gebhart/patrepeval huggingface dataset:
Neovasculature induced by vascular endothelial growth factor is fenestrated. (1997)

We have reported previously that topical administration of vascular endothelial growth factor165 (VEGF) to a microvascular bed supplied with a continuous endothelium can rapidly induce the formation of endothelial fenestrations (W. G. Roberts and G. E. Palade, J. Cell Sci., 108: 2369-2379, 1995). From these results, we hypothesized that tumor vasculature, in general, may also be fenestrated because it has been reported that tumor secretion of VEGF causes the surrounding host vasculature to invade and feed the growing tumor. Using electron microscopy to characterize the endothelial cell morphology in tumor vessels from either the periphery or the core of the tumor and immunoblotting to detect secreted VEGF, we analyzed the vasculature of human and murine neoplastic tumors grown s.c. in male nude mice. To clarify the role of VEGF165 two models were used: (a) Chinese hamster ovary (CHO) cells stably transfected with hu VEGF165 and injected into mice (VEGF:CHO tumors); and (b) slow-release pellets containing purified VEGF or basic fibroblast growth factor implanted on the rat cremaster muscle. All tumors had vessels with fenestrated endothelium, open interendothelial junctions, and clustered fused caveolae. From all of the peripheral tumor vessels observed, fenestrated endothelium was observed in 41% from EMT, 35% from M1S, 37% from U87, and 56% from VEGF:CHO tumors, whereas surrounding skin and muscle, from which tumor vessels were derived, had fenestrated endothelium in 2 and 0% of all vessels, respectively. Additionally, further analysis revealed a substantial decrease in the anionic glycocalyx on the luminal face of the fenestral diaphragms in endothelium from tumors (especially VEGF:CHO) when compared to intestine or pancreas. Because the host tissue microvascular endothelium which supplies the tumor is not fenestrated, tumors can transform nonproliferating, nonfenestrated vessels into proliferating vessels, many of which have fenestrated endothelium. These data provide evidence that chronic VEGF exposure can induce fenestrations in nonfenestrated endothelium similar to the fenestrated endothelium found in tumor vessels.
Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. (1995)

Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells. We show that both HIF-1 subunits are basic-helix-loop-helix proteins containing a PAS domain, defined by its presence in the Drosophila Per and Sim proteins and in the mammalian ARNT and AHR proteins. HIF-1 alpha is most closely related to Sim. HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. HIF-1 alpha and HIF-1 beta (ARNT) RNA and protein levels were induced in cells exposed to 1% O2 and decayed rapidly upon return of the cells to 20% O2, consistent with the role of HIF-1 as a mediator of transcriptional responses to hypoxia.
CMV-β-Actin Promoter Directs Higher Expression from an Adeno-Associated Viral Vector in the Liver than the Cytomegalovirus or Elongation Factor 1α Promoter and Results in Therapeutic Levels of Human Factor X in Mice (2001)

Although AAV vectors show promise for hepatic gene therapy, the optimal transcriptional regulatory elements have not yet been identified. In this study, we show that an AAV vector with the CMV enhancer/chicken beta-actin promoter results in 9.5-fold higher expression after portal vein injection than an AAV vector with the EF1 alpha promoter, and 137-fold higher expression than an AAV vector with the CMV promoter/enhancer. Although induction of the acute-phase response with the administration of lipopolysaccharide (LPS) activated the CMV promoter/enhancer from the context of an adenoviral vector in a previous study, LPS resulted in only a modest induction of this promoter from an AAV vector in vivo. An AAV vector with the CMV-beta-actin promoter upstream of the coagulation protein human factor X (hFX) was injected intravenously into neonatal mice. This resulted in expression of hFX at 548 ng/ml (6.8% of normal) for up to 1.2 years, and 0.6 copies of AAV vector per diploid genome in the liver at the time of sacrifice. Neonatal intramuscular injection resulted in expression of hFX at 248 ng/ml (3.1% of normal), which derived from both liver and muscle. We conclude that neonatal gene therapy with an AAV vector with the CMV-beta-actin promoter might correct hemophilia due to hFX deficiency.
Extension of the fragment method to calculate amino acid zwitterion and side chain partition coefficients (1987)

