gebhart/patrepeval huggingface dataset:
Zinc Finger Protein LipR Represses Docosahexaenoic Acid and Lipid Biosynthesis in Schizochytrium sp. (2022)

The heterotrophic marine microalgae <i>Schizochytrium</i> sp. is an important industrial producer of docosahexaenoic acid (DHA). Increased production of DHA and lipids in <i>Schizochytrium</i> sp. has been achieved by standard fermentation optimization and metabolic engineering methods; however, regulatory mechanisms for DHA and lipid biosynthesis remain unknown. In this study, the C<sub>2</sub>H<sub>2</sub> zinc finger protein LipR was identified in <i>Schizochytrium</i> sp. ATCC 20888 by transcriptional analysis. Deletion of the <i>lipR</i> gene significantly (<i>P < </i>0.001) increased production of total lipids and DHA by 33% and 48%, respectively. LipR repressed DHA and lipid production by directly inhibiting transcription of polyunsaturated fatty acid (PUFA) and fatty acid synthase (FAS) genes (<i>pfa1</i>, <i>pfa2</i>, <i>pfa3</i>, and <i>fas</i>). Specific binding of LipR to 9-bp recognition sequence 5'-(C/A)(A/G)CCATCTT-3' in upstream regions of target genes was demonstrated by electrophoretic mobility shift assays (EMSAs) and DNase I footprinting assays. Expression of several key genes (<i>acc</i>, <i>acl</i>, <i>ampD</i>, <i>fabD</i>, <i>mae</i>, <i>zwf</i>, and <i>dga1</i>) related to levels of precursors and NADPH, and to triacylglycerol storage rate, were also directly repressed by LipR. Our findings, taken together, indicate that the evolutionarily unique regulator LipR is an essential repressor of DHA and saturated fatty acid biosynthesis in <i>Schizochytrium</i> sp. <b>IMPORTANCE</b> Regulatory mechanisms for DHA and saturated fatty acid biosynthesis in the heterotrophic marine microalgae <i>Schizochytrium</i> sp. are unclear. We demonstrate here that deletion of the gene (<i>lipR</i>) encoding the C<sub>2</sub>H<sub>2</sub> zinc finger protein LipR promotes DHA and saturated fatty acid production in this genus. LipR acts as a key repressor of such production by binding to 9-bp consensus sequence 5'-(C/A)(A/G)CCATCTT-3' in the upstream regions of polyunsaturated fatty acid and fatty acid synthase genes (<i>pfa1</i>, <i>pfa2</i>, <i>pfa3</i>, and <i>fas</i>), and genes related to levels of precursors and NADPH (<i>acc</i>, <i>acl</i>, <i>ampD</i>, <i>fabD</i>, <i>mae</i>, and <i>zwf</i>), and to triacylglycerol storage rate (<i>dga1</i>). This is the first demonstration that a regulator inhibits synthesis of DHA and lipids in <i>Schizochytrium</i> sp. by directly controlling transcription of PUFA synthase and <i>fas</i> genes. Manipulation of the <i>lipR</i> gene provides a potential strategy for enhancing accumulation of polyunsaturated fatty acids and lipids in thraustochytrids.
Abstract 4855: Indotecan (LMP400), Imidotecan (LMP776) and LMP744: A new class of non-camptothecin TOP1 inhibitors selective for cancer cells with homologous recombination deficiencies and high SLFN11 expression (2018)

