a hypothetical yijP gene (also called f577) in the E. coli K-12 genome. Sequence analysis indicated that the E. coli K1 yijP gene likely encodes a 66. 6-kDa membrane protein. Deletion and complementation experiments indicated that the yijP gene was involved in E. coli K1 invasion of BMEC, i.e., the invasive ability of E. coli K1 was significantly reduced after yijP was deleted and was restored by complementation with a plasmid containing the yijP open reading frame. This is the first demonstration that the yijP gene locus plays a role in the pathogenesis of E. coli K1 meningitis.
Molecular cytogenetics: Rosetta stone for understanding cancer--twenty-ninth G. H. A. Clowes memorial award lecture. (1990)

This article provides me with an occasion to review our progress in a central area of cancer research, namely the genetic changes that occur within the cancer cell that are critically involved in the transformation of a normal to a malignant cell. I think it is especially appropriate that three named awards (Clowes, Rosenthal, and Rhoads) presented at the 1989 annual meeting of the American Association for Cancer Research went to investigators who have made contributions to our under standing of the genetic changes in cancer cells. Clearly, to concentrate on genes to the exclusion of cell biology would be too narrow and short-sighted an approach. Nonetheless, I am convinced that until we have isolated the genes that are centrally involved in at least some of the malignant processes in different cell types, we will be unable to answer the fundamental ques tions about malignant transformation. More importantly, we will be unable to answer the questions with precision. I will limit my consideration to those changes that have been detected by analyzing the karyotypic pattern of human cancer cells using chromosome banding, and in particular to those found in leu kemia. We are living in a golden age of the biomedicai sciences. Increasingly sophisticated instruments and creative scientific strategies allow remarkably precise understanding of some as pects of cancer biology. It is clear that during the course of the last three decades, the scientific community's assessment of the role of chromosome changes in the complex process of malig nant transformation has changed from considering them to be merely trivial epiphenomena to recognizing their fundamental involvement for at least some tumors. This change in attitude has occurred for at least two reasons. First, the demonstration of specific recurring chromosome rearrangements, including translocations and deletions, that were often uniquely associ ated with a particular type of leukemia, lymphoma, or sarcoma provided clear evidence that these rearrangements were criti cally involved in malignant transformation (1-3). About 70 recurring translocations as well as many nonrandom deletions and other structural abnormalities are listed in the chapter on structural chromosome changes in neoplasia included in Hu man Gene Mapping 10 (4). The evidence for the presence of recurring chromosome abnormalities in a wide variety of human neoplasms was the result of 30 years of painstaking chromo some analysis by my cytogenetic colleagues around the world. The honor attached to this Clowes award should be shared with all of them. A second, and I believe an even more powerful, force acting within the general scientific community to reassess the role of karyotypic alterations was the identification of the genes in volved in some of the chromosome rearrangements and the discovery that some of these genes were the human counterparts
Computational Identification of Key Biological Modules and Transcription Factors in Acute Lung Injury (2005)

We present a novel, unbiased, and powerful computational approach to investigate the synergistic effects of mechanical ventilation and LPS in promoting ALI. Our methodology is applicable to any expression profiling experiment involving eukaryotic organisms.
Percutaneous transluminal angioplasty in arteriosclerotic internal carotid artery stenosis. (1983)

Percutaneous transluminal angioplasty (PTA) of carotid arteries has been rarely reported. Dilatation of internal carotid artery stenosis has so far been performed only for fibromuscular dysplasia. Because of the risk of cerebral embolization the technique has not been used for arteriosclerotic stenosis, particularly since endarterectomy is known as a safe procedure. Three cases are reported of successful dilatation of arteriosclerotic internal carotid artery stenosis. A neurologic complication occurred in one patient. The primary indication for performing PTA in such cases is limited operability for medical reasons.
Elevated sympathetic nerve activity in borderline hypertensive humans. Evidence from direct intraneural recordings. (1989)

