gebhart/patrepeval huggingface dataset:
Abstract 625: Targeting of Heparin Binding EGF-like Growth Factor (HBEGF) Suppresses Hyperlipidemia and Atherosclerosis in LDL Receptor Deficient Mice (2016)

Objective: Elevation of apoB-containing lipoproteins is a well-established risk factor for the development of atherosclerosis. Previous reports showed that expression of heparin-binding EGF-like growth factor (HBEGF), a ligand of epidermal growth factor receptor (EGFR), is associated with atherosclerosis development. In this study, we examined in vivo effects of HBEGF targeting on hyperlipidemia-induced atherosclerosis by suppressing HBEGF expression using antisense oligonucleotide (ASO). Methods and Results: Female and male LDLR deficient mice were fed a high fat diet (HFD; 21% fat, 0.2% cholesterol) throughout the study. After 8 weeks of HFD feeding, mice were injected intraperitoneally with either control or HBEGF ASOs weekly for 12 weeks. At termination, we measured circulating lipid concentrations and atherosclerotic lesion size in the aorta. Compared to control ASO group, HBEGF ASO group had a significant reduction of circulating total cholesterol, triglyceride, and apoB-containing lipoprotein concentrations but no change of high-density lipoprotein (HDL) concentration. Importantly, HBEGF ASO injection significantly suppressed atherosclerosis in the aortic arch, thoracic, and abdominal aorta. HBEGF ASO suppressed sterol synthetic gene expression in the liver but elevated lipid contents in the liver. HBEGF gene silencing in a liver cell system induced downregulation of sterol regulatory element binding protein (SREBP) target genes including LDLR and Insig1. Conclusion: Targeting HBEGF using ASOs is an efficient approach to suppress dyslipidemia and hyperlipidemia-induced atherosclerosis. The differential gene expression analysis suggests that HBEGF ASO administration suppresses SREBP-regulated gene expression in the liver leading to downregulation of circulating cholesterol and TG concentrations.
Aeroelastic mode decomposition framework and mode selection mechanism in fluid-membrane interaction (2020)

In this study, we present a global Fourier mode decomposition framework for unsteady fluid-structure interaction. We apply the framework to isolate and extract the aeroelastic modes arising from a coupled three-dimensional fluid-membrane system. The proposed framework is employed to decompose the physical variables in the fluid and structural domains into frequency-ranked aeroelastic modes in a unified way. We observe the frequency synchronization between the vortex shedding and the structural vibration via mode decomposition analysis. We examine the role of flexibility in the aeroelastic mode selection and perform a systematic comparison of flow features among a rigid wing, a rigid cambered wing and a flexible membrane. With the aid of our mode decomposition technique, we find that the dominant structural mode exhibits a chordwise second and spanwise first mode at different angles of attack. The structural natural frequency corresponding to this mode is estimated using an approximate analytical formula. By examining the dominant frequency of the coupled system, we find that the dominant membrane vibrational mode is selected via the frequency lock-in between the dominant vortex shedding frequency and the structural natural frequency. From the fluid modes and the mode energy spectra at $\alpha=20^\circ$ and $25^\circ$, the aeroelastic modes corresponding to the non-integer frequency components lower than the dominant frequency are found to be associated with the bluff body vortex shedding instability. The non-periodic aeroelastic response observed at higher angles of attack are related to the interaction between aeroelastic modes caused by the frequency lock-in and the bluff-body-like vortex shedding.
Intranasal administration of midazolam in a cyclodextrin based formulation: bioavailability and clinical evaluation in humans. (2001)

Intranasal administration of midazolam has been of particular interest because of the rapid and reliable onset of action, predictable effects, and avoidance of injections. The available intravenous formulation (Dormicum i.v. solution from Hoffmann-La Roche) is however less than optimal for intranasal administration due to low midazolam concentration and acidity of the formulation (pH 3.0-3.3). In this study midazolam was formulated in aqueous sulfobutylether-beta-cyclodextrin buffer solution. The nasal spray was tested in 12 healthy volunteers and compared to intravenous midazolam in an open crossover trial. Clinical sedation effects, irritation, and serum drug levels were monitored. The absolute bioavailability of midazolam in the nasal formulation was determined to be 64 +/- 19% (mean +/- standard deviation). The peak serum concentration from nasal application, 42 +/- 11 ng ml-1, was reached within 10-15 min following administration and clinical sedative effects were observed within 5 to 10 min and lasted for about 40 min. Intravenous administration gave clinical sedative effects within 3 to 4 min, which lasted for about 35 minutes. Mild to moderate, transient irritation of nasal and pharyngeal mucosa was reported. The nasal formulation approaches the intravenous form in speed of absorption, serum concentration and clinical sedation effect. No serious side effects were observed.
Control of Plasmid R1 Replication: Functions Involved in Replication, Copy Number Control, Incompatibility, and Switch-off of Replication (1980)

