gebhart/patrepeval huggingface dataset:
Blood flow in irradiated mouse sarcoma as determined by the clearance of xenon-133. (1972)

133Xe dissolved in 0.9% NaCl solution was injected directly into KHT sarcomas in C3H mice in order to study tumor blood flow. The rate of blood flow in ml/100 g/min was calculated from the clearance half-time and the partition coefficient. The mean rate of blood flow in the tumors of unanesthetized control mice was 21.2 ± 0.8 ml/100 g/min, which was significantly faster than the blood flow in the tumors of pentobarbital-anesthetized control mice. 133Xe was cleared exponentially in virtually all tumors, and rate of clearance decreased with increasing tumor volume in tumors larger than approximately 500 to 600 cu mm; in smaller tumors there was no conclusive evidence of dependence of clearance rate on size. Clearance rate was unaffected by multiple daily injections of 133Xe. At 3 hr after localized tumor irradiation (250 kV; half-value layer, 5.9 mm Al) with doses greater than 1,000 rads, blood flow tended to decrease with increasing radiation dose. At 3 to 4 days postirradiation, rate of blood flow was significantly increased in tumors receiving 1,000 rads; blood flow was also increased in tumors exposed to 2,000 and 4,000 rads, but not until approximately 7 days. Rate of blood flow decreased at 3 hr and 3 to 4 days in tumors irradiated with 8,000 to 16,000 rads. The postirradiation increases in blood flow were not correlated simply with gross tumor shrinkage, although tumor growth was slowed proportionally to radiation dose. Thus, irradiation brought about changes in rate of blood flow in the KHT sarcoma, and these changes were dependent on both radiation dose and postirradiation time. The observed time course of radiation-induced blood flow changes may partially account for the tumor reoxygenation shown in our previous studies and those of others.
A Convenient Synthesis of Diketopiperazines via Aminolysis of N-Pyruvyl α-Amino Esters (1975)

Abstract Several years ago we began some preliminary synthetic studies directed toward sulfide-bridged 1, 4-diketopiperazines (III).2 These initial efforts were concerned with the cyclization reaction shown in Scheme I whereby precursor N-methyl α-sulfhydryl diketopiperazines (II) might be directly obtained from pyruvamide derivatives of α-amino esters (I).3,4
Mercerization of Ramie: Comparisons with Flax and Cotton (1989)

The effects of slack and tension mercerization on selected physical and accessibility characteristics of ramie were compared to the effects of the same treatments on flax and cotton. Slack mercerization of ramie and flax resulted in considerable losses in yam strength, while tension mercerization resulted in increased strength. Increased yarn strength was seen in both slack and tension mercerized cotton yarn. The effects of mercerization on ramie fiber cross-sectional parameters included increases in pe rimeter and area with no change in circularity. Little apparent change in fiber size or shape occurred in flax fibers, while the primary effect on cotton was increased circu larity. Increases in fiber accessibility were seen in all mercerized fibers, but the mag nitude of change in flax was approximately half of that in ramie and cotton. For all three fibers, the extent of swelling and modification in accessibility was greater under slack conditions.
Survey of renewable chemicals produced from lignocellulosic biomass during ionic liquid pretreatment (2013)

Abstract Background Lignin is often overlooked in the valorization of lignocellulosic biomass, but lignin-based materials and chemicals represent potential value-added products for biorefineries that could significantly improve the economics of a biorefinery. Fluctuating crude oil prices and changing fuel specifications are some of the driving factors to develop new technologies that could be used to convert polymeric lignin into low molecular weight lignin and or monomeric aromatic feedstocks to assist in the displacement of the current products associated with the conversion of a whole barrel of oil. We present an approach to produce these chemicals based on the selective breakdown of lignin during ionic liquid pretreatment. Results The lignin breakdown products generated are found to be dependent on the starting biomass, and significant levels were generated on dissolution at 160°C for 6 hrs. Guaiacol was produced on dissolution of biomass and technical lignins. Vanillin was produced on dissolution of kraft lignin and eucalytpus. Syringol and allyl guaiacol were the major products observed on dissolution of switchgrass and pine, respectively, whereas syringol and allyl syringol were obtained by dissolution of eucalyptus. Furthermore, it was observed that different lignin-derived products could be generated by tuning the process conditions. Conclusions We have developed an ionic liquid based process that depolymerizes lignin and converts the low molecular weight lignin fractions into a variety of renewable chemicals from biomass. The generated chemicals (phenols, guaiacols, syringols, eugenol, catechols), their oxidized products (vanillin, vanillic acid, syringaldehyde) and their easily derivatized hydrocarbons (benzene, toluene, xylene, styrene, biphenyls and cyclohexane) already have relatively high market value as commodity and specialty chemicals, green building materials, nylons, and resins.
CIX.—Bromo-derivatives of glyoxaline (1922)