Reports of elevated plasma catecholamine levels and augmented responses to autonomic blockade suggest increased sympathetic tone in borderline hypertension. It is not known if this reflects greater sympathetic neural outflow. We directly recorded muscle sympathetic nerve activity (microneurography) in 15 normotensive and 12 borderline hypertensive age-matched men to determine whether borderline hypertensive individuals have elevated sympathetic nerve activity. Supine heart rate, blood pressure, plasma norepinephrine, and efferent muscle sympathetic nerve activity (peroneal nerve) were measured after 6 days of both low and high dietary sodium intake (10 and 400 meq sodium/24 hr). Sympathetic nerve activity was elevated significantly in borderline hypertensive individuals on both low (37 +/- 1 in borderline hypertensive individuals vs. 29 +/- 1 bursts/min in normotensive individuals; p less than 0.01) and high (25 + 1 in borderline hypertensive individuals vs. 16 +/- 1 bursts/min in normotensive individuals; p less than 0.01) sodium diets. The borderline hypertensive group had higher systolic (p less than 0.01) and diastolic (p less than 0.05) blood pressures independent of sodium intake. Across both groups, high sodium intake reduced muscle sympathetic nerve activity (p less than 0.001), plasma norepinephrine (p less than 0.001), diastolic blood pressure (p less than 0.02), heart rate (p less than 0.002), and increased weight (p less than 0.005). A significant (p less than 0.05) group-by-diet interaction was observed for plasma norepinephrine levels. Specifically, compared with the normotensive group, plasma norepinephrine levels in the borderline hypertensive group tended to be higher on low sodium diet (p = 0.08) and lower on high sodium diet (p = 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)
Inflammation in age-related macular degeneration: pathological or physiological? (2009)

The RPE may secrete C3 to enhance removal of waste products in Bruch’s membrane, and CFH for self-defense, while other components may be derived from blood to form the membrane attack complex (C5b-...
Radiation Protection of the Gastrointestinal Tract and Growth Inhibition of Prostate Cancer Xenografts by a Single Compound (2014)

Normal tissue toxicity markedly reduces the therapeutic index of genotoxic anticancer agents, including ionizing radiation. Countermeasures against tissue damage caused by radiation are limited by their potential to also protect malignant cells and tissues. Here, we tested a panel of signal transduction modifiers for selective radioprotection of normal but not tumor tissues. These included three inhibitors of GSK3 (LiCl, SB216763, and SB415286) and two inhibitors of NF-κB (ethyl pyruvate and RTA 408). Among these, the thiol-reactive triterpenoid RTA 408 emerged as a robust and effective protector of multiple organ systems (gastrointestinal, skin, and hemopoietic) against lethal doses of radiation. RTA 408 preserved survival and proliferation of intestinal crypt cells in lethally irradiated mice while reducing apoptosis incidence in crypts and villi. In contrast, RTA 408 uniformly inhibited growth of established CWR22Rv1, LNCaP/C4-2B, PC3, and DU145 xenografts either alone or combined with radiation. Antitumor effects in vivo were associated with reduced proliferation and intratumoral apoptosis and with inhibition of NF-κB-dependent transcription in PC3 cells. Selective protection of normal tissue compartments by RTA 408 critically depended on tissue context and could not be replicated in vitro. Collectively, these data highlight the potential of RTA 408 as a cytoprotective agent that may be safely used in chemoradiation approaches.
Two-dimensional crystallization of membrane proteins (1992)

In spite of several great breakthroughs, the overall rate of progress in determining high-resolution structures of membrane proteins has been slow. This is entirely due to the scarcity of suitable, well-ordered crystals. Most membrane proteins are multimeric complexes with a composite molecular mass in excess of 50000 Da which puts them outside the range of current solution NMR techniques. For the foreseeable future, detailed information about the structure of large membrane proteins will therefore depend on crystallographic methods.
Adoptive T-cell therapies for refractory/relapsed leukemia and lymphoma: current strategies and recent advances (2015)

