gebhart/patrepeval huggingface dataset:
Abstract 226: PI3K pathway inhibition induces a different metabolic response in NSCLC cells harboring WT and G12C mutant KRAS (2016)

Abstract Lung cancer is the most common cancer worldwide and, because of its high fatality, it also represents the most common cause of cancer related deaths. Non-small-cell lung cancers (NSCLCs) constitute about 85% of lung cancers and the 5-year survival rate is currently below 20%. Only a limited number of NSCLC patients, carrying alterations in specific genes, can benefit from small molecules therapies, highlighting the need for new treatment strategies to improve the outcome of the remaining patients. KRAS is among the most frequently mutated oncogene in NSCLC and 90% of the mutations affect codon 12, with the G12C substitution being the most frequent. KRAS mutations in NSCLC are supposed to be associated to a poor prognosis and poor response to chemotherapy. Despite KRAS being one of the earliest known oncogenic drivers in NSCLC, it is considered practically undruggable. Mutations in KRAS gene lead to the activation of PI3K/akt/mTOR pathway, whose effective inhibition remains a challenging clinical target. Since PI3K/akt/mTOR pathway and KRAS oncogene mutations have both a role in cancer cell metabolism, we investigated whether the activity of PI3K/akt/mTOR inhibitors (BEZ235 and BKM120) in cells harboring different KRAS status is related to their effect at metabolic level.A targeted metabolomics approach was applied to a robust and well characterized isogenic system to profile the metabolic adaptations occurring in KRAS-G12C and KRAS-wild type (WT) cells in response to treatment with BEZ235 and BKM120. KRAS-G12C and KRAS-WT harboring cells displayed similar sensitivities to BEZ235 and BKM120 treatments. Metabolomics analysis indicated that the different KRAS isoforms induced a distinct metabolic response to PI3K inhibitor treatments. In particular, impairment of glutamine and serine metabolism, in KRAS-G12C and KRAS-WT respectively, was observed after pharmacological blockade of the PI3K signaling. In addition, PI3K inhibitors caused autophagy in KRAS-WT isoform, but not in KRAS-G12C, where a striking decreased in ammonia production was found as probable consequence of glutamine metabolism impairment. At doses relevant for autophagy, differences in apoptosis and cell cycle phase distribution were not detected in KRAS-WT and KRAS-G12C clones. These preliminary results would set the basis for more effective therapeutic combinations possibly exploiting the different metabolic response to PI3K/akt/mTOR inhibitors in NSCLC cells harboring a different KRAS status. Citation Format: Elisa Caiola, Laura Brunelli, Mirko Marabese, Roberta Pastorelli, Monica Lupi, Massimo Broggini. PI3K pathway inhibition induces a different metabolic response in NSCLC cells harboring WT and G12C mutant KRAS. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 226.
Effects of nutraceutical intervention on serum proteins in aged rats (2020)

Aging is associated with many pathophysiological changes that could lead to the onset of degenerative disease. Some of the physiological changes that occur with aging include increased inflammation and decreased stem cell proliferation, leading to decreased capacity for tissue regeneration and loss of function. In previous studies, we and others have found nutraceutical intervention to ameliorate some of the deleterious effects associated with aging. In particular, we have previously shown that NT-020, a supplement composed of a proprietary blend of blueberries, green tea, vitamin D3, and carnosine, is able to rescue age-related cognitive deficits, impaired neurogenesis, and inflammation in rats. We have also previously demonstrated that stem cells cultured with old serum showed decreased proliferation; however, when stem cells were cultured in serum from old rats given a diet supplemented with NT-020, proliferation did not differ from that of cells cultured with serum from young rats. While it is clear that NT-020 is exerting a therapeutic, anti-aging effect, the mechanisms of action were yet to be fully elucidated.To that end, in the present study, we conducted a bioinformatics experiment to examine the rat proteome of serum from young and old control rats and young and old rats given a diet supplemented with NT-020. Serum from old rats showed an increase in some inflammatory and pro-aging factors while serum from old rats given a diet supplemented with NT-020 showed an increase in some anti-aging factors, most notably proteins associated with the complement system and autophagy. A number of immune functions that increase with age were shown to be downregulated with NT-020 treatment.
Transspecies Transmission of the Endogenous Koala Retrovirus (2006)

