gebhart/patrepeval huggingface dataset:
Role of Gas6 in erythropoiesis and anemia in mice (2008)

Many patients with anemia fail to respond to treatment with erythropoietin (Epo), a commonly used hormone that stimulates erythroid progenitor production and maturation by human BM or by murine spleen. The protein product of growth arrest-specific gene 6 (Gas6) is important for cell survival across several cell types, but its precise physiological role remains largely enigmatic. Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. In the absence of Gas6, erythroid progenitors and erythroblasts were hyporesponsive to the survival activity of Epo and failed to restore hematocrit levels in response to anemia. In addition, Gas6 may influence erythropoiesis via paracrine erythroblast-independent mechanisms involving macrophages. When mice with acute anemia were treated with Gas6, the protein normalized hematocrit levels without causing undesired erythrocytosis. In a transgenic mouse model of chronic anemia caused by insufficient Epo production, Gas6 synergized with Epo in restoring hematocrit levels. These findings may have implications for the treatment of patients with anemia who fail to adequately respond to Epo.
Cell Biology of the 5-Lipoxygenase Pathway (1998)

The initial enzymatic steps in leukotriene synthesis occur at the nuclear envelope. Cytosolic phospholipase A2 translocates from the cytoplasm to selectively hydrolyze nuclear envelope phospholipids, releasing free arachidonate. 5-Lipoxygenase-activating protein, an arachidonate transfer protein, then binds arachidonate and presents it to 5-lipoxygenase (5-LO), which catalyzes a two-step reaction to produce leukotriene A4. In resting human and rat peripheral blood neutrophils, 5-LO is localized to the cytoplasm; in rat basophilic leukemia cells and human alveolar macrophages, however, it is found predominantly in the nucleus. Immunofluorescence microscopy studies demonstrate that both cytoplasmic and nuclear 5-LO move to the nuclear envelope following cell activation. Many questions remain unanswered regarding the significance of nuclear 5-LO, potential autocrine actions of leukotrienes, and intracellular trafficking of these enzymes and their products. Peters-Golden M. Cell biology of the 5-lipoxygenase pathway.
Preparation and analysis of protein crystals (1982)

A complete guide to techniques and procedures for the preparation of proteins for crystallographic studies. Describes methods for protein crystallization; formation of isomorphous heavy atoms; x-ray diffraction and analysis; and photographic and computerbased data collection methods and instrumentation.
Aptamer-Based Microfluidic Device for Enrichment, Sorting, and Detection of Multiple Cancer Cells (2009)

The ability to diagnose cancer based on the detection of rare cancer cells in blood or other bodily fluids is a significant challenge. To address this challenge, we have developed a microfluidic device that can simultaneously sort, enrich, and then detect multiple types of cancer cells from a complex sample. The device, which is made from poly(dimethylsiloxane) (PDMS), implements cell-affinity chromatography based on the selective cell-capture of immobilized DNA-aptamers and yields a 135-fold enrichment of rare cells in a single run. This enrichment is achieved because the height of the channel is on the order of a cell diameter. The sorted cells grow at the comparable rate as cultured cells and are 96% pure based on flow cytometry determination. Thus, by using our aptamer based device, cell capture is achieved simply and inexpensively, with no sample pretreatment before cell analysis. Enrichment and detection of multiple rare cancer cells can be used to detect cancers at the early stages, diagnose metastatic relapse, stratify patients for therapeutic purposes, monitor response to drugs and therapies, track tumor progression, and gain a deeper understanding of the biology of circulating tumor cells (CTCs).
Understanding the Role of Surface Charges in Cellular Adsorption versus Internalization by Selectively Removing Gold Nanoparticles on the Cell Surface with a I2/KI Etchant (2009)

This Letter presents a new method for differentiating the Au nanospheres attached to the cell surface from those being internalized into the cells. We introduced an etching solution based on I2 and KI that can selectively dissolve the Au nanospheres on the cell surface within a short period of time. The advantage of this etchant is its low toxicity to the cells because it is capable of etching away a relatively large amount of Au nanospheres at a low molar concentration. By combining with quantitative elemental analysis, we found that the deposition of Au nanospheres on the surface of cancer cells was highly dependent on the sign of surface charges on the Au nanospheres. In addition, by fitting the uptake data with a kinetic model, we were able to derive the overall and internalization rate constants for Au nanospheres and both of them were found to be governed by the surface charges on Au nanospheres.
Effective chelation of iron in beta thalassaemia with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one. (1987)

