gebhart/patrepeval huggingface dataset:
Safety, Pharmacokinetics, and Activity of GRN1005, a Novel Conjugate of Angiopep-2, a Peptide Facilitating Brain Penetration, and Paclitaxel, in Patients with Advanced Solid Tumors (2011)

GRN1005 is a novel peptide-drug conjugate composed of paclitaxel covalently linked to a peptide, angiopep-2, that targets the low-density lipoprotein receptor-related protein 1. This first-in-human study evaluated the safety, tolerability, pharmacokinetics, and efficacy of GRN1005 in patients with advanced solid tumors. Patients in sequential cohorts (one patient per cohort until grade 2 toxicity, then 3 + 3 design) received intravenous GRN1005 at escalating doses between 30 and 700 mg/m(2) once in every 21 days. In the maximum tolerated dose (MTD) expansion group, patients were required to have brain metastases. Fifty-six patients received GRN1005, including 41 with brain metastases (median number of prior therapies = 4). MTD was 650 mg/m(2); the main dose-limiting toxicity was myelosuppression. Sixteen of 20 patients dosed at the MTD had brain metastases. Pharmacokinetics was dose linear and the mean terminal-phase elimination half-life was 3.6 hours. No evidence of accumulation was observed after repeat dosing. No anti-GRN1005 antibodies were detected. Five of the 20 patients (25%) dosed at 650 mg/m(2) (MTD), three of whom had previous taxane therapy, achieved an overall partial response (breast, n = 2; non-small cell lung cancer, n = 2; and ovarian cancer, n = 1); responses in all five patients were also accompanied by shrinkage of brain lesions (-17% to -50%). In addition, six patients (11%; doses 30-700 mg/m(2)) experienced stable disease that lasted 4 months or more. GRN1005 was well tolerated and showed activity in heavily pretreated patients with advanced solid tumors, including those who had brain metastases and/or failed prior taxane therapy.
Black Swans, Adaptive Managment and the Future of the Salish Sea (2016)

The restoration and management of the Salish Sea, the classic large-scale system, without a structured decision making process is unworkable. Given the alterations in the environment induced by climate change, alterations in landuse, and changes in technology the future is full of Black Swans. The change in the goalposts for remediation and restoration brought about by changing cultural norms is the definition of Wicked Problems, those problems that do not have a final management solution. Adaptive management is often hailed as the process for the management of landscapes. Unfortunately the analytical tools necessary to implement an adaptive management approach have not developed to match the need. One of the assumptions of AM is that testable predictions are made that then can be tested by before and after management implementation (BACI) design. BACI designs have a number of assumptions, one of which is that natural factors are in a natural equilibrium be it static or dynamic. At a scale for large-scale restoration this assumption will be violated given climate change and technological innovation. Ecological risk assessment or derived approaches such as a probabilistic pressure assessments offer an alternate means of making predictions that embraces stakeholder values, environmental change and the associated uncertainty. Incorporating Bayesian networks into the relative risk model (BN-RRM) allows probabilistic predictions to be made regarding risks due to specific stressors. Management options can be evaluated and the magnitude of change in risk to endpoints evaluated. Sensitivity analysis points to the variables most important to monitor and with what degree of accuracy and precision. The models are updateable as new information is obtained from field monitoring or related research. If the goalposts move because of changing cultural values or new information, the distance to these new expectations can be calculated and new solutions proposed. We will demonstrate how the management scheme works with examples from contaminated sites, non-point contamination and invasive species.
Use of hTERT and HPV E6/E7 mRNA RT-qPCR TaqMan Assays in Combination for Diagnosing High-Grade Cervical Lesions and Malignant Tumors (2015)

These data suggest that the combination of HPV E6/E7 and hTERT mRNA expression levels could be used in a complementary manner in diagnosing high-grade cervical lesions and malignant tumors and might be useful as a predictive marker in monitoring low-grade cervical lesions.
Maize metacaspases modulate the defense response mediated by the NLR protein Rp1‐D21 likely by affecting its subcellular localization (2020)

