gebhart/patrepeval huggingface dataset:
The Role of Natural Products in the Discovery of New Drug Candidates for the Treatment of Neurodegenerative Disorders II: Alzheimers Disease (2011)

Neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS) are currently incurable pathologies with huge social and economic impacts closely related to the increasing of life expectancy in modern times. Although the clinical and neuropathological aspects of these debilitating disorders are distinct, they share a pattern of neurodegeneration in anatomically or functionally related regions. For each disease, presently available treatments only address symptoms and do not alter the course or progression of the underlying diseases. In this context, the search for new effective chemical entities, capable of acting on diverse biochemical targets, with new mechanisms of action and low toxicity are genuine challenges to research groups and the pharmaceutical industry. This medical need has led to the reemerging of modern natural products chemistry that has yielded sophisticated and complex new lead molecules for drug discovery and development. In this review we discuss some of the main contributions of the natural products chemistry that covers multiple and varied plant species. Advances in the discovery of active constituents of plants, herbs, and extracts prescribed by traditional medicine practices for the treatment of senile neurodegenerative disorders, especially for PD, in the period after the 2000s is reviewed. The most important contributions from the 1990s are also discussed. The review also focuses on the pharmacological mechanisms of action that might underlie the purported beneficial improvements in memory and cognition, neurovascular function, and in neuroprotection. It is concluded that natural product chemistry brings tremendous diversity and historical precedent to a huge area of unmet medical need.
Mechanism of gallium-67 accumulation in tumors. (1986)

Neoplasms are characterized by increased perfusion, increased permeability of their capillary beds to macromolecules, and a delay in new lymphatic vessel growth. These lead to the increased entry and residency time of macromolecules in the interstitial space of tumors. Multiple factors contribute to the localization of 67Ga in tumors. Adequate blood supply is essential; at areas with no blood supply such as the necrotic center of a large tumor, there is no 67Ga accumulation. Gallium-67, mainly in the form of transferrin-67Ga complex, is delivered to the tumor through capillaries with increased permeability. In tumors, some 67Ga is taken up by tumor cells; some may also be taken up by inflammatory cells when they are present. Gallium-67 binding proteins, such as lactoferrin or ferritin, may also contribute to the accumulation and retention of 67Ga in tumors; however, their roles are less clear. The intensity of these various factors determine their relative contribution and the degree of 67Ga accumulation in tumors.
[Neoadjuvant Chemotherapy in breast cancer]. (2006)

Neoadjuvant chemotherapy for breast cancer was originally used in locally advanced inoperable disease in order to achieve surgical resection. It was then extended to operable breast cancer with a view to downstaging tumors to facilitate breast-conserving surgery. Long-term results from randomized studies have shown no difference in disease-free or overall survival between neoadjuvant and adjuvant chemotherapy. The main benefit of neoadjuvant chemotherapy is its ability to downstage large tumors with a view to treatment by breast-conserving surgery. Since pathological complete response is thought to be main factor to achieve long-term survival, development of new agent or novel combination treatment is needed.
<title>Boeing active flow control system (BAFCS)-III</title> (2002)

The Boeing Active Flow Control (AFC) System is a DARPA sponsored program to develop AFC technology to achieve a significant increase in payload and/or range for rotorcraft applications such as the V-22 tiltrotor vehicle. The program includes Computational Fluid Dynamics analysis, 0.1 scale wind tunnel and 3D testing and development of smart material based AFC actuators. This paper will provide an overview of the program, concentrating on the development and testing of the AFC actuators, and is an update of references to 1 to 3.
Regulation of the Flavin Redox Potential by Flavin‐Binding Antibodies (1997)

Single-chain Fv antibody fragments binding different flavin forms [10-(5'-carboxybutyl-)flavin (Fl[ox]) and 10-(5'-carboxybutyl)-1,5-dihydroflavin (Fl[red])] have been generated from an antibody phage-display library to study how a protein environment regulates the redox potential, starting from a protein other than a natural flavoprotein. These 'flavobodies' are characterized by time-resolved and steady-state fluorescence spectroscopy, by competitive ELISA methods (mapping of the antigen-binding site), and by molecular modelling. The three-dimensional models of the antigen-binding sites are consistent with the experimental results. Binding of anti-Fl(red) 5 to flavin increases the redox potential, mainly due to an Arg residue interacting with the flavin N1. Thus anti-Fl(red) 5 shows an 'oxidase-like' redox-potential behaviour, confirming the idea that positively charged residues in the vicinity of N1 increase the redox potential. The results obtained with anti-Fl(ox), which do not resemble a natural flavoprotein, show that when the pyrimidine-like nucleus of the flavin is not involved in binding, the redox potential is not significantly affected. These results are in contrast to those obtained with chicken riboflavin-binding protein.
Sunitinib‐induced changes in circulating endothelial cell‐related proteins in patients with metastatic renal cell cancer (2011)

Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors are effective agents in the treatment of metastatic renal cell cancer (mRCC). We here investigated whether inhibition of VEGFR signalin by sunitinib causes changes in plasma proteins associated with tumor endothelium. Forty-three patients with mRCC received sunitinib 50 mg/day in a 4-weeks on 2-weeks off schedule. Sequential plasma samples were obtained before treatment (C1D1), on C1D14, on C1D28, and on C2D1 before start of cycle 2. Plasma levels were assessed for VEGF, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), von Willebrand factor (vWF), circulating angiopoietin-2 (Ang-2) and soluble Tie-2 (sTie-2). Total tumor burden was calculated at baseline and at first evaluation. Progression-free survival (PFS) and overall survival (OS) were determined. Tumor burden was positively associated with baseline circulating Ang-2 [Spearman's rho (ρ) = 0.378, p = 0.028] and vWF (ρ = 0.417, p = 0.008). During sunitinib treatment, circulating Ang-2 and sTie-2 significantly decreased (p < 0.001 for both), plasma levels of sVCAM-1 and VEGF significantly increased (p = 0.022 and p < 0.001), whereas those of sICAM-1 and vWF remained stable. These protein changes had recovered on C2D1. The reduction in circulating Ang-2 levels on C1D28 was positively correlated with the percentage decrease in tumor burden (ρ = 0.605; p = 0.002). Baseline protein levels and subsequent changes were not associated with PFS or OS. In conclusion, sunitinib-induced changes in Ang-2, sTie-2, sVCAM-1 and VEGF are related to the administration schedule, while reduction in Ang-2 is also associated with decrease in tumor burden.
Genetics and New Treatment Modalities for Familial Mediterranean Fever (2007)

Familial Mediterranean fever (FMF) is the most common of a rare group of disorders collectively termed familial hereditary periodic fever syndromes, also known as autoinflammatory syndromes. FMF is clinically characterized by intermittent bouts of fever with peritonitis and abdominal pain, pleuritis, arthritis, or erysipelas-like rashes. Amyloidosis due to chronic inflammation progressing to renal failure is one of the most serious potential complications of this disease. Individuals with FMF have identifiable genetic defects in the Mediterranean fever (MEFV) gene, which codes for the protein pyrin. Pyrin normally blunts neutrophil-mediated inflammation, likely via interleukin-1 (IL-1) downregulation, but is defective in FMF. Potential treatments include colchicine, with case reports of benefits with catecholamine blockade (prazosin), tumor necrosis factor (TNF) antagonism (etanercept, thalidomide), and IL-1 receptor blockade (anakinra).
Magnetic Resonance Elastography of the Liver in Patients Status-Post Fontan Procedure: Feasibility and Preliminary Results (2013)

Our preliminary findings suggest that MRE is a feasible method for evaluating the liver in Fontan patients who are undergoing surveillance cardiac MRI. Further investigation with histologic correlation is needed to determine the contributions of hepatic congestion and fibrosis to the liver stiffness in this population.
Report from the 4th International Meeting of the Attention Deficit Hyperactivity Disorder Molecular Genetics Network (2003)

