gebhart/patrepeval huggingface dataset:
Inhibition of LRRK2 Kinase Activity in the Treatment of Crohn’s Disease (2022)

Abstract The leucine-rich repeat kinase 2 (LRRK2) gene is a genetic hotspot for gain-of-function mutations associated with various diseases such as Crohn’s and Parkinson’s disease. These mutations enhance LRRK2 kinase activity and, consequently, various inhibitors of this activity are currently being tested as treatment modalities. Here, we report studies of two novel kinase inhibitors (Termed CS-190 and CS-82) with LRRK2 inhibition activity. In vitro studies disclosed that the two inhibitors suppress LRRK2 phosphorylation as well as its ability to phosphorylate the LRRK2 targets, Rab 10 and 12; in addition, they suppress human dendritic cell production of TNFa stimulated by several known LRRK2 activators including the Dectin-1-ligand, zymosan-depleted S. cerevisiae extract. Finally, the inhibitors exhibited powerful suppression of the ability of LRRK2 to mediate NLRC4 inflammasome production of IL-1beta. These in vitro finding correlated with in vivo studies showing that IP administration of one of the kinase inhibitors (CS-82) ameliorates colitis in the DSS-colitis model as evaluated by weight loss and inflammation scores. These findings suggest that these newly developed inhibitors are potential agents for treatment of Crohn’s disease.
G(RADA1): a new cell surface antigen of mouse leukemia defined by naturally occurring antibody and its relationship to murine leukemia virus. (1978)

A new cell surface antigenic system of the mouse, designated G(RADA1), is described. The antigen is defined by cytotoxic tests with the A strain X-ray-induced leukemia RADA1 and naturally occurring antibody from random-bred Swiss mice and can be distinguished from all other serologically detected cell surface antigens of the mouse. Absorption tests indicate that G(RADA1) is present in the normal lymphatic tissue and leukemias of mouse strains with high spontaneous leukemia-incidence, e.g., AKR, C58, and C3H/Figge. Low leukemia-incidence strains, e.g., C57BL/6, BALB/c, and A lack G(RADA1) in their normal tissues, but a proportion of leukemias and solid tumors arising in these strains are G(RADA1)+. The relation of G(RADA1) to MuLV is shown by G(RADA1) appearance after MuLV infection of permissive cells in vitro; four of five N-tropic MuLV isolates, one of four B-tropic MuLV, and none of four xenotropic MuLV induce G(RADA1). Two MCF MuLV, thought to represent recombinants between N-ecotropic and xenotropic MuLV, also induce G(RADA1). Serological and biochemical characterization indicates that G(RADA1) is a type-specific determinant of the gp70 component of certain MuLV. The presence of natural antibody to RADA1 in various mouse strains and the emergence of G(RADA1)+ leukemias and solid tumors in mice of G(RADA1)- phenotype suggest widespread occurrence of genetic information coding for this antigen.
External modulation of Terahertz quantum cascade lasers using metamaterials. (2016)

Abstract not provided.
Impact of Immunization with Glycoprotein D2/AS04 on Herpes Simplex Virus Type 2 Shedding into the Genital Tract in Guinea Pigs That Become Infected (2005)

In recent clinical trials, a vaccine that contained herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) and the adjuvant AS04 afforded HSV-seronegative women significant protection against HSV-2 genital disease and limited protection against infection. Similarly, in guinea pigs, immunization with the vaccine provided significant protection against genital HSV-2 disease but did not prevent mucosal infection. We explored the impact of immunization on the magnitude of latent virus infection and on the frequency and magnitude of virus reactivation as measured by both recurrent disease and viral shedding into the genital tract. Guinea pigs immunized with gD2/AS04 were shown by quantitative polymerase chain reaction (qPCR) analysis to have significantly less latent viral DNA in the ganglia than did naive control guinea pigs and to have a reduced incidence and frequency of recurrent disease. By contrast, all immunized guinea pigs shed virus into the genital tract with a frequency comparable to that seen in control guinea pigs. However, the amount of virus shed was significantly reduced, as measured by qPCR. These data suggest that immunization could affect transmission by altering viral shedding patterns.
Supplementary Movie from The Transcription Factor ZNF217 Is a Prognostic Biomarker and Therapeutic Target during Breast Cancer Progression (2023)

