gebhart/patrepeval huggingface dataset:
Bond selective photochemistry in CH2BrI through electronic excitation at 210 nm (1986)

To explore the possibility of bond selective photochemistry in an excited electronic state, we have studied the photolysis of CH2BrI in a molecular beam at 210 nm. Following the direct local excitation of a repulsive transition on the C–Br bond at 210 nm, the fragments were detected by time-of-flight mass spectrometry. The dominant channel was found to be C–Br fission (60%) releasing an average of 15 kcal/mol into translation with the remainder reacting to form CH2+IBr and CH2+I+Br. There was no evidence for the primary fission of the C–I bond, making this the first clear example of the selective cleavage of a stronger bond in a molecule over the weakest one.
Reserva de accion civil: formulación fuera de tiempo (2008)

We report the results of low temperature transport, specific heat, and magnetization measurements on high quality single crystals of the bilayer perovskite Sr3Ru2O7, which is a close relative of the unconventional superconductor Sr2RuO4. Metamagnetism is observed, and transport and thermodynamic evidence for associated critical fluctuations is presented. These relatively unusual fluctuations might be pictured as variations in the Fermi surface topography itself.
CYCLOPHILIN, A PRIMARY MOLECULAR TARGET FOR CYCLOSPORINE (1988)

An understanding of the mechanism of action of cyclosporine requires the identification and functional characterization of its molecular target or targets in the cell. Our laboratory has presented evidence that cyclophilin (CYP), a low-molecular-weight (Mr 17,737) basic protein, is the primary cytosolic receptor for CsA. The high affinity of CYP for CsA (Kd 30 nM) and specificity for immunosuppressive cyclosporine analogs implicate CYP as a pivotal regulator of T cell and B cell activation. CYP exists in at least two isoforms, is abundant (0.05% to 0.4% of total protein) in the cytosol, and is ubiquitous in cells and tissues of eukaryotic organisms. Its amino acid sequence is highly conserved and there is strong evidence that CYP is a member of a new multigene family. These features suggest that one or more CYP isoforms must play a crucial role in lymphocyte activation and perhaps a multifunctional role in cellular physiology. The ability of CsA to suppress expression of several lymphokine and proto-oncogene products via a transcriptional control mechanism suggests that CYP may function at some level in a signaling pathway linking membrane receptor stimulation to gene regulatory elements in lymphocytes, and possibly nonlymphoid cell types as well.
How to make spinal motor neurons (2014)

All muscle movements, including breathing, walking, and fine motor skills rely on the function of the spinal motor neuron to transmit signals from the brain to individual muscle groups. Loss of spinal motor neuron function underlies several neurological disorders for which treatment has been hampered by the inability to obtain sufficient quantities of primary motor neurons to perform mechanistic studies or drug screens. Progress towards overcoming this challenge has been achieved through the synthesis of developmental biology paradigms and advances in stem cell and reprogramming technology, which allow the production of motor neurons in vitro. In this Primer, we discuss how the logic of spinal motor neuron development has been applied to allow generation of motor neurons either from pluripotent stem cells by directed differentiation and transcriptional programming, or from somatic cells by direct lineage conversion. Finally, we discuss methods to evaluate the molecular and functional properties of motor neurons generated through each of these techniques.
NKTR-214 (CD122-biased agonist) plus nivolumab in patients with advanced solid tumors: Preliminary phase 1/2 results of PIVOT. (2018)

