gebhart/patrepeval huggingface dataset:
Spermine induces cell death in cultured human embryonic cerebral cortical neurons through N‐methyl‐D‐aspartate receptor activation (2007)

The polyamines putrescine, spermidine, and spermine play important roles in cell proliferation, differentiation, and modulation of ion channel receptors. However, the function of increased concentrations of these compounds in brain injury and disease is unclear, in that they have been proposed as being both neuroprotective and neurotoxic. The effects of spermine and putrescine were studied in human primary cerebral cortical cultures containing both neurons and glia. No toxic effects were induced at 8 days in vitro (DIV) by either of the two polyamines at concentrations ranging from 0.3 microM to 2 mM. However, when the oxidative metabolism of spermine that generates toxic byproducts was induced by the presence of fetal calf serum, spermine caused cellular death with an LC(50) of approximately 50 microM. At 14 DIV, the coapplication of spermine 2 mM and glutamate 5 mM induced neuron cell death, but the effect of applying both components separately was null. Both spermine and glutamate were toxic to older neurons (26-42 DIV cultures), and here the coapplication of glutamate was found always to intensify the effect of spermine. Spermine showed greater toxicity than glutamate in neurons. Another effect observed is that glutamate, but not spermine, induced astrocyte swelling. Spermine toxicity was inhibited by both MK801 and ifenprodil, indicating a mechanism involving N-methyl-D-aspartate (NMDA) receptor activation. Moreover, a strong spermine modulation of the NMDA receptor was demonstrated by the inhibition of glutamate toxicity by ifenprodil. Putrescine induced minor effects also as a neurotoxic agent. In conclusion, neuronal death by spermine can be induced by its toxic byproducts as well as through NMDA receptor action. The present results confirm the potentially harmful role of the polyamines in excitotoxicity-related human disorders.
Myodys, a full-length dystrophin plasmid vector for Duchenne and Becker muscular dystrophy gene therapy. (2008)

Transgene SA is developing Myodys, a non-viral plasmid gene therapy for the potential treatment of Duchenne muscular dystrophy and Becker muscular dystrophy. Phase I clinical trials have been completed, and a phase II clinical trial is planned.
Suppression of Cholangiocarcinoma Cell Growth by Human Umbilical Cord Mesenchymal Stem Cells: A Possible Role of Wnt and Akt Signaling (2013)

Emerging evidence indicates that human mesenchymal stem cells (hMSCs) can be recruited to tumor sites, and affect the growth of human malignancies. However, little is known about the underlying molecular mechanisms. Here, we observed the effects of hMSCs on the human cholangiocarcinoma cell line, HCCC-9810, using an animal transplantation model, and conditioned media from human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). Animal studies showed that hUC-MSCs can inhibit the growth of cholangiocarcinoma xenograft tumors. In cell culture, conditioned media from hUC-MSCs inhibited proliferation and induced apoptosis of tumor cells in a dose- and time-dependent manner. The proliferation inhibition rate increased from 6.21% to 49.86%, whereas the apoptosis rate increased from 9.3% to 48.1% when HCCC-9810 cells were cultured with 50% hUC-MSC conditioned media for 24 h. Immunoblot analysis showed that the expression of phosphor-PDK1 (Ser241), phosphor-Akt (Ser 437 and Thr308), phosphorylated glycogen synthase kinase 3β (phospho-GSK-3β(Ser9)), β-catenin, cyclin-D1, and c-myc were down-regulated. We further demonstrated that CHIR99021, a GSK-3β inhibitor reversed the suppressive effects of hUC-MSCs on HCCC-9810 cells and increased the expression of β-catenin. The GSK-3β activator, sodium nitroprusside dehydrate (SNP), augmented the anti-tumor effects of hUC-MSCs and decreased the expression of β-catenin. IGF-1 acted as an Akt activator, and also reversed the suppressive effects of hUC-MSCs on HCCC-9810 cells. All these results suggest that hUC-MSCs could inhibit the malignant phenotype of HCCC-9810 human cholangiocarcinoma cell line. The cross-talk role of Wnt/β-catenin and PI3K/Akt signaling pathway, with GSK-3β as the key enzyme bridging these pathways, may contribute to the inhibition of cholangiocarcinoma cells by hUC-MSCs.
Biomimetic Assembly of Zinc Oxide Nanorods onto Flexible Polymers (2007)