A small derivative of plasmid R1 was used to integratively suppress a chromosomal dnaA(Ts) mutation. The strain obtained grew normally at 42 degrees C. The integratively suppressed strain was used as recipient for various plasmid R1 derivatives. Plasmid R1 and miniplasmid derivatives of R1 could be established in the strain that carried an integrated R1 replicon, but they were rapidly lost during growth. However, plasmids also carrying ColE1 replication functions were almost completely stably inherited. The integratively suppressed strain therefore allows the establishment of bacteria diploid with respect to plasmid R1 and forms a useful and sensitive system for studies of interaction between plasmid R1 replication functions. Several of the chimeric plasmids caused inhibition of growth at high temperatures. All plasmids that inhibited growth carried one particular PstI fragment from plasmid R1 (the PstI F fragment), and in all cases the growth inhibition could be ascribed to repression of initiation of chromosome replication at 42 degrees C, i.e., they carry a trans-acting switch-off function. Furthermore, the analogous PstI fragments from different copy mutants of plasmid R1 were analyzed similarly, and one mutant was found to lack the switch-off function. The different chimeric plasmids were also tested for their incompatibility properties. All plasmids that carried the switch-off function (and no other plasmids) also carried R1 incompatibility gene(s). Since the PstI F fragment, which is present on all these plasmids, is very small (0.35 x 10(6)), it is suggested that the switch-off regulation of replication (by an inhibitor), incompatibility, and copy number control are governed by the same gene.
Abstract 619: Identification of clinically actionable genomic alterations in the tumor and circulation of pancreatic cancer patients (2015)

Abstract Pancreatic adenocarcinoma has the worst overall mortality of any solid tumor, with only 6% of patients surviving after 5 years. To evaluate the clinical implications of genomic alterations in this low cellularity tumor type, we deeply sequenced the genomes of 134 enriched pancreatic adenocarcinomas from patients who underwent potentially curative resections. Given the low neoplastic cellularity of pancreatic cancers, we enriched for neoplastic cells either by macrodissection of primary tumors or by flow-sorting of tumor nuclei, and performed deep sequencing (high coverage) of these enriched samples using next-generation sequencing approaches. We obtained a total of &amp;gt;1Tb of sequence data, resulting in an average coverage within the target regions of &amp;gt;200-fold for each tumor analyzed by whole-exome sequencing and &amp;gt;750-fold for each tumor analyzed by targeted cancer gene sequencing. These approaches allowed us to identify sequence changes, including single base and small insertion or deletion mutations, as well as copy number alterations in &amp;gt;20,000 genes in the whole-exome analyses and in 116 specific genes in the targeted analyses. These analyses revealed that somatic mutation of chromatin remodeling genes were associated with improved progression-free and overall survival. Alterations in genes with potential clinical utility were observed in a majority of cases and included alterations of AKT1, AKT2, BRCA2, ERBB2, KIT, and PIK3CA. Non-invasive liquid biopsy analyses were performed before and after surgery to evaluate the presence of circulating tumor DNA in the plasma of 83 patients. Through these approaches, we were able to diagnose early stage pancreatic tumors in the majority of patients and to detect the presence of circulating tumor DNA prior to clinical relapse. These observations provide genetic markers of clinical outcome in pancreatic cancer and suggest new avenues for personalized therapy. Citation Format: Mark Sausen, Jillian Phallen, Vilmos Adleff, Siân Jones, Rebecca J. Leary, Karli Lytle, Sonya Parpart-Li, Derek Murphy, Michael T. Barrett, David C. Linehan, Anirban Maitra, Ralph Hruban, Daniel D. Von Hoff, Julia S. Johansen, Luis A. Diaz, Jeffrey A. Drebin, Victor E. Velculescu. Identification of clinically actionable genomic alterations in the tumor and circulation of pancreatic cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 619. doi:10.1158/1538-7445.AM2015-619
Trunked mobile radio: towards a pan-European digital standard (2002)

