gebhart/patrepeval huggingface dataset:
Alcohol Regulates Gene Expression in Neurons via Activation of Heat Shock Factor 1 (2007)

Drinking alcohol causes widespread alterations in gene expression that can result in long-term physiological changes. Although many alcohol-responsive genes (ARGs) have been identified, the mechanisms by which alcohol alters transcription are not well understood. To elucidate these mechanisms, we investigated Gabra4, a neuron-specific gene that is rapidly and robustly activated by alcohol (10-60 mM), both in vitro and in vivo. Here we show that alcohol can activate elements of the heat shock pathway in mouse cortical neurons to enhance the expression of Gabra4 and other ARGs. The activation of Gabra4 by alcohol or high temperature is dependent on the binding of heat shock factor 1 (HSF1) to a short downstream DNA sequence, the alcohol response element (ARE). Alcohol and heat stimulate the translocation of HSF1 from the cytoplasm to the nucleus and the induction of HSF1-dependent genes, Hsp70 and Hsp90, in cultured neurons and in the mouse cerebral cortex in vivo. The reduction of HSF1 levels using small interfering RNA prevented the stimulation of Gabra4 and Hsp70 by alcohol and heat shock. Microarray analysis showed that many ARGs contain ARE-like sequences and that some of these genes are also activated by heat shock. We suggest that alcohol activates phylogenetically conserved pathways that involve intermediates in the heat shock cascade and that sequence elements similar to the ARE may mediate some of the changes in gene expression triggered by alcohol intake, which could be important in a variety of pathophysiological responses to alcohol.
Applications of numbered undirected graphs (1977)

Numbered undirected graphs are becoming an increasingly useful family of mathematical models for a broad range of applications. They have found usage in various coding theory problems, including the design of good radar-type codes, synch-set codes and convolutional codes with optimal autocorrelation properties. They facilitate the optimal nonstandard encodings of integers. They have also been applied to determining ambiguities in X-ray crystallographic analysis, to design of a communication network addressing system, to determination of optimal circuit layouts, and to problems in additive number theory. An attempt has been made to systematically present all of these diverse applications in a unifying framework and to indicate the existence of additional applications and to suggest directions for additional research.
The ERK2 Mitogen-Activated Protein Kinase Regulates the Timing of Oligodendrocyte Differentiation (2011)

Oligodendrocyte development is tightly controlled by a variety of extracellular growth and differentiation factors. The mitogen-activated protein kinases (MAPKs), ERK1 and ERK2, are critical intracellular signaling molecules important for transducing these extracellular signals. The extracellular signal-regulated kinases (ERKs) are ubiquitously expressed, coordinately regulated, and highly similar, but Erk2 deletion in mice is embryonic lethal whereas Erk1 deletion is not. Several studies have suggested that MAPK signaling is important for oligodendrocyte differentiation, although specific roles for the two ERK isoforms have not been investigated. In this study, we deleted Erk2 in the developing mouse cortex from GFAP-expressing radial glia that generate neurons and oligodendrocytes. In vitro analysis revealed that loss of ERK2 resulted in fewer galactocerebroside-expressing mature oligodendrocytes in cortical cultures. In vivo, a delay in the expression of the myelin protein MBP was observed in the corpus callosum at postnatal day 10 (P10). In contrast, Erk1 deletion did not affect oligodendrocyte differentiation. By P21, MBP expression was restored to wild-type levels, demonstrating that the loss of ERK2 results in a delay but not a complete arrest in the appearance of differentiated oligodendrocytes in vivo. Importantly, both the proliferation and total number of oligodendrocyte progenitor cells (OPCs) appeared normal in the Erk2 conditional knock-out cortex, demonstrating that ERK2 plays a specific role in the timing of forebrain myelination but is not critical for the proliferation or survival of OPCs. Oligodendrocyte-specific deletion of Erk2 also resulted in decreased levels of MBP, indicating a cell-autonomous effect of ERK2 in the oligodendrocyte lineage.
White Light‐Emitting Diodes with Excellent Color Rendering Based on Organically Capped CdSe Quantum Dots and Sr3SiO5:Ce3+,Li+ Phosphors (2008)