We employ principles derived from biomineralization to assemble functional nanoscale inorganic materials onto flexible polymer substrates under low-temperature, benign chemical conditions. Our biomimetic approach involves the selective functionalization of polymer surfaces to create regions of differing surface energy which can promote heterogeneous nucleation in designated regions while suppressing it in others. Specifically, ZnO is grown into ordered microarrays on flexible polycarbonate films and polyester filaments directly out of aqueous solutions. The resulting block, checkerboard, and grid shaped microarrays consist of either ZnO nanorods or microplates with feature sizes down to 4 μm. The approach reported is general, does not require traditional lithography, uses no seed layers or self-assembled monolayers, and can be easily applied to a variety of planar or three-dimensional polymer substrates enabling numerous applications in flexible macroelectronics and smart textiles.
Role of T-bet in Commitment of T H 1 Cells Before IL-12-Dependent Selection (2001)

How cytokines control differentiation of helper T (TH) cells is controversial. We show that T-bet, without apparent assistance from interleukin 12 (IL-12)/STAT4, specifies TH1 effector fate by targeting chromatin remodeling to individual interferon-gamma (IFN-gamma) alleles and by inducing IL-12 receptor beta2 expression. Subsequently, it appears that IL-12/STAT4 serves two essential functions in the development of TH1 cells: as growth signal, inducing survival and cell division; and as trans-activator, prolonging IFN-gamma synthesis through a genetic interaction with the coactivator, CREB-binding protein. These results suggest that a cytokine does not simply induce TH fate choice but instead may act as an essential secondary stimulus that mediates selective survival of a lineage.
Fibroblast growth factor-2 mediates pressure-induced hypertrophic response (1999)

In vitro, fibroblast growth factor-2 (FGF2) has been implicated in cardiomyocyte growth and reexpression of fetal contractile genes, both markers of hypertrophy. However, its in vivo role in cardiac hypertrophy during pressure overload is not well characterized. Mice with or without FGF2 (Fgf2(+/+) and Fgf2(-/-), respectively) were subjected to transverse aortic coarctation (AC). Left ventricular (LV) mass and wall thickness were assessed by echocardiography preoperatively and once a week postoperatively for 10 weeks. In vivo LV function during dobutamine stimulation, cardiomyocyte cross-sectional area, and recapitulation of fetal cardiac genes were also measured. AC Fgf2(-/-) mice develop significantly less hypertrophy (4-24% increase) compared with AC Fgf2(+/+) mice (41-52% increase). Cardiomyocyte cross-sectional area is significantly reduced in AC Fgf2(-/-) mice. Noncoarcted (NC) and AC Fgf2(-/-) mice have similar beta-adrenergic responses, but those of AC Fgf2(+/+) mice are blunted. A lack of mitotic growth in both AC Fgf2(+/+) and Fgf2(-/-) hearts indicates a hypertrophic response of cardiomyocytes. Consequently, FGF2 plays a major role in cardiac hypertrophy. Comparison of alpha- and beta-cardiac myosin heavy chain mRNA and protein levels in NC and AC Fgf2(+/+) and Fgf2(-/-) mice indicates that myosin heavy chain composition depends on hemodynamic stress rather than on FGF2 or hypertrophy, and that isoform switching is transcriptionally, not posttranscriptionally, regulated.
Marine Protection in the Ross Sea (2011)