The koala retrovirus (KoRV) is a gammaretrovirus closely related to the gibbon ape leukemia virus and induces leukemias and immune deficiencies associated with opportunistic infections, such as chlamydiosis. Here we characterize a KoRV newly isolated from an animal in a German zoo and show infection of human and rat cell lines in vitro and of rats in vivo, using immunological and PCR methods for virus detection. The KoRV transmembrane envelope protein (p15E) was cloned and expressed, and p15E-specific neutralizing antibodies able to prevent virus infection in vitro were developed. Finally, evidence for immunosuppressive properties of the KoRV was obtained.
Rational Design, Exploratory Synthesis and Lanthanide Emission Efficiency Comparison of Lanthanide(III)-cored Complexes Based on Naphthalene Acid Ligands for Efficient Energy Transfer Pathways (2006)

E-mail: hwanm@kki mail.hannamakrc..Received August 7, 2006Key Words : Naphthalene acid, Lanthanide complexes, Near-infrared emission, Energy transfer processThe development of luminescent lanthanide complexeshas been attracted considerable attention because of a widevariety of applications, such as planar waveguide ampli-fiers,
The Role of Transesophageal Echocardiography During Port‐Access Minimally Invasive Cardiac Surgery (1999)

The recent development of endovascular catheters that are placed via the femoral artery and vein has enabled patients to be placed on cardiopulmonary bypass without the need for direct visualization of the heart or great vessels via sternotomy. This has allowed cardiac surgery to be performed through smaller, thoracotomy incisions. Placement of these catheters initially was performed under fluoroscopic guidance, which has major imaging limitations. Now, transesophageal echocardiography (TEE) has replaced fluoroscopy as the primary imaging technique to assist in the placement of endovascular catheters during minimally invasive, port-access cardiac surgery. In our institution, 449 port-access procedures have been performed from May 1996 through July 1998. We found that TEE is able to adequately visualize the cardiac structures and assist in the placement of the endovascular catheters in all patients. Fluoroscopy is helpful only as an aid to the use of TEE for placement of the coronary sinus catheter.
Modification and Optimization of Conducting Polymer-Modified, Redox-Magnetohydrodynamics (R-MHD) Pumping for Enhanced and Sustained Microfluidics Applications (2019)

In this work, a novel microfluidic pumping approach, redox-magnetohydrodynamics (R-MHD) has improved by materials and device optimization to use in lab-on-a-chip applications. In R-MHD, magnetic flux (B) and ionic current density (j) interacts to generate body force (FB) in between active electrodes, according to the equation FB = j×B. This unique fluid pumping approach is scalable, tunable, generates flat flow profile, and does not require any channels or valves. Pumping performance, such as speed scales with the ionic current density (j) and duration depends on the total charge (Q). The ionic current density (j) results from the conversion of electronic current through redox reactions of a conducting polymer like PEDOT (poly-EDOT). The enhancement of j can be obtained by the modification of polymer morphology. Therefore, electropolymerization parameters such as solvent, monomer, electrolyte, and deposition method have been optimized to improve the electrochemical performance of PEDOT. Electrodeposited PEDOT film from propylene carbonate solvent and TBAPF6 electrolyte generated a maximum of 820 µm/s flow velocity and 210 s flow duration. This enhanced system used as an imaging cytometer by coupling with a light sheet confocal microscope. This microfluidic imaging platform was able to differentiate various leukocytes cells with ~ 5000 cell/s theoretical throughput and 0.6 µm image resolution. As, our existing microscope could not analyze the R-MHD velocity profile in height direction, astigmatism particle tracking velocimetry (APTV) was employed to analyze flow profiles in three dimensions. In a microfluidic setup, flow profile is dominated by stream wise component but with no significant contributions in y and z direction. Though we achieved significant improvement in fluidic speed, flow duration was still dependent upon the total charge. Therefore, an automated magnet switching device was built which synchronized the current and magnetic field to push fluid in single direction, for unlimited time.
Audio Interview: Studying Potential Covid-19 Therapies (2020)