I. E. Balaban and F. L. Pyman, J. Chem. Soc., Trans., 1922, 121, 947 DOI: 10.1039/CT9222100947
MyD88/TLR9 mediated immunopathology and gut microbiota dynamics in a novel murine model of intestinal graft-versus-host disease (2010)

These results emphasise the critical role of gut microbiota, innate immunity and TLR9 in iGvHD and highlight anti-TLR9 strategies as novel therapeutic options.
Delivery of Nerve Growth Factor to the Brain via the Olfactory Pathway (1998)

Purpose: To assess the potential of delivering nerve growth factor (NGF) to the brain along the olfactory neural pathway for the treatment of Alzheimer's disease. Methods: Recombinant human NGF (rhNGF) was given as nose drops to anesthetized rats. The rhNGF concentrations in the brain were determined by enzyme-linked immunosorbent assay (ELISA). Results: Following olfactory administration, rhNGF reached the brain within an hour, achieving a concentration of 3400 pM in the olfactory bulb, 660–2200 pM in other brain regions and, 240 pM and 180 pM in the hippocampus and the amygdala, respectively. In contrast, little or no rhNGF was found in the brain following intravenous administration. Conclusions: A significant amount of rhNGF can be delivered to the brain via the olfactory pathway. The detection of rhNGF by ELISA indicates that rhNGF is delivered to the brain relatively intact. The rapid appearance of rhNGF in the brain suggests that it may be transported by an extraneuronal route into the brain via intercellular clefts in the olfactory epithelium. Further work to clarify the transport mechanism is underway. The olfactory pathway is a promising, non-invasive route for drug delivery to the brain, which has potential for the treatment of neurodegenerative diseases including Alzheimer's disease.
Temporal phosphorylation of the Drosophila period protein. (1994)

The period gene (per) is required for Drosophila melanogaster to manifest circadian (congruent to 24 hr) rhythms. We report here that per protein (PER) undergoes daily oscillations in apparent molecular mass as well as abundance. The mobility changes are largely or exclusively due to multiple phosphorylation events. The temporal profile of the classic short-period form of PER (PERS) is altered in a manner consistent with the mutant strain's behavioral phenotype. As changes in abundance and phosphorylation persist under constant environmental conditions, they reflect or contribute to a free-running rhythm. We suggest that the phosphorylation status of PER is an important determinant in the Drosophila clock's time-keeping mechanism.
Inflammatory bowel disease Part 1: ulcerative colitis--pathophysiology and conventional and alternative treatment options. (2003)

Ulcerative colitis (UC), a subcategory of inflammatory bowel disease, afflicts 1-2 million people in the United States, and many more worldwide. Although the exact cause of ulcerative colitis remains undetermined, the condition appears to be related to a combination of genetic and environmental factors. While conventional treatments can be effective in maintaining remission and decreasing the length of active disease periods, the treatments are not without side effects, and a significant number of people suffering from UC fail to respond to even the strongest drugs. This article reviews potential unconventional treatments - transdermal nicotine, heparin, melatonin, DHEA, probiotics, fiber, dietary changes, botanicals, essential fatty acids, and other nutrients - that may be considered in conjunction with conventional approaches or as part of a comprehensive alternative treatment protocol. In addition this review addresses risk factors, pathogenesis, nutrient deficiencies, conventional treatment approaches, and extra-intestinal manifestations of the disease.
A 98 mm/sup 2/ die size 3.3-V 64-Mb flash memory with FN-NOR type four-level cell (1996)

