gebhart/patrepeval huggingface dataset:
Nerve growth factor in sympathetic ganglia and corresponding target organs of the rat: correlation with density of sympathetic innervation. (1983)

A two-site enzyme immunoassay is described which does not suffer from artifacts inherent in previous assays and has the necessary high sensitivity to determine the endogenous levels of nerve growth factor (NGF) in the sympathetic nervous system and its target organs. Monoclonal and affinity-purified polyclonal antibodies against mouse NGF (mNGF) were covalently linked to glass beads as the first site and coupled to the enzyme beta-galactosidase as the second site. Detection of the fluorescent beta-galactosidase reaction product permitted the determination of 0.01-0.02 fmol of mNGF per assay. The recovery of mNGF added to homogenates varied between 50% and 100%, depending on the tissue. Rat superior cervical and stellate ganglia were found to contain (mean +/- SEM) 25 +/- 4 and 19 +/- 3 ng of NGF per g wet weight, respectively, and the densely innervated submandibular gland, heart atrium, and iris contained 0.5 +/- 0.1, 1.0 +/- 0.1, and 1.9 +/- 0.3 ng of NGF per g wet weight, respectively. Heart ventricle and skeletal muscle, which are poorly innervated by the sympathetic nervous system, did not contain detectable levels of NGF (less than 0.3 ng/g wet weight). Serum contained less than 0.05 ng of NGF per ml. The correlation between NGF levels and density of innervation is consistent with the concept that the production of NGF in target organs determines their density of innervation by the sympathetic nervous system.
Expression of the haemopexin-transport system in cultured mouse hepatoma cells. Links between haemopexin and iron metabolism (1988)

Minimal deviation hepatoma (Hepa) cells, from the mouse hepatoma B7756, synthesize and secrete haemopexin and express both the haemopexin receptor and the membrane haem-binding protein (MHBP) associated with the receptor, making this cell line the first available for detailed study of both haemopexin metabolism and hepatic transport. The 17.5 kDa MHBP was detected in Triton X-100 extracts of Hepa cells by immunoblotting with goat anti-rabbit MHBP. Scatchard-type analysis of haem-125I-haemopexin binding at 4 degrees C revealed 35,000 receptors per cell of high affinity (Kd 17 nM). Haemopexin-mediated haem transport at 37 degrees C is saturable, having an apparent Km of 160 nM and a Vmax. of 7.5 pmol of haem/10(6) cells per h during exponential growth. Haem-transport capacity is highest in the period just before the cells enter their exponential phase of growth and slowest in stationary phase. Interestingly, haem-haemopexin serves as effectively as iron-transferrin as the sole source of iron for cell growth by Hepa cells. Furthermore, depriving Hepa cells of iron by treatment with desferrioxamine (DF) increases the number of cell-surface haemopexin receptors to 65,000 per cell and consequently increases haemopexin-mediated haem transport. The effects of DF do not appear to require protein synthesis since they are not prevented by cycloheximide. Treatment of Hepa cells with hydroxyurea, an inhibitor of the iron-requiring enzyme ribonucleotide reductase that is obligatory for DNA synthesis, enhanced haemopexin-mediated haem transport. Thus, these studies provide the first evidence for regulation of haem transport by the iron status of cells and suggest a linkage between haemopexin, iron homeostasis and cell growth.
Transfusions in the Less Severely Injured: Does Age of Transfused Blood Affect Outcomes? (2008)

In a mild to moderately injured intensive care unit patient cohort, the receipt of blood stored beyond 2 weeks was independently associated with mortality, renal failure, and pneumonia. The deleterious effect of older blood on patient outcome does not appear to be limited to the severely injured.
A new function of S-adenosylmethionine: The ribosyl moiety of AdoMet is the precursor of the cyclopentenediol moiety of the tRNA wobble base queuine (1993)