Studying Potential Covid-19 Therapies In this audio interview conducted on May 6, 2020, the editors discuss how to assess observational studies of potential Covid-19 therapies and the results of ne...
Popliteal artery injury complicating arthroscopic meniscectomy (1995)

We describe two patients who sustained serious vascular complications following arthroscopic lateral meniscectomy. Such injuries are rarely encountered or reported in the literature and, as such, the potential catastrophic sequelae of this particular complication of arthroscopy may be underestimated. Investigation of suspected popliteal artery injuries is outlined and the need for a high index of suspicion and early referral to a vascular surgeon is stressed.
The role of GM-CSF in adipose tissue inflammation (2008)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine that has a central action to reduce food intake and body weight. Consistent with this, GM-CSF knockout mice are more obese and hyperphagic than wild-type mice. However, in lung, GM-CSF is an important determinant of macrophage infiltration. Consequently, we sought to determine if GM-CSF might contribute to adipose tissue macrophage accumulation, insulin resistance, and low-grade inflammation that occurs when animals gain weight on a high-fat diet (HFD). We therefore determined how targeted genetic disruption of GM-CSF can affect adipose tissue macrophage and cytokine gene expression as well as glucose homeostasis by performing hyperinsulinemic-euglycemic clamps. The number of macrophages and CCR2 gene expression in adipose tissue of GM-CSF knockout mice was decreased relative to those in wild-type mice, and the adipocyte size of mesenteric fat was increased in GM-CSF knockout mice on a HFD compared with wild-type mice. The level of mRNA of the proinflammatory cytokines interleukin-1beta, tumor necrosis factor-alpha, and macrophage inflammatory protein-1alpha was significantly lower in mesenteric fat of GM-CSF knockout mice on the HFD than in wild-type mice. Using the hyperinsulinemic-euglycemic clamp technique, GM-CSF knockout mice had greater overall insulin sensitivity. This increase was due to enhanced peripheral uptake and utilization of glucose rather than to increased hepatic insulin sensitivity. Collectively, the data suggest that the GM-CSF knockout mutation ameliorates peripheral insulin resistance in spite of increased adiposity by reducing inflammation in adipose tissue in response to a HFD.
Efficiency of insertion versus replacement vector targeting varies at different chromosomal loci. (1994)

We have analyzed the targeting frequencies and recombination products generated with isogenic vectors at the fah and fgr loci in embryonic stem cells. A single vector which could be linearized at different sites to generate either a replacement or an insertion vector was constructed for each locus. A replacement event predominated when the vectors were linearized at the edge of the homologous sequences, while an insertion event predominated when the vectors were linearized within the homologous sequences. However, the ratio of the targeting frequencies exhibited by the different vector configurations differed for the two loci. When the fgr vector was linearized as an insertion vector, the ratio of targeted to random integrations was four- to eightfold greater than when the vector was linearized as a replacement vector. By contrast, the ratio of targeted to random integrations at the fah locus did not vary with the linearization site of the vector. The different relationships between the targeting frequency and the vector configuration at the fgr and fah loci may indicate a DNA sequence or chromatin structure preference for different targeting pathways.
Spectral Karyotypic and Comparative Genomic Analysis of the Endocrine Pancreatic Tumor Cell Line BON-1 (2009)