Abstract To relax DNA supercoiling, topoisomerase I (TOP1) induces DNA cleavage complexes (TOP1cc). These TOP1cc can be trapped by camptothecin, leading to replication induced DNA double-strand breaks (DSB). Widely used, camptothecin derivatives have known limitations. It is now possible to overcome these limitations with the non-camptothecin indenoisoquinolines currently in clinical trials (LMP400, LMP776 and LMP744). Homologous recombination (HR) and its key components BRCA1, BRCA2 and PALB2 are needed to repair DSB induced by TOP1 inhibitors (Maede, Y et al. 2014). It has been shown that BRCA1 is a determinant of response to camptothecins in addition to Olaparib. Also, Schlafen11 (SLFN11) expression has been demonstrated to be a highly penetrant determinant of response to camptothecin derivatives (Zoppoli, G et al. 2012). To rationally select patients for phase 2 clinical trials based on cancer-specific genomic alterations, we have determined whether HR components deficiency or SLFN11 expression are determinants of LMPs response. Using isogenic cell lines, we assessed the survival after treatment with the LMPs. We found that SLFN11-positives cells are 10-times hypersensitive to LMPs compare to WT cells. Also, BRCA1-, BRCA2- and PALB2-deficient cells are 3- to 5- times hypersensitive to the LMPs. Adding Olaparib led to a greater cell death, especially in HR-deficient (HRD) cells. Our results show that the indenoisoquinolines are active at nanomolar concentrations and that HR deficiency and SLFN11 expression are strong drug response determinants. They also demonstrate that the LMPs synergize with Olaparib. These findings provide a rationale for personalized treatment and further clinical trials with the indenoisoquinolines in HR-deficient cancers. Citation Format: Yves Pommier, Laetitia Marzi, Zoe Waever Ohler, Ludmila Szabova, Shyam Sharan, Junko Murai, Mark Cushman. Indotecan (LMP400), Imidotecan (LMP776) and LMP744: A new class of non-camptothecin TOP1 inhibitors selective for cancer cells with homologous recombination deficiencies and high SLFN11 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4855.
All-silicon monolithic optoelectronic platform for multi-analyte biochemical sensing (2013)

Despite the advances in optical biosensors, the existing technological approaches still face two major challenges: the inherent inability of most sensors to integrate the optical source in the transducer chip, and the need to specifically design the optical transducer per application. In this work, the development of a radical optoelectronic platform is demonstrated based on a monolithic optocoupler array fabricated by standard Si-technology and suitable for multi-analyte detection. The platform has been specifically designed biochemical sensing. In the all-silicon array of transducers, each optocoupler has its own excitation source, while the entire array share a common detector. The light emitting devices (LEDs) are silicon avalanche diodes biased beyond their breakdown voltage and emit in the VIS-NIR part of the spectrum. The LEDs are coupled to individually functionalized optical transducers that converge to a single detector for multiplexed operation. The integrated nature of the basic biosensor scheme and the ability to functionalize each transducer independently allows for the development of miniaturized optical transducers tailored towards multi-analyte tests. The monolithic arrays can be used for a plethora of bio/chemical interactions becoming thus a versatile analytical tool. The platform has been successfully applied in bioassays and binding in a real-time and label-free format and is currently being applied to ultra-sensitive food safety applications.
Assessment of diffuse coronary artery disease by quantitative analysis of coronary morphology based upon 3-D reconstruction from biplane angiograms (1995)

Quantitative evaluations on coronary vessel systems are of increasing importance in cardiovascular diagnosis, therapy planning, and surgical verification. Whereas local evaluations, such as stenosis analysis, are already available with sufficient accuracy, global evaluations of vessel segments or vessel subsystems are not yet common. Especially for the diagnosis of diffuse coronary artery diseases, the authors combined a 3D reconstruction system operating on biplane angiograms with a length/volume calculation. The 3D reconstruction results in a 3D model of the coronary vessel system, consisting of the vessel skeleton and a discrete number of contours. To obtain an utmost accurate model, the authors focussed on exact geometry determination. Several algorithms for calculating missing geometric parameters and correcting remaining geometry errors were implemented and verified. The length/volume evaluation can be performed either on single vessel segments, on a set of segments, or on subtrees. A volume model based on generalized elliptical conic sections is created for the selected segments. Volumes and lengths (measured along the vessel course) of those elements are summed up. In this way, the morphological parameters of a vessel subsystem can be set in relation to the parameters of the proximal segment supplying it. These relations allow objective assessments of diffuse coronary artery diseases.
Innovation in Bladder Cancer Immunotherapy (2016)

Bladder cancer is understudied despite its high prevalence and its remarkable response to immunotherapy. Indeed, funding for studies to explore mechanisms of tumor immunity and novel new therapeutics is disproportionately lower for bladder cancer in comparison with malignancies of the breast, prostate, or lung. However, the recent successes of checkpoint blockade therapy suggest that new therapeutic strategies are on the horizon for bladder cancer. Here, we give a perspective into the evolution of bladder cancer therapy, focusing on strategies to treat high-risk nonmuscle invasive disease, followed by a discussion of recent advances in the treatment of muscle invasive bladder cancer and their potential applicability to lower stage disease. Finally, we explore immunotherapeutic strategies, which have been demonstrated to be successful in the treatment of other malignancies, for their potential to treat and cure patients with nonmuscle and muscle invasive bladder cancer.
Complexation Dynamics of Xanthone and Thioxanthone to β-Cyclodextrin Derivatives (2001)

