gebhart/patrepeval huggingface dataset:
A Phase I Study of Adenovirus-Mediated Wild-Type p53 Gene Transfer in Patients with Advanced Non-Small Cell Lung Cancer (1998)

Mutations of the tumor suppressor gene p53 are the most common genetic alterations observed in human cancer. Loss of wild-type p53 function impairs cell cycle arrest as well as repair mechanisms involved in response to DNA damage. Further, apoptotic pathways as induced by radio- or chemotherapy are also abrogated. Gene transfer of wild-type p53 was shown to reverse these deficiencies and to induce apoptosis in vitro and in preclinical in vivo tumor models. A phase I dose escalation study of a single intratumoral injection of a replication-defective adenoviral expression vector encoding wild-type p53 was carried out in patients with incurable non-small cell lung cancer. All patients enrolled had p53 protein overexpression as a marker of mutant p53 status in pretreatment tumor biopsies. Treatment was performed either by bronchoscopic intratumoral injection or by CT-guided percutaneous intratumoral injection of the vector solution. Fifteen patients were enrolled in two centers, and were treated at four different dose levels ranging from 107 to 1010 PFU (7.5 × 109 to 7.5 × 1012 particles). No clinically significant toxicity was observed. Successful transfer of wild-type p53 was achieved only with higher vector doses. Vector-specific wild-type p53 RNA sequences could be demonstrated in posttreatment biopsies of six patients. Transient local disease control by a single intratumoral injection of the vector solution was observed in four of those six successfully transduced patients. There was no evidence of clinical responses at untreated tumor sites. Wild-type p53 gene therapy by intratumoral injection of a replication-defective adenoviral expression vector is safe, feasible, and biologically effective in patients with advanced non-small cell lung cancer. Gene transfer of the human wild-type (wt) p53 tumor suppressor gene into p53 mutant tumors has been shown to have antiproliferative and apoptotic effects in vitro and in vivo. Schuler et al. report on a phase I clinical study of local wt p53 gene therapy in patients with advanced non-small cell lung cancer. A recombinant replication-deficient adenovirus carrying the complete human wt p53 cDNA under the control of the CMV immediate/early gene promoter was devised as expression vector. Gene transfer was achieved at higher virus doses without occurrence of any relevant treatment-related toxicity. In addition, clinical effects suggestive of a moderate local antiproliferative activity were observed in some patients.
Identification and cellular distribution of distinct proteins forming human GM-CSF receptor. (1990)

Two proteins forming the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF)1 were identified and characterized. One with apparent Mr of about 80,000 was defined as alpha-chain and has Kd of 0.7-2.8 nM. The other binding molecule with apparent Mr of about 135,000 was defined as beta-chain and is related to the high-affinity binding with Kd of 10-40 pM. The binding kinetic studies confirmed that the 125I-GM-CSF associated slower to and dissociated more rapidly from the alpha-chain than the beta-chain. The alpha-chain is expressed not only on hemopoietic cells but also on full-term placental tissues, choriocarcinoma cells, and other solid tumor cells. In contrast, the distribution of the beta-chain is restricted on hemopoietic cells. The alpha-chain probably corresponds to the low-affinity GM-CSF receptor whose cDNA has been cloned and sequenced.
Synthesis and Evaluation of Urea and Thiourea Derivatives of Oxazolidinones as Antibacterial Agents (2007)

Urea and thiourea derivatives of oxazolidinones were synthesized and their inhibitory activity (MIC) was determined on the bacterial strains which includes clinical isolates and quality control organisms. The structure activity relationships were studied and a 3D-QSAR model was built using Genetic Function Approximation. Interestingly found that electron withdrawing groups at the ortho position of the phenyl ring enhances the activity.
Challenges in the pursuit of immune tolerance (2011)

