gebhart/patrepeval huggingface dataset:
Abstract 4512: Super-enhanced permeability and retention (SUPR) effect induced by photo-immunotherapy (PIT) can accommodate massive nano-sized reagents deep into tumors. (2013)

Abstract A major barrier to cancer treatment is the inability to deliver sufficient concentrations of drug to the interior of tumors without incurring systemic toxicities. Nanomaterials are appealing because they can carry a large drug payload, however, tumor delivery is limited by modest leakage and retention in most tumors. Photo-immunotherapy (PIT) is a newly developed therapy involving the injection of a conjugate composed of an armed monoclonal antibody (mAb) and a near infrared phthalocyanine dye, IR700 [Mitsunaga M. Nature Med 2011;17:1685]. When exposed to NIR light, the conjugate induces a highly-selective necrotic cell death only in mAb-IR700 bound cancer cells. This target-specific necrotic cell death occurs within 10 minutes of exposure to NIR light and results in rapid morphologic changes including cellular swelling, bleb formation, and rupture of vesicles indicating necrotic cell death. Meanwhile, immediately adjacent receptor-negative cells are unharmed. Because it damages cells immediately adjacent to the tumor vasculature, PIT results in marked increases in vascular permeability leading to 12- to 25-fold enhanced nano-particle delivery into cancer tissue, an effect termed “super-enhanced permeability and retention (SUPR)” to differentiate it from inherent enhanced permeability and retention (EPR). Of particular interest is that nano-sized reagents including macromolecules (dendrimers), particles (quantum dots, iron oxide nano-particles), and liposomes up to 300 nm in diameter rapidly enter and are retained within the tumor space following PIT. Therefore, although PIT might not be able to eliminate all cancer cells due to heterogeneity of tumor antigen expression, SUPR allows the delivery of extremely high concentrations of nano-sized anti-cancer reagents such as daunorubicin containing liposome (Daunoxome), resulted in significantly synergic therapeutic effects of PIT and nano-sized agents. In conclusion, target-selective PIT can induce a SUPR effect leading to the accumulation of relatively high concentrations of nano-sized reagents into the tumor bedthus improving effectiveness of PIT.. Citation Format: Hisataka Kobayashi, Kohei Sano, Takahito Nakajima, Peter L. Choyke. Super-enhanced permeability and retention (SUPR) effect induced by photo-immunotherapy (PIT) can accommodate massive nano-sized reagents deep into tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4512. doi:10.1158/1538-7445.AM2013-4512
ChemInform Abstract: THE SYNTHESIS OF 9‐EPI‐LEUCOMYCIN A(3), THE REVISED CONFIGURATIONAL ASSIGNMENT OF C‐9 IN NATURAL LEUCOMYCIN A(3) (1974)

Abstract Niddamycin (I) wird über z.B (II)‐(IV) in 9‐epi‐Leucomycin A3 (VII) sowie Carbomycin (IX) übergeführt.
Non-Interacting Control of Web Forces and Cut-Off Register Errors in Rotary Printing Presses with Electronic Line Shafts (2006)

Replacing the mechanical line shaft, which is necessary for the synchronous drive of the printing units of rotary offset printing presses, through an “electronic line shaft” consisting of highly precise speed-and angle-controlled AC motors a multi-variable control system is formed which offers much more degrees of freedom than before to control important process variables. Until now it was not possible to simultaeously control web tensile forces and register errors, especially the cut-off register error, which are coupled with each other. On the basis of an extended mathematical process model which has been derived it was possible to find algorithms for a non-interacting, stable and simultaneous control of these two variables in the same or in different paper sections using the angular velocities of non-printing nips as actuating variables. The new control scheme was implemented on the level of the electronic drive controls and tested with a commercial press for illustration printing. This results in a considerably faster, more accurate and wearless control, compared to the use of register rollers which are state of the art. Due to this the amount of waste paper is significantly reduced. Furthermore, the operation of the press is simplified because the tensile force profile can automatically be preselected dependent on the paper grade and converted to set point values for the machine control. These innovations increase the productivity of the plant.
Optimal excitation of a high speed switched reluctance generator (2002)