&lt;p&gt;PDF file - 12MB, Movie of SCp2 cells infected with vector (left movie) or Znf217 (right movie) following a scratch with a pipette tip. This movie ran for 20.25 hours&lt;/p&gt;
Purification to homogeneity of Charonia lampas α-fucosidase by using sequential ligand-affinity chromatography (1991)

An alpha-fucosidase from the liver of the marine gastropod Charonia lampas was purified to homogeneity using a procedure that included cation-exchange and gel-filtration chromatography, chromatofocusing and a final series of affinity-chromatography steps which involved the following gel-immobilized ligands: N-(5-carboxy-1-pentyl)-1,5-dideoxy-1,5-imino-L-fucitol, N-(5-carboxy-1-pentyl)-2-acetamido-1,5-imino-1,2,5-trideoxy-D-glucitol and thio-beta-D-galactoside. The enzyme was found to be a tetrameric glycoprotein with a native Mr of 208,000, and to exist in a number of isoforms displaying pI values in the range 6.0-6.4. Substrate-specificity studies using a number of fucosylated oligosaccharides of the lacto-N and lacto-N-neo series and a synthetic disaccharide confirmed that the enzyme catalyses the hydrolysis of a broad range of fucosidic linkages, and established the following hierarchy of susceptibility: Fuc alpha 2Gal beta 4Glc much much greater than Fuc alpha 6GlcNAc greater than Fuc alpha 2Gal beta 4GlcNAc greater than Gal beta 3(Fuc alpha 4)GlcNAC much much greater than Gal beta 4(Fuc alpha 3)GlcNAc. Similar relative rates of hydrolysis were also demonstrated using biantennary oligosaccharide alditols as substrates which contained fucose linked either alpha 3 or alpha 6 to the N-acetylglucosaminitol residue of the chitobiosyl core.
Ultra-low voltage circuits and processor in 180nm to 90nm technologies with a swapped-body biasing technique (2004)

A low-voltage swapped-body biasing technique where PMOS bodies are connected to ground and NMOS bodies to Vcc is evaluated. Available measurements show more than 2.6x frequency improvement at 0.5V Vcc and the ability to reduce Vcc by 0.2V for the same frequency compared to no body bias in 180 to 90nm CMOS technologies.
Heterogenised Molecular Catalysts for Sustainable Electrochemical CO2 Reduction (2022)

There has been a rapid rise in interest regarding the advantages of support materials to protect and immobilise molecular catalysts for the carbon dioxide reduction reaction (CO<sub>2</sub> RR) in order to overcome the weaknesses of many well-known catalysts in terms of their stability and selectivity. In this Review, the state of the art of different catalyst-support systems for the CO<sub>2</sub> RR is discussed with the intention of leading towards standard benchmarking for comparison of such systems across the most relevant supports and immobilisation strategies, taking into account these multiple pertinent metrics, and also enabling clearer consideration of the necessary steps for further progress. The most promising support systems are described, along with a final note on the need for developing more advanced experimental and computational techniques to aid the rational design principles that are prerequisite to prospective industrial upscaling.
The effect of spatial coupling on compressive sensing (2010)

Recently, it was observed that spatially-coupled LDPC code ensembles approach the Shannon capacity for a class of binary-input memoryless symmetric (BMS) channels. The fundamental reason for this was attributed to a threshold saturation phenomena derived in. In particular, it was shown that the belief propagation (BP) threshold of the spatially coupled codes is equal to the maximum a posteriori (MAP) decoding threshold of the underlying constituent codes. In this sense, the BP threshold is saturated to its maximum value. Moreover, it has been empirically observed that the same phenomena also occurs when transmitting over more general classes of BMS channels. In this paper, we show that the effect of spatial coupling is not restricted to the realm of channel coding. The effect of coupling also manifests itself in compressed sensing. Specifically, we show that spatially-coupled measurement matrices have an improved sparsity to sampling threshold for reconstruction algorithms based on verification decoding. For BP-based reconstruction algorithms, this phenomenon is also tested empirically via simulation. At the block lengths accessible via simulation, the effect is rather small but, based on the threshold analysis, we believe this warrants further study.
Prediction of Activity for Nonnucleoside Inhibitors with HIV-1 Reverse Transcriptase Based on Monte Carlo Simulations (2002)

