gebhart/patrepeval huggingface dataset:
Novel bis -Tetrahydrofuranylurethane-Containing Nonpeptidic Protease Inhibitor (PI) UIC-94017 (TMC114) with Potent Activity against Multi-PI-Resistant Human Immunodeficiency Virus In Vitro (2003)

We designed, synthesized, and identified UIC-94017 (TMC114), a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing a 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF) and a sulfonamide isostere which is extremely potent against laboratory HIV-1 strains and primary clinical isolates (50% inhibitory concentration [IC(50)], approximately 0.003 micro M; IC(90), approximately 0.009 micro M) with minimal cytotoxicity (50% cytotoxic concentration for CD4(+) MT-2 cells, 74 micro M). UIC-94017 blocked the infectivity and replication of each of HIV-1(NL4-3) variants exposed to and selected for resistance to saquinavir, indinavir, nelfinavir, or ritonavir at concentrations up to 5 micro M (IC(50)s, 0.003 to 0.029 micro M), although it was less active against HIV-1(NL4-3) variants selected for resistance to amprenavir (IC(50), 0.22 micro M). UIC-94017 was also potent against multi-PI-resistant clinical HIV-1 variants isolated from patients who had no response to existing antiviral regimens after having received a variety of antiviral agents. Structural analyses revealed that the close contact of UIC-94017 with the main chains of the protease active-site amino acids (Asp-29 and Asp-30) is important for its potency and wide spectrum of activity against multi-PI-resistant HIV-1 variants. Considering the favorable pharmacokinetics of UIC-94017 when administered with ritonavir, the present data warrant that UIC-94017 be further developed as a potential therapeutic agent for the treatment of primary and multi-PI-resistant HIV-1 infections.
Application of Latent HIV-1 Infected Cellular Models to Therapeutic Intervention (1992)

The 10-year period of clinical latency following infection with the human immunodeficiency virus type-1 remains as a tremendous opportunity for therapeutic intervention. To decipher the viral and cellular mechanisms involved in controlling active and nonproductive viral expression, chronically infected cell lines have been developed which mimic in vivo latency at a cellular level. This review compares these models of chronic infection, emphasizing the advantages and limitations of this approach to the understanding of AIDS progression. In addition, it accentuates the utility of these models of chronic infection in the development and testing of novel drugs aimed at altering the efferent component of the HIV--1 life cycle. It is this component of the viral life cycle that has remained largely unexplored and open to novel therapeutic strategies for the prevention of lethal immunosuppression.
Serum iron, total iron-binding capacity, and percentage saturation in normal subjects (1968)

The serum iron was determined in 60 normal subjects (38 males and 22 females) with a mean age of 32.0 and 36.2 years respectively. The plasma total iron-binding capacity (TIBC) was also determined in 54 of these subjects (32 males and 22 females). Serum iron and TIBC determinations were performed between 8.45 am and 9.15 am. The mean serum iron concentration is 138.3 +/- 4.3 mug/100 ml (SD +/- 32.9 mug/100 ml), and the mean TIBC is 470.1 +/- 6.8 mug/100 ml (SD +/- 50.1 mug/100 ml); the mean plasma siderophilin saturation is 30.0%. The mean values for serum iron, TIBC, and siderophilin saturation are similar in both sexes. They are normally distributed, and there is no significant correlation of serum iron and TIBC with age in either males or females.
Bioactivity of Gentamicin in Purulent Sputum from Patients with Cystic Fibrosis or Bronchiectasis: Comparison with Activity in Serum (1983)