3006 Background: PIVOT is an ongoing, open-label, phase 1/2 study of NKTR-214 (214; CD122-biased agonist) plus PD-1 inhibitor nivolumab (N) in patients (pts) with advanced cancers (MEL, RCC, NSCLC, TNBC, and UC). 214 monotherapy increases newly proliferative CD8+ T cells in tumors and increases cell surface PD-1 and PD-L1 expression, demonstrating a potentially synergistic mechanism with anti-PD-1 therapy. Methods: In P1 dose escalation, pts received 214 (0.003, 0.006 or 0.009 mg/kg) with N (240 mg or 360 mg) administered IV as outpatient Q2W or Q3W; in P2 expansion, the RP2D of 214 (0.006 mg/kg) with N (360 mg) Q3W was administered concurrently. Response was assessed Q8W by RECIST v1.1. Matched tumor samples were evaluated for changes from baseline in immune cell populations, gene expression, and T cell receptor repertoire. Tumor baseline and on treatment PD-L1 protein expression was assessed (28-8 IHC assay). Results: As of 7FEB2018, 162 pts (P1, n = 38; P2, n = 124) were evaluable for safety. The most common TRAEs of all grades at the RP2D ( > 25%) in pts were flu-like symptoms (63%), fatigue (39%), rash (38%) and pruritus (30%). G3+ TRAEs at the RP2D were 11%. No pts discontinued treatment or died from TRAEs. A total of 60 IO-treatment naïve stage IV pts (P1, n = 30; P2, n = 30) were efficacy evaluable (≥1 scan) (23 MEL, 24 RCC, 6 NSCLC, 4 UC, 3 TNBC). 22/30 P2 pts had only 1 scan. ORR (CR+PR) and DCR (CR+PR+SD) in 23 MEL (1L) pts was 52% and 78%. 18/23 MEL pts had known PD-L1 status. ORR was 5/9 (56%) for PD-L1(+) pts and 4/9 (44/%) for PD-L1(-) pts. ORR and DCR in 24 RCC (1L) pts was 54% and 79%. 20/24 RCC pts had known PD-L1 status. ORR was 4/7 (57%) for PD-L1(+) pts and 7/13 (54%) for PD-L1(-) pts. ORR and DCR in 6 NSCLC (1-2L) pts was 50% and 67%. 5/6 pts had known PD-L1 status. ORR was 3/5 (60%) in PD-L1(-) pts. ORR and DCR in 4 UC (1L) was 75% and 100%. ORR/DCR in 3 TNBC (1- 2L) pts was 33%. In 60 evaluable pts, 32/32 responses are ongoing (0.3+ to 12.0+ mos) with 45/60 pts still on treatment. Conclusions: 214 plus N was well-tolerated with no TRAE discontinuations. Preliminary efficacy shows encouraging ORR/DCR with responses observed in 5 of 5 tumor types in I-O treatment naïve 1-2L pts. Updated data to be presented. Clinical trial information: NCT02983045.
Unbundled and Highly Functionalized Carbon Nanotubes from Aqueous Reactions (2003)

In this communication, we show that aryldiazonium salts can react efficiently with individual SDS-coated SWNTs in water to form aryl functionalized SWNTs. Remarkably, the resulting SWNTs have up to 1 in 9 carbons along their backbones bearing an organic moiety and they remain unbundled throughout their entire lengths, even with these relatively small functional moieties.
mTOR in renal cell cancer: modulator of tumor biology and therapeutic target (2009)

Elucidation of the crucial role of the PI3K/Akt/mTOR pathway in the pathogenesis of cancer has led to the development of various drugs targeting this signaling cascade at distinct levels. mTOR, a serine/threonine kinase plays a pivotal role in coupling growth stimuli to cell cycle progression. There are two distinct macromolecular complexes of mTOR: mTORC1, which is rapamycin-sensitive and contains raptor; and mTORC2, which is rapamycin-insensitive and contains rictor. However, in recent preclinical studies a sustained exposure of cancer cells to rapamycin has been shown to inhibit the function of both mTORC1 and mTORC2 complexes. Downstream targets of these complexes, which involve HIF-1alpha and HIF-2alpha, cyclin D1 and PKC-alpha, are responsible for the activation of various intracellular processes leading to the activation of cell proliferation, and induction of angiogenesis, metastasis or chemoresistance. Since the biology of renal cell cancer (RCC) is tightly controlled by mTOR, targeted inhibition of mTOR function appeared to be a promising therapeutic approach for RCC patients. To date, results of two, large, Phase III clinical trials evaluating the efficacy of rapamycin derivatives (i.e., temsirolimus and everolimus) in the treatment of RCC have been published. First-line temsirolimus (CCI-779) administered to metastatic, poor-prognosis RCC patients significantly prolonged overall and progression-free survival when compared with IFN-alpha. Treatment of metastatic RCC patients refractory to tyrosine kinase inhibitors with everolimus (RAD-001) significantly prolonged progression-free survival when compared with placebo. Therapeutic strategies based on mTOR inhibition in RCC demonstrated a significant clinical activity. However, there are still patients refractory to mTOR inhibitors. Various molecular mechanisms of resistance to rapalogues have been identified and will have to be targeted simultaneously with mTOR in order to achieve a complete inhibition of signaling pathways crucial for the pathogenesis of RCC. Such clinical trials evaluating a combination of mTOR inhibitors with other targeted therapies are ongoing.
Resveratrol Induces the Heat-Shock Response and Protects Human Cells from Severe Heat Stress (2007)

