gebhart/patrepeval huggingface dataset:
Glucocorticoid-Dependent Hippocampal Transcriptome in Male Rats: Pathway-Specific Alterations With Aging (2013)

Although glucocorticoids (GCs) are known to exert numerous effects in the hippocampus, their chronic regulatory functions remain poorly understood. Moreover, evidence is inconsistent regarding the long-standing hypothesis that chronic GC exposure promotes brain aging/Alzheimer disease. Here, we adrenalectomized male F344 rats at 15 months of age, maintained them for 3 months with implanted corticosterone (CORT) pellets producing low or intermediate (glucocorticoid receptor-activating) blood levels of CORT, and performed microarray/pathway analyses in hippocampal CA1. We defined the chronic GC-dependent transcriptome as 393 genes that exhibited differential expression between intermediate and low CORT groups. Short-term CORT (4 days) did not recapitulate this transcriptome. Functional processes/pathways overrepresented by chronic CORT-up-regulated genes included learning/plasticity, differentiation, glucose metabolism, and cholesterol biosynthesis, whereas processes overrepresented by CORT-down-regulated genes included inflammatory/immune/glial responses and extracellular structure. These profiles indicate that GCs chronically activate neuronal/metabolic processes while coordinately repressing a glial axis of reactivity/inflammation. We then compared the GC transcriptome with a previously defined hippocampal aging transcriptome, revealing a high proportion of common genes. Although CORT and aging moved expression of some common genes in the same direction, the majority were shifted in opposite directions by CORT and aging (eg, glial inflammatory genes down-regulated by CORT are up-regulated with aging). These results contradict the hypothesis that GCs simply promote brain aging and also suggest that the opposite direction shifts during aging reflect resistance to CORT regulation. Therefore, we propose a new model in which aging-related GC resistance develops in some target pathways, whereas GC overstimulation develops in others, together generating much of the brain aging phenotype.
Water Dynamics:  Vibrational Echo Correlation Spectroscopy and Comparison to Molecular Dynamics Simulations (2004)

The dynamics of water are examined using ultrafast IR stimulated vibrational echo correlation spectroscopy. The OD hydroxyl stretch of HOD in H2O is probed with 45-fs pulses that have sufficient bandwidth (>400 cm-1) to span the entire broad spectrum. High-quality 2D correlation spectra are obtained having the correct phase relations across the broad hydroxyl band. The correlation spectra are found to evolve on multiple time scales. The time evolution of the vibrational echo correlation spectrum reflects the structural evolution of the hydrogen bond networks. The extended vibrational lifetime of the OD hydroxyl stretch of HOD in H2O facilitates the measurement of hydrogen bond dynamics for longer times than possible in previous studies of the OH stretch. Molecular dynamics simulations/electronic structure calculations are used to obtain the time correlation functions (TCF) for two water models, TIP4P and SPC/E. The TCFs are inputs to full time-dependent diagrammatic perturbation theory calculations, which yield theoretical correlation spectra. Quantitative comparison with the data demonstrates that the two water models somewhat overemphasize the fast fluctuations in water and do not contain a slow enough component to account for the slowest fluctuations. Fits to the data using a phenomenological triexponential TCF yield a slowest component of ∼2 ps, and TIP4P and SPC/E have slowest components of <1 ps. The TCF obtained from the water models and the triexponential TCF reproduce the linear absorption line shape equally well, but all miss to some extent the asymmetric “wing” on the low-energy side of the line. Therefore, the time dependence of the vibrational echo correlation spectra provides a good test for the TCF, but the absorption spectrum does not.
“Floating‐socket” total shoulder replacement: Anatomical, biomechanical, and surgical rationale (1978)

A prosthesis based on a new concept of gleno-humeral motion has been developed and clinically tested for the past 2 years. The "floating-socket" total shoulder replacement contains a nondislocatable, dual spherical bearing system consisting of a small sphere within a larger sphere with their centers offset to provide the physiologic "floating fulcrum" for mechanically advantageous motion. This geometric configuration allows a prosthetic range of motion in excess of anatomical limits to allow soft tissue structures to limit motion rather than mechanical impingement. The device is constructed from Co--Cr--Mo alloy and RCH-1000 polyethylene such that no metal--metal contact can occur. Experimental results in a 112-lb adult male chimpanzee and six clinical cases have revealed superior fixation strength of both glenoid and humeral components, as well as functional adaptation of the prosthesis without fracture of fixturing bone or prosthetic dislocation.
Induction and Bypass of p53 during Productive Infection by Polyomavirus (2002)

