gebhart/patrepeval huggingface dataset:
Lipid-independent Secretion of a Drosophila Wnt Protein (2008)

Wnt proteins comprise a large class of secreted signaling molecules with key roles during embryonic development and throughout adult life. Recently, much effort has been focused on understanding the factors that regulate Wnt signal production. For example, Porcupine and Wntless/Evi/Sprinter have been identified as being required in Wnt-producing cells for the processing and secretion of many Wnt proteins. Interestingly, in this study we find that WntD, a recently characterized Drosophila Wnt family member, does not require Porcupine or Wntless/Evi/Sprinter for its secretion or signaling activity. Because Porcupine is involved in post-translational lipid modification of Wnt proteins, we used a novel labeling method and mass spectrometry to ask whether WntD undergoes lipid modification and found that it does not. Although lipid modification is also hypothesized to be required for Wnt secretion, we find that WntD is secreted very efficiently. WntD secretion does, however, maintain a requirement for the secretory pathway component Rab1. Our results show that not all Wnt family members require lipid modification, Porcupine, or Wntless/Evi/Sprinter for secretion and suggest that different modes of secretion may exist for different Wnt proteins.
Analysis of the onset phase of olfactory bulb unit responses to odour pulses in the salamander (1977)

1. A method for delivering odour pulses of controlled onset, steady plateau and abrupt termination, has been developed and applied to a single unit study of mitral cell responses in the olfactory bulb of the salamander. The pulses have been monitored during the experiments near the site of stimulation on the olfactory mucosa.2. Responses have been categorized as excitatory or suppressive based on the initial response to the odour pulse.3. Initially excitatory responses had sustained discharges near threshold. With increasing concentration, the discharge changed to a brief burst followed by suppression. The briefest latency of a unit response was 120 msec, using stimulation of medium concentration, after the start of the pulse; the majority of units appeared to be excited within 200-300 msec. Ramp stimuli gave increasing periods of excitation as the rise time of the odour front became less abrupt.4. Initially suppressive responses showed suppression at all levels of concentration. The majority of units appeared to have an onset of suppression about 300-400 msec after the start of the pulse.5. These basic responses, involving suppression or excitatory-suppressive sequences, can be correlated with some basic properties of the synaptic circuits in the olfactory bulb. The time courses of the initial responses appear to be within the time periods of the inhalation cycle of the salamander, and therefore may reflect mechanisms of processing of natural olfactory stimuli.
The Effect of Nicotine on Spinocerebellar Ataxia (1955)

Each synapse is an apparatus for co-ordination." SHERRINGTON
The Biginelli dihydropyrimidone synthesis using polyphosphate ester as a mild and efficient cyclocondensation/dehydration reagent (2001)

4-Aryldihydropyrimidine-2-(1H)-ones 4a-z were synthesized by one-pot, polyphosphate estermediated Biginelli three-component condensation. The yields of dihydropyrimidones obtained via this novel protocol are significantly higher than those utilizing the conventional ethanol/HCl method. The mechanism of the polyphosphate ester based method and the formation of sideproducts are also described.
Characterization of the rat alpha(1,3)galactosyltransferase: evidence for two independent genes encoding glycosyltransferases that synthesize Galalpha(1,3)Gal by two separate glycosylation pathways (2002)

The important xenoepitope Galalpha(1,3)Gal was thought to be exclusively synthesized by a single alpha(1,3)galactosyltransferase. However, the cloning of the distant family member rat iGb3 synthase, which is also capable of synthesizing Galalpha(1,3)Gal as the glycolipid structure iGb3, challenges the notion that alpha(1,3)galactosyltransferase is the sole Galalpha(1,3)Gal-synthesizing enzyme. We describe the cloning of the rat homolog of alpha(1,3)galactosyltransferase, showing that indeed the rat expresses two distinct alpha(1,3)galactosyltransferases, alpha(1,3)GT and iGb3 synthase. Rat alpha(1,3)galactosyltransferase shows a high amino acid sequence identity with the alpha(1,3)galactosyltransferase of mouse (90%), pig (76%), and ox (75%), in contrast to the low amino acid sequence identity (42%) with iGb3 synthase. The rat alpha(1,3)galactosyltransferase is expressed in heart, brain, spleen, kidney, and liver and has a similar intron/exon structure to the mouse alpha(1,3)galactosyltransferase. Transfection studies show that in contrast to the iGb3 synthase, rat alpha(1,3)galactosyltransferase can synthesize Galalpha(1,3)Gal on glycoproteins but cannot synthesize the glycolipid iGb3, defining two separate glycosylation pathways for the synthesis of Galalpha(1,3)Gal. Furthermore iGb3 synthase was found to be distinct from alpha(1,3)GT with its ability to synthesize poly-alpha-Gal glycolipid structures.
Biofilm formation by Pseudomonas aeruginosa wild type, flagella and type IV pili mutants (2003)

