gebhart/patrepeval huggingface dataset:
A randomized phase III clinical trial of sequential capecitabine or 5-FU plus bevacizumab (Cape/5-FU+Bmab) followed by Cape/5-FU plus oxaliplatin plus Bmab (CapeOX/mFOLFOX6+Bmab) versus combination CapeOX/mFOLFOX6+Bmab in advanced colorectal cancer: The C-cubed (C3) study. (2018)

TPS872 Background: Less intensive regimens, focusing on survival and disease control, may be better first-line treatments in unresectable metastatic colorectal cancer (mCRC). Several randomized trials suggested that sequential cytotoxic agents in mCRC may improve overall survival compared with combination chemotherapy. This study investigated whether sequential treatment with Bmab-based first-line therapy with oxaliplatin has superior efficacy to combination treatment for unresectable mCRC. Methods: This study is a two-arm, multicenter, open-label, randomized phase III trial in Japan, comparing the efficacy and safety of sequential Cape/5-FU+Bmab with escalation to CapeOX/mFOLFOX6+Bmab versus combination CapeOX/mFOLFOX6+Bmab as the first-line treatment of mCRC. The primary endpoint is Time to failure of strategy (TFS). In the sequential arm (Arm A: oxaliplatin ‘wait-and-go’), treatment escalation from Cape/5-FU+Bmab to CapeOX/mFOLFOX6+Bmab is recommended for progressive disease. In the combination arm (Arm B: oxaliplatin ‘stop-and-go’), de-escalation from CapeOX/mFOLFOX6+Bmab to Cape/5-FU+Bmab is possible after 12 weeks of treatment. Re-escalation to CapeOX/mFOLFOX6+Bmab after progressive disease is considered only for patients who received de-escalation of oxaliplatin, not caused by oxaliplatin-associated toxicity, after 12 weeks of treatment. A target sample size of 304 evaluable patients is considered sufficient to detect a hazard ratio of 0.69 for the TFS of the sequential ‘wait-and-go’ approach compared with the combination ‘stop-and go’ approach with 80% power and a 2-sided significance level of 5%. From December 2014 to September 2016, 311 patients were enrolled across 81 centers in Japan. The follow-up period is until March 2018, and results are expected in 2019, and results are expected in 2019. Clinical trial information: 000015405.
Exosomes from human ovarian carcinoma SKOV3 cells are enriched in glycosylated proteins (2010)

Exosomes are small vesicles released by various cell types, including tumor cells, as a result of fusion of the multivesicular bodies with the plasma membrane. Exosomes can interact with target cells and mediate different processes, such as, tumor progression and intercellular transfer of proteins and RNA.

Although heavily glycosylated forms of some proteins were found in exosomes, the role of glycosylation on protein sorting to exosomes and on the recognition and uptake of these vesicles by cells is still not known.

The analysis of the glycosylation profiles of cellular extracts and exosomes from ovarian carcinoma SKOV3 cells, using lectins with different specificities, showed higher levels of protein glycosylation, in particular, sialylation in exosomes.

SKOV3 cells were found to internalize SKOV3 derived exosomes, labeled with carboxyfluoresceine diacetate succinimidyl-ester (Exos-CFSE), through an energy-dependent process that was almost completely inhibited at 4 oC. Digestion of Exos-CFSE and SKOV3 cells with proteinase K resulted in considerably lower levels of uptake indicating that proteins were required, at least in part, for internalization. Exos-CFSE uptake was slightly increased after exosomes desialylation with neuraminidase and blocking of cell surface glycan-receptors with different monosaccharides had no effect when compared with the control D-glucose.

In conclusion, the increase in protein glycosylation was not essential for exosomes recognition and uptake by target cells. The presence of some heavily glycosylated proteins in exosomes might be a consequence of their enrichment in specific domains of the plasma membrane from where exosomes emerge.
Compound biological signatures facilitate phenotypic screening and target elucidation (2016)