This paper presents a new approach for controlling a switched-reluctance generator (SRG). The control objective is to produce the required power using the excitation that produces the highest efficiency. The SRG considered here operates above base speed. The turn-on and the conduction angles are the only control parameters that can be used to optimize the power conversion. The conventional control method that advances the turn-on angle as the speed increases is not enough to produce optimum performance. The turn-on and the conduction angles together are the key elements for optimal excitation. Optimization of the excitation angles is performed using a machine model based on finite element analysis. For all of the operating speeds, all possible turn-on and conduction angles are simulated to get the desired power output. The excitation angles using the minimum RMS phase currents are chosen among those that give the desired output power. The control strategy is experimentally tested using a 6 kW 5000 rpm SRG. The control algorithm is able to provide required power with very good generator efficiency.
Listen-Before-Talk Versus Treating Interference as Noise for Spectrum Sharing (2008)

The spectrum sharing problem between heterogeneous networks that are not interoperable is considered. Two strategies for interference management are studied. First, by treating the possible interference from adjacent transmitters as noise, each transmitter can achieve a certain information rate which merely depends upon the channel quality, but does not depend upon the burstiness of packets arrival. Second, in an ideal listen-before-talk (LBT) strategy, where perfect sensing between transmitters is assumed, the stable achievable rates of the pairs of transceivers are analyzed, and shown to exhibit interaction and dependence upon the bursty arrivals of packets. It is revealed that, for receivers in certain regions which are exposed to strong interference and low traffic burstiness, LBT performs better; while in the other regions with decreased interference level or higher traffic loads, treating interference as noise leads to better performance.
Miniature time-of-flight mass spectrometer using a flexible circuitboard reflector (2000)

An innovative design for a miniature time-of-flight mass spectrometer has been developed employing several newly designed components. These include: (1) a gridless, focusing ion source allowing for the use of very high extraction energies in a maintenance-free design, (2) a new method of construction for an ion reflector using rolled flexible circuitboard material, and (3) an improved center-hole microchannel plate detector assembly that significantly reduces the noise (or 'ringing') inherent in the coaxial design. A prototype time-of-flight instrument was constructed and used to evaluate the performance of these components. Compared to previous designs, results indicate that background noise for data acquired on this instrument is substantially reduced, resolution is improved, and the potential for mass producing this instrument in an inexpensive and rugged package for field-portable and remote installations is significantly enhanced. Copyright 2000 John Wiley & Sons, Ltd.
Purification and Characterization of Thermostable Trehalose Phosphorylase from Thermoanaerobium brockii. (1999)

A thermostable trehalose phosphorylase (EC 2.4.1.64) from a thermophilic anaerobe, Thermoanaero bium brockii ATCC 35047, was purified to an electrophoretically homogeneous state by successive column chromatographies on DEAE-Toyopearl 6505, Butyl-Toyopearl 650 M and Ultrogel AcA 44 . The molecular weight of the enzyme was estimated to be 190, 000 Da by gel filtration, and 88, 000 Da by SDS-polyacrylamide gel electrophoresis. The enzyme showed the highest activity in the range of pH 7.0 to 7.5 for phosphorolysis, and pH 6.0 to 7.0 for synthesis . The optimum temperature of the enzyme was 70°C in both directions. The enzyme was stable from pH 6.0 to 9.0, and up to 60°C . This result showed that our trehalose phosphorylase was the most thermostable in those reported to date . Activity was inhibited by Cue, Hg2+, Mg2+, Mn2+, Pb2+, and Zn2+ The Kms for trehalose, Pi, D-glucose and R-D-glucose 1-phosphate were 0.97, 0.57, 2.4 and 0.75 mM, respectively.
VoCo (2017)

Editing audio narration using conventional software typically involves many painstaking low-level manipulations. Some state of the art systems allow the editor to work in a text transcript of the narration, and perform select, cut, copy and paste operations directly in the transcript; these operations are then automatically applied to the waveform in a straightforward manner. However, an obvious gap in the text-based interface is the ability to type new words not appearing in the transcript, for example inserting a new word for emphasis or replacing a misspoken word. While high-quality voice synthesizers exist today, the challenge is to synthesize the new word in a voice that matches the rest of the narration. This paper presents a system that can synthesize a new word or short phrase such that it blends seamlessly in the context of the existing narration. Our approach is to use a text to speech synthesizer to say the word in a generic voice, and then use voice conversion to convert it into a voice that matches the narration. Offering a range of degrees of control to the editor, our interface supports fully automatic synthesis, selection among a candidate set of alternative pronunciations, fine control over edit placements and pitch profiles, and even guidance by the editors own voice. The paper presents studies showing that the output of our method is preferred over baseline methods and often indistinguishable from the original voice.
Angiogenesis capacity as a diagnostic marker for human eye tumors. (1979)