Future evolution of private mobile radio systems in Europe is discussed, and a strategy for second-generation trunking based on the traditional strengths of dispatcher-type operation together with extensive provision of data and text services is proposed. Options for the radio interference, operating time-division multiple access (TDMA) are suggested as possible candidates for future trunking. Backed by the European Commission, the ETSI Technical Sub-Committee RES 6 is now coordinating the development of a digital pan-European trunking standard with the aim of making specifications available in 1994. The activities of ETSI-RES 6 are outlined, and criteria governing the development of a digital trunking standard are advanced. Suggestions for future services to be provided are then made, and possible scenarios for the physical layer are briefly discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Laser diodes with 353 nm wavelength enabled by reduced-dislocation-density AlGaN templates (2015)

We fabricated optically pumped and electrically injected ultraviolet (UV) lasers on reduced-threading-dislocation-density (reduced-TDD) AlGaN templates. The overgrowth of sub-micron-wide mesas in the Al<sub>0.32</sub>Ga<sub>0.68</sub>N templates enabled a tenfold reduction in TDD, to (2–3) × 10<sup>8</sup> cm<sup>–2</sup>. Optical pumping of AlGaN hetero-structures grown on the reduced-TDD templates yielded a low lasing threshold of 34 kW/cm<sup>2</sup> at 346 nm. Room-temperature pulsed operation of laser diodes at 353 nm was demonstrated, with a threshold of 22.5 kA/cm<sup>2</sup>. Furthermore, reduced-TDD templates have been developed across the entire range of AlGaN compositions, presenting a promising approach for extending laser diodes into the deep UV.
Expression of biologically active heterodimeric bovine follicle-stimulating hormone in milk of transgenic mice. (1991)

Follicle-stimulating hormone (FSH; follitropin) is a pituitary glycoprotein composed of two post-translationally modified subunits, which must properly assemble to be biologically active. FSH has been difficult to purify and to obtain in quantities sufficient for detailed biochemical studies. We have targeted FSH expression to the mammary gland of transgenic mice by using cDNAs encoding the bovine alpha and FSH beta subunits and a modified rat beta-casein gene-based expression system. Lines of bigenic mice expressing both subunits have been generated either by coinjection of the subunit transgenes or by mating mice that acquired and expressed transgenes encoding an individual subunit. Up to 60 international units (15 micrograms) of biologically active FSH per ml was detected in the milk of the bigenic mice. These lines provide a model system for studying the post-transcriptional mechanisms that effect the expression and secretion of this heterodimeric hormone.
Exploring the representation of complex processes in information-intensive services (2012)

It is well known that Information-Intensive Services (IIS), such as financial services, information technology services, healthcare, telecommunications and broadcasting, and education have shown some of the highest growth rates in the service sector of the US economy. In such services, the business processes are often complex, involving a number of different parties. For example, multiple people from both the service supplier and the customer participate to co-produce a desired service outcome. Through a few case studies, we observe a set of common characteristics of such complex service processes. To obtain a systematic understanding of such processes, we explore the possibility of applying existing modelling or representation frameworks and evaluate them based on how well they address the characteristics of complex processes in IIS as well as other analysis requirements.
Sequencing and mapping the Arabidopsis genome: a weed model for real crops. (1996)

