gebhart/patrepeval huggingface dataset:
The Yeast Glycerol 3-Phosphatases Gpp1p and Gpp2p Are Required for Glycerol Biosynthesis and Differentially Involved in the Cellular Responses to Osmotic, Anaerobic, and Oxidative Stress (2001)

We have characterized the strongly homologous GPP1/RHR2 and GPP2/HOR2 genes, encoding isoforms of glycerol 3-phosphatase. Mutants lacking both GPP1 and GPP2 are devoid of glycerol 3-phosphatase activity and produce only a small amount of glycerol, confirming the essential role for this enzyme in glycerol biosynthesis. Overproduction of Gpp1p and Gpp2p did not significantly enhance glycerol production, indicating that glycerol phosphatase is not rate-limiting for glycerol production. Previous studies have shown that expression of both GPP1 and GPP2 is induced under hyperosmotic stress and that induction partially depends on the HOG (high osmolarity glycerol) pathway. We here show that expression of GPP1 is strongly decreased in strains having low protein kinase A activity, although it is still responsive to osmotic stress. The gpp1Delta/gpp2Delta double mutant is hypersensitive to high osmolarity, whereas the single mutants remain unaffected, indicating GPP1 and GPP2 substitute well for each other. Transfer to anaerobic conditions does not affect expression of GPP2, whereas GPP1 is transiently induced, and mutants lacking GPP1 show poor anaerobic growth. All gpp mutants show increased levels of glycerol 3-phosphate, which is especially pronounced when gpp1Delta and gpp1Delta/gpp2Delta mutants are transferred to anaerobic conditions. The addition of acetaldehyde, a strong oxidizer of NADH, leads to decreased glycerol 3-phosphate levels and restored anaerobic growth of the gpp1Delta/gpp2Delta mutant, indicating that the anaerobic accumulation of NADH causes glycerol 3-phosphate to reach growth-inhibiting levels. We also found the gpp1Delta/gpp2Delta mutant is hypersensitive to the superoxide anion generator, paraquat. Consistent with a role for glycerol 3-phosphatase in protection against oxidative stress, expression of GPP2 is induced in the presence of paraquat. This induction was only marginally affected by the general stress-response transcriptional factors Msn2p/4p or protein kinase A activity. We conclude that glycerol metabolism plays multiple roles in yeast adaptation to altered growth conditions, explaining the complex regulation of glycerol biosynthesis genes.
Wettabilities of Self-Assembled Monolayers on Gold Generated from Progressively Fluorinated Alkanethiols (2003)

The conformational order and wettability of self-assembled monolayers (SAMs) on gold generated from a series of partially fluorinated alkanethiols (F(CF2)n(CH2)11SH, n = 1−10; FnH11SH, H11 series), possessing methylene spacers of equivalent length, and the corresponding n-alkanethiol (F0H11SH) were characterized by polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) and contact angle goniometry. The PM-IRRAS analyses revealed that the conformational order of the underlying methylene spacers remains constant with increasing n. Probing the wettabilities of the SAMs by contact angle goniometry using hydrocarbon and fluorocarbon contacting liquids revealed that the dispersive surface energies of the monolayers decreased as n increased from 0 to 6 and then remained constant for n = 6−10. Using cis-perfluorodecalin as the contacting liquid revealed that the decrease in the dispersive surface energies is due to a decrease in the surface density of the CF3 groups that occurs as the length of the perfluorocarbon segment increases with increasing n. The contact angles of the hydrocarbon liquids revealed that the presence of underlying CF2 groups can further reduce the strength of the dispersive interactions at the surface. The contact angles of polar contacting liquids on the SAMs were consistent with an increase in the distance of the oriented fluorocarbon−hydrocarbon (FC−HC) dipoles from the monolayer surface with increasing n. Calculation of the works of adhesion supported this model. Comparison of the data measured for SAMs derived from the H11 series to those measured for SAMs derived from a series of partially fluorinated alkanethiols whose total chain lengths were held constant (FnHmSH; n = 1−10, m = 15−6, respectively; n + m = 16; C16 series) and the corresponding n-alkanethiol (F0H15SH) revealed that differences in underlying monolayer structure fail to significantly influence the interfacial wettabilities of all of the contacting liquids. Calculation of the dispersive surface energies of the SAMs using the methods of both Zisman and Good, Girifalco, and Fowkes (GGF) revealed that both methods underestimate the energies of fluorocarbon surfaces when hydrocarbon contacting liquids are used, with Zisman's method providing lower estimates, compared to the energies estimated using a fluorocarbon contacting liquid in the GGF method. Overall, the results demonstrate that substituting fluorocarbon segments (n ≥ 6) for the terminal hydrocarbon segments in alkanethiol SAMs produces lower energy surfaces having wettabilities that are less sensitive to the underlying film structure.
Engagement of Collagen-Binding Integrins Promotes Matrix Metalloproteinase-9–Dependent E-Cadherin Ectodomain Shedding in Ovarian Carcinoma Cells (2007)