Lytic infection by polyomavirus leads to elevated levels of p53 and induction of p53 target genes p21Cip1/WAF1 (p21) and BAX. This is seen both in polyomavirus-infected primary mouse cell cultures and in kidney tissue of infected mice. Stabilization of p53 and induction of a p53 response are accompanied by phosphorylation of p53 on serine 18, mimicking a DNA damage response. Stabilization of p53 does not depend on p19Arf interaction with mdm2. Cells infected by a mutant virus defective in binding pRb and in inducing G(1)-to-S progression show a greatly diminished p53 response. However, cells infected by wild-type virus and blocked from entering S phase by addition of mimosine still show a p53 response. These results suggest a role of E2F target genes in inducing a p53 response. Polyomavirus large T antigen coprecipitates with p53 phosphorylated on serine 18 and also with p21Cip1/WAF1. Implications of these and other findings on possible mechanisms of induction and override of p53 functions during productive infection by polyomavirus are discussed.
Use of poly ADP-ribose polymerase [PARP] inhibitors in cancer cells bearing DDR defects: the rationale for their inclusion in the clinic (2016)

PARP inhibition is a potentially important strategy for managing a significant subset of tumors. The discovery of both germline and somatic DNA repair deficiencies in different cancer patients, together with the development of new PARP inhibitors that can kill selectively cancer cells is a potent example of targeting therapy to molecularly defined tumor subtypes.
Cross-regulation by XylR and DmpR activators of Pseudomonas putida suggests that transcriptional control of biodegradative operons evolves independently of catabolic genes (1994)

The Pu promoter of the toluene degradation plasmid pWW0 of Pseudomonas putida drives expression of an operon involved in the sequential oxidation of toluene and m- and p-xylenes to benzoate and toluates, respectively. Similarly, the Po promoter of plasmid pVI150 controls expression of an operon of Pseudomonas sp. strain CF600 which is required for the complete catabolism of phenol and cresols. These promoters, which both belong to the sigma 54-dependent class, are regulated by their cognate activators, XylR and DmpR, respectively. XylR and DmpR are homologous proteins, and both require aromatic compounds as effector molecules for activity. However, these two proteins respond to different profiles of aromatic compounds. The activity of each promoter in the presence of the heterologous regulator was monitored using lacZ and luxAB reporter systems. Genetic evidence is presented that the two activators can functionally substitute each other in the regulation of their corresponding promoters by binding the same upstream DNA segment. Furthermore, when coexpressed, the two proteins appear to act simultaneously on each of the promoters, expanding the responsiveness of these systems to the presence of effectors of both proteins. Potential mechanisms for the occurrence of evolutionary divergence between XylR and DmpR are discussed in view of the DNA sequence similarities among Pu, Po, and a third XylR-responsive promoter, Ps.
Sustainable Devices by Design: Thermal- and Plasma-Enabled Nanofabrication of Hierarchical Carbon Nanostructures for Bioelectronics and Supercapacitors (2017)

Graphene is promising to enable diverse technological advancements. However, major technical challenges arise in its fabrication and integration as active functional materials. This body of work exemplifies a host of thermal- and plasma-enabled techniques, designed to realize sustainable and controlled methodologies for nano-assembly. Importantly, these techniques may be tailored and broadly incorporated to harness the unique functional properties of graphene, and a host of other hierarchical nanomaterials. Together, these concepts may pave the realization of next-generation nanotechnologies which hold promise for a sustainable future.
Synthesis of 1,3-diol derivatives from sterically overcrowded oxiranes. Ring-opening reactions of 1-t-butyl-1,2-epoxycyclohexane. (1985)

