gebhart/patrepeval huggingface dataset:
Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. (1991)

In an effort to identify protein factors that play a regulatory role in the differentiation of adipocytes, we have isolated two genes that encode polypeptides related to CCAAT/enhancer-binding protein (C/EBP; hereafter termed C/EBP alpha). The proteins encoded by these C/EBP-related genes, termed C/EBP beta and C/EBP delta, exhibit similar DNA-binding specificities and affinities compared with C/EBP alpha. Furthermore, C/EBP beta and C/EBP delta readily form heterodimers with one another as well as with C/EBP alpha. The transcriptional activating capacity of these two newly identified C/EBP isoforms was demonstrated by transient transfection experiments in which expression vectors encoding C/EBP beta and C/EBP delta were observed to induce transcription from the promoter of the serum albumin gene in cultured hepatoma cells. The mRNAs encoding C/EBP beta and C/EBP delta were detected in a number of tissues, most of which corresponded to sites of expression of C/EBP alpha. The expression pattern of C/EBP beta and C/EBP delta during adipose conversion of 3T3-L1 cells was examined by Western and Northern blotting assays. In contrast to the expression profile of the gene encoding C/EBP alpha, whose product is not detectable until the late phase of adipocyte differentiation, the c/ebp beta and c/ebp delta genes were actively expressed very early during adipocyte differentiation. Moreover, transcription of the c/ebp beta and c/ebp delta genes was observed to be induced directly by adipogenic hormones. The accumulation of C/EBP beta and C/EBP delta reached a maximal level during the first 2 days of differentiation and declined sharply before the onset of C/EBP alpha accumulation. The temporal pattern of expression of these three C/EBP isoforms during adipocyte differentiation may reflect the underpinnings of a regulatory cascade that controls the process of terminal cell differentiation.
Transforming growth factor beta increases mRNA for matrix proteins both in the presence and in the absence of changes in mRNA stability. (1988)

Transforming growth factor-beta (TGF-beta) has been shown to stimulate synthesis of extracellular matrix proteins, both in animals and in cell culture. We found that mRNAs for alpha 1(I) collagen, fibronectin, and thrombospondin were markedly increased in TGF-beta-treated 3T3 (mouse) cells. For collagen and fibronectin this increase was 10-to 20-fold, as measured by quantitative blot hybridization analysis. A maximal value was reached at 16-24 hr, with a subsequent gradual decline. Concomitant treatment with cycloheximide prevented the stimulation observed with TGF-beta. Under conditions of confluent growth a clear increase in alpha 1(I) collagen mRNA stability was observed, whereas in subconfluent cells no change in mRNA half-life was found, despite an equally large increase in mRNA levels. We suggest that the mode of action of TGF-beta varies with the target cell and depends on the interplay of a number of complex cellular factors.
Hydrogen solubility in jojoba oil (1974)

Abstract The solubility of hydrogen in jojoba oil has been determined at temperatures of 50–250 C and pressures between 100–800 psig. The system behaves according to Henry's law with a heat of solution of 1240 cal/g mole and entropy of solution of 2.9 cal/K g mole. The partial volume of hydrogen varies between 24.6–62.9 ml/g mole in the temperature range considered.
Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome (2004)

Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel coronavirus, but its immunopathological mechanisms have not yet been fully elucidated. We investigated changes in plasma T helper (Th) cell cytokines, inflammatory cytokines and chemokines in 20 patients diagnosed with SARS. Cytokine profile of SARS patients showed marked elevation of Th1 cytokine interferon (IFN)-gamma, inflammatory cytokines interleukin (IL)-1, IL-6 and IL-12 for at least 2 weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumour necrosis factor (TNF)-alpha, anti-inflammatory cytokine IL-10, Th1 cytokine IL-2 and Th2 cytokine IL-4. The chemokine profile demonstrated significant elevation of neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-gamma-inducible protein-10 (IP-10). Corticosteroid reduced significantly IL-8, MCP-1 and IP-10 concentrations from 5 to 8 days after treatment (all P < 0.001). Together, the elevation of Th1 cytokine IFN-gamma, inflammatory cytokines IL-1, IL-6 and IL-12 and chemokines IL-8, MCP-1 and IP-10 confirmed the activation of Th1 cell-mediated immunity and hyperinnate inflammatory response in SARS through the accumulation of monocytes/macrophages and neutrophils.
Synthetic peptides based on motifs present in human band 3 protein inhibit cytoadherence/sequestration of the malaria parasite Plasmodium falciparum. (1993)

