gebhart/patrepeval huggingface dataset:
Physics-informed neural networks with hard constraints for inverse design (2021)

Inverse design arises in a variety of areas in engineering such as acoustic, mechanics, thermal/electronic transport, electromagnetism, and optics. Topology optimization is a major form of inverse design, where we optimize a designed geometry to achieve targeted properties and the geometry is parameterized by a density function. This optimization is challenging, because it has a very high dimensionality and is usually constrained by partial differential equations (PDEs) and additional inequalities. Here, we propose a new deep learning method -- physics-informed neural networks with hard constraints (hPINNs) -- for solving topology optimization. hPINN leverages the recent development of PINNs for solving PDEs, and thus does not rely on any numerical PDE solver. However, all the constraints in PINNs are soft constraints, and hence we impose hard constraints by using the penalty method and the augmented Lagrangian method. We demonstrate the effectiveness of hPINN for a holography problem in optics and a fluid problem of Stokes flow. We achieve the same objective as conventional PDE-constrained optimization methods based on adjoint methods and numerical PDE solvers, but find that the design obtained from hPINN is often simpler and smoother for problems whose solution is not unique. Moreover, the implementation of inverse design with hPINN can be easier than that of conventional methods.
New Statistics on the Cost of New Drug Development and the Trouble with CNS Drugs (2014)

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTNew Statistics on the Cost of New Drug Development and the Trouble with CNS DrugsCraig W. LindsleyCite this: ACS Chem. Neurosci. 2014, 5, 12, 1142Publication Date (Web):December 17, 2014Publication History Published online17 December 2014Published inissue 17 December 2014https://pubs.acs.org/doi/10.1021/cn500298zhttps://doi.org/10.1021/cn500298zeditorialACS PublicationsCopyright © 2014 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views3531Altmetric-Citations19LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (126 KB) Get e-AlertscloseSUBJECTS:Biotechnology,Drug discovery,Food,Mathematical methods,Pharmaceuticals Get e-Alerts
Specific reprogramming of alpha cells to insulin-producing cells by short glucagon promoter-driven Pdx1 and MafA (2023)

Endogenous reprogramming of pancreas-derived non-beta cells into insulin-producing cells is a promising approach to treat type 1 diabetes (T1D). One strategy that has yet to be explored is the specific delivery of insulin-producing essential genes, Pdx1 and MafA, to pancreatic alpha cells to reprogram the cells into insulin-producing cells in an adult pancreas. In this study, we used an alpha cell-specific glucagon (GCG) promoter to drive Pdx1 and MafA transcription factors to reprogram alpha cells to insulin-producing cells in chemically induced and autoimmune diabetic mice. Our results showed that a combination of a short glucagon-specific promoter with AAV serotype 8 (AAV8) can be used to successfully deliver Pdx1 and MafA to pancreatic alpha cells in the mouse pancreas. Pdx1 and MafA expression specifically in alpha cells were also able to correct hyperglycemia in both induced and autoimmune diabetic mice. With this technology, targeted gene specificity and reprogramming were accomplished with an alpha-specific promotor combined with an AAV-specific serotype and provide an initial basis to develop a novel therapy for the treatment of T1D.
Synthesis and Cytotoxic Activity of Carboxamide Derivatives of Benzo[b][1,6]naphthyridines (2003)

The reaction of 4-dimethylaminomethylene-6-methyl-4H-pyrano[4,3-b]quinoline-1,3-dione with a range of primary amines gave rise to a series of 2-substituted 6-methyl-1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carboxylic acids. The derived 4-N-[2-(dimethylamino)ethyl]carboxamides were tested for growth inhibitory properties against murine P388 leukemia, Lewis lung carcinoma (LLTC), and human Jurkat leukemia cell lines. Most compounds were potent cytotoxins, with some having IC(50) values less than 10 nM. Five were tested in vivo against subcutaneous colon 38 tumors in mice, and a single dose (3.9 mg/kg) proved to be curative for the 2-methyl and 2-(3,4-dimethoxyphenyl) derivatives in this refractory model.
BIM-23244, a Somatostatin Receptor Subtype 2- and 5-Selective Analog with Enhanced Efficacy in Suppressing Growth Hormone (GH) from Octreotide-Resistant Human GH-Secreting Adenomas1 (2001)