Despite significant advancements in the treatment and outcome of hematologic malignancies, prognosis remains poor for patients who have relapsed or refractory disease. Adoptive T-cell immunotherapy offers novel therapeutics that attempt to utilize the noted graft versus leukemia effect. While CD19 chimeric antigen receptor (CAR)-modified T cells have thus far been the most clinically successful application of adoptive T immunotherapy, further work with antigen specific T cells and CARs that recognize other targets have helped diversify the field to treat a broad spectrum of hematologic malignancies. This article will focus primarily on therapies currently in the clinical trial phase as well as current downfalls or limitations.
Tandem Mass Spectrometry - Applications and Principles (2012)

Tandem Mass Spectrometry - Applications and Principles presents comprehensive coverage of theory, instrumentation and major applications of tandem mass spectrometry. The areas covered range from the analysis of drug metabolites, proteins and complex lipids to clinical diagnosis. This book serves multiple groups of audiences; professional (academic and industry), graduate students and general readers interested in the use of modern mass spectrometry in solving critical questions of chemical and biological sciences.
Radiolocation using AM broadcast signals (2002)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2002.
Regulation of expression of the glutamine synthetase GLN-[alpha] gene of phaseolus vulgaris L (1992)

The expression of the glutamine synthetase a subunit gene (gln-a) is known to be high in young tissues such as root tips, plumules developing nodules and developing leaves. An experiment using nodules were Fix- and began to senesce prematurely, suggested that gln-a and a phenylalanine ammonia-lyase gene (PAL 1) were co-induced. &#13;\nThis phenomenon was further studied in various systems including nodules derived with Rhizobium mutants, cell cultures treated with fungal elicitors, wounded hypocotyls and leaves infected with compatible and incompatible strains of Pseudomonas phaseolicola. Expression of these two genes and in some cases the glutamine synthetase ß subunit gene (gln-ß) was observed to be related although experiments with short periods between samples suggested that the expression of the two glutamine synthetase genes was delayed with respect to the expression of the PAL 1 gene, the peak of expression occuring a few hours later. Work on cell cultures suggests that the stimulus for the induction of the two glutamine synthetase genes is possibly a product of the phenylpropanoid pathway although other stimuli present in both stress conditions and in young tissues may induce either of the two glutamine synthetase genes&#13;\n
Multiple mechanisms for transcriptional regulation of the myc gene family in small-cell lung cancer. (1988)

The molecular mechanisms reported to regulate the expression of myc family genes are multiple and complex and include gene amplification, transcriptional activation, transcriptional attenuation, and mRNA stability. We have investigated which of these mechanisms are responsible for the extreme variation in myc gene family mRNA levels observed in human small-cell lung cancer cell lines. In addition to gene amplification, a block to nascent mRNA chain elongation, causing attenuation of transcription, is an important regulatory mechanism controlling the steady-state levels of c-myc and L-myc mRNA. The loss of transcriptional attenuation is correlated with overexpression of these two genes in cell lines which do not show gene amplification. Expression of c-myc mRNA appears to be dependent on promoter activity and attenuator function. In contrast, regulation of expression of the N-myc gene does not involve transcriptional attenuation; steady-state mRNA levels are correlated with promoter activity as well as gene amplification. We conclude that transcriptional regulation of each member of the myc gene family is accomplished by a different assortment of complex mechanisms, including gene copy number, promoter activation, and transcriptional attenuation. Interference at multiple points in this complex regulatory process appears to be an important mechanism by which small-cell lung cancer and other human tumors evade growth control.
The chronic myelocytic cell line K562 contains a breakpoint in bcr and produces a chimeric bcr/c-abl transcript. (1986)