Biofilm formation by Gfp-tagged Pseudomonas aeruginosa PAO1 wild type, flagella and type IV pili mutants in flow chambers irrigated with citrate minimal medium was characterized by the use of confocal laser scanning microscopy and comstat image analysis. Flagella and type IV pili were not necessary for P. aeruginosa initial attachment or biofilm formation, but the cell appendages had roles in biofilm development, as wild type, flagella and type IV pili mutants formed biofilms with different structures. Dynamics and selection during biofilm formation were investigated by tagging the wild type and flagella/type IV mutants with Yfp and Cfp and performing time-lapse confocal laser scanning microscopy in mixed colour biofilms. The initial microcolony formation occurred by clonal growth, after which wild-type P. aeruginosa bacteria spread over the substratum by means of twitching motility. The wild-type biofilms were dynamic compositions with extensive motility, competition and selection occurring during development. Bacterial migration prevented the formation of larger microcolonial structures in the wild-type biofilms. The results are discussed in relation to the current model for P. aeruginosa biofilm development.
A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy (2012)

These results confirm that the CTGF/VEGF ratio is a strong predictor of vitreoretinal fibrosis in PDR, and show that intravitreal anti-VEGF treatment causes increased fibrosis in PDR patients. These findings provide strong support for the model that the balance of CTGF and VEGF determines the angiofibrotic switch, and identify CTGF as a possible therapeutic target in the clinical management of PDR.
Changes in uncoupling protein and GLUT4 glucose transporter expressions in interscapular brown adipose tissue of diabetic rats: relative roles of hyperglycaemia and hypoinsulinaemia (1993)

We have studied the time course and relative effects of hypoinsulinaemia and hyperglycaemia on concentrations of uncoupling protein (UCP) and glucose transporter (GLUT4) and their mRNAs in brown adipose tissue (BAT) during the early phase of diabetes induced by streptozotocin. Two days after intravenous injection of streptozotocin, plasma insulin concentration was at its lowest and glycaemia was higher than 22 mmol/l. After 3 days, a 60% decrease in BAT UCP mRNA concentration and a 36% decrease in UCP was observed. Concomitantly, there was an 80% decrease in GLUT4 mRNA and a 44% decrease in GLUT4 levels. When hyperglycaemia was prevented by infusing phlorizin into diabetic rats, BAT UCP mRNA and protein levels were further decreased (respectively 90% and 60% lower than in control rats). In contrast, the marked decreases in GLUT4 mRNA and protein concentrations in BAT were similar in hyperglycaemic and normoglycaemic diabetic rats. Infusion of physiological amounts of insulin restored normoglycaemia in diabetic rats, and BAT UCP and GLUT4 mRNA and protein concentrations were maintained at the level of control rats. When insulin infusion was stopped, a 75% decrease in BAT UCP mRNA level and a 75% decrease in GLUT4 mRNA level were observed after 24 h, but UCP and GLUT4 concentrations did not decrease. This study shows that insulin plays an important role in the regulation of UCP and GLUT4 mRNA and protein concentrations in BAT. Hyperglycaemia partially prevents the rapid decrease in concentration of UCP and its mRNA observed in insulinopenic diabetes whereas it did not affect the decrease in GLUT4 mRNA and protein concentration. It is suggested that UCP is produced by a glucose-dependent gene.
[A comparative trial of levo-praziquantel and praziquantel in the treatment of human Clonorchis sinensis infection]. (1992)

Seventy patients with clonorchis sinensis infection were divided randomly into two groups and treated with levo-praziquantel and praziquantel in the same dosage of 12.5 mg/kg twice a day for two consecutive days (total dosage of 75 mg/kg). Follow-up stool examination three and six months after treatment showed that the egg negative conversion rates with levo-praziquantel group were 92.86% and 92.59%, while those of praziquantel group were 58.62% and 53.57% respectively. The results showed that levo-praziquantel was significantly superior to praziquantel (P < 0.001). The side reactions in both group were mild and transient.
Synthesis of Oligonucleotides Carrying Thiol Groups Using a Simple Reagent Derived from Threoninol (2012)