At the bottom reaches of the earth lies an ecosystem still largely untouched by humans. The Ross Sea continental shelf ecosystem is found 155 degrees west longitude lying adjacent to the Antarctic continent, with depths less than 3,000 metres, it stretches over almost a million kilometres (Hance, 2010). Its beautiful, rich and abundant nature somewhat protected from human exploitation by its extensive sea ice, brutal weather, and remote environment. Marine animals including killer whales, sea-birds, penguins, whales, giant fish and species not found elsewhere in the world continue to thrive and exist with limited manmade disturbance. Natural processes, species interaction, interconnections, food-webs, complexities not yet understood and other unknown mysteries abound. For this reason the establishment of a marine protected area (MPA) has recently been proposed by the Antarctic and Southern Ocean Coalition (ASOC). This follows suggestions by the World Summit for Sustainable Development, and the 5th World Parks Congress to establish a global and representative network of marine protected areas by 2012 (ASOC, 2010). This article will look at the Commission and the Convention currently governing fishing in the Ross Sea, as well as at the MPA proposal put forward.
Modeling the space of camera response functions (2004)

Many vision applications require precise measurement of scene radiance. The function relating scene radiance to image intensity of an imaging system is called the camera response. We analyze the properties that all camera responses share. This allows us to find the constraints that any response function must satisfy. These constraints determine the theoretical space of all possible camera responses. We have collected a diverse database of real-world camera response functions (DoRF). Using this database, we show that real-world responses occupy a small part of the theoretical space of all possible responses. We combine the constraints from our theoretical space with the data from DoRF to create a low-parameter empirical model of response (EMoR). This response model allows us to accurately interpolate the complete response function of a camera from a small number of measurements obtained using a standard chart. We also show that the model can be used to accurately estimate the camera response from images of an arbitrary scene taken using different exposures. The DoRF database and the EMoR model can be downloaded at http://www.cs.columbia.edu/CAVE.
Two regions of mature periplasmic maltose-binding protein of Escherichia coli involved in secretion (1988)

Six mutations in malE, the structural gene for the periplasmic maltose-binding protein (MBP) from Escherichia coli, prevent growth on maltose as a carbon source, as well as release of the mutant proteins by the cold osmotic-shock procedure. These mutations correspond to insertion of an oligonucleotide linker, concomitant with a deletion. One of the mutations (malE127) affects the N-terminal extension (the signal peptide), whereas the five others lie within the mature protein. As expected, the export of protein MalE127 is blocked at an early stage. This protein is neither processed to maturity nor sensitive to proteinase K in spheroplasts. In contrast, in the five other mutants, the signal peptide is cleaved and the protein is accessible to proteinase K added to spheroplasts. This indicates that the five mutant proteins are, at least in part, exported through the inner membrane. We propose that the corresponding mutations define two regions of the mature protein (between residues 18 and 42 and between residues 280 and 306), which are important for release of the protein from the inner membrane into the periplasm. We discuss the results in terms of possible conformational changes at this late step of export to the periplasm.
Temperature Dependence of the Visible-Near-Infrared Absorption Spectrum of Liquid Water (2001)

Optical absorptivity spectra of ultrapure liquid water over the wavelength range from 550 to 900 nm and over the temperature range from ∼15 to 60 °C are presented. The measured temperature dependence compares well with those reported by most previous workers. The linear dependence of the absorption spectrum on temperature is discussed in terms of structural changes occurring in liquid water as a function of temperature. The two-state, outer-neighbor bonding model of Robinson and co-workers is found to provide a good microscopic explanation of our data.
Octamer-based genome scanning distinguishes a unique subpopulation of Escherichia coli O157:H7 strains in cattle (1999)

Multilocus-genotyping methods have shown that Escherichia coli O157:H7 is a geographically disseminated clone. However, high-resolution methods such as pulse-field gel electrophoresis demonstrate significant genomic diversity among different isolates. To assess the genetic relationship of human and bovine isolates of E. coli O157:H7 in detail, we have developed an octamer-based genome-scanning methodology, which compares the distance between over-represented, strand-biased octamers that occur in the genome. Comparison of octamer-based genome-scanning products derived from >1 megabase of the genome demonstrated the existence of two distinct lineages of E. coli O157:H7 that are disseminated within the United States. Human and bovine isolates are nonrandomly distributed among the lineages, suggesting that one of these lineages may be less virulent for humans or may not be efficiently transmitted to humans from bovine sources. Restriction fragment length polymorphism analysis with lambdoid phage genomes indicates that phage-mediated events are associated with divergence of the lineages, thereby providing one explanation for the degree of diversity that is observed among E. coli O157:H7 by other molecular-fingerprinting methods.
The VLSI implementation of STONN (1990)