The complexation dynamics of xanthone to substituted β-cyclodextrins (CDs) and of thioxanthone to β-CD was studied by directly following the relocation of the excited triplet-state ketones from the CD cavity to the aqueous phase. Equilibrium constants for the ground-state complexation of both ketones with CDs were determined from fluorescence studies. The complexation efficiency and dynamics of thioxanthone with β-CD were the same as previously observed for the xanthone/β-CD system. Substitution of some of the hydrogens on the alcohol groups by methyl moieties at both entrances to the β-CD cavity increased the equilibrium constant for ground-state xanthone, but decreased that for the excited triplet state, leading to a larger difference for the binding behavior of these two electronic states of the guest. Addition of one pendant arm containing a carboxyl moiety to the rim where xanthone is bound does not change the binding efficiency of the ground state or the binding dynamics of triplet xanthone. In contrast, when this arm contains an ethyl ester moiety, the binding efficiencies of both the ground and excited triplet states are increased. The higher binding constant for triplet xanthone is due to an increase of the association rate constant and a decrease for the dissociation rate constant.
Spectrum of Liver Disease in Type 2 Diabetes and Management of Patients With Diabetes and Liver Disease (2007)

It is estimated that 20.8 million people, i.e., 7.0% of the U.S. population, have diabetes (1). Type 2 diabetes, with its core defects of insulin resistance and relative insulin deficiency, accounts for 90–95% of those with the disease. Another 5.2 million people are estimated to have undiagnosed type 2 diabetes. It is the sixth leading cause of death (1) in the U.S. and accounts for 17.2% of all deaths for those aged >25 years (2).

Liver disease is an important cause of death in type 2 diabetes. In the population-based Verona Diabetes Study (3), cirrhosis was the fourth leading cause of death and accounted for 4.4% of diabetes-related deaths. The standardized mortality ratio (SMR), i.e., the relative rate of an event compared with the background rate, for cirrhosis was 2.52 compared with 1.34 for cardiovascular disease (CVD). In another prospective cohort study (4), cirrhosis accounted for 12.5% of deaths in patients with diabetes.

Diabetes, by most estimates, is now the most common cause of liver disease in the U.S. Cryptogenic cirrhosis, of which diabetes is, by far, the most common cause, has become the third leading indication for liver transplantation in the U.S. (5,6). Virtually the entire spectrum of liver disease is seen in patients with type 2 diabetes. This includes abnormal liver enzymes, nonalcoholic fatty liver disease (NAFLD), cirrhosis, hepatocellular carcinoma, and acute liver failure. In addition, there is an unexplained association of diabetes with hepatitis C. Finally, the prevalence of diabetes in cirrhosis is 12.3–57% (7). Thus, patients with diabetes have a high prevalence of liver disease and patients with liver disease have a high prevalence of diabetes.

The management of diabetes in patients with liver disease is theoretically complicated by liver-related alterations in drug metabolism, potential interactions between the drugs, and a low, albeit …
TRANSFERABILITY OF RUBUS MICROSATELLITE MARKERS TO BLACK RASPBERRY (2010)

Microsatellite or simple sequence repeat (SSR) markers have been developed from genomic and expressed sequence tag (EST) libraries in red raspberry (Rubus idaeus, subgenus Idaeobatus) and also in blackberry (Rubus subgenus Rubus). Recently, there has also been increased interest in the use of SSR markers in black raspberry (R. occidentalis subgenus Idaeobatus) to aid in the identification and characterization of new sources of genetic diversity for breeding, and to aid in the development of a core collection of the 208 seed and clonal accessions at the US Department of Agriculture, Agricultural Research Service, National Clonal Germplasm Repository in Corvallis, Oregon. The objective of this study was to determine the suitability of SSR markers developed in other Rubus species for use in black raspberry. Amplification and optimum annealing temperatures of 112 Rubus SSR primer pairs were determined in the black raspberry 'Munger' by gradient polymerase chain reaction. A panel of 15 cultivars and wild black raspberry accessions was used to evaluate these SSR primers for polymorphism, using 3% agarose gel electrophoresis. This led to the identification of 27 primer pairs that appeared to generate polymorphic markers. Marker quality and genetic relationships were evaluated by fragment analysis in 12 cultivated and 4 wild genotypes using 20 of these markers after separation by capillary electrophoresis.
Test structure measuring inter- and intralayer coupling capacitance of interconnection with subfemtofarad resolution (2004)