Oligonucleotides carrying thiol groups are useful intermediates for a remarkable number of applications involving nucleic acids. In this study, DNA oligonucleotides carrying tert-butylsulfanyl protected thiol groups have been prepared. A building block derived from threoninol has been developed to introduce a thiol group at any predetemined position of an oligonucleotide. The resulting thiolated oligonucleotides have been used for the preparation of oligonucleotide conjugates and for the functionalization of gold nanoparticles using the reactivity of the thiol groups.
Insulinotropic actions of nateglinide in type 2 diabetic patients and effects on dipeptidyl peptidase-IV activity and glucose-dependent insulinotropic polypeptide degradation (2009)

Although considerably less potent than specified DPP-IV inhibitors, the possibility that some of the beneficial actions of nateglinide are indirectly mediated through DPP-IV inhibition and increased bioavailability of GIP and other incretins merits consideration.
Timed sequential therapy of acute leukemia with flavopiridol: in vitro model for a phase I clinical trial. (2003)

Flavopiridol induces apoptosis in marrow blasts from patients with refractory acute leukemias. Furthermore, flavopiridol pretreatment increases the proapoptotic and cytotoxic effects of ara-C. The advantage of sequential FP(250)A(1) over either agent alone is seen for both acute myelogenous leukemia and acute lymphoblastic leukemia. These findings support a clinical trial of timed sequential therapy where flavopiridol is given for cytoreduction and subsequent priming of remaining leukemic cells for enhanced cycle-dependent drug cytotoxicity.
The proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma tumor cells to chemotherapeutic agents. (2003)

Increased nuclear factor kappaB (NF-kappaB) activity is associated with increased tumor cell survival in multiple myeloma. The function of NF-kappaB is inhibited through binding to its inhibitor, IkappaB. Release of activated NF-kappaB follows proteasome-mediated degradation of IkappaB resulting from phosphorylation of the inhibitor and, finally, conjugation with ubiquitin. We report that myeloma cells have enhanced IkappaBalpha phosphorylation and increased NF-kappaB activity compared with normal hematopoietic cells. The proteasome inhibitor PS-341 blocked nuclear translocation of NF-kappaB, blocked NF-kappaB DNA binding, and demonstrated consistent antitumor activity against chemoresistant and chemosensitive myeloma cells. The sensitivity of chemoresistant myeloma cells to chemotherapeutic agents was markedly increased (100,000-1,000,000-fold) when combined with a noncytotoxic dose of PS-341 without affecting normal hematopoietic cells. Similar effects were observed using a dominant negative super-repressor for IkappaBalpha. Thus, these results suggest that inhibition of NF-kappaB with PS-341 may overcome chemoresistance and allow doses of chemotherapeutic agents to be markedly reduced with antitumor effects without significant toxicity.
Novel fusion of GLP-1 with a domain antibody to serum albumin prolongs protection against myocardial ischemia/reperfusion injury in the rat (2013)

Cardioprotection provided by GAlbudAb, a long acting GLP-1 mimetic, following myocardial I/R injury was comparable in magnitude, but more sustained in duration than that produced by short-acting exendin-4. Very low plasma concentrations of exendin-4 failed to protect the heart from myocardial I/R injury, suggesting that sustained GLP-1 receptor activation plays an important role in providing cardioprotection in the setting of acute myocardial I/R injury. Long-acting GLP-1 agonists such as GAlbudAb may warrant additional evaluation as novel therapeutic agents to reduce myocardial I/R injury during acute coronary syndrome.
Comparison between different real-time harmonic analysis methods for control of electrical machines (1994)

This paper proposes a critical analysis of different methods to analyse waveforms in power electronic systems. After having presented classical methods, it is shown that a generalised Park transformation is well suited to the case of electrical drives. This method allows the harmonic analysis of signals. The two signals resulting from the transformation have two DC components and ripple. The two DC components contain the amplitude and the phase of the harmonic selected. As a conclusion, it is shown that the interest of this method is that the undesirable ripple has a frequency at least six times higher than the fundamental frequency. Consequently the response time of the low-pass filter is very attractive. This method seems the more suitable for real-time measurements of the electrical machine drive.
Methane control in United States coal mines, 1972. [34 references] (1973)