Reversible modulation of cell-cell adhesion, cell-matrix adhesion, and proteolytic activity plays a critical role in remodeling of the neoplastic ovarian epithelium during metastasis, implicating cadherins, integrins, and proteinases in i.p. metastatic dissemination of epithelial ovarian carcinoma (EOC). Aberrant epithelial differentiation is an early event in ovarian carcinogenesis; thus, in contrast to most carcinomas that lose E-cadherin expression with progression, E-cadherin is abundant in primary EOC. Metastasizing EOCs engage in integrin-mediated adhesion to submesothelial interstitial collagens and express matrix metalloproteinases (MMP) that facilitate collagen invasion, thereby anchoring secondary lesions in the submesothelial matrix. As metalloproteinases have also been implicated in E-cadherin ectodomain shedding, the current study was undertaken to model the effects of matrix-induced integrin clustering on proteinase-catalyzed E-cadherin ectodomain shedding. Aggregation of collagen-binding integrins induced shedding of an 80-kDa E-cadherin ectodomain [soluble E-cadherin (sE-cad)] in a MMP- and Src kinase-dependent manner, and sE-cad was prevalent in ascites from ovarian cancer patients. Expression of MMP-9 was elevated by integrin aggregation, integrin-mediated ectodomain shedding was inhibited by a MMP-9 function blocking antibody, and incubation of cells with exogenous MMP-9 catalyzed E-cadherin ectodomain shedding. In contrast to other tumors wherein sE-cad is released into the circulation, EOC tumors maintain direct contact with sE-cad-rich ascites at high concentration, and incubation of EOC cells with physiologically relevant concentrations of recombinant sE-cad disrupted adherens junctions. These data support a novel mechanism for posttranslational modification of E-cadherin function via MMP-9 induction initiated by cell-matrix contact and suggest a mechanism for promotion of EOC metastatic dissemination.
Cystic Fibrosis Is Treatment with Ursodeoxycholic Acid of Value? (1994)

Liver and biliary diseases are common complications in cystic fibrosis (CF) and may even be so severe that liver transplantation is indicated in cases with mild pulmonary disease. The most common complications are steatosis, fibrosis/cirrhosis, micro gallbladder, cholelithiasis, and sclerosing cholangitis. Ursodeoxycholic acid (UDCA) has been used in the treatment of gallstones and pathological liver function in CF. The effect on gallstones has been contradictory, and the effect on liver function tests has been shown to be dose-dependent. A significantly better effect has been shown on liver function tests during treatment over 1 year with doses of 15-20 mg/kg/day. Although supplementation with taurine did not further improve this effect, it has been used in many studies. The biliary bile acid pool was enriched by UDCA from about 10% to 35-40%, but a similar increase was not seen in serum. We have studied the long-term effect of UDCA in 10 patients with liver fibrosis or cirrhosis and/or sclerosing cholangitis. Liver function and liver morphology examined on liver biopsies by both light and transmission electron microscopy (TEM) were followed for 2 years. Preliminary results of this study are encouraging. UDCA is an interesting drug which binds to the hepatocyte membranes, stabilizing membrane structure in in vitro experiments and increasing the bicarbonate excretion in bile in pigs. The mechanism of the effect of UDCA in CF might not only be an increased choleresis; further studies will focus on these aspects.
Ultraviolet-laser desorption/ionization mass spectrometry of femtomolar amounts of large proteins (1989)