The acid-catalysed ring-opening reactions of 1-t-butyl-1,2-epoxycyclohexane (1)(methanolysis, hydrolysis, and trichloroacetolysis in non-protic solvents) lead to very complex mixtures. In these reactions, in addition to the usual 1,2-primary addition products, and to the non-addition products in which the t-butyl skeleton is still present, considerable amounts of other products are formed. These compounds include 1,3-secondary addition products and other rearranged non-addition products which arise by rearrangement of the original skeleton of (1), by methyl group migration; the aldehyde (20) which is lacking both the t-butyl group and the cyclohexane skeleton is also obtained. However, the opening reactions of (1) in acid media are highly regioselective, most of the reaction products arising from C–O breaking on the tertiary carbon. The structures and the configurations of all the reaction products have been well established by a study of their i.r. and n.m.r. data; however, in some cases the structures and the configurations were confirmed either through unequivocal syntheses and/or chemical correlations. The stereoselectivity of the trichloroacetolysis reactions of (1) is not completely anti, even if the amounts of 1,2 adducts formed are somewhat small, and the syn/anti ratio increases with the polarity of the solvent. The results obtained were rationalized through a mechanism analogous to that previously proposed for 2-aryl- and 2-ethynyl-oxiranes in which different kinds of carbenium ion species are involved.
Resistance to Antiretroviral Agents in Individuals with HIV-1 Non-B Subtypes (2002)

Naturally occurring polymorphisms at positions involved in resistance to antiretroviral agents are frequently seen in HIV-1 non-B subtypes. Although they do not seem to affect significantly the susceptibility to antiretroviral drugs in vitro, they may facilitate the selection of different pathways and/or a more rapid emergence of drug resistance and treatment failure under not fully suppressive treatment regimens.
Softening of phonon spectra in metallic glasses (2016)

Abstract The vibrational spectra of a series of MgZnCa amorphous alloys were computed using density functional theory and implementing the small displacement method. The atomic structures of the alloys were obtained by ab initio molecular dynamics simulations. The vibrational thermodynamic properties were calculated as a function of temperature and, in particular, the specific heat at low temperature was approximated by temperature cubed based on the Debye model. We computed the contribution of Mg vibrations to the specific heat and investigated the softening of Mg phonon spectra, where the maximum allowed vibrational frequency is lowered and highly collective diffusion processes are promoted. The statistical correlation between the reported critical casting thickness of the alloys and softening of Mg phonons was obtained. Similar calculations were performed for two distinctively different amorphous ZrTiCuAl alloys with large and small reported critical casting thickness, respectively. The findings were consistent with those of the MgZnCa alloys.
Spectrophotometric determination of aliphatic isocyanates in the occupational atmosphere. Part 1. Determination of total isocyanate concentration (1979)

This paper describes a spectrophotometric method for use in the field for the determination of aliphatic isocyanates and their oligomers in air. The atmosphere being tested is drawn through a mixture of hydrochloric acid and dimethyl sulphoxide at a sampling rate of 2 l min–1 for 10 min. Any isocyanates or oligomer present are hydrolysed to the corresponding amine. 1-Fluoro-2,4-dinitrobenzene is added and forms coloured derivatives with the amines. The absorbance of each derivative is measured at approximately 353 nm, and can be directly related to the amount of isocyanate. Concentrations down to 0.002 p.p.m. can be determined.
Supplementary Figures S1-S4 and Tables S1-S2 from Protein Kinase Inhibitor H89 Enhances the Activity of <i>Pseudomonas</i> Exotoxin A–Based Immunotoxins (2023)

&lt;p&gt;Fig S1. H89 increased ADP-ribosylation and MCL-1 degradation in SEM cells Fig S2. Combination of RIT and H89 lowers MCL1 and induces PARP-cleavage Fig S3. PKA regulator, S6K1-, or ROCK2-inhibitor show little change in LMB-11 activity Fig S4. Combination of LMB-11 and S6K1 inhibitor PF4708671 enhances MCL1 degradation but not ADP-ribosylation Table S1. Cytotoxic activity (IC50) of immunotoxins with and without H89 Table S2. In vitro screening for H89 inhibited kinases&lt;/p&gt;
A completey on-chip voltage regulation technique for low power digital circuits (1999)

