gebhart/patrepeval huggingface dataset:
Immunogenicity and safety of a recombinant vaccinia virus vaccine expressing the carcinoembryonic antigen gene in a nonhuman primate. (1992)

We have previously reported the development of a recombinant vaccinia virus vaccine expressing the human carcinoembryonic antigen (CEA) gene, designated rV(NYC)-CEA. This construct has been shown to elicit specific anti-CEA immune responses and an antitumor effect in a murine tumor model. In the studies reported here, the safety and immunogenicity of this recombinant vaccinia virus were evaluated in a rhesus monkey model. Human CEA is a M(r) 180,000 glycoprotein expressed in approximately 90% of gastrointestinal carcinomas and in some breast and non-small cell lung carcinomas. This family also includes normal cross-reacting antigen (NCA). Rhesus monkeys, like humans, have some NCA on the surface of their granulocytes. Eight monkeys were immunized 3 or 4 times by skin scarification with the recombinant CEA vaccine and four monkeys received wild-type vaccinia virus as control. After three vaccinations, all rV(NYC)-CEA-vaccinated animals exhibited a strong anti-CEA antibody response as measured by enzyme-linked immunosorbent assay. The functional ability of these antibodies to mediate lysis of a CEA-bearing tumor cell was demonstrated using human effector cells. This response could be enhanced by interleukin 2. Cellular immunity to CEA was measured by delayed-type hypersensitivity upon intradermal challenge with purified CEA. Only those animals receiving the recombinant vaccine displayed significant anti-CEA responses. Furthermore, peripheral blood mononuclear cells from immunized monkeys were found to proliferate in response to CEA stimulation. All vaccinated monkeys developed local skin irritation at the site of the vaccination, regional lymphadenopathy, and low-grade fevers after immunization. Following immunization with rV(NYC)-CEA, the response was consistent with the usual constitutional symptoms seen with human smallpox virus immunization. Blood counts, differentials, and hepatic and renal chemistries remained normal in all animals throughout the study and for up to 1 year following the primary vaccination. No evidence of immunological cross-reactivity to NCA was found by either a fall in the granulocyte count or analyses for anti-NCA antibodies. Thus, the rV(NYC)-CEA vaccine appears to be safe in rhesus monkeys. The administration of a CEA recombinant vaccine to rhesus monkeys induces both a humoral and a cell-mediated immune response directed against human CEA.
Efficient site-directed saturation mutagenesis using degenerate oligonucleotides. (2007)

We describe a reliable protocol for constructing single-site saturation mutagenesis libraries consisting of all 20 naturally occurring amino acids at a specific site within a protein. Such libraries are useful for structure-function studies and directed evolution. This protocol extends the utility of Stratagene's QuikChange Site-Directed Mutagenesis Kit, which is primarily recommended for single amino acid substitutions. Two complementary primers are synthesized, containing a degenerate mixture of the four bases at the three positions of the selected codon. These primers are added to starting plasmid template and thermal cycled to produce mutant DNA molecules, which are subsequently transformed into competent bacteria. The protocol does not require purification of mutagenic oligonucleotides or PCR products. This reduces both the cost and turnaround time in high-throughput directed evolution applications. We have utilized this protocol to generate over 200 site-saturation libraries in a DNA polymerase, with a success rate of greater than 95%.
Localization of the receptor-binding region of Clostridium perfringens enterotoxin utilizing cloned toxin fragments and synthetic peptides. The 30 C-terminal amino acids define a functional binding region (1991)

In this study a short sequence encoding the receptor-binding activity of the much larger 35-kDa enterotoxin elaborated by Clostridium perfringens was localized by recombinant DNA techniques. Defined fragments corresponding to portions of the enterotoxin gene were cloned into an Escherichia coli expression vector system, and these lysates were analyzed for their ability to compete for binding with native C. perfringens enterotoxin (CPE). The lysate containing CPE290-319 (CPE sequence encompassing residues 290-319) was shown to compete with 125I-CPE for specific binding sites on rabbit intestinal brush border membranes. To confirm this finding, a peptide corresponding to the CPE amino acid sequence 290-319 was synthesized and found to completely block CPE specific binding. To demonstrate directly that CPE290-319 can act as a competitive antagonist of CPE cytotoxicity for physiologic receptors, Vero cells were preincubated with either E. coli lysates containing CPE290-319 or the synthetic peptide corresponding to this sequence. Preincubation of Vero cells with either the lysate or the peptide completely protected these cells from CPE challenge. This information localizes the C-terminal 30 residues of CPE (CPE290-319) as a linear sequence sufficient for recognition and binding to the eukaryotic CPE receptor.
Arrays of chemisensitive monolayer-capped metallic nanoparticles for diagnostic breath testing (2010)

