gebhart/patrepeval huggingface dataset:
Studies on the intracerebral injection of bleomycin free and entrapped within liposomes in the rat. (1984)

Reverse phase prepared liposomes of defined composition (dipalmitoyl phosphatidyl choline, cholesterol and dipalmitoyl phosphatidic acid; 7:2:1; DPC) when injected intracerebrally in the rat produced no tissue damage beyond that of the penetrating wound, or altered behaviour pattern over 1 week of observation. The cerebral tissue response and behaviour of rats injected with bleomycin of increasing concentration, free and entrapped within liposomes was studied in short and long term experiments. In separate experiments blood, urine and tissue levels of bleomycin were measured after intracerebral injection of free and liposome entrapped bleomycin in the rat. These studies demonstrated that bleomycin when entrapped within liposomes and injected intracerebrally was of low toxicity to normal cerebral tissue, and was cleared more slowly from the injection site than when the free drug was injected. The results obtained indicated a potential application for drugs entrapped within liposomes acting as a depot preparation in the treatment of cerebral gliomas.
Principles of Fermentation Technology Ed. 3 (2016)

The successful structure of the previous edition of Principles of Fermentation Technology has been retained in this third edition, which covers the key component parts of a fermentation process including growth kinetics, strain isolation and improvement, inocula development, fermentation media, fermenter design and operation, product recovery, and the environmental impact of processes. This accurate and accessible third edition recognizes the increased importance of animal cell culture, the impact of the post-genomics era on applied science and the huge contribution that heterologous protein production now makes to the success of the pharmaceutical industry. This title is ideally suited for both newcomers to the industry and established workers as it provides essential and fundamental information on fermentation in a methodical, logical fashion. Stanbury, Whitaker and Hall have integrated the biological and engineering aspects of fermentation to make the content accessible to members of both disciplines with a focus on the practical application of theory. This text collates all the fermentation fundamentals into one concise reference, making it a valuable resource for fermentation scientists, as well as those studying in the field. Retains its successful structure and covers all components of the fermentation processIntegrates the biological and engineering aspects of fermentation to discuss the most recent developments and advancements in the fieldWritten in a style accessible to readers from either a biological or engineering background with each chapter supported by an extensive bibliography
Acquisition of iron from human transferrin by Porphyromonas gingivalis: a role for Arg‐ and Lys‐gingipain activities (2001)

Porphyromonas gingivalis, a key causative agent of adult periodontitis, is known to produce a variety of virulence factors including proteases. The aim of this study was to evaluate the participation of Arg- and Lys-gingipain activities of P. gingivalis in the acquisition of iron from human transferrin and its subsequent utilization in growth. Iron-saturated transferrin was found to support the long-term growth of P. gingivalis. Our results indicated that P. gingivalis does not produce siderophore and does not possess ferric reductase and transferrin-binding activities. Incubating transferrin with P. gingivalis resulted in degradation of the protein, a step that may be critical for the acquisition of iron from transferrin. Spontaneous and site-directed mutants of P. gingivalis deficient in one or several proteases were used to demonstrate the key role of specific enzymes in degradation of transferrin and subsequent utilization for growth. The lack of both Arg- and Lys-gingipain activities (mutants M1 and KDP128) was associated with an absence of degradation of transferrin and the incapacity of bacteria to grow in the presence of transferrin as the sole source of iron. It was also found that the Lys-gingipain activity is more critical than the Arg-gingipain activity since the mutant KDP112 (deficient in Arg-gingipain A and B) could grow whereas the mutant KDP129 (deficient in Lys-gingipain) could not. The fact that growth of mutant KDP112 was associated with a lower final optical density and a generation time much longer compared with the parent strain suggests that the Arg-gingipain activity also participates in the acquisition of iron from transferrin. Selected inhibitors of cysteine proteases (TLCK, leupeptin and cathepsin B inhibitor II) were tested for their capacity to reduce or inhibit the growth of P. gingivalis under different iron conditions. All three inhibitors were found to completely inhibit growth of strain ATCC 33277 in a medium supplemented with transferrin as the source of iron. The inhibitors had no effects when the bacteria were grown in a medium containing hemin instead of transferrin. The ability of P. gingivalis to cleave transferrin may be an important mechanism for the acquisition of iron from this protein during periodontitis.
High-speed multi-exposure laser speckle contrast imaging with a single-photon counting camera (2015)