BON-1 is a human serotonin-producing endocrine pancreatic tumor (EPT) cell line, which has been used for various studies of tumorigenesis and treatment. Because its genotype, phenotype and degree of differentiation may underlie events that are instrumental to the development of endocrine tumors and, moreover, may vary between labs and over time, we decided to comprehensively characterize the chromosomal constitution of BON-1 by applying conventional GTG-banding, spectral karyotyping (SKY), comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). BON-1 cells proved to be hyperdiploid containing a modal chromosome number of 57 (range 56-64). SKY identified a stemline containing 6 clonal aberrations including del(1p), t(9;12)del(9p)x2, der(10)t(5;10), der(19)t(8;19), der(14)t(9;14)t(9;10), and a sideline harboring an additional del(12q). CGH and FISH confirmed the SKY results and, in addition, highlighted the chromosomal regions involved in the rearrangements. Moreover, they identified a homozygous deletion of the key tumor suppressor genes CDKN2A and CDKN2B at 9p21.3, in accordance with absence of p16(INK4A) and p14(ARF) expression as revealed by immunocytochemistry. Apart from deregulation of the cell cycle and p53 pathway this finding indicates escape from replicative senescence (induced by mutated NRAS) and detachment-induced apoptosis as molecular mechanisms underlying the tumorigenesis of BON-1 cells. Immunostaining results for p53, MDM2 and pRb expression were consistent with previously published data using Western analysis. In conclusion, we provide here a comprehensive cytogenetic profile of BON-1. This cell line harbors both numerical and structural genomic alterations indicative for malignant EPTs.
Isocitrate-dehydrogenase-mutant lower grade glioma in elderly patients: treatment and outcome in a molecularly characterized contemporary cohort (2023)

Abstract Purpose Lower-grade glioma (LGG) is rare among patients above the age of 60 (“elderly”). Previous studies reported poor outcome, likely due to the inclusion of isocitrate dehydrogenase (IDH) wildtype astrocytomas and advocated defensive surgical and adjuvant treatment. This study set out to question this paradigm analyzing a contemporary cohort of patients with IDH mutant astrocytoma and oligodendroglioma WHO grade 2 and 3. Methods Elderly patients treated in our department for a supratentorial, hemispheric LGG between 2009 and 2019 were retrospectively analyzed for patient-, tumor- and treatment-related factors and progression-free survival (PFS) and compared to patients aged under 60. Inclusion required the availability of subtype-defining molecular data and pre- and post-operative tumor volumes. Results 207 patients were included, among those 21 elderlies (10%). PFS was comparable between elderly and younger patients (46 vs . 54 months; p = 0.634). Oligodendroglioma was more common in the elderly (76% vs . 46%; p = 0.011). Most patients underwent tumor resection (elderly: 81% vs . younger: 91%; p = 0.246) yielding comparable residual tumor volumes (elderly: 7.8 cm 3 ; younger: 4.1 cm 3 ; p = 0.137). Adjuvant treatment was administered in 76% of elderly and 61% of younger patients (p = 0.163). Uni- and multi-variate survival analyses identified a tumor crossing the midline, surgical strategy, and pre- and post-operative tumor volumes as prognostic factors. Conclusion Elderly patients constitute a small fraction of molecularly characterized LGGs. In contrast to previous reports, favorable surgical and survival outcomes were achieved in our series comparable to those of younger patients. Thus, intensified treatment including maximal safe resection should be advocated in elderly patients whenever feasible.
NEUROPATHOLOGICAL EFFECTS OF INTRACEREBRAL PLATINUM SALT INJECTIONS (1977)