Two mechanisms of potential biologic antagonism of gentamicin in purulent sputum from patients with cystic fibrosis or bronchiectasis were studied: reduction of activity by ions and antibiotic binding. Antagonism by ions was assessed by examination of the activity of gentamicin against Pseudomonas aeruginosa in dialysates of serum or sputum in ion-depleted broth. The ionic content of the dialysates increased and reflected differences in the ion content of serum and sputum. Gentamicin had significantly less activity against P aeruginosa in sputum or serum dialysates than in ion-depleted broth alone. When gentamicin was mixed with serum or sputum before dialysis, the level of antipseudomonas activity of the sputum dialysates was significantly lower than that of the serum dialysate; this finding was correlated with greater binding by sputum. Thus, both binding and antagonism by ions evidently reduce the level of bioactivity of gentamicin in serum and in sputum. Purulent sputum, whether from children with cystic fibrosis or adults which bronchiectasis, is more inhibitory than serum; the greater degree of binding, rather than differences in the composition or quantity of cations, explains this difference.
Abnormalities in protein kinase C signaling and the pathophysiology of bipolar disorder (1999)

Protein kinase C (PKC) is a group of calcium and phospholipid-dependent enzymes, which plays a pivotal role in cell signaling systems. Recently accumulated evidence indicates that alterations in PKC activity play a significant role in the pathophysiology of bipolar disorder. A number of laboratories investigated the effect of mood stabilizers on the regulation of PKC activity in bipolar patients, in animals, and in cultured cells. Following chronic lithium treatment, PKC activation was significantly reduced in rat brains, as measured by the translocation of cytoplasmic PKC to the membrane compartment, or by quantitative binding of the PKC ligand, PDBu. The effect of the therapeutic concentration of lithium in attenuating PKC-dependent intracellular parameters was also demonstrated in cultured cells. More importantly, alterations in platelet PKC was shown in bipolar patients during the manic state of the illness. In comparison to patients with major depressive disorder, schizophrenia, or healthy controls, PKC activity was significantly increased in manic patients, suggesting that changes in PKC may be an illness-specific marker. Interestingly, enhanced PKC activity during mania was suppressed following mood-stabilizer treatment as manic symptoms improved. In parallel to the findings in platelets, postmortem studies demonstrate that membrane-associated PKC and stimulation-induced translocation of cytosolic enzyme to the membrane were also increased in frontal cortex of bipolar patients. Other studies suggest alterations in other signal transduction mechanisms in bipolar disorder. These include alterations in G protein activation, phosphatidylinositol (PI) signaling, cyclic AMP formation, and intracellular calcium homeostasis. The alterations of PKC activity in bipolar disorder may be related to changes in these other intracellular signaling mechanisms. Alternatively, the changes of PKC activity may be the core pathology of the illness. More studies are required to further characterize the association of PKC changes with bipolar disorder, using a proper neuronal model.
A Phase II Trial of Intraperitoneal High-Dose Carboplatin and Etoposide with Granulocyte Macrophage-Colony Stimulating Factor Support in Patients with Ovarian Carcinoma (1995)

Based upon results obtained in a Phase I study, we conducted a Phase II trial of high-dose CBDCA and etoposide administered via the intraperitoneal (IP) route in patients with ovarian cancer. CBDCA at a dose of 600 mg/m2 and etoposide at a dose of 400 mg/m2 were administered rapidly into the peritoneal cavity. The total dose of each agent was calculated and given daily over 3 days in amounts equal to one-third of the total dose. On day 1 of therapy, one-third of the dose was mixed in 2 liters of D5W and administered intraperitoneally as rapidly as possible. On days 2 and 3, one-third of the dose was mixed in 1 liter of D5W and administered similarly. GM-CSF was begun on day 4 as a subcutaneous injection at a dose of 500 micrograms/m2/day. A total 53 courses of treatment was administered to 18 patients; 9 of 13 patients (69%) with evaluable disease demonstrated evidence consistent with a partial response; however, the majority were response determined by a decrease in tumor marker (CA-125). One patient who had pathologic evidence of disease at second look laparotomy, but no measurable disease, was treated and shown at subsequent reexploration to have no further evidence of disease. This patient remains free of disease at 17+ months. The toxicity encountered in this trial was formidable, resulting in the removal of 78% of the patients from the study prior to completing 6 cycles of therapy.
Metal Ionophore Treatment Restores Dendritic Spine Density and Synaptic Protein Levels in a Mouse Model of Alzheimer's Disease (2011)