White LEDs are fabricated through a combination of blue LEDs with Sr3 SiO5 :Ce(3+) ,Li(+) phosphors and organically capped CdSe quantum dots (QDs), which exhibit a 2D superlattice. The combination of blue emission from the LEDs, greenish-yellow emission from the phosphors, and red emission from the QDs generates white light. As-synthesized white LEDs show excellent color rendering properties and stable color coordinates against increasing forward bias currents.
Cytotoxic Human HLA Class II Restricted Purified Protein Derivative‐Reactive T‐Lymphocyte Clones (1987)

Human T-lymphocyte clones specific for antigenic components of purified protein derivative (PPD) of tuberculin were generated by limiting dilution using in vitro PPD-activated peripheral blood mononuclear cells from a single donor. The HLA restriction specificity of eight clones that were cytotoxic against autologous PPD-pulsed monocyte targets, was examined against a panel of allogeneic PPD pulsed targets. In agreement with our findings with bulk-expanded PPD-reactive cytotoxic T lymphocytes, all clones were restricted by HLA class II antigens: seven by HLA-DR 2 and one by HLA-DRw10--the other HLA-DR antigen of the donor. All clones were CD3+, CD4+, CD8-. One clone exhibited, in addition to HLA-DR2 restriction, unrestricted cytotoxic alloreactivity against HLA-DR1. In monoclonal antibody-blocking experiments the latter clone was the only one that was blocked. Its lytic ability was abolished by two monoclonal antibodies against monomorphic HLA-DR determinants. The antigen specificity of the clones was studied by using autologous monocyte targets pulsed with antigens prepared from a range of different mycobacterial species. All seven HLA-DR2-restricted clones reacted with the majority of antigens tested. In contrast, the HLA-DRw10-restricted clone reacted exclusively with an antigen unique to PPD.
Influence of thermal annealing on the perpendicular magnetic anisotropy of Pt/Co/AlOx trilayers (2009)

The influence of thermal annealing on Pt/Co/AlOx trilayers has been investigated up to $450\text{ }\ifmmode^\circ\else\textdegree\fi{}\text{C}$ as a function of the plasma oxidation time of the AlOx layer. Both magnetic properties of the Co layer and transport properties are strongly modified upon annealing. The perpendicular magnetic anisotropy reaches very large values, while the Hall angle increases with annealing temperature. This study reveals that this trilayer system possesses tunable magnetic anisotropy properties, which can be controlled by varying either oxidation time or annealing temperature. These results are compared with those obtained on standard Pt/Co/Pt trilayers which show, on the contrary, a continuous degradation of their magnetic properties upon annealing.
Rhesus brain microvascular endothelial cells are permissive for rhesus cytomegalovirus infection (2005)

Endothelial cells (EC) are an important cell type for human cytomegalovirus (CMV) pathogenesis. To characterize better the role of EC in primate CMV natural history, rhesus macaque microvascular EC (MVEC) were purified from fetal brain and analysed for infectivity by rhesus cytomegalovirus (RhCMV). Rhesus brain MVEC (BrMVEC) in culture were positive for von Willebrand factor and CD105 expression, uptake of acetylated low-density lipoprotein, and formation of capillary-like tubules on Matrigel, all phenotypic hallmarks of EC. BrMVEC were fully permissive for infection by RhCMV strain 68-1, and detectable plaques formed within 5 days of infection. Infectivity of BrMVEC by RhCMV could be reduced, but not abolished, by treatment of cells either before or during infection with pro-inflammatory mediators tumour necrosis factor-alpha, interleukin-1beta or phorbol 12-myristate 13-acetate. These results demonstrate that in vitro infection of rhesus BrMVEC is a dynamic process that is influenced by activation conditions.
Immunohistochemical localization of pancreatic secretory trypsin inhibitor in fetal and adult pancreatic and extrapancreatic tissues. (1986)

