gebhart/patrepeval huggingface dataset:
Studies on the Nitroreductase Prodrug-Activating System. Crystal Structures of Complexes with the Inhibitor Dicoumarol and Dinitrobenzamide Prodrugs and of the Enzyme Active Form (2003)

The E. coli nitroreductase enzyme (NTR) has been widely used in suicide gene therapy (GDEPT and ADEPT) applications as a activating enzyme for nitroaromatic prodrugs of the dinitrobenzamide class. NTR has been previously shown to be a homodimeric enzyme with two active sites. We present here the crystal structures of the reduced form of NTR and its complexes with the inhibitor dicoumarol and three dinitrobenzamide prodrugs. Comparison of the structures of the oxidized and reduced forms of the native enzyme shows that the principal structural changes occur in the FMN cofactor and indicate that the enzyme itself is a relatively rigid structure that primarily provides a rigid structural framework on which hydride transfer occurs. The aziridinyldinitrobenzamide prodrug CB 1954 binds in nonidentical ways in both of the two active sites of the homodimeric enzyme, employing both hydrophobic and (in active site B) a direct H-bond contact to the side chain of Lys14. In active site A the 2-nitro group stacks above the FMN, and in active site B the 4-nitro group does, explaining why reduction of either nitro group is observed. In contrast, the larger mustard group of the dinitrobenzamide mustard compound SN 23862 forces the prodrug to bind at both active sites with only the 2-nitro group able to participate in hydride transfer from the FMN, explaining why only the 2-hydroxylamine reduction product is observed. In each site, the nitro groups of the prodrug make direct H-bond contacts with the enzyme; in active Site A the 2-nitro to Ser40 and the 4-nitro to Asn71, while in active Site B the 2-nitro contacts the main chain nitrogen of Thr41 and the 4-nitro group the Lys14 side chain. The related amide-substituted mustard SN 27217 binds in a broadly similar fashion, but with the larger amide group substituent able to reach and contact the side chain of Arg107, further restricting the prodrug conformations in the binding site. The inhibitor dicoumarol appears to bind primarily by pi-stacking interactions and hydrophobic contacts, with no conformational changes in the enzyme. One of the hydroxycoumarin subunits stacks above the plane of the FMN via pi-overlap with the isoalloxazine ring, penetrating deep into the groove, with the other less well-defined. These studies suggest guidelines for further prodrug design. Steric bulk (e.g., mustard rather than aziridine) on the ring can limit the possible binding orientations, and the reducible nitro group must be located para to the mustard. Substitution on the carboxamide side chain still allows the prodrugs to bind, but also limits their orientation in the binding site. Finally, modulating substrate specificity by alteration of the structure of the enzyme rather than the prodrug might usefully focus on modifying the Phe124 residue and those surrounding it.
Experimental Study on Low Noise FansFlow Visualization and Pressure Fluctuations on Blade Surface. (1992)

Air flows near the leading edge of the axial fan blades in an automobile radiator cooling system were studied by flow visualization and surface pressure measurements in order to reduce the noise emitted from the fan. In the region where the flow separated from the blade surface, fluctuations of the static pressure were largely increased, resulting in the generation of a higher noise level. Using two-dimensional aerofoils of different cambers, effects of the camber on the pressure fluctuations were examined, and an aerofoil with a camber of 4 percent was found to exhibit the minimum pressure fluctuation at the same value of a lift coefficient CL=0.6.
Electrostatic Discharge Control and Visualization in Spray Nozzle (2018)

The general method to remove contaminated particles in the non-pattern cleaning such as pre-photo cleaning, post-deposition cleaning, and post-CMP cleaning is to physically remove particles using spray nozzle. However, high-speed fluids for increasing particle removal efficiency cause static electricity due to friction between liquid and nozzle surfaces, resulting in unexpected charge defects. In this study, we propose a method to reduce static electricity by changing the material of nozzle and grounding by visualizing static electricity according to electric voltage.
Supplemental Figure 1 from An Integrated Molecular Analysis of Lung Adenocarcinomas Identifies Potential Therapeutic Targets among TTF1-Negative Tumors, Including DNA Repair Proteins and Nrf2 (2023)

&lt;p&gt;Supplemental Figure 1. Comparison of TTF1 by RPPA and mRNA in TCGA shiws a string positive correlation.&lt;/p&gt;
Progress in the manufacture of ultra flat optics for very high concentration flat panels (2003)

