gebhart/patrepeval huggingface dataset:
Cooperative bit-loading and fairness bandwidth allocation in ADSL systems (2003)

This paper examines the performance of bundled ADSL systems and proposes an extension to their bit-loading mechanism that results in fair allocation of the available bandwidth. The "rate-maximization" bit-loading method provides less average data rate compared to the optimum "target-rate" strategy, which depends on the number of active lines in the system and the length of the DSL loop. Under a non-cooperative bit-loading approach, the total data rate is not distributed uniformly among the different active lines. The individual data rate depends on the activation time of each modem relative to the total number of lines in the system. The proposed bit-loading mechanism is applied to the downstream ADSL traffic, is executed by a management unit of the central office, uses the results of the single-user bit-loading mechanism and leads to fair data rate distribution.
Molecular determinants for CC-chemokine recognition by a poxvirus CC-chemokine inhibitor (2001)

Poxviruses express a family of secreted proteins that bind with high affinity to chemokines and antagonize the interaction with their cognate G protein-coupled receptors (GPCRs). These viral inhibitors are novel in structure and, unlike cellular chemokine receptors, are able to specifically interact with most, if not all, CC-chemokines. We therefore sought to define the structural features of CC-chemokines that facilitate this broad-spectrum interaction. Here, we identify the residues present on human monocyte chemoattractant protein-1 (MCP-1) that are required for high-affinity interaction with the vaccinia virus 35-kDa CC-chemokine binding protein (VV-35kDa). Not only do these residues correspond to those required for interaction with the cognate receptor CCR2b but they are also conserved among many CC-chemokines. Thus, the results provide a structural basis for the ability of VV-35kDa to promiscuously recognize CC-chemokines and block binding to their receptors.
3-Alkoxy-pyrrolo[1,2-b]pyrazolines as Selective Androgen Receptor Modulators with Ideal Physicochemical Properties for Transdermal Administration (2014)

We describe the synthesis and characterization of 3-alkoxy-pyrrolo[1,2-b]pyrazolines as novel selective androgen receptor (AR) modulators that possess excellent physicochemical properties for transdermal administration. Compound 26 bound to human AR with an IC50 of 0.7 nM with great selectivity over other nuclear hormone receptors and potently activated AR in a C2C12 muscle cell reporter gene assay with an EC50 of 0.5 nM. It showed high aqueous solubility of 1.3 g/L at pH 7.4, and an in silico model as well as a customized parallel artificial membrane permeability assay indicated good skin permeation. Indeed, when measuring skin permeation through excised human skin, an excellent flux of 2 μg/(cm(2)·h) was determined without any permeation enhancers. In a 2 week Hershberger model using castrated rats, the compound showed dose-dependent effects fully restoring skeletal muscle weight at 0.3 mg/kg/day after subcutaneous administration with high selectivity over prostate stimulation.
Photoreactive analog of peptide FN‐C/H‐V from the carboxy‐terminal heparin‐binding domains of fibronectin supports endothelial cell adhesion and spreading on biomaterial surfaces (1996)

The extracellular matrix protein fibronectin (FN) plays an important role in cell adhesion, spreading, and motility. Several cell-adhesion promoting domains exist within fibronectin, and peptide sequences from these domains have been shown to play an important role in cell interactions with fibronectin. Recently, a peptide sequence (FN-C/H-V) from the 33/66 kD carboxy-terminal heparin-binding domains of fibronectin was shown to promote the adhesion and spreading of vascular endothelial cells in vitro. Endothelial cell spreading on this peptide was followed by cytoskeletal reorganization, focal contact formation, and, ultimately, cell migration. In the current study, a photoreactive analog of FN-C/H-V (ASD-V) was generated using a heterobifunctional photoreactive crosslinking agent, sulfosuccinimidyl 2-(p-azidosalicylamido) ethyl-1,3′-dithio-propionate. ASD-V was then covalently coupled to polystyrene (PS) and polyethylene terephthalate film (PET) in order to assess the utility of ASD-V for preparing biomaterial surfaces with endothelial cell-adhesion promoting properties. The effects of pre-adsorption time and initial coating concentration on the efficiency of ASD-V coupling to PS and to PET were examined. Contact angle measurements and atomic force microscopy were used to characterize ASD-V-modified surfaces. Finally, the adhesion and spreading of vascular endothelial cells on ASD-V-modified surfaces was assessed. Our results suggest that photoreactive peptides are an effective and convenient means of modifying biomaterial surfaces to impart adhesion-promoting properties and that ASD-V, when coupled to PS and PET, promotes endothelial cell adhesion and spreading and may therefore be useful as a biomaterial surface modification in applications where re-endothelialization is desired (e.g., autologous endothelial seeding of vascular grafts, or transplantation of genetically engineered endothelial cells via polymer-coated stents). © 1996 John Wiley & Sons, Inc.
Hepoxilins raise circulating insulin levels in vivo (1999)