Pancreatic secretory trypsin inhibitor (PSTI) has been thought to be only a secretory trypsin inhibitor of human pancreas, but the serum content of immunoreactive PSTI is elevated without pancreatic disease. Using the peroxidase-antiperoxidase method, immunoreactive cells for PSTI were found in human pancreas, stomach, duodenum, appendix, colon and urinary tract of both fetus and adult, adult gall bladder, and fetal lung. PSTI-immunoreactive cells were identified in fetal pancreas at the tenth gestational week, and in extrapancreatic tissues at the sixteenth (gastrointestinal and urinary tract) and twentieth weeks (lung). PSTI-immunoreactive cells of fetal lung were present in neuroepithelial bodies. Strongly positive cells in fetal duodenum were argyrophilic and resembled endocrine cells. Immunohistochemical study was also performed on tissues associated with inflammatory diseases of gastrointestinal tract. The distribution pattern of immunoreactive cells in the stomach varied in accordance with chronic gastritis. Immunoreactive cells were also found in endocrine micro-nests and in a carcinoid tumor associated with fundic gastritis. These results suggest that PSTI may play some physiological role other than secretory trypsin inhibition of the pancreas.
Pilot Randomized Clinical Trial of Prehospital Induction of Mild Hypothermia in Out-of-Hospital Cardiac Arrest Patients With a Rapid Infusion of 4°C Normal Saline (2007)

These pilot data suggest that infusion of up to 2 L of 4 degrees C normal saline in the field is feasible, safe, and effective in lowering temperature. We propose that the effect of this cooling method on neurological outcome after cardiac arrest be studied in larger numbers of patients, especially those whose initial rhythm is ventricular fibrillation.
Abstract P3-04-27: Delineating novel molecular pathways driving endocrine resistance in breast cancer (2017)

Abstract Background Estrogen receptor (ER) is a main driver of tumor progression in ER+ metastatic breast cancer (MBC). The use of endocrine therapy can effectively control the disease in a large proportion of patients. However, the majority of MBC eventually become resistant and progress. To elucidate the mechanisms of acquired resistance to endocrine treatment is key in order to better select therapeutic partners and delay disease progression. Methods A panel of ER+ breast cancer cell lines initially sensitive to the selective estrogen receptor degrader (SERD) fulvestrant was exposed to increasing concentrations of this drug over several months to induce resistance. Cell proliferation was determined with the xCELLigence system. Protein expression was measured by phospho-kinase array and western blotting. RNA expression was evaluated by gene expression microarray analysis (Illumina) and validated by RT-qPCR. Cell cycle distribution was analyzed by flow cytometry. Results Using an unbiased approach to identify pathways that drive endocrine resistance, both the parental and the resistant cell models were studied. As expected, fulvestrant treatment resulted in G1-cell cycle arrest in the parental cell lines. In stark contrast, resistant cells bypassed fulvestrant-induced proliferation block despite a lower expression of genes driving mitotic progression compared to untreated parental cells. This gene expression pattern was coupled with a reduction of ER protein level in the resistant cells, which was in line with a significant decrease in the expression of ER-target genes. Our phospho-screen analysis showed a genotype specific down-modulation of p53 and up-regulation of several signaling components of mitogenic pathways in resistant cells compared to parental cells. Conclusions Our results suggest that acquired endocrine resistance is driven by multiple cell-specific mechanisms rather than a common molecular underpinning. Strikingly, there is one unique feature in our models, which is a cellular switch towards an ER-independent gene expression program. Ongoing in vitro and in vivo studies, aimed at further characterizing these cellular models, will provide valuable insights into the heterogeneity underlying the response to endocrine treatment observed in MBC patients. Citation Format: Bosch A, Staaf J, Akrap N, Kaminska KK, Borgquist S, Borg Å, Honeth G. Delineating novel molecular pathways driving endocrine resistance in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-04-27.
Patterning of (Pb, La)(Zr, Ti)O3 waveguides for fabricating micro-optics using wet etching and solid-phase epitaxy (1999)

The patterning process of (Pb, La)(Zr, Ti)O3 heterostructure waveguides was examined for fabricating micro-optics, including channels and lenses. After the patterning of the amorphous thin films derived from spin-cast methoxyethoxide precursors by a wet etching, the patterned amorphous film was crystallized by solid-phase epitaxy. A 5-μm-wide ridge-type channel waveguide was fabricated in a Pb0.91La0.09(Zr0.65Ti0.35)O3/Pb(Zr0.52Ti0.48)O3 heterostructure on a SrTiO3 (100) substrate by the process. The optical confinement was successfully observed. A mode index lens was also fabricated in the Pb0.91La0.09(Zr0.65Ti0.35)O3/Pb(Zr0.30Ti0.70)O3 heterostructure on the SrTiO3 (100) substrate. A deflection of the collimated light by the lens was observed.
Kinetic Properties of Polymorphic Variants and Pathogenic Mutants in Human Cystathionine γ-Lyase (2008)