The main iron chelator used for transfusional iron overload is desferrioxamine, which is expensive, has toxic side effects, and has to be given subcutaneously. An orally active iron chelator is therefore required. The effects of oral 1,2-dimethyl-3-hydroxypyrid-4-one on urinary iron excretion were studied in eight patients who had received multiple transfusions: four had myelodysplasia and four beta thalassaemia major. Different daily doses of the drug up to 100 mg/kg/day, alone or in combination with ascorbic acid, were used. In three patients with thalassaemia the effect of the drug was compared with that of subcutaneous desferrioxamine at the same daily dose. In all eight patients a single dose of oral 1,2-dimethyl-3-hydroxypyrid-4-one resulted in substantial urinary iron excretion, mainly in the first 12 hours. Urinary iron excretion increased with the dose and with the degree of iron loading of the patient. Giving two or three divided doses over 24 hours resulted in higher urinary iron excretion than a single dose of the same amount over the same time. In most patients coadministration of oral ascorbic acid further increased urinary iron excretion. 1,2-Dimethyl-3-hydroxypyrid-4-one caused similar iron excretion to that achieved with subcutaneous desferrioxamine at a comparable dose. In some cases the iron excretion was sufficiently high (maximum 99 mg/day) to suggest that a negative iron balance could be easily achieved with these protocols in patients receiving regular transfusions. No evidence of toxicity was observed on thorough clinical examination or haematological and biochemical testing in any of the patients. None of the patients had any symptoms that could be ascribed to the drug. These results suggest that the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one is as effective as subcutaneous desferrioxamine in increasing urinary iron excretion in patients loaded with iron. Its cheap synthesis, oral activity, and lack of obvious toxicity at effective doses suggest that it should be developed quickly and thoroughly tested for the management of transfusional iron overload.
Evaluation of platinol analogs using the M5076 murine sarcoma. (1986)

The M5076 sarcoma was used to evaluate the antitumor activities of several analogs of Platinol presently undergoing clinical trials. The objective was to find a model yielding preclinical data which correlated with evolving clinical results, and thus potentially provide a validated model for the subsequent testing of new Platinol analogs. The model found to be useful consisted of mice implanted s.c. with M5076 tumor fragments. Platinol, carboplatin, and iproplatin were consistently active (T/C values greater than or equal to 125%), whereas spiroplatin was consistently inactive. These findings reflect the clinical activities of Platinol, carboplatin, and iproplatin and the essential clinical inactivity of spiroplatin thus far reported.
Carbapenem-Resistant Enterobacteriaceae (2008)

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The nutritional management of hepatic encephalopathy in patients with cirrhosis: International society for hepatic encephalopathy and nitrogen metabolism consensus (2013)

Effective management of these patients requires an integrated multidimensional approach. However, further research is needed to fill the gaps in the current evidence base to optimize the nutritional management of patients with cirrhosis and HE.
Plasma proteins in a standardised skin mini-erosion (II): effects of extraction pressure (2002)

Samples of IF extracted at 0 h at -200 mmHg contained lower protein concentrations, indicating an increased water fraction and an intact sieve function of the vascular wall. The difference in protein concentration extracted at higher and lower pressure from 24 h onward was less pronounced. Lower pressure should be used to sample substances of greater molecular size.
Cyclic AMP modulation of Fc receptor expression on a pre-B cell lymphoma. (1980)

Cyclic AMP-elevating agents have been shown to increase the expression of Fc receptors on the Abelson virus-induced pre-B cell tumor ABE-8. Such agents included isoproterenol, PGE1, 3-isobutyl-1-methyl xanthine, and 8 BrcAMP. The positive inductive effect produced by these agents was inhibited by 8 BrcGMP and PGF2 alpha, which putatively elevate cyclic GMP levels. Other agents also shown to induce Fc receptor expression were LPS and certain batches of fetal calf sera. In contrast to the inductive effect produced by cyclic AMP elevating agents, 8 BrcGMP and PGF2 alpha were unable to reverse the increased Fc receptor expression produced by LPS and fetal calf sera. Thus, these latter agents may act via a qualitatively different mechanism in producing a change in phenotypic expression. The results of this study are discussed in terms of the use of tumor cells as a model system for studying the pharmacologic control of lymphocyte differentiation.
The EUROclass trial: defining subgroups in common variable immunodeficiency (2007)