We have demonstrated over a decade ago that hepoxilins cause the release of insulin from isolated pancreatic islets of Langerhans in vitro. However, no studies are available so far to indicate whether these compounds are active in vivo. The present study is the first to our knowledge which demonstrates that hepoxilins administered intra-arterially in the anaesthetized rat cause the release of insulin in the circulation. This release is dependent on the glucose status of the rat. Hence, animals fasted overnight do not respond to hepoxilin administration, while animals that have had free access to food respond to hepoxilins with a rise in insulin concentrations in blood. The hepoxilin effect is rapid and varies with different hepoxilins, the most potent of which is hepoxilin A(3) (HxA(3)) (both the 8S and the 8R enantiomers). Administration of 100 microg HxA(3) produces a rise in blood insulin equivalent to that caused by the administration of 5 mg glucose. In view of earlier evidence showing that these compounds cause a rise in intracellular calcium levels in vitro at a <1 microg/ml concentration through a receptor-mediated mechanism, we speculate that the actions of hepoxilins in causing the release of insulin from the pancreas may be due to alterations in calcium levels within the beta-cell. We believe that hepoxilins may represent new lead compounds as therapeutics in type II diabetes mellitus.
[2-(Dimethylsulfonio)-1-hydroxy-1-phosphonoethyl]phosphonate monohydrate (2006)

In the title crystal structure, C4H12O7P2S·H2O, the sulfonium groups have a pyramidal geometry and bridging water mol­ecules form a complex three-dimensional hydrogen-bond network involving neighboring phospho­nate groups.
Proteolytic maturation and activation of autotaxin (NPP2), a secreted metastasis-enhancing lysophospholipase D (2005)

Autotaxin (NPP2) is an extracellular protein that is upregulated in various malignancies, including breast and lung cancer. It potently stimulates cell proliferation, cell motility and angiogenesis, which is accounted for by its intrinsic lysophospholipase-D activity that generates the lipid mediators lysophosphatidic acid and sphingosine-1-phosphate. Based on its structural similarities with the better characterized nucleotide pyrophosphatase/phosphodiesterase NPP1, it has always been assumed that NPP2 is also synthesized as a type-II integral membrane protein and that extracellular NPP2 is generated from this membrane precursor. We show here, however, using domain swapping and mutagenesis experiments as well as N-terminal protein sequencing, that NPP2 is actually synthesized as a pre-pro-enzyme and that the proteolytically processed protein is secreted. Following the removal of a 27-residue signal peptide by the signal peptidase, NPP2 is subsequently cleaved by proprotein convertases (PCs). The removal of an N-terminal octapeptide by PCs is associated with an enhanced activity of NPP2 as a lysophospholipase D. These novel insights in the maturation of NPP2 have also implications for the development of NPP2 inhibitors as potential anti-cancer agents.
Neural Enquirer: Learning to Query Tables with Natural Language (2015)

We proposed Neural Enquirer as a neural network architecture to execute a natural language (NL) query on a knowledge-base (KB) for answers. Basically, Neural Enquirer finds the distributed representation of a query and then executes it on knowledge-base tables to obtain the answer as one of the values in the tables. Unlike similar efforts in end-to-end training of semantic parsers, Neural Enquirer is fully "neuralized": it not only gives distributional representation of the query and the knowledge-base, but also realizes the execution of compositional queries as a series of differentiable operations, with intermediate results (consisting of annotations of the tables at different levels) saved on multiple layers of memory. Neural Enquirer can be trained with gradient descent, with which not only the parameters of the controlling components and semantic parsing component, but also the embeddings of the tables and query words can be learned from scratch. The training can be done in an end-to-end fashion, but it can take stronger guidance, e.g., the step-by-step supervision for complicated queries, and benefit from it. Neural Enquirer is one step towards building neural network systems which seek to understand language by executing it on real-world. Our experiments show that Neural Enquirer can learn to execute fairly complicated NL queries on tables with rich structures.
Building zinc fingers by selection: toward a therapeutic application. (1995)