Laser speckle contrast imaging (LSCI) has emerged as a valuable tool for cerebral blood flow (CBF) imaging. We present a multi-exposure laser speckle imaging (MESI) method which uses a high-frame rate acquisition with a negligible inter-frame dead time to mimic multiple exposures in a single-shot acquisition series. Our approach takes advantage of the noise-free readout and high-sensitivity of a complementary metal-oxide-semiconductor (CMOS) single-photon avalanche diode (SPAD) array to provide real-time speckle contrast measurement with high temporal resolution and accuracy. To demonstrate its feasibility, we provide comparisons between in vivo measurements with both the standard and the new approach performed on a mouse brain, in identical conditions.
Neuropeptides in skin disease: increased VIP in eczema and psoriasis but not axillary hyperhidrosis (1991)

The neuropeptides vasoactive intestinal polypeptide (VIP), substance P and somatostatin were studied in skin biopsies from patients with eczema, psoriasis and axillary hyperhidrosis. VIP concentrations were elevated in skin affected by eczema and psoriasis, whereas substance P and somatostatin levels did not differ from controls. There was a higher concentration of VIP, but not of substance P or somatostatin, in normal axillary skin when compared to adjacent trunk skin, with abundant VIP-containing fibres surrounding eccrine sweat glands. The VIP concentration was unchanged in skin affected by axillary hyperhidrosis. VIP may increase local blood flow in eczema and psoriasis, but does not appear to play a role in axillary hyperhidrosis.
A NEW BIOCHEMICAL MARKER FOR JOINT INJURY. ANALYSIS OF YKL-40 IN SERUM AND SYNOVIAL FLUID (1993)

We report the development of the first radioimmunoassay for YKL-40, a M(r) = 40 kDa protein which is secreted at high levels by human synovial cells and articular cartilage chondrocytes, and by the human osteosarcoma cell line MG63. This assay uses YKL-40 purified from the conditioned medium of MG63 cells as standard and tracer, and as antigen for immunizing rabbits. With this assay we have discovered high levels of YKL-40 antigen in serum and SF. The molecular weight of serum and SF YKL-40 is identical to purified YKL-40. To evaluate the possible utility of YKL-40 in the assessment of joint disease, we measured YKL-40 in serum and SF of 49 patients with various forms of inflammatory and degenerative joint disease and in the serum of 50 normal adults. The YKL-40 level in serum was significantly higher (P < 0.001) in the patients compared to the normal adults, but there was no difference in serum YKL-40 between the patients with inflammatory joint diseases and OA. The SF levels of YKL-40 were 15-fold higher than serum levels and there was a significant correlation (r = 0.55, P < 0.001) between YKL-40 concentration in SF and serum. Although the tissue distribution of YKL-40 secretion is presently unknown, these observations suggest that a major portion of serum YKL-40 in fact arises from the joint.(ABSTRACT TRUNCATED AT 250 WORDS)
Human Kallikrein 8 Protease Confers a Favorable Clinical Outcome in Non–Small Cell Lung Cancer by Suppressing Tumor Cell Invasiveness (2006)

The human kallikrein 8 (KLK8) gene, a member of the human tissue kallikrein gene family, encodes a serine protease. The KLK8 protein (hK8) is known to be a favorable prognostic marker in ovarian cancer, but the biological basis of this is not understood. We found that overexpressing the KLK8 gene in highly invasive lung cancer cell lines suppresses their invasiveness. This role in invasiveness was further confirmed by the fact that inhibition of endogenous KLK8 expression with a specific short hairpin RNA reduced cancer cell invasiveness. In situ degradation and cell adhesion assays showed that proteins produced from KLK8 splice variants modify the extracellular microenvironment by cleaving fibronectin. DNA microarray experiments and staining of cells for actin filaments revealed that the degradation of fibronectin by hK8 suppresses integrin signaling and retards cancer cell motility by inhibiting actin polymerization. In addition, studies in a mouse model coupled with the detection of circulating tumor cells by quantitative PCR for the human Alu sequence showed that KLK8 suppresses tumor growth and invasion in vivo. Finally, studies of clinical specimens from patients with non-small cell lung cancer showed that the time to postoperative recurrence was longer for early-stage patients (stages I and II) with high KLK8 expression (mean, 49.9 months) than for patients with low KLK8 expression (mean, 22.9 months). Collectively, these findings show that KLK8 expression confers a favorable clinical outcome in non-small cell lung cancer by suppressing tumor cell invasiveness.
Deciphering Trends in Mobile Search (2007)