Arabidopsis is a crucifer weed with a small genome of about 120 Mbp which has been chosen as a model species for plant molecular genetics. Four years ago, a consortium of nine French laboratories, including ours, initiated a project aimed at mapping the transcribed regions of the genome. The strategy employed was to systematically and randomly sequence cDNA clones isolated from libraries made from different tissues and organs of plants grown under various physiological conditions. The consortium released about 7,000 expressed sequenced tags (ESTs) in the dbEST database corresponding to approximately 3,500 unique genes. In the next phase of the programme, a YAC library with average inserts of 500 kbp has been prepared. We have now started to use the EST information to map the cDNA clones on these YACs. The most recent aspect of Arabidopsis sequencing is the ESSA (European Scientists Sequencing Arabidopsis) project, in which the aim is to describe 2.5 Mbp by the end of 1996. Genomic sequencing has revealed a very high gene density. Comparison of present genomic sequencing results with the EST data suggests that up to half of the genes might already be tagged with an EST. In collaboration with Carlos Quiros' group in Davis we have also analysed the conservation of a 30 kbp locus (Em 1, a late embryogenesis abundant protein gene) on chromosome 3 between Arabidopsis and several Brassica species. Progress on these various aspects will be reviewed. We shall also present some sequence comparisons between Arabidopsis and rice ESTs. These results suggest that it should be possible in the very near future to map a pool of common genes onto many different plant genomes. This should provide a common framework to integrate maps from different species and facilitate mapbased cloning of genes of agronomical importance.
Immunohistochemical Expression of PD-L1 and MDR1 in Breast Tumors: Association with Clinico-Pathological Parameters and Treatment Outcome (2022)

Abstract Antitumor immune evasion is a hallmark for the development and progression of cancer. Tumor cells adopt various mechanisms to escape the host immune system recognition. One such mechanism is the over expression of programmed death ligand (PD-L1), a negative T cell regulatory molecule. Because PD-L1 overexpression causes resistance to chemotherapeutic response in many cancers, herein we explored the relationship between PD-L1 and multidrug resistance protein MDR1 in breast cancer. Immunohistochemical evaluation of PD-L1 and MDR1 proteins in 194 breast cancer tissue samples were carried out. The relationship between PD-L1 and MDR1 expression on cancer cells with clinicopathological factors and prognosis was investigated. IHC showed a significant correlation between PD-L1 and MDR1 expression on tumor cells. Increased PD-L1 expression was also associated with lymph node status and tumor grade of the patient. Our results also revealed that the expression of PD-L1 and MDR1 was higher in TNBC subtype compared to other breast cancer subtypes. Therefore a better understanding of the molecular mechanism through which PD-1/PD-L1 pathway contribute to the chemoresistance might bring forth the prognostic significance of PD-L1 and selection of patients who may benefit from immunotherapy.
Phosphorus-Chiral Diphosphines as Ligands in Hydroformylation. An Investigation on the Influence of Electronic Effects in Catalysis (2000)

The phosphorus-chiral diphosphine 1,1‘-bis(1-naphthylphenylphosphino)ferrocene (1a) and its new electronically modified derivatives 1b−d bearing methoxy and/or trifluoromethyl groups in para positions of the phenyl rings were investigated as ligands in rhodium-catalyzed (asymmetric) hydroformylation. Depending on ligand basicity, high-pressure NMR and IR characterization of the respective (diphosphine) rhodium dicarbonyl hydride precursor complexes revealed subtle differences in the occupation of bis-equatorial (ee) and equatorial−apical (ea) coordination geometries. The high ee:ea ratio of the four complexes contrasted with the clear ea preference observed for the related achiral compound dppf (1,1‘-bis(diphenylphosphino)ferrocene). In the hydroformylation of styrene the best result (50% ee) was obtained by employing the best π-acceptor ligand 1c, incorporating two p-trifluoromethyl substituents. Substrate electronic variations using 4-methoxystyrene and 4-chlorostyrene showed a pronounced influence on turnover frequencies, branched/linear aldehyde product ratios, and enantiodiscrimination, whereas in the hydroformylation of 1-octene ligand electronic perturbations did affect only the rate, but not the selectivity of the reaction.
Islet‐infiltrating T cell clones from non‐obese diabetic mice that promote or prevent accelerated onset diabetes (1991)

