gebhart/patrepeval huggingface dataset:
A Blood-Based Proteomic Classifier for the Molecular Characterization of Pulmonary Nodules (2013)

Each year, millions of pulmonary nodules are discovered by computed tomography and subsequently biopsied. Because most of these nodules are benign, many patients undergo unnecessary and costly invasive procedures. We present a 13-protein blood-based classifier that differentiates malignant and benign nodules with high confidence, thereby providing a diagnostic tool to avoid invasive biopsy on benign nodules. Using a systems biology strategy, we identified 371 protein candidates and developed a multiple reaction monitoring (MRM) assay for each. The MRM assays were applied in a three-site discovery study (n = 143) on plasma samples from patients with benign and stage IA lung cancer matched for nodule size, age, gender, and clinical site, producing a 13-protein classifier. The classifier was validated on an independent set of plasma samples (n = 104), exhibiting a negative predictive value (NPV) of 90%. Validation performance on samples from a nondiscovery clinical site showed an NPV of 94%, indicating the general effectiveness of the classifier. A pathway analysis demonstrated that the classifier proteins are likely modulated by a few transcription regulators (NF2L2, AHR, MYC, and FOS) that are associated with lung cancer, lung inflammation, and oxidative stress networks. The classifier score was independent of patient nodule size, smoking history, and age, which are risk factors used for clinical management of pulmonary nodules. Thus, this molecular test provides a potential complementary tool to help physicians in lung cancer diagnosis.
Deep Brain Stimulation in Patients with Refractory Temporal Lobe Epilepsy (2007)

This open pilot study demonstrates the potential efficacy of long-term DBS in MTL structures that should now be further confirmed by multicenter randomized controlled trials.
Effect of interstitial and/or systemic delivery of tirapazamine on the radiosensitivity of human glioblastoma multiforme in nude mice (1998)

The purpose of this study was to investigate the feasibility and the efficacy of administering tirapazamine by a slow-releasing polymer disc that was implanted interstitially into a U251 (human glioblastoma multiforme) tumor grown in nude mice. Tumor-bearing animals, with a tumor nodule 0.8 cm3 in size, were distributed to groups receiving combinations of empty or drug-containing polymer implants in the tumor or contralateral leg, intraperitoneal (i.p.) drug, and/or irradiation. The drug (i.p.) alone (14 mg/kg x6) or in combination with tumor drug implant (2 mg) did not significantly increase the tumor volume doubling time compared to that of control animals. Given with 12 Gy of irradiation in twice a day 2-Gy fractions, combined i.p. drug and tumor drug implant significantly delayed tumor growth compared to irradiation alone, which was not achieved with either drug treatment alone added to irradiation. Toxicity, as manifested by transient weight loss, was primarily seen in animals receiving radiation and i.p. tirapazamine. These results indicated that a slow-releasing tirapazamine disc can be produced and the addition of an interstitially implanted tirapazamine disc further increased the effectiveness of i.p. tirapazamine.
Metabolic engineering of Escherichia coli for high-specificity production of isoprenol and prenol as next generation of biofuels (2013)

To the best of our knowledge, this is the first successful report on high-specificity production of isoprenol and prenol by microbial fermentation. Over 1.3 g/L isoprenol achieved in shake-flask experiments represents a quite encouraging titer of higher alcohols. In addition, the substrate specificities of ADP-ribose pyrophosphatases were determined and successfully applied for the high-specificity synthesis of isoprenol and prenol. Altogether, this work presents a promising strategy for high-specificity production of two excellent biofuels, isoprenol and prenol.
Synthetic Nucleic Acid Delivery Systems: Present and Perspectives (2015)

Self-assembled synthetic gene delivery systems represent the bottom-up approach to gene delivery and gene silencing, in which scientists are designing novel cationic and procationic amphiphiles that can pack, transport, and deliver nucleic acids to various targets in the body in a controlled manner. These supramolecular assemblies are safer than viruses, but they are lagging behind them in efficiency. We are presenting recent progress that has narrowed this gap through better understanding the delivery barriers and incorporation of this knowledge in the design of novel synthetic amphiphiles, formulations, and revolutionary screening and optimization processes. Structure-properties and structure-activity relationships were drawn within each amphiphile class, presenting the cellular and animal models used to generate them. We are also revealing pertinent in vitro/in vivo correlations that emphasize promising amphiphiles and successful formulation optimization efforts for efficient in vivo nucleic acid delivery, together with main organ targets and diseases treatable with these revolutionary technologies.
Reactivities of Polyclonal and Monoclonal Antibodies Raised to the Major Capsid Protein of Human Papillomavirus Type 16 (1989)

