gebhart/patrepeval huggingface dataset:
Effect of Nitroreduction on the Alkylating Reactivity and Cytotoxicity of the 2,4-Dinitrobenzamide-5-aziridine CB 1954 and the Corresponding Nitrogen Mustard SN 23862:  Distinct Mechanisms of Bioreductive Activation (2003)

The dinitrobenzamide aziridine CB 1954 (1) and its nitrogen mustard analogue SN 23862 (6) are prodrugs that are activated by enzymatic nitroreduction in tumors. Bioactivation of 1 is considered to be due to reduction of its 4-nitro group to the hydroxylamine and subsequent formation of the N-acetoxy derivative; this acts as a reactive center, in concert with the aziridine moiety, to provide a bifunctional DNA cross-linking agent (Knox model). It is currently unclear whether bioactivation of 6 occurs by the same mechanism or results from the electronic effects of nitroreduction on reactivity of the nitrogen mustard moiety. To discriminate between these mechanisms, we have synthesized the hydroxylamine and amine derivatives of 1 and 6, plus related compounds, and determined their alkylating reactivities in aqueous solution, using LC/MS to identify reaction pathways. The relationships between substituent electronic effects, reactivity, and cytotoxicity were determined using the UV4 cell line, which is defective in nucleotide excision repair (thus avoiding differences in repair kinetics). Alkylating reactivity correlated with the electron-donating character of the ortho or para substituent in the case of the mustards, with a less marked electronic effect for the aziridines. Importantly, there was a highly significant linear relationship between cytotoxic potency and alkylating reactivity in both the aziridine and the mustard series, with the notable exception of 4, the 4-hydroxylamine of 1, which was 300-fold more toxic than predicted by this relationship. This demonstrates that the high potency of 4 does not result from activation of the aziridine ring, supporting the Knox model. The single-step bioactivation of 6, to amino or hydroxylamine metabolites with similar potency to 4, is a potential advantage in the use of dinitrobenzamide mustards as prodrugs for activation by nitroreductases.
The importance of the preactivation peptide in the two-stage mechanism of human plasminogen activation. (1975)

The two stages in the activation of human plasminogen by urokinase have been examined kinetically in order to evaluate the significance of each stage in the activation process. The cleavage of the preactivation peptide from the NH2 terminus of native plasminogen (NH2-terminal glutamic acid) is clearly catalyzed by urokinase and is the rate-limiting first step in activation (Stage 1); this reaction is 20-fold slower than the conversion of the intermediate plasminogen (NH2-terminal lysine) to plasmin (Stage 2). Both lysine and its analogoue, epsilon-aminocaproic acid, exert two effects on the activation of native plasminogen. At low concentrations of these agents, activation is greatly accelerated. Analysis of activation in the presence and absence of these agents by sodium dodecyl sulfate gel electrophoresis indicates that the activation pathway is the same in both cases with the formation of a transient intermediate plasminogen; only the kinetics of proteolysis are altered. This enhancement in the rate of activation results solely from acceleration of the Stage 1 reaction; Stage 2 is essentially unaffected at low concentrations. Stage 1 is maximally enhanced (75-fold) at either 0.0025 M epsilon-aminocaproic acid or 0.025 M lysine and occurs 4 times more rapidly than Stage 2, which becomes the rate-limiting step at these concentrations. Plasmin also cleaves the preactivation peptide from native plasminogen and this reaction rate is enhanced by the same concentrations of lysine and epsilon-aminocaproic acid. These data suggest that lysine and epsilon-aminocaproic acid, which are known to bind to plasminogen and significantly alter its conformation, may thereby enhance preactivation peptide cleavage and consequently, plasminogen activation. At high concentrations, both Stages 1 and 2 are similarly inhibited by these agents, which suggests that this effect may be exerted by the direct inhibition of urokinase. The relative rates of preactivation peptide cleavage by the enzymes urokinase, plasmin, thrombin, and ancrod were also determined. Urokinase is 10 times more effective than plasmin in catalyzing this reaction and 1.8 X 10(4) times more effective than thrombin, while ancrod does not exert an effect. No plasmin is formed by either thrombin or ancrod.
Aerial imaging study of the mask-induced line-width roughness of EUV lithography masks (2016)