A phage display approach was utilized to modify the specificity of each of the three fingers of the murine transcription factor Zif268. Selections were performed by using the consensus binding sequence of the natural protein and a conserved sequence in the genome of the type 1 human immunodeficiency virus. By using an extensive randomization strategy, the entire 3-bp specificity of a finger has been changed. Rapid analysis of selected zinc fingers was facilitated by the development of an immunoscreening assay for DNA binding and specificity. To investigate the mechanism of binding and specificity, the binding kinetics of Zif268 and 10 selected variants were determined in real time with an assay based on surface plasmon resonance. Differential mechanisms for sequence-specific recognition were observed. No evidence in support of a single general coding relationship between zinc finger and target DNA sequence was observed. The prospects for the development of this class of proteins in human therapy are considered.
Adaptation to oxygen deprivation in cultures of human pluripotent stem cells, endothelial progenitor cells, and umbilical vein endothelial cells (2010)

Hypoxia plays an important role in vascular development through hypoxia-inducible factor-1alpha (HIF-1alpha) accumulation and downstream pathway activation. We sought to explore the in vitro response of cultures of human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), human endothelial progenitor cells (hEPCs), and human umbilical cord vein endothelial cells (HUVECs) to normoxic and hypoxic oxygen tensions. We first measured dissolved oxygen (DO) in the media of adherent cultures in atmospheric (21% O(2)), physiological (5% O(2)), and hypoxic oxygen conditions (1% O(2)). In cultures of both hEPCs and HUVECs, lower oxygen consumption was observed when cultured in 1% O(2). At each oxygen tension, feeder-free cultured hESCs and iPSCs were found to consume comparable amounts of oxygen. Transport analysis revealed that the oxygen uptake rate (OUR) of hESCs and iPSCs decreased distinctly as DO availability decreased, whereas the OUR of all cell types was found to be low when cultured in 1% O(2), demonstrating cell adaptation to lower oxygen tensions by limiting oxygen consumption. Next, we examined HIF-1alpha accumulation and the expression of target genes, including VEGF and angiopoietins (ANGPT; angiogenic response), GLUT-1 (glucose transport), BNIP3, and BNIP3L (autophagy and apoptosis). Accumulations of HIF-1alpha were detected in all four cell lines cultured in 1% O(2). Corresponding upregulation of VEGF, ANGPT2, and GLUT-1 was observed in response to HIF-1alpha accumulation, whereas upregulation of ANGPT1 was detected only in hESCs and iPSCs. Upregulation of BNIP3 and BNIP3L was detected in all cells after 24-h culture in hypoxic conditions, whereas apoptosis was not detectable using flow cytometry analysis, suggesting that BNIP3 and BNIP3L can lead to cell autophagy rather than apoptosis. These results demonstrate adaptation of all cell types to hypoxia but different cellular responses, suggesting that continuous measurements and control over oxygen environments will enable us to guide cellular responses.
Pro-phenol oxidase activating proteinase from an insect, Manduca sexta: A bacteria-inducible protein similar to Drosophila easter (1998)

Activation of pro-phenol oxidase (proPO) in insects and crustaceans is important in defense against wounding and infection. The proPO zymogen is activated by a specific proteolytic cleavage. PO oxidizes phenolic compounds to produce quinones, which may help to kill pathogens and can also be used for synthesis of melanin to seal wounds and encapsulate parasites. We have isolated from the tobacco hornworm, Manduca sexta, a serine proteinase that activates proPO, and have cloned its cDNA. The isolated proPO activating proteinase (PAP) hydrolyzed artificial substrates but required other protein factors for proPO activation, suggesting that proPO-activating enzyme may exist as a protein complex, one component of which is PAP. PAP (44 kDa) is composed of two disulfide-linked polypeptide chains (31 kDa and 13 kDa). A cDNA for PAP was isolated from a hemocyte library, by using a PCR-generated probe based on the amino-terminal amino acid sequence of the 31-kDa catalytic domain. PAP belongs to a family of arthropod serine proteinases containing a carboxyl-terminal proteinase domain and an amino-terminal "clip" domain. The member of this family most similar in sequence to PAP is the product of the easter gene from Drosophila melanogaster. PAP mRNA was present at a low level in larval hemocytes and fat body, but became much more abundant in fat body after insects were injected with Escherichia coli. Sequence data and 3H-diisopropyl fluorphosphate labeling results suggest that the same PAP exists in hemolymph and cuticle.
Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells. (1997)