Strategies for inducing immune tolerance are fundamentally similar across a spectrum of immune-mediated disorders, including allergic disease, autoimmunity, and rejection of allografts. In each case, the objective of establishing an immunoregulatory balance is challenged by variable upswings in effector cell populations and proinflammatory mediators of immunity, requiring careful, and innovative therapeutic intervention to restore stability. The Immune Tolerance Network, an international consortium sponsored by the National Institutes of Health, seeks to advance both the scientific understanding and the clinical success of immune therapies for these disorders, through an innovative and collaborative effort involving clinical trials and mechanistic studies. Over the last decade, scientists have evaluated cell-based ablation and deviation strategies in trials using lymphocyte-specific targeting, induction of host-donor hematopoietic chimerism, induction of antigen-specific immune regulation, and a variety of antigen desensitization approaches. In this article, we review some of the highlights of this experience and discuss the potential for progress, utilizing new insights into regulatory mechanisms and biomarker signatures of tolerance.
Hepatic denervation impairs the assembly and secretion of VLDL‐TAG (2008)

VLDL secretion is a regulated process that depends on the availability of lipids, apoB and MTP. Our aim was to investigate the effect of liver denervation upon the secretion of VLDL and the expression of proteins involved in this process. Denervation was achieved by applying a 85% phenol solution onto the portal tract, while control animals were treated with 9% NaCl. VLDL secretion was evaluated by the Tyloxapol method. The hepatic concentration of TAG and cholesterol, and the plasma concentration of TAG, cholesterol, VLDL-TAG, VLDL-cholesterol and HDL-cholesterol were measured, as well as mRNA expression of proteins involved in the process of VLDL assembly. Hepatic acinar distribution of MTP and apoB was evaluated by immunohistochemistry. Denervation increased plasma concentration of cholesterol (125.3 +/- 10.1 vs. 67.1 +/- 4.9 mg dL(-1)) and VLDL-cholesterol (61.6 +/- 5.6 vs. 29.4 +/- 3.3 mg dL(-1)), but HDL-cholesterol was unchanged (45.5 +/- 6.1 vs. 36.9 +/- 3.9 mg dL(-1)). Secretion of VLDL-TAG (47.5 +/- 23.8 vs. 148.5 +/- 27.4 mg dL h(-1)) and mRNA expression of CPT I and apoB were reduced (p < 0.01) in the denervated animals. MTP and apoB acinar distribution was not altered in the denervated animals, but the intensity of the reaction was reduced in relation to controls.
The Microtubule Stabilizing Agent Laulimalide Does Not Bind in the Taxoid Site, Kills Cells Resistant to Paclitaxel and Epothilones, and May Not Require Its Epoxide Moiety for Activity (2002)

Laulimalide is a cytotoxic natural product that stabilizes microtubules. The compound enhances tubulin assembly, and laulimalide is quantitatively comparable to paclitaxel in its effects on the reaction. Laulimalide is also active in P-glycoprotein overexpressing cells, while isolaulimalide, a congener without the drug's epoxide moiety, was reported to have negligible cytotoxic and biochemical activity [Mooberry et al. (1999) Cancer Res. 59, 653-660]. We report here that laulimalide binds at a site on tubulin polymer that is distinct from the taxoid site. We found that laulimalide, while as active as paclitaxel, epothilone A, and eleutherobin in promoting the assembly of cold-stable microtubules, was unable to inhibit the binding of radiolabeled paclitaxel or of 7-O-[N-(2,7-difluoro-4'-fluoresceincarbonyl)-L-alanyl]paclitaxel, a fluorescent paclitaxel derivative, to tubulin. Confirming this observation, we demonstrated that microtubules formed in the presence of both laulimalide and paclitaxel contained near-molar quantities, relative to tubulin, of both drugs. Laulimalide was active against cell lines resistant to paclitaxel or epothilones A and B on the basis of mutations in the M40 human beta-tubulin gene. We also report that a laulimalide analogue lacking the epoxide moiety, while less active than laulimalide in biochemical and cellular systems, is probably more active than isolaulimalide. Further exploration of the role of the epoxide in the interaction of laulimalide with tubulin is therefore justified.
Nucleic Acid Sequence-Based Amplification Assays for Rapid Detection of West Nile and St. Louis Encephalitis Viruses (2001)

