gebhart/patrepeval huggingface dataset:
A complementary new drug for PNH (2020)

continued up to 24 hours. Accumulation of neutrophils was many times higher in animals with CGD than in wild-type animals. In a similar manner, the concentration of LTB4 increased significantly in CGD animals. By using neutrophil-depleted mice, they verified that neutrophils are responsible for the majority of LTB4 production in the lungs, although other leukocytes are also capable of synthesizing LTB4. To prove the concept, Song et al show that the zymosan-induced hyperinflammation in CGD mice can be almost completely prevented by inhibiting LTB4 synthesis or by blocking LTB4 receptors. With these findings, the important role of neutrophil-derived LTB4 in induction of sterile lung inflammation in CGD mice is clearly supported.
Selection of Wine Yeasts for Growth and Fermentation in the Presence of Ethanol and Sucrose (1983)

To optimize the conversion of carbohydrates to ethanol, strains of several Saccharomyces species were examined for the ability to grow and ferment in a range of sucrose and ethanol concentrations. A total of 632 wine yeasts, most of them isolated from wineries in Andalusia and Extremadura, southwestern Spain, were subjected to screening and selection. Growth and fermentative capacity in different ethanol and sucrose concentrations varied from one strain to another. There was no correlation between growth and fermentative capacity. The best 35 strains grew in 15% ethanol and fermented in 18% ethanol. Ethanol accumulated, although at a reduced rate, after the cells stopped growing. Most yeast strains were highly fermentative in 50% sucrose. Some of them effectively utilized the carbohydrates of the culture, yielding final ethanol concentrations of > 14%. Of the 35 selected strains, 16 were promising for genetic analysis and breeding because of their capacity to sporulate. These strains were homothallic, and their spores were viable. The meiotic products analyzed so far were also homothallic.
Demodex folliculorumand topical treatment: acaricidal action evaluated by standardized skin surface biopsy (1998)

A standardized skin surface biopsy was performed in 34 patients suffering from skin diseases with high Demodex folliculorum density (Dd) > 5D/cm2 before, during and after topical treatment. The patients were randomized into six comparable groups to study six topical treatments: metronidazole 2%, permethrin 1%, sublimed sulphur 10%, lindane 1%, crotamiton 10% and benzyl benzoate (BB) 10%. Their acaricidal activity was measured according to three criteria: (i) for each treatment, decrease of Dd to under the normal threshold (< or = 5 D/cm2); (ii) for each treatment, a significant decrease in Dd; and (iii) comparison of the relative difference in Dd between treatments. These three criteria converged to establish the acaricidal activity of BB on D. folliculorum; the efficacy of crotamiton was demonstrated by the second criterion. An important irritating effect was observed with BB and sulphur.
JAK2 V617F Tyrosine Kinase Mutation in Leukemia Cell Lines. (2005)

Abstract It has recently been shown that the majority of patients with polycythemia vera, and substantial numbers of patients with idiopathic myelofibrosis and essential thrombocythemia, carry a single nucleotide mutation in the JAK2 gene. The JAK2 V617F mutation was also found in patients with other myeloproliferative disorders, though at lower percentages. The JAK2 point mutation may contribute to the development of these diseases, and the elucidation of the cellular function of mutated JAK2 might facilitate the development of a suitable drug. In numerous cases, the effects of a mutationally altered protein on cellular functions like proliferation, differentiation or apoptosis, have been revealed using immortalized cell lines that carry the mutation in question. To find such a model system for JAK2 V617F in hematopoietic neoplasia, we tested a panel of 37 cell lines from patients with myeloproliferative disorders, myelodysplastic syndromes (MDS) and the megakaryoblastic variant of acute myeloid leukemia (AML M7) and compared these with cell lines derived from other types of AML (M1-M6), and acute lymphoblastic leukemia (ALL). Cell lines were tested for JAK2 V617F expression applying a DNA tetra-primer amplification refractory mutation system (ARMS), a method that specifically amplifies the normal and mutant sequences plus a positive control band in a single reaction. According to this method, three cell lines carried the JAK2 V167F mutation: cell line MB-02 derived from a patient with a history of myelofibrosis and myeloid metaplasia that developed into AML M7; cell line MUTZ-8 established from a patient with AML M4 25 years after onset of MDS; cell line SET-2 from a patient at the stage of leukemic transformation of essential thrombocythemia. We present data on these cell lines including JAK2 ARMS and sequencing results, cytogenetic analysis focusing on chromosome 9, and JAK-2 protein expression and activation. In summary, we detected three leukemia cell lines that carry the recently discovered JAK2 mutation. These cell lines promise to represent important research tools in the further analysis of this genetic alteration.
Wastepaper as a feedstock for ethanol production (1991)