Human cystathionine-gamma-lyase (CGL) is a pyridoxal-5'-phosphate (PLP)-dependent enzyme, which functions in the transsulfuration pathway that converts homocysteine to cysteine. In addition, CGL is one of two major enzymes that can catalyze the formation of hydrogen sulfide, an important gaseous signaling molecule. Recently, several mutations in CGL have been described in patients with cystathioninuria, a rare but poorly understood genetic disease. Moreover, a common single nucleotide polymorphism in CGL, c.1364G>T that converts serine at position 403 to isoleucine, has been linked to elevated plasma homocysteine levels. In this study, we have characterized the pathogenic T67I and Q240E missense mutations and the polymorphic variants at amino acid residues 403 using kinetic and spectrophotometric methods. We report that the polymorphism does not influence the cofactor content of the enzyme or its steady-state kinetic properties. In contrast, the T67I mutant exhibits a 3.5-fold decrease in V max compared to that of wild-type CGL, while the Q240E mutant exhibits a 70-fold decrease in V max. The K Ms for cystathionine for both pathogenic mutants are comparable to that of wild type CGL. The PLP content of the T67I and Q240E mutants were about 4-fold and 80-fold lower than that of wild-type enzyme, respectively. Preincubation of the T67I mutant with PLP restored activity to wild-type levels while the same treatment resulted in only partial restoration of activity of the Q240E mutant. These results reveal that both mutations weaken the affinity for PLP and suggest that cystathionuric patients with these mutations should be responsive to pyridoxine therapy.
Erosive Esophagitis and Nonerosive Reflux Disease (NERD) (2007)

Nonerosive reflux disease (NERD) and erosive esophagitis are the main presentations of gastroesophageal reflux disease. However, NERD is the most common presentation of gastroesophageal reflux disease in community-based patients. Patients with NERD differ in demographic characteristics from patients with erosive esophagitis, primarily in sex distribution, weight/body mass index, and prevalence of hiatal hernia. Physiologically, patients with NERD tend to have normal lower esophageal sphincter resting pressure, minimal esophageal body motility abnormalities, low esophageal acid exposure profile and minimal nighttime esophageal acid exposure. Patients with NERD have a lower symptom response rate to proton pump inhibitor once daily than patients with erosive esophagitis. Additionally, NERD patients demonstrate a longer lag-time for symptom resolution and lack of difference in symptom response rate between half to full dose proton pump inhibitor as compared with patients with erosive esophagitis.
Transcriptional control of yeast plasma membrane H(+)-ATPase by glucose. Cloning and characterization of a new gene involved in this regulation. (1994)

The expression of the ATPase gene (PMA1) is regulated by glucose (Rao, R., Drummond-Barbosa, D., and Slayman, C. W. (1993) Yeast 9, 1075-1084) and by the TUF/RAP1/GRF1 transcription factor (Capieaux, E., Vignais, M.-L., Sentenac, A., and Goffeau, A. (1989) J. Biol. Chem. 264, 7437-7446). In this work, we describe the isolation of mutations on seven genes that affect the levels of ATPase. One of these genes (APA1) was cloned by complementation and shown to encode a protein with six putative transmembrane stretches. Expression of APA1 gene is regulated by the carbon source and requires the protein GCR1. Deletion of APA1 causes a defective regulation of the PMA1 expression by glucose but has not noticeable effect on the expression of other TUF-regulated genes. Nevertheless the expression of glucose-repressible HXT3 and SNF3 genes is significantly reduced. These results suggest a model in which APA1 acts on a glucose-signaling pathway that controls the expression of several genes that are transcriptionally regulated by glucose.
Mechanism of Telomere Shortening by Oxidative Stress (2004)

