gebhart/patrepeval huggingface dataset:
Ethanol-Related Behaviors in Mouse Lines Selectively Bred for Drinking to Intoxication (2021)

Alcohol use disorder (AUD) is a devastating psychiatric disorder that has significant wide-reaching effects on individuals and society. Selectively bred mouse lines are an effective means of exploring the genetic and neuronal mechanisms underlying AUD and such studies are translationally important for identifying treatment options. Here, we report on behavioral characterization of two replicate lines of mice that drink to intoxication, the High Drinking in the Dark (HDID)-1 and -2 mice, which have been selectively bred (20+ generations) for the primary phenotype of reaching high blood alcohol levels (BALs) during the drinking in the dark (DID) task, a binge-like drinking assay. Along with their genetically heterogenous progenitor line, Hs/Npt, we tested these mice on: DID and drinking in the light (DIL); temporal drinking patterns; ethanol sensitivity, through loss of righting reflex (LORR); and operant self-administration, including fixed ratio (FR1), fixed ratio 3:1 (FR3), extinction/reinstatement, and progressive ratio (PR). All mice consumed more ethanol during the dark than the light and both HDID lines consumed more ethanol than Hs/Npt during DIL and DID. In the dark, we found that the HDID lines achieved high blood alcohol levels early into a drinking session, suggesting that they exhibit front loading like drinking behavior in the absence of the chronicity usually required for such behavior. Surprisingly, HDID-1 (female and male) and HDID-2 (male) mice were more sensitive to the intoxicating effects of ethanol during the dark (as determined by LORR), while Hs/Npt (female and male) and HDID-2 (female) mice appeared less sensitive. We observed lower HDID-1 ethanol intake compared to either HDID-2 or Hs/Npt during operant ethanol self-administration. There were no genotype differences for either progressive ratio responding, or cue-induced ethanol reinstatement, though the latter is complicated by a lack of extinguished responding behavior. Taken together, these findings suggest that genes affecting one AUD-related behavior do not necessarily affect other AUD-related behaviors. Moreover, these findings highlight that alcohol-related behaviors can also differ between lines selectively bred for the same phenotype, and even between sexes within those same line.
A data‐driven disease progression model of fluid biomarkers in genetic FTD (2021)

Abstract Background Several fluid biomarkers for genetic frontotemporal dementia (FTD) have been proposed, including those reflecting neuroaxonal loss (neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH)), synapse dysfunction (neuronal pentraxin 2 (NPTX2)), gliosis (glial fibrillary acidic protein (GFAP)) and complement activation (C3b, C1q). Determining the sequence in which biomarkers become abnormal over the course of disease could facilitate disease staging in FTD and enable us to identify mutation carriers with prodromal or early‐stage FTD, which is especially important as pharmaceutical interventions emerge. We aimed to model the sequence of biomarker abnormalities in presymptomatic and symptomatic genetic FTD using cross‐sectional data from the Genetic Frontotemporal dementia Initiative (GENFI). Method 276 presymptomatic and 142 symptomatic carriers of mutations in GRN, C9orf72 or MAPT , as well as 247 non‐carriers, were selected from the GENFI cohort based on availability of one or more of the aforementioned biomarkers. Nine presymptomatic carriers developed symptoms within 18 months of data collection (‘converters’). Sequences of biomarker abnormalities were modelled for the entire group using discriminative event‐based modelling (DEBM) and for each genetic subgroup using co‐initialized DEBM. These models estimate probabilistic biomarker abnormalities in a data‐driven way and do not rely on prior diagnostic information or biomarker cut‐off points. We estimated individual disease severity scores based on the position of subjects along the disease progression timeline through cross‐validation. Result Cerebrospinal fluid (CSF) NPTX2 was the first detectable abnormal biomarker, followed by blood and CSF NfL, blood GFAP, blood pNfH and finally CSF C1q and C3b (Fig. 1). Biomarker orderings did not differ significantly between genetic subgroups. Estimated disease severity scores (Fig. 2) could distinguish symptomatic from presymptomatic carriers and non‐carriers with areas under the curve (AUC) of 0.84 and 0.90 respectively. The AUC to distinguish converters from non‐converting presymptomatic carriers was 0.85. Conclusion In our data‐driven disease progression models of genetic FTD, NPTX2 and NfL were the first biomarkers to become abnormal. Further research should focus on their utility as candidate selection tools for pharmaceutical trials. Estimating disease stages using DEBM could enable us to identify presymptomatic carriers approaching symptom onset and track the efficacy of therapeutic interventions.
A 390ps 1000-gate array using GaAs super-buffer FET logic (1985)