We have produced transgenic mice whose livers express a dominant positive NH2-terminal fragment of sterol regulatory element binding protein-1c (SREBP-1c). Unlike full-length SREBP-1c, the NH2-terminal fragment enters the nucleus without a requirement for proteolytic release from cell membranes, and hence it is immune to downregulation by sterols. We compared SREBP-1c transgenic mice with a line of transgenic mice that produces an equal amount of the NH2-terminal fragment of SREBP-1a. SREBP-1a and -1c are alternate transcripts from a single gene that differ in the first exon, which encodes part of an acidic activation domain. The 1a protein contains a long activation domain with 12 negatively charged amino acids, whereas the 1c protein contains a short activation domain with only 6 such amino acids. As previously reported, livers of the SREBP-1a transgenic mice were massively enlarged, owing to accumulation of triglycerides and cholesterol. SREBP-1c transgenic livers were only slightly enlarged with only a moderate increase in triglycerides, but not cholesterol. The mRNAs for the LDL receptor and several cholesterol biosynthetic enzymes were elevated in SREBP-la transgenic mice, but not in 1c transgenic mice. The mRNAs for fatty acid synthase and acetyl CoA carboxylase were elevated 9- and 16-fold in la animals, but only 2- and 4-fold in 1c animals. Experiments with transfected cells confirmed that SREBP-1c is a much weaker activator of transcription than SREBP-1a when both are expressed at levels approximating those found in nontransfected cells. SREBP-1c became a strong activator only when expressed at supraphysiologic levels. We conclude that SREBP-1a is the most active form of SREBP-1 and that SREBP-1c may be produced when cells require a lower rate of transcription of genes regulating cholesterol and fatty acid metabolism.
IL-15 stimulates the expansion of AIDS virus-specific CTL (1996)

It has been assumed that the maturation of pre-CTL to virus-specific effector CTL is dependent upon IL-2-mediated T cell triggering through the IL-2R. In view of its similarity to IL-2 in its effects on immune cells, we sought to determine whether IL-15 can induce the expansion of AIDS virus-specific pre-CTL to mature CTL. PBL of SIV(mac)-infected rhesus monkeys or HIV-1-infected humans have previously been shown to expand to effector CTL when cultivated with a predicted CTL epitope peptide and rIL-2. We now demonstrate that rIL-15 facilitates this expansion of effector CTL. In fact, rIL-15-driven expansion of virus-specific CTL occurs in the presence of IL-2-neutralizing or anti-IL-2R Abs, indicating that this cellular maturation can occur in an IL-2-independent fashion. These studies suggest a mechanism by which CTL may be capable of expanding in vivo in the absence of IL-2 and functional CD4+ T lymphocytes.
Pilot study on lipocalin expression into extracellular fluids of women in fertile age. (2002)

The positive results of this study seem to strengthen the hypothesis related to NGAL biological functions, specifically the ones that suggest its role into cell differentiation, embryonic development and inflammation. Therefore the female reproductive tract is suggested as a new promising study object in this research field.
Lentiviral-Mediated RNA Interference (2002)

RNA interference (RNAi) is a form of posttranscriptional gene silencing mediated by short double-stranded RNA, known as small interfering RNA (siRNA). These siRNAs are capable of binding to a specific mRNA sequence and causing its degradation. The recent demonstration of a plasmid vector that directs siRNA synthesis in mammalian cells prompted us to examine the ability of lentiviral vectors to encode siRNA as a means of providing long-term gene silencing in mammalian cells. The RNA-polymerase III dependent promoter (H1-RNA promoter) was inserted in the lentiviral genome to drive the expression of a small hairpin RNA (shRNA) against enhanced green fluorescent protein (EGFP). This construct successfully silenced EGFP expression in two stable cell lines expressing this protein, as analyzed by fluorescence microscopy, flow cytometry, and Western blotting. The silencing, which is dose dependent, occurs as early as 72 hr postinfection and persists for at least 25 days postinfection. The ability of lentiviruses encoding siRNA to silence genes specifically makes it possible to take full advantage of the possibilities offered by the lentiviral vector and provides a powerful tool for gene therapy and gene function studies.
Transfollicular drug delivery: current perspectives (2016)

