gebhart/patrepeval huggingface dataset:
Vascular endothelial growth factor in human glioma cell lines: induced secretion by EGF, PDGF-BB, and bFGF (1995)

Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is an endothelial cell-specific mitogen that is structurally related to platelet-derived growth factor (PDGF). Vascular endothelial growth factor/vascular permeability factor induces angiogenesis in vivo and may play a critical role in tumor angiogenesis. Using immunohistochemical analysis, the authors demonstrated the presence of VEGF/VPF protein in surgical specimens of glioblastoma multiforme and cultured glioma cells. By means of an enzyme-linked immunosorbent assay (ELISA) of cell supernatants, the authors showed that VEGF/VPF is variably secreted by all nine cultured human malignant glioma cell lines (CH-235MG, D-37MG, D-54MG, D-65MG, U-87MG, U-105MG, U-138MG, U-251MG, U-373MG) and by a single meningioma cell line (CH-157MN). An immunocytochemical survey of these cell lines revealed a cytoplasmic and cell-surface distribution of VEGF/VPF. In the U-105MG glioma cell line, VEGF/VPF secretion was induced with physiological concentrations of epidermal growth factor, PDGF-BB, or basic fibroblast growth factor, but not with PDGF-AA. Moreover, it was observed that activation of convergent growth factor signaling pathways led to increased glioma VEGF secretion. Similar results were obtained using these growth factor combinations in the D-54MG glioma cell line. The data obtained suggest a potential role for VEGF/VPF in tumor hypervascularity and peritumoral edema. These observations may lead to development of new therapeutic strategies.
Protein Posttranslational Modifications: The Chemistry of Proteome Diversifications (2005)

Abstract The diversity of distinct covalent forms of proteins (the proteome) greatly exceeds the number of proteins predicted by DNA coding capacities owing to directed posttranslational modifications. Enzymes dedicated to such protein modifications include 500 human protein kinases, 150 protein phosphatases, and 500 proteases. The major types of protein covalent modifications, such as phosphorylation, acetylation, glycosylation, methylation, and ubiquitylation, can be classified according to the type of amino acid side chain modified, the category of the modifying enzyme, and the extent of reversibility. Chemical events such as protein splicing, green fluorescent protein maturation, and proteasome autoactivations also represent posttranslational modifications. An understanding of the scope and pattern of the many posttranslational modifications in eukaryotic cells provides insight into the function and dynamics of proteome compositions.
Acetal-Derivatized Dextran: An Acid-Responsive Biodegradable Material for Therapeutic Applications (2008)

Dextran, a biocompatible, water-soluble polysaccharide, was modified at its hydroxyls with acetal moieties such that it became insoluble in water but freely soluble in common organic solvents enabling its use in the facile preparation of acid-sensitive microparticles. These particles degrade in a pH-dependent manner: FITC-dextran was released with a half-life at 37 degrees C of 10 h at pH 5.0 compared to a half-life of approximately 15 days at pH 7.4. Both hydrophobic and hydrophilic cargoes were successfully loaded into these particles using single and double emulsion techniques, respectively. When used in a model vaccine application, particles loaded with the protein ovalbumin (OVA) increased the presentation of OVA-derived peptides to CD8+ T-cells 16-fold relative to OVA alone. Additionally, this dextran derivative was found to be nontoxic in preliminary in vitro cytotoxicity assays. Owing to its ease of preparation, processability, pH-sensitivity, and biocompatibility, this type of modified dextran should find use in numerous drug delivery applications.
Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): Initial KarMMa results. (2020)