Polyclonal and monoclonal antibodies have been raised against a fusion protein containing beta-galactosidase and part of the major capsid protein L1 of the human papillomavirus (HPV) type 16. The polyclonal antibodies cross-reacted with the L1 protein of several HPV types including HPV-1, -2, -6 and -11 when reacted with virus-infected tissue sections, and with HPV-6 and -18 L1 fusion proteins on Western blotting. Monoclonal antibodies against the L1 fusion protein of HPV-16 reacted only with HPV-16 L1 fusion proteins on Western blots and with HPV-16-containing biopsy sections as assessed by in situ DNA-DNA hybridization. These antibodies did not detect HPV-6 L1 protein after Western blotting or in HPV-6-infected tissue sections, although one did react with an HPV-18 fusion protein after Western blotting. The monoclonal antibodies were able to detect HPV-16 antigens in routine formaldehyde-fixed, wax-embedded sections of cervical intraepithelial neoplasia sections. HPV-16 L1 proteins were seen in one-third of biopsies that were positive using the polyclonal cross-reacting antisera. Polyclonal antibodies to fusion proteins containing part of the minor capsid protein L2 of HPV-6 or -16 appeared to be more type-specific as no cross-reactivity was seen when these antibodies were reacted with HPV-1- and -2-infected tissue sections.
Mass spectrometric quantification of amino acid oxidation products in proteins: insights into pathways that promote LDL oxidation in the human artery wall (1999)

Oxidatively damaged low density lipoprotein (LDL) may play an important role in atherogenesis, but the physiologically relevant pathways have proved difficult to identify. Mass spectrometric quantification of stable compounds that result from specific oxidation reactions represents a powerful approach for investigating such mechanisms. Analysis of protein oxidation products isolated from atherosclerotic lesions implicates tyrosyl radical, reactive nitrogen species, and hypochlorous acid in LDL oxidation in the human artery wall. These observations provide chemical evidence for the reaction pathways that promote LDL oxidation and lesion formation in vivo.--Heinecke, J. W. Mass spectrometric quantification of amino acid oxidation products in proteins: insights into pathways that promote LDL oxidation in the human artery wall.
The gene for Nijmegen breakage syndrome (V2) is not located on chromosome 11. (1996)

Ataxia telanglectasia (AT) is an autosomal recessive disorder characterized by oculocutaneous telangiectasia and cerebellar ataxia. Individuals with this disorder display immunological impairments, hypersensitivity to ionizing radiation, and a predisposition to cancer. There has been reported genetic heterogeneity in AT, which appeared to include four genetic complementation groups in classical AT - i.e., A, B/C, D, E - and two variants, so-called Nijmegen breakage syndrome (NBS), V1 and V2. Among the four groups of classical AT, no significant differences in clinical appearance have been seen. Familial linkage analyses have produced evidence that genes for all four complementation groups in classical AT reside in a narrow region on chromosome 11q22-23. On the other hand, NBS patients have neither cerebellar ataxia nor telanglectasia but do display microcephaly and a developmental delay. However, patients share features with AT, such as high radiosensitivity, radioresistant DNA synthesis (RDS), and chromosome instability, suggesting that the same pathway (or part thereof) is impaired in both syndromes. The underlying gene for NBS has not yet been identified, and its location in the human genome is still unknown. 15 refs., 3 figs.
Thermal expansion and length stability of Zerodur in dependence on temperature and time (1985)

The lengths and the thermal expansion values of the glass ceramic Zerodur show a reversible dependence on the thermal history within two temperature intervals. Typical effects associated with this dependence are, for example, isothermal length changes within and permanent length changes below the temperature intervals. It is assumed that relaxation causes the observed effects. The phenomena in the upper temperature range from 130°C to 300°C are related to the MgO content. The reversibility of the relaxation effects allows adjustment for lengths and thermal expansion values by appropriate cooling processes.
In Vitro Activities and Postantifungal Effects of the Potent Dolastatin 10 Derivative Auristatin PHE (2001)