A report on SBFL and DCFL 1000 gate GaAs arrays will be offered. It was found that superior SBFL drive capability provided a 2× performance improvement (390ps) over DCFL at the same power level.
Inhibition of Caspase-8 Activity Caused by Overexpression of BCL10 Contributes to the Pathogenesis of High-Grade MALT Lymphoma, (2011)

Abstract Abstract 3694 Mucosa-associated lymphoid tissue (MALT) lymphoma comprises approximately 8% of all non-Hodgkin lymphomas and is the most common lymphoma in the gastrointestinal tract. B-cell lymphoma/leukemia 10 (BCL10) overexpression and nuclear expression has been associated with high-grade MALT lymphomas unresponsive to H. pylori eradication treatment. To explore the molecular mechanism of BCL10 overexpression on the pathogenesis and malignant phenotype of MALT lymphoma, we generated EμSR-BCL10 transgenic mice. Results in our previous report showed that predisposition to marginal zone B-cell lymphoma (MZL) development was enhanced in these transgenic mice. MALT lymphoma precursor cells - marginal zone (MZ) B cells - are expanded in BCL10 transgenic mice. Constitutive activation of both canonical and noncanonical NF-κB pathways was identified in these MZ B cells. Elevated expression of BAFF, a NF-κB downstream gene, may be in part responsible for increased tumor cell survival in MALT lymphomas. In this continuing study, quantitative analysis of BCL10 protein levels and the extent of MZ B cell expansion in heterozygous (Tg/+) and homozygous (Tg/Tg) EμSR-BCL10 transgenic mice demonstrated a direct pathogenic effect of BCL10 protein on MALT lymphomagenesis. The activities of caspase-8 and caspase-3, but not caspase-9, were inhibited with increasing BCL10 protein levels in a dose-dependent manner. Apoptosis induced by anti-IgM was selectively inhibited in MZ B cells from transgenic mice, but no differences were observed following treatment with dexamethasone, γ-irradiation or anti-CD95, implying that overexpressed BCL10 exerts anti-apoptotic effects through the B-cell antigen receptor pathway. Expression of API2, another NF-κB downstream gene, was also elevated in a dose-dependent manner with BCL10 protein level in the MZ B cells. Overexpressed BCL10 protein co-immunoprecipitated with caspase-8 and API2, suggesting an in vivo interaction leading to inhibition of caspase-8 activity. Our current data suggests a novel effect of overexpressed BCL10 in the pathogenesis of high-grade MALT lymphoma by increasing expression of API2 and recruitment of API2 and caspase-8 to form a protein complex leading to the suppression of caspase-8 activity in MZ B cells. Disclosures: No relevant conflicts of interest to declare.
Phenotype of the Obese Koletsky (f) Rat Due to Tyr763Stop Mutation in the Extracellular Domain of the Leptin Receptor (Lepr): Evidence for Deficient Plasma-to-CSF Transport of Leptin in Both the Zucker and Koletsky Obese Rat (1997)

The obese phenotypes of the diabetes (db) mouse and fatty fa) rat are due to functional null mutations of the leptin receptor (Lepr). The recessive mutation in the Koletsky (f) obese rat maps to the same genetic intervals as db and fa and fails to complement the fa mutation. Comparison of the sequence of brain Lepr cDNA from +/+ and f/f animals reveals a T2349A transversion resulting in a Tyr763Stop nonsense mutation in the gene just before the transmembrane domain. Virtual absence of Lepr mRNA in whole brain from f/f animals is consistent with the presence of a null mutation. The predicted reduced cerebrospinal fluid (CSF) transport of leptin in both f/f and fa/fa mutants is reflected in the approximately 10-fold lower ratio of CSF/plasma leptin concentration in the obese versus lean animals. However, equivalent CSF leptin concentration between lean and obese rats (fa/fa, f/f) indicates that leptin can enter the CSF through a non-Lepr-mediated mechanism, which may be saturated at normal physiological plasma leptin concentration.
POWER SYSTEM STABILITY ENHANCEMENT USING FACTS CONTROLLERS: A REVIEW (2009)