8503 Background: Outcomes are poor in triple-class exposed RRMM patients (pts) who progress on immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), and CD38 antibodies (mAbs). Ide-cel, a BCMA targeted CAR T cell therapy, showed promising tolerability and efficacy in RRMM pts in the phase I CRB-401 study ( NEJM2019;380:1726). We present primary efficacy and safety data from the pivotal phase II KarMMa trial of ide-cel in RRMM (NCT03361748). Methods: Enrolled pts had ≥3 prior regimens (including IMiD, PI, and CD38 mAb) and were refractory to their last regimen per IMWG criteria. After lymphodepletion (cyclophosphamide 300 mg/m 2 + fludarabine 30 mg/m 2 x 3), pts received 150─450 × 10 6 CAR+ T cells (target dose range). Endpoints included overall response rate (ORR; primary), complete response (CR) rate, duration of response (DoR), and PFS. Results: Of 140 pts enrolled, 128 received ide-cel. Median age was 61 y; median no. of prior regimens was 6; 84% were triple- and 26% were penta-refractory. Most pts (88%) had bridging therapy. At data cutoff (16 Oct 2019), median follow up was 11.3 mo. ORR was 73% and median PFS was 8.6 mo; both increased with higher dose (Table). All subgroups had an ORR ≥50%, including older and high-risk pts. Most common any-grade (Gr) toxicities were cytopenias (97%) and cytokine release syndrome (CRS; 84%). CRS was mainly Gr 1/2; 5 pts (5%) had Gr 3, 1 had Gr 4, and 1 had Gr 5 (at 300 × 10 6 ). Neurotoxicity developed in 23 pts (18%); 4 (3%) Gr 3 and 0 Gr ≥4. Median peak CAR+ T cell expansion occurred at 11 d. Expansion was higher in responders and parameters (AUC 0 −28d , C max ) increased with higher dose, with exposure overlap across doses. Persistence was durable, with CAR+ T cells detected in 29/49 (59%) and 4/11 pts (36%) at 6 and 12 mo. Conclusions: Ide-cel demonstrated deep, durable responses in heavily pretreated RRMM pts. Efficacy and safety reflected prior reports and support a favorable ide-cel clinical benefit-risk profile across the target dose range. Clinical trial information: NCT03361748 . [Table: see text]
Gene expression in cotton (Gossypium hirsutum L.) fiber: cloning of the mRNAs. (1992)

Cotton, an important natural fiber, is a differentiated epidermal cell. The number of genes that are active in fiber cells is similar to those in leaf, ovule, or root tissues. Through differential screening of a fiber cDNA library, we isolated five cDNA clones that are preferentially expressed in fiber. One of the cDNA clones, pCKE6, corresponded to an abundant mRNA in fiber. Transcripts for E6 were detected throughout the development of the fiber. Immunoprecipitation of in vitro translation products and Western blot analysis of fiber proteins showed two polypeptides in the range of 30-32 kDa as the products of E6 mRNA. Sequence analysis and hybrid-selected RNA translation also suggest that E6 mRNAs encode two polypeptides. Concentrations of E6 mRNA and protein are highest during the late primary cell wall and early secondary cell wall synthesis stages. Sequence comparison of E6 with other known eukaryotic and prokaryotic genes reveals no significant homology (GenBank; December 1991). E6 or a homologous gene(s) is conserved in several members of Malvaceae as well as in one other fiber-producing plant, kapok, but is not found in several other plants examined or in Acetobacter xylinum. A genomic clone corresponding to pCKE6 was isolated, and the promoter element of the E6 gene was shown to direct the expression of a carrot extensin mRNA in a tissue-specific and developmentally regulated fashion in transgenic cotton plants.
Thymus cell migration: Quantitative aspects of cellular traffic from the thymus to the periphery in mice (1980)

We have used intrathymic injection of fluorescein isothiocyanate to label thymocytes in situ. The method gives random labeling of the thymocyte population and so can be used to quantitate the extent of migration of cells from the thymus to the periphery. Migrant cells can be visualized in frozen sections or cell suspensions of peripheral organs by their fluorescence. Our data show that in young adults, about 1% of thymocytes leave the thymus per day. Since the bulk of thymocytes turn over every 5 to 7 days, this indicates that the vast majority (95%) of thymocytes die within the thymus. Cells that do leave the thymus, go mainly to the T areas of lymph nodes, spleen and Peyer's patches. Migrants are extremely rare in bone marrow, gut and liver. Migration is about the same in neonates as in adults relative to the size of the thymus, but is considerably lower in older animals where it is only about 0.1% of thymocytes per day at the age of six months.
Two New Mycobacterium Strains and Their Role in Toluene Degradation in a Contaminated Stream (1998)

Two toluene-degrading strains, T103 and T104, were isolated from rock surface biomass in a freshwater stream contaminated with toluene. The strains exhibit different capacities for degradation of toluene and other aromatic compounds and have characteristics of the genus Mycobacterium. Both are aerobic, rod-shaped, gram-positive, nonmotile, and acid-alcohol fast and produce yellow pigments. They have mainly straight-chain saturated and monounsaturated fatty acids with 10 to 20 carbon atoms and large amounts of tuberculostearic acid that are typical of mycobacteria. Fatty acid analyses indicate that T103 and T104 are different mycobacterial strains that are related at the subspecies level. Their identical 16S rDNA sequences are most similar to Mycobacterium aurum and Mycobacterium komossense, and they constitute a new species of fast-growing mycobacteria. Ecological studies reveal that toluene contamination has enriched for toluene-degrading bacteria in the epilithic microbial community. Strains T103 and T104 play only a small role in toluene degradation in the stream, although they are present in the habitat and can degrade toluene. Other microorganisms are consequently implicated in the biodegradation.
Solution structure of a 142-residue recombinant prion protein corresponding to the infectious fragment of the scrapie isoform (1997)