A 100000-transistor digital CMOS Hopfield neural network is presented, and its performance is discussed. STONN uses space efficient stochastic logic and bitwise pipelining to achieve massive parallelism and high operational speeds. The architecture produces solutions to optimization problems with a quality equivalent to that of solutions produced by analog networks and nearly as good as those found using simulated annealing. The massively parallel nature of STONN increases its speed of convergence by orders of magnitude over uniprocessor implementations. The completely digital STONN design provides dynamically reprogrammable parameters and a practical system implementation which can be expanded using several identical chips
Involvement of nitric oxide in the inhibition of aortic smooth muscle cell proliferation by calcium dobesilate (1999)

Vascular smooth muscle cell (SMC) proliferation is a key process in the pathogenesis of atherosclerosis. Numerous factors are involved in the regulation of SMC growth. Nitric oxide (NO) induces the inhibition of SMC proliferation whereas oxidized low-density lipoproteins (LDL) have a mitogenic effect. Calcium dobesilate (Doxium) is an angioprotective agent for treating vascular diseases. It has been shown to increase NO production and to have antioxidant properties but its mechanism of action is not yet fully understood. This study investigated the effect of calcium dobesilate on proliferation of rat aortic SMC in culture. Proliferation was evaluated by cell number and DNA synthesis. Orally administered calcium dobesilate (30, 100, or 200 mg/kg/day for 7 days) induced a dose-dependent decrease of proliferation of SMC in primary culture compared with controls.In vitro treatment with calcium dobesilate (0.05–5 mM) inhibited both DNA synthesis and proliferation in a time- and concentration-dependent manner. In bothex vivo andin vitro models, the inhibition was reversible upon removal of the drug. Calcium dobesilate also stimulated NO production and NO synthase activity. Inhibitors of NO synthesis attenuated the inhibitory effect of calcium dobesilate (300 μM) on DNA synthesis. In addition, calcium dobesilate (2.5–40 μM) induced a dose-dependent protection of cooper-induced LDL oxidation. These results showed that calcium dobesilate inhibits SMC proliferation, partly by a NO-dependent mechanism, and suggest that it could be effective in the treatment of pathological disorders associated with vascular SMC proliferation.
Stop-flow lithography in a microfluidic device (2007)

Polymeric particles in custom designed geometries and with tunable chemical anisotropy are expected to enable a variety of new technologies in diverse areas such as photonics, diagnostics and functional materials. We present a simple, high throughput and high resolution microfluidic method to synthesize such polymeric particles. Building off earlier work that we have done on continuous flow lithography (CFL) (D. Dendukuri, D. C. Pregibon, J. Collins, T. A. Hatton, P. S. Doyle, Nat. Mater., 2006, 5, 365-369; ref. 1), we have devised and implemented a new setup that uses compressed air driven flows in preference to syringe pumps to synthesize particles using a technique that we call stop-flow lithography (SFL). A flowing stream of oligomer is stopped before polymerizing an array of particles into it, providing for much improved resolution over particles synthesized in flow. The formed particles are then flushed out at high flow rates before the cycle of stop-polymerize-flow is repeated. The high flow rates enable orders-of-magnitude improvements in particle throughput over CFL. However, the deformation of the PDMS elastomer due to the imposed pressure restricts how quickly the flow can be stopped before each polymerization event. We have developed a simple model that captures the dependence of the time required to stop the flow on geometric parameters such as the height, length and width of the microchannel, as well as on the externally imposed pressure. Further, we show that SFL proves to be superior to CFL even for the synthesis of chemically anisotropic particles with sharp interfaces between distinct sections.
Juvenile idiopathic arthritis: Diagnosis and differential diagnosis (2010)