Solid tumors have the capacity to continuously stimulate the proliferation of new capillaries. Aliquots (0.1 cc) of aqueous humor were aspirated from the anterior chamber of the eye of 38 patients undergoing elective ophthalmologic surgery. The material was lyophilized and then inplanted on the chorioallantoic membrane (CAM) of 10-day-old chick embryos for bioassay. The angiogenesis capacity of each sample was graded as negative or positive. Nine of 10 patients with histologically proven retinoblastoma had positive vascular responses. Seven of 11 patients with choroidal malignant melanoma had a positive response to their aqueous humor on the CAM. Aqueous samples from eyes with an iris and ciliary body malignant melanoma and a metastatic breast carcinoma to the iris had a positive angiogenic response. By contrast, only one of 15 patients undergoing operation for cataracts, glaucoma, or other nonmalignant ocular disease showed an angiogenesis response. The one patient who a positive assay later developed lymphocytic leukemia. These studies show that certain intraocular tumors display angiogenesis capacity before clinically evident neovascular changes of floating tumor cells are seen. Patients without tumors showed no angiogenesis response.
Effectively targeting small airways using controlled inhalation for peripheral corticosteroid deposition (2014)

Rationale: Long-term oral corticosteroid (OCS) therapy is associated with significant side effects. Reducing OCS doses causes lung function decline in OCS-dependent asthma patients, with small airways contributing significantly. A computer-controlled inhalation system (AKITA) as add-on therapy to GINA step 5 treatment (OCS) was used to deliver consistent doses of budesonide to the peripheral lungs to effectively target small airway inflammation. Methods: Phase 2/3 randomized, four-arm parallel-group, placebo-controlled trial, conducted in 27 outpatient centers. Adult patients (18-65 years) with OCS-dependent asthma were randomly assigned (2:1:1:1) to 18-weeks, BID, double-blind add-on treatment with AICS (AKITA inhaled corticosteroid)-Bud 1 mg, AICS-Bud 0.5 mg, AICS-placebo, or add-on open-label treatment with Bud 1 mg via conventional nebulizer (CN-Bud). OCS doses were tapered until week 14 and patients were followed until week 20. Lung function parameters (including FEV 1 and FEF 25-75 ) were recorded. Results: OCS dose could be reduced in all treatment arms. Mean [SD] FEV 1 significantly improved for AICS-Bud 1 mg (239 [460] mL; p<0.001) and AICS-Bud 0.5 mg (126 [345] mL; p=0.01) but not placebo (93 [419] mL; p=0.36) or CN-Bud (137 [459] mL: p=0.18). Mean (SD) change in FEF 25-75 from baseline to week 18 was +0.20 (0.60) L/sec for AICS-Bud 1 mg and 0.00 (0.40) L/sec for placebo (p=0.03). Conclusions: AICS-Bud 1 mg significantly improved lung function, while maintaining asthma control, in patients with OCS-dependent asthma compared with placebo. This therapeutic benefit likely resulted from consistent, targeted dosing, and would substantially benefit OCS-dependent asthma patients.
Synthesis of Novel High Silicate-Substituted Hydroxyapatite by Co-Substitution Mechanisms (2007)

Silicate substituted hydroxyapatite bioceramics have been shown to enhance bone repair in vivo compared to hydroxyapatite (HA), although the amount of silicate ions that can be substituted alone into the hydroxyapatite structure is limited to approximately 5.2 wt%, or 1.6 wt% Si. This study describes the substitution of greater levels of silicate ions via co-substitution of silicate ions with trivalent yttrium ions, without resulting in the formation of any secondary phases. This substitution mechanism involves a coupled substitution of yttrium and silicate ions for calcium and phosphate ions, respectively, and enables a level of silicate substitution up to approximately 9 wt%. Two different substitution mechanisms result in subtle differences in the crystal structure. When the mechanism xY3+ + xSiO4 4- was used, a small decrease in the a-axis, but no change in the c-axis, of the unit cell compared to HA was observed. In contrast, when the mechanism x/2Y3+ + xSiO4 4- was used, a significant increase in the c-axis of the unit cell was observed, compared to HA. XRF analysis and FTIR spectroscopy supported the proposed substitution mechanisms. These novel substitution mechanisms not only enable greater levels of silicate-substitution in HA to be prepared, but also allow the production of compositions with the same level of silicate substitution, and with subtle differences in chemical structure.
A comparative study of korean with caucasian breast cancer reveals frequency of methylation in multiple genes correlates with breast cancer in young, ER, PR-negative breast cancer in korean women (2007)