A very high concentration in photovoltaics has been achieved using systems based on GaAs solar cells and TIR-R lens working at very high concentration of incident light (1000/spl times/). The reasons for this renewed study is the potential for a drastic reduction of cost with concentration and the highly compact optics design suitable for flat panels. This paper deals with the design, manufacture and characterisation of the ultra-flat optics needed for collecting over the receiver, about 1000 Suns of concentrated sunlight. A description of the details related to the manufacturing of the moulds of the lens, plastic injection process and characterisation of the lens for achieving an acceptance angle (for 90% relative transmission) of /spl alpha/ = /spl plusmn/1.3/spl deg/, an optical efficiency (at /spl lambda/=630 nm) /spl eta//sub opt/ = 86.5% and a peak irradiance on cell surface (at 850 W/m/sup 2/) < 6000, is presented. The goal of this optics is a geometrical concentration of 1250/spl times/.
Immunogenicity and Reactogenicity of an Inactivated Quadrivalent Influenza Vaccine Administered Intramuscularly to Children 6 to 35 Months of Age in 2012–2013: A Randomized, Double-Blind, Controlled, Multicenter, Multicountry, Clinical Trial (2014)

In children aged 6 to 35 months, a QIV has superior immunogenicity for the added B strain and acceptable immunogenicity for shared strains, with no notable difference in reactogenicity and safety when compared to a TIV.
Operation of a Gasoline Direct Injection Compression Ignition Engine on Naphtha and E10 Gasoline Fuels (2016)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;Gasoline Direct Injection Compression Ignition (GDCI) is a partially premixed low temperature combustion process that has demonstrated high fuel efficiency with full engine load range capabilities, while emitting very low levels of particulate matter (PM) and oxides of nitrogen (NO&lt;sub&gt;x&lt;/sub&gt;). In the current work, a comparison of engine combustion, performance, and emissions has been made among E10 gasoline and several full-boiling range naphtha fuels on a Gen 2 single-cylinder GDCI engine with compression ratio of 15:1. Initial results with naphtha demonstrated improved combustion and efficiency at low loads. With naphtha fuel, hydrocarbon and carbon monoxide emissions were generally reduced at low loads but tended to be higher at mid-loads despite the increased fuel reactivity. At higher loads, naphtha required less boost pressure compared to gasoline, however, up to 20% additional EGR was required to maintain combustion phasing. The higher reactivity of naphtha did cause some reduction of peak load for the operating strategy tested, when constrained to the targets used in this study. For all fuels, particle size distributions were bimodal and had similar numbers of particles larger than 40 nm, while there were some differences in numbers of smaller particles. Based on an efficiency loss analysis, the fuels exhibited generally similar performance over the load range.&lt;/div&gt;&lt;/div&gt;
A New Flow-Through Wind Tunnel Balance Concept for Retropropulsion Testing (2022)

View Video Presentation: https://doi.org/10.2514/6.2022-2301.vid Supersonic retropropulsion, or the use of retrorockets starting at supersonic conditions, is an enabling technology for large-scale human Mars lander vehicle concepts. A new flow-through balance was designed and fabricated to support an upcoming retropropulsion test campaign at the NASA Langley Unitary Plan Wind Tunnel. The balance employs membranes in place of bellows, which have historically been used, and passes the flow through load bearing parts of the balance. Flow through the balance is optimized via the addition of flow guides, which are manufactured as separate parts, and attached to the balance. Calibration of this new flow-through balance demonstrates that it can suitably characterize the load and pressure ranges it was designed for, which provides aero researchers a new tool to directly measure supersonic retropropulsion performance of powered descent vehicles.
Characterizing ontogeny of quantity discrimination in zebrafish (2022)

A sense of non-symbolic numerical magnitudes is widespread in the animal kingdom and has been documented in adult zebrafish. Here, we investigated the ontogeny of this ability using a group size preference (GSP) task in juvenile zebrafish. Fish showed GSP from 21 days post-fertilization and reliably chose the larger group when presented with discriminations of between 1 versus 3, 2 versus 5 and 2 versus 3 conspecifics but not 2 versus 4 conspecifics. When the ratio between the number of conspecifics in each group was maintained at 1 : 2, fish could discriminate between 1 versus 2 individuals and 3 versus 6, but again, not when given a choice between 2 versus 4 individuals. These findings are in agreement with studies in other species, suggesting the systems involved in quantity representation do not operate separately from other cognitive mechanisms. Rather they suggest quantity processing in fishes may be the result of an interplay between attentional, cognitive and memory-related mechanisms as in humans and other animals. Our results emphasize the potential of the use of zebrafish to explore the genetic and neural processes underlying the ontogeny and function of number cognition.
Cryptography for Efficiency: Authenticated Data Structures Based on Lattices and Parallel Online Memory Checking. (2011)