We have previously demonstrated that brief treatment of APP transgenic mice with metal ionophores (PBT2, Prana Biotechnology) rapidly and markedly improves learning and memory. To understand the potential mechanisms of action underlying this phenomenon we examined hippocampal dendritic spine density, and the levels of key proteins involved in learning and memory, in young (4 months) and old (14 months) female Tg2576 mice following brief (11 days) oral treatment with PBT2 (30 mg/kg/d). Transgenic mice exhibited deficits in spine density compared to littermate controls that were significantly rescued by PBT2 treatment in both the young (+17%, p<0.001) and old (+32%, p<0.001) animals. There was no effect of PBT2 on spine density in the control animals. In the transgenic animals, PBT2 treatment also resulted in significant increases in brain levels of CamKII (+57%, p = 0.005), spinophilin (+37%, p = 0.04), NMDAR1A (+126%, p = 0.02), NMDAR2A (+70%, p = 0.05), pro-BDNF (+19%, p = 0.02) and BDNF (+19%, p = 0.04). While PBT2-treatment did not significantly alter neurite-length in vivo, it did increase neurite outgrowth (+200%, p = 0.006) in cultured cells, and this was abolished by co-incubation with the transition metal chelator, diamsar. These data suggest that PBT2 may affect multiple aspects of snaptic health/efficacy. In Alzheimer's disease therefore, PBT2 may restore the uptake of physiological metal ions trapped within extracellular β-amyloid aggregates that then induce biochemical and anatomical changes to improve cognitive function.
Hormone-responsive expression of an endogenous proviral gene of mouse mammary tumor virus after molecular cloning and gene transfer into cultured cells. (1981)

A recombinant lambda phage containing mouse mammary tumor virus (MMTV) proviral DNA was isolated from a gene library constructed from GR mouse liver DNA. Restriction enzyme analyses reveal that the cloned molecule contains a copy of one of the GR endogenous MMTV proviruses flanked on both sides by 2--3 kb of mouse genomic DNA. In this report we have examined the expression of the cloned MMTV provirus after cotransfection with the herpes thymidine kinase (TK; ATP:thymidine 5'-phosphotransferase,, EC 2.7.1.21) gene and integration into mouse LTK- cells. Nine individual TK+ transformants were selected, and all were found to contain MMTV-transfected DNA. One of the TK+ transformants was chosen for further study. Total poly(A)-containing RNA was isolated from the cells, and liquid hybridization analyses with MMTV cDNA showed that it contained 0.02% MMTV-specific RNA. The sizes of the MMTV-specific species were determined and found to correspond to the 35S and 24S mRNAs synthesized in MMTV-infected cells. Glucocorticoid hormones have been shown to increase the concentration of MMTV RNA in virus-infected cultured cells. Therefore, we tested the effect of dexamethasone on the concentration of MMTV-specific RNA in cells transfected with the MMTV proviral DNA. The amount of MMTV-specific poly(A)-containing RNA found in the cells grown in the presence of hormone was 0.17%. Therefore, dexamethasone causes an 8-fold increase in the amount of MMTV-specific RNA in mouse cells containing several copies of a cloned and transfected MMTV proviral gene.
The effect of neuropeptide Y and peptide YY on electrogenic ion transport in rat intestinal epithelia. (1988)