Synthetic peptides patterned on the amino acid sequences found in two exofacial regions of band 3 protein (residues 824-829 of loop 7 and residues 547-553 of loop 3) blocked, in a dose-dependent fashion, the in vitro adherence of Plasmodium falciparum-infected erythrocytes to C32 amelanotic melanoma cells. Intravenous infusion of these synthetic peptides into Aotus and Saimiri monkeys infected with sequestering isolates of P. falciparum resulted in the appearance of mature forms of the parasite in the peripheral circulation. The finding that the peptides were effective as adhesion blockers in the micromolar range suggests that cerebral malaria could be managed through antiadhesion therapy.
Multiple Object Recognition with Visual Attention (2014)

We present an attention-based model for recognizing multiple objects in images. The proposed model is a deep recurrent neural network trained with reinforcement learning to attend to the most relevant regions of the input image. We show that the model learns to both localize and recognize multiple objects despite being given only class labels during training. We evaluate the model on the challenging task of transcribing house number sequences from Google Street View images and show that it is both more accurate than the state-of-the-art convolutional networks and uses fewer parameters and less computation.
Monoclonal Antibodies (1981)

FOR many years antibodies have had a major role in the diagnosis of a wide variety of diseases. Radioimmunoassays and other immunologic assays are now used extensively in diagnostic laboratories to detect and quantitate drugs, bacterial and viral products, tumor antigens, and circulating immunoglobulins. However, immunologic assays have always been plagued by uncertainties that result from the unpredictability and heterogeneity of the immune response. Immunization is still more of an art than a science, and serologists have had to be satisfied with whatever quality and quantity of antibodies an immunized animal will provide.Even when apparently pure antigen is used . . .
B-Cell Kinase Lyn Deficiency in Patients with Systemic Lupus Erythematosus (2001)

Decreased expression of Lyn in some patients with SLE represents a B-cell defect that may enhance our understanding of SLE molecular pathogenesis by providing rational therapeutic targets.
Heparin Inhibits Retrovirus Binding to Fibronectin as Well as Retrovirus Gene Transfer on Fibronectin Fragments (2001)

Fibronectin fragments have been shown to improve retrovirus gene transfer efficiency by binding retrovirus and target cells. Using a novel virus adhesion assay, we confirmed binding of type C oncoretrovirus vectors to the heparin II domain of fibronectin and demonstrated inhibition of viral binding and gene transfer by heparin.
BCL-2 family member BOK promotes apoptosis in response to endoplasmic reticulum stress (2015)

B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) is a BCL-2 family protein with high homology to the multidomain proapoptotic proteins BAX and BAK, yet Bok(-/-) and even Bax(-/-)Bok(-/-) and Bak(-/-)Bok(-/-) mice were reported to have no overt phenotype or apoptotic defects in response to a host of classical stress stimuli. These surprising findings were interpreted to reflect functional compensation among the BAX, BAK, and BOK proteins. However, BOK cannot compensate for the severe apoptotic defects of Bax(-/-)Bak(-/-) mice despite its widespread expression. Here, we independently developed Bok(-/-) mice and found that Bok(-/-) cells are selectively defective in their response to endoplasmic reticulum (ER) stress stimuli, consistent with the predominant subcellular localization of BOK at the ER. Whereas Bok(-/-) mouse embryonic fibroblasts exposed to thapsigargin, A23187, brefeldin A, DTT, geldanamycin, or bortezomib manifested reduced activation of the mitochondrial apoptotic pathway, the death response to other stimuli such as etoposide, staurosporine, or UV remained fully intact. Multiple organs in Bok(-/-) mice exhibited resistance to thapsigargin-induced apoptosis in vivo. Although the ER stress agents activated the unfolded protein response, both ATF4 and CHOP activation were diminished in Bok(-/-) cells and mice. Importantly, BAX and BAK were unable to compensate for the defective apoptotic response to ER stress observed in SV40-transformed and primary Bok(-/-) cells, and in vivo. These findings support a selective and distinguishing role for BOK in regulating the apoptotic response to ER stress, revealing--to our knowledge--the first bona fide apoptotic defect linked to Bok deletion.
Basic fibroblast growth factor does not protect against classical radiation pneumonitis in two strains of mice. (1995)