Proteins with molecular weights between 14 000 and 175 000 daltons were investigated by matrix-assisted laser desorption/ionization mass spectrometry. High abundance molecular ions were obtained with absolute sample amounts ranging from 5 pmol down to 50 fmol, allowing molecular weight determination with an accuracy between 0.1 and 0.2%. The amount of sample needed for an analysis is determined by the preparation rather than by the mass analysis step; the majority of the sample can be regained after analysis.
Dual Signaling Functions of the Hybrid Sensor Kinase RpfC of Xanthomonas campestris Involve Either Phosphorelay or Receiver Domain-Protein Interaction (2006)

The hybrid sensor kinase RpfC positively regulates the expression of a range of virulent genes and negatively modulates the synthesis of the quorum sensing signal diffusible signal factor (DSF) in Xanthomonas campestris. Three conserved amino acid residues of RpfC implicated in phosphorelay (His(198) in the histidine kinase domain, Asp(512) in the receiver domain, and His(657) in the histidine phosphotransfer domain) were essential for activation of the production of extracellular enzymes and extracellular polysaccharide (EPS) virulence factors but were not essential for repression of DSF biosynthesis. Domain deletion and subsequent in trans expression analysis revealed that the receiver domain of RpfC alone was sufficient to repress DSF overproduction in an rpfC deletion mutant. Further deletion and alanine scanning mutagenesis analyses identified a peptide of 107 amino acids and three amino acid residues (Gln(496), Glu(504), and Ile(552)) involved in modulating DSF production. Co-immunoprecipitation and far Western blot analyses suggested an interaction between the receiver domain and RpfF, the enzyme involved in DSF biosynthesis. These data support a model in which RpfC modulates two different functions (virulence factor synthesis and DSF synthesis) by utilization of a conserved phosphorelay system and a novel domain-specific protein-protein interaction mechanism, respectively. This latter mechanism represents an added dimension to conventional two-component signaling paradigms.
In-Center Hemodialysis Six Times per Week versus Three Times per Week (2010)

Frequent hemodialysis, as compared with conventional hemodialysis, was associated with favorable results with respect to the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT00264758.).
Extracellular Cyclophilins Contribute to the Regulation of Inflammatory Responses (2005)

The main regulators of leukocyte trafficking during inflammatory responses are chemokines. However, another class of recently identified chemotactic agents is extracellular cyclophilins, the proteins mostly known as receptors for the immunosuppressive drug, cyclosporine A. Cyclophilins can induce leukocyte chemotaxis in vitro and have been detected at elevated levels in inflamed tissues, suggesting that they might contribute to inflammatory responses. We recently identified CD147 as the main signaling receptor for cyclophilin A. In the current study we examined the contribution of cyclophilin-CD147 interactions to inflammatory responses in vivo using a mouse model of acute lung injury. Blocking cyclophilin-CD147 interactions by targeting CD147 (using anti-CD147 Ab) or cyclophilin (using nonimmunosuppressive cyclosporine A analog) reduced tissue neutrophilia by up to 50%, with a concurrent decrease in tissue pathology. These findings are the first to demonstrate the significant contribution of cyclophilins to inflammatory responses and provide a potentially novel approach for reducing inflammation-mediated diseases.
FLT3-Ligand Administration Inhibits Liver Metastases: Role of NK Cells (1998)

FLT3-ligand (FL) is a recently described cytokine that stimulates the proliferation and differentiation of hematopoietic progenitors both in vivo and in vitro and, when administered to mice, induces an accumulation of dendritic cells (DC) in different lymphoid and nonlymphoid organs and tissues, including the liver. We have studied the antitumor effect of FL administered alone or in combination with IL-12 in a day 3 murine liver metastasis model. FL significantly reduced the number of hepatic metastases (36.00 +/- 11.00 vs 92.00 +/- 10.19 in control group, p < 0.05). Histologic evaluation of the livers revealed that FL induced a significant infiltration of the tumor border by lymphocytes and DC associated with increased number of apoptotic figures. Immunohistochemical analysis demonstrated that FL significantly enhanced the number of DC in the liver parenchyma and within the liver metastases, as well as the number of CD4+ and CD8+ T lymphocytes. These data support the suggestion that DC may be directly involved in the antitumor effect of FL. Interestingly, the antitumor effect of FL was greatly reduced by the NK depletion. Combination of FL and IL-12 resulted in greater antitumor efficacy than these cytokines alone. In summary, we have shown that FL has significant antitumor effect on preexisting murine C3 liver tumors that is mediated by NK cells. We have also demonstrated that the FL/IL-12 combination has an enhanced antitumor activity in the same murine tumor model.
The Promise of Computerized Feedback Systems for Diabetes Care (1996)