1. Neuropeptide Y (NPY), peptide YY (PYY) and, to a lesser extent, human pancreatic polypeptide (HPP) reduced short-circuit current (SCC) in a concentration-dependent manner in epithelial preparations of rat jejunum and descending colon. 2. From concentration-response curves in the jejunum EC50 values of 3 nM for PYY and 10 nM for NPY were obtained. HPP was much less potent, the threshold concentration being around 100 nM, and NPY 13-36 was inactive. 3. Repeated exposure of jejunal preparations to either NPY or PYY led to a rapid desensitization. Cross-desensitization to the actions of these two peptides was also observed. Neither tetrodotoxin (TTX) nor phentolamine affected responses to either NPY or PYY on the jejunum. 4. Responses to both peptides were inhibited by the presence of transport inhibitors, particularly diphenylamine-2-carboxylate (DPC, a chloride channel blocker) and piretanide (Na+-K+-2Cl- co-transport inhibitor). These results may indicate that the reduction in SCC caused by the neuropeptides is due to a net increase in chloride movement in the apical to basolateral direction. 5. 36Cl-flux studies identified an inhibition of chloride secretion as the predominant mechanism of action of NPY and PYY, together with a smaller stimulation of chloride absorption. No significant changes in the movement of 22Na were seen in either direction. 6. The cyclo-oxygenase inhibitors piroxicam (5 microM) and indomethacin (5 microM) significantly reduced the responses to both NPY and PYY in rat jejunum. From this and other evidence it was concluded that the peptides depended for their effect on the endogenous formation of eicosanoids, the prevention of which attenuated the SCC reduction due to the peptides.
Problem Based Learning Applied to a New Unit of Study on Programmable Logic Design (2008)

A problem-based-learning (PBL) approach has been used in the development of a new unit of study, ELEC241 Programmable Logic Design, in the Department of Electronic Engineering of Macquarie University. A major component of this unit is a team-based project to design and build a digital controller to control the traffic lights of a complex traffic intersection. The project supports the CDIO (Conceive, Design, Implement, Operate) approach to engineering education that is being advocated by many university teaching-and-learning committees and educational/professional associations world-wide. The conceive, design, implement and operate stages of the project are described. Programmable logic devices (Generic Array Logic or Field-Programmable Gate Arrays) are used for the implementation of the controller. Notes on PBL issues are given.
Classification of ‘activation’ antibodies against integrin β1 chain (1997)

We compared the effects of two anti-beta1 integrin activating antibodies, TS2/16 and AG89, on K562 cell adhesion to fibronectin. Though both antibodies effectively induced cell adhesion, the EC50 for AG89 was more than 200-fold higher than that for TS2/16. Scatchard analysis of the data from [125I]Fab fragment binding to the cells revealed that the TS2/16 epitope is exposed constitutively on all the beta1 integrin molecules, while only 3% of the beta1 integrins on resting K562 cells bear the AG89 epitope. Calculation of the actual number of each antibody bound to the cell during the cell adhesion assay revealed that induction of cell adhesion can be accomplished by binding much fewer AG89 molecules compared to TS2/16. Thus, AG89 and TS2/16 represent distinct classes of anti-integrin activating antibodies that show completely different binding characteristics as well as different activation effects on the integrin molecule upon binding.
Role of gamma/delta T cell receptor-expressing lymphocytes in cutaneous infection caused byStaphylococcus aureus (2003)

The high number of gamma/delta-expressing T cells found in the epithelial lining layer suggests that they form a first line of defence against invading pathogens. To evaluate the role of gamma/delta T cell-receptor (TCR)-expressing cells in cutaneous infection caused by Staphylococcus aureus, mice lacking gamma/delta-expressing T cells (TCRdelta-/-) were inoculated intradermally with S. aureus, and compared with S. aureus-infected congeneic TCRdelta+/- control mice. The number of bacteria recovered from the skin of TCRdelta-/- mice was significantly higher (P = 0.0071) at early time-points after inoculation compared to the number of bacteria isolated from infected TCRdelta+/- congeneic controls. Nevertheless, inflammatory responses measured as serum IL-6 levels, were significantly lower in TCRdelta-/- mice than in the control group. A possible explanation for this discrepancy was the observation of significantly decreased overall numbers of infiltrating cutaneous T lymphocytes, which are important producers of IL-6. These results support the notion that the gamma/delta-expressing T cells that reside at the epithelial lining layer of the skin is of importance for early containment of the bacteria, thereby limiting their replication and spread.
An advanced hybrid peer-to-peer botnet (2007)