Basic fibroblast growth factor recently has been reported to confer significant protection against death from radiation pneumonitis in C3H/HeJ mice. Although the mechanism of this protection remains unknown, one hypothesis, based on in vitro data, is that basic fibroblast growth factor protects against radiation-induced apoptosis in pulmonary endothelial cells. Because of the potential clinical importance of these data, we repeated our experiments in two strains of mice with differing sensitivities to radiation pneumonitis. One mouse strain, C3Hf/Kam, originated from the same C3H/He strain as the C3H/HeJ mouse used by Fuks et al. in their 1994 study. The other strain, the NCR/Sed-nu/+ strain, is a white mouse heterozygous for the nude trait. In our laboratory, the LD50 for radiation pneumonitis between 12 and 28 weeks after irradiation, the standard assay time for this phase of radiation-induced lung damage, is 12.5 Gy in the C3Hf/Kam and 8.5 Gy in the NCR/Sed-nu/+ strain. Contrary to previous results in the literature, we found that basic fibroblast growth factor did not protect against radiation pneumonitis in either C3Hf/Kam or NCR/Sed-nu/+ mice. Quantitation of apoptosis after both doses to the lungs of the two strains showed that the incidence of apoptosis was less than 1% in C3Hf/Kam mice and 0.5% in NCR/Sed-nu/+ mice. These apoptotic bodies were scattered throughout the lung and were not located selectively in endothelial cells of any size blood vessels.
Cysteine Proteinase Inhibitors Decrease Articular Cartilage and Bone Destruction in Chronic Inflammatory Arthritis (1994)

Abstract Objective . To determine the effects of peptidyl fluoromethyl ketones on the in vitro activity of purified cathepsins B and L, on tissue cysteine proteinase activity, and on cartilage and bone destruction in experimental arthritis. Methods . The effects of the fluoroketones on cathepsins B and L in vitro and the effects of oral administration of fluoroketones on ex vivo cysteine proteinase activity in tissue homogenates were determined by measuring the inhibition of fluorogenic substrate cleavage. To determine the effects on arthritis, animals were injected with adjuvant or type II collagen, treated orally with the fluoroketones, and the severity of arthritis was assessed by clinical, histologic, and radiologic methods. Results . All of the fluoroketones tested were potent inhibitors of purified cathepsins B and L activity. Oral administration of the fluoroketones reduced tissue cysteine proteinase activity by up to 77%. In addition, fluoroketone treatment significantly reduced the severity of clinical joint disease and decreased the destruction of articular cartilage and bone. Quantitative analysis of radiographic images indicated that treatment significantly reduced soft tissue changes, periosteal proliferation, and bone erosion, but only partially reduced juxtaarticular osteoporosis. Conclusion . These studies suggest that cysteine proteinase inhibitors may limit tissue destruction in diseases such as rheumatoid arthritis.
Recombinant vesicular stomatitis virus vectors as oncolytic agents in the treatment of high-grade gliomas in an organotypic brain tissue slice—glioma coculture model (2004)

Data in this study provide in vitro proof-of-principle that rVSV-deltaG is an effective oncolytic agent that has minimal toxic side effects to neurons compared with rVSV-wt and therefore should be considered for development as an adjuvant to surgery in the treatment of glioma.
Fluorescent core–shell silica nanoparticles: towards “Lab on a Particle” architectures for nanobiotechnology (2006)

Novel nanoscale fluorescent materials are integral to the progress of emergent fields such as nanobiotechnology and facilitate new research in a variety of contexts. Sol–gel derived silica is an excellent host material for creating fluorescent nanoparticles by the inclusion of covalently-bound organic dyes. Significant enhancements in the brightness and stability of organic dye emission can be achieved for silica-based core–shell nanoparticle architectures at length scales down to tens of nanometers with narrow size distributions. This tutorial review will highlight these findings and describe the evolution of the fluorescent core–shell silica nanoparticle concept towards integration of multiple functionalities including mesoporosity, metal nanoshells and quantitative chemical sensing. These developments point towards the development of “lab on a particle” architectures with promising prospects for nanobiotechnology, drug development and beyond.
Structurally Modified Firefly Luciferase. Effects of Amino Acid Substitution at Position 286 (1997)

