gebhart/patrepeval huggingface dataset:
Molecular and functional properties of two-pore-domain potassium channels (2000)

The two-pore-domain K(+) channels, or K(2P) channels, constitute a novel class of K(+) channel subunits. They have four transmembrane segments and are active as dimers. The tissue distribution of these channels is widespread, and they are found in both excitable and nonexcitable cells. K(2P) channels produce currents with unusual characteristics. They are quasi-instantaneous and noninactivating, and they are active at all membrane potentials and insensitive to the classic K(+) channel blockers. These properties designate them as background K(+) channels. They are expected to play a major role in setting the resting membrane potential in many cell types. Another salient feature of K(2P) channels is the diversity of their regulatory mechanisms. The weak inward rectifiers TWIK-1 and TWIK-2 are stimulated by activators of protein kinase C and decreased by internal acidification, the baseline TWIK-related acid-sensitive K(+) (TASK)-1 and TASK-2 channels are sensitive to external pH changes in a narrow range near physiological pH, and the TWIK-related (TREK)-1 and TWIK-related arachidonic acid-stimulated K(+) (TRAAK) channels are the first cloned polyunsaturated fatty acids-activated and mechanogated K(+) channels. The recent demonstration that TASK-1 and TREK-1 channels are activated by inhalational general anesthetics, and that TRAAK is activated by the neuroprotective agent riluzole, indicates that this novel class of K(+) channels is an interesting target for new therapeutic developments.
Carbon nitrides: synthesis and characterization of a new class of functional materials (2017)

Carbon nitride compounds with high N : C ratios and graphitic to polymeric structures are being investigated as potential next-generation materials for incorporation in devices for energy conversion and storage as well as for optoelectronic and catalysis applications. The materials are built from C- and N-containing heterocycles with heptazine or triazine rings linked via sp<sup>2</sup>-bonded N atoms (N(C)<sub>3</sub> units) or -NH- groups. The electronic, chemical and optical functionalities are determined by the nature of the local to extended structures as well as the chemical composition of the materials. Because of their typically amorphous to nanocrystalline nature and variable composition, significant challenges remain to fully assess and calibrate the structure-functionality relationships among carbon nitride materials. It is also important to devise a useful and consistent approach to naming the different classes of carbon nitride compounds that accurately describes their chemical and structural characteristics related to their functional performance. Here we evaluate the current state of understanding to highlight key issues in these areas and point out new directions in their development as advanced technological materials.
Role of the SIKVAV Site of Laminin in Promotion of Angiogenesis and Tumor Growth: An In Vivo Matrigel Model (1992)

These data demonstrate that the laminin-derived SIKVAV-containing peptide is angiogenic in a new in vivo model system and can enhance tumor vascularization and growth.
Late ureteral obstruction after kidney transplantation. (1997)

Abstract Today, the incidence of urological complications following renal transplantation is 2 %-10 %. Most of these complications occur within the 1st year and affect the distal ureter. We report on two patients who developed very late ureteral obstruction, 14 and 18 years after transplantation. Both patients had rejection episodes 1 and 10 months prior to the ureteral stenosis. Histological examination of one resected ureter revealed findings strongly suggestive of a rejection process. Open surgery with antirefluxive reimplantation into the bladder was successful in both patients, with a postoperative observation time of 20 and 8 months, respectively. We conclude that a percutaneous nephrostomy may be required in patients with rising creatinine and incipient hydronephrosis even long after transplantation has been performed.
Liposomal encapsulation enhances the activity of immunostimulatory oligonucleotides (2006)