Plants usually employ resistance (R) genes to defend against the infection of pathogens, and most R genes encode intracellular nucleotide-binding, leucine-rich repeat (NLR) proteins. The recognition between R proteins and their cognate pathogens often triggers a rapid localized cell death at the pathogen infection sites, termed the hypersensitive response (HR). Metacaspases (MCs) belong to a cysteine protease family, structurally related to metazoan caspases. MCs play crucial roles in plant immunity. However, the underlying molecular mechanism and the link between MCs and NLR-mediated HR are not clear. In this study, we systematically investigated the MC gene family in maize and identified 11 ZmMCs belonging to two types. Further functional analysis showed that the type I ZmMC1 and ZmMC2, but not the type II ZmMC9, suppress the HR-inducing activity of the autoactive NLR protein Rp1-D21 and of its N-terminal coiled-coil (CC<sub>D21</sub> ) signaling domain when transiently expressed in Nicotiana benthamiana. ZmMC1 and ZmMC2 physically associate with CC<sub>D21</sub> in vivo. We further showed that ZmMC1 and ZmMC2, but not ZmMC9, are predominantly localized in a punctate distribution in both N. benthamiana and maize (Zea mays) protoplasts. Furthermore, the co-expression of ZmMC1 and ZmMC2 with Rp1-D21 and CC<sub>D21</sub> causes their re-distribution from being uniformly distributed in the nucleocytoplasm to a punctate distribution co-localizing with ZmMC1 and ZmMC2. We reveal a novel role of plant MCs in modulating the NLR-mediated defense response and derive a model to explain it.
Cell-Cycle Analysis in 20 Minutes (1974)

Mithramycin added to mammalian cells fixed in aqueous ethanol is bound to DNA and fluoresces in direct proportion to the cellular DNA content. Quantitative fluorescence measurement by means of a high-speed flow system instrument provides a rapid method for cell-cycle analysis and for the first time permits continuous monitoring of cell-cycle kinetics during ongoing experiments.
Mechanistic Insights into the Activity of Mo-Carbide Clusters for Methane Dehydrogenation and Carbon–Carbon Coupling Reactions To Form Ethylene in Methane Dehydroaromatization C (2018)

Methane dehydrogenation and C–C coupling reactions to form ethylene on two different carbide clusters of molybdenum (Mo₄C₂ and Mo₂C₆) were studied. Density functional theory (DFT) calculations were performed to understand the reactivity of the two clusters, linking it to the overall methane dehydroaromatization (MDA) process. The electronic effect of catalyst reduction procedures and anchoring of the cluster on the zeolite framework was captured in simulations with varying positive charge on the cluster. In general, with one exception, DFT calculations suggested a reduction in dehydrogenation activation energies with more reduced (lesser positive charge) clusters. Similarly, activation barriers for the transfer of a H atom from the carbon to the neighboring Mo site were calculated to be lower on more reduced clusters. In contrast, the coupling reactions of the two CH₃ and the two H atoms on the surface showed a reverse trend. The activation energies of the C–C and the H–H coupling steps were observed to be lower on less reduced (higher positive charge) clusters. On comparing the two (Mo₄C₂ and Mo₂C₆) clusters with similar charges, the activation energies for the first methane dehydrogenation were observed to be of similar value on both clusters for the neutral charge. However, second methane dehydrogenation was calculated to show a significantly higher barrier on the Mo₂C₆ cluster for both neutral and +1 charges. In addition, the CH₃ coupling reaction was facilitated with a relatively lower activation barrier on the Mo₂C₆ cluster as compared to that on the Mo₄C₂ cluster. Thus, Mo₂C₆ sites in the vicinity of the Bronsted acid sites of the zeolite are likely to be more active for the coupling of the two CH₃ species and helpful in MDA. This alluded to the operando experimental findings by Lezcano-Gonzalez [ Angew. Chem., Int. Ed.2016, 55, 5215−5219], wherein it was suggested that methane might be activated on carbide and oxycarbide species; however, formation of MoC₃-type species on stream was linked directly to MDA.
Spontaneous pneumothorax and ozone levels: is there a relation? C'è un rapporto tra pneumotorace spontaneo e livelli di ozono? (2011)