The fragment method of calculating partition coefficients (P) has been extended to include the common amino acids (AAs). The results indicate that polar and charged side chains influence the hydrophobicity of atoms in the side chain in a predictable manner. Field effects, as evidenced through polar proximity factors and bond factors, need to be considered for accurate estimation of transfer phenomena. The calculated log P and delta G degree ' values of the 20 AAs agree well with the observed values. Pro calculates to be more hydrophilic than the observed log P. Hydrophobicity scales for peptide side chain residues are compared and evaluated in terms of suitability. Calculated pi values for nonpolar side chain residues agree well with the observed values; calculated values for uncharged polar side chain residues deviate by about 0.6 log units except for Gln and Cys; and polar side chain residues with charged side chains calculate as too hydrophilic. Reasons for the differences are explored. We also suggest that tightly bound water to polar moieties in amino acids and peptides may be transferred into the octanol phase during partitioning experiments. A quantitative methodology is presented which characterizes the thermodynamic partitioning of groups and individual atoms in amino acids and proteins.
Artifact-resistant power-efficient design of finger-ring plethysmographic sensors (2001)

A miniaturized, telemetric, photoplethysmograph (PPG) sensor for long-term, continuous monitoring is presented in this paper. The sensor, called a "ring sensor," is attached to a finger base for monitoring beat-to-beat pulsation, and the data is sent to a host computer via a radio-frequency transmitter. Two major design issues are addressed: one is to minimize motion artifact and the other is to minimize the consumption of battery power. An efficient double ring design is developed to lower the influence of external force, acceleration, and ambient light, and to hold the sensor gently and securely on the skin, so that the circulation at the finger may not be obstructed. Total power consumption is analyzed in relation to characteristics of individual components, sampling rate, and CPU clock speed. Optimal operating conditions are obtained for minimizing the power budget. A prototype ring sensor is designed and built based on the power budget analysis and the artifact-resistive attachment method. It is verified through experiments that the ring sensor is resistant to interfering forces and acceleration acting on the ring body. Benchmarking tests with FDA-approved PPG and electrocardiogram reveal that the ring sensor is comparable to those devices in detecting beat-to-beat pulsation despite disturbances.
Structure-Function Studies of Two Synthetic Anti-vascular Endothelial Growth Factor Fabs and Comparison with the Avastin™ Fab (2005)

In the quest to discover new research tools and to develop better agents in the fight against cancer, two antibodies, G6 and B20-4, were isolated from synthetic antibody phage libraries. Unlike the AVASTINtrade mark antibody, a recently approved agent for the treatment of patients with colorectal cancer, B20-4 and G6 bind and block both human and murine vascular endothelial growth factor (VEGF). Here we have analyzed and compared the binding epitopes on VEGF for these three antibodies using alanine-scanning mutagenesis and structural analyses. The epitopes recognized by both synthetic antibodies are conserved between human and mouse VEGF, and they match closely to the receptor epitopes both structurally and functionally. In contrast, the Avastin epitope overlaps minimally with the receptor binding surface and centers around a residue that is not conserved in mouse. Our structural and functional analyses elucidate the cross-species reactivity of all three antibodies and emphasize the potential advantages of antibody generation using phage display as the resulting antibodies do not depend on sequence differences across species and preferentially target natural protein-protein interaction surfaces.
Quantitation and biological activities of native tumour necrosis factor from LPS‐stimulated human monocytes (1990)

Human mononuclear cells (MNC) were stimulated in culture with LPS to produce tumour necrosis factor (TNF). The natural tumour necrosis factor (nTNF) was quantitated by ELISA and immunoblotting using rabbit antibodies to human recombinant TNF (rTNF) and the biotin-avidin-peroxidase system. Biologically active nTNF was determined by its cytotoxic activity for actinomycin-D treated mouse fibroblasts and by its lethal effect in D-galactosamine sensitized endotoxin-resistant mice. Two different LPS preparations (Salmonella abortus equi and Pseudomonas aeruginosa) induced the formation of comparable amounts of nTNF. MNC from different donors, however, showed large variations in their ability to produce nTNF. The amount of nTNF induced in response to LPS could be enhanced by priming the MNC with interferon. The amounts of nTNF determined by ELISA generally correlated well with the activity of the nTNF in the two biological assays. On a weight basis, the lethal activity of nTNF in D-galactosamine treated mice was very similar to that of human rTNF. Immunoblotting revealed a single band of nTNF with the same molecular weight (17 kD) as human rTNF. The lethality induced by nTNF was inhibited by rabbit anti-human rTNF antibodies.
Fermentative production of L-glutamine by sulfaguanidine resistant mutants derived from L-glutamate producing bacteria. (1987)