Feedback control is an important mechanism for reaching a targeted goal. Biologic examples range from achieving the appropriate blood pressure level to glycemia control. Computer-based feedback control systems have many potential applications in medicine. Closed-loop systems directly sense the state of the patient and then deliver an intervention without human action. Closed-loop systems have been used to control postoperative fluid infusion, reduce malignant hypertension to a reasonable range through nitroprusside infusions, and control continuous insulin infusions-in effect, an artificial pancreas. Sensory problems have limited the direct application of closed-loop systems to date; most current medical uses of computer-based feedback control are open loop, where a human is interposed between the suggested intervention and the delivered treatment. Because many variables important to the management of diabetes are objective, many opportunities exist for open-loop control in diabetes management. Open-loop systems have already been used to suggest insulin dosage adjustments and treatment for hypercholesterolemia and to remind physicians of various mellitus. However, existing applications have only scratched the surface. Many more facets of diabetes management could be standardized and assisted by open-loop control systems if the management rules could be more exactly specified, a task requiring substantial time commitments by diabetologists. Efforts to translate existing knowledge bases into precise guidelines will be helpful, but new primary studies and decision analyses are needed to define the optimal use of some interventions.
Ion creation, ion focusing, ion/molecule reactions, ion separation, and ion detection in the open air in a small plastic device (2014)

A method is presented in which ions are generated and manipulated in the ambient environment using polymeric electrodes produced with a consumer-grade 3D printer. The ability to focus, separate, react, and detect ions in the ambient environment is demonstrated and the data agree well with simulated ion behaviour.
Spatiotemporal analysis of experimental differences in event‐related potential data with partial least squares (2001)

One challenge in the analysis of event-related potentials (ERPs) is to identify task-related differences in scalp topography. The multivariate Partial Least Squares (PLS) analysis was used to identify the spatiotemporal distribution of ERP differences related to experimental manipulations. Two simulations included latency shifts and amplitude changes at peaks with temporal overlap. PLS identified effects only at modeled timepoints and electrodes. In contrast, principal components analysis identified differences at most timepoints. We also demonstrated that PLS identified combinations of waveform differences, not isolated sources. ERP components in an auditory oddball task were also assessed with PLS. The primary distinction was between ERPs on hit and correct rejection trials, expressed at multiple timepoints and electrodes. PLS provides a mechanism to describe experimental differences in ERP waveforms, simultaneously across the head.
Growth Hormone and Its Receptors in the Central Nervous System &ndash; Location and Functional Significance (1996)

During the past few years, there has been increasing interest in functions that growth hormone (GH) may play in the central nervous system. Accumulating evidence that the hormone may pass the blood-brain barrier and the psychological improvements seen in adults following GH therapy have received particular attention. This paper will review our recent studies on GH receptors in the human and rat brain. A recent study on the effects of GH treatment in adult growth hormone-deficient patients on quality of life and cerebrospinal fluid levels of various hormones and neurotransmitters is also included.
Stable transduction of quiescent CD34+CD38−human hematopoietic cells by HIV-1-based lentiviral vectors (1999)