Investigators from around the world have convened annually since 1999 to share their work on the molecular genetic basis of attention deficit hyperactivity disorder (ADHD). The 4th meeting of the ADHD Molecular Genetics Network was held in May 2002. This conference began with a discussion of ongoing and proposed collaborative projects. Ongoing collaborations include the International Multi-Center ADHD Genetics (IMAGE) project, a study of additive and interactive effects of DAT1 and DRD4 on ADHD and a meta-analysis of association studies of ADHD and the DRD5 gene. A new collaborative project regarding DNA pooling was also proposed. Over 20 investigators presented recent findings from their individual research sites. Participants also broke up into working groups to discuss additional projects and topics of mutual interest, including population genetic studies using dimensional phenotypic data and a QTL approach, endophenotypes for ADHD and the genetics of ADHD in adults. Finally, participant feedback was obtained about the utility of the ADHD Molecular Genetics Network conferences and the e-mail network. Although technological and statistical advances in the field of molecular genetics have allowed researchers to begin to identify specific genes that are associated with ADHD, continued collaborative efforts are needed to fully elucidate the genetic underpinnings of this complex phenotype. Data collected at the current conference indicate that the ADHD Molecular Genetics Network has facilitated new collaborative as well as single-site projects among ADHD researchers.
Discovery of<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mmultiscripts><mml:mi>Xe</mml:mi><mml:mprescripts/><mml:none/><mml:mn>109</mml:mn></mml:mmultiscripts></mml:math>and<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mmultiscripts><mml:mi>Te</mml:mi><mml:mprescripts/><mml:none/><mml:mn>105</mml:mn></mml:mmultiscripts></mml:math>: Superallowed<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mi>α</mml:mi></mml:math>Decay near Doubly Magic<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mmultiscripts><mml:mi>Sn</mml:mi><mml:mprescripts/><mml:none/><mml:mn>100</mml:mn></mml:mmultiscripts></mml:math> (2006)

Two new alpha emitters 109Xe and 105Te were identified through the observation of the 109Xe --> 105Te --> 101Sn alpha-decay chain. The 109Xe nuclei were produced in the fusion-evaporation reaction 54Fe(58Ni,3n)109Xe and studied using the Recoil Mass Spectrometer at the Holifield Radioactive Ion Beam Facility. Two transitions at Ealpha = 4062 +/- 7 keV and Ealpha = 3918 +/- 9 keV were interpreted as the l = 2 and l = 0 transitions from the 7/2+ ground state in 109Xe (T1/2 = 13 +/- 2 ms) to the 5/2+ ground state and a 7/2+ excited state, located at 150 +/- 13 keV in 105Te. The observation of the subsequent decay of 105Te marks the discovery of the lightest known alpha-decaying nucleus. The measured transition energy Ealpha = 4703 +/- 5 keV and half-life T1/2 = 620 +/- 70 ns were used to determine the reduced alpha-decay width delta2. The ratio delta105Te(2)/delta213Po(2) of approximately 3 indicates a superallowed character of the alpha emission from 105Te.
Some ideas on support for fault tolerance in COMANDOS, an object oriented distributed system (1990)

The distributed systems group in Trinity have been concerned with fault tolerance for a number years and are now turning our attention to the topic with renewed interest (and urgency). Specifically we are concerned to provide mechanisms for fault tolerance in thc Oisin kernel [5] - the local implementation of the COMANDOS object oriented distributed system [12]. This short position paper outlines our experience gained to date, some of the lessons we have learned and the avenues which we are currently investigating in order to make Oisin reliable.
[Obtaining stem borer-resistant homozygous transgenic lines of Minghui 81 harboring novel cry1Ac gene via particle bombardment]. (2002)

A modified cry1Ac gene was generated by fusing with Lys-Asp-Glu-Lue (KDEL), an endoplasmic reticulum retention signal at the 3'-ends, with signal peptide coding sequence of Soybean kunitz trypsin inhibitor (SKTI) at the 5'-ends. Vector containing the modified cry1Ac gene coding region flanked by the corn ubiquitin 1 promoter and the nopaline synthase gene (nos) terminator with Hygromycin Phosphotransferase (hpt) gene as a plant selection marker was constructed. The modified cry1Ac gene in which toxic protein targeted to endoplasmic retention was successfully transferred into Minghui 81 (Oryza sativa L. subsp. indica), an elite restoring line of commercial CMS indica hybrid rice, through particle bombardment and obtained fertile transformants. Homozygous transgenic rice lines were obtained in the third generation exploiting self-seed set reproduction and HygromycinB selection. These transgenic lines were confirmed with polymerase chain reaction (PCR) amplification, Southern blotting and ELISA detection. Pest insect-resistant bioassay indicated that some of the homozygous cry1Ac-transgenic rice plants of T2 progeny showed high-level resistance against striped stem borer (Chilo suppressalis) at field trials.
Survival and Recovery of Thermally Stressed Yeast in Orange Juice (1981)