The pentapeptide dolavaline-valine-dolaisoleuine-dolaproine-phenylalanine-methyl ester (auristatin PHE) is a derivative of the anticancer drug dolastatin 10 (dolavaline-valine-dolaisoleuine-dolaproine-dolaphenine). Broth microdilution assays with a wide variety of yeast and filamentous fungal species demonstrated the specificity of auristatin PHE for Cryptococcus neoformans and several species of Trichosporon. The duration of the postantifungal effect (PAFE) for C. neoformans was determined for exposure times ranging from 30 min to 2 h. For the derivative, a PAFE was detectable after 45 min of exposure. The effect plateaued after 1 h of exposure, with a PAFE of approximately 6.5 h at four or eight times the auristatin PHE MIC. In contrast, there was no measurable PAFE after 1 h of exposure to dolastatin 10. Human serum greatly prolonged the PAFE of auristatin PHE at eight times the MIC. Auristatin PHE arrested C. neoformans in the budding stage, possibly due to a tubulin-inhibitory action. Auristatin PHE has potential as a narrow-spectrum fungicidal agent and as a probe that can be used to study cryptococcal cell division.
Pathology of lumbar nerve root compression Part 2: Morphological and immunohistochemical changes of dorsal root ganglion (2003)

It is important to be aware that in patients with nerve root compression due to lumbar disc herniation or lumbar canal stenosis, dysfunction is not confined to degeneration at the site of compression, but also extends to the primary sensory neurons within the dorsal root ganglion as a result of the axon reaction. Patients with sensory disturbance should therefore be fully informed of the fact that these symptoms will not resolve immediately after surgery.
N-to-C Solid-Phase Peptide and Peptide Trifluoromethylketone Synthesis Using Amino Acid tert-Butyl Esters. (2002)

Solid-phase peptide synthesis in the N-to-C direction, opposite to the classical C-to-N direction of peptide synthesis, provides the synthetically versatile C-terminal carboxyl group for further modification into C-terminally modified peptide mimetics. These are of general interest as potential bioactive agents, particularly as protease inhibitors. Elaboration of peptide mimetics on the solid-phase would facilitate synthesis of peptide mimetic combinatorial libraries. This report describes an effective strategy for solid-phase inverse peptide synthesis based on readily available amino acid tert-butyl esters. The potential of this approach for peptide mimetic synthesis is demonstrated by the solid-phase synthesis of two peptide trifluoromethylketones.
Comparison of latent and nominal rabbit Ig VHa1 allotype cDNA sequences. (1988)

The genetic basis for the expression of a latent VH allotype in the rabbit was investigated. VH region cDNA libraries were produced from spleen mRNA derived from a homozygous a2a2 rabbit expressing an induced latent VHa1 allotype and, for comparison, from a normal homozygus a1a1 rabbit expressing nominal VHa1 allotype. The deduced amino acid sequences of the nominal VHa1 cDNA were concordant with previously published VHa1 protein sequences. A comparison of two complete VH-DH-JH and six partial VHa1 sequences reveals highly conserved sequence within VH framework regions (FR) and considerable diversity in complementarity-determining regions and D region sequences. Two functional JH genes or alleles are evident. Amino acid sequencing of the N-terminal 15 residues of pooled affinity-purified latent VHa1 H chain showed complete sequence identity with the nominal VHa1 sequences. Possible latent VHa1-encoding cDNA clones, derived from the a2a2 rabbit, were selected by hybridization with oligonucleotide probes corresponding to the VHa1 allotype-associated segments of the first and third framework regions (FR1 and FR3). cDNA sequence analysis reveals that the 5' untranslated regions of nominal and latent VHa1 cDNA were virtually identical to each other and to previously reported sequences associated with VHa2 and VHa-negative genes. Moreover, some latent VHa1 genes encode FR1 segments that are essentially homologous to the corresponding segment of a nominal VHa1 allotype. In contrast, other putative latent genes display blocks of VHa1 sequence in either FR1 or FR3 that are flanked by blocks of sequence identical to other rabbit VH genes (i.e., VHa2 or VHa-negative). These composite sequences may be directly encoded by composite germ-line VH genes or may be the products of somatically generated recombination or gene conversion between genes encoding latent and nominal allotypes. The data do not support the hypothesis that latent genes are the result of extensive modification by somatic point mutation.
Transmural dispersion of repolarization and the T wave (2001)

