gebhart/patrepeval huggingface dataset:
A phase II trial of the proteosome inhibitor PS-341 in patients with metastatic colorectal cancer (2004)

3109 Background: The ubiquitinin-proteosome proteolytic pathway regulates the metabolism of critical proteins involved in the cell cycle, apoptosis and metastasis such as p53, p21, p27 and NFκB. PS341(Bortezomib; Velcade) is a specific and selective inhibitor of the 26S proteosome. PS341 results in significant regression in a human colon cancer xenograft model. Methods: This phase II study aimed to assess the activity of PS341 in patients with metastatic colorectal cancer who had received no more than 1 prior line of chemotherapy with irinotecan (or oxaliplatin)/5 fluorouracil for metastatic disease. Primary endpoints were objective response or disease stabilization; with a multinomial stopping rule and secondary endpoints included assessment of molecular changes with therapy, survival and tolerability. PS 341 at a dose of 1.3mg/m2/day was administered as an intravenous bolus days 1,4,8 and 11 of a 21 day cycle. Tumor response was assessed by RECIST criteria every 2 cycles. Tumor biopsies were performed prior to treatment and on day 9 of the first treatment cycle. Results: 19 patients (9M:10F), median age 62 (range 46–81) years received 41 (range 1–4) cycles of treatment. 3 patients had stable disease (SD), 14 had progressive disease (PD) and 2 were non- evaluable . Of the 2 patients with SD at cycle 2, two patients discontinued treatment during cycle 4 due to grade 3 abdominal pain and grade 3 peripheral neuropathy. One patient had SD after 3 cycles but was withdrawn due to a cerebrovascular accident (CVA). The most common adverse events (AEs), any grade, were lymphopenia (80% of cycles), fatigue (77%), anemia (66%), constipation (61%), nausea(51%) and headache (42%). Discontinuation of treatment occurred due to the following AEs: grade 3 peripheral neuropathy (2 patients), CVA and grade 3 abdominal pain, myalgia and rash. Paired tumor biopsies were obtained from 9 patients and examined for transcription factors NFkβ and HIF-1α, p53, p27, and p21 by immunohistochemistry. Data will be presented at the meeting. Conclusions: PS341 has insufficient activity in colorectal cancer and the study has closed to accrual. No significant financial relationships to disclose.
Protein kinase C-β contributes to NADPH oxidase activation in neutrophils (2000)

We have analysed the involvement of the beta isotype of the protein kinase C (PKC) family in the activation of NADPH oxidase in primary neutrophils. Using immunofluorescence and cell fractionation, PKC-beta is shown to be recruited to the plasma membrane upon stimulation with phorbol ester and to the phagosomal membrane upon phagocytosis of IgG-coated particles (Fcgamma-receptor stimulus). The time course of recruitment is similar to that of NADPH oxidase activation by these stimuli. The PKC-beta specific inhibitor 379196 inhibits the response to PMA as well as to IgG-coated bacteria. Partial inhibition occurs between 10 and 100 nM of inhibitor, the concentration at which PKC-beta, but not other PKC isotypes, is targeted. Neutrophils isolated from a mouse that lacks PKC-beta also showed an inhibition of NADPH oxidase activation by PMA and IgG-coated particles. The level of inhibition is comparable to that achieved with 379196 in human neutrophils. Thus the PKC-beta isotype mediates activation of NADPH oxidase by PMA and by stimulation of Fcgamma receptors in neutrophils.
Expression of seven herpes simplex virus type 1 glycoproteins (gB, gC, gD, gE, gG, gH, and gI): comparative protection against lethal challenge in mice (1994)