Queuosine (Q) [7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deaz agu anosine] usually occurs in the first position of the anticodon of tRNAs specifying the amino acids asparagine, aspartate, histidine, and tyrosine. The hypermodified nucleoside is found in eubacteria and eucaryotes. Q is synthesized de novo exclusively in eubacteria; for eucaryotes the compound is a nutrient factor. In Escherichia coli the Q precursor (oQ), carrying a 2,3-epoxy-4,5-dihydroxycyclopentane ring, is formed from tRNA precursors containing 7-(aminomethyl)-7-deazaguanine (preQ1) by the queA gene product. A genomic queA mutant accumulating preQ1 tRNA was constructed. The QueA enzyme was overexpressed as a fusion protein with the glutathione S-transferase from Schistosoma japonicum and purified to homogeneity by affinity and anion-exchange chromatography. The enzyme QueA synthesizes oQ from preQ1 in a single S-adenosylmethionine- (AdoMet-) requiring step, indicating that the ribosyl moiety of AdoMet is transferred and isomerized to the epoxycyclopentane residue of oQ. The identity of oQ was verified by HPLC and directly combined HPLC/mass spectrometry. The formation of oQ was reconstituted in vitro, applying a synthetic RNA. A 17-nucleotide microhelix (corresponding to the anticodon stem and loop of tRNA(Tyr) from E. coli) is sufficient to act as the RNA substrate for oQ synthesis. We propose that QueA is an S-adenosylmethionine:tRNA ribosyltransferase-isomerase.
Molecular Profiling of theClostridium leptumSubgroup in Human Fecal Microflora by PCR-Denaturing Gradient Gel Electrophoresis and Clone Library Analysis (2006)

A group-specific PCR-based denaturing gradient gel electrophoresis (DGGE) method was developed and combined with group-specific clone library analysis to investigate the diversity of the Clostridium leptum subgroup in human feces. PCR products (length, 239 bp) were amplified using C. leptum cluster-specific primers and were well separated by DGGE. The DGGE patterns of fecal amplicons from 11 human individuals revealed host-specific profiles; the patterns for fecal samples collected from a child for 3 years demonstrated the structural succession of the population in the first 2 years and its stability in the third year. A clone library was constructed with 100 clones consisting of 1,143-bp inserts of 16S rRNA gene fragments that were amplified from one adult fecal DNA with one forward universal bacterial primer and one reverse group-specific primer. Eighty-six of the clones produced the 239-bp C. leptum cluster-specific amplicons, and the remaining 14 clones did not produce these amplicons but still phylogenetically belong to the subgroup. Sixty-four percent of the clones were related to Faecalibacterium prausnitzii (similarity, 97 to 99%), 6% were related to Subdoligranulum variabile (similarity, approximately 99%), 2% were related to butyrate-producing bacterium A2-207 (similarity, 99%), and 28% were not identified at the species level. The identities of most bands in the DGGE profiles for the same adult were determined by comigration analysis with the 86 clones that harbored the 239-bp group-specific fragments. Our results suggest that DGGE combined with clone library analysis is an effective technique for monitoring and analyzing the composition of this important population in the human gut flora.
Human Immunodeficiency Virus Type 1-Specific Immunity after Genetic Immunization Is Enhanced by Modification of Gag and Pol Expression (2001)

Immunity to human immunodeficiency virus virion-like structures or a polyprotein has been examined after DNA immunization with Rev-independent expression vectors. A Gag-Pol fusion protein stimulated cytotoxic T lymphocyte and antibody responses to Gag and Pol, while a Gag-Pol pseudoparticle did not elicit substantial Pol responses. This fusion protein may be useful for AIDS vaccines.
Low-Friction Nanoscale Linear Bearing Realized from Multiwall Carbon Nanotubes (2000)

We demonstrate the controlled and reversible telescopic extension of multiwall carbon nanotubes, thus realizing ultralow-friction nanoscale linear bearings and constant-force nanosprings. Measurements performed in situ on individual custom-engineered nanotubes inside a high-resolution transmission electron microscope demonstrated the anticipated van der Waals energy-based retraction force and enabled us to place quantitative limits on the static and dynamic interwall frictional forces between nested nanotubes. Repeated extension and retraction of telescoping nanotube segments revealed no wear or fatigue on the atomic scale. Hence, these nanotubes may constitute near perfect, wear-free surfaces.
Biobased adhesives, gums, emulsions, and binders: current trends and future prospects (2012)