EUV lithography uses reflective photomasks to print features on a wafer through the formation of an aerial image. The aerial image is influenced by the mask’s substrate and pattern roughness and by photon shot noise, which collectively affect the line-width on wafer prints, with an impact on local critical dimension uniformity (LCDU). We have used SHARP, an actinic mask-imaging microscope, to study line-width roughness (LWR) in aerial images at sub-nanometer resolution. We studied the impact of photon density and the illumination partial coherence on recorded images, and found that at low coherence settings, the line-width roughness is dominated by photon noise, while at high coherence setting, the effect of speckle becomes more prominent, dominating photon noise for exposure levels of 4 photons/nm<sup>2</sup> at threshold on the mask size.
Magnetron experiments on the short-pulse &#x201C;SINUS-6&#x201D; accelerator (2008)

We have been able to show using MAGIC (a 3-dimensional fully relativistic particle-in-cell code) simulations that the output characteristics of magnetrons can be significantly improved using the transparent cathode. To demonstrate the advantages of the transparent cathode we chose the well-known A6 magnetron geometry. At the University of New Mexico we are focusing magnetron operation in the short-pulse regime for reasons discussed. To verify our simulation results experimentally we use the electron beam accelerator "SINUS-6," details of which are outlined in the following section.
Terminal-Side Interference Mitigation for Spectral Coexistence of Satellite and Terrestrial Systems in Non-Exclusive Ka-band (2016)

peer reviewed
Amyotrophic lateral sclerosis: Is the spinal fluid pathway involved in seeding and spread? (2015)

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder manifested primarily by loss of upper and lower motor neurons. Current explanations for disease progression invoke regional spread attributed to the transfer of pathogenic factors among physically contiguous neurons. However, this explanation incompletely explains certain clinical and in vitro data. Considering this, we propose that the cerebrospinal fluid (CSF) pathway is likely to be a key vector for seeding local and distal disease. Subsequent disease progression would be expected to occur independently via either axonal or CSF transmission. If one accepts the hypothesis that the CSF pathway is involved in ALS progression, it follows that the choroid plexus (CP) might well be a driver of the disease process. In support of this, we briefly review the anatomical and physiological features of the CSF pathway and the choroid plexus responsible for secreting CSF. In addition, we draw attention to the interface of the CP and CSF with the immune system. We then summarize both clinical and cell culture research that supports a key role of the CSF in the establishment and inter-neuronal spread of ALS, and which suggest directions for translational research.
ESR and ENDOR investigations of phenanthrenesemiquinones (1988)

Abstract A series of phenanthrenesemiquinone–diphenylthallium complexes were prepared in solution from the corresponding quinones. ESR, ENDOR and TRIPLE spectra provided the proton coupling constants and the unambiguous assignment to distinct molecular positions. The thallium splitting becomes considerably less negative if the semiquinones are twisted by steric hindrance in the 4‐ and 5‐positions. On the other hand, substitution in the 1‐ and 8‐positions renders a TI more negative. These results are interpreted in terms of steric hindrance of the ion‐pair solvation.
Nonlinear Optical Properties of the Au-SiO2 Nanocomposite Superresolution Near-field Thin Film (2004)

A Au-SiO 2 superresolution nanocomposite active nonlinear optical thin film is fabricated reproducibly by cosputtering method with the size of Au nano particles around 2 to 10 nm. Results of the Z-scan indicate that these nanocomposite Au-SiO 2 films have nonlinear optical properties and enhanced transmittance at the focusing position. For a 15-nm-thick Au-SiO 2 nanocomposite thin film, the transmittance can be 135% for a sample with an average grain size of around 5 nm.
CHAPTER 20. Lead Generation (2015)

In an industry focused on reducing attrition, lead generation represents a critical stage in drug discovery wherein a considered choice of lead series can significantly reduce the time and resources committed to unpromising chemical series. To aid identification and selection of series with a specific mechanism of action, within property space suitable for the intended mode of administration, many modalities are brought into play and are discussed in this chapter. Aspects covered include the approaches used to find chemical start points, as well as some of the blind alleys that the investigator should avoid, and the need to consider lead-like properties in context of a line-of-sight to the final drug candidate. By way of help, examples are given of both successful and unsuccessful lead generation.
3D modeling for communications (2002)