Understanding the needs of mobile search will help improve the user experience and increase the service's usage. An analysis of search data from a large US carrier showed that cell-phone subscribers are typing longer queries in less time and clicking on more results.
Translational Efficiency Is Up-Regulated by Alternative Exon in Murine IL-15 mRNA (1998)

IL-15 promotes the growth of T cells and shares properties of IL-2. IL-2 is produced exclusively by T cells, while IL-15 message is expressed by a variety of tissues. However, it has been difficult to demonstrate IL-15 in the supernatants of many cells that express message for this cytokine. This suggests that IL-15 production is regulated by post-transcriptional controls. In this study, we cloned three types of murine IL-15 cDNA isoforms generated by alternative splicing and compared the translational efficiency among these isoforms. The translational efficiency of isoforms with alternative exon 5 containing another 3' splice site was significantly higher than that of IL-15 cDNA with originally described exon 5, which is generated by internal splicing of alternative exon 5. The translation product of the isoform containing alternative exon 5 has a shorter open reading frame due to stop codons in additional sequence, followed by a new AUG codon, and displays a shorter leader sequence. The shorter isoform of the IL-15 was detected in peritoneal macrophages stimulated with IFN-gamma and LPS, which expressed an abundant level of alternative exon 5. These results suggest that normal IL-15 production in stimulated macrophages is regulated by splicing of alternative exon 5.
Interleukin-6 biology is coordinated by membrane bound and soluble receptors. (2003)

Cytokine receptors exist in membrane bound and soluble form. Both forms bind their ligands with comparable affinity. While most soluble receptors are antagonists in that they compete for the ligands with their membrane counterparts, some soluble receptors are agonists. In this case, the complex of ligand and soluble receptor binds on target cells to a second receptor subunit and initiates signal transduction. Soluble receptors of the IL-6 family of cytokines are agonists. In vivo, the IL-6/soluble IL-6R complex stimulates several types of target cells not stimulated by IL-6 alone, since they do not express the membrane bound IL-6R. This process has been named transsignaling. We have shown that in several chronic inflammatory diseases like chronic inflammatory bowl disease, peritonitis and rheumatoid arthritis, transsignaling via the soluble IL-6R complexed to IL-6 is a crucial point in the transition from the acute to the chronic state of the disease. The mechanism by which the IL-6/ soluble IL-6R complex regulates the inflammatory state is discussed.
EVALUATION AND TRIALS OF AN AUTOMATIC LICENSE PLATE RECOGNITION SYSTEM EMPLOYING NEURAL NETWORK TECHNIQUES (1994)

Automatic vehicle license plate recognition (ALPR) is receiving significant attention at the present time, for applications including travel time measurement, origin-destination survey, tolls, car park control and security, and various law enforcement tasks. This paper discusses the challenges imposed by open road environments, the solutions under development and trial results obtained so far. A prototype equipment is described which employs a recognition algorithm based on a neural network technique. The authors believe that such an approach will lead to significant performance improvements over conventional template matching schemes. Modular cost-effective systems can now be produced that yield good performance in a wide range of deployment situations.
Secretion of Heterologous Proteins from Saccharomyces Cerevisiae (1987)

Abstract In recent years considerable progress has been achieved on the heterologous gene expression and protein secretion in the yeast Saccharomyces cerevisiae. The variety of natural yeast secretory signal sequences being utilized for heterologous protein secretion are reviewed. The usefulness of the yeast pheromone , α‐ factor leader sequence on the secretion of foreign proteins is emphasized.
Capacity Electrode for Chronic Stimulation (1960)