Excellent L-glutamine producers were screened for among sulfaguanidine resistant mutants derived from the wild type L-glutamic acid-producing bacteria, Brevibacterium flavum, Brevibacterium lactofermentum, Corynebacterium glutamicum and Microbacterium ammoniaphilum. The best strain, No. 1-60, was a sulfaguanidine resistant mutant derived from B. flavum 2247 by mutation. Strain No. 1-60 accumulated 41.0mg/ml of L-glutamine after 48 hr of cultivation from 10% glucose as a carbon source. This yield was the highest among those so far reported. The addition of Mn2+ (2ppm) to the standard medium for B. flavum 2241 decreased the L-glutamine production and increased the L-glutamic acid excretion markedly. On the contrary, strain 1-60 was not affected the Mn2+ (2ppm) addition at all. Glutamate kinase activity and the intracellular content of ATP in sulfaguanidine resistant mutant No. 1-60 were higher than those in the parent strain, B. flavum 2247. It was confirmed that the increase in glutamate kinase and the increase in internal ATP, which were important for the L-glutamine synthesis, were very effective for the improvement of L-glutamine-producing mutants.
Minocycline therapy in acne vulgaris. (1976)

A double-blind, random distribution study showed that a lower than recommended dose of minocycline--50 mg twice daily--was as effective as a dose of 250 mg twice daily of tetracycline for treatment of acne vulgaris in comparable patient groups, and that minocycline produced no vestibular side effects at the lower dosage. Like tetracycline, minocycline did not produce the phototoxicity associated with demeclocycline or the life-threatening colitis associated with clindamycin. Patients in this study did not develop a resistance either to minocycline or to tetracycline. Studies of the use of minocycline in patients who have developed tetracycline resistance and long-range studies of patients on the new lower dose of minocycline are now underway.
Multiplexing of Extrinsic Fabry-Perot Optical Fiber Sensors for Strain Measurements (2003)

Elevators are a necessary component of the modern urban and suburban life. The guide rails the car and counterweight move on are the most sensitive parts when it comes to de-habilitating damage that can be caused by an earthquake. Conventional sensors are becoming obsolete in sensing for today’s multistory buildings because they don’t monitor the structural health of the guide rails. This sensing task falls into the fiber sensing niche market because of a fiber sensor’s ability to be multiplexed. Previous work by Taplin and Jackson showed demodulation of the interference spectrum of two Fabry-Perot cavities using Fourier analysis. The goal of this thesis research is to use Fourier analysis to demodulate the spectrum of multiplexed extrinsic Fabry-Perot fiber interferometers for strain measurements. Comparisons of fiber, foil, and theoretical strains are made. Also, experiments showing the system’s air-gap stability and crosstalk are provided.
Efficacy of Topical Treatment of Pigmentation Skin Disorders with Plant Hydroquinone Glucosides as Assessed by Quantitative Color Analysis (1998)

Hydroquinone is a well known reagent used in the treatment of pigmentation disorders. The instability of the quinones and the required active concentration make topical treatment rather difficult. We tested the efficacy of an ascorbate-phytohydroquinone complex that inhibits the synthesis of melanin and promotes the degradation of the existing melanin. Lentigo senile lesions were evaluated before and after 1 month of treatment. Objective skin color evaluation was performed instrumentally. After one month of treatment, a clear depigmentation of the macules was measured. None of the volunteers reported any side effects from the prolonged treatment with the hydroquinone containing product.
Invited Review: Molecular mechanisms of phenotypic plasticity in smooth muscle cells (2001)