We compared the efficiency of transduction by an HIV-1-based lentiviral vector to that by a Moloney murine leukemia virus (MLV) retroviral vector, using stringent in vitro assays of primitive, quiescent human hematopoietic progenitor cells. Each construct contained the enhanced green fluorescent protein (GFP) as a reporter gene. The lentiviral vector, but not the MLV vector, expressed GFP in nondivided CD34(+) cells (45.5% GFP+) and in CD34(+)CD38(-) cells in G0 (12.4% GFP+), 48 hr after transduction. However, GFP could also be detected short-term in CD34(+) cells transduced with a lentiviral vector that contained a mutated integrase gene. The level of stable transduction from integrated vector was determined after extended long-term bone marrow culture. Both MLV vectors and lentiviral vectors efficiently transduced cytokine-stimulated CD34(+) cells. The MLV vector did not transduce more primitive, quiescent CD34(+)CD38(-) cells (n = 8). In contrast, stable transduction of CD34(+)CD38(-) cells by the lentiviral vector was seen for over 15 weeks of extended long-term culture (9.2 +/- 5.2%, n = 7). GFP expression in clones from single CD34(+)CD38(-) cells confirmed efficient, stable lentiviral transduction in 29% of early and late-proliferating cells. In the absence of growth factors during transduction, only the lentiviral vector was able to transduce CD34(+) and CD34(+)CD38(-) cells (13.5 +/- 2.5%, n = 11 and 12.2 +/- 9.7%, n = 4, respectively). The lentiviral vector is clearly superior to the MLV vector for transduction of quiescent, primitive human hematopoietic progenitor cells and may provide therapeutically useful levels of gene transfer into human hematopoietic stem cells.
Oral contraceptives in women with systemic lupus erythematosus. (1996)

Oral contraceptives (OCs) are generally not prescribed for women with SLE due to the widely-held view that they may activate disease. This practice is based on the greater incidence of SLE in women than in men, biologic abnormalities od estrogen metabolism, murine models of lupus, several anecdotes of patients having disease flares while receiving exogenous hormones, and a single retrospective study in patients with pre-existing renal disease. In contrast, recent retrospective patient surveys, albeit limited by the absence of formal analyses of disease activity, suggest that the rate of flare is not significantly increased in patients taking OCs. The preexisting data are insufficient to warrant the dismissal of a potentially important birth control option in a disease which predominantly affects women in their reproductive years and whose fertility is not altered by the disease. In counseling patients regarding lupus and pregnancy, there are clinical predictors of pregnancy outcome; patients in remission tend to do well. The same principles may be true regarding advice on the use of OCs; patients with inactive or stable/moderate disease and at low risk for thrombosis may benefit without a change in lupus activity. OCs with the lowest estrogen content should be used and consideration given to progestin only pills in situations where there is some risk of increased clotting. Large prospective double-blind placebo-controlled studies inclusive of all ethnic groups should provide the basis for more definitive recommendations.
Timing of oocyte activation, pronucleus formation and cleavage in humans after intracytoplasmic sperm injection (ICSI) with testicular spermatozoa and after ICSI or in-vitro fertilization on sibling oocytes with ejaculated spermatozoa (1998)

In the first study, we evaluated 101 oocytes [2, 4, 6, 8, 16, 18 and 20 h after intracytoplasmic sperm injection (ICSI)] that had been microinjected with testicular spermatozoa. Of the 70 normally fertilized oocytes (69%) 30 (43%) had two pronuclei by 6 h after ICSI. Fifty-one (73%) by 8 h, 69 (99%) by 16 h and four of them by 20 h cleaved to the 2-cell stage. In the second study, 95 cumulus-corona-oocyte complexes (CCOC) were divided into two groups. Forty-seven CCOC were inseminated by conventional in-vitro fertilization (IVF) and 40 metaphase-II oocytes by ICSI. Oocytes were evaluated at 2, 4, 6 (only after ICSI), 8, 10, 12, 18, 20, 22, 24, 26, 28 and 30 h after both ICSI and IVF. After IVF, 35 oocytes were fertilized normally (75%), four of which (11%) had two pronuclei by 8 h, 11 (31%) by 10 h, 27 (77%) by 12 h and 35 (100%) by 14 h. The first cleavages had occurred by 24 h after insemination (four oocytes, 11%). After ICSI, 34 oocytes were fertilized normally (79%), 13 of which (38%) had two pronuclei by 6 h, 27 (79%) by 8 h and 32 (94%) by 10 h. Three oocytes cleaved by 20 h after microinjection (9%) and 19 by 24 h (56%). Pronuclei developed asynchronously in six oocytes after ICSI (18%) as opposed to 16 oocytes after IVF (46%). The results of this study suggest that the timing of pronuclear formation is no different when a testicular spermatozoon is microinjected into the oocytes from when an ejaculated spermatozoon is injected. Secondly, pronuclear development and first cleavage generally take place 4 h sooner after ICSI than after IVF. On the other hand, a higher proportion of oocytes develop two pronuclei asynchronously after IVF than after ICSI.