In order to realize high-capacity and low-cost flash memory, we have developed a 64-Mb flash memory with multilevel cell operation scheme. The 64-Mb flash memory has been achieved in a 98 mm/sup 2/ die size by using four-level per cell operation scheme, NOR type cell array, and 0.4-/spl mu/m CMOS technology. Using an FN type program/erase cell allows a single 3.3 V supply voltage. In order to establish fast programming operation using Fowler-Nordheim (FN)-NOR type memory cell, we have developed a highly parallel multilevel programming technology. The drain voltage controlled multilevel programming (DCMP) scheme, the parallel multilevel verify (PMV) circuit, and the compact multilevel sense-amplifier (CMS) have been implemented to achieve 128 b parallel programming and 6.3 /spl mu/s/Byte programming speed.
Selection-free genome editing of the sickle mutation in human adult hematopoietic stem/progenitor cells (2016)

Genetic diseases of blood cells are prime candidates for treatment through ex vivo gene editing of CD34<sup>+</sup> hematopoietic stem/progenitor cells (HSPCs), and a variety of technologies have been proposed to treat these disorders. Sickle cell disease (SCD) is a recessive genetic disorder caused by a single-nucleotide polymorphism in the β-globin gene (HBB). Sickle hemoglobin damages erythrocytes, causing vasoocclusion, severe pain, progressive organ damage, and premature death. We optimize design and delivery parameters of a ribonucleoprotein (RNP) complex comprising Cas9 protein and unmodified single guide RNA, together with a single-stranded DNA oligonucleotide donor (ssODN), to enable efficient replacement of the SCD mutation in human HSPCs. Corrected HSPCs from SCD patients produced less sickle hemoglobin RNA and protein and correspondingly increased wild-type hemoglobin when differentiated into erythroblasts. When engrafted into immunocompromised mice, ex vivo treated human HSPCs maintain SCD gene edits throughout 16 weeks at a level likely to have clinical benefit. These results demonstrate that an accessible approach combining Cas9 RNP with an ssODN can mediate efficient HSPC genome editing, enables investigator-led exploration of gene editing reagents in primary hematopoietic stem cells, and suggests a path toward the development of new gene editing treatments for SCD and other hematopoietic diseases.
Abstract P3-04-10: Utility of the orally bioavailable selective estrogen receptor degrader AZD9496 in ESR1 mutant preclinical models of estrogen receptor positive breast cancer (2017)

Abstract Approximately 70% of breast cancers express estrogen receptor alpha (ERα) and anti-hormonal therapies which either block the production of estrogen (e.g. anastrozole) or directly block ERα function (e.g. tamoxifen) remain the mainstay of treatment for these patients. While these therapies are highly effective resistance can occur. A common resistance mechanism to anti-hormonal agents is the mutation of ESR1, the gene that encodes ERα, which leads to ligand independent activity. Evidence is emerging that the selective estrogen receptor degrader (SERD) fulvestrant is effective in patients with ESR1 mutations. However, given the low bioavailability of fulvestrant and the still detectable levels of ER in clinical samples after treatment with fulvestrant it is hypothesised that SERDs with improved pharmacokinetic properties which are able to drive greater degradation of ERα may provide additional clinical benefit. We have previously described the discovery and characterisation of the orally bioavailable SERD AZD9496, which is currently in phase I clinical trials in ER+ breast cancer patients. Here we report the preclinical activity of AZD9496 in cell line and patient derived xenograft models expressing clinically relevant ESR1 mutations. We have engineered MCF-7 cells to express Y537S ESR1 which confers the ability to proliferate in the absence of estradiol, consistent with ligand independent activation of ER signalling. AZD9496 is able to inhibit proliferation of these cells and downregulate progesterone receptor protein expression at low nanomolar concentrations. Furthermore, when MCF-7 Y537S ESR1 cells are implanted as xenografts they grow in the absence of exogenous estradiol, are as sensitive to AZD9496 as parental MCF7 xenografts and demonstrate downregulation of ER dependent biomarkers. AZD9496 also has anti-tumour and pharmacodynamic efficacy in patient derived xenograft models expressing D538G ESR1. Taken together, these data strengthen the body of data suggesting that SERDs may be active in patients with tumours containing ESR1 mutations and supports the inclusion of this patient population in AZD9496 clinical trials. Citation Format: Morrow CJ, Lawson M, Ladd B, de Almeida C, James N, Curwen JO, Hanson L, Bell K, Goeppert A, Fisher D, Gangl E, De Savi C, Scott JS, D'Cruz C, Klinowska T, Weir HM. Utility of the orally bioavailable selective estrogen receptor degrader AZD9496 in ESR1 mutant preclinical models of estrogen receptor positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-04-10.
Structural and kinetic characterization of the simplified SH3 domain FP1 (2003)

