gebhart/patrepeval huggingface dataset:
Metallofullerene-Nanoplatform-Delivered Interstitial Brachytherapy Improved Survival in a Murine Model of Glioblastoma Multiforme (2012)

Fullerenes are used across scientific disciplines because of their diverse properties gained by altering encapsulated or surface-bound components. In this study, the recently developed theranostic agent based on a radiolabeled functionalized metallofullerene ((177)Lu-DOTA-f-Gd(3)N@C(80)) was synthesized with high radiochemical yield and purity. The efficacy of this agent was demonstrated in two orthotopic xenograft brain tumor models of glioblastoma multiforme (GBM). A dose-dependent improvement in survival was also shown. The in vivo stability of the agent was verified through dual label measurements of biological elimination from the tumor. Overall, these results provide evidence that nanomaterial platforms can be used to deliver effective interstitial brachytherapy.
Characterization of peripheral-compartment kinetics of antibiotics by in vivo microdialysis in humans (1996)

The calculation of pharmacokinetic/pharmacodynamic surrogates from concentrations in serum has been shown to yield important information for the evaluation of antibiotic regimens. Calculations based on concentrations in serum, however, may not necessarily be appropriate for peripheral-compartment infections. The aim of the present study was to apply the microdialysis technique for the study of the peripheral-compartment pharmacokinetics of select antibiotics in humans. Microdialysis probes were inserted into the skeletal muscle and adipose tissue of healthy volunteers and into inflamed and noninflamed dermis of patients with cellulitis. Thereafter, volunteers received either cefodizime (2,000 mg as an intravenous bolus; n = 6), cefpirome (2,000 mg as an intravenous bolus; n = 6), fleroxacin (400 mg orally n = 6), or dirithromycin (250 mg orally; n = 4); the patients received phenoxymethylpenicillin (4.5 x 10(6) U orally; n = 3). Complete concentration-versus-time profiles for serum and tissues could be obtained for all compounds. Major pharmacokinetic parameters (elimination half-life, peak concentration in serum, time to peak concentration, area under the concentration-time curve [AUC], and AUC/MIC ratio) were calculated for tissues. For cefodizime and cefpirome, the AUCtissue/AUCserum ratios were 0.12 to 0.35 and 1.20 to 1.79, respectively. The AUCtissue/AUCserum ratios were 0.34 to 0.38 for fleroxacin and 0.42 to 0.49 for dirithromycin. There was no visible difference in the time course of phenoxymethylpenicillin in inflamed and noninflamed dermis. We demonstrated, by means of microdialysis, that the concept of pharmacokinetic/pharmacodynamic surrogate markers for evaluation of antibiotic regimens originally developed for serum pharmacokinetics can be extended to peripheral-tissue pharmacokinetics. This novel information may be useful for the rational development of dosage schedules and may improve predictions regarding therapeutic outcome.
Structure and thermoelectric properties of EuTi(O,N)3 ± δ (2013)

After partial substitution of nitrogen for oxygen in EuTiO3, the crystal structure, thermoelectric properties, morphology, and electronic structure of the products were analyzed and compared with pristine EuTiO3. The space group of EuTi(O,N)3 ± δ was orthorhombic Pnma due to the tilt and rotation of the anion octahedra, compared to cubic Pm3¯m of EuTiO3 (at room temperature). The thermoelectric properties of oxynitride polycrystalline bodies sintered in three different ways were investigated in the temperature range of 300 K &amp;lt; T &amp;lt; 950 K. The Seebeck coefficients (S) of the oxynitrides were lower compared with the oxide, and the electrical resistivities (ρ) were increased about one order of magnitude. The activation energies (EA) indicated a larger band gap of EuTi(O,N)3 ± δ when compared to the pristine EuTiO3 (∼1.3 eV compared to 0.98 eV). A morphological characterization by transmission electron microscopy and scanning electron microscopy illustrated intrinsic nanopores within the individual particles and weak grain-interconnections indicating poor intergrain electron transport. Ab initio calculations of the electronic structures confirmed a larger band gap of the distorted crystal structure of the oxynitride and showed a decrease of the density of states at the Fermi level, explaining the reduction of the measured S.
An in-situ resistance measurement to extract IMC resistivity and kinetic parameter of alternative metallurgies for 3D stacking (2018)