Results of Monte Carlo (MC) simulations for more than 200 nonnucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) representing eight diverse chemotypes have been correlated with their anti-HIV activities in an effort to establish simulation protocols and methods that can be used in the development of more effective drugs. Each inhibitor was modeled in a complex with the protein and by itself in water, and potentially useful descriptors of binding affinity were collected during the MC simulations. A viable regression equation was obtained for each data set using an extended linear response approach, which yielded r(2) values between 0.54 and 0.85 and an average unsigned error of only 0.50 kcal/mol. The most common descriptors confirm that a good geometrical match between the inhibitor and the protein is important and that the net loss of hydrogen bonds with the inhibitor upon binding is unfavorable. Other physically reasonable descriptors of binding are needed on a chemotype case-by-case basis. By including descriptors in common from the individual fits, combination regressions that include multiple data sets were also developed. This procedure led to a refined "master" regression for 210 NNRTIs with an r(2) of 0.60 and a cross-validated q(2) of 0.55. The computed activities show an rms error of 0.86 kcal/mol in comparison with experiment and an average unsigned error of 0.69 kcal/mol. Encouraging results were obtained for the predictions of 27 NNRTIs, representing a new chemotype not included in the development of the regression model. Predictions for this test set using the master regression yielded a q(2) value of 0.51 and an average unsigned error of 0.67 kcal/mol. Finally, additional regression analysis reveals that use of ligand-only descriptors leads to models with much diminished predictive ability.
Is Peripheral Neuropathy Associated With Retinopathy and Albuminuria in Individuals With Impaired Glucose Metabolism?: The 1999-2000 AusDiab (2006)

Individuals with impaired glucoses tolerance (IGT) or impaired fasting glucose (IFG) are at substantially increased risk of developing diabetes and cardiovascular disease (1). The extent to which individuals with IGT/IFG are also at risk of microvascular complications, such as neuropathy, retinopathy, and nephropathy, has not been as well defined. Some (2,3), but not all (4–7), studies have shown that microvascular complications are more common in individuals with IGT/IFG than those with normal glucose metabolism.

Peripheral neuropathy, a common microvascular complication of diabetes (8), is often associated with concomitant retinopathy (9) and albuminuria (9,10). Whether peripheral neuropathy is also associated with retinopathy and albuminuria in people with IGT/IFG is unclear and is examined in the current study.

The Australian, Diabetes, Obesity, and Lifestyle Study (AusDiab) is a population-based survey of Australian adults aged ≥25 years (11). Glucose tolerance status was determined by a 75-g oral glucose tolerance test (12). The prevalence of diabetes in the AusDiab was 7.4%, while 16.4% had IGT or IFG (13). All participants with diabetes, IGT, IFG, and a random sample of normal control subjects were invited for complications testing (6). This analysis is based on the 1,154 individuals with IGT or IFG who attended the complications screening.

Neuropathy was classified by 1 ) the modified neuropathy symptom score (NSS), 2 ) the modified neuropathy disability score (NDS), 3 ) the pressure perception score (PPS), and 4 ) a postural systolic blood pressure drop score of ≥20 mmHg. The NSS measured …
The antiepileptic drug levetiracetam selectively modifies kindling‐induced alterations in gene expression in the temporal lobe of rats (2004)