Morphological, functional, molecular and cell biology studies have revealed a striking multifunctional nature of individual smooth muscle cells (SMC). SMCs manifest phenotypic plasticity in response to changes in environment and functional requirements, acquiring a range of structural and functional properties bounded by two extremes, called "synthetic" and "contractile." Each phenotypic state is characterized by expression of a unique set of structural, contractile, and receptor proteins and isoforms that correlate with differing patterns of gene expression. Recent studies have identified signaling pathways and transcription factors (e.g., RhoA GTPase/ROCK, also known as Rho kinase, and serum response factor) that regulate the transcriptional activities of genes encoding proteins associated with the contractile apparatus. Mechanical plasticity of contractile-state smooth muscle further extends SMC functional diversity. This may also be regulated, in part, by the RhoA GTPase/ROCK pathway, via reorganization of cytoskeletal and contractile proteins. Future studies that define transcriptional and posttranscriptional mechanisms of SMC plasticity are necessary to fully understand the role of SMC in the pathogenesis and morbidity of human diseases of the airways, vasculature, and gastrointestinal tract.
Bronchial thermoplasty for asthma: A critical review of a new therapy (2008)

Bronchial thermoplasty (BT) is a novel experimental procedure involving the application of controlled heat from a radiofrequency source to the airway wall as a means to reduce airway smooth muscle in the airway wall. After BT was shown to reduce airway smooth muscle in preclinical studies in dogs, clinical studies in humans revealed that BT resulted in a significant improvement in asthma outcomes including mild asthma exacerbations, asthma symptom-free days, asthma rescue medication use, and airway hyperresponsiveness as measured by methacholine PC(20). A second trial in humans revealed that BT was safe and effective in patients with severe asthma refractory to the current standard of care. While current trials are ongoing, BT holds promise as an exciting novel therapy in the management of patients with asthma.
Brain-derived Neurotrophic Factor Improved Insulin Sensitivity in Obese Fatty (fa/fa) Zncker Rats (2002)

it is thought that all type 2 diabetic patients usually pass through a phase of impaired glucose tolerance (IGT) before developing diabetes. Since patients with IGT have high risk of developing type 2 diabetes as well as cardiovascular diseases, it is very important to manage such reversible disease state to prevent more serious diseases. We and others reported that peripheral injection of brain-derived neurotrophic factor (BDNF) exhibits hypophagic and hypoglycemic effects in obese hyperglycemic animals, indicating its antiobesity and antidiabetic effects. BDNF belongs to a family of neurotropl1ins and plays a crucial role in the survival and differentiation of central and peripheral neurons. To evaluate the effect of BDNF on insulin sensitivity in Zucker fatty (ZF) rats, animal models of IGT, we applied the glucose clamp technique. Chronic treatment with BDNF significantly improved insulin sensitivity of ZF rats, as determined by the increase in glucose infusion rates to maintain euglycemia under hyperinsulinemic condition. The result showed for the first time that BDNF improved insulin sensitivity in an animal model of IGT as well as overt diabetes. \ Type 2 diabetes is well recognized to be one of the major health problems in many civilized countries.
Targeting microglia for the treatment of Alzheimer’s disease (2014)

A hopeful approach to a disease-modifying treatment of AD is to administer agents that inhibit the inflammatory stimulation of microglia or successfully convert them to an M2 state. However, any such treatment must be started early in the disease.
Über die Synthese 9‐substituierter Purinderivate. I. Die Darstellung 2,9‐; 2,6,9‐ und 6,9‐substituierter Purine (1961)

Abstract Es wird über die Synthese einiger neuer 9‐substituierter Purinderivate berichtet, die von Pyrimidinabkömmlingen ausgeht, die in 4‐Stellung eine sekundäre Aminogruppe tragen. Gleichzeitig sind Substituenten in den Stellungen 2; 2,6 oder 6 vorhanden.
Oncogene amplification correlates with dense lymphocyte infiltration in human breast cancers: A role for hematopoietic growth factor release by tumor cells? (1990)