To test whether promoter hypermethylation in breast cancer provides a basis for the interethnic difference in breast cancer incidence and distribution, we compared the methylation profiles of tumors arising in native Korean women with Caucasian women in the United States. Methylation-specific PCR analysis of seven genes frequently methylated in breast cancer (HIN-1, Twist, Cyclin D2, RARbeta, GSTP1, RASSF1A and CDH1) was performed on DNA from 67 Korean and 50 Caucasian invasive ductal breast cancers which were categorized into four subgroups by ER status and age. Methylation frequencies for individual genes were similar between the two races. However, tumors in Korean women of age (< or = 50) at diagnosis had a trend of higher prevalence of promoter hypermethylation for all seven genes compared to those in women at an older age (> 50). Furthermore, methylation of multiple genes (four or more genes per case) was associated with younger age at diagnosis (OR = 3.2; 95% CI = 1.2-8.7; p = 0.03). In contrast, there was no association between promoter hypermethylation and age at diagnosis in Caucasian women. A significantly higher frequency of methylation, for all seven genes and in multiple genes, was observed in ER-/PR breast carcinomas in Korean women of age < or = 50 compared to the same subgroup of tumors in Caucasians. In contrast, compared to Korean breast cancer, the subgroup of ER+/PR+ breast carcinomas arising in Caucasian women age > 50 had a significantly higher frequency of methylation in three of seven genes. Our data suggest that promoter hypermethylation is a prevalent phenomenon in breast cancer of young Korean women. By analyzing the methylation patterns in tumors stratified by race, ER/PR status, and age, dissimilarities in promoter hypermethylation profiles, particularly in the ER-/PR- tumors arising in young women, were revealed that characterize tumors of one ethnicity from the other.
MRONLINE (2014)

MapReduce job parameter tuning is a daunting and time consuming task. The parameter configuration space is huge; there are more than 70 parameters that impact job performance. It is also difficult for users to determine suitable values for the parameters without first having a good understanding of the MapReduce application characteristics. Thus, it is a challenge to systematically explore the parameter space and select a near-optimal configuration. Extant offline tuning approaches are slow and inefficient as they entail multiple test runs and significant human effort.
A Structural Model for Bax∆2-Mediated Activation of Caspase 8-Dependent Apoptosis (2020)

Bax∆2 is a pro-apoptotic anti-tumor protein in the Bax family. While most of the Bax family causes cell death by targeting mitochondria, Bax∆2 forms cytosolic aggregates and activates caspase 8-dependent cell death. We previously showed that the Bax∆2 helix α9 is critical for caspase 8 recruitment. However, the interaction between these two proteins at the structural level is unknown. In this in silico study, we performed molecular dynamics (MD) simulations and protein-protein docking on Bax∆2 variants. The results suggest that the Bax∆2 variants have different stable states. Mutating the Baxα mitochondria-targeting signal [L26P/L27P] appears to introduce a kink into helix α1. Protein-protein docking suggests that helices α9 of both wild-type Bax∆2 and Bax∆2 caspase 8 binding-deficient mutant [L164P] can fit in the same caspase 8 binding site, but the mutant is unable to fit as well as wild-type Bax∆2. Together, these data point to a structural basis for explaining Bax∆2 function in caspase 8-dependent cell death.
Pre-Clinical Study of a Novel Recombinant Botulinum Neurotoxin Derivative Engineered for Improved Safety (2016)