We developed a statistical method, BIOSEA, able to identify molecules that are capable of reproducing a desired cellular phenotype, by scanning a large compound collection based on biological similarity. Our method leverages highly incomplete and noisy compound bioactivity signatures from historical high-throughput screening campaigns. We applied our approach in a phenotypic screening workflow and found novel nanomolar inhibitors of cell division that reproduce the mode of action of reference natural products. In a drug discovery setting, our biological hit expansion protocol revealed new inhibitors of the NKCC1 co-transporter for autism spectrum disorders. Furthermore, we demonstrate BIOSEA’s capabilities to predict novel targets for old compounds. We report new activities for the drugs nimedipine, fluspirilene and pimozide applicable for compound repurposing and rationalizing drug side effects. Our results highlight the opportunities of reusing public bioactivity data for prospective drug discovery applications where the target or mode of action is not known.
Overexpression of the human 72 kDa heat shock protein in renal tubular cells confers resistance against oxidative injury and cisplatin toxicity (1999)

These results indicate that overexpressed HSP72 plays a direct role in protecting renal tubular cells against oxidative injury and cisplatin toxicity.
Signal transduction by tumor necrosis factor mediated by JNK protein kinases. (1994)

JNK protein kinases are distantly related to mitogen-activated protein kinases (ERKs) and are activated by dual phosphorylation on Tyr and Thr. The JNK protein kinase group includes the 46-kDa isoform JNK1. Here we describe the molecular cloning of a second member of the JNK group, the 55-kDa protein kinase JNK2. The activities of both JNK isoforms are markedly increased by exposure of cells to UV radiation. Furthermore, JNK protein kinase activation is observed in cells treated with tumor necrosis factor. Although both JNK isoforms phosphorylate the NH2-terminal activation domain of the transcription factor c-Jun, the activity of JNK2 was approximately 10-fold greater than that of JNK1. This difference in c-Jun phosphorylation correlates with increased binding of c-Jun to JNK2 compared with JNK1. The distinct in vitro biochemical properties of these JNK isoforms suggest that they may have different functions in vivo. Evidence in favor of this hypothesis was obtained from the observation that JNK1, but not JNK2, complements a defect in the expression of the mitogen-activated protein kinase HOG1 in the yeast Saccharomyces cerevisiae. Together, these data indicate a role for the JNK group of protein kinases in the signal transduction pathway initiated by proinflammatory cytokines and UV radiation.
Electroabsorption and electrorefraction effects in quantum-well modulators (1994)

We present a comprehensive numerical study of electroabsorption and electrorefraction in quantum-well modulators. Our analysis properly incorporates both the k\ensuremath{\cdot}p subband matrix elements and the excitonic wave functions and further contains several alternative techniques for solving the exciton equation. Excellent agreement with experiment is achieved in both the discrete and continuum regions.
A role for nuclear lamins in nuclear envelope assembly (2001)

The molecular interactions responsible for nuclear envelope assembly after mitosis are not well understood. In this study, we demonstrate that a peptide consisting of the COOH-terminal domain of Xenopus lamin B3 (LB3T) prevents nuclear envelope assembly in Xenopus interphase extracts. Specifically, LB3T inhibits chromatin decondensation and blocks the formation of both the nuclear lamina–pore complex and nuclear membranes. Under these conditions, some vesicles bind to the peripheral regions of the chromatin. These “nonfusogenic” vesicles lack lamin B3 (LB3) and do not bind LB3T; however, “fusogenic” vesicles containing LB3 can bind LB3T, which blocks their association with chromatin and, subsequently, nuclear membrane assembly. LB3T also binds to chromatin in the absence of interphase extract, but only in the presence of purified LB3. Additionally, we show that LB3T inhibits normal lamin polymerization in vitro. These findings suggest that lamin polymerization is required for both chromatin decondensation and the binding of nuclear membrane precursors during the early stages of normal nuclear envelope assembly.
Optical scanner system for high resolution measurement of lubricant distributions on metal strips based on laser induced fluorescence (2017)