In this work, an in-situ resistance measurement method is proposed to investigate the interfacial solid state reaction of alternative metallurgies, such as Ni and Cu/Ni as UBM materials, with Sn solders. The electrical properties of formed IMC phases for different metallurgies systems are extracted and discussed. Kinetic parameters, such as activation energy and power factor, of Ni/Sn and Cu/Ni/Sn solid-state reaction are extracted from in-situ resistance measurement. Power factor of Ni/Sn and Cu/Ni/Sn kinetic reaction indicate that the IMC evolution behaviors involve bulk diffusion-controlled (the time exponent n = 0.5) for Ni/Sn, while the growth evolution of (Cu,Ni) <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sub> Sn <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sub> in Cu/Ni/Sn solid state reaction involves grain-boundary diffusion controlled (the time exponent n = 0.33) from in-situ resistance measurement. This proposed in-situ measurement methodology has the advantages of being quick and accurate to understand and characterize the reaction and phase formation between UBM and solder materials for 3D applications.
Disentanglement effects in linear and branched polyolefins (1998)

It is well known throughout the literature (Prichard et Wissbrunn, 1969; Fujiki, 1971) that shear working can appreciably change the rheological behaviour of branched polymers, while the primary molecular parameters like the molecular mass and molecular mass distribution remain unchanged. This effect is called “shear modification”. Linear polymers do not show comparable behaviour.
Gold‐Redoxkatalyse für die selektive Oxidation von Methan zu Methanol (2004)

So gut wie Gold: Die Aktivierung und selektive Oxidation inerter C-H-Bindungen ist ein anspruchsvolles Problem. Kürzlich wurde gezeigt, dass Methan mit Gold als Katalysator und H2SeO4 als Oxidationsmittel bei 28 % CH4-Umsatz mit 94 % Selektivität in CH3OSO3H umgewandelt wird (siehe Schema). Gold bietet somit eine Alternative zu anderen Edelmetallen.
Analysis of tunneling magnetoresistance test structures by low energy electron nanoscale-luminescence spectroscopy (2001)

The performance of state-of-the-art tunneling magnetoresistive (TMR) heads depends on the thickness of insulating layers less than a few nanometers thick that separate two magnetic films. We have used low energy electron nanoscale-luminescence (LEEN) spectroscopy to observe optical emission from TMR test structures with buried insulating oxides less than a few nanometers thick. TMR structures grown by metal evaporation consisted of a 0.8–3 nm Al oxide layer on a 2.4 nm CoFe alloy (84:16) on a multilayer metal-on-Si substrate, all capped with a 0.4 nm CoFe with Pt overlayer. LEEN studies with excitation energies ranging from 0.5 to 3 keV enabled emissions from the buried oxide layers versus the free surface to be distinguished. We used different compositions, thicknesses, and oxidation exposures to separate Al oxide from transition metal oxide emissions, as well as from the ambient-exposed Pt surface. A broad peak centered at 2.2–2.5 eV increased with O plasma exposure to Al films on the CoFe alloy. Emission from oxidized CoFe without Al consists of a broad emission centered at 2.5 eV. Common to all these spectra is emission at 1.8 eV, which energy-dependent LEEN demonstrates is due to the ambient-exposed Pt. Spectral changes versus oxygen exposure reveal the regime separating oxidation of the magnetic and nonmagnetic layers.
C1-inhibitor efficiently inhibitsEscherichia coli-induced tissue factor mRNA up-regulation, monocyte tissue factor expression and coagulation activation in human whole blood (2013)