In humans and non-obese diabetic mice (NOD), insulin-dependent diabetes mellitus (IDDM) results from a spontaneous T cell-dependent autoimmune destruction of the insulin-producing pancreatic beta cells. Previous data suggest that a delicate balance between autoaggressive T cells and suppressor-type immune phenomena determine whether expression of autoimmunity is limited to insulitis or progresses to IDDM. To resolve the cellular basis of this intricate network of pathogenic CD4+ and CD8+ T cells and the role of T cells in suppressive immune phenomena. T cell clones were propagated directly from islets of NOD mice at the onset of insulitis. Insofar as insulitis, but not IDDM, is universal in NOD mice, we have screened for the in vivo effects of the islet-infiltrating T cell clones upon expression of IDDM, not insulitis. A CD4+ T cell clone, IS-3S7D, proliferates in response to islet antigen(s) and its transfer into prediabetic NOD mice promotes the rapid onset of IDDM. An interleukin 2 (IL 2)-dependent noncytolytic, V beta 11+ CD8+. T cell clones IS-2.15, prevents an accelerated onset diabetes in two distinct models. The present study, which documents the presence of CD4+ diabetogenic T cell clones and CD8+ T cell clones that dampen autoimmunity, gives tangible evidence that opposing autoimmune processes may determine whether an autoimmune-prone host develops frank disease.
O2–02–01: Patterns of atrophy on voxel based morphometry differ between amnestic MCI converters and nonconverters (2007)

Amnestic mild cognitive impairment (aMCI) represents the clinically evident prodromal phase of Alzheimer's disease (AD). While the majority of aMCI subjects progress to AD, a proportion remains relatively stable. Identifying characteristics that distinguish aMCI subjects who convert more vs. less rapidly is useful for clinical and disease characterization purposes. To compare patterns of grey matter loss in subjects with aMCI who convert to AD within a fixed time interval vs. those who do not convert. Thirty-seven aMCI subjects were identified that converted to AD within 18 months of the baseline MRI scan (aMCI converters). In addition, a group of 18 aMCI subjects were identified that remained stable for their entire clinical course, where the minimum required follow-up time from baseline MRI was set at three years (aMCI non-converters). Each subject was age- and gender-matched to a control. Voxel-based morphometry (VBM) was used to assess patterns of grey matter atrophy in the aMCI converters and non-converters compared to the control group, and compared to each other. An optimized version of VBM was applied using customized templates and prior probability maps. The aMCI converters showed a bilateral pattern of loss affecting the mesial and inferior temporal lobe, the temporoparietal association neocortex and the frontal lobes, compared to controls. The aMCI non-converters showed no regions of grey matter loss when compared to controls. When the converters and non-converters were compared directly, the converters showed greater grey matter loss in the mesial and inferior temporal lobes, the temporoparietal neocortex, posterior cingulate, precuneus, anterior cingulate, and frontal lobes than the non-converters (Figure; results shown on a 3D render and on representative slices corrected for multiple comparisons using the FDR, p<0.05). The regions of loss observed in aMCI converters are typical of subjects with AD, and fit the known pattern of pathological progression in AD. The lack of grey matter loss in non-converter aMCI subjects is consistent with the notion that patterns of atrophy on MRI at baseline map well onto the subsequent clinical course.
Electrical properties of N2O/NH3 plasma grown oxynitride on strained-Si (1998)

Growth of ultrathin (<100 /spl Aring/) oxynitride on strained-Si using microwave N/sub 2/O and NH/sub 3/ plasma is reported. X-ray photoelectron spectroscopy (XPS) results indicate a nitrogen-rich layer at the strained-Si/SiO/sub 2/ interface. The electrical properties of oxynitrides have been characterized using a metal-insulator-semiconductor (MIS) structure. A moderately low value of insulator charge density (6.1/spl times/10/sup 10/ cm/sup -2/) has been obtained for NH/sub 3/ plasma treated N/sub 2/O oxide sample. Nitrided oxide shows a larger breakdown voltage and an improved charge trapping properties under Fowler-Nordheim (F-N) constant current stress.
THE ADEQUACY OF THE AIR-MIX CONTROL IN VENTILATORS OPERATED FROM AN OXYGEN SOURCE. (1964)

Mean inspired oxygen levels, delivered by the Bennett PR1 and Bird Mark 7 ventilators, were measured at various cycling pressures. Using the Bird ventilator, oxygen levels varied from 51.5 to 96.8%, being highest at low flows and at high cycling pressures. The Bennett PR1 delivers more constant percentages of oxygen, in the range 61.5 to 72.3%. With both makes of machine, each ventilator provides different inspired oxygen levels under comparable circumstances. It is recommended that this type of equipment be driven by compressed air, oxygen being added as required.