The heterogeneity of common variable immunodeficiency (CVID) calls for a classification addressing pathogenic mechanisms as well as clinical relevance. This European multicenter trial was initiated to develop a consensus of 2 existing classification schemes based on flowcytometric B-cell phenotyping and the clinical course. The clinical evaluation of 303 patients with the established diagnosis of CVID demonstrated a significant coincidence of granulomatous disease, autoimmune cytopenia, and splenomegaly. Phenotyping of B-cell subpopulations confirmed a severe reduction of switched memory B cells in most of the patients that was associated with a higher risk for splenomegaly and granulomatous disease. An expansion of CD21(low) B cells marked patients with splenomegaly. Lymphadenopathy was significantly linked with transitional B-cell expansion. Based on these findings and pathogenic consideration of B-cell differentiation, we suggest an improved classification for CVID (EUROclass), separating patients with nearly absent B cells (less than 1%), severely reduced switched memory B cells (less than 2%), and expansion of transitional (more than 9%) or CD21(low) B cells (more than 10%). Whereas the first group contains all patients with severe defects of early B-cell differentiation, severely reduced switched memory B cells indicate a defective germinal center development as found in inducible constimulator (ICOS) or CD40L deficiency. The underlying defects of expanded transitional or CD21(low) B cells remain to be elucidated. This trial is re-gistered at http://www.uniklinik-freiburg.de/zks/live/uklregister/Oeffentlich.html as UKF000308.
Synthesis of star‐shaped poly(ethylene oxide) (1988)

Abstract Three different methods to synthesize star‐shaped poly(ethylene oxide) are discussed in the present article. In all three cases, the branches are grown from a plurifunctional initiator. It is established that even though the early stages of the polymerization occur in heterogeneous phase, the consequences on the polymers formed are of minor importance. The most significant method is a core‐first process, involving multifunctional poly‐DVB cores as the initiating species, made anionically in dilute solution. Although strong association phenomena are occurring during the growth of the branches, star‐shaped poly(ethylene oxide)s with a high number of functionalized branches are obtained. The polymers arising from all three methods were characterized accurately.
Regulation of the permeability of the gonococcal cell envelope by the mtr system (1994)

The mtrR gene of Neisseria gonorrhoeae controls the level of susceptibility to hydrophobic antibiotics and detergents. The mtrR gene was cloned and shown to encode a putative transcriptional repressor. The mtr region was homologous to the envCD and acrAB regions of Escherichia coli, which are also involved in susceptibility to hydrophobic compounds. A homologous repressor protein was encoded by a previously unrecognized open reading frame within both the envCD and acrAB regions. Deletion of mtrR resulted in increased resistance to antibiotics and detergents: the mtrR mutations in two penicillin-resistant clinical isolates resulted in a change of His-105 to Tyr. We propose that the mtrR repressor allows gonococci to regulate the permeability of its cell envelope in response to environmental signals, so that they can grow in the presence of toxic faecal lipids in the rectum as well as in the genital tract.
“White Graphenes”: Boron Nitride Nanoribbons via Boron Nitride Nanotube Unwrapping (2010)

Inspired by rich physics and functionalities of graphenes, scientists have taken an intensive interest in two-dimensional (2D) crystals of h-BN (analogue of graphite, so-called "white" graphite). Recent calculations have predicted the exciting potentials of BN nanoribbons in spintronics due to tunable magnetic and electrical properties; however no experimental evidence has been provided since fabrication of such ribbons remains a challenge. Here, we show that few- and single-layered BN nanoribbons, mostly terminated with zigzag edges, can be produced under unwrapping multiwalled BN nanotubes through plasma etching. The interesting stepwise unwrapping and intermediate states were observed and analyzed. Opposed to insulating primal tubes, the nanoribbons become semiconducting due to doping-like conducting edge states and vacancy defects, as revealed by structural analyses and ab initio simulations. This study paves the way for BN nanoribbon production and usage as functional semiconductors with a wide range of applications in optoelectronics and spintronics.
Gluing the Respiratory Chain Together (2002)