The media and communications providers share an increasing interest in 3D models of people, objects, and scenes. The paper focuses on features that 3D acquisition systems ought to have in order to optimally serve these markets, where emphasis is on realistic visualisation. It is argued that 3D acquisition techniques developed for traditional applications such as visual inspection aren't necessarily the best option. Techniques should be developed that are dedicated to visualisation-specific requirements. This is exemplified with two systems that have been developed recently. One takes uncalibrated video data as input from which it generates a 3D model. A second system projects a grid of lines and gets dense 3D from a single image. This system needs some calibration, but the corresponding procedure is extremely simple. It can also be used to capture detailed, 3D scene dynamics.
The Jak2 Inhibitor, G6, Alleviates Jak2-V617F–Mediated Myeloproliferative Neoplasia by Providing Significant Therapeutic Efficacy to the Bone Marrow (2011)

We recently developed a Janus kinase 2 (Jak2) small-molecule inhibitor called G6 and found that it inhibits Jak2-V617F-mediated pathologic cell growth in vitro, ex vivo, and in vivo. However, its ability to inhibit Jak2-V617F-mediated myeloproliferative neoplasia, with particular emphasis in the bone marrow, has not previously been examined. Here, we investigated the efficacy of G6 in a transgenic mouse model of Jak2-V617F-mediated myeloproliferative neoplasia. We found that G6 provided therapeutic benefit to the peripheral blood as determined by elimination of leukocytosis, thrombocytosis, and erythrocytosis. G6 normalized the pathologically high plasma concentrations of interleukin 6 (IL-6). In the liver, G6 eliminated Jak2-V617F-driven extramedullary hematopoiesis. With respect to the spleen, G6 significantly reduced both the splenomegaly and megakaryocytic hyperplasia. In the critically important bone marrow, G6 normalized the pathologically high levels of phospho-Jak2 and phospho-signal transducer and activator of transcription 5 (STAT5). It significantly reduced the megakaryocytic hyperplasia in the marrow and completely normalized the M/E ratio. Most importantly, G6 selectively reduced the mutant Jak2 burden by 67%on average, with virtual elimination of mutant Jak2 cells in one third of all treated mice. Lastly, clonogenic assays using marrow stem cells from the myeloproliferative neoplasm mice revealed a time-dependent elimination of the clonogenic growth potential of these cells by G6. Collectively, these data indicate that G6 exhibits exceptional efficacy in the peripheral blood, liver, spleen, and, most importantly, in the bone marrow, thereby raising the possibility that this compound may alter the natural history of Jak2-V617F-mediated myeloproliferative neoplasia.
Development of a Multiplex PCR Assay for Rapid Molecular Serotyping of Haemophilus parasuis (2015)

Haemophilus parasuis causes Glässer's disease and pneumonia in pigs. Indirect hemagglutination (IHA) is typically used to serotype this bacterium, distinguishing 15 serovars with some nontypeable isolates. The capsule loci of the 15 reference strains have been annotated, and significant genetic variation was identified between serovars, with the exception of serovars 5 and 12. A capsule locus and in silico serovar were identified for all but two nontypeable isolates in our collection of >200 isolates. Here, we describe the development of a multiplex PCR, based on variation within the capsule loci of the 15 serovars of H. parasuis, for rapid molecular serotyping. The multiplex PCR (mPCR) distinguished between all previously described serovars except 5 and 12, which were detected by the same pair of primers. The detection limit of the mPCR was 4.29 × 10(5) ng/μl bacterial genomic DNA, and high specificity was indicated by the absence of reactivity against closely related commensal Pasteurellaceae and other bacterial pathogens of pigs. A subset of 150 isolates from a previously sequenced H. parasuis collection was used to validate the mPCR with 100% accuracy compared to the in silico results. In addition, the two in silico-nontypeable isolates were typeable using the mPCR. A further 84 isolates were analyzed by mPCR and compared to the IHA serotyping results with 90% concordance (excluding those that were nontypeable by IHA). The mPCR was faster, more sensitive, and more specific than IHA, enabling the differentiation of 14 of the 15 serovars of H. parasuis.
E-beam shot count estimation at 32 nm HP and beyond (2009)