We have constructed recombinant baculoviruses individually expressing seven of the herpes simplex virus type 1 (HSV-1) glycoproteins (gB, gC, gD, gE, gG, gH, and gI). Vaccination of mice with gB, gC, gD, gE, or gI resulted in production of high neutralizing antibody titers to HSV-1 and protection against intraperitoneal and ocular challenge with lethal doses of HSV-1. This protection was statistically significant and similar to the protection provided by vaccination with live nonvirulent HSV-1 (90 to 100% survival). In contrast, vaccination with gH produced low neutralizing antibody titers and no protection against lethal HSV-1 challenge. Vaccination with gG produced no significant neutralizing antibody titer and no protection against ocular challenge. However, gG did provide modest, but statistically significant, protection against lethal intraperitoneal challenge (75% protection). Compared with the other glycoproteins, gG and gH were also inefficient in preventing the establishment of latency. Delayed-type hypersensitivity responses to HSV-1 at day 3 were highest in gG-, gH-, and gE-vaccinated mice, while on day 6 mice vaccinated with gC, gE, and gI had the highest delayed-type hypersensitivity responses. All seven glycoproteins produced lymphocyte proliferation responses, with the highest response being seen with gG. The same five glycoproteins (gB, gC, gD, gE, and gI) that induced the highest neutralization titers and protection against lethal challenge also induced some killer cell activity. The results reported here therefore suggest that in the mouse protection against lethal HSV-1 challenge and the establishment of latency correlate best with high preexisting neutralizing antibody titers, although there may also be a correlation with killer cell activity.
Social Response to the FDA Authorization of Heated Tobacco Products (HTPs) (2020)

Objectives: The US Food and Drug Administration (FDA) approved sales of heated tobacco products (HTPs) on April 30, 2019. In this paper, I provide a preliminary analysis of social media conversations regarding HTPs and the FDA authorization in the first 60 days. Methods: I examined 574 tweets regarding HTPs to assess tweet characteristics and semantic networks of HTPs. Results: Tweets were more likely to be neutral or anti-HTPs than pro-HTPs regardless of the author type (except for tobacco industry) or genre of the post. There was a small gap (6.4%) between the proportion of pro-HTPs and anti-HTPs among personal tweets. The proportion of pro-HTPs was larger in tweets posted by men (vs women and no sex specified) and from rural areas (vs urban). Nearly one-third of the sample mentioned cigarettes or e-cigarettes, even though the size of posts making claims on inferiority/superiority of HTPs was small. Conclusions: Social media conversations on risks of HTPs as well as surveillance on young consumer target marketing is occurring, and it will be important to assess the impact of tobacco companies' launch of HTP sales in the US to assess public perceptions on HTPs. Continuing surveillance of HTP marketing and risk perceptions will inform tobacco regulations.
Biomechanical Rationale for Using Polyetheretherketone (PEEK) Spacers for Lumbar Interbody Fusion–A Finite Element Study (2006)

Spacers less stiff than the graft will: (1) provide stability similar to titanium cages in the presence of posterior instrumentation, (2) reduce the stresses in endplates adjacent to the spacers, and (3) increase the load transfer through the graft, as evident from the increase in stresses in graft.
Optimal feedforward estimation of frequency-selective fading, radio channels using statistical channel information (2003)

The optimal feedforward channel estimator relying only on known training symbols is systematically derived. Statistical channel information is assumed to be available. The resulting estimator is shown to decompose into the two subtasks of maximum likelihood (ML) acquisition and subsequent Wiener filtering. When using optimal training sequences, the corresponding channel estimator becomes very efficient and flexible. A design example of a near-optimal HF channel estimator is presented and its performance was verified by simulation. Bit error rate simulation results of an entire near-optimal maximum likelihood sequence estimation (MLSE) receiver employing feedforward synchronization demonstrate the superiority and robustness of Wiener channel estimation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
ENCYCLOPEDIA OF CHEMICAL TECHNOLOGY (1978)

v.1. A to Anthrimides.--v.2. Anthrone to carbon-arc.--v.3. Carbon (cont'd) to cinchophen.--v.4. Cineole to dextrose.--v.5. Di- to explosives.-- v.6. Explosives (cont'd) to furfural.--v.7. Furnaces to iolite.--v.8. Ion exchange to metal plating.--v.9. Metal surface treatment to penicillin.--v.10. Pentacene to polymethine dyes.--v.11. Polyols to rutin.--v.12. Sabadine to Stilbestrol.--v.13. Stillbite to thermochemistry.--v.14. Thermodynamics to waterproofing.--v.15. Waxes to zymosterol. Index to vol. 1-15.
Potentiation and inhibition of Ca2+ release‐activated Ca2+ channels by 2‐aminoethyldiphenyl borate (2‐APB) occurs independently of IP3 receptors (2001)