A bstract : We investigated whether oxidative stress, which contributes to aging, accelerates the telomere shortening in human cultured cells. The terminal restriction fragment (TRF) from WI‐38 fibroblasts irradiated with UVA (365‐nm light) decreased with increasing of the irradiation dose. Furthermore, UVA irradiation dose‐dependently increased the formation of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodG) in both WI‐38 fibroblasts and HL‐60 cells. In order to clarify the mechanism of the acceleration of telomere shortening, we investigated site‐specific DNA damage induced by UVA irradiation in the presence of endogenous photosensitizers using 32 P 5′ end‐labeled DNA fragments containing telomeric oligonucleotide (TTAGGG) 4 . UVA irradiation with riboflavin induced 8‐oxodG formation in the DNA fragments containing telomeric sequence, and Fpg protein treatment led to chain cleavages at the central guanine of 5′‐GGG‐3′ in telomere sequence. Human 8‐oxodG‐DNA glycosylase introduces a chain break in a double‐stranded oligonucleotide specifically at an 8‐oxodG residue. The amount of 8‐oxodG formation in DNA fragment containing telomere sequence [5′‐CGC(TTAGGG) 7 CGC‐3′] was approximately five times more than that in the DNA fragment containing nontelomere sequence [5′‐CGC(TGTGAG) 7 CGC‐3′]. Furthermore, H 2 O 2 plus Cu(II) caused DNA damage, including 8‐oxodG formation, specifically at the GGG sequence in the telomere sequence (5′‐TTAGGG‐3′). It is concluded that the formation of 8‐oxodG at the GGG triplet in telomere sequence induced by oxidative stress could participate in acceleration of telomere shortening.
The pro-apoptotic action of stilbene-induced COX-2 in cancer cells: Convergence with the anti-apoptotic effect of thyroid hormone (2009)

Constitutively expressed cyclooxygenase-2 (COX-2) is a marker of tumor cell aggressiveness. Inducible COX-2 has also been described in cancer cells and localizes in the cancer cell nucleus, where formation of a complex of mitogen-activated protein kinase (MAPK) and COX-2 is antecedent to p53-dependent apoptosis. The stilbene resveratrol is a model pharmacologic activator of this pro-apoptotic mechanism. Physiological concentrations of thyroid hormone are anti-apoptotic in several types of tumor cells. A mechanism by which the hormone is anti-apoptotic is disruption of the nuclear MAPK-COX-2 complex. We review here the apoptosis-relevant effects of resveratrol and thyroid hormone and then speculate about the significance of convergence of these actions in cancer cells in the intact organism. Clinical activity of resveratrol may be modulated by normal tissue levels of endogenous thyroid hormone, and hypothyroidism in the cancer patient -- whether spontaneous or induced by chemotherapeutic agents -- may permit full expression of the apoptotic activity of the administered stilbene. Chronic pharmacologic inhibition of COX-2 may oppose the pro-apoptotic effect of resveratrol.
Feeder-Layer Free Culture System for Human Embryonic Stem Cells (2007)

Human embryonic stem cells (hESCs) are pluripotent stem cells derived from the inner cell mass of the blastocyst. Due to their unique properties, hESCs might be used for research fields such as self-renewal, specific lineage differentiation, human developmental biology, and teratology. hESCs also have outstanding potential to serve for clinical purposes as a source for cell-based therapies. Traditionally, these cells are cultured and derived with mouse embryonic fibroblast as supportive layer, using a medium supplemented with fetal bovine serum. Future industrial and clinical implementation of hESCs will require the use of a defined medium and an animal-free culture method that will prevent their possible exposure to animal pathogens. This chapter discusses the advancements in the development of methods for the defined culture of hESCs and describes a simple method for animals serum-free and feeder layer-free culture of hESCs.
Dopamine D1 and D2 Receptor Co-activation Generates a Novel Phospholipase C-mediated Calcium Signal (2004)

Although dopamine D1 and D2 receptors belong to distinct subfamilies of dopamine receptors, several lines of evidence indicate that they are functionally linked. However, a mechanism for this linkage has not been elucidated. In this study, we demonstrate that agonist stimulation of co-expressed D1 and D2 receptors resulted in an increase of intracellular calcium levels via a signaling pathway not activated by either receptor alone or when only one of the co-expressed receptors was activated by a selective agonist. Calcium signaling by D1-D2 receptor co-activation was abolished following treatment with a phospholipase C inhibitor but not with pertussis toxin or inhibitors of protein kinase A or protein kinase C, indicating coupling to the G(q) pathway. We also show, by co-immunoprecipitation from rat brain and from cells co-expressing the receptors, that D1 and D2 receptors are part of the same heteromeric protein complex and, by immunohistochemistry, that these receptors are co-expressed and co-localized within neurons of human and rat brain. This demonstration that D1 and D2 receptors have a novel cellular function when co-activated in the same cell represents a significant step toward elucidating the mechanism of the functional link observed between these two receptors in brain.