The pilosebaceous unit is the collective form of a hair follicle, hair shaft, and sebaceous gland. Within the skin, this three-dimensional composite shows a distinctive biochemistry, metabolism, and immunology. Presently, most researchers in this area are focused on the hair follicles, as they see these as a potential pathway for both localized and systemic delivery of various chemotherapeutics. Better understanding of the configuration of the hair follicle is mulled over in order to design rational drug formulations to achieve targeted follicular delivery. Targeted drug delivery may enhance the efficacy of current therapeutics to treat diseases of follicular origin. The present review covers follicular drug delivery with the potential to target the pilosebaceous unit.
Brain Bioavailability of Human Intravenous Immunoglobulin and its Transport through the Murine Blood–Brain Barrier (2013)

Intravenous immunoglobulin (IVIg) is currently evaluated in clinical trials for the treatment of various disorders of the central nervous system. To assess its capacity to reach central therapeutic targets, the brain bioavailability of IVIg must be determined. We thus quantified the passage of IVIg through the blood-brain barrier (BBB) of C57Bl/6 mice using complementary quantitative and qualitative methodologies. As determined by enzyme-linked immunosorbent assay, a small proportion of systemically injected IVIg was detected in the brain of mice (0.009±0.001% of injected dose in the cortex) whereas immunostaining revealed localization mainly within microvessels and less frequently in neurons. Pharmacokinetic analyses evidenced a low elimination rate constant (0.0053 per hour) in the cortex, consistent with accumulation within cerebral tissue. In situ cerebral perfusion experiments revealed that a fraction of IVIg crossed the BBB without causing leakage. A dose-dependent decrease of brain uptake was consistent with a saturable blood-to-brain transport mechanism. Finally, brain uptake of IVIg after a subchronic treatment was similar in the 3xTg-AD mouse model of Alzheimer disease compared with nontransgenic controls. In summary, our results provide evidence of BBB passage and bioavailability of IVIg into the brain in the absence of BBB leakage and in sufficient concentration to interact with the therapeutic targets.
<title>Adaptive public watermarking of DCT-based compressed images</title> (1997)

We propose an adaptive scheme to embed watermark information in DCT blocks of compressed image data. our scheme is designed to avoid artifacts and prevent an increase in the bit rate of the compressed watermarked image. This is essentially done by judicious selection of appropriate blocks for watermark insertion. We also introduce a block-dependent seed generation algorithm to determine the specific coefficients to modify in a particular block. Our proposed technique is simple to implement in software, and hence suitable for real-time software-only insertion of invisible watermarks in JPEG compressed images, and MPEG or MJPEG video streams. We also demonstrate experimentally that our proposed watermarking scheme actually results in bit rate reduction of JPEG compressed images. The proposed technique can also complement existing DCT-based watermarking schemes for copy protection and detection applications.
Gastroretentive drug delivery systems: a review (2010)

Amit Kumar Nayak *, Ruma Maji, Biswarup Das Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Jharpokharia, Mayurbhanj – 757089. Orissa, India. Address for correspondence: Mr. Amit Kumar Nayak, Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Jharpokharia, Mayurbhanj – 757089. Orissa, India. E-mail: amitkrnayak@yahoo.co.in The purpose of writing this review on gastroretentive drug delivery systems was to compile the recent literature with special focus on various gastroretentive approaches that have recently become leading methodologies in the field of site-specific orally administered controlled release drug delivery. In order to understand various physiological difficulties to achieve gastric retention, we have summarized important factors controlling gastric retention. Afterwards, we have reviewed various gastroretentive approaches designed and developed until now, i.e. high density (sinking), floating, bio- or mucoadhesive, expandable, unfoldable, super porous hydrogel and magnetic systems. Finally, advantages of gastroretentive drug delivery systems were covered in detail.