The simplified SH3 domain sequence, FP1, obtained in phage display selection experiments has an amino acid composition that is 95% Ile, Lys, Glu, Ala, Gly. Here we use NMR to investigate the tertiary structure of FP1. We find that the overall topology of FP1 resembles that of the src SH3 domain, the hydrogen-deuterium exchange and chemical shift perturbation profiles are similar to those of naturally occurring SH3 domains, and the (15)N relaxation rates are in the range of naturally occurring small proteins. Guided by the structure, we further simplify the FP1 sequence and compare the effects on folding kinetics of point mutations in FP1 and the wild-type src SH3 domain. The results suggest that the folding transition state of FP1 is similar to but somewhat less polarized than that of the wild-type src SH3 domain.
Classification of invariant image representations using a neural network (1990)

A neural network (NN) based approach for classification of images represented by translation-, scale-, and rotation-invariant features is presented. The utilized network is a multilayer perceptron (MLP) classifier with one hidden layer. Back-propagation learning is used for its training. Two types of features are used: moment invariants derived from geometrical moments of the image, and features based on Zernlike moments, which are the mapping of the image onto a set of complex orthogonal polynomials. The performance of the MLP is compared to the Bayes, nearest-neighbor, and minimum-mean-distance statistical classifiers. Through extensive experimentation with noiseless as well as noisy binary images of all English characters (26 classes), the following conclusions are reached: (1) the MLP outperforms the other three classifiers, especially when noise is present; (2) the nearest-neighbor classifier performs about the same as the NN for the noiseless case; (3) the NN can do well even with a very small number of training samples; (4) the NN has a good degree of fault tolerance; and (5) the Zernlike-moment-based features possess strong class separability power and are more powerful than moment invariants.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
21.3: 4.0 In. QVGA AMOLED Display Using In‐Ga‐Zn‐Oxide TFTs with a Novel Passivation Layer (2009)

Abstract We have developed a 4.0 inch QVGA AMOLED display using amorphous In‐Ga‐Zn‐Oxide TFTs, focusing on a passivation layer. Threshold voltage of the TFTs can be controlled to have “normally off” characteristics by using SiO x with a low hydrogen content. Besides, small subthreshold swing and high saturation mobility are obtained.
Synthesis and Characterization of Luciferin Derivatives for Use in Bioluminescence Enhanced Enzyme Immunoassays. New Ultrasensitive Detection Systems for Enzyme Immunoassays, I. (1987)

Derivatives of luciferin, D-luciferin methyl ester, D-luciferyl-L-phenylalanine, D-luciferyl-L-N alpha-arginine, D-luciferin-O-sulphate and D-luciferin-O-phosphate, were synthesized for use as highly sensitive substrates for enzyme assays. The luciferin derivatives were characterized by ultraviolet and fluorescence spectrophotometry, by amino acid analysis and by fast atom bombardement mass spectrometry. Enzymatic cleavage of the compounds by enzymes leading to the release of D-luciferin was demonstrated. Kinetic constants were determined for the following enzyme/substrate pairs: D-luciferin methyl ester/carboxylic esterase, D-luciferyl-L-phenylalanine/carboxypeptidase A, D-luciferyl-L-N alpha-arginine/carboxypeptidase B, D-luciferin-O-sulphate/arylsulphatase, D-luciferin-O-phosphate/alkaline phosphatase. All compounds proved to be acceptable substrates for the respective enzymes, D-luciferin-O-phosphate being accompanied by an especially high turnover number (kcat = 1010 s-1) with alkaline phosphatase.
Involvement of extracellular calcium in phosphatidylserine exposure during apoptosis (1996)