Biopolymers derived from renewable resources are an emerging class of advanced materials that offer many useful properties for a wide range of food and nonfood applications. Current state of the art in research and development of renewable polymers as adhesives, gums, binders, and emulsions is the subject of this review. Much of the focus will be on major biopolymers such as starch, proteins, lignin, oils, and their derivatives found in both natural and modified forms, but other biopolymers of promising commercial interest will also be included where warranted. Polymers produced in nature are remarkably diverse in their chemistry, thermomechanical properties, rheology, plasticity, and chemical reactivity. In particular, their capacity to undergo a wide array of chemical modifications yields materials with tailored properties suitable for use as adhesives, gums, coatings, emulsions, and binders. Many such materials are now widely used in commercial products like building materials, lubricants, sealants, coatings, bonding aids, pharmaceuticals, paper, glues, flocculants, processed and frozen foods, as well as tissue engineering and bone repair products. This review provides a general overview of biobased polymers highlighting their source, availability, properties, and usage in industrial products along with the future prospects, challenges, and opportunities they offer.
Hydrogen Peroxide Is Generated during the Very Early Stages of Aggregation of the Amyloid Peptides Implicated in Alzheimer Disease and Familial British Dementia (2005)

Alzheimer disease and familial British dementia are neurodegenerative diseases that are characterized by the presence of numerous amyloid plaques in the brain. These lesions contain fibrillar deposits of the beta-amyloid peptide (Abeta) and the British dementia peptide (ABri), respectively. Both peptides are toxic to cells in culture, and there is increasing evidence that early "soluble oligomers" are the toxic entity rather than mature amyloid fibrils. The molecular mechanisms responsible for this toxicity are not clear, but in the case of Abeta, one prominent hypothesis is that the peptide can induce oxidative damage via the formation of hydrogen peroxide. We have developed a reliable method, employing electron spin resonance spectroscopy in conjunction with the spin-trapping technique, to detect any hydrogen peroxide generated during the incubation of Abeta and other amyloidogenic peptides. Here, we monitored levels of hydrogen peroxide accumulation during different stages of aggregation of Abeta-(1-40) and ABri and found that in both cases it was generated as a short "burst" early on in the aggregation process. Ultrastructural studies with both peptides revealed that structures resembling "soluble oligomers" or "protofibrils" were present during this early phase of hydrogen peroxide formation. Mature amyloid fibrils derived from Abeta-(1-40) did not generate hydrogen peroxide. We conclude that hydrogen peroxide formation during the early stages of protein aggregation may be a common mechanism of cell death in these (and possibly other) neurodegenerative diseases.
Quantitative Analysis of Circulating Methylated DNA as a Biomarker for Hepatocellular Carcinoma (2008)

Detection and quantification of circulating methylated RASSF1A sequences are useful for HCC screening, detection, and prognostication.
Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies from an HIV-1 Vaccine Efficacy Trial Target Multiple Epitopes and Preferentially Use the VH1 Gene Family (2012)

The ALVAC-HIV/AIDSVAX-B/E RV144 vaccine trial showed an estimated efficacy of 31%. RV144 secondary immune correlate analysis demonstrated that the combination of low plasma anti-HIV-1 Env IgA antibodies and high levels of antibody-dependent cellular cytotoxicity (ADCC) inversely correlate with infection risk. One hypothesis is that the observed protection in RV144 is partially due to ADCC-mediating antibodies. We found that the majority (73 to 90%) of a representative group of vaccinees displayed plasma ADCC activity, usually (96.2%) blocked by competition with the C1 region-specific A32 Fab fragment. Using memory B-cell cultures and antigen-specific B-cell sorting, we isolated 23 ADCC-mediating nonclonally related antibodies from 6 vaccine recipients. These antibodies targeted A32-blockable conformational epitopes (n = 19), a non-A32-blockable conformational epitope (n = 1), and the gp120 Env variable loops (n = 3). Fourteen antibodies mediated cross-clade target cell killing. ADCC-mediating antibodies displayed modest levels of V-heavy (VH) chain somatic mutation (0.5 to 1.5%) and also displayed a disproportionate usage of VH1 family genes (74%), a phenomenon recently described for CD4-binding site broadly neutralizing antibodies (bNAbs). Maximal ADCC activity of VH1 antibodies correlated with mutation frequency. The polyclonality and low mutation frequency of these VH1 antibodies reveal fundamental differences in the regulation and maturation of these ADCC-mediating responses compared to VH1 bNAbs.
<title>Photopolymer media for digital holographic data storage</title> (1998)