The scrapie prion protein (PrPSc) is the major, and possibly the only, component of the infectious prion; it is generated from the cellular isoform (PrPC) by a conformational change. N-terminal truncation of PrPSc by limited proteolysis produces a protein of approximately 142 residues designated PrP 27-30, which retains infectivity. A recombinant protein (rPrP) corresponding to Syrian hamster PrP 27-30 was expressed in Escherichia coli and purified. After refolding rPrP into an alpha-helical form resembling PrPC, the structure was solved by multidimensional heteronuclear NMR, revealing many structural features of rPrP that were not found in two shorter PrP fragments studied previously. Extensive side-chain interactions for residues 113-125 characterize a hydrophobic cluster, which packs against an irregular beta-sheet, whereas residues 90-112 exhibit little defined structure. Although identifiable secondary structure is largely lacking in the N terminus of rPrP, paradoxically this N terminus increases the amount of secondary structure in the remainder of rPrP. The surface of a long helix (residues 200-227) and a structured loop (residues 165-171) form a discontinuous epitope for binding of a protein that facilitates PrPSc formation. Polymorphic residues within this epitope seem to modulate susceptibility of sheep and humans to prion disease. Conformational heterogeneity of rPrP at the N terminus may be key to the transformation of PrPC into PrPSc, whereas the discontinuous epitope near the C terminus controls this transition.
Sleep and Adaptive Link Rate Control for Power Saving in 10G-EPON Systems (2009)

This paper proposes a novel power-saving mechanism for the 10 Gbit/s Ethernet passive optical network (10G-EPON) systems that are currently being discussed in IEEE 802.3av. The proposed power-saving mechanism includes a sleep control function and an adaptive link rate (ALR) control function. The sleep control function switches the modes of optical network units (ONUs), i.e. active and sleep modes, depending on the presence or absence of traffic. The ALR control function switches the link rate between the optical line terminal (OLT) and an ONU, i.e. 1 Gbit/s or 10 Gbit/s, depending on the quantity of traffic. The proposed hybrid mechanism offers effective power management of ONUs on the basis of the traffic conditions. The proposed hybrid mechanism is validated by some numerical simulations.
A platform for efficient, thiol-stable conjugation to albumin's native single accessible cysteine (2015)

Herein we report the use of bromomaleimides for the construction of stable albumin conjugates via conjugation to its native, single accessible, cysteine followed by hydrolysis. Advantages over the classical maleimide approach are highlighted in terms of quantitative hydrolysis and absence of undesirable retro-Michael deconjugation.
Intestinal alkaline phosphatase: role in the depressed gut lipid transport after trauma-hemorrhagic shock. (1997)

Although studies have indicated that the gut lipid absorptive capacity is impaired after trauma and hemorrhagic shock, the mechanism responsible for this remains unknown. The aim of this study, therefore, was to determine whether intestinal alkaline phosphatase (IAP) plays any role in the depressed gut lipid absorptive function observed under such conditions. To determine this, 5 cm midline laparotomy (i.e., trauma induced) was performed in the rats, and animals were then bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of shed blood volume was returned in the form of Ringer's lactate. The rats were resuscitated with four times the volume of maximal bleedout with Ringer's lactate over 60 min. For in vivo lipid loading test, 1 mL olive oil was given intraduodenally upon the completion of resuscitation. The enterocytes were isolated at either 0, 1.5, or 5 h after fat feeding, and the soluble, membranous and pre-chylomicron (pre-CM) IAP activities as well as triglyceride contents were determined thereafter. The results indicated that the soluble IAP activity in the villus tip cells isolated from trauma-hemorrhaged rats increased significantly at 0, 1.5, or 5 h after fat feeding. The pre-CMIAP activity, however, decreased markedly in villus tip cells at 1.5 or 5 h after lipid administration, which was associated with the decreased pre-CM triglyceride contents in villus tip cells under such conditions. The altered IAP activity in villus tip cells, therefore, appears to play a role in the depressed gut lipid absorption and transport following trauma-hemorrhage and resuscitation.
Rapid immune activation by CpG motifs in bacterial DNA. Systemic induction of IL-6 transcription through an antioxidant-sensitive pathway (1996)