Gene expression profiling by microarrays is a powerful tool for identification of genes that may encode key proteins involved in molecular mechanisms underlying epileptogenesis. Using the Affymetrix oligonucleotide microarray, we have surveyed the expression levels of more than 26,000 genes and expressed sequence tags (ESTs) in the amygdala-kindling model of temporal lobe epilepsy. Furthermore, the effect of the antiepileptic drug levetiracetam (LEV) on kindling-induced alterations of gene expression was studied. Treatment of rats with LEV during kindling acquisition significantly suppressed kindling development. For gene expression profiling, six groups of rats were included in the present study: (i) and (ii) sham-operated rats treated with saline or LEV; (iii) and (iv) electrode-implanted but non-kindled rats treated with saline or LEV; (v) and (vi) kindled rats treated with saline or LEV. Treatment was terminated after 11 or 12 daily amygdala stimulations, when all vehicle-treated rats had reached kindling criterion, i.e. a stage 5 seizure. Twenty-four hours later, the ipsilateral temporal lobe was dissected for mRNA preparation. Six temporal lobe preparations from each group were analysed for differential gene expression. In control (non-kindled) rats, LEV treatment was devoid of any significant effect on gene expression. In saline-treated kindled rats, a large number of genes were observed to display mRNA expression alterations compared with non-kindled rats. LEV treatment induced marked effects on gene expression from kindled rats. Previously described epilepsy-related genes, such as neuropeptide Y (NPY), thyrotropin-releasing hormone (TRH) and glial fibrillary acidic protein (GFAP) were confirmed to be up-regulated by kindling and partially normalized by LEV treatment. Real-time quantitative polymerase chain reaction confirmed NPY, TRH and GFAP expression data from chip experiments. Furthermore, a number of novel genes were identified from the gene chip experiments. A subgroup of these genes demonstrated correlation between expression changes and kindled phenotype measurements. In summary, this study identified many genes with potentially important roles in epileptogenesis and highlighted several important issues in using the gene chip technology for the study of animal models of CNS disorders.
High-Current Photodetectors as Efficient, Linear, and High-Power RF Output Stages (2008)

Recent progress in high-current photodiodes now makes it possible to efficiently generate over 26 dBm of RF power directly from the output of a photodiode. This paper describes two photodetector designs which demonstrate excellent large- and small-signal behavior. Maximum small-signal compression currents have increased to over 700 mA at 300 MHz. Output RF power amplifier stage efficiencies of over 45% (class AB operation) and 35% (class A) have been achieved from 0.3 to 6 GHz with RF power outputs over 26 dBm. The linearity figure of merit (LFOM) is also shown to be greater than 50, leading to the possibility of implementing very high linearity RF power amplifiers in the future.
The Effect of a Randomised Controlled Lifestyle Intervention on Weight Loss and Plasma Proneurotensin (2021)

Abstract Aims: Proneurotensin is a strong predictor of cardiometabolic disease, however, the effect of lifestyle change on proneurotensin has not been investigated. Middle Eastern (ME) immigrants represent the largest and fastest growing minority population in Europe and are a high-risk population for obesity and type 2 diabetes. In this randomised controlled lifestyle intervention (RCT) addressing ME immigrants to Sweden where weight-loss was previously studied as the main outcome, as a secondary analysis we aimed to study change in proneurotensin during follow-up and if baseline proneurotensin predicted weight loss.Methods: Immigrants from the Middle East at high risk for type 2 diabetes were invited to participate in this RCT adapted lifestyle intervention of four months’ duration. The intervention group (N=48) received a culturally adapted lifestyle intervention comprising seven group sessions and a cooking class addressing healthier diet and increased physical activity. The control group (N=44) received treatment as usual with information to improve lifestyle habits on their own. Data assessed using mixed effects regression.Outcomes: Primary outcome; change in proneurotensin. Secondary outcome; change in BMI in relation to baseline plasma concentration of proneurotensin.Results: During the four months follow up, weight was significantly reduced in the intervention (-2.5 kg) compared to the control group (0.8 kg) (β -0.12, 95% CI -0.24 to -0.01, P =0.028). Proneurotensin increased to a significantly greater extent in the intervention compared to the control group during follow up (28.2 vs 3.5 pmol/L) (β 11.4; 4.8 to 18.02, P &lt;0.001). Change over time in BMI was associated with baseline proneurotensin (β 0.02; 0.01 to 0.04, P =0.041).Conclusion: In consistence with data from surgical weight loss, this RCT paradoxically shows increased levels of proneurotensin during a multifactorial lifestyle intervention resulting in weight loss. Long term studies of proneurotensin following weight loss are needed. Trial registration: This study is a secondary analysis of the RCT trial registered at www.clinicaltrials.gov NCT01420198 (date of registration Aug 19 th 2011).The performance and results of this trial conform to the CONSORT 2010 guidelines.
Long term performance analysis of solar spectral irradiance meters (2016)