The possibility of using wastepaper as a cheap feedstock for production of ethanol is discussed. As the single largest material category in the municipal solid waste (MSW) stream, wastepaper is the main target of efforts to reduce the volume of MSW. And in the process for producing ethanol from lignocellulosics, the feedstock represents the highest cost. If wastepaper could be obtained cheaply in large enough quantities and if conversion process cost and efficiency prove to be similar to those for wood, the cost of ethanol could be significantly reduced. At the same time, the volume of wastepaper that must be disposed of in landfills could be lessened. 13 refs., 3 figs., 7 tabs.
Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts (2014)

β-Cells generated from large-scale sources can overcome current shortages in clinical islet cell grafts provided that they adequately respond to metabolic variations. Pancreatic (non)endocrine cells can develop from human embryonic stem (huES) cells following in vitro derivation to pancreatic endoderm (PE) that is subsequently implanted in immune-incompetent mice for further differentiation. Encapsulation of PE increases the proportion of endocrine cells in subcutaneous implants, with enrichment in β-cells when they are placed in TheraCyte-macrodevices and predominantly α-cells when they are alginate-microencapsulated. At posttransplant (PT) weeks 20-30, macroencapsulated huES implants presented higher glucose-responsive plasma C-peptide levels and a lower proinsulin-over-C-peptide ratio than human islet cell implants under the kidney capsule. Their ex vivo analysis showed the presence of single-hormone-positive α- and β-cells that exhibited rapid secretory responses to increasing and decreasing glucose concentrations, similar to isolated human islet cells. However, their insulin secretory amplitude was lower, which was attributed in part to a lower cellular hormone content; it was associated with a lower glucose-induced insulin biosynthesis, but not with lower glucagon-induced stimulation, which together is compatible with an immature functional state of the huES-derived β-cells at PT weeks 20-30. These data support the therapeutic potential of macroencapsulated huES implants but indicate the need for further functional analysis. Their comparison with clinical-grade human islet cell grafts sets references for future development and clinical translation.
Immunogenetic control of brain tumor growth in rats. (1977)

&lt;p&gt;We demonstrate all-optical seed-pulse extractor for DPSK and OOK packet synchronization and all-optical header extractor at 10 Gbit/s exploiting a novel approach based on self-induced effect in passive, low-power, polarization-independent, compact vertical cavity-semiconductor switch.&lt;/p&gt;
Isolation of circulating cancer cells from whole blood by immunomagnetic cell enrichment and unenriched immunocytochemistry in vitro. (2003)

Compared with unenriched immunocytochemistry immunomagnetic enrichment significantly improves the detection of epithelial cells added to blood. A significant advantage was observed for positive selection. Immunomagnetic enrichment may be important for clinical practice in the future.
Large Scale Preparation of Protected 4-Aminomethylbenzamidine. Application to The Synthesis of the Thrombin Inhibitor, Melagatran (1998)

Abstract To allow the preparation of melagatran on a multigram scale, we have investigated several approaches for the synthesis of the key intermediate 4-aminomethylbenzamidine. The only industrially suitable pathway relies on the preparation of an N-hydroxyimino intermediate.
A fully active variant of dihydrofolate reductase with a circularly permuted sequence (1992)