Multiple intracerebral injections of a mixture of platinum salts were made in 9 adult cats and the brains studied by light and electron microscopy at 5-12 days post injection. At the center of the lesions normal cortical architecture was completely replaced by edematous areas containing lipid-laden macrophages and cellular debris. The lesion periphery was characterized by perivascular edema and degenerative changes including cytoplasmic lipid inclusions and vacuolations with selective vulnerability of neurons. Membranous cytoplasmic bodies (MCB), zebra bodies and multiple nucleoli were observed in several cell types. This ultrastructural pattern, mimicked to some extent, that observed following electrical stimulation of brain following chronically implanted platinum and rhodium electrodes. The induction of zebra bodies and MCB, both of which are morphologic features of human neurolipidoses associated with congenital enzyme deficiencies, suggests an inhibitory effect of platinum on brain enzymes. Functional electrical stimulation of brain and other organs is currently being employed in a wide variety of clinical applications (14, 15). A mandatory consideration is that of the long-term effects of the stimuli as well as the electrodes themselves on the tissues involved. The histological effects and mechanisms of tissue damage following chronic application of electrical stimuli to brain have been the subject of several investigations in this laboratory (1, 14-18). Factors contributing to neural damage induced by electrical stimulation include noxious products resulting from electrode dissolution. In vitro studies employing electrochemical (3,9) and scanning electron microscopy (6) techniques have established that erosion of noble metal electrodes occurs, even when passing relatively small stimulation currents. Such electrode dissolution is of particular importance in long term applications of neural prostheses. The present study was initiated to assess the contribution of platinum electrode erosion products to neurla damage following electrical stimulation of brain, specifically to distinguish morphological changes resulting directly from electrode solubilization as opposed to electrical factors. Accordingly, intracerebral injections of graded volumes of platinum salts were made in an attempt to stimulate the presence of platinum electrode dissolution products.
Convergent, Parallel Synthesis of a Series of β‐Substituted 1,2,4‐Oxadiazole Butanoic Acids as Potent and Selective α<sub>v</sub>β<sub>3</sub> Receptor Antagonist. (2006)

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, please click on HTML or PDF.
Fractionation of ‘water-soluble lignocellulose’ into C<sub>5</sub>/C<sub>6</sub> sugars and sulfur-free lignins (2014)

Lignocellulose undergoes deep depolymerization by mechanocatalysis, quantitatively forming ‘water-soluble lignocellulose’. The saccharification of the aqueous ‘wood solution’ at 140 °C for 1 h forms C<sub>5</sub> and C<sub>6</sub> sugars at high yields in addition to sulfur-free lignins.
Gradient Magnitude Similarity Deviation: A Highly Efficient Perceptual Image Quality Index (2014)

It is an important task to faithfully evaluate the perceptual quality of output images in many applications, such as image compression, image restoration, and multimedia streaming. A good image quality assessment (IQA) model should not only deliver high quality prediction accuracy, but also be computationally efficient. The efficiency of IQA metrics is becoming particularly important due to the increasing proliferation of high-volume visual data in high-speed networks. We present a new effective and efficient IQA model, called gradient magnitude similarity deviation (GMSD). The image gradients are sensitive to image distortions, while different local structures in a distorted image suffer different degrees of degradations. This motivates us to explore the use of global variation of gradient based local quality map for overall image quality prediction. We find that the pixel-wise gradient magnitude similarity (GMS) between the reference and distorted images combined with a novel pooling strategy-the standard deviation of the GMS map-can predict accurately perceptual image quality. The resulting GMSD algorithm is much faster than most state-of-the-art IQA methods, and delivers highly competitive prediction accuracy. MATLAB source code of GMSD can be downloaded at http://www4.comp.polyu.edu.hk/~cslzhang/IQA/GMSD/GMSD.htm.
Population depletion activates autonomous CD154-dependent survival in biopsylike Burkitt lymphoma cells (2002)

Population size is governed through cells reacting to a variety of intrinsic and extrinsic cues. Tumors, while liberated from many of the homeostatic constraints placed on physiologic counterparts, can nonetheless remain subject to both social and environmental control. Burkitt lymphoma cells faithful to the biopsy phenotype were used to model the reliance of the colony, if any, on an inbuilt population sensor. Below a normally suicidal threshold number of cells, low picomolar quantities of exogenous CD40 ligand (CD40L/CD154) were found to sustain the clone without the discernible shift in phenotype that accompanies high CD40L encounter. Although CD154 was undetectable in populous cultures, message was induced as numbers became limiting. Correspondingly, attempts to neutralize endogenous CD40L activity failed to perturb cells at optimal densities but resulted in their marked decline as the critical threshold was approached. These data reveal an auto-inducible survival mechanism seemingly regulated through the monitoring of population size, a process somewhat akin to that of "quorum sensing" among gram-negative bacteria in which diffusible molecules provide a means of communication to coordinate gene expression with population density. This process could be activated as cells discern depletions in their community or when deprived of signals otherwise furnished within an appropriate environmental niche.