The appearance of phosphatidylserine (PS) on the outer surface of apoptotic cells is an important signal for their ingestion. In platelets, elevation of intracellular Ca2+ with thapsigargin can trigger large amounts of PS exposure within minutes. We detected PS exposure in U937 promonocytes and Jurkat T-cells after incubation with thapsigargin, but in only 10% of the cells, and it took up to 6 h to occur. Tumor necrosis factor and anti-Fas antibody rapidly trigger apoptosis in these cells, and chelation of extracellular Ca2+ with 5 mM EGTA inhibited PS exposure by 65% and 50%, respectively. Chelation of intracellular Ca2+ with BAPTA-AM had no effect. Other parameters of apoptosis, including cell blebbing, shrinkage, nuclear fragmentation, activation of the ICE-like proteases, and fodrin cleavage, were not inhibited by extracellular EGTA. We conclude that while an elevation of intracellular Ca2+ is an ineffective trigger of apoptosis in the cells investigated, extracellular Ca2+ is required for efficient PS exposure during apoptosis.
Closure of leaking filtering blebs with cyanoacrylate tissue adhesive. (1991)

Five leaking filtering blebs, occurring between 10 months and 21 years after trabeculectomy, were closed with cyanoacrylate tissue adhesive. Filtering bleb integrity was preserved in four cases, so that additional microsurgery was avoided. The only problem associated with use of tissue adhesive was the development of corneal abrasions in three cases. Although it is an accepted treatment for these conjunctival fistulas, only nine previous cases have been reported to our knowledge. We strongly recommend the use of tissue adhesive as a presurgical treatment in the management of leaking filtering blebs which present as a late postoperative complication of glaucoma surgery.
Origin of coronary endothelial cells from epicardial mesothelium in avian embryos (2002)

It has been established that coronary vessels develop through self-assembly of mesenchymal vascular progenitors in the subepicardium. Mesenchymal precursors of vascular smooth muscle cells and fibroblasts are known to originate from an epithelial-to-mesenchymal transformation of the epicardial mesothelium, but the origin of the coronary endothelium is still obscure. We herein report that at least part of the population of the precursors of the coronary endothelium are epicardially-derived cells (EPDCs). We have performed an EPDC lineage study through retroviral and fluorescent labelling of the proepicardial and epicardial mesothelium of avian embryos. In all the experiments onlythe surface mesothelium was labelled after 3 h of reincubation. However, endothelial cells from subepicardial vessels were labelled after 24-48 h and endothelial cells of intramyocardial vessels were also labelled after 48-96 h of reincubation. In addition, the development of the coronary vessels was studied in quail-chick chimeras, obtaining results which also support a mesothelial origin for endothelial and smooth muscle cells. Finally, quail proepicardial explants cultured on Matrigel showed colocalization of cytokeratin and QH1 (mesothelial and endothelial markers, respectively) after 24 h. These results, taken together, suggest that EPDC show similar competence to that displayed by bipotential vascular progenitor cells [Yamashita et al., Nature 408: 92-96 (2000)] which are able to differentiate into endothelium or smooth muscle depending on their exposure to VEGF or PDGF-BB. It is conceivable that the earliest EPDC differentiate into endothelial cells in response to myocardially-secreted VEGF, while further EPDC would be recruited by the nascent capillaries via PDGFR-beta signalling, giving rise to mural cells.
Characterization of a novel interleukin-6 autocrine-dependent human plasma cell line. (1994)

The systematic use of lidocaine in EGD is safe but does not improve the tolerance in all outpatients. Only the Mallampati index has been identified as a prognosis factor of good response to lidocaine administration. Additionally the nursing-endoscopist could be a very important factor in the scores obtained independently of lidocaine.
Collision detection for volumetric objects (1997)

We propose a model for the handling of complicated interactions between volumetric objects. In our model each volume is associated with a probability that assigns a to each space point according to local volume properties. The interaction between two volumes is then described by finding the intersecting regions between the volumes, and calculating the probabilities at each intersecting point from the surface crossing probabilities. To enable fast and efficient calculations, we introduce the concept of a distance map and develop two hierarchical collision detection algorithms, taking advantage of the uniform structure of volumetric datasets.