Cytochrome bc(1) complex (complex III) and cytochrome c oxidase complex (complex IV) are multisubunit homodimers that are essential components of the mitochondrial respiratory chain. Complexes III and IV associate to form a supercomplex that can be displayed using blue native polyacrylamide gel electrophoresis. Both homodimeric complexes contain tightly associated cardiolipin (CL) required for function. We report here that in a crd1Delta strain of yeast (null in expression of CL synthase) approximately 90% of complexes III and IV were observed as individual homodimers; only the supercomplex was observed with CRD1 wild type cells. Introduction of a plasmid born copy of the CRD1 gene under exogenous regulation by doxycycline made possible controlled variation in the in vivo CL levels. At an intermediate level of CL, a mixture of individual homodimers (30%) and supercomplex (70%) was observed. These results strongly indicate that CL plays a central role in higher order organization of components of the respiratory chain of mitochondria.
Chemotherapy-Induced Weakness and Fatigue in Skeletal Muscle: The Role of Oxidative Stress (2011)

Further research investigating antioxidants could provide relief for cancer patients from debilitating muscle weakness, leading to improved quality of life.
Erythropoietic cellular analyses in luspatercept-treated lower-risk myelodysplastic syndromes (MDS): Phase 2 PACE-MDS study. (2018)

7018 Background: Luspatercept (ACE-536) is a TGF-β family ligand trap promoting late-stage erythroid (E) differentiation and increases in hemoglobin. Endpoints of the ongoing, phase 2, open-label study in MDS include E response (IWG HI-E), RBC transfusion independence (RBC-TI, ≥8 weeks), and molecular/bone marrow (BM) morphological characteristics associated with response. Methods: MDS IPSS low or int-1 patients (pts) were treated every 3 weeks subcutaneously (up to 1.75 mg/kg) in the base/extension studies (NCT01749514/NCT02268383). BM and blood samples were analyzed prior to and at the end of 5 cycles of treatment (EOT) by central morphology and flow cytometry according to ELN guidelines to investigate E precursors, soluble transferrin receptor (sTfR), and reticulocytes (retics) in relation to response. Results: Data (as of 08Sept2017) were available for 49 pts (≥0.75 mg/kg) with evaluable flow and BM data. HI-E and RBC-TI responses were 61% (30/49 pts) and 55% (16/29 pts), respectively. At baseline, M/E ratio was lower and sTfR two-fold higher in R vs NR, mirrored by an increase in erythroid precursors. By EOT, retics were increased in R and remained unchanged in NR. Conclusions: These data suggest that expanded late-stage erythropoiesis at baseline is associated with a response to luspatercept. Responses were accompanied by further expansion of erythropoiesis (or activation of bone marrow) and increased release of reticulocytes, supporting luspatercept as an erythroid-maturation agent (EMA). Clinical trial information: NCT01749514, NCT02268383.HI-E responder characteristics. (n) Baseline EOT M/E ratio (BM morphology) R (30)** 1.0 (0.3, 11.5) 0.9 (0.1, 3) NR (19) 2.1 (0.6, 9)* 1.5 (0.2, 32.3)* BM erythroid precursors (%, flow cytometry) R (30) 9.5 (0.9, 43.6) 14.7 (3, 53.3) NR (19) 4.5 (1.2, 24.3)* 5.6 (0.6, 41)* BM proerythroblasts (%, flow cytometry) R (30) 8 (1, 22.2) 5.9 (0.6, 30.7) NR (19) 10.9 (1, 57.5) 11.2 (3.9, 32.3)* sTfR (nmol/L) R (29)** 68.4 (23.7, 181.1) 79.6 (10.6, 270) NR (19)** 35.6 (8.8, 249.7)* 44.7 (11.6, 279.9)* n = 17 Absolute retics (10^9/L) R (26)** 35.9 (7, 154) 53.2 (9.9, 200) n = 25 NR (15) 29.2 (21, 168) 38.6 (14, 183) n = 16 Median (min, max) *p < 0.05 R vs NR **p < 0.05 baseline vs EOT M = myeloid; NR = non responder; R = responder
Isolation of Human Monoclonal Antibodies Using Guided Selection with Mouse Monoclonal Antibodies (2003)