ABSTRACT Injury and survival of thermally stressed yeast in orange juice were assessed by plating on plate count agar, acidified potato dextrose agar, and orange serum agar. Thermally stressed yeast were found to have reduced plate counts on both orange serum agar and acidified potato dextrose agar in comparison to plate count agar. Severely injured populations were not able to repair injury in orange juice held at 25°C but survived storage at 25, 6, and ‐18°C.
Sequence of Morphologic Events in Experimental Smoke Inhalation (1989)

The experimentally induced smoke inhalation injury in sheep is in many respects similar to that observed in smoke-injured humans. Our sheep model allows us to describe a sequence of morphologic changes that may be divided into four fairly discrete although overlapping phases. The magnitude of the destructive process and the length and characteristics of each phase are related to the severity of the injury and the superimposed complications. The availability of this animal model may allow the experimental manipulation of each of the four described phases to investigate physiopathologic and therapeutic implications toward the prompt normalization of pulmonary function.
An Optoelectronic Graphics Display Processor (1993)

Abstract : The first three months of this grant period have seen significant progress toward the project goals. A one bit optoelectronic counter has been constructed as a prototypical of an optoelectronic control unit. The counter runs at 305 MHz, and provided us much information on the timing and synchronization of such processor We are beginning our work on developing or acquiring the optoelectronic integrated circuits and holographic optical elements that are necessary to the development of the optoelectronic graphic display processor, OGDP. We have also begun work on a CAD system for designing and constructing such processors. The CAD efforts have begun with development of algorithms for computing bit error rate in these systems We are also in the midst of developing the logical architecture for the OGDP, including control unit and front end processor design.
ChemInform Abstract: The Chemistry of 2H‐3,1‐Benzoxazine‐2,4(1H)‐dione (Isatoic Anhydride). Part 20. Synthesis and Wittig Reactions of Dimethyl (4‐Oxo‐1,4‐dihydroquinolin‐2‐yl)methanephosphonates. (1988)

Abstract The 2‐oxoalkanephosphonates (II) react after lithiation with the isatoic anhydrides (I) to yield the phosphonates (III) mentioned in the title.
Reactions of Nitric Oxide with the Reduced Non-Heme Diiron Center of the Soluble Methane Monooxygenase Hydroxylase (1999)

The soluble methane monooxygenase system from Methylococcus capsulatus (Bath) catalyzes the oxidation of methane to methanol and water utilizing dioxygen at a non-heme, carboxylate-bridged diiron center housed in the hydroxylase (H) component. To probe the nature of the reductive activation of dioxygen in this system, reactions of an analogous molecule, nitric oxide, with the diiron(II) form of the enzyme (Hred) were investigated by both continuous and discontinuous kinetics methodologies using optical, EPR, and Mössbauer spectroscopy. Reaction of NO with Hred affords a dinitrosyl species, designated Hdinitrosyl, with optical spectra (lambdamax = 450 and 620 nm) and Mössbauer parameters (delta = 0.72 mm/s, DeltaEQ = 1.55 mm/s) similar to those of synthetic dinitrosyl analogues and of the dinitrosyl adduct of the reduced ribonucleotide reductase R2 (RNR-R2) protein. The Hdinitrosyl species models features of the Hperoxo intermediate formed in the analogous dioxygen reaction. In the presence of protein B, Hdinitrosyl builds up with approximately the same rate constant as Hperoxo ( approximately 26 s-1) at 4 degrees C. In the absence of protein B, the kinetics of Hdinitrosyl formation were best fit with a biphasic A --> B --> C model, indicating the presence of an intermediate species between Hred and Hdinitrosyl. This result contrasts with the reaction of Hred with dioxygen, in which the Hperoxo intermediate forms in measurable quantities only in the presence of protein B. These findings suggest that protein B may alter the positioning but not the availability of coordination sites on iron for exogenous ligand binding and reactivity.
The Mode Method as a Framework for Theoretical Studies of Ultrasonic Waves Diffraction in Non-homogeneous Layered Structures (2015)

Fundamentals of the mode method including orthogonality conditions between different modes and derivations of coupled equations systems for unknown expansion coefficients are given in the paper for the case of 2D isotropic structures. Using the mode method, several concrete problems of ultrasonic waves diffraction in non-homogeneous layered structures are presented in the paper such as: Scholte-Stoneley wave excitation and conversion at the edge of a liquid loaded plate, interaction of Lamb waves with delaminations in plates coated by highly absorbing materials and nonlinear modulation of Lamb modes by clapping delaminations.
Metabolomics Reveals Phospholipids as Important Nutrient Sources during Salmonella Growth in Bile In Vitro and <i>In Vivo</i> (2011)