Arrays of cross-reactive sensors are well suited to detect subtle changes in clinical samples resulting from internal diseases. Monolayer-capped metallic nanoparticles (MCNPs) are ideal base materials for such sensor arrays because they are chemically versatile, easily fabricated, and readily integrated into chemiresistive sensing platforms using microelectrodes. In this review, we present the main concepts and approaches related to the use of MCNPs in chemiresistors and show their applicability to exhaled breath testing, which is a new non-invasive frontier of medical diagnostics.
Nasosinus mucin expression in normal and inflammatory conditions (2008)

Nasosinus mucin expression is very complicated. Studies including large numbers of samples are needed to investigate the role of different physiological and pathological variables, including inflammatory mediators, in the control of nasosinus mucin expression. This is essential for better understanding of clinical implications of altered nasosinus mucin expression and for future therapeutic applications.
c-Abl kinase inhibitors overcome CD40-mediated drug resistance in CLL: implications for therapeutic targeting of chemoresistant niches (2008)

In lymph node (LN) proliferation centers in chronic lymphocytic leukemia (CLL), the environment protects from apoptotic and cytotoxic triggers. Here, we aimed to define the molecular basis for the increased drug resistance and searched for novel strategies to circumvent it. The situation in CLL LN could be mimicked by prolonged in vitro CD40 stimulation, which resulted in up-regulation of antiapoptotic Bcl-xL, A1/Bfl-1, and Mcl-1 proteins, and afforded resistance to various classes of drugs (fludarabine, bortezomib, roscovitine). CD40 stimulation also caused ERK-dependent reduction of Bim-EL protein, but ERK inhibition did not prevent drug resistance. Drugs combined with sublethal doses of the BH3-mimetic ABT-737 displayed partial and variable effects per individual CD40-stimulated CLL. The antiapoptotic profile of CD40-triggered CLL resembled BCR-Abl-dependent changes seen in chronic myeloid leukemia (CML), which prompted application of c-Abl inhibitors imatinib or dasatinib. Both compounds, but especially dasatinib, prevented the entire antiapoptotic CD40 program in CLL cells, and restored drug sensitivity. These effects also occurred in CLL samples with dysfunctional p53. Importantly, ex vivo CLL LN samples also displayed strong ERK activation together with high Bcl-xL and Mcl-1 but low Bim levels. These data indicate that CLL cells in chemoresistant niches may be sensitive to therapeutic strategies that include c-Abl inhibitors.
Scanning transmission ion microscope with a field ion source. (1975)

Experiments with a low-resolution scanning transmission ion microscope, using hydrogen ions from a field ionization source, indicate that it will be feasible by this approach to aim at high-resolution ion microscopy. Micrographs of unstained biological specimens have been obtained by critical range absorption of a 55 keV hydrogen ion beam at a resolution of 2000 A.
Epileptic amnesic attacks (1985)

We studied two sexagenarians who had recurrent circumscribed attacks of amnesia. Their EEGs showed frequent bilateral spikes that arose independently from the temporal lobes, primarily from mesiobasal structures. Amnesic attacks ceased after treatment with antiepileptic drugs. Neuropsychological tests demonstrated selective cognitive impairments, and short-term memory improved after treatment in one patient. Epileptic amnesic attacks should be distinguished from transient global amnesia, which is clinically similar.
The Effects of an Arabinogalactan-Protein from the White-Skinned Sweet Potato (Ipomoea batatas L.) on Blood Glucose in Spontaneous Diabetic Mice (2011)

We examined the effects of an arabinogalactanprotein (WSSP-AGP) from Ipomoea batatas L. on hyperglycemia in db/db mice. An oral glucose tolerance test indicated significantly decreased plasma glucose levels by WSSP-AGP. Additionally, an insulin tolerance test found improvement in insulin sensitivity due to treatment with WSSP-AGP. This suggests that amelioration of insulin resistance by WSSP-AGP causes to lead its hypoglycemic effects.
Molecular evolution and epidemiology of four serotypes of dengue virus in Thailand from 1973 to 2007 (2012)