1. The effects of the IP(3)-receptor antagonist 2-aminoethyldiphenyl borate (2-APB) on the Ca(2+) release-activated Ca(2+) current (I(CRAC)) in Jurkat human T cells, DT40 chicken B cells and rat basophilic leukaemia (RBL) cells were examined. 2. 2-APB elicited both stimulatory and inhibitory effects on Ca(2+) influx through CRAC channels. At concentrations of 1-5 microM, 2-APB enhanced Ca(2+) entry in intact cells and increased I(CRAC) amplitude by up to fivefold. At levels > or = 10 microM, 2-APB caused a transient enhancement of I(CRAC) followed by inhibition. 3. 2-APB altered the kinetics of fast Ca(2+)-dependent inactivation of I(CRAC). At concentrations of 1-5 microM, 2-APB increased the rate of fast inactivation. In contrast, 2-APB at higher concentrations (> or = 10 microM) reduced or completely blocked inactivation. 4. 2-APB inhibited Ca(2+) efflux from mitochondria. 5. 2-APB inhibited I(CRAC) more potently when applied extracellularly than intracellularly. Furthermore, increased protonation of 2-APB at low pH did not affect potentiation or inhibition. Thus, 2-APB may have an extracellular site of action. 6. Neither I(CRAC) activation by passive store depletion nor the effects of 2-APB were altered by intracellular dialysis with 500 microg ml(-1) heparin. 7. I(CRAC) is present in wild-type as well as mutant DT40 B cells lacking all three IP(3) receptor isoforms. 2-APB also potentiates and inhibits I(CRAC) in both cell types, indicating that 2-APB exerts its effects independently of IP(3) receptors. 8. Our results show that CRAC channel activation does not require physical interaction with IP(3) receptors as proposed in the conformational coupling model. Potentiation of I(CRAC) by 2-APB may be a useful diagnostic feature for positive identification of putative CRAC channel genes, and provides a novel tool for exploring the physiological functions of store-operated channels.
Synthesis and evaluation of novel fluorogenic substrates for the detection of bacterial beta-galactosidase (2001)

The present study suggests that EHC-GAL should be evaluated as a substrate for the detection of coliforms in water analysis, due to a combination of the following favourable features: (i) reduced toxicity; (ii) increased fluorescence; (iii) pH stability of fluorescence; and (iv) rapid detection.
Aggrecan degradation in chondrocytes is mediated by reactive oxygen species and protected by antioxidants (1999)

Reactive oxygen species (ROS) are implicated in aging of cartilage and in the pathogenesis of osteoarthritis. However, the biological role of chondrocytes-derived ROS has not been elucidated. An in-vitro model was developed to study the role of chondrocyte-derived ROS in cartilage matrix degradation. The primary articular chondrocytes were cultured and the aggrecan matrix was radiolabeled with 35-sulfate. The labeled aggrecan matrix was washed to remove unincorporated label and chondrocytes were returned to serum free balanced salt solution. The cell-monolayer-matrix sensitivity to oxidative damage due to either hydrogen peroxide or glucose oxidase was established by monitoring the release of labeled aggrecan into the medium. Lipopolysaccharide (LPS) treatment of chondrocyte-monolayer enhanced the release of labeled aggrecan. Catalase significantly prevented the release of labeled aggrecan in LPS-chondrocyte cultures, suggesting a role for chondrocyte-derived hydrogen peroxide in aggrecan degradation. Superoxide dismutase or boiled catalase had no such inhibitory effect. The effect of several antioxidants on LPS-chondrocyte-dependent aggrecan degradation was examined. Hydroxyl radical scavengers (mannitol and thiourea) significantly decreased aggrecan degradation. A spin trapping agent N-tert-butyl-phenylnitrone (but not its inactive analog tert-butyl-phenylcarbonate) significantly decreased aggrecan degradation. Butylated hydroxytoluene also inhibited aggrecan degradation, whereas the other lipophilic antioxidant tested, propyl gallate, had a marked dose-dependent inhibitory effect. These data indicate that general antioxidants, hydroxyl radical scavengers, antioxidant vitamins, iron chelating agents, lipophilic antioxidants, and spin trapping agents can influence chondrocyte-dependent aggrecan degradation. These studies support the role of a chondrocyte-dependent oxidative mechanism in aggrecan degradation and indicate that antioxidants can prevent matrix degradation and therefore may have a preventive or therapeutic value in arthritis. The enhancement of oxidative activity in chondrocytes and its damaging effect on matrix may be an important mechanism of matrix degradation in osteoarthritis.
Integrin α5β1 Mediates Attachment, Migration, and Proliferation in Human Retinal Pigment Epithelium: Relevance for Proliferative Retinal Disease (2009)