We present a new test structure measuring inter- and intralayer coupling capacitance parasitic to the same target interconnection with subfemtofarad resolution. The coupling capacitance as well as fringing capacitance measured by the test structure are demonstrated for two-level copper interconnections used in 90-nm technology node. In addition, we demonstrate that the accuracy of layout parameters extraction is improved by nondestructive inverse modeling of a copper interconnect cross-sectional structure, which reproduces the pitch dependence of the measured inter- and intralayer coupling capacitance within about a 1% error.
Theoretical study of the gas-phase reaction between formyl cation and aromatics (2008)

Theoretical calculations of the reaction of formyl cation (CHO+) with toluene, cumene and p-cresol showed that proton transfer is thermodynamically preferred over acylation. For toluene, acylation of the aromatic ring, to form the Wheland complex, is 11.7 kcal mol-1 higher in energy (ΔH) than protonation, at MP4(SDTQ)/6-31++G(d,p)//MP2(full)/6-31G(d,p) level of theory. This difference reduces upon introduction of a hydroxy group in the ring (p-cresol) or replacing the methyl group by an isopropyl group (cumene). Protonation of toluene by H3+ and isoformyl cation is 88.6 and 84.5 kcal mol-1, respectively, more exothermic than acylation, at MP4(SDTQ)/6-31++G(d,p)//MP2(full)/6-31G(d,p). The proton affinity of p-cresol was calculated to be 195.4 kcal mol-1.
Concept of predictable disinfection in endodontics. (2010)

Factors influencing the appropriate time to obturate a tooth are the patient's signs and symptoms, pulp and periradicular status, degree of difficulty, and patient management. The current consensus is that one-step treatment procedures are acceptable in cases where the patient exhibits a vital pulp. The removal of normal or inflamed pulp tissue and performance of the procedure under aseptic conditions should result in a successful outcome because of the absence of bacterial contamination. Obturation at the initial visit also precludes the contamination as a result of leakage during the period between the patient's visits. When patients present with acute symptoms caused by pulp necrosis and acute periradicular abscess, the obturation is generally delayed until the patient is asymptomatic. The interappointment antimicrobial dressing is indicated before the definitive obturation (Ref. 15).
DESIGN STUDY OF RADIO FREQUENCY SYSTEMS FOR THE UNIVERSITY OF MICHIGAN 83 INCH CYCLOTRON. Report 200-86-1-R1 (1961)

R-f systems covering the range of 6.5 to 15 Mc providing 70 kv peak to ground on two dees were studied. Conceptual mechanical designs and electrical voltage, current, and power calculations are included for several systems. Two systems were considered in detail. These were a quarterwave vacuum-insulated system and a half-wave system with insulators at the dee tank wall. Either of these aystems was considered feasible and neither was considered to have an outstanding advantage over the other. (auth)
Tissue Lignification, Cell Wall p-Coumaroylation and Degradability of Maize Stems Depend on Water Status (2018)

Water supply and valorization are two urgent issues in the utilization of maize biomass in the context of climate change and replacement of fossil resources. Maximizing maize biomass valorization is of interest to make biofuel conversion competitive, and to increase forage energetic value for animal fodder. One way to estimate biomass valorization is to quantify cell wall degradability. In this study, we evaluated the impact of water supply on cell wall degradability, cell wall contents and structure, and distribution of lignified cell types in maize internodes using dedicated high-throughput tools to effectively phenotype maize internodes from 11 inbred lines under two contrasting irrigation scenarios in field trials over three years. Overall, our results clearly showed that water deficit induced significant changes in lignin content and distribution along with a reduction in lignin p-coumaroylation, thereby impacting cell wall degradability. Additionally, we also observed that responses to a water deficit varied between the lines examined, underscoring biochemical and histological target traits for plant breeding.
Oxidation of Histidine Residues in Copper−Zinc Superoxide Dismutase by Bicarbonate-Stimulated Peroxidase and Thiol Oxidase Activities: Pulse EPR and NMR Studies (2010)