Molecular chaperones play key roles in protein quality control, signal transduction, proliferation, and cell death, and confer cytoprotection and assure survival after environmental stress. The heat-shock response is implicated in a variety of conditions including ischemic diseases, infection and immunity, neurodegeneration, and aging. Physiologic and pharmacologic chaperone inducers were shown to be an efficient therapeutic approach in different acute and chronic diseases. Here we characterize resveratrol, a polyphenol from red wine, as an inducer of the heat-shock response. Resveratrol activated the heat-shock promoter and the expression of the major chaperone Hsp70 in cell lines and in human peripheral lymphocytes, comparable to moderate heat stress. This effect was not due to its antioxidant property, because 5 mM N-acetylcysteine was unable to activate the heat-shock response. Moreover, resveratrol failed to upregulate Grp78, and tunicamycin was unable to induce Hsp70, suggesting that the resveratrol-induced heat-shock response was not mediated by canonic endoplasmic reticulum stress. Resveratrol synergized with mild to moderate heat shock and conferred cytoprotection against severe heat stress. Our results reveal resveratrol as a chaperone inducer that may contribute to its pleiotropic effects in ameliorating stress and promoting longevity.
FUNCTIONAL ACTIVITY OF ANTI-C6 ANTIBODIES ELICITED IN C6-DEFICIENT RATS RECONSTITUTED BY LIVER ALLOGRAFTS (1996)

A critical role of the complement membrane attack complex (C5b-9) in mediating hyperacute rejection has been demonstrated previously in fully C6-deficient PVG (C-)(RT1c) rats that reject guinea pig cardiac xenografts at a delayed tempo (45 +/- 9 hr; n=16) compared with C6-sufficient PVG (C+)(RT1c) hosts (0.5 +/- 2 hr; n=6). We have investigated whether selective depletion of C6 from Lewis rats by antibody therapy prevents hyperacute rejection. A polyclonal rat-antirat C6 antibody was induced in PVG (C-) recipients by orthotopic liver transplants from congenic PVG (C+) donors. These liver grafts produced high levels of C6 that reconstituted the complement function of PVG (C-) hosts by 7 days, but the recipients responded within 28 days with the synthesis of an IgG1 antibody to rat C6. The antiserum inhibited hemolytic complement activity of Lewis (RT1(1)) rats in vivo and in vitro. The effect of C6 depletion on Xg survival was investigated by injecting Lewis rats with 2 ml of rat-antirat C6 antiserum before and 1 ml after reperfusion of the guinea pig cardiac xenograft. Lewis rats rejected guinea pig cardiac xenografts after treatment with this rat-antirat C6 antiserum in 38 +/ -11 hr (n=3). Treatment with normal control sera from PVG (C-) rats did not prolong guinea pig cardiac xenograft survival in the Lewis rats (1 +/- 0.7 hr; n=3)(P<0.0043). Injection of 3 ml of the IgG fraction purified from the rat-antirat C6 antibody (33 mg/ml) prolonged xenograft survival to 13.6 +/- 4 hr (n=4) compared with the survival of 0.61 +/- 0.3 hr (n=4) after injection of control rat IgG (33 mg/ml) (P<0.005). These results demonstrate that specific depletion of C6 by antibody therapy has a significant effect on guinea pig cardiac xenograft survival in the Lewis rat. These findings further suggest that C6 depletion may be beneficial to patients undergoing hyperacute rejection of xenografts or allografts.
In vitro formation of tetraploid rat blastocysts after fusion of two‐cell embryos (2002)

Gene targeting technology is not available in the rat which is an animal model of major importance, e.g., in cardiovascular research. This is due to the fact that the rat embryonic stem cell (ESC)-like cells established by several groups do not form germ-line chimeras when injected into blastocysts. In the mouse, the aggregation of ESC with tetraploid embryos has allowed the generation of animals completely derived from these cells. However, aggregation of rat ESC-like cells with tetraploid rat embryos has not yet been attempted to evaluate their developmental capacity. Therefore, we established a method to produce tetraploid rat embryos by fusion at the two-cell stage. Chemical fusion by polyethylene glycol (PEG) was shown to be less efficient (56.3% fused embryos) than electrofusion (96.1% fused embryos). The rate of development of fused embryos to blastocysts was independent of the fusion method and similar to the rate of control embryos. However, this rate was lower when the embryos had been cultured from the zygote state before fusion (14-20%) compared to freshly isolated two-cell embryos (41-63%). Alike for the mouse, blastocysts derived from fused two-cell rat embryos contained about half the number of cells as control blastocysts and were homogeneously tetraploid with no evidence of mosaicism. This method may be useful for the establishment of gene-targeting technology in the rat.
Linux Device Drivers, 3rd Edition (2005)