A brief summary of the explosion trends in United States coal mines for the past 160 years is presented. These trends show that in spite of the overall improvements in mine safety, the number of fatalities from ignitions of methane has actually increased in recent years. While significant advances have been made in reducing the hazards associated with the mining of coal, the ignition and explosion hazards associated with the presence of methane and other combustibles have actually increased. From the data obtained in recent years, it can be expected that additional problems will arise as mining rates and depths are increased. Accordingly, special emphasis must be given to the use of established methane control procedures in all phases of underground mining and to the refinement of these techniques by a larger number of mining companies through application and innovation.
Phase I trial of taxol given as a 24-hour infusion every 21 days: responses observed in metastatic melanoma. (1987)

Taxol, a plant product, has significant activity against certain rodent and human xenograft tumors. It promotes microtubule assembly in vitro, in contrast to vinca alkaloids, which inhibit assembly. In this phase I study, taxol was administered as a 24-hour continuous intravenous (IV) infusion in 65 courses to 26 patients. A premedication regimen of dexamethasone, cimetidine, and diphenhydramine was used to prevent the acute hypersensitivity reactions observed in previous studies of taxol. Only one episode of mild stridor occurred in this study. Peripheral neuropathy was the dose-limiting toxicity and was observed in 40% of patients treated at a dose of 250 mg/m2. Significant neutropenia of brief duration was also common. Pharmacokinetic studies by a high-performance liquid chromatography (HPLC) method demonstrated that drug plasma concentrations increased during the 24-hour infusion and then declined rapidly. Peak plasma concentrations correlated with dose, and less than 5% of taxol was excreted in the urine. Most of the drug was bound to serum components. Partial responses of more than 3 months' duration were observed in four of 12 melanoma patients treated. The recommended phase II dose of taxol on this schedule is 250 mg/m2. Priority should be given to the study of taxol in melanoma.
Proliferative capacity of human peripheral blood lymphocytes sorted on the basis of glutathione content (1990)

Glutathione (GSH) is important in defense against oxygen free radical damage, in detoxification of xenobiotics, and in mitogenesis. The reducing conditions provided by low molecular weight thiols such as 2-mercaptoethanol (ME) have been shown to promote the growth of lymphocytes in culture. We wished to determine the effects of 2-ME on GSH content, and to determine to what extent GSH status affected lymphocyte proliferation. GSH content was quantitated in human peripheral blood lymphocytes (PBL) using a flow cytometric assay with monochlorobimane. This analysis was performed on PBL as well as on the CD4+ T-cell subset, as identified with fluorescent anti-CD4 monoclonal antibodies (mAb). Cells were viably sorted on the basis of their GSH content, and incubated for 3 days with mitogenic concentrations of PHA (for PBL) or anti-CD3 mAb (for CD4+ cells) in the presence of bromodeoxyuridine (BrdU). BrdU/Hoechst cell cycle analysis was then performed on these cells. High GSH sorted cells had a higher percentage of cells capable of entering the cell cycle than low GSH sorted cells. This data indicates that some of the heterogeneity in proliferative capacity within PBL in culture is directly or indirectly related to GSH content. Incubation of cells in 2-ME prevented the loss of GSH that occurs when cells are cultured. 2-ME improved the proliferative capacity of unsorted cells, and of cells sorted for high and low GSH. Acridine orange staining of anti-CD3 mAb stimulated cells sorted for high and low GSH indicated that an early event in cell activation was affected by GSH content.
Hospitalized Community-acquired Pneumonia in the Elderly: Age- and Sex-related Patterns of Care and Outcome in the United States (2002)