SUMMARY Thailand was a hyper-endemic country for dengue with co-circulation of four serotypes and tens of thousands of infected cases annually. Taking into consideration the large number of local dengue virus (DENV) sequences available in GenBank, Thailand was the most ideal locality to study co-evolution of DENV. Therefore, we undertook a large-scale molecular epidemiological analysis of all DENV strains isolated in Thailand. In this study, we demonstrated that DENV strains of four serotypes post-1990 grouped into distinct clades, and that specific mutations in the envelope protein were first confirmed in these clades. Compared to the DENV1, DENV2 and DENV3 clades, the DENV4 clade evolved markedly more slowly (6·4 × 10 −5 substitutions/site per year). Our results also showed that the genetic diversity of the predominant genotype of each serotype tended to slightly increase over time with fluctuating changes, followed by a stationary phase after 2000. This suggests that the four DENV clades became the predominant strains due to DENV possessing improved fitness after long-term selection.
The last book (1997)

In this paper we describe our efforts at the Massachusetts Institute of Technology Media Laboratory toward realizing an electronic book comprised of hundreds of electronically addressable display pages printed on real paper substrates. Such pages may be typeset in situ, thus giving such a book the capability to be any book. We outline the technology we are developing to bring this about and describe a number of applications that such a device enables.
Nonvisual Opsins and the Regulation of Peripheral Clocks by Light and Hormones (2015)

The molecular clock machinery is conserved throughout evolution. However, how environmental cues are perceived has evolved in such a way that peripheral clocks in mammals require a variety of signals, including hormones. On the other hand, in nonmammalian cells able to directly detect light, light seems to play a major role in the synchronization of the clock. The interaction between perception of circadian light by nonvisual opsins and hormones will be discussed under the perspective of clock synchronization at the molecular level.
Apolipoprotein E Induces Antiinflammatory Phenotype in Macrophages (2011)

ApoE signaling via VLDL-R or apoER2 promotes macrophage conversion from the proinflammatory M1 to the antiinflammatory M2 phenotype. This effect may represent a novel antiinflammatory activity of apoE.
The serologically unique cell surface antigen of zajdela ascitic hepatoma is also its tumor‐associated transplantation antigen (1984)

A unique cell surface antigen of a chemically induced rat hepatoma (Zajdela Ascitic Hepatoma, ZAH) has been identified serologically and purified to apparent homogeneity. ZAH cells, when injected subcutaneously or intradermally into syngeneic hosts, elicit a weak humoral antibody response directed against a single cell surface antigen. In spite of prolonged and extensive immunization, the syngeneic anti-tumor antibodies are solely of the IgM class. Antisera from such immunized animals lyse tumor cells in the presence of complement. These observations were utilized in developing methods for the identification and purification of the antigen. It was observed that administration of purified preparations of this antigen confers ZAH-specific tumor immunity in syngeneic animals. Hence the serologically unique antigen is also the tumor-associated transplantation antigen (TATA) of this tumor. This is the first reported purification of a TATA from a rat tumor. There is considerable earlier evidence for the existence of tumor-associated factors which elicit a strong suppressor-cell response in tumor-bearing rats. The availability of the purified TATA from a rat tumor provides, for the first time, a handle for the identification and further characterization of such molecular species.
Coeno-Storyboard: An Augmented Surface fpr Storyboard Presentations (2005)

In this paper, we present Coeno-Storyboard, an around-the-table application designed for storyboard presentations. The demonstration is based on a flexible plug-in framework that allows fast development of tabletop applications. Moreover, we integrated different well-known interaction metaphors into the environment to find out which of the metaphors are accepted mostly by users during a discussion.
Phase I trial of weekly gemcitabine at 3-h infusion in refractory, heavily pretreated advanced solid tumors (2001)