Both the complement system and tissue factor (TF), a key initiating component of coagulation, are activated in sepsis, and cross-talk occurs between the complement and coagulation systems. C1-inhibitor (C1-INH) can act as a regulator in both systems. Our aim in this study was to examine this cross-talk by investigating the effects of C1-INH on Escherichia coli-induced haemostasis and inflammation. Fresh human whole blood collected in lepirudin was incubated with E. coli or ultrapurified E. coli lipopolysaccharide (LPS) in the absence or presence of C1-INH or protease-inactivated C1-INH. C3 activation was blocked by compstatin, a specific C3 convertase inhibitor. TF mRNA was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and TF surface expression was measured by flow cytometry. In plasma, the terminal complement complex, prothrombin F1·2 (PTF1·2) and long pentraxin 3 (PTX3) were measured by enzyme-linked immunosorbent assay (ELISA). Cytokines were analysed using a multiplex kit. C1-INH (1·25-5 mg/ml) reduced both LPS- and E. coli-induced coagulation, measured as a reduction of PTF1·2 in plasma, efficiently and dose-dependently (P < 0·05). Both LPS and E. coli induced marked up-regulation of TF mRNA levels and surface expression on whole blood monocytes. This up-regulation was reduced efficiently by treatment with C1-INH (P < 0·05). C1-INH reduced the release of PTX3 (P < 0·05) and virtually all cytokines measured (P < 0·05). Complement activation was inhibited more efficiently with compstatin than with C1-INH. C1-INH inhibited most of the other readouts more efficiently, consistent with additional non-complement-dependent effects. These results indicate that complement plays a role in activating coagulation during sepsis and that C1-INH is a broad-spectrum attenuator of the inflammatory and haemostatic responses.
Collective Self-Reliance: The Case of the Caribbean Community (CARICOM) (2019)

Collective self-reliance has become widely accepted as the most appropriate strategy for overcoming the constraints on development experienced by the Third World, both at the national and international levels. Collective self-reliance appears contradictory, particularly at the international level, where it is being enunciated simultaneously with the declaration to establish a New International Economic Order. The adoption of collective self-reliance at the regional level presupposes complementary policies of self-reliant development at the national level and a willingness on the part of national governments to coordinate their planning to achieve appropriate complementarity in policy and production. Caribbean Community (CARICOM) appears to lack the support of the population, which could bring to bear the requisite influence on decision makers at the national level that would force them to pursue national policies consistent with the objectives of collective self-reliance at the regional level. CARICOM has demonstrated the wide gap between the declaration of goals of self-reliance and their transformation into concrete and successful policies.
Abstract: Impact of Technique and Patient Subtype on Abdominoplasty Outcomes: A 12-year Massachusetts General Hospital Experience (2016)

PURPOSE: The traditional abdominoplasty continues to be one of the most common surgical procedures performed in the United States. However, variations in technique and patient population have introduced complexity into our understanding of abdominoplasty outcomes, warranting additional investigation. This study evaluates the impact of different surgical techniques and clinical patient factors on outcomes following abdominoplasty at a single institution. METHODS: Retrospective review of consecutive patients undergoing abdominoplasty from 1/2003–12/2014 at the Massachusetts General Hospital was performed. Complication rates among different patient subtypes were analyzed with an average 41-month follow-up. Statistics were performed using chi-square, Fisher’s exact test, and logistic regression. RESULTS: Data analysis revealed 779 patients with a mean age of 43.7 years and BMI of 27 that underwent abdominoplasty. The majority were female (92.9%) and MWL was present in 34.8%. Abdominoplasty techniques utilized included traditional (59.4%), belt lipectomy (17.9%), fleur-de-lis (16.4%), umbilical float (9.2%), and mini-abdominoplasty (2.8%). Half of the study population (n=384, 49.3%) had concurrent surgical procedures. Total complications (23.0%) primarily consisted of wound and scar-related complications (15.3%). Infection (2.4%) and seroma (2.3%) rates were low. About 60% of patients received heparin chemoprophylaxis with overall thromboembolic and hematoma rates <1%. Univariate analysis revealed that MWL (p=0.04), particularly from weight loss surgery (p=0.02), fleur-de-lis (p=0.03) or belt lipectomy (p=0.05) technique, and concurrent medial thigh lift (p<0.001) all significantly increased complications. Previous scars, amount of weight loss, operative time, liposuction, and other concurrent procedures did not affect total complications. Male gender (OR 1.96, p=0.04), fleur-de-lis technique (OR 1.71, p=0.04), and medial thigh lift (OR 3.3, p<0.001) were independent risk factors for total postoperative complications on logistic regression. CONCLUSIONS: The impact of different abdominoplasty techniques on outcomes, in the setting of a diverse patient population, has not been rigorously studied. Our unique study demonstrates that abdominoplasty can be performed safely, with an acceptable complication profile. However, an increased risk of complications may be seen with male patients, a fleur-de-lis technique, and in combination with medial thigh lift. Understanding the impact of these clinical and surgical variables will help plastic surgeons individualize their operative and post-operative plans for each patient, while minimizing risk.
Solid state polymerization of the unsymmetrical [1]ferrocenophane Fe(η-C5H4)2SiMePh; synthesis of the first stereoregular organometallic polymer (1998)