In recent years, power demand has increased substantially while the expansion of power generation and transmission has been severely limited due to limited resources and environmental restrictions. As a consequence, some transmission lines are heavily loaded and the system stability becomes a power transfer-limiting factor. Flexible AC transmission systems (FACTS) controllers have been mainly used for solving various power system steady state control problems. However, recent studies reveal that FACTS controllers could be employed to enhance power system stability in addition to their main function of power flow control. The literature shows an increasing interest in this subject for the last two decades, where the enhancement of system stability using FACTS controllers has been extensively investigated. This paper presents a comprehensive review on the research and developments in the power system stability enhancement using FACTS damping controllers. Several technical issues related to FACTS installations have been highlighted and performance comparison of different FACTS controllers has been discussed. In addition, some of the utility experience, real-world installations, and semiconductor technology development have been reviewed and summarized. Applications of FACTS to other power system studies have also been discussed. About two hundred twenty seven research publications have been classified and appended for a quick reference.
Power quality measurements of wind energy converters with full-scale converter according to IEC 61400-21 (2009)

Wind energy has reached remarkable shares in the electrical energy production in many countries worldwide. However, the connection of multi-megawatt wind farms leads to the necessity to examine the impact on the grid closely. The International Electrotechnical Commission (IEC) developed and released the IEC-standard 61400-21 as part of the IEC 61400 standards for testing and assessing power quality characteristics of grid-connected wind energy converters (WECs) in a consistent and accurate way. To easily compare WECs of different types it defines a measurement excerpt that states the key power quality characteristics: wind turbine specifications, active and reactive power output, flicker, harmonics, control of active and reactive power, protection, voltage dip response and reconnection time. Based on the measurement results in that excerpt the maximum grid connection capacity can be determined for a chosen connection point in order to fulfil the given national or international power quality requirements. Different wind turbine types have different power quality characteristics. As a pioneer in advanced WEC technology and grid integration, ENERCON has developed a range of certified WEC types to address the most demanding international grid codes. In recent years the power quality characteristics of all these types were tested and certified according to IEC 61400-21 by independent testing institutes. Reasons for the good power quality characteristics can be found in the design of these WECs based on an annular generator, injecting power via full-scale power electronics and associated control systems. Additional control features like soft-start without inrush currents, storm control and wind farm control systems to control the voltage, power factor or reactive power can, to a certain extent, even improve power quality in power systems.
Supplementary Methods from Patient-Driven Discovery, Therapeutic Targeting, and Post-Clinical Validation of a Novel <i>AKT1</i> Fusion–Driven Cancer (2023)

&lt;p&gt;Supplementary Methods&lt;/p&gt;
A New Anti‐inflammatory Derivative of Imidazole which is Less Ulcerogenic than Indomethacin in Rats (1979)

The mechanism of the anti-inflammatory activity and ulcerogenicity of (2-dimethylamino-1(2)-methyl) ethyl ester of the 1-(2-carboxyethyl)-2-(p-chlorophenyl)-4,5-bis-(p-methoxyphenyl)-imidazole (A-162-ester) was compared with that of indomethacin in rats and enzymatic preparations derived from other species. A-162-ester was found to be deesterified in plasma to A-162. A-162-ester was about 3 times less anti-inflammatory and about 17 times less ulcerogenic than indomethacin. A-162-ester, when given orally, decreased prostaglandin I2 (PGI2) biosynthesis by gastric mucosa. The IC50 was close to the ulcerogenic ED50. Indomethacin--in the same test--was 37 times more potent than A-162-ester and the PGI2 inhibition and ulcerogenic dose-response curves for indomethacin were parallel. In other in vitro systems of prostaglandin (PG) biosynthesis, the inhibitory activity of A-162 was comparable to that of indomethacin. It is concluded that the ulcerogenicity of indomethacin results from a high affinity of this drug to gastric mucosal wall PG-synthetase which leads to decreased PGI3 formation at this site. The relatively low ulcerogenicity of A-162-ester most probable results from a lower affinity of this drug to the same site.
Nano-dimensional measurement using optically trapped probe enhanced by interferometric scale (2009)

Abstract − We propose a new dimensional measurement technique that is capable of measuring the bottom surface of a stepwise shape. The measurement system is composed of a length scale and a sensor probe to read the scale. The probe is trapped and controlled three-dimensionally by laser trapping technique. The scale is arisen by optical interference, which is extended straight to the measured surface from the probe. Firstly measurement principle is theoretically explained. Remarkable feature of this technique is feasibility to access the area as narrow as 15 μm. Vertical resolution of this measurement technique is experimentally estimated as 10 nm. The measurable range of the inclination angle of surface is less than 15 ˚. In terms of the measurement accuracy, it is evaluated around 100 nm.