We present a new optical setup, which uses scanning mirrors in combination with laser induced fluorescence to monitor the spatial distribution of lubricant on metal sheets. <br/> <br/> Current trends in metal processing industry require forming procedures with increasing deformations. Thus a welldefined amount of lubricant is necessary to prevent the material from rupture, to reduce the wearing of the manufacturing tool as well as to prevent problems in post-deforming procedures. Therefore spatial resolved analysis of the thickness of lubricant layers is required. Current systems capture the lubricant distribution by moving sensor heads over the object along a linear axis. However the spatial resolution of these systems is insufficient at high strip speeds, e.g. at press plants. <br/> <br/> The presented technology uses fast rotating scanner mirrors to deflect a laser beam on the surface. This 405 nm laser light excites the autofluorescence of the investigated lubricants. A coaxial optic collects the fluorescence signal which is then spectrally filtered and recorded using a photomultiplier. From the acquired signal a two dimensional image is reconstructed in real time. This paper presents the sensor setup as well as its characterization. For the calibration of the system reference targets were prepared using an ink jet printer. <br/> <br/> The presented technology for the first time allows a spatial resolution in the millimetre range at production speed. The presented test system analyses an area of 300 x 300 mm² at a spatial resolution of 1.1 mm in less than 20 seconds. Despite this high speed of the measurement the limit of detection of the system described in this paper is better than 0.05 g/m² for the certified lubricant BAM K-009.
Microchip-based ethanol/oxygen biofuel cell (2005)

One of the limitations of lab-on-a-chip technology has been the lack of integrated power supplies for powering various devices on the chip. This research focused on design of a stackable, microchip-based biofuel cell. The biofuel cell is powered by the addition of ethanol through a flow channel to a bioanode. The bioanode contains a micromolded carbon ink anode that has been modified with two layers. The first layer is poly(methylene green), which is an electrocatalyst for NADH oxidation; the second layer is a membrane that contains an immobilized enzyme, alcohol dehydrogenase. Each layer was characterized electrochemically. It was found that the poly(methylene green) layer is kinetically-limited, but when the complete bioanode is formed, the bioanode is diffusion-limited due to slow mass transport of NADH within the modified Nafion membrane. When used relative to an external platinum cathode, the biofuel cell showed maximum open circuit potentials of 0.34 V and maximum current densities of 53.0 +/- 9.1 microA cm(-2). This research demonstrates the feasibility of a microfabricated biofuel cell device.
AAV vector re-targeting: A small step on the way to cardiac-specific gene transfer (2006)

See article by Muller et al. [8] (pages 70–78) in this issue .

Gene and stem cell therapy are two visions of modern medicine that could have the potential to redirect patient treatment from a pharmacological/interventional to a molecular approach. The idea behind both strategies is the perspective to causally treat disease. Both visions are attractive, both promise causal therapies. Therefore, it is not too astonishing that both approaches have caused hopes and hypes. However, as sometimes observed when a new field moves from the first spectacular results into broader investigation, problems and pitfalls become apparent that dampen the expectations of fast solutions.

In 1999, the field of gene therapy was shaken by the case of Jesse Gelsinger, who died in a clinical gene therapy trial for liver disease. Three years later, in French clinical trials to cure children with severe combined immunodeficiency, three children treated with retrovirally transduced cells developed cancer, most likely as a result of insertional mutagenesis by the retrovirus. Consequently, gene therapy trials were put on hold and doubts came up whether gene therapy represents a realistic future option in medicine [1]. These cases also showed in a tragic manner the need to send researchers from the bedside back to the bench to solve basic problems of somatic gene therapy.

In general, somatic gene therapy requires the solution of a complex set of problems that are all connected to the following three questions briefly addressed below:

1. What is my therapeutic gene?
 The identification of the therapeutic gene is, of course, closely related to the biological dysfunction that is to be cured. In the cardiovascular field, … 

* Corresponding author. Tel.: +49 211 8112675; fax: +49 211 8112675. Email address: Axel.Goedecke{at}uni-duesseldorf.de
Hiding and revealing information using the mechanochromic system of a 2,5-dicarbazole-substituted terephthalate derivative (2018)

Information written using mechanical force in a 2,5-dicarbazole-substituted terephthalate derivative system can be hidden, revealed and erased again by basic vapor, acidic vapor and thermal annealing, respectively.
Crystallization-Induced Orientation for Microstructures of Poly(l-lactide)-b-poly(ε-caprolactone) Diblock Copolymers (2003)