In this work, we investigated the oxidative modification of histidine residues induced by peroxidase and thiol oxidase activities of bovine copper-zinc superoxide dismutase (Cu-ZnSOD) using NMR and pulse EPR spectroscopy. 1D NMR and 2D-NOESY were used to determine the oxidative damage at the Zn(II) and Cu(II) active sites as well as at distant histidines. Results indicate that during treatment of SOD with hydrogen peroxide (H(2)O(2)) or cysteine in the absence of bicarbonate anion (HCO(3)(-)), both exchangeable and nonexchangeable protons were affected. Both His-44 and His-46 in the Cu(II) active site were oxidized based on the disappearance of NOESY cross-peaks between CH and NH resonances of the imidazole rings. In the Zn(II) site, only His-69, which is closer to His-44, was oxidatively modified. However, addition of HCO(3)(-) protected the active site His residues. Instead, resonances assigned to the His-41 residue, 11 Å away from the Cu(II) site, were completely abolished during both HCO(3)(-)-stimulated peroxidase activity and thiol oxidase activity in the presence of HCO(3)(-) . Additionally, ESEEM/HYSCORE and ENDOR studies of SOD treated with peroxide/Cys in the absence of HCO(3)(-) revealed that hyperfine couplings to the distal and directly coordinated nitrogens of the His-44 and His-46 ligands at the Cu(II) active site were modified. In the presence of HCO(3)(-), these modifications were absent. HCO(3)(-)-mediated, selective oxidative modification of histidines in SOD may be relevant to understanding the molecular mechanism of SOD peroxidase and thiol oxidase activities.
Ozone Predictions in Atlanta, Georgia: Analysis of the 1999 Ozone Season (2001)

Ozone prediction has become an important activity in many U.S. ozone nonattainment areas. In this study, we describe the ozone prediction program in the Atlanta metropolitan area and analyze the performance of this program during the 1999 ozone-forecasting season. From May to September, a team of 10 air quality regulators, meteorologists, and atmospheric scientists made a daily prediction of the next-day maximum 8-hr average ozone concentration. The daily forecast was made aided by two linear regression models, a 3-dimensional air quality model, and the no-skill ozone persistence model. The team's performance is compared with the numerical models using several numerical indicators. Our analysis indicated that (1) the team correctly predicted next-day peak ozone concentrations 84% of the time, (2) the two linear regression models had a better performance than a 3-dimensional air quality model, (3) persistence was a strong predictor of ozone concentrations with a performance of 78%, and (4) about half of the team's wrong predictions could be prevented with improved meteorological predictions.
Role of the four conserved histidine residues in the amidotransferase domain of carbamoyl phosphate synthetase (1991)

Carbamoyl phosphate synthetase from Escherichia coli catalyzes the formation of carbamoyl phosphate from ATP, bicarbonate, and glutamine. The amidotransferase activity of this enzyme is catalyzed by the smaller of the two subunits of the heterodimeric protein. The roles of four conserved histidine residues within this subunit were probed by site-directed mutagenesis to asparagine. The catalytic activities of the H272N and H341N mutants are not significantly different than that of the wild-type enzyme. The H353N mutant is unable to utilize glutamine as a nitrogen source in the synthetase reaction or the partial glutaminase reaction. However, binding to the glutamine active site is not impaired in the H353N enzyme since glutamine is found to activate the partial ATPase reaction by 40% with a Kd of 54 microM. The H312N mutant has a Michaelis constant for glutamine that is 2 orders of magnitude larger than the wild-type value, but the maximal rate of glutamine hydrolysis is unchanged. These results are consistent with His-353 functioning as a general acid/base catalyst for proton transfers while His-312 serves a critical role for the binding of glutamine to the active site.
The possibilities of phosphorescence measurement in chemical analysis: tests with a new instrument (1962)

The first page of this article is displayed as the abstract.
Autonomous Robotic System for Pin Pulling Operation in Rail Yard (2015)

The railroad industry expends significant effort to increase operational safety and efficiency by using a variety of sensors for machine health monitoring and inspection purposes. This paper proposes to advance rail technology even further to use similar sensor data for the control of a robotic system designed to automate the uncoupling of freight cars, a hazardous operation that currently requires human operators to interact with moving trains. To automate this process, an intelligent robotic system was developed to detect, track, approach, grasp, and manipulate semi-constrained objects on equipment in motion. This work presents a system prototype that utilizes machine vision, force feedback, and complex end-effector technology capable of autonomously uncoupling full-scale freight cars using visual and tactile feedback. Laboratory tests have proven that modern robotic and sensing hardware can be used to reliably separate pairs of rolling stock at 3.25 kilometers per hour. The results to date suggest that speeds of up to 7 km/h are feasible for a system deployed in a rail yard.