The development and application of nucleic acid sequence-based amplification (NASBA) assays for the detection of West Nile (WN) and St. Louis encephalitis (SLE) viruses are reported. Two unique detection formats were developed for the NASBA assays: a postamplification detection step with a virus-specific internal capture probe and electrochemiluminescence (NASBA-ECL assay) and a real-time assay with 6-carboxyfluorescein-labeled virus-specific molecular beacon probes (NASBA-beacon assay). The sensitivities and specificities of these NASBA assays were compared to those of a newly described standard reverse transcription (RT)-PCR and TaqMan assays for SLE virus and to a previously published TaqMan assay for WN virus. The NASBA assays demonstrated exceptional sensitivities and specificities compared to those of virus isolation, the TaqMan assays, and standard RT-PCR, with the NASBA-beacon assay yielding results in less than 1 h. These assays should be of utility in the diagnostic laboratory to complement existing diagnostic testing methodologies and as a tool in conducting flavivirus surveillance in the United States.
Site-directed mutagenesis of proteinase 3C results in a poliovirus deficient in synthesis of viral RNA polymerase (1987)

We used a synthetic double-stranded oligonucleotide to introduce amino acid substitutions into the proteinase 3C region of a poliovirus type 1 cDNA clone. The six different mutant viruses recovered exhibited a small-plaque phenotype when assayed on HeLa cells. Further investigation revealed that all the mutations (with the exception of one) yielded P3 region proteins that displayed altered mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A conservative Val----Ala change at amino acid 54 of the proteinase resulted in a virus that was deficient in the production of the mature viral RNA polymerase 3D. Although this mutant achieved less than one-half of the wild-type levels of RNA synthesis during the course of infection, it still grew to nearly wild-type titers.
Photothermally Enhanced Photodynamic Therapy Delivered by Nano-Graphene Oxide (2011)

Graphene with unique physical and chemical properties has shown various potential applications in biomedicine. In this work, a photosensitizer molecule, Chlorin e6 (Ce6), is loaded on polyethylene glycol (PEG)-functionalized graphene oxide (GO) via supramolecular π-π stacking. The obtained GO-PEG-Ce6 complex shows excellent water solubility and is able to generate cytotoxic singlet oxygen under light excitation for photodynamic therapy (PDT). Owing to the significantly enhanced intracellular trafficking of photosensitizers, our GO-PEG-Ce6 complex offers a remarkably improved cancer cell photodynamic destruction effect compared to free Ce6. More importantly, we show that the photothermal effect of graphene can be utilized to promote the delivery of Ce6 molecules by mild local heating when exposed to a near-infrared laser at a low power density, further enhancing the PDT efficacy against cancer cells. Our work highlights the promise of using graphene for potential multifunctional cancer therapies.
Oil Core/Polymer Shell Microcapsules by Internal Phase Separation from Emulsion Droplets. II:  Controlling the Release Profile of Active Molecules (2005)

Microcapsules with oil cores and solid polymer shells have been prepared by precipitation of the polymer from the internal phase of an oil-in-water emulsion. The dispersed phase consists of a polymer, a good solvent for the polymer (dichloromethane), and a poor solvent for the polymer (hexadecane). Removal of the good solvent results in phase separation of the polymer within the emulsion droplet, leading to the formation of a polymeric shell surrounding the poor solvent. A UV-active organic molecule is added to the oil phase prior to emulsification. Provided this molecule has some water solubility, the release profile of the molecule from the capsule can be determined. While the microcapsule size was kept approximately constant, the influence of a wide range of factors on the release profile has been studied. These include the type and molecular weight of the shell-forming polymer, the molecular weight of the active ingredient molecule, the shell thickness, the use of copolymers or polymer blends to form the shell, the effect of cross-linking the shell or heating the capsule to temperatures above the T(g) value of the polymer after the shell has been formed, and the effect of changes in the pH of the release solution in the case when a weak polyelectrolyte is used as the shell polymer. The differences in behavior are discussed in terms of the properties of the polymer shell, in particular the thickness, the polymer/release molecule interaction, and the free volume/porosity. Variation of these parameters allows one to control both the final release yield and the rate of release for time periods between a few hours and days.
Low density parity check codes based on finite geometries: a rediscovery (2002)