Recent Low k1 era requires aggressive OPC technology with advanced lithography technology. The aggressive OPC contains the rounded pattern and a lot of assistant pattern which are the main source to increase the shot division. We have defined the shot complexity, which is defined by the ratio of number of shot between the interested pattern and the 1:1 L/S pattern. Based on shot complexity parameter, we have estimated the writing time as the device node decreases. We expect that the aggressive OPC and the high dose could generate severely the writing time issue in 32nm node era.
A new acoustic lens design for electromagnetic shock wave lithotripters. (2010)

The third-generation electromagnetic (EM) shock wave lithotripters often have narrow focal width and high-peak pressure compared to the original HM-3. In addition, the pressure waveform produced by a typical EM lithotripter has a secondary compressive wave that suppresses lithotripter pulse induced cavitation, which is an important mechanism for stone comminution. These features have been contributed to the reduced effectiveness of the modern EM lithotripters. To overcome these drawbacks, we have designed a new acoustic lens for the Siemens Modularis EM lithotripter that produces an idealized pressure waveform similar to the HM-3 with broad focal width and low-peak pressure. At acoustic pulse energy of 53 mJ, the new lens design enlarges the −6 dB focal width of the Modularis by 47% while significantly reducing the second compressive wave throughout its focal plane. After 2000 shocks, in vitro comminution produced by the original and new lens designs are 100% and 99% at the lithotripter focus, and (49.7±15.0)% and (75.3±8.74)% (p &amp;lt; 0.001) at 10 mm off axis, respectively. Corresponding values in vivo are (63.4±17.4)% and (83.3±8.5)% (p &amp;lt; 0.01), demonstrating the significant performance improvement provided by the new lens design. [Work supported by NIH Grant Nos. R01DK052985 and S10RR016802.]
A Critical Review and Annotated Bibliography for Heat Exchanger Network Synthesis in the 20th Century (2002)

This paper provides a critical review of the literature on heat-exchanger network synthesis, the most commonly studied problem in process synthesis. After a review of solution methods, we present the chronological milestones in the development of the field and we discuss separately each of 461 related works leading up to the turn of the century. Then, we present several classification schemes of this body of work based on a number of modeling and algorithmic criteria. Finally, we offer a critical assessment of the current status of research in this area and provide suggestions for future research.
Low-risk Prostate Cancer Patients Without Visible Tumor (T1c) On Multiparametric MRI Could Qualify for Active Surveillance Candidate Even If They Did Not Meet Inclusion Criteria of Active Surveillance Protocol (2013)

Introduction: We compared the pathologic outcomes of prostate cancer patients who did not qualify for active surveillance according to the tumor visibility on multiparametric magnetic resonance imaging. Material and methods: We retrospectively analyzed 464 prostate cancer patients who
Chemical Durability of Savannah River Plant Waste Glass as a Function of Waste Loading (1983)

The leachability of Savannah River Plant (SRP) waste forms was assessed for glass containing up to 50 wt% simulated waste oxides. Leach tests included standard MCC‐1 static tests and pH‐buffered solution experiments. An integrated approach combining leachate solution analysis with both bulk and surface analyses was used to study waste‐glass corrosion as a function of waste loading. Scouting tests on key processing and product parameters, such as viscosity, electrical resistivity, and density were also performed. Results of this study show that the durability of SRP waste glass improves due to the presence of the waste, for waste loadings up to 50 wt% because of the formation of protective surface layers. In addition, the data indicate that the practical limit of waste loading will be determined not by chemical durability of the product, but by processing considerations.
Urotensin II causes fatal circulatory collapse in anesthesized monkeys in vivo: a “vasoconstrictor” with a unique hemodynamic profile (2004)