See article byTaggart et al. [50] ( pages 454-462) in or endocardium in response to a slowing of rate and / or in this issue.response to agents that normally prolong the action potential [3].These features of the M cell are due at least Studies conducted over the past dozen years or so have in part to the presence of a smaller slowly activating demonstrated that ventricular myocardium is not homoge-delayed rectifier current (I ) [15], a larger late sodium Ks neous, as previously thought, but is comprised of at least current (late I ) [1,16] and a larger sodium-calcium Na three electrophysiologically distinct cell types: epicardial, exchange current [17].The rapidly activating delayed M and endocardial cells (see [1,2] for reviews).These rectifier (I ) and inward rectifier (I ) currents appear to Kr
Optoelectronic holographic otoscope for measurement of nano-displacements in tympanic membranes (2009)

Current methodologies for characterizing tympanic membrane (TM) motion are usually limited to either average acoustic estimates (admittance or reflectance) or single-point mobility measurements, neither of which suffices to characterize the detailed mechanical response of the TM to sound. Furthermore, while acoustic and single-point measurements may aid in diagnosing some middle-ear disorders, they are not always useful. Measurements of the motion of the entire TM surface can provide more information than these other techniques and may be superior for diagnosing pathology. We present advances in our development of a new compact optoelectronic holographic otoscope (OEHO) system for full field-of-view characterization of nanometer-scale sound-induced displacements of the TM surface at video rates. The OEHO system consists of a fiber optic subsystem, a compact otoscope head, and a high-speed image processing computer with advanced software for recording and processing holographic images coupled to a computer-controlled sound-stimulation and recording system. A prototype OEHO system is in use in a medical research environment to address basic science questions regarding TM function. The prototype provides real-time observation of sound-induced TM displacement patterns over a broad frequency range. Representative time-averaged and stroboscopic holographic interferometry results in animals and human cadaver samples are shown, and their potential utility is discussed.
Selective peroxisome proliferator-activated receptorα modulators (SPPARMα): The next generation of peroxisome proliferator-activated receptor α-agonists (2013)

Dyslipidemia is a major risk factor for cardiovascular (CV) disease - the primary cause of death, worldwide. Although reducing levels of low-density lipoprotein-cholesterol can significantly reduce CV risk, a high level of residual risk persists, especially in people with obesity-related conditions, such as metabolic syndrome and type 2 diabetes mellitus. Peroxisome proliferator-activated receptor alpha- (PPARα-) agonists (e.g. fibrates), play a central role in the reduction of macro- and microvascular risk in these patients. However, the currently available fibrates are weak (PPARα-agonists) with limited efficacy due to dose-related adverse effects. To address this problem, a new generation of highly potent and selective PPARα-modulators (SPPARMα) is being developed that separate the benefits of the PPARα-agonists from their unwanted side effects. Among these, aleglitazar (a dual PPARα/γ agonist) and GFT505 (a dual PPAR α/δ agonist) have recently entered late-phase development. Although both compounds are more potent PPARα-activators than fenofibrate in vitro, only aleglitezar is more effective in lowering triglycerides and raising high-density lipoprotein-cholesterol (HDL-C) in humans. However, it is also associated with a potential risk of adverse effects. More recently, a highly potent, specific PPARα-agonist (K-877) has emerged with SPPARMα characteristics. Compared to fenofibrate, K-877 has more potent PPARα-activating efficacy in vitro, greater effects on triglycerides- and HDL-C levels in humans, and a reduced risk of adverse effects. If successful, K-877 has the potential to supersede the fibrates as the treatment of choice for patients with residual CV risk associated with metabolic syndrome and type 2 diabetes.
RNA polymerase β-subunit-based phylogeny of Ehrlichia spp., Anaplasma spp., Neorickettsia spp. and Wolbachia pipientis (2003)