A botnet consists of a network of compromised computers controlled by an attacker (botmaster). Recently, botnets have become the root cause of many Internet attacks. To be well prepared for future attacks, it is not enough to study how to detect and defend against the botnets that have appeared in the past. More importantly, we should study advanced botnet designs that could be developed by botmasters in the near future. In this paper, we present the design of an advanced hybrid peer-to-peer botnet. Compared with current botnets, the proposed botnet is harder to be shut down, monitored, and hijacked. It provides robust network connectivity, individualized encryption and control traffic dispersion, limited botnet exposure by each bot, and easy monitoring and recovery by its botmaster. In the end, we suggest and analyze several possible defenses against this advanced botnet. © 2010 IEEE.
o-Nitrosobenzamide. A Possible Intermediate in the von Richter Reaction (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTo-Nitrosobenzamide. A Possible Intermediate in the von Richter ReactionKhairat M. Ibne-Rasa and Edward KoubekCite this: J. Org. Chem. 1963, 28, 11, 3240–3241Publication Date (Print):November 1, 1963Publication History Published online1 May 2002Published inissue 1 November 1963https://pubs.acs.org/doi/10.1021/jo01046a524https://doi.org/10.1021/jo01046a524research-articleACS PublicationsRequest reuse permissionsArticle Views241Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Coupled hydrogeophysical inversion of time-lapse surface GPR data to estimate hydraulic properties of a layered subsurface (2013)

[1] A major challenge in vadose zone hydrology is to obtain accurate information on the temporal changes of the vertical soil water distribution and its feedback with the atmosphere and groundwater. A state of the art coupled hydrogeophysical inversion scheme is applied to evaluate soil hydraulic properties of a synthetic model and a field soil in southern Ontario based on time-lapse monitoring of soil dynamics with surface ground-penetrating radar (GPR). Film flow was included in the hydrological model to account for noncapillary water flow in a sandy medium during dry conditions. The synthetic study illustrated that GPR data contain sufficient information to accurately constrain soil hydraulic parameters within a coupled inversion framework and led to an accurate estimation of the soil hydraulic properties. When film flow was not accounted for within the inversion, an equally good fit could still be achieved. In this case, errors introduced by neglecting film flow were compensated by different hydraulic parameters. For the field data, the coupled inversion reduced the overall misfit compared to an uncalibrated model using hydraulic parameters obtained from laboratory data. Although the data fit improved significantly for water content in the deeper soil layers, accounting for film flow in the uppermost subsurface layer did not lead to a better fit of the GPR data. Further research is needed to describe the processes controlling water content in the dry range, in particular coupled heat and vapor transport. This study illustrates the suitability of surface GPR measurements combined with coupled inversion for near-surface characterization of soil hydraulic parameters.
The Core Symptoms of Schizophrenia (1996)

The diagnosis of schizophrenia is made on the basis of a diverse set of characteristic signs and symptoms. These include disturbances in perception and inference, abnormalities in communication, behaviour and motor activity, and deficits in emotional expressivity, hedonic capacity and drive. No single symptom or set of symptoms is pathognomonic, and the question of which symptoms are indeed at the 'core' of schizophrenia has been an issue of much debate, opinion and study since the disorder was first described a century ago. In this review, the symptoms emphasized in current diagnostic criteria for schizophrenia are described and the relative importance of these symptoms in the evolution of the schizophrenia construct is discussed.
Imiquimod has strain-dependent effects in mice and does not uniquely model human psoriasis (2017)

These findings demonstrate strain-dependent aspects of IMQ dermatitis in mice. We have shown that IMQ does not uniquely model psoriasis but in fact triggers a core set of pathways active in diverse skin diseases. Nonetheless, our findings suggest that B6 mice provide a better background than other strains for modeling psoriasis disease mechanisms.