Study objectives: Although links between meteor ological conditions and spontaneous pneumothorax (SP) have been proposed, the reports are controversial. In this study ozone levels, which are known to have some adverse effects on lung tissues, were investigated as a potential triggering factor of SP. At present there is not sufficient information about the effects of ozone on SP. Methods: Of a total 79 pneumothorax patients recruited for the study, 21 secondary pneumothorax cases were excluded. In the remaining 58 SP patients, meteorological data at the time of SP occurrence were recorded. Results: The number of SP patients was higher in spring than in the other seasons (p < 0.05). There was an association between the SP frequency and the average ozone level at different seasons (F 3,52 = 19.45, p = 0.001). The average ozone level was higher in spring (363 ± 25 Dobson) than during the other seasons (autumn 296 ± 18 Dobson; summer 321 ± 26 Dobson; winter 324 ± 32 Dobson) (p = 0.001). There was a positive correlation between SP frequency and the average ozone values for each season (r = 0.301, p = 0.024). There was no significant correlation between the severity of SP and ozone level (r = 0.236, p = 0.16). Conclusions: The number of SP patients increases in spring when ozone levels are highest. Ozone is known to affect alveolar cells and cause interstitial edema. Ozone causes damage to the lung interstitium by way of oxidative stress. Rupture of unrecognized underlying blebs/bullae has been proposed as a cause of SP. Increased levels of ozone may be a triggering factor for these ruptures.
Effect of intestinal bypass on the expression of actin mRNA in ileal smooth muscle (1990)

In this study, messenger RNAs (mRNAs) for actin isoforms were assessed in longitudinal smooth muscle from the ileum of unoperated rats and from rats that had undergone bypass of the middle 70% of the small intestine. The plasmid clone pGEM 10C, which contains a DNA insert complementary to the 3' untranslated region and the region of mRNA that codes for the synthesis of alpha-smooth muscle actin protein, was used to synthesize two riboprobes. One probe, complementary to the coding region of the insert, hybridizes to most, if not all, actin isoform mRNAs. The second probe, complementary to the 3' untranslated region of the insert, hybridizes only to alpha-smooth muscle actin mRNA. RNA was isolated from animals 4 to 5 days after operation, size fractionated by denaturing gel electrophoresis, transferred to nylon membranes, and exposed to the two 32P-labeled riboprobes. Both probes hybridized to RNA of about 1.3 kilobases long. Longitudinal muscle from both groups of animals contained alpha-smooth muscle actin mRNA as well as mRNA for other actin isoforms. Dot blots of varying amounts of RNA were hybridized to the riboprobes to determine the proportions of actin mRNAs. The content and concentration of mRNAs for all actins, and of mRNA for alpha-smooth muscle actin, were significantly greater in muscle from the functioning ileum of bypassed animals 4-5 days after the operation. Thus the operation induces a rapid, specific activation of these contractile protein genes.
Putative Role of Isoquinoline Alkaloids in Alcoholism: A Link to Opiates (1978)

Although the isoquinoline hypothesis has stimulated and even tantalized the scientific inquiry of a small number of investigators, it has been an area of widespread controversy. For the most part, until recently, alcohol researchers would ascribe very little importance to the role played by insoquinolines in alcohol actions or in the disease state known as alcoholism. To most, there was adequate evidence that these condensation amines had potent pharmacologic properties but little was known about their biochemical and behavioral interaction with ethanol or opiates. As pointed out here, there is an increasing amount of evidence that indicates the putative role of isoquinolines as regulators of alcohol dependence. There is even evidence that suggests a possible "link" to opiates. If this turns out to be the case, then it is rational to consider the possibility that when one imbibes alcohol a central opiate-like substance is, in essence, produced. It would appear that the sum total of evidence to date supports the notion that there are common territories between the two highly addictive classes of drugs--alcohol and opiates. Although still not definite, future studies may well confirm the intermediacy of the TIQ compounds.
Electromagnetic and Laplace domain analysis of memristance and associative learning using memristive synapses modeled in SPICE (2012)