We report on the holographic storage of multiple digital data pages in photopolymer media. The results demonstrate the potential of these materials for high density data storage.
Terminally differentiated skeletal myotubes are not confined to G0 but can enter G1 upon growth factor stimulation. (1996)

Terminally differentiated cells are specialized cells unable to proliferate that constitute most of the mammalian body. Despite their abundance, little information exists on the characteristics of cell cycle control in these cells and the molecular mechanisms that prevent their proliferation. They are generally believed to be irreversibly restricted to the G0 state. In this report, we define some features of a paradigmatic terminally differentiated system, the skeletal muscle, by studying its responses to various mitogenic stimuli. We show that forced expression of a number of cell cycle-regulatory genes, including erbB-2, v-ras, v-myc, B-myb, ld-1, and E2F-1, alone or in combinations, cannot induce terminally differentiated skeletal muscle cells (myotubes) to synthesize DNA. However, serum-stimulated myotubes display a typical immediate-early response, including the up-regulation of c-fos, c-jun, c-myc, and ld-1. They also elevate the expression of cyclin D1 after 4 hours of serum treatment. All these events take place in myotubes in a way that is indistinguishable from that of quiescent, undifferentiated myoblasts reactivated by serum. Moreover, pretreatment with serum shortens the time required by E1A to induce DNA synthesis, confirming that myotubes can partially traverse G1. Serum growth factors do not activate late-G1 genes in myotubes, suggesting that the block that prevents terminally differentiated cells from proliferating acts in mid-G1. Our results show that terminally differentiated cells are not confined to G0 but can partially reenter G1 in response to growth factors; they contribute to a much-needed definition of terminal differentiation. The important differences in the control of the cell cycle between terminally differentiated and senescent cells are discussed.
An intelligent, predictive control approach to the high-speed cross-country autonomous navigation problem (1996)

Autonomous robot vehicles promise many ultimate civilian, military, and space applications. Off-road autonomous vehicles must engage the world exactly as they find it without relying on having it engineered to suit them. For this reason, offroad autonomous navigation is one of the most difficult automation challenges. Previous work in the area has been disappointing from the perspective of the speeds attained, and the inability of systems to travel long distances autonomously. Indeed, no system has travelled an autonomous mile or exceeded 3 m/s speeds. To date, no off-road system has approached the capabilities needed to address real applications. This thesis examines and proposes a solution to the problem of high speed autonomous navigation of outdoor vehicles. As a systems-level effort, aspects of perception, path planning, position estimation, and to a lesser extent, strategic planning and motion control are considered. The emphasis of the work has been to assess the fundamental requirements of the problem, and to validate the conclusions
Traceable Multifunctional Micellar Nanocarriers for Cancer-Targeted Co-delivery of MDR-1 siRNA and Doxorubicin (2011)

In this article we report on the development of polymeric micelles that can integrate multiple functions in one system, including the capability to accommodate a combination of therapeutic entities with different physicochemical properties (i.e., siRNA and doxorubicin; DOX), passive and active cancer targeting, cell membrane translocation, and pH-triggered drug release. A micellar system was constructed from degradable poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) block copolymers with functional groups on both blocks. The functional group on the PCL block was used to incorporate short polyamines for complexation with siRNA or to chemically conjugate DOX via a pH-sensitive hydrazone linkage. A virus mimetic shell was conferred by attaching two ligands, i.e., the integrin αvβ3-specific ligand (RGD4C) for active cancer targeting and the cell-penetrating peptide TAT for membrane activity. This system was used to improve the efficacy of DOX in multidrug-resistant MDA-MB-435 human tumor models that overexpress P-glycoprotein (P-gp), by simultaneous intracellular delivery of DOX and siRNA against P-gp expression. The carrier was tagged with near-infrared fluorescent imaging probes to provide a means to follow the fate of the system in vivo upon intravenous administration. Dy677-labeled siRNA was also used to assess the in vivo stability of the siRNA carrier. This multifunctional polymeric micellar system was shown to be capable of DOX and siRNA delivery to their intracellular targets, leading to the inhibition of P-gp-mediated DOX resistance in vitro and targeting of αvβ3-positive tumors in vivo.
Novel therapeutic strategies. (1999)