One hundred six primary breast cancer samples were analysed for c-erbB2, int-2, and c-myc gene amplification. Surgically confirmed nodal involvement was observed in 42%. Level of gene amplification was studied by Southern and/or slot blot techniques. Amplified c-erbB2 gene sequences were present in 21.5% of all samples. Int-2 was amplified in 13.1% and c-myc was amplified in 10.3%. In a non-parametric test (Kruskal-Wallis) a strong negative association was found between high levels of c-erbB2 amplification and absence of estrogen receptor (ER) (P = .0009) or progesterone receptor (PR) (P = .011) expression. No correlations were found between all or high levels of amplification of each oncogene separately or combined with T, N, grade, multifocality of tumor, or associated carcinoma in situ. There was a trend approaching statistical significance for patients with c-erbB2 amplifications to have positive lymph nodes at surgery (P = 0.09). A somewhat surprising finding however was a very strong association between oncogene amplification and dense lymphocyte infiltration of the tumor (P = .05). This correlation is even stronger when only high levels of amplification are considered, either for each oncogene separately (P = .0048) or in combination (P = .0007). We propose that malignant cell cytokine production may help explain this observation.
Structures of herpes simplex virus type 1 genes required for replication of virus DNA (1988)

Recently, a method has been developed to identify regions in the genome of herpes simplex virus type 1 (HSV-1) which contain genes required for DNA synthesis from an HSV-1 origin of DNA replication, and seven genomic loci have been identified as representing the necessary and sufficient gene set for such replication (C. A. Wu, N. J. Nelson, D. J. McGeoch, and M. D. Challberg, J. Virol. 62:435-443, 1988). Two of the loci represent the well-known genes for DNA polymerase and major DNA-binding protein, but the remainder had little or no previous characterization. In this report we present the DNA sequences of the five newly identified genes and their deduced transcript organizations and encoded amino acid sequences. These genes were designated UL5, UL8, UL9, UL42, and UL52 and were predicted to encode proteins with molecular weights of, respectively, 99,000, 80,000, 94,000, 51,000, and 114,000. All of these genes had clear counterparts in the genome of the related alphaherpesvirus varicella-zoster virus, but only UL5 and UL52 were detectably conserved in the distantly related gammaherpesvirus Epstein-Barr virus, as judged by amino acid sequence similarity. The sequence of the UL5 protein, and of its counterparts in the other viruses, contained a region closely resembling known ATP-binding sites; this could be indicative, for instance, of a helicase or primase activity.
Anti-G(D2) antibody treatment of minimal residual stage 4 neuroblastoma diagnosed at more than 1 year of age. (1998)

Despite high-risk nature of stage 4 NB, long-term remission without autologous (A)BMT can be achieved with 3F8 treatment. Its side effects were short-lived and manageable. The potential benefits of 3F8 in consolidating remission warrant further investigations.
Early and late ovarian hyperstimulation syndrome: early pregnancy outcome and profile (2004)

The early OHSS pattern is associated with exogenously administered HCG and a higher risk of preclinical miscarriage, whereas late OHSS may be closely associated with the conception cycles, especially multiple pregnancies, and is more likely to be severe. Further clarification of these two different clinical entities could have implications for research protocols as well as for preventive and management strategies for OHSS.
Selection of optical biosensors from chemisynthetic antibody libraries (2004)

We describe a method for creating antibodies with a fluorescent reporter integrated into the antigen-binding site. A reporter molecule was chemically linked to a hypervariable loop of an antibody repertoire displayed on phage, and this repertoire was selected for antigen binding. In one selected antibody, the fluorescence of the probe responded quantitatively to antigen binding. The method may have application for the engineering of homogeneous immunoassays.
评马克思主义对《纯粹理性批判》的理解 (1981)

1.关于哲学的“性质、方法和概念”,在最近一百五十年的哲学史上有过许多争论。元哲学讨论占去了哲学思考和反哲学思考的一大部分时间。这有时就被解释为“哲学的终结”(海德格尔语)或一种“神经病”(赖尔语)。除了这些评价之外,这些讨论对于阐明作为活动的哲学的性质,是富有成果的和必要的。这种元哲学反思的一个重要方面,是说明什么是哲学问题这样一个问题。哲学家们的众所周知的不一致,也扩及到这个问题上来。但不管他们采取什么理论立