Unmethylated CpG dinucleotides (CpG motif) in bacterial DNA or synthetic oligodeoxynucleotides (CpG DNA) rapidly activate murine B cells to secrete IL-6 and IgM, as well as to proliferate. Within 30 min after CpG DNA stimulation in vivo, IL-6 mRNA levels were increased in liver, spleen, and thymus cells. Serum IL-6 protein was markedly increased within 1 h of stimulation. Treatment of a B cell line with CpG DNA led to an increase in the transcriptional activity of the IL-6 promoter. This CpG DNA-induced IL-6 production was not mediated via either a protein kinase C (PKC)-, protein kinase A (PKA)-, or nitric oxide (NO.)-dependent pathway but was inhibited by an antioxidant. In addition, the level of intracellular reactive oxygen species was increased within 20 min after CpG DNA, but not control non-CpG DNA, treatment. These results suggest that CpG DNA-induced IL-6 production is mediated through a reactive oxygen intermediate-dependent pathway. CpG DNA-mediated IL-6 production was enhanced by simultaneous signals delivered through the Ag receptor. The addition of neutralizing Abs against IL-6 to B cell cultures along with CpG oligodeoxynucleotides essentially abolished the CpG DNA-induced increased IgM secretion but had no significant effect on the B cell proliferation induced by the CpG motif. Our results suggest that the induction of IL-6 expression in response to CpG motifs in bacterial DNA may be an important immune defense mechanism that facilitates a rapid response to microbial infection.
America’s Amazons: Women soldiers of the American Civil War (2013)

During the American Civil War, hundreds of women disguised as men enlisted into the Union and Confederate armies to fight for their chosen cause. Until recently, historians have mostly ignored the presence of these women. This article discusses some of the women soldiers' motivations to partake so directly in the war effort.
Chimeric Glycosaminoglycan Oligosaccharides Synthesized by Enzymatic Reconstruction and Their Use in Substrate Specificity Determination of Streptococcus Hyaluronidase (2000)

A method was developed for the reconstruction of glycosaminoglycan (GAG) oligosaccharides using the transglycosylation reaction of an endo-beta-N-acetylhexosaminidase, testicular hyaluronidase, under optimal conditions. Repetition of the transglycosylation using suitable combinations of various GAGs as acceptors and donors made it possible to custom-synthesize GAG oligosaccharides. Thus we prepared a library of chimeric GAG oligosaccharides with hybrid structures composed of disaccharide units such as GlcA-GlcNAc (from hyaluronic acid), GlcA-GalNAc (from chondroitin), GlcA-GalNAc4S (from chondroitin 4-sulfate), GlcA-GalNAc6S (from chondroitin 6-sulfate), IdoA-GalNAc (from desulfated dermatan sulfate), and GlcA-GalNAc4,6-diS (from chondroitin sulfate E). The specificity of the hyaluronidase from Streptococcus dysgalactiae (hyaluronidase SD) was then investigated using these chimeric GAG oligosaccharides as model substrates. The results indicate that the specificity of hyaluronidase SD is determined by the following restrictions at the nonreducing terminal side of the cleavage site: (i) at least one disaccharide unit (GlcA-GlcNAc) is necessary for the enzymatic action of hyaluronidase SD; (ii) cleavage is inhibited by sulfation of the N-acetylgalactosamine; (iii) hyaluronidase SD releases GlcA-GalNAc and IdoA-GalNAc units as well as GlcA-GlcNAc. At the reducing terminal side of the cleavage site, the sulfated residues on the N-acetylgalactosamines in the disaccharide units were found to have no influence on the cleavage. Additionally, we found that hyaluronidase SD can specifically and endolytically cleave the internal unsulfated regions of chondroitin sulfate chains. This demonstration indicates that custom-synthesized GAG oligosaccharides will open a new avenue in GAG glycotechnology.
Deleted HTLV-I Provirus in Blood and Cutaneous Lesions of Patients with Mycosis Fungoides (1991)