The apical localization of alpha5beta1 and the secretion of fibronectin to the apical bath suggest the presence of an autocrine loop that can guide the migration of RPE. The strong inhibitory effects of JSM6427 on human RPE cell attachment, proliferation, and migration is probably mediated by F-actin cytoskeletal disruption in proliferating cells and suggests a potential clinical use of this compound in proliferative retinopathies.
Transient Receptor Potential Vanilloid 1 Antagonist, Capsazepine, Improves Survival in a Rat Hemorrhagic Shock Model (2007)

TRPV1 may be involved in the regulation of the cardiovascular responses to HS, at least in part, by recruiting catecholaminergic neurons in the RVLM. CPZ appears to induce metabolic compensations, which may be potentially useful in HS.
Exogenous glutathione protects intestinal epithelial cells from oxidative injury. (1986)

Exogenous GSH provided rat small-intestinal epithelial cells with significant protection against injury induced by t-butyl hydroperoxide or menadione. This protection was found to be dependent upon uptake of intact GSH. Uptake of GSH occurred by a Na+-dependent electrogenic system found in the basolateral membrane. Thus, rat small-intestinal epithelial cells can utilize plasma GSH to support intracellular detoxication systems that function in protection against chemically induced injury.
Transient Kinetic Studies on the Interaction of Ras and the Ras-Binding Domain of c-Raf-1 Reveal Rapid Equilibration of the Complex (1998)

Transient kinetic methods have been used to analyze the interaction between the Ras-binding domain (RBD) of c-Raf-1 and a complex of H-Ras and a GTP analogue. The results obtained show that the binding is a two-step process, with an initial rapid equilibrium step being followed by an isomerization reaction occurring at several hundred per second. The reversal of this step determines the rate constant for dissociation, which is on the order of 10 s-1. The lifetime of the complex is therefore on the order of 50-100 ms, which is much shorter than the lifetime of GTP at the active site of H-Ras as determined by the intrinsic GTPase reaction. This suggests that multiple interactions of a single activated Ras molecule and Raf can occur, the number being limited by the competing interaction with GAP. The GDP complex of H-Ras binds more than 2 orders of magnitude more weakly than the GTP-analogue complex, mainly due to a significant weakening of the initial binding equilibrium reaction in the GDP state, thereby avoiding even short-lived recruitment of Raf to the plasma membrane by the inactive Ras form.
Disseminated Intravascular Coagulation in Trauma Patients (2001)

Disseminated intravascular coagulation (DIC) is characterized by the in vivo activation of the coagulation system, which results in the intravascular deposition of fibrin and consumption bleeding. DIC is a serious hemostatic complication of trauma. It can be clearly distinguished from physiological hemostatic response to trauma by using sensitive coagulofibrinolytic molecular markers. Physiological hemostasis to injuries is similar in all kinds of trauma without exception. There is an increase in circulating proinflammatory cytokines in DIC patients after trauma. Elevated cytokines induce tissue factor-mediated activation of coagulation, suppression of the anticoagulant pathway, and plasminogen activator inhibitor-1 (PAI-1)-mediated inhibition of fibrinolysis followed by disseminated fibrin deposition in the microvasculature. In addition to the occlusive microvascular thrombosis and hypoxia, sustained systemic inflammatory response characterized by neutrophil activation and endothelial damage plays a pivotal role in the development of multiple organ dysfunction syndrome (MODS) in posttrauma DIC patients. DIC associated with sustained systemic inflammatory response syndrome (SIRS) after trauma leads to the development of MODS, which is the main determinant of patients' outcome after trauma.
MDM2 Small-Molecule Antagonist RG7112 Activates p53 Signaling and Regresses Human Tumors in Preclinical Cancer Models (2013)