Ser was replaced at position 286 of firefly luciferase (Luciola mingrelica) by a series of naturally occurring and unnatural amino acids. The effect of these substitutions on the properties of luciferase, such as thermostability, pH dependence, and color of light emitted, was investigated. For these purposes, the Ser286 codon (AGT) was replaced by an amber stop codon (TAG) within the luciferase gene and transformed into Escherichia coli strains producing specific amber suppressor tRNA's to express luciferase with different substitutions at this position. The incorporation of Leu, Lys, Tyr, or Gln at this position reduced the thermostability of mutated luciferases. The color of emitted light changed upon substitution from yellow-green (λmax 582 nm) for the wild-type enzyme having Ser286 to, for example, red (λmax 622 nm) for luciferase having Leu286. For further evaluation of the structural relationship between the amino acid position at 286 and the wavelength of emitted light, we used the method of in vitro incorporation of unnatural amino acids, which involves readthrough of a nonsense (UAG) codon by a misacylated suppressor tRNA. The amino acids incorporated at position 286 in this fashion included O-glucosylated serine, serine phosphonate, tyrosine phosphate, and tyrosine methylenephosphonate. The wavelength of light emitted by the luciferase analogues was measured. While the introduction of serine phosphonate and glucosylated serine did not change the λmax of light produced by luciferase, the incorporation of tyrosine phosphate and tyrosine methylenephosphonate into position 286 altered the spectra of emitted light compared with those of Ser286 and Tyr286. The pH dependence of the wavelength of light emitted by the luciferases containing the negatively charged phosphorylated Tyr analogues was demonstrated and could be rationalized in terms of the pKa's of the phosph(on)ate oxygens.
Genomic Approaches Uncover Increasing Complexities in the Regulatory Landscape at the Human SCL (TAL1) Locus (2010)

The SCL (TAL1) transcription factor is a critical regulator of haematopoiesis and its expression is tightly controlled by multiple cis-acting regulatory elements. To elaborate further the DNA elements which control its regulation, we used genomic tiling microarrays covering 256 kb of the human SCL locus to perform a concerted analysis of chromatin structure and binding of regulatory proteins in human haematopoietic cell lines. This approach allowed us to characterise further or redefine known human SCL regulatory elements and led to the identification of six novel elements with putative regulatory function both up and downstream of the SCL gene. They bind a number of haematopoietic transcription factors (GATA1, E2A LMO2, SCL, LDB1), CTCF or components of the transcriptional machinery and are associated with relevant histone modifications, accessible chromatin and low nucleosomal density. Functional characterisation shows that these novel elements are able to enhance or repress SCL promoter activity, have endogenous promoter function or enhancer-blocking insulator function. Our analysis opens up several areas for further investigation and adds new layers of complexity to our understanding of the regulation of SCL expression.
STABLE: protein‐DNA fusion system for screening of combinatorial protein libraries in vitro (1999)

We have developed a new method that permits the complete in vitro construction and selection of peptide or protein libraries. This method relies on an in vitro transcription/translation reaction compartmentalized in water in oil emulsions. In each emulsion compartment, streptavidin (STA)-fused polypeptides are synthesized and attached to the encoding DNA via its biotin label. The resulting protein-DNA fusion molecules recovered from the emulsion can be subjected to affinity selection based on the properties of the peptide portion, whose sequence can be determined from that of its DNA-tag. This method, named 'STABLE' (STA-biotin linkage in emulsions), should be useful for rapid in vitro evolution of proteins and for ligand-based selection of cDNA libraries.
Comparing the angiogenic potency of naïve marrow stromal cells and Notch-transfected marrow stromal cells (2013)

These data indicate that SB623 cell-secreted angiogenic factors promoted several aspects of angiogenesis, which likely contribute to promoting recovery in the injured brain.
Characterization of the epitope for anti-human respiratory syncytial virus F protein monoclonal antibody 101F using synthetic peptides and genetic approaches (2007)

