gebhart/patrepeval huggingface dataset:
Platelet‐derived growth factor and its receptors are related to the progression of human muscular dystrophy: an immunohistochemical study (2003)

Abstract This study has examined the immunological localization of platelet‐derived growth factor (PDGF)‐A, PDGF‐B, and PDGF receptor (PDGFR) alpha and beta to clarify their role in the progression of muscular dystrophy. Biopsied frozen muscles from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and congenital muscular dystrophy (CMD) were analysed immunohistochemically using antibodies raised against PDGF‐A, PDGF‐B, and PDGFR alpha and beta. Muscles from two dystrophic mouse models ( dy and mdx mice) were also immunostained with antibodies raised against PDGFR alpha and beta. In normal human control muscle, neuromuscular junctions and vessels were positively stained with antibodies against PDGF‐A, PDGF‐B, PDGFR alpha and PDGFR beta. In human dystrophic muscles, PDGF‐A, PDGF‐B, PDGFR alpha and PDGFR beta were strongly immunolocalized in regenerating muscle fibres and infiltrating macrophages. PDGFR alpha was also immunolocalized to the muscle fibre sarcolemma and necrotic fibres. The most significant finding in this study was a remarkable overexpression of PDGFR beta and, to a lesser extent, PDGFR alpha in the endomysium of DMD and CMD muscles. PDGFR was also overexpressed in the interstitium of muscles from dystrophic mice, particularly dy mice. Double immunolabelling revealed that activated interstitial fibroblasts were clearly positive for PDGFR alpha and beta. However, DMD and CMD muscles with advanced fibrosis showed very poor reactivity against PDGF and PDGFR. Those findings were confirmed by immunoblotting with PDGFR beta. These findings indicate that PDGF and its receptors are significantly involved in the active stage of tissue destruction and are associated with the initiation or promotion of muscle fibrosis. They also have roles in muscle fibre regeneration and signalling at neuromuscular junctions in both normal and diseased muscle. Copyright © 2003 John Wiley &amp; Sons, Ltd.
Slow feature analysis yields a rich repertoire of complex cell properties (2005)

In this study we investigate temporal slowness as a learning principle for receptive fields using slow feature analysis, a new algorithm to determine functions that extract slowly varying signals from the input data. We find a good qualitative and quantitative match between the set of learned functions trained on image sequences and the population of complex cells in the primary visual cortex (V1). The functions show many properties found also experimentally in complex cells, such as direction selectivity, non-orthogonal inhibition, end-inhibition, and side-inhibition. Our results demonstrate that a single unsupervised learning principle can account for such a rich repertoire of receptive field properties.
A kinetic‐based approach to understanding heterologous mevalonate pathway function in E. coli (2014)

To aid in debugging efforts to increase yield, titer, and productivity of engineered metabolic pathways, computational models are increasingly needed to predict how changes in experimentally manipulable variables such as enzyme expression map to changes in pathway flux. Here, an ordinary differential equation model is developed for a heterologous mevalonate pathway in E. coli using kinetic parameters culled from literature and enzyme concentrations derived from Selective Reaction Monitoring Mass Spectrometry (SRM-MS). To identify parameters most important to further experimental investigation, a global sensitivity analysis was performed, which pointed to amorphadiene synthase activity as the main limiting factor for amorphadiene production. Furthermore, the model predicted that in this local enzyme expression regime, the overall pathway flux is insensitive to farnesyl pyrophosphate (FPP)-mediated inhibition of mevalonate kinase, not supporting a hypothesis that had previously been posited to be limiting amorphadiene production. To test these predictions experimentally, two strains were constructed: (1) a strain containing a homologous mevalonate kinase with weaker feedback inhibition, and (2) a strain with greater amorphadiene synthase expression. The experimental results validate the qualitative model hypotheses and accurately match the predicted productivities for the two strains, particularly when an in vivo-derived kcat for amorphadiene synthase was substituted for the literature value. These results demonstrate the utility of using kinetic representations of engineered metabolic pathways parameterized with experimentally derived protein concentrations and enzyme kinetic constants to predict productivities and test hypotheses about engineering strategies.
The immunoregulatory cytokine interleukin‐10—a therapy for Crohn’s disease? (2001)