The amino acid sequence of mouse dihydrofolate reductase was permuted circularly at the level of the gene. By transposing the 3'-terminal half of the coding sequence to its 5' terminus, the naturally adjacent amino and carboxyl termini of the native protein were fused, and one of the flexible peptide loops at the protein surface was cleaved. The steady-state kinetic constants, the dissociation constants of folate analogues, and the degree of activation by both mercurials and salt as well as the resistance toward digestion by trypsin were almost indistinguishable from those of a recombinant wild-type protein. Judged by these criteria, the circularly permuted variant has the same active site and overall structure as the wild-type enzyme. The only significant difference was the lower stability toward guanidinium chloride and the lower solubility of the circularly permuted variant. This behavior may be due to moving a mononucleotide binding fold from the interior of the sequence to the carboxyl terminus. Thus, dihydrofolate reductase requires neither the natural termini nor the cleaved loop for stability, for the conformational changes that accompany catalysis as well as the binding of inhibitors, and for the folding process.
Inflammation and its role in age-related macular degeneration (2016)

Inflammation is a cellular response to factors that challenge the homeostasis of cells and tissues. Cell-associated and soluble pattern-recognition receptors, e.g. Toll-like receptors, inflammasome receptors, and complement components initiate complex cellular cascades by recognizing or sensing different pathogen and damage-associated molecular patterns, respectively. Cytokines and chemokines represent alarm messages for leukocytes and once activated, these cells travel long distances to targeted inflamed tissues. Although it is a crucial survival mechanism, prolonged inflammation is detrimental and participates in numerous chronic age-related diseases. This article will review the onset of inflammation and link its functions to the pathogenesis of age-related macular degeneration (AMD), which is the leading cause of severe vision loss in aged individuals in the developed countries. In this progressive disease, degeneration of the retinal pigment epithelium (RPE) results in the death of photoreceptors, leading to a loss of central vision. The RPE is prone to oxidative stress, a factor that together with deteriorating functionality, e.g. decreased intracellular recycling and degradation due to attenuated heterophagy/autophagy, induces inflammation. In the early phases, accumulation of intracellular lipofuscin in the RPE and extracellular drusen between RPE cells and Bruch's membrane can be clinically detected. Subsequently, in dry (atrophic) AMD there is geographic atrophy with discrete areas of RPE loss whereas in the wet (exudative) form there is neovascularization penetrating from the choroid to retinal layers. Elevations in levels of local and systemic biomarkers indicate that chronic inflammation is involved in the pathogenesis of both disease forms.
Application of ultrasonic stress measurement to engineering components (1997)

Ultrasonic techniques offer several unique advantages in nondestructive stress measurement. Most importantly, the ultrasonic energy propagates below the material surface, giving information on stress distributions away from the surface effects. Additionally, surface preparation requirements are minimal, enabling rapid collection of stress information from several locations in a component. Finally, the instrumentation necessary to collect and analyze the ultrasonic traveltimes required for stress evaluation is available in relatively light, compact, computer driven units that are easily moved into the industrial or laboratory work space. A brief overview will be given of the acoustoelastic effect, which is the basis for ultrasonic stress measurement. Both the acousticbirefringence (shear wave) and the critically refracted longitudinal wave (LCR) methods will be described. Examples of applications of the latter method for stress measurement in turbine components, rolled plate, ductile iron, and railroad rail and wheels will be described.
Identification of thioredoxin-interacting protein (TXNIP) as a downstream target for IGF1 action (2018)

Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is the best-characterized entity among the congenital insulin-like growth factor 1 (IGF1) deficiencies. Life-long exposure to minute endogenous IGF1 levels is linked to low stature as well as a number of endocrine and metabolic abnormalities. While elevated IGF1 is correlated with increased cancer incidence, epidemiological studies revealed that patients with LS do not develop tumors. The mechanisms associated with cancer protection in LS are yet to be discovered. Recent genomic analyses identified a series of metabolic genes that are overrepresented in patients with LS. Given the augmented expression of these genes in a low IGF1 milieu, we hypothesized that they may constitute targets for IGF1 action. Thioredoxin-interacting protein (TXNIP) plays a critical role in cellular redox control by thioredoxin. TXNIP serves as a glucose and oxidative stress sensor, being commonly silenced by genetic or epigenetic events in cancer cells. Consistent with its enhanced expression in LS, we provide evidence that <i>TXNIP</i> gene expression is negatively regulated by IGF1. These results were corroborated in animal studies. In addition, we show that oxidative and glucose stresses led to marked increases in <i>TXNIP</i> expression. Supplementation of IGF1 attenuated TXNIP levels, suggesting that IGF1 exerts its antiapoptotic effect via inhibition of <i>TXNIP</i> Augmented <i>TXNIP</i> expression in LS may account for cancer protection in this condition. Finally, TXNIP levels could be potentially useful in the clinic as a predictive or diagnostic biomarker for IGF1R-targeted therapies.
Identification of genes and molecular pathways involved in the progression of premalignant oral epithelia (2005)