AbstractA tremendous level of interest has surrounded the field of immunostimulatory oligonucleotides (IS-ODNs) over recent years, fueled by promising results from preclinical and clinical studies in malignant, infectious and autoimmune diseases. Despite these results, clinical utility of free ODNs is faced with several significant challenges, including poor in vivo stability, acute adverse side effects, unfavorable pharmacokinetic and biodistribution profiles and poor cellular uptake characteristics. For these reasons, there has been considerable interest in the development of liposomal delivery strategies for IS-ODNs. This review provides a brief overview of IS-ODNs, their mechanism of action and the preclinical and clinical studies supporting its potential as an immunotherapeutic agent. Furthermore, it outlines problems associated with the clinical utility of free ODNs and the solutions offered by liposomal encapsulation. Finally, effects of liposomal delivery on IS-ODN immunopotency and prophylactic and therapeutic activity in disease models are discussed.Keywords: CpGencapsulationimmunostimulatoryimmunotherapyliposomeoligonucleotide
Multicenter Study To Determine Antibody Concentrations and Assess the Safety of Administration of INH-A21, a Donor-Selected Human Staphylococcal Immune Globulin, in Low-Birth-Weight Infants (2005)

Nosocomial or late-onset sepsis is a common complication among premature infants, with a frequency inversely correlated with birth weight. Increased susceptibility to infection is due in part to an immature humoral (antibody-mediated) immune response. This study investigated the pharmacokinetics (PKs) and safety of a donor-selected specific intravenous immune globulin (IVIG) preparation, INH-A21 (Veronate), for prevention of sepsis in premature infants. Thirty-six infants weighing between 500 and 1,250 g during the first postnatal week were eligible to begin a series of up to four intravenous infusions of 500 or 750 mg/kg of body weight INH-A21. Blood samples were analyzed for antibodies against the Ser-Asp dipeptide repeat G (SdrG) and clumping factor A (ClfA) surface proteins of staphylococci. Sparse sampling and population PK analyses were performed to derive PK parameters. Following administration of the 500- and 750-mg/kg doses, the estimated average steady-state levels of anti-ClfA were 6.1 U/ml and 9.2 U/ml, respectively, and those of anti-SdrG were 5.2 U/ml and 7.7 U/ml, respectively. The elimination half-lives for anti-ClfA and anti-SdrG were 719 h and 701 h, respectively, and the clearances were 0.18 ml/h and 0.21 ml/h, respectively. In the final model, the values of the PK parameters were independent of gestational age. Both doses of INH-A21 were well tolerated, and the safety profile was similar to those of other IVIG preparations. These results suggest that a shorter dosing interval should be utilized between the first and second doses to achieve and maintain higher titers of anti-ClfA and anti-SdrG antibodies. Further studies examining INH-A21 for the prevention of late-onset sepsis in infants within the weight range studied are warranted.
Rearrangements on chromosome 11q23 in hematopoietic tumor-associated t(11;14) and t(11;19) translocations. (1991)

We previously demonstrated that the breakpoint of t(11;14)(q23;q32) in the RC-K8 B cell lymphoma cell line lies between CD3 and THY1/ETS1 on chromosome 11q23, and we cloned this region and named it the rck locus. Pulsed-field gel electrophoresis showed that the rck probe B (distal to the breakpoint) and the porphobilinogen deaminase (PBGD) probe detect the same germ line band and also the same rearranged band when DNA from RC-K8 cells was digested with NotI enzyme. Furthermore, Southern blot analysis with somatic cell hybrids showed that the PBGD gene moved to the 14q+chromosome, which confirmed PBGD to be more distal to the centromere than the rck locus. These data allowed us to construct the following order of genes: 11 cen-q23-CD3-rck-PBGD-THY1/ETS1. In this study, three infantile leukemia cell lines with t(11;19)(q23;p13) translocation were also analyzed by pulsed-field gel electrophoresis. CD3D probe detected the rearranged bands in DNA from two of them after digestion with NotI and SacII enzymes, demonstrating that the breakpoints of both cell lines were estimated to be within 360 kilobases of CD3D.
Development of a New Amperometric Biosensor for Lactose Determination (2003)