The formation of large-sized, well-oriented microdomains of poly(l-lactide)-b-poly(ε-caprolactone) (PLLA−PCL) was successfully achieved by using different crystalline substrates including benzoic acid (BA) and hexamethylbenzene (HMB), whereas spherulitic crystalline texture was obtained on amorphous substrates. Crystallization-induced orientation of PLLA−PCL microstructures is attributed to directional crystallization of eutectic type between crystalline PLLA and substrate, regardless of microphase separation. Surprisingly, a flat-on crystalline morphology (i.e., with the chain axis normal to the substrate) was obtained, as evidenced by single-crystal-like [001] zonal electron diffraction (ED). By contrast, an edge-on crystalline morphology (i.e., with the chain axis parallel to the substrate) was observed for PLLA homopolymer under the same condition. The crystallographic organization of PLLA−PCL microdomains as observed by transmission electron microscopy, ED, and scanning probe microscopy suggests that the growth direction of PLLA crystals is along the a-axis direction, which suggests that the growth direction of PLLA crystals is along the a-axis direction that corresponds well with the preferential growth direction (i.e., b-axis direction) of BA or HMB crystals. As a result, the phase-separated lamellar morphology consists of an alternation of a flat-on layer of PLLA lamellae and of an amorphous layer of PLLA and PCL components.
La construction navale à Québec au XIXème siècle: un point de vue organisationnel (2005)

La ville de Québec était, au XIXe siècle, un des centres de la construction navale mondiale. Après en avoir décrit l'évolution en termes macroéconomiques, l'auteur utilise un schéma théorique fondé sur la sociologie des organisations pour comprendre l'interaction entre les forces économiques et le contexte socioculturel de ces entreprises. Cette industrie fut implantée par les immigrants écossais puis anglais et irlandais à la suite de la Conquête. Les Canadiens français y seront ouvriers ou sous-traitants ne devenant entrepreneurs qu'à la fin de l'industrie. Opposés par leur langue, leur religion et leurs valeurs industrielles, les rapports entre les patrons et les ouvriers favoriseront l'apparition d'un mode d'organisation du travail original, les métiers de masse.
Dynamics of hippocampal acetylcholine release during lithium‐pilocarpine‐induced status epilepticus in rats (2014)

The lithium-pilocarpine model is a rat model of epilepsy that mimics status epilepticus in humans. Here, we report changes of acetylcholine (ACh) release in the hippocampus before, during and after status epilepticus as monitored by microdialysis in unanesthetized rats. Administration of pilocarpine (30 mg/kg s.c.) to rats pretreated with lithium chloride (127 mg/kg i.p.) caused a massive, six-fold increase of hippocampal ACh release, paralleling the development of tonic seizures. When seizures were stopped by administration of diazepam (10 mg/kg i.p.) or ketamine (75 mg/kg i.p.), ACh levels returned to normal. Extracellular concentrations of glutamate remained unchanged during this procedure. Administration of atropine (1 mg/kg i.p.) 2 h after pilocarpine caused a further increase of ACh but did not affect seizures, whereas injection of mecamylamine (5 mg/kg i.p.) reduced ACh levels and seizures in a delayed fashion. Local infusion of tetrodotoxin, 1 μM locally) or hemicholinium (10 μM locally) strongly reduced ACh release and had delayed effects on seizures. Administration of glucose or inositol (250 mg/kg each i.p.) had no visible consequences. In parallel experiments, lithium-pilocarpine-induced status epilepticus also enhanced striatal ACh release, and hippocampal ACh levels equally increased when status epilepticus was induced by kainate (30 mg/kg i.p.). Taken together, our results demonstrate that seizure development in status epilepticus models is accompanied by massive increases of extracellular ACh, but not glutamate, levels. Treatments that reduce seizure activity also reliably reduce extracellular ACh levels.
Update on clinical significance of coagulase-negative staphylococci (1994)