An early interventional effort in oral premalignancy requires novel molecular targets and diagnostic biomarkers to delay or reverse incidences of malignant progression. Microarray-based transcriptional profiling in disease states provides global insight into the causal biomolecular processes and novel pathways involved. In this study, we investigated transcript profiles in precancerous oral lesions to identify nearly 1,700 genes as significantly overexpressed or underexpressed and a primarily affected metabolic pathway that may be responsible for irreversible transition to progressive stages of oral cancer. For the first time, we show a convergence of several genes and pathways known for their oncogenic capabilities, in progression of premalignant oral epithelial tissues. This study consequently provides a molecular basis for persistent proinflammatory conditions in oral premalignant tissues. We found that lipocalin-type prostaglandin D(2) synthase (PTGDS), a key enzyme in the arachidonic acid metabolism pathway, as repressed in premalignant stages. We show the protective role of these enzyme-derived metabolites in inhibiting cell proliferation using an in vitro oral cancer progression model. We have also confirmed the overexpression of two invasion-related biomarkers, psoriasin (PSOR1) and versican (CSPG2), in oral premalignant and malignant archival tissues. Our results clearly indicate that pharmacologic intervention with anti-inflammatory prostaglandin D(2)-like analogues may help prevent or delay oral epithelial carcinogenesis because of metabolic restoration of a negative feedback regulatory loop through its several cognate receptors or target molecules. Further studies directed toward a multitude of possible protective mechanisms of this lipocalin-type enzyme or its products in oral cancer progression are warranted.
Embryonic stem cells alone are able to support fetal development in the mouse (1990)

The developmental potential of embryonic stem (ES) cells versus 3.5 day inner cell mass (ICM) was compared after aggregation with normal diploid embryos and with developmentally compromised tetraploid embryos. ES cells were capable of colonizing somatic tissues in diploid aggregation chimeras but less efficiently than ICMs of the same genotype. When ICM in equilibrium with tetraploid and ES in equilibrium with tetraploid chimeras were made, the newborns were almost all completely ICM- or ES-derived, as judged by GPI isozyme analysis, but tetraploid cells were found in the yolk sac endoderm and trophectoderm lineage. Investigation of ES contribution in 13.5 day ES in equilibrium with tetraploid chimeras by DNA in situ hybridization confirmed the complete tetraploid origin of the placenta (except the fetal blood and blood vessels) and the yolk sac endoderm. However, the yolk sac mesoderm, amnion and fetus contained only ES-derived cells. ES-derived newborns failed to survive after birth, although they had normal birthweight and anatomically they appeared normal. This phenomenon remains unexplained at the moment. The present results prove that ES cells are able to support complete fetal development, resulting in ES-derived newborns, and suggest a useful route for studying the development of genetically manipulated ES cells in all fetal lineages.
An improved colloidal silver staining method of protein blots on nitrocellulose membranes. (1987)

A simple method of revealing proteins on nitrocellulose blots is described. It is based on high affinity of colloidal silver for proteins. The sensitivity is about the same as that of colloidal gold and it appears to be about 20 times higher than the presently used staining methods. The whole procedure is very simple and does not take more than 30 min.
The Human Experience With Ghrelin Administration (2013)

Existing literature supports the short-term safety of ghrelin administration and its efficacy as an appetite stimulant in diverse patient populations. There is some evidence to suggest that ghrelin has wider ranging therapeutic effects, although these areas require further investigation.
Effect of Abomasal Infusion of Propionate on the GnRH-Induced Luteinizing Hormone Release in Prepuberal Heifers3 (1983)