Urotensin II (UII) is a vasoactive peptide that has recently emerged as a likely contributor to cardiovascular physiology and pathology. Acute infusion of UII into nonhuman primates results in circulatory collapse and death; however, the exact cause of death is not well understood. This study was undertaken to elucidate the mechanism underlying the fatal cardiovascular event on UII application in vivo in nonhuman primates. To this end, cynomolgus monkeys (n = 4) were anesthetized and tracheal intubation was performed. One internal jugular vein was cannulated for administration of drugs, and one femoral artery for recording of blood pressure and heart rate using a transonic pressure transducer. Cardiac parameters were not significantly changed after administration of 0.003 nmol/kg human UII. A bolus of human UII (0.03 nmol/kg) caused a decrease of heart rate (HR) (13%), mean blood pressure (MBP) (18%), and first-order derivative of left ventricular pressure (dP/dt) (11%). Carotid and coronary blood flow were reduced by 9% and 7%, respectively; 0.3 nmol/kg of human UII resulted in a further reduction of HR (50.3%), MBP (65%), dP/dt (45%), carotid (38%), and coronary blood flow (30%), ultimately leading to cardiovascular breakdown and death. Pulmonary pressure, however, was increased by 30%. Plasma histamine levels were found to be unaffected by administration of UII. Our results indicate that systemic administration of human UII has negative inotropic and chronotropic effects and reduces total peripheral resistance ultimately leading to severe myocardial depression, pulmonary hypertension, and fatal circulation collapse in nonhuman primates. We suggest that successful design of UII antagonists might offer a new therapeutic principle in treating cardiovascular diseases.
Salmonella typhimurium mediastinal abscess in a patient with systemic lupus erythematosus (2003)

We describe a case of a Salmonella typhimurium mediastinal abscess in a patient with systemic lupus erythematosus (SLE). Patients with SLE are predisposed to nontyphoidal salmonella infection with a high incidenceof bacteraemiaand abscessformation.Our case is the first report of a mediastinalabscess from Salmonella typhimurium in an SLE patient and highlights the need for thorough assessment and treatment of SLE patients who have this organism identified.
Impact of KIR/KIR ligand genotype for neuroblastoma patients in a phase III COG immunotherapy trial. (2016)

e14014 Background: High-risk neuroblastoma (NBL) patients (pts) enrolled in a COG phase III clinical trial (ANBL0032) were randomized to isotretinoin (RA) alone or RA + immunotherapy (IM): dinutuximab (anti-GD2 mAb) + IL2 + GMCSF (Yu et al., NEJM363:1324, 2010). Dinutuximab acts via antibody-dependent cell-mediated cytotoxicity by innate immune cells, including NK cells. NK cells express Killer Immunoglobulin-like Receptors (KIRs) that bind KIR-Ligands (KIR-Ls), MHC Class I molecules. Prior studies suggest that KIR/KIR-L status impacts outcome for pts with NBL. We investigated whether KIR/KIR-L genotype was associated with event-free survival (EFS) and overall survival (OS) in this trial. Methods: Of the 226 pts randomized, 174 pts had DNA allowing evaluation of genotype correlations with outcome (IM: n=88; RA: n=86; >5yr follow-up if no event). For the inhibitory KIRs, we assessed the impact of all KIR-Ls present vs. missing at least one KIR-L (KIR-L missing) on outcome. Cox regression models and log-rank tests were used to evaluate EFS/OS with genotypes. Results: In contrast to prior reports, outcome for IM pts was not associated with KIR-L present vs. KIR-L missing genotypes (EFS p=0.35; OS p=0.33; Table). Interestingly, we found that IM therapy benefited those pts with KIR-L present as opposed to those with KIR-L missing (OS: p=0.01 vs. p=0.77; Table). Conclusions: IM (vs. RA) treatment resulted in improved outcome (Yu et al., 2010), but IM can have toxic side effects. Our data suggest that KIR/KIR-L genotype could be used prospectively to identify pts most likely to benefit from this therapy. We are continuing to evaluate KIR/KIR-L genotypes in this study to determine if there are certain genotypes that are likely to respond to IM (eg. KIR-L present, Table), and identify KIR/KIR-L genotypes that might benefit from alternate treatment regimens (eg. KIR-L Missing, Table). Clinical trial information: NCT00026312.Treatment EFS OS KIR-L present KIR-L missing Genotype p-value KIR-L present KIR-L missing Genotype p-value RA 5 yr % 39 48 0.24 42 66 0.06 [95% CI] [22-55] [34-61] [24-58] [52-78] Events/n 19/31 27/55 18/31 21/55 RA + IM 5 yr % 72 52 0.35 80 71 0.33 [95% CI] [50-86] [39-64] [58-91] [59-81] Events/n 9/25 30/63 7/25 25/63 Treatment p-value 0.03 0.54 0.01 0.77