Of the many sessions during the first day of the EPHAR meeting, several interesting topics emerged. Among these were a number of presentations investigating novel anti-inflammatory targets, including the search for a selective COX-2 inhibitor and the potential of cytokines/cytokine receptor targets (eg TNFalpha) as treatments for rheumatoid arthritis (RA) and other chronic inflammatory conditions. Recent advances in the understanding of the pathogenesis of diabetes and obesity have highlighted the need for a multi-therapeutic approach to treatment; several drugs in preclinical investigations were highlighted. Attention was drawn to the potential of AMPA/kainate receptors, historically investigated for the treatment of neurodegenerative disease, which are now showing promise as anti-ischemic therapeutics. Many novel therapeutics strategies were discussed in detail, including the CCK-B antagonists with considerable anxiolytic potential, mitochondrial mechanisms as targets for the treatment of brain injury and the use of stress-activated proteins in anti-ischemic research.
Cancer Epigenetics: Modifications, Screening, and Therapy (2007)

Deregulation of gene expression is a hallmark of cancer. Although genetic lesions have been the focus of cancer research for many years, it has become increasingly recognized that aberrant epigenetic modifications also play major roles in the tumorigenic process. These modifications are imposed on chromatin, do not change the nucleotide sequence of DNA, and are manifested by specific patterns of gene expression that are heritable through many cell divisions. We review these modifications in normal and cancer cells and the evolving approaches used to study them. Additionally, we outline advances in their potential use for cancer diagnostics and targeted epigenetic therapy.
Recombinant Protein Complex Expression in E. coli (2008)

This unit provides procedures to design, create, and utilize polycistronic plasmids that express multicomponent protein complexes in E. coli. Both the original pST39 polycistronic expression system, which permits four genes to be coexpressed from a single plasmid, and the more recent pST44 polycistronic system, which facilitates incorporation of affinity tags and simplifies the construction of variant deletion or point mutation polycistronic plasmids, are described. Emphasis is placed on practical details for creating polycistronic expression plasmids, expressing the protein complex in E. coli, purifying the protein complex, and troubleshooting potential expression problems.
Interstitial Chemotherapy with Carmustine-loaded Polymers for High-grade Gliomas: A Randomized Double-blind Study (1997)

Carmustine applied locally in a biodegradable polymer at the time of primary operation, seems to have a favorable effect on the life span of patients with high-grade gliomas.
Glucagon‐like peptide‐1(9‐36)amide metabolite inhibits weight gain and attenuates diabetes and hepatic steatosis in diet‐induced obese mice (2010)

GLP-1(9-36)amide exerts insulin-like actions in the presence of insulin resistance and prevents the development of metabolic syndrome. Curtailment of weight gain in the face of increased caloric intake suggests that GLP-1(9-36)amide increases energy expenditure. These findings suggest the possibility of the use of GLP-1(9-36)amide, or a peptide mimetic derived there from, for the treatment of obesity, insulin resistance and the metabolic syndrome.
Familial Aggregation of Alzheimer's Disease and Related Disorders: A Collaborative Re-Analysis of Case-Control Studies (1991)

Case-control studies of Alzheimer's disease were re-analysed to examine the association of Alzheimer's disease with family history in first degree relatives of dementia, Down's syndrome and Parkinson's disease. Overall, the relative risk of Alzheimer's disease for those with at least one first degree relative with dementia was 3.5 (95% confidence interval 2.6-4.6). Stratification according to age of onset of Alzheimer's disease showed that the relative risk decreased with increasing onset age. However, among patients with an onset of disease after 80 years, there were still significantly more subjects with one or more first degree relatives with dementia as compared to controls (relative risk 2.6; 95% confidence interval 1.3-5.2). The relative risk of Alzheimer's disease was significantly lower in patients who had one first degree relative with dementia (relative risk 2.6; 95% confidence interval 2.0-3.5) as compared to those who had two or more affected relatives (relative risk 7.5; 95% confidence interval 3.3-16.7). Furthermore, the re-analysis showed a significant association between Alzheimer's disease and family history of Down's syndrome (relative risk 2.7; 95% confidence interval 1.2-5.7), which was strongest in those patients who had a positive family history of dementia. The relative risk of Alzheimer's disease for those with a positive family history of Parkinson's disease was 2.4 (95% confidence interval 1.0-5.8).