During the colonization of hosts, bacterial pathogens are presented with many challenges that must be overcome for colonization to occur successfully. This requires the bacterial sensing of the surroundings and adaptation to the conditions encountered. One of the major impediments to the pathogen colonization of the mammalian gastrointestinal tract is the antibacterial action of bile. Salmonella enterica serovar Typhimurium has specific mechanisms involved in resistance to bile. Additionally, Salmonella can successfully multiply in bile, using it as a source of nutrients. This accomplishment is highly relevant to pathogenesis, as Salmonella colonizes the gallbladder of hosts, where it can be carried asymptomatically and promote further host spread and transmission. To gain insights into the mechanisms used by Salmonella to grow in bile, we studied the changes elicited by Salmonella in the chemical composition of bile during growth in vitro and in vivo through a metabolomics approach. Our data suggest that phospholipids are an important source of carbon and energy for Salmonella during growth in the laboratory as well as during gallbladder infections of mice. Further studies in this area will generate a better understanding of how Salmonella exploits this generally hostile environment for its own benefit.
Engrailed, a homeodomain protein, can repress in vitro transcription by competition with the TATA box-binding protein transcription factor IID. (1990)

Engrailed (En) is a homeodomain protein that binds to a consensus sequence (NP) and plays an important role during Drosophila development. Purified En, which is produced in Escherichia coli, binds not only to this consensus sequence but also to the TATA box of the Drosophila Hsp70 promoter and of other eukaryotic promoters. Interestingly, En represses transcription of these promoters in an in vitro-reconstituted mammalian transcription system and footprint analyses show that En competes with the TATA box-binding protein transcription factor IID for binding to the TATA box. In contrast, a stable template-committed complex formed by preincubation of transcription factor IID with the promoter is not disrupted by addition of En, and in this case transcription is not repressed. These in vitro studies suggest a transcriptional repression mechanism, involving competition between En and transcription factor IID for TATA box binding, that may be involved in En-mediated repression in vivo.
Putting the Knife Edge to the Eye (1976)

The optical systems of an electro-optical instrument which measures the refractive error of human eyes are described. The analog printout enables one to read off the refractive correction as sphere, cylinder, and cylinder axis. The principle involved is a variation of the Foucault knife-edge test. Validation studies are summarized and various applications are briefly mentioned.
Effect of somatostatin on growth hormone and prolactin response to dermorphin in man (1985)

The effects of iv somatostatin (somatotrophin release inhibiting factor (SRIF) on growth hormone (GH) and prolactin (Prl) response to dermorphin (D) were tested in 6 healthy men. In all subjects D induced a significant increase in GH and Prl levels, as expected. SRIF completely blocked the GH-releasing activity of D, whereas it only reduced the Prl-releasing activity. The results confirm that D is a potent stimulant for GH and Prl release in man, and furthermore demonstrate that the action of D on GH secretion can be completely overridden by SRIF.
Separation of Boron Isotopes by Means of Strong Base Exchang Resin in Fluoride Form (1973)

基性陰イオン交換樹脂Diaion SA 20 A, R-F形,50～100メッシュを充テソしたダイフロン製ム(0.8cm2x45 cm, O.8cm2x95 cm bed)に, O.1mo1/1ホウ酸水溶液を漉し,純水で溶離すンド実験を行なった。流出群群のホウ酸の定量は中和滴定により行なった。Bの原子分率の測定arian Mat CH 5型同位体比測定用質量分析計を用いて表面電離法により行なった。バンド実験,(1)負荷するホウ酸量,(2)ホウ酸の負荷および溶離のさいの流速,(3)カラムの長さ(量)を変化させ,これらの因子が解離曲線およびホウ素同位体の濃縮におよぼす影響を検討した。その結果,つぎのことが明らかにされた。(1)バンドの先端部および後端部においてそれぞれXBおi,Bの顕著な濃縮がみられた。(2)フッ化物イナソの流出はほとんど(10-3 mol/1以下)みられず荷したホウ酸は純水によりほぼ完全に溶離された。(3)流速が遅いほど,溶離曲線がシャープに同位体の濃縮度も増大した。(4)カラムの長さおよび負荷したホウ酸の量の増加とともに,ホウ位体の濃縮量も増加した。