A new amperometric biosensor for lactose determinaion in raw milk was developed through the simultaneous immobilization of -galactosidase and galactose oxidase on a derivatised polyethersulphone membrane. -galactosidase catalyses the hydrolysis of lactose into galactose and glucose and galactose oxidase catalyses the oxidation of galactose into galactonic acid and H 2 O 2 . The membranes with the two immobilized enzymes were then used in an amperometric sensor, by oxidation of the H 2 O 2 formed, at a Pt electrode of an Universal Sensors electrode base system. The sensitivity and the reproducibility of the biosensor thus formed were found to be 6.81 and 0.72 nA.M -1 , respectively. Biosensors were found to be stable for 20 days.
Two Families of Chaperonin: Physiology and Mechanism (2007)

Chaperonins are large ring assemblies that assist protein folding to the native state by binding nonnative proteins in their central cavities and then, upon binding ATP, release the substrate protein into a now-encapsulated cavity to fold productively. Two families of such components have been identified: type I in mitochondria, chloroplasts, and the bacterial cytosol, which rely on a detachable "lid" structure for encapsulation, and type II in archaea and the eukaryotic cytosol, which contain a built-in protrusion structure. We discuss here a number of issues under current study. What is the range of substrates acted on by the two classes of chaperonin, in particular by GroEL in the bacterial cytoplasm and CCT in the eukaryotic cytosol, and are all these substrates subject to encapsulation? What are the determinants for substrate binding by the type II chaperonins? And is the encapsulated chaperonin cavity a passive container that prevents aggregation, or could it be playing an active role in polypeptide folding?
Molecular model of the action potential sodium channel. (1986)

Secondary and tertiary structural models of sodium channel transmembrane segments were developed from its recently determined primary sequence in Electrophorus electricus. The model has four homologous domains, and each domain has eight homologous transmembrane segments, S1 through S8. Each domain contains three relatively apolar segments (S1, S2 and S3) and two very apolar segments (S5 and S8), all postulated to be transmembrane alpha-helices. S4 segments have positively charged residues, mainly arginines, at every third residue. The model channel lining is formed by four S4 transmembrane alpha-helices and four negatively charged S7 segments. S7 segments are postulated to be short, partially transmembrane amphipathic alpha-helices in three domains and a beta-strand in the last domain. S7 segments are preceded by short apolar segments (S6) postulated to be alpha-helices in three domains and a beta-strand in the last domain. Positively charged side chains of S4 form salt bridges with negatively charged side chains on S7 and near the ends of S1 and S3. Putative extracellular segments that contain 5 of the 10 potential N-glycosylation sites link S5 to S6. Channel activation may involve a 'helical screw' mechanism in which S4 helices rotate around their axes as they move toward the extracellular surface.
Visceral vasodilatation and somatic vasoconstriction evoked by acid challenge of the rat gastric mucosa: diversity of mechanisms. (1995)

1. Acid back-diffusion through a disrupted gastric mucosal barrier increases blood flow to the stomach without any change in systemic blood pressure. This study was undertaken to examine the gastric acid-evoked changes in blood flow in a number of visceral and somatic arterial beds and to elucidate the mechanisms which lead to the regionally diverse haemodynamic responses. 2. The gastric mucosa of urethane-anaesthetized rats was challenged with acid by perfusing the stomach with ethanol (15%, to disrupt the gastric mucosal barrier) in 0.15 M HCl. Blood flow was estimated by laser Doppler flowmetry, the hydrogen clearance method or the ultrasonic transit time shift technique. 3. Gastric acid challenge increased blood flow in the gastric mucosa and left gastric artery while blood flow in the femoral artery and skin declined. 4. Afferent nerve stimulation by intragastric administration of capsaicin enhanced blood flow in the left gastric artery but did not diminish blood flow in the femoral artery when compared with the vehicle. 5. The gastric acid-evoked dilatation of the left gastric artery was depressed by acute extrinsic denervation of the stomach, capsaicin-induced ablation of afferent neurones or hexamethonium-induced blockade of autonomic ganglionic transmission. 6. The gastric acid-induced constriction of the femoral artery was attenuated by acute extrinsic denervation of the stomach but left unaltered by capsaicin, hexamethonium, guanethidine, indomethacin, telmisartan (an angiotensin II antagonist), [d(CH2)5(1), Tyr(Me)2, Arg8]-vasopressin (a vasopressin antagonist), bosentan (an endothelin antagonist) and acute ligation of the blood vessels to the adrenal glands. 7. These data show that acid challenge of the gastric mucosa elicits visceral vasodilatation and somatic vasoconstriction via divergent mechanisms. The gastric hyperaemia is brought about by extrinsic vasodilator nerves, whereas the reduction of somatic blood flow seems to be mediated by non-neural, probably humoral, vasoconstrictor messengers that remain to be identified.
Adaptive Control at Low Glucose Concentration of HEK-293 Cell Serum-Free Cultures (1999)