Juvenile idiopathic arthritis (JIA) is comprised of a heterogeneous group of several disease subtypes that are characterized by the onset of arthritis before the age of 16 years and has symptoms lasting at least 6 weeks. The previous classification of JIA included seven different categories, whereas its current classification was compiled by the International League of the Association for Rheumatology, and replaced the previous terms of "juvenile chronic arthritis" and "juvenile rheumatoid arthritis," which were used in Europe or North America, respectively, with the single nomenclature of JIA. As mentioned above, JIA is defined as arthritis of unknown etiology that manifests itself before the age of 16 years and persists for at least 6 weeks, while excluding other known conditions. The clinical symptoms of JIA can be quite variable. Several symptoms that are characteristic of arthritis are not necessarily diagnostic of JIA and may have multiple etiologies that can be differentiated with careful examination of patient history. The disease may develop over days or sometimes weeks, thereby making the diagnosis difficult at the time of presentation. To make a clinical diagnosis of JIA, the first step is to exclude arthritis with known etiologies. Of note, late treatment due to excessive delay of diagnosis can cause severe damage to joints and other organs and impair skeletal maturation. Therefore, early detection of JIA is critical to ensure prompt treatment and to prevent long-term complications including the likelihood of disability in childhood.
Novel, Bedside, Tissue Factor–Dependent Clotting Assay Permits Improved Assessment of Combination Antithrombotic and Antiplatelet Therapy (2000)

The assay developed should facilitate improved dose selection, titration, and monitoring of combination antithrombotic and antiplatelet treatment regimens.
Stable expression of high affinity NK1 (substance P) and NK2(neurokinin A) receptors but low affinity NK3 (neurokinin B) receptors in transfected CHO cells (1992)

Stable CHO cell clones which selectively express all three rat tachykinin receptors were established by transfection. The binding of radiolabled substance P and neurokinin A (substance K) to CHO clones expressing the NK1 and NK2 receptors, respectively, were saturatable and of high affinity (Kd = 0.17 nM (NK1); 3.4 nM (NK2)). Scatchard analysis of the binding data indicated for both receptors binding to a single population of binding sites, and competition binding studies showed that the binding specificities of the receptors corresponded to those of classical NK1 and NK2 receptors. In contrast, the binding of eledoisin to the NK3 receptor expressed in the transfected CHO cells was of low affinity (IC50 = 240 nM) compared to the high affinity of the receptor found when it was transiently expressed in COS-7 cells (IC50 = 8 nM). However, in both cases the receptor exhibited the specificity of a classical NK3 receptor. The established cell clones may provide an important tool for further analysis of the molecular mechanisms involved in binding, activation, and coupling of receptors for tachykinin peptides.
Transcriptomics identified a critical role for Th2 cell-intrinsic miR-155 in mediating allergy and antihelminth immunity (2014)

Allergic diseases, orchestrated by hyperactive CD4(+) Th2 cells, are some of the most common global chronic diseases. Therapeutic intervention relies upon broad-scale corticosteroids with indiscriminate impact. To identify targets in pathogenic Th2 cells, we took a comprehensive approach to identify the microRNA (miRNA) and mRNA transcriptome of highly purified cytokine-expressing Th1, Th2, Th9, Th17, and Treg cells both generated in vitro and isolated ex vivo from allergy, infection, and autoimmune disease models. We report here that distinct regulatory miRNA networks operate to regulate Th2 cells in house dust mite-allergic or helminth-infected animals and in vitro Th2 cells, which are distinguishable from other T cells. We validated several miRNA (miR) candidates (miR-15a, miR-20b, miR-146a, miR-155, and miR-200c), which targeted a suite of dynamically regulated genes in Th2 cells. Through in-depth studies using miR-155(-/-) or miR-146a(-/-) T cells, we identified that T-cell-intrinsic miR-155 was required for type-2 immunity, in part through regulation of S1pr1, whereas T-cell-intrinsic miR-146a was required to prevent overt Th1/Th17 skewing. These data identify miR-155, but not miR-146a, as a potential therapeutic target to alleviate Th2-medited inflammation and allergy.