The clinical significance of coagulase-negative Staphylococcus species (CNS) continues to increase as strategies in medical practice lead to more invasive procedures. Hospitalized patients that are immunocompromised and/or suffering from chronic diseases are the most vulnerable to infection. Since CNS are widespread on the human body and are capable of producing very large populations, distinguishing the etiologic agent(s) from contaminating flora is a serious challenge. For this reason, culture identification should proceed to the species and strain levels. A much stronger case can be made for the identification of a CNS etiologic agent if the same strain is repeatedly isolated from a series of specimens as opposed to the isolation of different strains of one or more species. Strain identity initially can be based on colony morphology, and then one or more molecular approaches can be used to gain information on the genotype. Many of the CNS species are commonly resistant to antibiotics that are being indicated for staphylococcal infections, with the exception of vancomycin. The widespread use of antibiotics in hospitals has provided a reservoir of antibiotic-resistant genes. The main focus on mechanisms of pathogenesis has been with foreign body infections and the role of specific adhesins and slime produced by Staphylococcus epidermidis. Slime can reduce the immune response and opsonophagocytosis, thereby interfering with host defense mechanisms. As we become more aware of the various strategies used by CNS, we will be in a better position to compromise their defense mechanisms and improve treatment.
The chemical nature of royal jelly (1940)

MOST chemical investigations of substances important in nutrition have dealt with foods used by mammals.The work to be reported is an attempt to deter- mine the chemical nature of the components of royal jelly, the peculiar nutriment which is fed to queen bees by their subjects throughout life.Royal jelly is a thick, milky material which is generally believed to be a secretion of the pharyn: geal glands of the nurse bees (young workers).For a proper appreciation of the nutritional significance of royal jelly the following facts about the natural history of bees should be recalled.,A colony of bees consists of one queen, several hundred drones or males and from 25,000 to 100,000 worker bees, sexually undeveloped females.This large number of workers are all the daughters of one queen.As the bees die off constantly the queen may, during the whole season, become the mother of a quarter of a million bees.At the height of the season, queens have been known to lay more than 2000 eggs (over their own weight in eggs) in one day.Such fecundity must be associated with a very active metabolism and the nature of the food which makes this possible is of interest.But of greater nutritional significance is ihe fact that the anatomical and physiological differentiation of the female larvae is dependent upon the nature of their diet.Two types of eggs.are laid by the queen: (1) unfertilized eggs which give rise only to drones (male bees), and (2) fertile eggs which give rise to females, either workers (sexually immature females) or queens.By grafting young larvae, it has been proven
SCA2 and SCA3 mutations in young‐onset dopa‐responsive parkinsonism (2003)

In this study no one of our 85 patients of Serbian origin with young-onset (</= 45 years) dopa-responsive parkinsonism (YOP), previously proved negative for PARK1 and PARK2 mutations, had either spinocerebellar ataxia type 2 (SCA2) or SCA3 mutation. These data do not prove the significance of these two mutations in either sporadic or familial YOP suggestive of Parkinson's disease.
Radiographic Investigation of the Distal Extension of Fractures Into the Articular Surface of the Tibia (The RIDEFAST Study) (2017)

Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Expression and purification of the mitochondrial transmembrane protein FAM210A in Escherichia coli (2023)

The protein Family with sequence similarity 210 member A (FAM210A) is a mitochondrial inner membrane protein that regulates the protein synthesis of mitochondrial DNA encoded genes. However, how it functions in this process is not well understood. Developing and optimizing a protein purification strategy will facilitate biochemical and structural studies of FAM210A. Here, we developed a method to purify human FAM210A with deleted mitochondrial targeting signal sequence using the MBP-His <sub>10</sub> fusion in <i>Escherichia coli</i> . The recombinant FAM210A protein was inserted into the <i>E. coli</i> cell membrane and purified from isolated bacterial cell membranes, followed by a two-step process using Ni-NTA resin-based immobilized-metal affinity chromatography (IMAC) and ion exchange purification. A pulldown assay validated the functionality of purified FAM210A protein interacting with human mitochondrial elongation factor EF-Tu in HEK293T cell lysates. Taken together, this study developed a method for purification of the mitochondrial transmembrane protein FAM210A partially complexed with <i>E.coli</i> derived EF-Tu and provides an opportunity for future potential biochemical and structural studies of recombinant FAM210A protein.
Doppler parameters of uterine and ovarian stromal blood flow in women with polycystic ovary syndrome and normally ovulating women undergoing controlled ovarian stimulation (1998)

It seems that polycystic ovaries do not bear an inherent disturbance in blood flow dynamics of the uterine and ovarian arteries, as measured by color Doppler, which would explain the increased sensitivity of polycystic ovaries to stimulation with gonadotropins.
ChemInform Abstract: Charge Disproportionation and Charge Transfer in A‐Site Ordered Perovskites Containing Iron. (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.