In the DNAs of all Ph1-positive chronic myelocytic leukemia patients studied to date, a breakpoint on chromosome 22 (the Ph1 chromosome) can be demonstrated with a probe from the bcr (breakpoint cluster region). Although the K562 cell line was established from cells of a chronic myelocytic leukemia patient, we have been unable to detect the Ph1 chromosome by cytogenetic means. Employing a probe from the 5' region of bcr, we have cloned an amplified Ph1 breakpoint fragment from K562. This demonstrates that K562 contains multiple remnants of a Ph1 chromosome with a breakpoint within bcr and thus may serve as a model system for the study of Ph1-positive chronic myelocytic leukemia at a molecular level. The isolation of bcr cDNA sequences shows that parts of bcr encode a protein. Employing K562, we demonstrate the presence of an abnormally sized mRNA species hybridizing to c-abl and to a bcr cDNA probe, indicating the possible consequence of the Ph1 translocation on a transcriptional level in chronic myelocytic leukemia. The isolation and sequencing of a cDNA containing the breakpoint area of this mRNA provide further evidence for its chimeric structure. Cloning of large stretches of chromosomal DNA flanking bcr and c-abl sequences in K562 and identification of the exons participating in the formation of the chimeric mRNA shows that a splice of at least 99 kilobases is made to fuse the 3' bcr exon to the 5' c-abl exon. Furthermore two chimeric cDNAs were isolated containing chromosome 9 sequences that map 43.5 kilobases downstream from the K562 breakpoint. These chromosome 9 sequences neither hybridize to the 8.5-kilobase chimeric c-abl mRNA nor to normal c-abl mRNAs in Hela cells and probably represent incorrect splicing products present in the K562 cell line.
Adeno-associated virus 2-mediated high efficiency gene transfer into immature and mature subsets of hematopoietic progenitor cells in human umbilical cord blood. (1994)

Recombinant adeno-associated virus 2 (AAV) virions were constructed containing a gene for resistance to neomycin (neoR), under the control of either the herpesvirus thymidine kinase (TK) gene promoter (vTK-Neo), or the human parvovirus B19 p6 promoter (vB19-Neo), as well as those containing an upstream erythroid cell-specific enhancer (HS-2) from the locus control region of the human beta-globin gene cluster (vHS2-TK-Neo; vHS2-B19-Neo). These recombinant virions were used to infect either low density or highly enriched populations of CD34+ cells isolated from human umbilical cord blood. In clonogenic assays initiated with cells infected with the different recombinant AAV-Neo virions, equivalent high frequency transduction of the neoR gene into slow-cycling multipotential, erythroid, and granulocyte/macrophage (GM) progenitor cells, including those with high proliferative potential, was obtained without prestimulation with growth factors, indicating that these immature and mature hematopoietic progenitor cells were susceptible to infection by the recombinant AAV virions. Successful transduction did not require and was not enhanced by prestimulation of these cell populations with cytokines. The functional activity of the transduced neo gene was evident by the development of resistance to the drug G418, a neomycin analogue. Individual high and low proliferative colony-forming unit (CFU)-GM, burst-forming unit-erythroid, and CFU-granulocyte erythroid macrophage megakaryocyte colonies from mock-infected, or the recombinant virus-infected cultures were subjected to polymerase chain reaction analysis using a neo-specific synthetic oligonucleotide primer pair. A 276-bp DNA fragment that hybridized with a neo-specific DNA probe on Southern blots was only detected in those colonies cloned from the recombinant virus-infected cells, indicating stable integration of the transduced neo gene. These studies suggest that parvovirus-based vectors may prove to be a useful alternative to the more commonly used retroviral vectors for high efficiency gene transfer into slow or noncycling primitive hematopoietic progenitor cells, without the need for growth factor stimulation, which could potentially lead to differentiation of these cells before transplantation.
Reference data for commonly used sensory and motor nerve conduction studies (2009)

Efforts to develop reference data require careful selection of study subjects; sufficient sample size; adjustment for relevant covariates; and appropriate statistical methods for analysis. Reference data that cannot be estimated reliably due to absent potentials or data variability must be interpreted with caution. We present data for a range of clinically applicable reference percentiles, but judgment regarding which is most appropriate for diagnostic purpose awaits empiric evaluation in a disease population.
Correlation Between Elevated Levels of Amyloid β-Peptide in the Brain and Cognitive Decline (2000)

In this study, levels of total A(beta)x-40 and A(beta)x-42 were elevated early in dementia and levels of both peptides were strongly correlated with cognitive decline. Of particular interest, in the frontal cortex, Abeta was elevated before the occurrence of significant tau pathology. These results support an important role for Abeta in mediating initial pathogenic events in AD dementia and suggest that treatment strategies targeting the formation, accumulation, or cytotoxic effects of Abeta should be pursued.