Fed-batch cultures were implemented to study the metabolism of HEK-293 cells. Glucose, measured every 30 min by a FIA biosensor system, was maintained at 1 mM throughout the culture using an adaptive nonlinear controller based on minimal process modeling. The controller performed satisfactorily at both low and high cell concentrations without the need for retuning between different culture phases. Overall, lactate production was significantly reduced by maintaining a low glucose concentration, thus decreasing the rate of glycolysis. The rates of glucose and glutamine uptake as well as the lactate and ammonia production were compared to those obtained in batch mode with an initial glucose concentration of 21 mM. Basically, three phases were observed in both culture modes. The metabolic shift from the first to the second phase was characterized by a significant reduction in glucose consumption and lactate production while maximum growth rate was maintained. The specific respiration rate appeared unchanged during the first two phases, suggesting that no change occurred in the oxidative pathway capacity. In the third phase, cell growth became slower very likely due to glutamine limitation.
Overexpression of neurofilament H disrupts normal cell structure and function (2002)

Studying exogenously expressed tagged proteins in live cells has become a standard technique for evaluating protein distribution and function. Typically, expression levels of experimentally introduced proteins are not regulated, and high levels are often preferred to facilitate detection. However, overexpression of many proteins leads to mislocalization and pathologies. Therefore, for normative studies, moderate levels of expression may be more suitable. To understand better the dynamics of intermediate filament formation, transport, and stability in a healthy, living cell, we inserted neurofilament heavy chain (NFH)-green fluorescent protein (GFP) fusion constructs in adenoviral vectors with tetracycline (tet)-regulated promoters. This system allows for turning on or off the synthesis of NFH-GFP at a selected time, for a defined period, in a dose-dependent manner. We used this inducible system for live cell imaging of changes in filament structure and cell shape, motility, and transport associated with increasing NFH-GFP expression. Cells with low to intermediate levels of NFH-GFP were structurally and functionally similar to neighboring, nonexpressing cells. In contrast, overexpression led to pathological alterations in both filament organization and cell function.
Integrins in Head and Neck Squamous Cell Carcinoma Invasion (2002)

The UM-SCC-1 carcinoma cells are more invasive than JHU-022-SCC cells and may be related to differential expression of the integrins alpha6beta4, alpha3beta1, and alpha2beta1.
An Acylation Cycle Regulates Localization and Activity of Palmitoylated Ras Isoforms (2005)

We show that the specific subcellular distribution of H- and Nras guanosine triphosphate-binding proteins is generated by a constitutive de/reacylation cycle that operates on palmitoylated proteins, driving their rapid exchange between the plasma membrane (PM) and the Golgi apparatus. Depalmitoylation redistributes farnesylated Ras in all membranes, followed by repalmitoylation and trapping of Ras at the Golgi, from where it is redirected to the PM via the secretory pathway. This continuous cycle prevents Ras from nonspecific residence on endomembranes, thereby maintaining the specific intracellular compartmentalization. The de/reacylation cycle also initiates Ras activation at the Golgi by transport of PM-localized Ras guanosine triphosphate. Different de/repalmitoylation kinetics account for isoform-specific activation responses to growth factors.
Disruption of T helper 2-immune responses in Epstein–Barr virus-induced gene 3-deficient mice (2002)