Gemcitabine (2',2'-difluorodeoxycytidine) is a nucleoside analog with antitumor activity against a variety of malignancies. The critical enzyme cytidine kinase is saturated at plasma concentrations achieved after a 30-min infusion at conventional doses. Prolonged infusion time may yield higher intracellular dFdCTP concentrations. A phase I study was designed to determine the maximum tolerated dose (MTD) of gemcitabine, given by infusion for 3 h, in heavily pretreated patients. Twenty-seven patients (13 head and neck cancer, seven sarcoma, three esophageal cancer, three non-small-cell lung cancer and one ovarian cancer) were enrolled. Twenty patients were defined as refractory at first- or second-line chemotherapy. Four different entry dose levels (300, 400, 450 and 500 mg/m(2)) were evaluated for gemcitabine administered on days 1, 8 and 15 of a 28-day cycle. The MTD was defined as 450 mg/m(2), with granulocytopenia, thrombocytopenia and asthenia being dose limiting. The maximum grade III/IV patient toxicities for hemoglobin, leukocytes, neutrophils and platelets for all doses were 7, 19, 19 and 11%, respectively. Non-hematological toxicities included asthenia, nausea/vomiting and diarrhea. Thus, gemcitabine administered at a fixed 3-h infusion was well tolerated up to 450 mg/m(2) in heavily pretreated patients. Myelosupression and asthenia were dose-limiting toxicities.
Seeing the Machinery of Live Cells (1998)

As biochemistry and genetics uncover more of the molecules responsible for life, we need to see how these molecules interact with each other in space and time as they orchestrate cellular responses. Observation of fluorescently labeled macromolecules in live cells can reveal such dynamics, both for
Point process Respiratory Sinus Arrhythmia analysis during deep tissue pain stimulation (2011)

We present an analysis of autonomic nervous system responses to deep tissue pain by using an instantaneous point process assessment of Heart Rate Variability (HRV) and Respiratory Sinus Arrhythmia (RSA). Ten subjects received pressure stimuli at 8 individually calibrated intensities (7 painful) over three separate runs. An inverse Gaussian point process framework modeled the R-R interval (RR) by defining a bivariate regression incorporating both past RRs and respiration values observed at the beats. Instantaneous indices of sympatho-vagal balance and RSA were estimated combining a maximum-likelihood algorithm with time-frequency analysis. The model was validated by Kolmogorov-Smirnov goodness-of-fit and independence tests. Results show that, in comparison to the resting period, all three pain runs elicited a significant decrease in RSA by over 21% (p=0.0547, 0.0234, 0.0547) indicating a reduced parasympathetic tone during pain, with RSA estimates negatively correlated with the calibrated stimulus intensity levels (slope = −0.4123, p=0.0633).
DNA aptamers block L-selectin function in vivo. Inhibition of human lymphocyte trafficking in SCID mice. (1996)

Selectins participate in the initial events leading to leukocyte extravasation from the blood into tissues. Thus the selectins have generated much interest as targets for antiinflammatory agents. Therapeutic molecules based on the monomeric carbohydrate ligand sialyl Lewis X (SLe(X)) have low affinities and are not specific for a given selectin. Using SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technology, we have generated aptamers specific for L-selectin that require divalent cations for binding and have low nanomolar affinity. In vitro, the deoxyoligonucleotides inhibit L-selectin binding to immobilized SLe(X) in static assays and inhibit L-selectin-mediated rolling of human lymphocytes and neutrophils on cytokine-activated endothelial cells in flow-based assays. These aptamers also block L-selectin-dependent lymphocyte trafficking in vivo, indicating their potential utility as therapeutics.
Glycosylation changes in membrane glycoproteins after transfection of NIH 3T3 with human tumor DNA. (1985)

Glycoproteins from NIH 3T3 transformed by transfection with human tumor DNA had altered glycosylation. That is, the glycoproteins have a decrease in biantennary oligosaccharides with a concomitant increase in tri- and tetraantennary oligosaccharides. After swainsonine treatment, glycosylation of oncogene transfected NIH 3T3 was more similar to the normal counterpart. Thus, this inhibitor of glycoprotein processing is able to reverse at least one phenotypic expression of transformation, the formation of more highly branched oligosaccharides. The mechanism may be by inhibition of a specific glycosyl transferase.
Elevation of Factor VIII (Antihemophilic Factor) during Pregnancy in Normal Persons and in a Patient with von Willebrand's Disease (1963)

DURING pregnancy increased blood levels of fibrinogen,1 , 2 factor VII (SPCA, proconvertin) and factor X (Stuart–Prower factor),3 4 5 6 as well as increased platelet adhesiveness,7 have been observed. This has been linked with a hypercoagulable state existing during pregnancy. It has been stated that factor VIII (antihemophilic factor) levels were not altered during this period.6 , 8 Recent experience in our laboratory, however, has demonstrated significant elevations of factor VIII levels gradually taking place during the course of pregnancy in all subjects thus far studied. Of interest in this connection is a recent report describing elevations of factor VII and VIII in women under hormonal . . .
Purification and characterization of the cytokine-induced macrophage nitric oxide synthase: an FAD- and FMN-containing flavoprotein. (1991)