Device drivers literally drive everything you're interested in--disks, monitors, keyboards, modems--everything outside the computer chip and memory. And writing device drivers is one of the few areas of programming for the Linux operating system that calls for unique, Linux-specific knowledge. For years now, programmers have relied on the classic Linux Device Drivers from O'Reilly to master this critical subject. Now in its third edition, this bestselling guide provides all the information you'll need to write drivers for a wide range of devices. Over the years the book has helped countless programmers learn:how to support computer peripherals under the Linux operating systemhow to develop and write software for new hardware under Linuxthe basics of Linux operation even if they are not expecting to write a driver The new edition of Linux Device Drivers is better than ever. The book covers all the significant changes to Version 2.6 of the Linux kernel, which simplifies many activities, and contains subtle new features that can make a driver both more efficient and more flexible. Readers will find new chapters on important types of drivers not covered previously, such as consoles, USB drivers, and more. Best of all, you don't have to be a kernel hacker to understand and enjoy this book. All you need is an understanding of the C programming language and some background in Unix system calls. And for maximum ease-of-use, the book uses full-featured examples that you can compile and run without special hardware. Today Linux holds fast as the most rapidly growing segment of the computer market and continues to win over enthusiastic adherents in many application areas. With this increasing support, Linux is now absolutely mainstream, and viewed as a solid platform for embedded systems. If you're writing device drivers, you'll want this book. In fact, you'll wonder how drivers are ever written without it.
Glycals in Organic Synthesis: The Evolution of Comprehensive Strategies for the Assembly of Oligosaccharides and Glycoconjugates of Biological Consequence (1996)

Abstract This review provides a personal account of the explorations of a research group in oligosaccharide and glycoconjugate construction. The journey began twenty years ago with the study of Diels–Alder reactions of complex dienes. By extending this methodology to aldehydo‐type heterodienophile equivalents, access to unnatural glycals was gained (LACDAC reaction). From this point a broad‐ranging investigation of the use of glycals in the synthesis of oligosaccharides and other glycoconjugates was begun. Mobilization of glycals both as glycosyl donors and glycosyl acceptors led to the strategy of glycal assembly. Several new glycosylation techniques were developed to provide practical underpinning for this logic of glycal assembly. Glycal‐based paradigms have been shown to be nicely adaptable to solid phase supported synthesis. Moreover, glycal assembly—both in solution and on solid phases—has been used to gain relatively concise and efficient entry to a variety of biologically interesting and potentially valuable constructs. Some of these syntheses, particularly in the field of tumor antigens, have led to novel compounds which are in the final stages of preclinical assessment. This review presents an account of the chemical reasoning at the center of the program.
Interleukin 22 Is a Candidate Gene forTmevp3, a Locus Controlling Theiler's Virus-Induced Neurological Diseases (2007)

After intracerebral inoculation, Theiler's virus induces in its natural host, the mouse, an acute encephalomyelitis followed, in susceptible animals, by chronic inflammation and primary demyelination. Susceptibility to demyelination among strains of laboratory mice is explained by the capacity of the immune system to control viral load during persistence. Also, differences of susceptibility to viral load between the susceptible SJL strain and the resistant B10.S strain are mainly due to two loci, Tmevp2 and Tmevp3, located close to the Ifng locus on chromosome 10. In this article, we show that the Tmevp3 locus controls both mortality during the acute encephalomyelitis and viral load during persistence. Most probably, two genes located in the Tmevp3 interval control these two different phenotypes with efficiencies that depend on the age of the mouse at inoculation. Il22, a member of the IL-10 cytokine family, is a candidate gene for the control of mortality during the acute encephalomyelitis.
Structural and optical quality of GaN/metal/Si heterostructures fabricated by excimer laser lift-off (1999)