Chimeric 101F (ch101F) is a mouse-human chimeric anti-human respiratory syncytial virus (HRSV) neutralizing antibody that recognizes residues within antigenic site IV, V, VI of the fusion (F) glycoprotein. The binding of ch101F to a series of peptides overlapping aa 422-438 spanning antigenic site IV, V, VI was analysed. Residues 423-436 comprise the minimal peptide sequence for ch101F binding. Substitution analysis revealed that R429 and K433 are critical for ch101F binding, whilst K427 makes a minor contribution. Binding of ch101F to a series of single mutations at positions 427, 429 and 433 in the F protein expressed recombinantly on the cell surface confirmed the peptide results. Sequence analysis of viruses selected for resistance to neutralization by ch101F indicated that a single change (K433T) in the F protein allowed ch101F escape. The results confirm that ch101F and palivizumab have different epitope specificity and define key residues for ch101F recognition.
Toxicity of the topoisomerase I inhibitors (2005)

The topoisomerase I inhibitors represent a class of antineoplastic agents with a wide spectrum of activity against malignancies. Currently available topo-isomerase I inhibitors are derivatives of the parent compound, camptothecin. Irinotecan is most active against gastrointestinal (GI) tumours, and has predominantly GI and haematological toxicities. Significant pharmacokinetic variability occurs in patients with hepatic dysfunction, particularly those with glucuronidation pathway deficiencies. The toxicity of topotecan is principally haematological with little extramedullary toxicity. Topotecan is well-tolerated in patients with significant hepatic dysfunction; however, patients with even mild renal insufficiency require significant dose reductions. This article discusses the toxicities of these drugs in detail, including the need for dose adjustments in selected patient populations.
Nuclear shift of hnRNP K protein in neoplasms and other states of enhanced cell proliferation (2003)

The heterogeneous nuclear ribonucleoprotein K (hnRNP K), is a ubiquitously expressed protein that interacts with signal transducers, proteins that modulate gene expression and selective RNA and DNA motifs. K protein is modified in response to extracellular signals and directly regulates rates of transcription and translation. We used serum-treated hepatocyte culture, liver after partial hepatectomy and hepatic neoplasms as systems to compare expression, subcellular distribution and tyrosine phosphorylation of K protein in quiescent and dividing cells. The results show that expression of K protein mRNA was increased in states of enhanced proliferation. Levels of nuclear K protein were also higher in proliferating compared to resting cells. In contrast, levels of cytoplasmic K protein were the same or lower in dividing compared to quiescent cells. States of enhanced proliferation were also associated with increased levels of K protein tyrosine phosphorylation. Nuclear shift of K protein in dividing cells may reflect involvement of K protein in signalling multiple events that regulate expression of genes in proliferating cells.
Expression of insulin-like growth factor-binding protein 6 complementary DNA alters neuroblastoma cell growth. (1998)

Insulin-like growth factors I and II (IGF-I and IGF-II) are actively involved in neuroblastoma cell growth. In all biological fluids, they are noncovalently bound to high-affinity binding proteins. At least six species of these IGF-binding proteins (IGFBPs) have been identified, but their precise roles remain unclear. One of them, IGFBP-6, is produced by neuroblastoma cells in culture under certain experimental conditions and seems to be associated with the arrest of cell growth. We stably transfected IGR-N-91 and SK-N-SH neuroblastoma cells with an expression vector comprising IGFBP-6 cDNA, whose expression was placed under the control of the constitutive and ubiquitous cytomegalovirus promoter. Analyses of the cell cycle (flux cytofluorometry), mitogenic activity (radiolabeled thymidine incorporation), and the number of viable cells (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test) showed that the mitogenic effects of serum, IGF-I, IGF-II, and des (1-3) IGF-I, a truncated IGF-I analogue with no affinity for IGFBP-6, were depressed in both transfected cell lines. With s.c. injection of transfected IGR-N-91 cells into nude mice, tumors developed in only 50-70% of cases, 1 or 2 weeks after those in controls, and were 60-90% smaller. Our findings show that IGFBP-6 influences neuroblastoma cell growth, both in vitro and in experimental xenograft development.