Cyto-012 is a recombinant derivative of Botulinum neurotoxin Type A (BoNT/A). It primarily differs from wild type (wt) BoNT/A1 in that it incorporates two amino acid substitutions in the catalytic domain of the light chain (LC) metalloprotease (E224 > A and Y366 > A), designed to provide a safer clinical profile. Cyto-012 is specifically internalized into rat cortical and hippocampal neurons, and cleaves Synaptosomal-Associated Protein 25 (SNAP-25), the substrate of wt BoNT/A, but exhibits slower cleavage kinetics and therefore requires a higher absolute dose to exhibit pharmacologic activity. The pharmacodynamics of Cyto-012 and wt BoNT/A have similar onset and duration of action using the Digital Abduction Assay (DAS). Intramuscular LD50 values for Cyto-012 and wt BoNT/A respectively, were 0.63 ug (95% CI = 0.61, 0.66) and 6.22 pg (95% CI = 5.42, 7.02). ED50 values for Cyto-012 and wt BoNT/A were respectively, 0.030 ug (95% CI = 0.026, 0.034) and 0.592 pg (95% CI = 0.488, 0.696). The safety margin (intramuscular LD50/ED50 ratio) for Cyto-012 was found to be improved 2-fold relative to wt BoNT/A (p < 0.001). The DAS response to Cyto-012 was diminished when a second injection was administered 32 days after the first. These data suggest that the safety margin of BoNT/A can be improved by modulating their activity towards SNAP-25.
High-power mode-locked semiconductor lasers using flared waveguides (1995)

We describe the use of flared waveguide diode lasers for obtaining increased output power under mode-locked operation. The flared waveguide expands the optical mode from a narrow region which gives a single lateral optical mode, to a wider multimode region for higher pulse saturation energy. Flared gain and flared absorber section geometry devices are compared to devices with conventional uniform waveguides. Using flared gain section devices, improvements in both pulse energy (6.8 pJ) and pulsewidth (3.3 ps) were measured compared to uniform waveguide devices. Peak powers of over 2 W are obtained, which, to our knowledge, is the highest peak power obtained directly from mode-locked single stripe diode lasers.
A New 180kDa. Urine Protein Marker Associated with Bladder Cancer (1990)

We surveyed the tumor-related proteins present in the urine specimens of 118 bladder cancer patients to seek a possible marker enabling future diagnosis and prognosis of this disease. We identified a protein of 180 kDa. by sodium dodecyl sulfate polyacrylamide gel electrophoresis in urine samples subjected to prior adsorption by protein-A conjugated to a sepharose bead. This protein appears to be a glycoprotein because it binds to concanavalin A-conjugated sepharose and can be eluted by alpha-methyl D-mannoside. It does not react immunochemically with antibodies prepared against either carcinoembryonic antigen or epidermal growth factor receptor, both of which have an apparent molecular weight close to 180 kDa. We found this protein in the urine of 74.3% of the patients with transitional cell carcinoma. It was not present in age-matched controls, patients with benign prostatic hyperplasia or patients with 10 other cancers. There was 1 false positive result in a patient with prostate cancer. It does not appear to be associated with urinary tract infection, blood contamination, premedication or anesthesia.
Crystal structure of the CRISPR RNA–guided surveillance complex from <i>Escherichia coli</i> (2014)

Clustered regularly interspaced short palindromic repeats (CRISPRs) are essential components of RNA-guided adaptive immune systems that protect bacteria and archaea from viruses and plasmids. In Escherichia coli, short CRISPR-derived RNAs (crRNAs) assemble into a 405-kilodalton multisubunit surveillance complex called Cascade (CRISPR-associated complex for antiviral defense). Here we present the 3.24 angstrom resolution x-ray crystal structure of Cascade. Eleven proteins and a 61-nucleotide crRNA assemble into a seahorse-shaped architecture that binds double-stranded DNA targets complementary to the crRNA-guide sequence. Conserved sequences on the 3' and 5' ends of the crRNA are anchored by proteins at opposite ends of the complex, whereas the guide sequence is displayed along a helical assembly of six interwoven subunits that present five-nucleotide segments of the crRNA in pseudo-A-form configuration. The structure of Cascade suggests a mechanism for assembly and provides insights into the mechanisms of target recognition.
Multifunctional perfluorocarbon nanoemulsions for 19F-based magnetic resonance and near-infrared optical imaging of dendritic cells (2009)

A novel type of bimodal imaging nanoprobe based on (19)F-based magnetic resonance imaging and near-infrared optical imaging has been synthesized and applied for the labeling and imaging of dendritic cells both in vitro and in vivo.