In this work, we initially design a new authenticated data structure for a dynamic table with n entries. We present the first dynamic authenticated table that is update-optimal, using a lattice-based construction. In particular, the update complexity is O(1), improving in this way the “a priori” O(logn) update bounds of previous constructions, such as the Merkle tree. Moreover, the space complexity of our authenticated data structure is O(n) and logarithmic bounds hold for other performance measures, such as proof complexity (number of group elements contained in the proof). To achieve this result, we establish and exploit a property that we call repeated linearity of lattice-based hash functions and show how the security of lattice-based digests can be guaranteed under updates. An one-time preprocessing stage of O(n logn) complexity is also required at setup. This is the first construction achieving a constant update bound without causing other complexities to increase beyond logarithmic. All previous solutions enjoying such a complexity bound for updates enforce Ω(n ) proof or query complexity. As an application, we provide the first construction of an authenticated Bloom filter, an update-intensive data structure that falls into our
Multiple sclerosis cortical lesion detection with deep learning at ultra-high-field MRI (2022)

Abstract Manually segmenting multiple sclerosis (MS) cortical lesions (CL) is extremely time-consuming, and past studies have shown only moderate inter-rater reliability. To accelerate this task, we developed a deep learning-based framework (CLAIMS: Cortical Lesion Artificial Intelligence-based assessment in Multiple Sclerosis) for the automated detection and classification of MS CL with 7T MRI. Two 7T datasets, acquired at different sites, were considered. The first consisted of 60 scans that include 0.5mm isotropic MP2RAGE acquired 4 times (MP2RAGEx4), 0.7mm MP2RAGE, 0.5mm T2*-weighted GRE, and 0.5mm T2*-weighted EPI. The second dataset consisted of 20 scans including only 0.75×0.75×0.9 mm MP2RAGE. CLAIMS was first evaluated using 6-fold cross-validation with single and multi-contrast 0.5mm MRI input. Second, performance of the model was tested on 0.7mm MP2RAGE images after training with either 0.5mm MP2RAGEx4, 0.7mm MP2RAGE, or alternating the two. Third, its generalizability was evaluated on the second external dataset and compared with a state-of-the-art technique based on partial volume estimation and topological constraints (MSLAST). CLAIMS trained only with MP2RAGEx4 achieved comparable results to the multi-contrast model, reaching a CL true positive rate of 74% with a false positive rate of 30%. Detection rate was excellent for leukocortical and subpial lesions (83%, and 70%, respectively), whereas it reached 53% for intracortical lesions. The correlation between disability measures and CL count was similar for manual and CLAIMS lesion counts. Applying a domain-scanner adaptation approach and testing CLAIMS on the second dataset, the performance was superior to MSLAST when considering a minimum lesion volume of 6μL (lesion-wise detection rate of 71% vs 48%). The proposed framework outperforms previous state-of-the-art methods for automated CL detection across scanners and protocols. In the future, CLAIMS may be useful to support clinical decisions at 7T MRI, especially in the field of diagnosis and differential diagnosis of multiple sclerosis patients.
A Redundant Unit to Form T-Type Three-Level Inverters Tolerant of IGBT Open-Circuit Faults in Multiple Legs (2019)

T-type multilevel (T <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ML) inverters feature low total harmonic distortion and high efficiency. Reliability improvement is particularly important for T <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ML inverters because they have high power device count. Methods that provide T <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ML inverters with the ability to tolerate simultaneous failures of multiple switches in several legs have not been addressed in the existing literature. This paper proposes a redundant unit that can be shared across phases in a T-type three-level inverter topology to manage open-circuit faults in multiple legs. The redundant unit includes two switches and six diodes, with the extra active switches connected by diodes to each middle switch of the base inverter. Under fault conditions, a standby parallel leg consisting of middle switches and the added redundant devices can be formed in each phase of the inverter to provide an extra current path connecting the dc bus and loads. The middle switches can share the redundant unit simultaneously to replace faulted half-bridge switches. By these means, open-circuit faults in multiple legs can be tolerated simultaneously and the rated output capacity can be maintained during faulted operation. Experimental tests are given to verify the effectiveness and feasibility of this proposed fault-tolerant method.
Insertion of transition metal ions into cationic sites of high silica zeolites by reaction in the solid phase. II. Interaction of mordenite and pentasils with Cr, Mo, and V compounds (1986)

Roasting of mechanical mixtures of the H forms of such zeolites as mordenite and pentasils with some compounds of Cr (III), Cr(VI), Mo(V), and V(V) is accompanied, as in the case of copper compounds, by migration of a part of the ions into the zeolites channels and their localization in the cationic sites. In pentasils the major part of the ions is localized as isolated cations accessible to molecules in the gas phase, this being confirmed by the strong influence of O/sub 2/ on the ESR spectra of Cr(V), Mo(V), and V(IV). The possibility of ion insertion by a reaction in the solid phase stems from the presence in the zeolite of cationic vacancies which act as acid centers. Up to 820degreesC the reactions of substitution of Na/sup +/ by multicharged cations in the solid phase are slow.
Kisten ras mutations in patients with colorectal cancer: the “RASCAL II” study. (2001)