Two generations of solar spectral irradiance meters (SolarSIMs), D1 and D2, are evaluated against reference instrumentation at the University of Ottawa SUNLAB outdoor test facility since their commissioning on September, 2014 and October, 2015, respectively. The average spectral direct normal irradiance (DNI) of the instruments was found to be well within ±1% at the six measured bands, centred at 420, 500, 610, 780, 880, and 940 nm, and mainly within ±2% for the remaining wavelengths in the 280-4000 nm range as compared to the reference SolarSIMs. The difference in cumulative energy densities as measured by the SolarSIMs and an Eppley model NIP pyrheliometer was found to be less than 0.5%. No degradation was observed during 19 months of operation.
Taming Cross-Layer Attacks in Wireless Networks: A Bayesian Learning Approach (2018)

Wireless networks are extremely vulnerable to a plethora of security threats, including eavesdropping, jamming, and spoofing, to name a few. Recently, a number of next-generation cross-layer attacks have been unveiled, which leverage small changes on one network layer to stealthily and significantly compromise another target layer. Since cross-layer attacks are stealthy, dynamic, and unpredictable in nature, novel security techniques are needed. Since models of the environment and attacker's behavior may be hard to obtain in practical scenarios, machine learning techniques become the ideal choice to tackle cross-layer attacks. In this paper, we propose FORMAT, a novel framework to tackle cross-layer security attacks in wireless networks. FORMAT is based on Bayesian learning and made up by a detection and a mitigation component. On one hand, the attack detection component constructs a model of observed evidence to identify stealthy attack activities. On the other hand, the mitigation component uses optimization theory to achieve the desired trade-off between security and performance. The proposed FORMAT framework has been extensively evaluated and compared with existing work by simulations and experiments obtained with a real-world testbed made up by Ettus Universal Software Radio Peripheral (USRP) radios. Results demonstrate the effectiveness of the proposed methodology as FORMAT is able to effectively detect and mitigate the considered cross-layer attacks.
X-ray grating interferometry at photon energies over 180 keV (2015)

We report on the implementation and characterization of grating interferometry operating at an x-ray energy of 183 keV. With the possibility to use this technique at high x-ray energies, bigger specimens could be studied in a quantitative way. Also, imaging strongly absorbing specimens will benefit from the advantages of the phase and dark-field signals provided by grating interferometry. However, especially at these high photon energies the performance of the absorption grating becomes a key point on the quality of the system, because the grating lines need to keep their small width of a couple of micrometers and exhibit a greater height of hundreds of micrometers. The performance of high aspect ratio absorption gratings fabricated with different techniques is discussed. Further, a dark-field image of an alkaline multicell battery highlights the potential of high energy x-ray grating based imaging.
Adaptive Spatiotemporal SVD Clutter Filtering for Ultrafast Doppler Imaging Using Similarity of Spatial Singular Vectors (2018)

Singular value decomposition of ultrafast imaging ultrasonic data sets has recently been shown to build a vector basis far more adapted to the discrimination of tissue and blood flow than the classical Fourier basis, improving by large factor clutter filtering and blood flow estimation. However, the question of optimally estimating the boundary between the tissue subspace and the blood flow subspace remained unanswered. Here, we introduce an efficient estimator for automatic thresholding of subspaces and compare it to an exhaustive list of thirteen estimators that could achieve this task based on the main characteristics of the singular components, namely the singular values, the temporal singular vectors, and the spatial singular vectors. The performance of those fourteen estimators was tested in vitro in a large set of controlled experimental conditions with different tissue motion and flow speeds on a phantom. The estimator based on the degree of resemblance of spatial singular vectors outperformed all others. Apart from solving the thresholding problem, the additional benefit with this estimator was its denoising capabilities, strongly increasing the contrast to noise ratio and lowering the noise floor by at least 5 dB. This confirms that, contrary to conventional clutter filtering techniques that are almost exclusively based on temporal characteristics, efficient clutter filtering of ultrafast Doppler imaging cannot overlook space. Finally, this estimator was applied in vivo on various organs (human brain, kidney, carotid, and thyroid) and showed efficient clutter filtering and noise suppression, improving largely the dynamic range of the obtained ultrafast power Doppler images.