The unique properties of memristors could possibly be used in non-volatile memories and neuromorphic computing to drastically reduce area and power dissipation. In this paper, an attempt is made to understand the concept of memristance from an electromagnetic theory perspective and derive an expression for memristance in Laplace domain involving only fundamental material properties. Further, a parameterized SPICE model for the memristor is shown to mimic a synapse in a typical neural network. An ultra-low power and compact neural network is constructed using memristors and the leaky-integrate-fire neuron model to demonstrate associative learning. This shows promise that memristive neuromorphic computing has potential to achieve the ultimate challenge of mimicking the human brain.
Program translation via abstraction and reimplementation (1988)

An abstraction-and-reimplementation paradigm is presented in which the source program is first analyzed in order to obtain a programming-language-independent abstract understanding of the computation performed by the program as a whole. The program is then reimplemented in the target language based on this understanding. The key to this approach is the abstract understanding obtained. It allows the translator to benefit from an appreciation of the global features of the source program without being distracted by what are considered irrelevant details. Knowledge-based translation via abstraction and reimplementation is described as one of the goals of the Programmer's Apprentice project. A translator which translates Cobol programs into Hibol (a very-high-level business data processing language) has been constructed. A computer which generates extremely efficient PDP-11 object code for Pascal programs has been designed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
How I treat severe combined immunodeficiency (2013)

Severe combined immunodeficiency (SCID) arises from different genetic defects associated with lymphocyte development and function and presents with severe infections. Allogeneic hematopoietic stem cell transplantation is an extremely effective way of restoring immunity in these individuals. Numerous multicenter studies have identified the factors determining successful outcome, and survival for SCID has shown great improvement. Advances in understanding the genetic basis of disease also mean that we increasingly tailor transplant protocols to the specific SCID form. Wherever possible, we attempt to transplant SCID patients without the use of cytoreductive conditioning, but it is clear that this is only successful for specific SCID forms and, although survival is good, in specific patients there are ongoing humoral defects. We aim to use matched related and unrelated donors (including cord blood) whenever possible and have limited the use of mismatched haploidentical donors. The development of autologous hematopoietic stem cell gene therapy provides another treatment of the X-linked and adenosine deaminase-deficient forms of SCID, and we discuss how we have integrated gene therapy into our treatment strategy. These developments together with the advent of universal newborn screening for SCID should allow for a highly favorable outcome for this otherwise lethal condition.
Tension Band Fixation of Medial Malleolus Fractures (1992)

A prospective study on tension band fixation of medial malleolus fractures was performed on 30 consecutive patients with 31 fractures from October 1987 until December 1990. All patients had at least a displaced medial malleolus fracture unreduced by closed methods. The fractures were classified into small, medium and large using a modified Lauge-Hansen classification. There were no nonunions or movements of wires postoperatively and only two patients had subjective complaints with reference to the wires that required hardware removal. There was one 2-mm malreduction and one patient with a wound slough and subsequent osteomyelitis. One fragment had 2 mm of displacement after fixation but went on to union. A biomechanical study was undertaken to compare fixation of the medial malleolus with K wires alone, K wires plus a tension band, and two cancellous screws. The tension band fixation provided the greatest resistance to pronation forces: for times stiffer than the two screws and 62% of the intact specimen. Tension band fixation of the medial malleolus is a biomechanically strong and clinically acceptable method of treatment for displaced medial malleolus fractures. This method of fixation may be especially useful for small fragments and in osteoporotic bone.
Interstitial Branches Develop from Active Regions of the Axon Demarcated by the Primary Growth Cone during Pausing Behaviors (1998)