LDPC codes with iterative decoding based on belief propagation have been shown to achieve astonishing error performance. But no algebraic or geometric method has been found for constructing these codes. Codes that have been found are largely computer generated, especially long codes. In this paper, we present two classes of high rate LDPC codes whose constructions are based on the lines of two-dimensional finite Euclidean and projective geometries, respectively.
OPTIMAL PREDICTORS OF PROSTATE CANCER ON REPEAT PROSTATE BIOPSY: A PROSPECTIVE STUDY OF 1,051 MEN (2000)

At least 10% of patients with negative initial prostatic biopsy results will be diagnosed with prostate cancer on repeat biopsy. Percent free PSA and transition zone PSA density enhance the specificity of PSA testing compared to total PSA or PSA density when determining which patients should undergo repeat biopsy. Repeat biopsy should be performed in patients with percent free PSA less than 30% or transition zone PSA density 0.26 ng./ml./cc or greater. In our study percent free PSA was the most accurate predictor of prostate cancer in repeat biopsy specimens.
Receptor-Mediated Uptake of Antigen/Heat Shock Protein Complexes Results in Major Histocompatibility Complex Class I Antigen Presentation via Two Distinct Processing Pathways (1999)

Heat shock proteins (HSPs) derived from tumors or virally infected cells can stimulate antigen-specific CD8(+) T cell responses in vitro and in vivo. Although this antigenicity is known to arise from HSP-associated peptides presented to the immune system by major histocompatibility complex (MHC) class I molecules, the cell biology underlying this presentation process remains poorly understood. Here we show that HSP 70 binds to the surface of antigen presenting cells by a mechanism with the characteristics of a saturable receptor system. After this membrane interaction, processing and MHC class I presentation of the HSP-associated antigen can occur via either a cytosolic (transporter associated with antigen processing [TAP] and proteasome-dependent) or an endosomal (TAP and proteasome-independent) route, with the preferred pathway determined by the sequence context of the optimal antigenic peptide within the HSP-associated material. These findings not only characterize two highly efficient, specific pathways leading to the conversion of HSP-associated antigens into ligands for CD8(+) T cells, they also imply the existence of a mechanism for receptor-facilitated transmembrane transport of HSP or HSP-associated ligands from the plasma membrane or lumen of endosomes into the cytosol.
The Polyomavirus Enhancer Activates Chromatin Accessibility on Integration into the HPRT Gene (1992)

Recent studies suggest that enhancers may increase the accessibility of chromatin to transcription factors. To test the effects of a viral enhancer on chromatin accessibility, we have inserted minigenes with or without the polyomavirus enhancer into the third exon of the hypoxanthine phosphoribosyltransferase (HPRT) gene by homologous recombination and have prepared high-resolution maps of gene accessibility by using a novel polymerase chain reaction assay for DNase I sensitivity. In its native state, we find that the HPRT gene has low sensitivity to DNase I in fibrosarcoma cells. Insertion of the polyomavirus enhancer and neo reporter gene into exon 3 confers altered HPRT DNase I sensitivity for several kilobases on either side of the enhancer. The changes in DNase I sensitivity peak near the enhancer and decline with distance from the enhancer. The increase in HPRT DNase I sensitivity persisted when the tk promoter was deleted from the inserted construct but disappeared when the enhancer was deleted. These experiments identify the polyomavirus enhancer as a cis-acting initiator of chromatin accessibility.
Widespread Lewy body and tau accumulation in childhood and adult onset dystonia-parkinsonism cases with PLA2G6 mutations (2010)

The 2 major types of neurodegeneration with brain iron accumulation (NBIA) are the pantothenate kinase type 2 (PANK2)-associated neurodegeneration (PKAN) and NBIA2 or infantile neuroaxonal dystrophy (INAD) due to mutations in the phospholipase A2, group VI (PLA2G6) gene. We have recently demonstrated clinical heterogeneity in patients with mutations in the PLA2G6 gene by identifying a poorly defined subgroup of patients who present late with dystonia and parkinsonism. We report the clinical and genetic features of 7 cases with PLA2G6 mutations. Brain was available in 5 cases with an age of death ranging from 8 to 36 years and showed widespread alpha-synuclein-positive Lewy pathology, which was particularly severe in the neocortex, indicating that the Lewy pathology spread corresponded to Braak stage 6 and was that of the "diffuse neocortical type". In 3 cases there was hyperphosphorylated tau accumulation in both cellular processes as threads and neuronal perikarya as pretangles and neurofibrillary tangles. Later onset cases tended to have less tau involvement but still severe alpha-synuclein pathology. The clinical and neuropathological features clearly represent a link between PLA2G6 and parkinsonian disorders.
Abnormal glucose tolerance is a predictor of steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease (2005)