An electrode is described which can be used for electrical stimulation over prolonged periods without danger of contaminating tissue with electrode products. Use of a thoroughly insulated metal surface precludes all electrode processes, although a transient current can occur to stimulate the tissue.
Recovery of biologically active enzymes after HPLC separation. (1991)

The mass and activity recovery of eight different enzymes (two monomeric, six oligomeric) with molecular masses between 25,000 and 240,000 daltons were tested after HPLC separation on three different HPLC instruments (two with stainless steel and one with titanium flow paths). Most of the tested proteins are known to be sensitive to heavy metal ions. Eight wide pore, ion-exchange columns, two size-exclusion columns and two hydrophobic-interaction columns were used. Both stainless steel and glass column hardware were used in all three separation modes. The elution times were between 8 and 12 minutes. In almost all cases, the activity recovery was between 90% and 100% compared with a control sample incubated in the chromatographic elution buffer for the same time at the same temperature. A severe activity loss (about 30%) was observed with only one ion-exchange column and one enzyme. Neither the column hardware nor the material of the HPLC equipment had any negative effect on the activity recovery of the enzymes tested.
Neural Animation and Reenactment of Human Actor Videos (2018)

We propose a method for generating (near) video-realistic animations of real humans under user control. In contrast to conventional human character rendering, we do not require the availability of a production-quality photo-realistic 3D model of the human, but instead rely on a video sequence in conjunction with a (medium-quality) controllable 3D template model of the person. With that, our approach significantly reduces production cost compared to conventional rendering approaches based on production-quality 3D models, and can also be used to realistically edit existing videos. Technically, this is achieved by training a neural network that translates simple synthetic images of a human character into realistic imagery. For training our networks, we first track the 3D motion of the person in the video using the template model, and subsequently generate a synthetically rendered version of the video. These images are then used to train a conditional generative adversarial network that translates synthetic images of the 3D model into realistic imagery of the human. We evaluate our method for the reenactment of another person that is tracked in order to obtain the motion data, and show video results generated from artist-designed skeleton motion. Our results outperform the state-of-the-art in learning-based human image synthesis. Project page: http://gvv.mpi-inf.mpg.de/projects/wxu/HumanReenactment/
Extracellular Domain N-Glycosylation Controls Human Thrombopoietin Receptor Cell Surface Levels (2011)

The thrombopoietin receptor (TpoR) is a type I transmembrane protein that mediates the signaling functions of thrombopoietin (Tpo) in regulating megakaryocyte differentiation, platelet formation, and hematopoietic stem cell renewal. We probed the role of each of the four extracellular domain putative N-glycosylation sites for cell surface localization and function of the receptor. Single N-glycosylation mutants at any of the four sites were able to acquire the mature N-glycosylated pattern, but exhibited a decreased Tpo-dependent JAK2-STAT response in stably transduced Ba/F3 or Ba/F3-JAK2 cell lines. The ability of JAK2 to promote cell surface localization and stability of TpoR required the first N-glycosylation site (Asn117). In contrast, the third N-glycosylation site (Asn298) decreased receptor maturation and stability. TpoR mutants lacking three N-glycosylation sites were defective in maturation, but N-glycosylation on the single remaining site could be detected by sensitivity to PNGaseF. The TpoR mutant defective in all four N-glycosylation sites was severely impaired in plasma membrane localization and was degraded by the proteasome. N-glycosylation receptor mutants are not misfolded as, once localized on the cell surface in overexpression conditions, they can bind and respond to Tpo. Our data indicate that extracellular domain N-glycosylation sites regulate in a combinatorial manner cell surface localization of TpoR. We discuss how mutations around TpoR N-glycosylation sites might contribute to inefficient receptor traffic and disease.
In vivo imaging reveals a tumor-associated macrophage–mediated resistance pathway in anti–PD-1 therapy (2017)