A soluble nitric oxide (NO) synthase activity was purified 426-fold from a mouse macrophage cell line activated with interferon gamma and bacterial lipopolysaccharide by sequential anion-exchange, affinity, and gel filtration chromatography. SDS/PAGE of the purified NO synthase gave three closely spaced silver-staining protein bands between 125 and 135 kDa. When assayed in the presence of L-arginine, NADPH, tetrahydrobiopterin, FAD, and reduced thiol, purified NO synthase had a specific activity of 1313 nmol of NO2- plus NO3- per min per mg. The apparent Km of the enzyme for L-arginine and NADPH was 2.8 and 0.3 microM, respectively. Addition of calcium ions with or without calmodulin did not increase the activity of the purified enzyme, and NO synthesis was not altered by calmodulin inhibitors. Gel filtration chromatography indicated that the induced NO synthase was catalytically competent as a dimer of approximately 250 kDa but could be dissociated into inactive monomers of approximately 130 kDa in the absence of L-arginine, FAD, and tetrahydrobiopterin. Upon heat denaturation, NO synthase released 1.1 mol of FAD and 0.55 mol of FMN per mol of 130-kDa subunit. Thus, inducible macrophage NO synthase differs in several respects from constitutive NO synthases and is one of very few eukaryotic enzymes containing both FAD and FMN.
Selectivity of commonly used pharmacological inhibitors for cystathionine β synthase (CBS) and cystathionine γ lyase (CSE) (2013)

In conclusion, although PAG, AVG and BCA exhibit selectivity in inhibiting CSE versus CBS, no selective pharmacological CBS inhibitor is currently available.
Production of Glycerol from Methanol by a Mutant Strain ofCandida boidiniiNo. 2201 (1989)

Journal Article Production of Glycerol from Methanol by a Mutant Strain of Candida boidinii No. 2201 Get access Keiko Yamada, Keiko Yamada Research Center for Cell and Tissue Culture, Faculty of Agriculture, Kyoto University, Kyoto 606, Japan Search for other works by this author on: Oxford Academic Google Scholar Shinobu Kuwae, Shinobu Kuwae Research Center for Cell and Tissue Culture, Faculty of Agriculture, Kyoto University, Kyoto 606, Japan Search for other works by this author on: Oxford Academic Google Scholar Yoshiki Tani Yoshiki Tani Research Center for Cell and Tissue Culture, Faculty of Agriculture, Kyoto University, Kyoto 606, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 53, Issue 2, 1 February 1989, Pages 541–543, https://doi.org/10.1080/00021369.1989.10869334 Published: 01 February 1989 Article history Received: 09 August 1988 Published: 01 February 1989
Cellular Lipid Metabolism and the Role of Lipids in Progressive Renal Disease (2004)

Dyslipidemia contributes to the rate of progression of atherosclerosis and chronic kidney disease. Also, chronic kidney disease leads to the development of secondary abnormalities in lipid metabolism that contribute to increased cardiovascular morbidity and mortality. This review presents the mechanisms that underlie this risk. The mechanisms of normal cellular lipid metabolism and the abnormalities that develop in association with inflammation are reviewed. There is a special emphasis on foam cells in the kidney and on lipid-mediated changes in intrinsic kidney cells that lead to glomerulosclerosis and interstitial fibrosis. Correlates to studies performed in whole animals and humans are included.
Dengue vaccine: opportunities and challenges. (2008)

Despite many successes in the field of vaccinology over the past century, several important scourges for which effective vaccines remain elusive continue to be threats to public health. The mosquito-borne dengue virus causes millions of infections in tropical and subtropical regions throughout the world, and is responsible for an annual mortality that measures in the thousands. The ubiquitous presence of dengue virus, and its potentially lethal complications, have made the development of an effective vaccine against the virus a priority. However, before such a vaccine can be created, the basic immunology surrounding dengue infection must be clarified. Such research is underway, including efforts focusing on the response of T-cells and the potentially central role of this response in dengue pathophysiology. 'Shaping' the T-cell response may be the key to successful dengue vaccine design.