The gastrointestinal tract serves as a barrier between the host and the vast array of foreign antigens that are contained within its lumen. The mucosal immune system must balance two opposing functions: to mount an immune response to pathogens, whilst maintaining tolerance to antigens derived from commensal bacteria and food. This balance is regulated by both cellular interactions and the release of soluble mediators called cytokines. Diseases such as ulcerative colitis and Crohn's disease are characterized by alterations in the balance of pro-inflammatory and regulatory cytokines. Interleukin-10 is a regulatory cytokine which inhibits both antigen presentation and subsequent pro-inflammatory cytokine release. In addition, there is evidence that it promotes the formation of antigen-specific regulatory T-cell clones. The pivotal role played by interleukin-10 within the mucosal immune system is demonstrated both by the chronic ileocolitis that develops in gene-targeted interleukin-10 knock-out mice, and by its therapeutic efficacy in several animal models of colitis. However, trials of daily systemic interleukin-10 administration in patients with Crohn's disease have reported only a modest clinical response. Advances in the analysis of functional polymorphisms in the interleukin-10 gene may allow therapy to be targeted to patients who will respond. Finally, therapeutic strategies utilizing gene therapy may enhance mucosal delivery and increase therapeutic response.
Role of the C-terminal YG repeats of the primer-dependent streptococcal glucosyltransferase, GtfJ, in binding to dextran and mutan (2002)

The recombinant primer-dependent glucosyltransferase GtfJ of Streptococcus salivarius possesses a C-terminal glucan-binding domain composed of eighteen 21 aa YG repeats. By engineering a series of C-terminal truncated proteins, the position at which truncation prevented further mutan synthesis was defined to a region of 43 aa, confirming that not all of the YG motifs were required for the formation of mutan by GtfJ. The role of the YG repeats in glucan binding was investigated in detail. Three proteins consisting of 3.8, 7.2 or 11.0 C-terminal YG repeats were expressed in Escherichia coli. Each of the three purified proteins bound to both the 1,6-alpha-linked glucose residues of dextran and the 1,3-alpha-linked glucose residues of mutan, indicating that a protein consisting of nothing but 3.8 YG repeats could attach to either substrate. Secondary structure predictions of the primary amino acid sequence suggested that 37% of the amino acids were capable of forming a structure such that five regions of beta-sheet were separated by regions capable of forming beta-turns and random coils. CD spectral analysis showed that the purified 3.8 YG protein possessed an unordered secondary structure with some evidence of possible beta-sheet formation and that the protein maintained this relatively unordered structure on binding to dextran.
In Vitro Synthesis of Mullerian-Inhibiting Hormone by Seminiferous Tubules Isolated from the Calf Fetal Testis (1973)

Fetal calf testicular tissue was submitted to microdissection. Whole testicular tissue, isolated seminiferous tubules and interstitial tissue were cultured in association with fetal rat reproductive tracts. Mullerian inhibition was achieved only in explants containing seminiferous tubules. The possibility that the mullerian-inhibiting hormone is produced by the fetal Sertoli cells is suggested. (Endocrinology93: 829, 1973)
Allergy and Cancer: Organ Site-Specific Results from the Adventist Health Study (1992)

The relation between allergy and risk of cancer was evaluated in a cohort study of 34,198 Seventh-day Adventists in California. Information on prevalence of asthma, hay fever, and reactions to chemicals, medications, bee stings, and poison oak (or ivy) was obtained by questionnaire in 1976. The reported allergies must have been serious enough to require treatment by a physician. The cohort was then followed for 6 years (1977-1982). Both stratified analysis and Cox proportional hazards regression analyses were utilized to evaluate the relation of allergy to cancer after taking into account several potentially confounding variables. For all cancer sites combined in males, there was a 33% increased risk associated with reaction to medications. In contrast, among females, reaction to medications was associated with a 21% decrease in risk. Both results were statistically significant. Prostate and breast cancer risk were elevated in persons who reported any type of allergic history, as was risk of lymphatic or hematopoietic cancers and sarcoma. For each of these types of cancer, risk increased with increasing numbers of allergies. However, ovarian cancer risk was decreased in persons with any allergic history and increasing numbers of allergies was associated with decreasing risk of this form of cancer. These results suggest that the association between allergy and cancer is complex and depends on the specific allergy and the specific organ site under consideration.
Down-regulation of Lysyl Oxidase-induced Tumorigenic Transformation in NRK-49F Cells Characterized by Constitutive Activation of Ras Proto-oncogene (2001)