Gallium nitride (GaN) thin films grown on sapphire substrates were successfully bonded and transferred onto Si substrates using a Pd–In metallic bond. After bonding, a single 600 mJ/cm2, 38 ns KrF (248 nm) excimer laser pulse was directed through the transparent sapphire followed by a low-temperature heat treatment to remove the substrate. Channeling-Rutherford backscattering measurements revealed the thickness of the defective interfacial region to be approximately 350 nm. The full width at half maximum, low-temperature (4 K), donor-bound exciton photoluminescence (PL) peak was larger by 25% on the exposed interfacial layer compared to the original GaN surface. Ion milling of the exposed interface to a depth of 400 nm was found to remove the interfacial layer and associated defects. The minimum channeling yield and PL linewidths from the exposed interface were found to be comparable to those obtained from the original GaN surface after ion milling.
Dynamics of Radiation Damage in a Body-Centered Cubic Lattice (1964)

Radiation damage has been studied by numerically integrating the equations of motion of a large set of atoms on a high-speed computer. In this paper the method is applied to a model of $\ensuremath{\alpha}$ iron. Low energy events have been extensively investigated. The primary knock-on atom is found to initiate an extended sequence of correlated replacements, producing an interstitial at some distance and a vacancy on its original site. The interstitial is found to have a split configuration, as was found earlier in copper, but its axis lies along $〈110〉$. Collision chains are found to be prominent in $〈111〉$ and $〈100〉$, and attenuation rates and focusing parameters for these chains are determined. The threshold energy for displacing an atom is found to be highly dependent on the direction of the knock-on. The lowest threshold is found to be 17 eV, for knock-ons directed near $〈100〉$, and to be about 34 eV and 38 eV for those directed near $〈110〉$ and $〈111〉$, respectively. The probability of displacement for a randomly directed knock-on of energy $E$ is determined for $E$ between 0 and 60 eV. The results are in approximate agreement with experiments of Lucasson and Walker, although more structure is found in the calculated curve than could be tested by the experiments. Pronounced directional effects in low energy electron bombardments of $\ensuremath{\alpha}$ iron single crystals are predicted.
Inhibition of growth and induction of differentiation of colon cancer cells by peach and plum phenolic compounds. (2008)

The action of extracts from anthocyanin-enriched plums and peaches on growth and differentiation was studied with human colon cancer cells. Growth inhibitory effects were observed in Caco-2, SW1116, HT29 and NCM460 cells. In Caco-2 cells but not in the other cells studied there was evidence for increased differentiation as judged by increased activity of alkaline phosphatase and dipeptidyl peptidase. A differentiating effect on Caco-2 cells was not seen with cyanidin or cyanidin-3-glucoside but the action of the fruit extracts was additive with the action of butyrate and with the MEK1/2 inhibitor U0126. Fractionation using C18 indicated activity resided within a fraction containing anthocyanins but further fractionation using LH-20 suggested that most of the activity was in a fraction containing polyphenols other than anthocyanins. It was concluded that several peach and plum phenolic molecules can influence growth and differentiation in human colon cancer cells.
Reduction of Nitro-Substituted Tertiary Alkanes (1995)

In the course of preparing a series of convenient building blocks for the construction of cascade macromolecules, the need for facile, high yield procedures for amino-tert-alkanes from the corresponding nitroalkanes was apparent. This review summarizes the reduction of nitro-substituted tertiary alkanes.
The Efficient Functioning of Photosynthesis and Respiration in Synechocystis sp. PCC 6803 Strictly Requires the Presence of either Cytochrome c6 or Plastocyanin (2004)

In cyanobacteria, cytochrome c6 and plastocyanin are able to replace each other as redox carriers in the photosynthetic and respiratory electron transport chains with the synthesis of one or another protein being regulated by the copper concentration in the culture medium. However, the presence of a third unidentified electron carrier has been suggested. To address this point, we have constructed two deletion mutants of the cyanobacterium Synechocystis sp. PCC 6803, each variant lacking either the petE or petJ gene, which respectively codes for the copper or heme protein. The photoautotrophic and heterotrophic growth rate of the two mutants in copper-free and copper-supplemented medium as well as their photosystem I reduction kinetics in vivo were compared with those of wild-type cells. The two mutant strains grow at equivalent rates and show similar in vivo photosystem I reduction kinetics as wild-type cells when cultured in media that allow the expression of just one of the two electron donor proteins, but their ability to grow and reduce photosystem I is much lower when neither cytochrome c6 nor plastocyanin is expressed. These findings indicate that the normal functioning of the cyanobacterial photosynthetic and respiratory chains obligatorily depends on the presence of either cytochrome c6 or plastocyanin.
ChemInform Abstract: Reaction of C60F18 with Diethyl Bromomalonate: Diversion of the Bingel Reaction and Formation of the First 18π Annulenic Fullerene. (2002)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.