Repertoires of antibody (Ab) V genes derived from nonimmunized human donors (1) or made synthetically (2 3) have been cloned for display on filamentous bacteriophage as either scFvs or Fabs fused to the minor phage coat protein (pIII) (4). Phage Ab repertoires can be subjected to multiple rounds of panning on individual immobilized antigens (Ags) in order to isolate individual Ag-binding clones. This approach has been successfully applied to numerous purified soluble molecules, yielding high-affinity Abs (5). Selection against almost any soluble Ag is now theoretically feasible.
Personality as manifest in word use: Correlations with self-report, acquaintance report, and behavior. (2008)

The use of words is one of the most direct means of expressing thoughts and feelings. However, past studies have had limited success in correlating word use with personality. The purpose of the present study was to identify categories of word use relevant to personality using a broad range of personality data. Using data from 181 participants, the present study correlated word use within a 1-hr life history interview with self-judgments of personality, judgments of personality provided by close acquaintances (who were not exposed to the language sample), and behavioral ratings based on direct observation from a context entirely separate from that from which the language sample was derived. Several categories of word use yielded a large number of correlates with self- and acquaintance personality ratings and behavior. It is suggested that word use is related to personality to a larger degree than previously observed and deserves increased attention as a source of data in personality assessment.
Differential Clearance and Immune Responses to Tick Cell-Derived versus Macrophage Culture-DerivedEhrlichia chaffeensisin Mice (2006)

Human monocytic ehrlichiosis is caused by a tick-transmitted rickettsia, Ehrlichia chaffeensis. We recently reported that E. chaffeensis grown in tick cells expresses different proteins than bacteria grown in macrophages. Therefore, we tested the hypothesis that immune responses against E. chaffeensis would be different if the mice are challenged with bacteria grown in macrophages or tick cells. We assessed the E. chaffeensis clearance from the peritoneum, spleen, and liver by C57BL/6J mice using a TaqMan-based real-time reverse transcription-PCR assay. Macrophage-grown E. chaffeensis was cleared in 2 weeks from the peritoneum, whereas the pathogen from tick cells persisted for nine additional days and included three relapses of increasing bacterial load separated by three-day intervals. Tick cell-grown bacteria also persisted in the livers and spleens with higher bacterial loads compared to macrophage-grown bacteria and fluctuated over a period of 35 days. Three-day periodic cycles were detected in T-cell CD62L/CD44 ratios in the spleen and bone marrow in response to infections with both tick cell- and macrophage-grown bacteria and were accompanied by similar periodic cycles of spleen cell cytokine secretions and nitric oxide and interleukin-6 by peritoneal macrophages. The E. chaffeensis-specific immunoglobulin G response was considerably higher and steadily increased in mice infected with the tick cell-derived E. chaffeensis compared to DH82-grown bacteria. In addition, antigens detected by the immunoglobulins were significantly different between mice infected with the E. chaffeensis originating from tick cells or macrophages. The differences in the immune response to tick cell-grown bacteria compared to macrophage-grown bacteria reflected a delay in the shift of gene expression from the tick cell-specific Omp 14 gene to the macrophage-specific Omp 19 gene. These data suggest that the host response to E. chaffeensis depends on the source of the bacteria and that this experimental model requires the most natural inoculum possible to allow for a realistic understanding of host resistance.
Genetically modified pigs are protected from classical swine fever virus (2018)

Classical swine fever (CSF) caused by classical swine fever virus (CSFV) is one of the most detrimental diseases, and leads to significant economic losses in the swine industry. Despite efforts by many government authorities to stamp out the disease from national pig populations, the disease remains widespread. Here, antiviral small hairpin RNAs (shRNAs) were selected and then inserted at the porcine Rosa26 (pRosa26) locus via a CRISPR/Cas9-mediated knock-in strategy. Finally, anti-CSFV transgenic (TG) pigs were produced by somatic nuclear transfer (SCNT). Notably, in vitro and in vivo viral challenge assays further demonstrated that these TG pigs could effectively limit the replication of CSFV and reduce CSFV-associated clinical signs and mortality, and disease resistance could be stably transmitted to the F1-generation. Altogether, our work demonstrated that RNA interference (RNAi) technology combining CRISPR/Cas9 technology offered the possibility to produce TG animal with improved resistance to viral infection. The use of these TG pigs can reduce CSF-related economic losses and this antiviral strategy may be useful for future antiviral research.