Mycosis fungoides, a rare form of cutaneous T cell leukemia/lymphoma, is suspected of having a viral etiology on the basis of certain similarities to adult T cell leukemia, which is associated with human T cell leukemia/lymphoma virus type I (HTLV-I) infection. Cell lines were established from peripheral blood mononuclear cells (PBMC) of an HTLV-I-seronegative patient with mycosis fungoides. DNA hybridization analysis revealed the presence of HTLV-I-related sequences with unusual restriction endonuclease sites. Sequence analysis of subcloned fragments demonstrated the presence of a monoclonally integrated provirus with a 5.5-kilobase deletion involving large regions of gag and env and all of pol. Additional evidence for the presence of deleted proviruses was found by polymerase chain reaction (PCR) amplification of DNA from cutaneous lesions of five other HTLV-I-seronegative patients. The findings suggest that HTLV-I infection may be involved in the etiology of at least certain cases of mycosis fungoides.
Nanoheteroepitaxy of GaN on a nanopore array Si surface (2003)

We report the growth by molecular beam epitaxy and the optical characterization of GaN films nucleated on a Si(111) surface that has been patterned by dry etching an ordered array of nanometer-scale pores prior to the growth. The etching is performed using an anodized aluminum oxide membrane as a mask. The nanopore array surface with the pore diameter of 60 nm and periodicity of 110 nm exhibits significant effects on emissivity and the optical properties of the resulting film. Room-temperature photoluminescence intensity increases by a factor of 5 for GaN grown on nanoporous Si. Peak shifts in photoluminescence and Raman spectroscopy suggest that the material grown on nanopores may be more relaxed than films grown on flat substrates. The effects of nanopore topography on the nucleation of GaN films offer a potential path to significant improvement of III-nitride heteroepitaxy for device applications.
Mouse Models of Atherosclerosis (1996)

As a species the mouse is highly resistant to atherosclerosis. However, through induced mutations it has been possible to develop lines of mice that are susceptible to this disease. For example, mice that are deficient in apolipoprotein E, a ligand important in lipoprotein clearance, develop atherosclerotic lesions resembling those observed in humans. These lesions are exacerbated when the mice are fed a high-cholesterol, high-fat, Western-type diet. Other promising models are mice that are deficient in the low density lipoprotein receptor and transgenic mice that express human apolipoprotein B and transdominant mutant forms of apolipoprotein E. These models are now being used to study the pathogenesis of atherosclerotic lesions, as well as the influence of genetics, environment, hormones, and drugs on lesion development.
Inhibition of Androgen Synthesis in Human Testicular and Prostatic Microsomes and in Male Rats by Novel Steroidal Compounds (1999)

The C17,20-lyase and 5α-reductase are key enzymes in the biosynthesis of androgens. The effects of novel steroidal compounds were evaluated as inhibitors against both human C17,20-lyase and 5α-reductase in vitro. The concentrations of testosterone (T) and dihydrotestosterone (DHT) in the prostate, testis and serum and changes in the tissue weights were also determined in rats treated with the novel inhibitors. L-12 and L-26 showed potent inhibition of human testicular C17,20-lyase with IC50 values of 50 and 25 nm, respectively. L-12, L-38, and I-47 showed moderate inhibition of human testicular C17,20-lyase with IC50 values of 75, 108, and 70 nm, respectively similar to ketoconazole (78 nm). Interestingly, L-6, L-26, and L-38 also showed some inhibitory activity against 5α-reductase with IC50 values of 75, 125, and 377 nm, respectively. Finasteride, an inhibitor of 5α-reductase had an IC50 value of 33 nm. However, ketoconazole did not inhibit 5α-reductase nor did finasteride inhibit C17,20-lyase. Treatment of normal male rats with several of these novel inhibitors (50 mg/kg·day, sc, for 14 consecutive days) caused about 45–91% decrease in serum, testicular and prostatic T concentration. Similarly, serum and prostatic DHT concentration were significantly decreased in rats treated with these novel compounds by 50–90% compared with controls. Surgical castration caused almost complete elimination of circulating T and DHT concentration in rat tissues. L-6 and L-12 were the most effective and reduced the wet weight of the prostate by 50%. Although future improvements in their bioavailability are necessary, these novel steroidal compounds show promise as potential agents for reducing T and DHT levels in patients with androgen dependent diseases.
Fabric quality evaluation by objective measurement (1994)

The objective measurement of hand and related attributes of fabrics which determine their value to the consumer, has been well recognized by the manufacturing industries and consumers. This article describes in brief the concept of fabric objective measurement and its potential in today's advanced, quality-conscious and competitive market. The measurement principle and the various profitable application areas of objective evaluation of fabrics are also described. In addition, a brief outline of the instruments developed under the trade name of KES and FAST systems for measuring fabric performance characteristics is given.