Interstitial branches arise from the axon shaft, sometimes at great distances behind the primary growth cone. After a waiting period that can last for days after extension of the primary growth cone past the target, branches elongate toward their targets. Delayed interstitial branching is an important but little understood mechanism for target innervation in the developing CNS of vertebrates. One possible mechanism of collateral branch formation is that the axon shaft responds to target-derived signals independent of the primary growth cone. Another possibility is that the primary growth cone recognizes the target and demarcates specific regions of the axon for future branching. To address whether behaviors of the primary growth cone and development of interstitial branches are related, we performed high-resolution time-lapse imaging on dissociated sensorimotor cortical neurons that branch interstitially in vivo. Imaging of entire cortical neurons for periods of days revealed that the primary growth cone pauses in regions in which axon branches later develop. Pausing behaviors involve repeated cycles of collapse, retraction, and extension during which growth cones enlarge and reorganize. Remnants of reorganized growth cones are left behind on the axon shaft as active filopodial or lamellar protrusions, and axon branches subsequently emerge from these active regions of the axon shaft. In this study we propose a new model to account for target innervation in vivo by interstitial branching. Our model suggests that delayed interstitial branching results directly from target recognition by the primary growth cone.
Early regression of cervical lesions in HIV-seropositive women receiving highly active antiretroviral therapy (1998)

Our observations demonstrate that active antiretroviral therapy may result in a reduced prevalence of cervical squamous intra-epithelial lesions despite the absence of clearance of HPV infection.
Oxygen Reduction Activities of Praseodymium Manganites in Alkaline Solution (1997)

A series of praseodymium manganites, Pr1-xAxMnO3 (A=Ca, Sr, Ba, 0≤x≤1.0), were examined for their electrode-catalytic activities as incorporated into a gas diffusion-type oxygen reduction electrode working in an alkaline solution. Among the oxides tested, Pr0.6Ca0.4MnO3 gave the highest electrode performance (320mA·cm-2 at -150mV vs. Hg/HgO) in 8mol·dm-3 KOH aqueous solution at 60°C under air flow. The electrode performances were found to be well correlated with the activities of the oxides for the 4-electron reduction of oxygen (O2+2H2O+4e-→4OH-) evaluated from a rotating ring-disk electrode analysis. The oxidation state of Mn ions of the oxides was investigated by means of iodometry, X-ray photoelectron spectroscopy, temperature-programmed oxygen desorption and electron spin resonance. The results obtained suggest that the active sites for the 4-electron reduction of oxygen involve Mn3+ ions and that their activities increase profoundly as the Mn3+ ions neighbor Mn4+ to form Mn3+-Mn4+ pairs. The electrode loaded with Pr0.6Ca0.4MnO3 was confirmed to continue to work rather stably for a test period of 200h under the galvanostatic condition of 300mA·cm-2, the oxide being kept intact as revealed by X-ray diffraction analysis after the test. The same electrode was shown to exhibit a promising performance when incorporated into a zinc-air cell.
Detecting opinion spams and fake news using text classification (2017)

In recent years, deceptive content such as fake news and fake reviews, also known as opinion spams, have increasingly become a dangerous prospect for online users. Fake reviews have affected consumers and stores alike. Furthermore, the problem of fake news has gained attention in 2016, especially in the aftermath of the last U.S. presidential elections. Fake reviews and fake news are a closely related phenomenon as both consist of writing and spreading false information or beliefs. The opinion spam problem was formulated for the first time a few years ago, but it has quickly become a growing research area due to the abundance of user‐generated content. It is now easy for anyone to either write fake reviews or write fake news on the web. The biggest challenge is the lack of an efficient way to tell the difference between a real review and a fake one; even humans are often unable to tell the difference. In this paper, we introduce a new n‐gram model to detect automatically fake contents with a particular focus on fake reviews and fake news. We study and compare 2 different features extraction techniques and 6 machine learning classification techniques. Experimental evaluation using existing public datasets and a newly introduced fake news dataset indicate very encouraging and improved performances compared to the state‐of‐the‐art methods.
EDCA: Efficient diffusion cipher and authentication scheme for Wireless Sensor Networks. (2014)

International audience