Several investigations have suggested a putative tumor suppressor role for lysyl oxidase because it is down-regulated in many human and oncogene-induced tumors. To address this issue we down-regulated the enzyme in normal rat kidney fibroblasts by stable transfection of its cDNA in an antisense orientation. The selected clones revealed an absence of lysyl oxidase and dramatic phenotypic changes, interpretable as signs of transformation. The antisense lysyl oxidase clones showed, indeed, loose attachment to the plate and anchorage-independent growth and were highly tumorigenic in nude mice. Moreover, we found an impaired response of the PDGF and IGF-1 receptors to their ligands. In particular, the transformed cells showed a down-regulation of both PDGF receptors and expressed the 105-kDa isoform of the IGF-1 beta receptor, which was not present in the normal control cells. The lack of response to PDGF-BB has been described as a feature of many ras-transformed phenotypes. Therefore, we looked at the status of the p21(ras). Indeed, we found a significantly higher level of active p21(ras) both during steady-state growth and prolonged starvation. Our data reveal new evidence for a tumor suppressor activity of lysyl oxidase, highlighting its particular role in controlling Ras activation and growth factor dependence.
Structural Relationship of Bacterial RecA Proteins to Recombination Proteins from Bacteriophage T4 and Yeast (1993)

RecA protein is essential in eubacteria for homologous recombination and promotes the homologous pairing and strand exchange of DNA molecules in vitro. Recombination proteins with weak sequence similarity to bacterial RecA proteins have been identified in bacteriophage T4, yeast, and other higher organisms. Analysis of the primary sequence relationships of DMC1 from Saccharomyces cerevisiae and UvsX of T4 relative to the three-dimensional structure of RecA from Escherichia coli suggests that both proteins are structural homologs of bacterial RecA proteins. This analysis argues that proteins in this group are members of a single family that diverged from a common ancestor that existed prior to the divergence of prokaryotes and eukaryotes.
Inhibition of Listeria locomotion by mosquito oostatic factor, a natural oligoproline peptide uncoupler of profilin action (1995)

Mosquito oostatic factor, a naturally occurring decapeptide (YDPAPPPPPP), strikingly resembles the primary structure of oligoproline-rich regions within the protein ActA, a bacterial surface protein required for Listeria motility in host cells. When microinjected into Listeria-infected PtK2 cells, the insect oostatic factor rapidly blocks Listeria-induced actin rocket tail assembly as well as intracellular locomotion of this pathogen. At intracellular concentrations of about 90 nM, transient inhibition of rocket tail formation and bacterial locomotion occurs, followed by full recovery of tail length and motility. However, at 0.9 microM oostatic factor, both processes are permanently arrested. Introduction of oostatic factor by microinjection also causes PtK2 peripheral membrane retraction in both Listeria-infected and uninfected cells. Epifluorescence microscopy with bodipy-phallacidin reveals that cells microinjected with the insect factor lose all actin stress fibers and accumulate F-actin in regions of membrane retraction. When the insect peptide is combined with profilin as an equimolar binary solution (1 microM [final concentration] each), intracellular addition fails to inhibit Listeria rocket-tail formation, fails to block intracellular bacterial movement, and no longer causes marked membrane retraction. The ability of profilin to neutralize the inhibitory action of oostatic factor is consistent with complex formation, and this finding suggests that profilin may interact directly with ActA peptide as well as a host cell peripheral membrane component to promote actin filament assembly by locally generating ATP-actin. Dispersal of profilin from such sites by oligoproline-rich peptide inhibitors suggests that profilin is directly involved in intracellular pathogen locomotion and reorganization of actin cytoskeleton of the host cell peripheral membrane.
Induction of growth inhibition and apoptosis in prostate cancer cells by flavopiridol. (2000)