J. Rasburn, D. A. Foucher, W. F. Reynolds and G. Julius Vancso, Chem. Commun., 1998, 843 DOI: 10.1039/A801042K
Supplementary Data 3 from Discovery of JNJ-63576253, a Next-Generation Androgen Receptor Antagonist Active Against Wild-Type and Clinically Relevant Ligand Binding Domain Mutations in Metastatic Castration-Resistant Prostate Cancer (2023)

&lt;p&gt;The synthetic androgen R1881 induces maximum proliferation in LNCaP AR/cs and LNCaP F877L cell lines at 0.1nM concentrations&lt;/p&gt;
Looking at Cellular Networks Through Canonical Domains and Conformal Mapping (2015)

In order to cope with the rapidly increasing service demand in cellular networks, more cells are needed with better resource usage efficiency. This poses challenges for the network planning since service demand in practical networks is not geographically uniform and, to cope with the non-uniform service demand, network deployments are becoming increasingly irregular. This paper introduces a new idea to deal with the non-uniform network topology. Rather than capturing the network character (e.g. load distribution) by means of stochastic methods, the proposed novel approach aims at transforming the analysis from the physical (irregular) domain to a canonical/dual (uniform) domain that simplifies the work due to its symmetry. To carry out this task, physical and canonical domains are connected using the conformal (Schwarz-Christoffel) mapping, that makes the rich and mature theory of Complex Analysis available. The main contribution of this paper is to introduce and validate the usability of conformal mapping in the load coupling analysis of cellular networks.
Comparative Tumor Imaging and PDT Efficacy of HPPH Conjugated in the Mono- and Di-Forms to Various Polymethine Cyanine Dyes: Part - 2 (2013)

Previous reports from our laboratory have shown that a bifunctional agent obtained by conjugating a photosensitizer (HPPH) to a cyanine dye (CD) can be used for fluorescence image-guided treatment of tumor by photodynamic therapy (PDT). However, the resulting HPPH-CD conjugate showed a significant difference between the tumor-imaging and therapeutic doses. It was demonstrated that the singlet oxygen ( (1) O 2 (*), a key cytotoxic agent in PDT) produced by the conjugate upon excitation of the HPPH moiety was partially quenched by the CD-moiety; this resulted in a reduced PDT response when compared to HPPH-PDT under similar treatment parameters. To improve the therapeutic potential of the conjugate, we synthesized a series of dual functional agents in which one or two HPPH moieties were separately conjugated to three different dyes (Cypate, modified IR820 or modified IR783). The newly synthesized conjugates were compared with our lead compound HPPH-CD in terms of photophysical properties, in vitro and in vivo PDT efficacy, tumor uptake and imaging potential. Among the analogs investigated, the conjugate, in which two HPPH moieties were linked to the modified IR820 produced enhanced tumor uptake and tumor contrast in both Colon 26 (a murine Colon carcinoma) and U87 (a human glioblastoma) cell lines. The long-term PDT efficacy (cure) of this conjugate in BALB/c mice, bearing Colon 26 tumors was also enhanced; however, its efficacy in Nude mice bearing U87 tumors was slightly reduced. It was also found that in all the conjugates the singlet oxygen generation and, consequently, PDT efficacy were compromised by a competing pathway, whereby an electronic excitation of HPPH, the energy donor, is deactivated through an electronic excitation energy transfer (Forster Resonance Energy Transfer, FRET) to the CD fluorophore, the energy acceptor, resulting in overall reduction of the singlet oxygen production. Conjugates with increased FRET showed reduced singlet oxygen production and PDT efficacy. Among the conjugates investigated, the bifunctional agent in which two HPPH moieties were linked to the benzoindole-based cyanine dye 11 showed superiority over the lead candidate 9 (mono HPPH-cyanine dye).
Economic assessment of lithography strategies for the 22nm technology node (2009)