This paper describes a completely on-chip voltage regulation technique for locally generating an adaptive low voltage power supply rail from a given higher voltage power supply without requiring any external component. The on-chip regulator, based on delay servoing, primarily comprises of a critical path replica, charge pump and a high performance voltage buffer which is the most critical component of the design. Simulation results in OSl.trn CMOS process demonstrate that the buffer offers a low DC output impedance, a high degree of voltage regulation (output ripple of 12% of Vdd) and a superior line regulation (upto the maximum clock frequency of SOMHz) even under strongly varying load conditions. The regulator response for a typical worst case load exhibits a maximum voltage fluctuation of 4% of Vdd with a reasonably fast response time.
From Neutral to Ionic Species: Syntheses and X‐ray Crystallographic and Multinuclear NMR Spectroscopic Studies of Li···P(SiMe3)–PtBu2 and Its Solvent Complexes (2013)

Abstract Li(THF) 3 P(SiMe 3 )–P t Bu 2 ( 1 , THF = tetrahydrofuran) has been prepared by the reaction of (Me 3 Si) 2 P–P t Bu 2 with n ‐butyllithium in THF and isolated in good yields. Compound 1 eliminates THF in vacuo to yield the dimeric [Li(THF)P(SiMe 3 )–P t Bu 2 ] 2 ( 2 ). By metalation of H(SiMe 3 )P–P t Bu 2 with n ‐butyllithium in hexane, the solvent‐free derivative [Li(Me 3 Si)P–P t Bu 2 ] 4 ( 3 ) has been prepared. Compounds 1 – 3 form the ionic species [Li(TMEDA) 2 ] + [(Me 3 Si)P–P t Bu 2 ] – [ 4 , TMEDA = Me 2 N(CH 2 ) 2 NMe 2 ] and [Li(12‐crown‐4) 2 ] + [(SiMe 3 )P–P t Bu 2 ] – ( 5 ) with TMEDA and 12‐crown‐4, respectively, in solution. The molecular structures of 1 – 5 were established by single‐crystal X‐ray diffraction. Compound 3 forms a cyclic tetramer with a flat butterfly geometry. Extensive solution NMR spectroscopic investigations have shown that all species except for 3 exist in the same form in solution as in the solid state. Moreover, multinuclear variable‐temperature NMR studies showed that 2 is involved in a rapid conversion between conformers at 298 K, which can be slowed down on the NMR timescale at 183 K.
Design aspects of high torque density-low speed permanent magnet motor for electric two wheeler applications (2013)

This paper focuses on practical aspects of designing a direct drive electric motor having extremely high torque density for a two wheeler electric/hybrid vehicle. The design starts with arrival of motor specification based on the vehicle requirements, progress with finalizing the sizing parameters and examining the aspects which affect the performance of the motor with high torque density. Skin effect, magnet demagnetization, eddy current loss, thermal stability and cycle efficiency are the main concerns which are examined. The use of strip conductors to reduce the resistance and enhance the thermal stability is also discussed. Finally, the prototype is made and the experimental results are presented.
Design, characterisation and operation of an inverted cylindrical magnetron for metal deposition (2004)

An inverted cylindrical magnetron device for a continuous all-side deposition of metal films onto wires and temperature-sensitive synthetic fibres was designed and tested. Design features of interest include easy assembly and disassembly of the device for maintenance and upgrading. Using silver as a sputter target, the important performance characteristics including the influence of magnetic field strength, the IV-characteristics, the deposition rate and homogeneity, the erosion profiles of the cathode and the heat load on free-standing substrates were determined. The deposition rate and the substrate temperature were found to be closely related to the sputtering power. Optimum operating conditions, combining a low heat load and a high deposition rate, were determined. In the centre region, a maximum deposition rate of 1800 nm/min was achieved. The erosion profile of the sputter target resulted in a utilisation efficiency of 57%.
Identifying modifier genes in Autoimmune Lymphoproliferative Syndrome (P4084) (2013)