Flavopiridol is an inhibitor of several cyclin-dependent kinases, and exhibits potent growth-inhibitory activity against a number of human tumor cell lines both in vitro, and when grown as xenografts in mice. It has shown promising antineoplastic activity and is currently undergoing clinical phase II testing. Prostate cancer (PCa) remains a leading cause of morbidity and mortality among males in the United States. There are no effective treatments for hormone and/or radiation refractory PCa, suggesting that novel and newer treatment strategy may be useful in the management of PCa. Our previous study showed that flavopiridol induces cell growth inhibition and apoptosis in breast cancer cells. Here, we investigated whether flavopiridol was effective against prostate cancer cells. Flavopiridol was found to inhibit growth of PC3 prostate cancer cells. Induction of apoptosis was also observed in PC3 cells treated with flavopiridol, as measured by DNA laddering and PARP cleavage. We also found a significant down-regulation of Bcl-2 in flavopiridol-treated cells. These findings suggest that down-regulation of Bcl-2 may be one of the molecular mechanisms through which flavopiridol induces apoptosis and inhibits cell growth, suggesting that flavopiridol may be an effective chemotherapeutic agent against prostate cancer.
Traumatic brain injury‐induced acute gene expression changes in rat cerebral cortex identified by GeneChip analysis (2002)

Proper CNS function depends on concerted expression of thousands of genes in a controlled and timely manner. Traumatic brain injury (TBI) in mammals results in neuronal death and neurological dysfunction, which might be mediated by altered expression of several genes. By employing a CNS-specific GeneChip and real-time polymerase chain reaction (PCR), the present study analyzed the gene expression changes in adult rat cerebral cortex in the first 24 hr after a controlled cortical impact injury. Many functional families of genes not previously implicated in TBI-induced brain damage are altered in the injured cortex. These include up-regulated transcription factors (SOCS-3, JAK-2, STAT-3, CREM, IRF-1, SMN, silencer factor-B, ANIA-3, ANIA-4, and HES-1) and signal transduction pathways (cpg21, Narp, and CRBP) and down-regulated transmitter release mechanisms (CITRON, synaptojanin II, ras-related rab3, neurexin-1beta, and SNAP25A and -B), kinases (IP-3-kinase, Pak1, Ca(2+)/CaM-dependent protein kinases), and ion channels (K(+) channels TWIK, RK5, X62839, and Na(+) channel I). In addition, several genes previously shown to play a role in TBI pathophysiology, including proinflammatory genes, proapoptotic genes, heat shock proteins, immediate early genes, neuropeptides, and glutamate receptor subunits, were also observed to be altered in the injured cortex. Real-time PCR analysis confirmed the GeneChip data for many of these transcripts. The novel physiologically relevant gene expression changes observed here might explain some of the molecular mechanisms of TBI-induced neuronal damage.
A comparison of Pedestrian Dead-Reckoning algorithms using a low-cost MEMS IMU (2009)

Human localization is a very valuable information for smart environments. state-of-the-art local positioning systems (LPS) require a complex sensor-network infrastructure to locate with enough accuracy and coverage. Alternatively, inertial measuring units (IMU) can be used to estimate the movement of a person, by detecting steps, estimating stride lengths and the directions of motion; a methodology that is called pedestrian dead-reckoning (PDR). In this paper, we use low-performance microelectromechanical (MEMS) inertial sensors attached to the foot of a person. This sensor has triaxial orthogonal accelerometers, gyroscopes and magnetometers. We describe, implement and compare several of the most relevant algorithms for step detection, stride length, heading and position estimation. The challenge using MEMS is to provide location estimations with enough accuracy and a limited drift. Several tests were conducted outdoors and indoors, and we found that the stride length estimation errors were about 1%. The positioning errors were almost always below 5% of the total travelled distance. The main source of positioning errors are the absolute orientation estimation.
Generating antialiased images at low sampling densities (1987)

Ray tracing produces point samples of an image from a 3-D model. Constructing an antialiased digital picture from point samples is difficult without resorting to extremely high sampling densities. This paper describes a program that focuses on that problem. While it is impossible to eliminate aliasing totally, it has been shown that nonuniform sampling yields aliasing that is less conspicuous to the observer. An algorithm is presented for fast generation of nonuniform sampling patterns that are optimal in some sense. Some regions of an image may require extra sampling to avoid strong aliasing. Deciding where to do extra sampling can be guided by knowledge of how the eye perceives noise as a function of contrast and color. Finally, to generate the digital picture, the image must be reconstructed from the samples and resampled at the display pixel rate. The nonuniformity of the samples complicates this process, and a new nonuniform reconstruction filter is presented which solves this problem efficiently.
Options for biochemical production of 4‐hydroxybutyrate and its lactone as a substitute for petrochemical production (2007)