MDM2 negatively regulates p53 stability and many human tumors overproduce MDM2 as a mechanism to restrict p53 function. Thus, inhibitors of p53-MDM2 binding that can reactivate p53 in cancer cells may offer an effective approach for cancer therapy. RG7112 is a potent and selective member of the nutlin family of MDM2 antagonists currently in phase I clinical studies. RG7112 binds MDM2 with high affinity (K(D) ~ 11 nmol/L), blocking its interactions with p53 in vitro. A crystal structure of the RG7112-MDM2 complex revealed that the small molecule binds in the p53 pocket of MDM2, mimicking the interactions of critical p53 amino acid residues. Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis. RG7112 showed potent antitumor activity against a panel of solid tumor cell lines. However, its apoptotic activity varied widely with the best response observed in osteosarcoma cells with MDM2 gene amplification. Interestingly, inhibition of caspase activity did not change the kinetics of p53-induced cell death. Oral administration of RG7112 to human xenograft-bearing mice at nontoxic concentrations caused dose-dependent changes in proliferation/apoptosis biomarkers as well as tumor inhibition and regression. Notably, RG7112 was highly synergistic with androgen deprivation in LNCaP xenograft tumors. Our findings offer a preclinical proof-of-concept that RG7112 is effective in treatment of solid tumors expressing wild-type p53.
Development of Head-Mounted Projection Displays for Distributed, Collaborative, Augmented Reality Applications (2005)

Distributed systems technologies supporting 3D visualization and social collaboration will be increasing in frequency and type over time. An emerging type of head-mounted display referred to as the head-mounted projection display (HMPD) was recently developed that only requires ultralight optics (i.e., less than 8 g per eye) that enables immersive multiuser, mobile augmented reality 3D visualization, as well as remote 3D collaborations. In this paper a review of the development of lightweight HMPD technology is provided, together with insight into what makes this technology timely and so unique. Two novel emerging HMPD-based technologies are then described: a teleportal HMPD (T-HMPD) enabling face-to-face communication and visualization of shared 3D virtual objects, and a mobile HMPD (M-HMPD) designed for outdoor wearable visualization and communication. Finally, the use of HMPD in medical visualization and training, as well as in infospaces, two applications developed in the ODA and MIND labs respectively, are discussed.
Chemistry of Boranes. IX. Halogenation of B10H10-2 and B12H12-2 (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry of Boranes. IX. Halogenation of B10H10-2 and B12H12-2W. H. Knoth, H. C. Miller, J. C. Sauer, J. H. Balthis, Y. T. Chia, and E. L. MuettertiesCite this: Inorg. Chem. 1964, 3, 2, 159–167Publication Date (Print):February 1, 1964Publication History Published online1 May 2002Published inissue 1 February 1964https://pubs.acs.org/doi/10.1021/ic50012a002https://doi.org/10.1021/ic50012a002research-articleACS PublicationsRequest reuse permissionsArticle Views1765Altmetric-Citations211LEARN 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
Albumin Microbubble Echo-Contrast Material as an Enhancer for Ultrasound Accelerated Thrombolysis (1995)

The presence of the echo-contrast agent induced further acceleration of thrombolysis by US energy. It is suggested that this diagnostic echo-contrast material can be used as an alternative therapeutic US drug enhancer for thrombolysis.
Cell Type-Specific Adenoviral Transgene Expression in the IntactOvine Pituitary Gland after Stereotaxic Delivery: An in VivoSystem for Long-Term Multiple Parameter Evaluation of HumanPituitary Gene Therapy**This work was supported by the Medical Research Council, the Biotechnology and Biological Sciences Research Council, and the Royal Society. (2001)

Ablative therapies for pituitary tumors commonly cause irreversible damage to normal pituitary cells. Toxin gene therapy should therefore ideally be targeted to specific cell types to avoid collateral cell damage. To evaluate cell-type-specific adenoviral gene transfer in the intact pituitary gland we have used stereotaxic transcranial delivery of recombinant adenoviruses in the sheep with continuous assessment of endocrine function. Adenoviral β-galactosidase expression was driven either by the human cytomegalovirus (hCMV) promoter or the human PRL gene promoter. The hCMV promoter directed adenoviral β-galactosidase expression in all pituitary cell types, but the PRL promoter restricted this exclusively to lactotropic cells, indicating that this promoter conferred appropriate cell type specificity in the context of adenoviral transduction in vivo. Serial measurements of plasma hormones showed no disruption of endocrine function over 7 days after intrapituitary injection. In summary, this work shows cell type-specific expression of an adenoviral transgene in the mixed cell population of the intact pituitary gland in vivo in a large animal model and indicates that stereotaxic intrapituitary delivery does not disrupt normal endocrine function.