Both NASH and fibrosis are frequently present among patients with NAFLD and sustained elevation of LFT. The probability of these potentially progressive stages of NAFLD increases with the presence of abnormal glucose tolerance.
Sulforhodamine B interacts with albumin to lower surface tension and protect against ventilation injury of flooded alveoli (2014)

In the acute respiratory distress syndrome, alveolar flooding by proteinaceous edema liquid impairs gas exchange. Mechanical ventilation is used as a supportive therapy. In regions of the edematous lung, alveolar flooding is heterogeneous, and stress is concentrated in aerated alveoli. Ventilation exacerbates stress concentrations and injuriously overexpands aerated alveoli. Injury degree is proportional to surface tension, T. Lowering T directly lessens injury. Furthermore, as heterogeneous flooding causes the stress concentrations, promoting equitable liquid distribution between alveoli should, indirectly, lessen injury. We present a new theoretical analysis suggesting that liquid is trapped in discrete alveoli by a pressure barrier that is proportional to T. Experimentally, we identify two rhodamine dyes, sulforhodamine B and rhodamine WT, as surface active in albumin solution and investigate whether the dyes lessen ventilation injury. In the isolated rat lung, we micropuncture a surface alveolus, instill albumin solution, and obtain an area with heterogeneous alveolar flooding. We demonstrate that rhodamine dye addition lowers T, reduces ventilation-induced injury, and facilitates liquid escape from flooded alveoli. In vitro we show that rhodamine dye is directly surface active in albumin solution. We identify sulforhodamine B as a potential new therapeutic agent for the treatment of the acute respiratory distress syndrome.
Insulin and Ketone Responses to Ingestion of Medium and Long-chain Triglycerides in Man (1969)

The effects of medium chain triglyceride (MCT), corn oil, and water on serum glucose, ketones, and immunoreactive insulin (IRI) were compared. Fourteen normal subjects ingested 1 gm. per kg. of MCT (composed principally of C8 and CIO fatty acids) and on another occasion an equal volume of water. After water ingestion, glucose, ketones, and IRI did not change appreciably up to five hours. After MCT, a significant rise in serum ketones and IRI was associated with a slight fall in serum glucose. Fourteen normal subjects ingested 1 gm. per kg. corn oil, and on another occasion an equal volume of water. Serum glucose, ketone and IRI concentrations again did not change up to five hours after ingestion of water. After corn oil, no significant rise in ketones occurred. There was a small rise in IRI and a slight fall in glucose. In the eight subjects in whom MCT, corn oil and water were compared a certain degree of insulin secretory response was obtained after MCT and corn oil but not after water ingestion. However, the IRI response after MCT was highest. The rise in IRI without a corresponding change in serum ketones after ingestion of the long chain triglyceride might be attributed to a gastrointestinal β-cytotropic effect. The mechanism of IRI stimulation by MCT also has been related to MCT-induced hyperketonemia and possibly toa direct effect on insulin secretion of small amounts of octanoate in peripheral blood.
Integrating Combinatorial Synthesis and Bioassays (2000)

The increasing demand for large chemical libraries of potential drug candidates is accompanied by the need for efficient methods for identifying biologically active compounds in these libraries. In this TechView, Rademann and Jung (p.
 1947) discuss strategies for creating efficient interfaces between combinatorial synthesis and screening and hereby extracting biologically relevant information from libraries of chemical compounds.
Temporal Pooling And Multiscale Learning For Automatic Annotation And Ranking Of Music Audio. (2011)

[TODO] Add abstract here.