Sequence analysis of rpoB, the gene encoding the beta-subunit of RNA polymerase, was used in a phylogenetic investigation of nine species from the genera Ehrlichia, Neorickettsia, Wolbachia and Anaplasma. The complete nucleotide sequences obtained for Anaplasma phagocytophilum (HGE agent), Ehrlichia chaffeensis, Neorickettsia sennetsu, Neorickettsia risticii, Anaplasma marginale and Wolbachia pipientis were amongst the longest rpoB sequences in GenBank and ranged from 4074 bp for N. sennetsu to 4311 bp for W. pipientis. Additional partial rpoB sequences were obtained for Ehrlichia canis, Ehrlichia ruminantium and Ehrlichia muris. Identical phylogenetic trees were inferred from multiple sequence alignments of the nucleotide sequences and the derived amino acid sequences using either distance, maximum-likelihood or parsimony methods. This study confirms the phylogeny previously inferred from sequence analyses of the 16S rRNA gene, groESL and gltA and allows the confirmation of four monophyletic clades. The rpoB nucleotide sequences were more variable than the 16S rRNA gene and groESL sequences at the species level.
Synthesis and Biological Evaluation of 14‐Alkoxymorphinans. Part 9. 14‐O‐ethyl‐5‐methylnaltrexone, and opioid antagonist with unusual selectivity (1993)

Abstract 14 O ‐Ethyl‐5m‐ethylnaloxone ( 7 ) and 14 O ‐ethyl‐5‐methylnaltrexone ( 8 ) have been prepared starting from 14 O ‐ethyl‐5‐methyloxycodone ( 9 ) in several steps. Both, 7 and 8 , were found to be opioid antagonists in vitro and in vivo . Compound 7 exhibited some selectivity for μ opioid receptors, whereas compound 8 did not show selectivity for any of the receptor types. In the AcOH‐writhing antagonism test, 8 was not able to antagonize morphine‐induced antinociception, but antagonized fentanyl‐ and sufentanil‐induced antinociception.
Peripheral Oxyntomodulin Reduces Food Intake and Body Weight Gain in Rats (2004)

Oxyntomodulin (OXM) is a circulating gut hormone released post prandially from cells of the gastrointestinal mucosa. Given intracerebroventricularly to rats, it inhibits food intake and promotes weight loss. Here we report that peripheral (ip) administration of OXM dose-dependently inhibited both fast-induced and dark-phase food intake without delaying gastric emptying. Peripheral OXM administration also inhibited fasting plasma ghrelin. In addition, there was a significant increase in c-fos immunoreactivity, a marker of neuronal activation, in the arcuate nucleus (ARC). OXM injected directly into the ARC caused a potent and sustained reduction in refeeding after a fast. The anorectic actions of ip OXM were blocked by prior intra-ARC administration of the glucagon-like peptide-1 (GLP-1) receptor antagonist, exendin(9-39), suggesting that the ARC, lacking a complete blood-brain barrier, could be a potential site of action for circulating OXM. The actions of ip GLP-1, however, were not blocked by prior intra-ARC administration of exendin(9-39), indicating the potential existence of different OXM and GLP-1 pathways. Seven-day ip administration of OXM caused a reduction in the rate of body weight gain and adiposity. Circulating OXM may have a role in the regulation of food intake and body weight.
CRISPR-Cas9 nuclear dynamics and target recognition in living cells (2016)

The bacterial CRISPR-Cas9 system has been repurposed for genome engineering, transcription modulation, and chromosome imaging in eukaryotic cells. However, the nuclear dynamics of clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) guide RNAs and target interrogation are not well defined in living cells. Here, we deployed a dual-color CRISPR system to directly measure the stability of both Cas9 and guide RNA. We found that Cas9 is essential for guide RNA stability and that the nuclear Cas9-guide RNA complex levels limit the targeting efficiency. Fluorescence recovery after photobleaching measurements revealed that single mismatches in the guide RNA seed sequence reduce the target residence time from >3 h to as low as <2 min in a nucleotide identity- and position-dependent manner. We further show that the duration of target residence correlates with cleavage activity. These results reveal that CRISPR discriminates between genuine versus mismatched targets for genome editing via radical alterations in residence time.