Monoclonal antibodies (mAbs) targeting the immune checkpoint anti-programmed cell death protein 1 (aPD-1) have demonstrated impressive benefits for the treatment of some cancers; however, these drugs are not always effective, and we still have a limited understanding of the mechanisms that contribute to their efficacy or lack thereof. We used in vivo imaging to uncover the fate and activity of aPD-1 mAbs in real time and at subcellular resolution in mice. We show that aPD-1 mAbs effectively bind PD-1<sup>+</sup> tumor-infiltrating CD8<sup>+</sup> T cells at early time points after administration. However, this engagement is transient, and aPD-1 mAbs are captured within minutes from the T cell surface by PD-1<sup>-</sup> tumor-associated macrophages. We further show that macrophage accrual of aPD-1 mAbs depends both on the drug's Fc domain glycan and on Fcγ receptors (FcγRs) expressed by host myeloid cells and extend these findings to the human setting. Finally, we demonstrate that in vivo blockade of FcγRs before aPD-1 mAb administration substantially prolongs aPD-1 mAb binding to tumor-infiltrating CD8<sup>+</sup> T cells and enhances immunotherapy-induced tumor regression in mice. These investigations yield insight into aPD-1 target engagement in vivo and identify specific Fc/FcγR interactions that can be modulated to improve checkpoint blockade therapy.
Characteristics of the amino acids as components of a peptide hormone sequence (1976)

In the living organism the polypeptide chains of proteins are used for the most diverse purposes: structural support and protection, catalysis of a wide range of chemical reactions, energy transduction, food storage, transport, and—among many others—regulation and co-ordination by information transfer (including humoral transmission by hormones). Molecules with the varied properties required for these multifarious functions are built up of a mere 20 units: the protein-constituent amino acids, connected primarily in a single structural mode (a linear sequence) but finally arranged in space in intricate ways to molecules of the required size, shape and properties. Although the peptide hormones fulfil such a highly specialised role, there is nothing to distinguish, a priori, their sequences from other polypeptide or protein sequences with different biological functions, or no function at all.
Stanol Ester Margarine Alone and With Simvastatin Lowers Serum Cholesterol in Families With Familial Hypercholesterolemia Caused by the FH–North Karelia Mutation (2000)

In heterozygous familial hypercholesterolemia (FH), serum low density lipoprotein (LDL) cholesterol levels are already elevated at birth. Premature coronary heart disease occurs in approximately 30% of heterozygous untreated adult patients. Accordingly, to retard development of atherosclerosis, preventive measures for lowering cholesterol should be started even in childhood. To this end, 19 FH families consumed dietary stanol ester for 3 months. Stanol ester margarine lowers the serum cholesterol level by inhibiting cholesterol absorption. Each individual in the study replaced part of his or her daily dietary fat with 25 g of 80% rapeseed oil margarine containing stanol esters (2.24 g/d stanols, mainly sitostanol). The families who consumed this margarine for 12 weeks included 24 children, aged 3 to 13 years, with the North Karelia variant of FH (FH-NK), 4 FH-NK parents, and 16 healthy family members, and a separate group of 12 FH-NK adults who consumed the margarine for 6 weeks and who were on simvastatin therapy (20 or 40 mg/d). Fat-soluble vitamins were measured by high-pressure liquid chromatography, and cholesterol precursor sterols (indexes of cholesterol synthesis) and cholestanol and plant sterols (indexes of cholesterol absorption efficiency) were assayed by gas-liquid chromatography. No side effects occurred. Serum LDL cholesterol levels were reduced by 18% (P<0.001), 11%, 12% (P<0.001), and 20% (P<0.001) in the 4 groups, respectively. The serum campesterol-to-cholesterol ratios fell by 31% (P<0.001), 29%, 23% (P<0.001), and 36% (P<0.001), respectively, suggesting that cholesterol absorption efficiency was inhibited. Serum lathosterol ratios were elevated by 38% (P<0.001), 11%, 15% (P<0.001), and 19% (P<0.001), respectively, suggesting that cholesterol synthesis was compensatorily upregulated. The FH-NK children increased their serum lathosterol ratio more than did the FH-NK adults treated with stanol ester margarine and simvastatin (P<0.01). In the FH-NK children, serum retinol concentration and alpha-tocopherol-to-cholesterol ratios were unchanged by stanol ester margarine, but alpha- and beta-carotene concentrations and ratios were decreased. As assayed in a genetically defined population of FH patients, a dietary regimen with stanol ester margarine proved to be a safe and effective hypolipidemic treatment for children and adults. In FH-NK adults on simvastatin therapy, serum LDL cholesterol levels could be reduced even further by including a stanol ester margarine in the regimen.