Abstract Autoimmune Lymphoproliferative Syndrome (ALPS) is an inherited disorder of defective lymphocyte apoptosis, characterized by chronic lymphadenopathy and/or splenomegaly, autoimmune cytopenias, and the expansion of a unique population of CD4-CD8- α/β T cells. ALPS is predominately caused by mutations in Fas with incomplete penetrance. In order to identify modifier genes and understand the mechanism of incomplete penetrance of disease in ALPS, we performed a linkage study using five large families with multiple ALPS patients and healthy Fas mutation-positive relatives (HMPRs) in each family. We identified a putative modifier locus shared by two of the families and a few potential linkage intervals shared by two of the other families. To screen large numbers of family members for an apoptosis defect, we developed a fast assay for testing lymphocyte Fas-mediated apoptosis susceptibility ex vivo, which we have named the FasT Kill assay. The conventional in vitro apoptosis assay takes over a week to obtain results whereas our assay using multi-parameter flow cytometry to specifically analyze apoptosis of the Fas-sensitive effector memory T cells in PBMCs can yield a diagnosis within a single workday. Using the FasT Kill assay, we could rapidly identify patients with apoptosis defects for the diagnosis of ALPS and compare the severity of apoptosis defects among ALPS patients or HMPRs. The results of these genetic analyses will be discussed.
A Potential Role for P2X7R in Allergic Airway Inflammation in Mice and Humans (2010)

P2X₇R deficiency is associated with a less severe outcome in acute and chronic inflammatory disorders. Recently, we demonstrated that extracellular adenosine triphosphate is involved in the pathogenesis of asthma by modulating the function of dendritic cells (DCs). However, the role of the purinergic receptor subtype P2X₇ is unknown. To elucidate the role of P2X₇R in allergic airway inflammation (AAI) in vitro and in vivo, P2X₇R expression was measured in lung tissue and immune cells of mice or in humans with allergic asthma. By using a specific P2X₇R-antagonist and P2X₇R-deficient animals, the role of this receptor in acute and chronic experimental asthma was explored. P2X₇R was found to be up-regulated during acute and chronic asthmatic airway inflammation in mice and humans. In vivo experiments revealed the functional relevance of this finding because selective P2X₇R inhibition or P2X₇R deficiency was associated with reduced features of acute and chronic asthma in the ovalbumin-alum or HDM model of AAI. Experiments with bone marrow chimeras emphasized that P2X₇R expression on hematopoietic cells is responsible for the proasthmatic effects of P2X₇R signaling. In the DC-driven model of AAI, P2X₇R-deficient DCs showed a reduced capacity to induce Th2 immunity in vivo. Up-regulation of P2X₇R on BAL macrophages and blood eosinophils could be observed in patients with chronic asthma. Our data suggest that targeting P2X₇R on hematopoietic cells (e.g., DCs or eosinophils) might be a new therapeutic option for the treatment of asthma.
Products of the surface oxidation of methyl linoleate (2004)

Abstract Methyl linoleate with 5% by weight of methyl palmitate as an internal standard was deposited as a monolayer (20% by weight) on Silica gel H and oxidized at 7,25, and 40°C. Oxidation was followed by iodometric PV practiced directly on aliquots of the silica gel. Lower temperatures gave higher PV maxima but after longer times. Oxidation of methyl linoleate at all three temperatures followed first‐order kinetics, and the energy of activation was 15.0 kcal/mol. The products recovered from the chloroform‐acetic acid layer of the peroxide determination were analyzed by GC and identified by El‐ and CI‐MS. Calculation based on methyl palmitate as an internal standard showed that the total peak area decreased to about 40% that of the original methyl linoleate when the residual methyl linoleate was reduced to less than 2%. The chief nonscission products (NSP) of linoleate oxidation were epoxy, hydroxy, hydroxy‐epoxy, dihydroxy, and trihydroxy methyl esters. The greatest NSP concentrations were obtained about the time of the greatest PV, and the yield at 40°C was greater than those at 7 and 25°C. Scission products (SP) increased rapidly until the greatest PV was reached. After this time, SP declined slightly and plateaued at 40°C, but at 7 and 25°C, SP continued to increase slowly with further oxidation.
MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data (2003)

MAPPFinder is a tool that creates a global gene-expression profile across all areas of biology by integrating the annotations of the Gene Ontology (GO) Project with the free software package GenMAPP http://www.GenMAPP.org . The results are displayed in a searchable browser, allowing the user to rapidly identify GO terms with over-represented numbers of gene-expression changes. Clicking on GO terms generates GenMAPP graphical files where gene relationships can be explored, annotated, and files can be freely exchanged.