Each of 12 prepuberal Brangus heifers (8 to 10 mo of age; 167 to 196 kg) was fitted with an abomasal cannula and assigned to one of two infusion treatments (six heifers/treatment): 1,150 ml of water/d (C) or 200 g of propionate (9% of digestible energy) plus 950 ml of water (P). The heifers were individually fed twice daily 4.50 kg of a diet consisting of 45% cottonseed hulls, 35% corn, 15% soybean meal, 3.5% molasses and 1.5% dicalcium-phosphate, salt and vitamins A, D and E. The infusion treatments were delivered continuously via a peristaltic pump throughout the trial. The heifers were given two 100-µg gonadotropin releasing hormone (GnRH) challenges, administered im 6 h apart, at three periods of the trial: Period 1–24 h after the start of the infusion treatment; Period 2–after at least 21 d from the start of the infusion treatment and Period 3–24 h after the infusion treatments were switched. Infusion treatments were switched immediately after sampling was completed at Period 2 and treatment was continued until sampling was completed at Period 3. Blood samples for luteinizing hormone (LH) were collected via jugular cannula prior to each initial GnRH injection and then at 10-min intervals for 12 h. At each period approximately 6 h after feeding, an additional blood sample was collected for determination of plasma glucose levels. There was no difference in the magnitude of the LH surge between C and P heifers at Period 1, although P heifers had an LH surge of longer duration (P<.025) after the first GnRH injection than did C heifers. Pro-pionate-treated heifers also had a lower concentration of plasma glucose (P<.10) than did C heifers at Period 1. At Period 2, the magnitude of the LH response to the first GnRH injection was greater in P than in C heifers (P<.005). Propionate-treated heifers also had a slightly higher peak LH concentration and a slightly greater area under the LH curve after GnRH injection than did C heifers (P>.10). Plasma glucose concentration at Period 2 was greater (P<.10) in P than in C heifers. At Period 3, P heifers switched to C maintained a greater LH response to both the first (P<.05) and the second (P<.025) GnRH injection than did C heifers switched to P. There was no difference in plasma glucose levels between C heifers switched to P and P heifers switched to C at this period. We conclude from these data that abomasal infusion of propionate enhances the ability of the prepuberal heifer to respond to a GnRH challenge. The design of the experiment did not allow us to distinguish between a direct propionate effect or a general energy level effect.
Heparan Sulfate Modification of the Transmembrane Receptor CD47 Is Necessary for Inhibition of T Cell Receptor Signaling by Thrombospondin-1 (2011)

Cell surface proteoglycans on T cells contribute to retroviral infection, binding of chemokines and other proteins, and are necessary for some T cell responses to the matricellular glycoprotein thrombospondin-1. The major cell surface proteoglycans expressed by primary T cells and Jurkat T cells have an apparent M(r) > 200,000 and are modified with chondroitin sulfate and heparan sulfate chains. Thrombospondin-1 bound in a heparin-inhibitable manner to this proteoglycan and to a soluble form released into the medium. Based on mass spectrometry, knockdown, and immunochemical analyses, the proteoglycan contains two major core proteins as follows: amyloid precursor-like protein-2 (APLP2, apparent M(r) 230,000) and CD47 (apparent M(r) > 250,000). CD47 is a known thrombospondin-1 receptor but was not previously reported to be a proteoglycan. This proteoglycan isoform of CD47 is widely expressed on vascular cells. Mutagenesis identified glycosaminoglycan modification of CD47 at Ser(64) and Ser(79). Inhibition of T cell receptor signaling by thrombospondin-1 was lost in CD47-deficient T cells that express the proteoglycan isoform of APLP2, indicating that binding to APLP2 is not sufficient. Inhibition of CD69 induction was restored in CD47-deficient cells by re-expressing CD47 or an S79A mutant but not by the S64A mutant. Therefore, inhibition of T cell receptor signaling by thrombospondin-1 is mediated by CD47 and requires its modification at Ser(64).