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer. © 2001 Cancer Research Campaign www.bjcancer.com
P3‐398: EARLY STAGE METABOLITE DIFFUSION IN A MOUSE MODEL OF ALZHEIMER'S DISEASE (2018)

Alzheimer's disease develops small neuronal alterations: axonal transport deficits and localized cell swelling, from the onset of amyloid plaque deposition and neurofibrillary tangles. It is significantly important to develop non-invasive biomarkers in vivo utilizing these early neuronal changes. Diffusion-weighted spectroscopy (DWS), which measures metabolite diffusion using MRI, has been providing useful information about tissue microstructure and function, and is expected to provide specific information about neuronal changes by probing diffusion properties of intra-neuronal specific metabolites. In the present study, we applied DWS to investigate metabolite diffusion of the early stages in an AD mouse model. This study was approved by the institutional IACUC. Twelve male 3xTg-AD transgenic mice (average age 25.6 weeks) and ten wild-type littermate controls (WT) (average age 19.1 weeks) were used. Diffusion-weighted spectra were measured by using DWS in a region (5x2x2 mm3) containing both hippocampi on a 14-T MRI (Avance III, Bruker BioSpin Corp). Mean diffusivity (MD) of major metabolites (N-acetylaspartate (NAA), Creatine (Cr), Choline (Cho)) and water were estimated from the measured spectra by calculating signal attenuation due to diffusion-weighting. MDs of water and metabolites were compared between WT and AD (Fig. 1). Student t-test was performed between WT and AD after outliers were excluded. Only NAA shows significantly higher MD in AD than in WT (38% in average, P = 0.03), but the other metabolites and water do not show significant differences in MD between AD and WT (Table 1). This result suggests that early small neuronal changes of AD can be detected by only NAA diffusion because NAA mostly exists in neurons; however, Cho and Cr exist also in glial cells, and water exists intra- and extracellular spaces. Further investigation is needed to clarify the mechanism associating MD change of NAA with neuronal changes, because axonal transport deficits and localized cell swelling have an opposite effect on NAA diffusion. Tukey boxplots show MD of water and metabolites compared between WT and AD mice. ° = outlier, ∗ = statistically significance (P < 0.05). Metabolite diffusion of a mouse model of AD was measured using DWS. Increased NAA diffusion demonstrates that DWS will be useful in investigating early neuronal changes in AD because DWS can provide focused information about intra-neuronal properties.
Altered glycosylation of platelet-derived von Willebrand factor confers resistance to ADAMTS13 proteolysis (2013)

Platelet-von Willebrand factor (VWF) is stored within α-granules and accounts for ∼20% of total VWF in platelet-rich plasma. This platelet-VWF pool is distinct from plasma-VWF and is enriched in high molecular weight multimers (HMWM). Previous studies have described significant functional discrepancies between platelet-VWF and plasma-VWF; however, the molecular basis of these differences is not well understood. We have characterized terminal glycan expression on platelet-VWF. Our findings demonstrate that platelet-VWF exists as a distinct natural glycoform. In particular, N-linked sialylation is markedly reduced (>50%) compared with plasma-VWF. Moreover, unlike plasma-VWF, platelet-VWF does not express AB blood group determinants, although precursor H antigen expression is similar to that on plasma-VWF. Because of this differential glycosylation, platelet-VWF exhibits specific resistance to ADAMTS13 proteolysis. Thus platelet activation at sites of vascular injury results in the release of high local concentrations of HMWM platelet-VWF that is more resistant to ADAMTS13, thereby facilitating platelet-plug formation.
An optimization-based approach to automated design (2023)

We propose a model-based, automated, bottom-up approach for design, which is applicable to various physical domains, but in this work we focus on the electrical domain. This bottom-up approach is based on a meta-topology in which each link is described by a universal component that can be instantiated as basic components (e.g., resistors, capacitors) or combinations of basic components via discrete switches. To address the combinatorial explosion often present in mixed-integer optimization problems, we present two algorithms. In the first algorithm, we convert the discrete switches into continuous switches that are physically realizable and formulate a parameter optimization problem that learns the component and switch parameters while inducing design sparsity through an $L_1$ regularization term. The second algorithm uses a genetic-like approach with selection and mutation steps guided by ranking of requirements costs, combined with continuous optimization for generating optimal parameters. We improve the time complexity of the optimization problem in both algorithms by reconstructing the model when components become redundant and by simplifying topologies through collapsing components and removing disconnected ones. To demonstrate the efficacy of these algorithms, we apply them to the design of various electrical circuits.