Epstein-Barr virus-induced gene 3 (EBI3) is a widely expressed IL-12p40-related protein that associates as a heterodimer with either IL-12p35 or an IL-12p35 homologue, p28, to create a new cytokine (IL-27). To define the function of EBI3 in vivo, we generated knockout mice in which the ebi3 gene was targeted by homologous recombination. EBI3-/- mice exhibited normal numbers of both naive and mature CD4+ and CD8+ T cells and B cells, but markedly decreased numbers of invariant natural killer T cells (iNKT) as defined by staining with an alpha-galactosylceramide (alphaGalCer)-loaded CD1d-tetramer. iNKT cells from EBI3-/- mice exhibited decreased IL-4 and, to a lesser extent, IFN-gamma production after alphaGalCer stimulation in vitro. A sustained decrease in IL-4 production was also observed in EBI3-/- mice after alphaGalCer stimulation in vivo in contrast to IFN-gamma production, which was only transiently decreased under such stimulation. Notably, EBI3-/- mice were resistant to the induction of immunopathology associated with oxazolone-induced colitis, a colitis model mediated primarily by T helper (Th) 2-type cytokine production by iNKT cells. In contrast, trinitrobenzene sulfonic acid-induced colitis, a predominantly Th1-mediated colitis model, was unaffected. Thus, EBI3 plays a critical regulatory role in the induction of Th2-type immune responses and the development of Th2-mediated tissue inflammation in vivo, which may be mediated through the control of iNKT cell function.
Abstract 3200: A Novel Functional Role of ARF in Prostate Cancer (2010)

Abstract A Novel Functional Role of ARF in Prostate Cancer Zhenbang Chen,1,2,6 Arkaitz Carracedo,1,2 Hui-Kuan Lin,2 Jason A. Koutcher,3 Nille Behrendt,2 Ainara Egia,1,2 Andrea Alimonti1,2, Brett S. Carver,4 William Gerald,2 Julie Teruya-Feldstein,2 Massimo Loda,5 Pier Paolo Pandolfi 1,2* 1Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, New Research Building, 330 Brookline Avenue, Boston, MA 02115, USA. 2Department of Pathology, 3Departments of Medicine, Radiology and Medical Physics, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA. 4Human Oncology and Pathologenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. 5Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. 6Department of Biochemistry and Cancer Biology, Meharry Medical College, 1005 D. B. Todd Jr. Blvd., Nashville, TN 37208, USA Abstract PTEN and p53 are the two most frequently mutated and/or deleted genes in human cancers including prostate cancer, and their causal and synergistic cooperation remains elusive. Acute Pten inactivation induces a striking cellular senescence response both in mouse prostates and in primary mouse embryonic fibroblasts (MEFs) by activation of p19ARF-p53 pathway. Inactivation of Trp53 alone in mouse prostates fails to generate a tumor phenotype whereas complete inactivation of Pten in the prostate results in non-lethal invasive prostate cancer with long latency. Notably, concomitant inactivation of Trp53 and Pten in the prostate completely overcomes Pten-loss induced cellular senescence and invariably leads to a lethal cancer phenotype by 7 months of age. On the basis of the function coupling relationship between p19ARF and p53 proteins, we investigated the roles of p19ARF in prostate cancer. Surprisingly, we found that unlike Trp53, co-targeted inactivation of p19ARF and Pten in the prostate does not accelerate-but rather partially inhibits- the prostate cancer phenotype of Pten-deficient mice. Moreover, striking senescence features and a further reduction in the number of pre-neoplastic glands are observed in p19ARF-Pten compound mutants. Importantly, in both prostate epithelium and MEFs, induction of Trp53 protein abundance upon Pten loss is not affected by p19ARF deficiency. Surprisingly, p19ARF-deficiency significantly suppresses prostate cancer progression of Pten-Trp53 conditional double-mutant mice. In agreement with these findings, we find that in human prostate cancers, loss of PTEN was not associated with loss of p14ARF (human analog of mouse p19ARF). Collectively, our results reveal novel p53-uncoupled consequences for p19ARF loss leading to antitumor functions in prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3200.