Community-acquired pneumonia (CAP) is a frequent cause of hospital admission and death among elderly patients, but there is little information on age- and sex-specific incidence, patterns of care (intensive care unit admission and mechanical ventilation), resource use (length of stay and hospital costs), and outcome (mortality). We conducted an observational cohort study of all Medicare recipients, aged 65 years or older, hospitalized in nonfederal U.S. hospitals in 1997, who met ICD-9-CM-based criteria for CAP. We identified 623,718 hospital admissions for CAP (18.3 per 1,000 population > or = 65 years), of which 26,476 (4.3%) were from nursing homes and of which 66,045 (10.6%) died. The incidence rose five-fold and mortality doubled as age increased from 65-69 to older than 90 years. Men had a higher mortality, both unadjusted (odds ratio [OR]: 1.21 [95% CI: 1.19-1.23]) and adjusted for age, location before admission, underlying comorbidity, and microbiologic etiology (OR: 1.15 [95% CI: 1.13-1.17]). Mean hospital length of stay and costs per hospital admission were 7.6 days and $6,949. For those admitted to the intensive care unit (22.4%) and for those receiving mechanical ventilation (7.2%), mean length of stay and costs were 11.3 days and $14,294, and 15.7 days and $23,961, respectively. Overall hospital costs were $4.4 billion (6.3% of the expenditure in the elderly for acute hospital care), of which $2.1 billion was incurred by cases managed in intensive care units. We conclude that in the hospitalized elderly, CAP is a common and frequently fatal disease that often requires intensive care unit admission and mechanical ventilation and consumes considerable health care resources. The sex differences are of concern and require further investigation.
Synthesis and Structural Characterization of Helix-Forming β-Peptides:  trans-2-Aminocyclopentanecarboxylic Acid Oligomers (1999)

Synthetic protocols and circular dichroism (CD) spectra are reported for a series of oligomers of (R,R)-trans-2-aminocyclopentanecarboxylic acid (trans-ACPC). The two longest oligomers, a hexamer and an octamer, have also been examined crystallographically. Both crystal structures show that the β-peptide backbone adopts a regular helix that is defined by a series of interwoven 12-membered ring hydrogen bonds ("12-helix"). Each hydrogen bond links a carbonyl oxygen to an amide proton three residues toward the C-terminus. CD data suggest that the conformational preference of trans-ACPC oligomers in methanol is strongly length-dependent, which implies that 12-helix formation is a cooperative process, as seen for the α-helix formed by conventional peptides. Previous work has established that oligomers and polymers of β-amino acids can adopt helical conformations, but the 12-helix is an unprecedented β-peptide secondary structure.
Inhibition of mTOR attenuates store-operated Ca2+ entry in cells from endarterectomized tissues of patients with chronic thromboembolic pulmonary hypertension (2009)

Pulmonary vascular remodeling occurs in patients with chronic thromboembolic pulmonary hypertension (CTEPH). One factor contributing to this vascular wall thickening is the proliferation of pulmonary artery smooth muscle cells (PASMC). Store-operated Ca(2+) entry (SOCE) and cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)) in PASMC are known to be important in cell proliferation and vascular remodeling in pulmonary hypertension. Rapamycin is widely known for its antiproliferative effects in injured coronary arteries. Although several reports have suggested favorable effects of rapamycin in animal models of pulmonary hypertension, no reports have been published to date in human tissues. Here we report that rapamycin has an inhibitory effect on SOCE and an antiproliferative effect on PASMC derived from endarterectomized tissues of CTEPH patients. Cells were isolated from endarterectomized tissues obtained from patients undergoing pulmonary thromboendarterectomy (PTE). Immunohistochemical analysis indicated high deposition of platelet-derived growth factor (PDGF) in tissue sections from PTE tissues and increased PDGF receptor expression. PDGF transiently phosphorylated Akt, mammalian target of rapamycin (mTOR), and p70S6 kinase in CTEPH cells from CTEPH patients. Acute treatment (30 min) with rapamycin (10 nM) slightly increased cyclopiazonic acid (10 microM)-induced Ca(2+) mobilization and significantly reduced SOCE. Chronic treatment (24 h) with rapamycin reduced Ca(2+) mobilization and markedly inhibited SOCE. The inhibitory effects of rapamycin on SOCE were less prominent in control cells. Rapamycin also significantly reduced PDGF-stimulated cell proliferation. In conclusion, the data from this study indicate the importance of the mTOR pathway in the development of pulmonary vascular remodeling in CTEPH and suggest a potential therapeutic benefit of rapamycin (or inhibition of mTOR) in these patients.
Intrastromal Correction of Presbyopia Using a Femtosecond Laser System (2009)

The INTRACOR intrastromal procedure using the TECHNOLAS femtosecond laser is a promising procedure for presbyopia correction. It preserves the corneal epithelium and anterior stromal fibers.