The unavailability of extreme ultra violet lithography (EUVL) for mass production of the 22nm technology node has created a significant void for mainstream lithography solutions. To fill this void, alternate lithography solutions that were earlier deemed to be technically and economically infeasible, such as double patterning technologies (DPT), source mask optimization (SMO), massively parallel direct write ebeam (MEBM) and Interference assisted lithography (Intf), are being proposed, developed and adopted to ensure the timely deployment of the 22nm technology node. While several studies have been undertaken to estimate the lithography process costs for volume production with the aforementioned technologies, these studies have provided only a partial analysis since they have not taken into account the impact on design density and product yield. In this paper we use the cost-per-good-die metric in order to capture process costs as well as yield and design density. We have developed a framework that estimates the lithography cost-per-good-die for SRAM arrays and have applied it to evaluate the economical feasibility of the various lithography strategies under consideration for the 22nm technology node. Specifically, we compare the cost-per-good-die for different 32MB SRAM arrays, each optimized for a different lithography solution. Our analysis shows that the selection of the best lithography strategy is both layer and volume specific. The use of DPT solutions is recommended for Active and Contact layers. The use of Intf is recommended for layers such as Poly, Metals and Vias in the case of low volume products. For medium to high volume products the use of SMO is recommended for Poly, Metals and Vias. This paper provides quantifies of economic benefit of the proposed lithography strategy.
Mechanism of inactivation of chymotrypsin by 3-benzyl-6-chloro-2-pyrone (1984)

The mechanism of inactivation of chymotrypsin by 3-benzyl-6-chloro-2-pyrone has been studied. Chloride analysis of the inactivated enzyme suggests that the complex does not contain intact chloropyrone or an acid chloride. 13C NMR studies of the enzyme inactivated with 13C-enriched chloropyrones show that (1) the pyrone ring is no longer intact, (2) C-6 becomes a carboxylate group and C-2 becomes esterified to the enzyme, probably to serine-195, and (3) a double bond is present adjacent to the serine ester. The inactivated enzyme slowly regains catalytic activity with the concomitant release of (E)-4-benzyl-2-pentenedioic acid. It is concluded that double bond migration occurs during reactivation since the position of the double bond in the released diacid product is different than in the inactivator-enzyme complex. When the reactivation is carried out in [18O]H2O-enriched water, a single oxygen-18 is incorporated into the released product and is further evidence that the inactivator is bound to the enzyme only through a single ester linkage. A deuterium isotope effect on reactivation is observed when a chloropyrone deuterated at C-5 is used. This result demonstrates that removal of a proton from C-5 is required for reactivation and that isomerization of the double bond and not hydrolysis of the acyl-enzyme is rate determining. A variety of amines accelerate the rate of reactivation by functioning as general bases and not as nucleophiles. A reaction scheme is presented that accounts for the formation of the stable inactivator-enzyme complex as well as the production of two products derived from enzymatic hydrolysis of the chloropyrone.(ABSTRACT TRUNCATED AT 250 WORDS)
CogMol: Target-Specific and Selective Drug Design for COVID-19 Using Deep Generative Models (2020)

The novel nature of SARS-CoV-2 calls for the development of efficient de novo drug design approaches. In this study, we propose an end-to-end framework, named CogMol (Controlled Generation of Molecules), for designing new drug-like small molecules targeting novel viral proteins with high affinity and off-target selectivity. CogMol combines adaptive pre-training of a molecular SMILES Variational Autoencoder (VAE) and an efficient multi-attribute controlled sampling scheme that uses guidance from attribute predictors trained on latent features. To generate novel and optimal drug-like molecules for unseen viral targets, CogMol leverages a protein-molecule binding affinity predictor that is trained using SMILES VAE embeddings and protein sequence embeddings learned unsupervised from a large corpus. CogMol framework is applied to three SARS-CoV-2 target proteins: main protease, receptor-binding domain of the spike protein, and non-structural protein 9 replicase. The generated candidates are novel at both molecular and chemical scaffold levels when compared to the training data. CogMol also includes insilico screening for assessing toxicity of parent molecules and their metabolites with a multi-task toxicity classifier, synthetic feasibility with a chemical retrosynthesis predictor, and target structure binding with docking simulations. Docking reveals favorable binding of generated molecules to the target protein structure, where 87-95 % of high affinity molecules showed docking free energy &lt; -6 kcal/mol. When compared to approved drugs, the majority of designed compounds show low parent molecule and metabolite toxicity and high synthetic feasibility. In summary, CogMol handles multi-constraint design of synthesizable, low-toxic, drug-like molecules with high target specificity and selectivity, and does not need target-dependent fine-tuning of the framework or target structure information.