Options are discussed for biochemical production of 4-hydroxybutyrate (4-HB) and its lactone, gamma-butyrolactone (GBL), from renewable sources. In the first part of the study, the thermodynamic feasibility of four potential metabolic pathways from glucose to 4-HB are analyzed. The calculations reveal that when the pathways are NAD(+) dependent the intermediate succinate semialdehyde (SSA) accumulates leading to low 4-HB yields at equilibrium. For NADP(+) dependent pathways the calculated yield of 4-HB improves, up to almost 100%. In the second part of this study, continuous removal of 4-HB from the solution is considered to shift SSA conversion into 4-HB so that SSA accumulation is minimized. One option is the enzymatic production of GBL from 4-HB. Candida antarctica Lipase B shows good lactonization rates at pH 4, but unfortunately this conversion cannot be performed in-vivo during 4-HB production because of the neutral intracellular pH.
Snap-and-go (2005)

Snapping is a widely used technique that helps users position graphical objects precisely, e.g., to align them with a grid or other graphical objects. Unfortunately, whenever users want to position a dragged object close to such an aligned location, they first need to deactivate snapping. We propose snap-and-go, a snapping technique that overcomes this limitation. By merely stopping dragged objects at aligned positions, rather than "warping" them there, snap-and-go helps users align objects, yet still allows placing dragged objects anywhere else. While this approach of inserting additional motor space renders snap-and-go slightly slower than traditional snapping, snap-and-go simplifies the user interface by eliminating the need for a deactivation option and thereby allows introducing snapping to application scenarios where traditional snapping is inapplicable. In our user studies, participants were able to align objects up to 138% (1D) and 231% (2D) faster with snap-and-go than without and snap-and-go proved robust against the presence of distracting snap targets.
The pharmacogenetics of NAT: structural aspects (2002)

Arylamine N-acetyltransferases (NATs) catalyze the transfer of an acetyl group from acetyl-CoA to arylhydrazines and to arylamine drugs and carcinogens or to their N-hydroxylated metabolites. NAT plays an important role in detoxification and metabolic activation of xenobiotics and was first identified as the enzyme responsible for inactivation of the antitubercular drug isoniazid, an arylhydrazine. The rate of inactivation was polymorphically distributed in the population: the first example of interindividual pharmacogenetic variation. Polymorphism in NAT activity is primarily due to single nucleotide polymorphisms (SNPs) in the coding region of NAT genes. NAT enzymes are widely distributed in eukaryotes and genome sequences have revealed many homologous members of this enzyme family in prokaryotes. The structures of S almonella typhimurium and Mycobacterium smegmatis NATs have been determined, revealing a unique fold in which a catalytic triad (Cys-His-Asp) forms the active site. Determination of prokaryotic and eukaryotic NAT structures could lead to a better understanding of their role in xenobiotics and endogenous metabolism.
Fibrinogen Binding to ICAM-1 on EA.hy 926 Endothelial Cells Is Dependent on an Intact Cytoskeleton (1996)

Fibrinogen is a ligand for Intercellular Adhesion Molecule-1 (ICAM-1), and enhances monocyte-endothelial cell interaction by coupling Mac-1 on monocytes to ICAM-1 on endothelial cells. We investigated the role of the cytoskeleton in fibrinogen binding to the human endothelial cell line EA.hy 926 using immunofluorescence techniques. In this cell line TNF alpha induced the simultaneous appearance of stress fibers and of ICAM-1, which was clustered predominantly on endothelial cell projections. Incubation of TNF alpha-stimulated endothelial cells with fibrinogen resulted in binding of fibrinogen to ICAM-1 on these cell projections. Disruption of the cytoskeleton by cytocholasin B abolished fibrinogen binding. Activation of protein kinase C with 12-O-tetradecanoyl phorbol-13-acetate resulted in simultaneous loss of both stress fibers and fibrinogen binding. These results suggest that a connection between ICAM-1 and the cytoskeleton results in clustering of ICAM-1 on cell projections, which is required for fibrinogen binding.