Although both somatostatin receptor subtype 2 (SSTR2) and SSTR5 messenger ribonucleic acid (mRNA) are consistently expressed in GH-secreting adenomas, SSTR2 has been believed to be the key modulator of somatostatin-mediated inhibition of GH release. The somatostatin agonists currently in clinical use, octreotide and lanreotide, are directed mainly to SSTR2 (IC(50) 12- to 18-fold higher than for SSTR5). Recently, however, it was demonstrated that an SSTR5 preferential agonist, BIM-23268, not only suppressed PRL release from prolactinomas and mixed GH-PRL adenomas, but also inhibited GH release in about half of GH adenomas. In addition, the SSTR5-preferring analog showed a slight additive effect when used in combination with SSTR2 preferential drugs at submaximal concentrations in octreotide partially sensitive adenomas. In the present study we quantified SSTR2 and SSTR5 mRNA expression and the GH-suppressive effects of somatostatin-14; octreotide; a SSTR2-preferential compound, BIM-23197; a SSTR5-preferential compound, BIM-23268; and a new SSTR2- and SSTR5-bispecific compound, BIM-23244, in GH-secreting tumors classified as either full responders to octreotide (n = 5) or partially sensitive to octreotide (n = 5). The octreotide-sensitive GH secretory adenomas presented with a high level of both SSTR2 and SSTR5 mRNA expression [222 +/- 61 and 327 +/- 136 pg/pg glyceraldehyde-3-phosphate dehydrogenase (GAPDH), respectively]. In these tumors the suppression of GH release was similarly achieved at picomolar ranges by octreotide, BIM-23197, and BIM-23244 (EC(50) = 25 +/- 15, 3 +/- 2, and 3 +/- 3 pmol/L, respectively). The compounds preferential for only SSTR5 were unable to inhibit GH release in such tumors. Among the octreotide partially responsive tumors, SSTR2 mRNA expression was 9-fold lower than in the octreotide-sensitive tumors (25 +/- 12 vs. 222 +/- 61 pg/pg GAPDH; P < 0.015), whereas SSTR5 mRNA expression was approximately 7-fold higher than in the octreotide-sensitive tumors (2271 +/- 1197 pg/pg GAPDH). In these octreotide partially responsive tumors, the SSTR5-preferential compound, BIM-23268, and the SSTR2- and SSTR5-bispecific compound, BIM-23244, were quite effective in suppressing GH secretion (EC(50) = 25 +/- 13 and 50 +/- 31 pmol/L, respectively). Similarly, BIM-23244, was able to suppress by 51 +/- 5% PRL release from five mixed GH- and PRL-secreting adenomas. These data indicate that due to heterogeneous expression of SSTR2 and SSTR5 receptor subtypes, in GH-secreting tumors, a bispecific analog, such as BIM-23244, that can activate both receptors could achieve better control of GH hypersecretion in a larger number of acromegalic patients.
Catalysts, systems, and methods for the conversion of biomass to chemicals (2023)

The present disclosure relates to a composition that includes a solid support, a metal positioned on the solid support, and an oxide coating positioned to at least partially cover the metal. The compositions described herein may be utilized in methods that include contacting muconic acid and hydrogen to convert at least a portion of the muconic acid to adipic acid.
ChemInform Abstract: FOTOCYCLISIERUNG VON N‐TOSYL‐N‐(BETA‐BENZOYLETHYL)GLYCINESTERN (1981)

Abstract In einer Mannich‐ Reaktion werden aus Glycinesterhydrochloriden (I) die N‐(Benzoylethyl)‐Derivate (IV) hergestellt, die zu (VI) tosyliert werden.
Ultrafast Spectroscopic Study of the Photochemistry and Photophysics of Arylhalodiazirines:  Direct Observation of Carbene and Zwitterion Formation (2006)

Ultrafast photolysis (lambdaex = 270, 350, or 360 nm) of bromophenyl, chlorophenyl, fluorophenyl, and fluoro-para-trifluoromethylphenyl diazirines produces transient species which absorb broadly in the UV and visible regions. Transient decay can be fit to either mono- or biexponential functions (tau1 approximately 0.3-10 ps, tau2 approximately 10-350 ps; dependent on solvent and halogen). Fluoro- and chlorophenylcarbene are formed within the time resolution of the spectrometer (300 fs, 270 nm excitation). Bromophenyl diazirine decay (270 nm excitation) correlates with the growth of bromophenylcarbene. Solvent and substituent effects on the slower decays of the transient absorptions are consistent with assigning the carriers of transient absorption in the visible region to ring-opened zwitterionic species.
The role of homoacetogenic bacteria as efficient hydrogen scavengers in microbial electrochemical cells (MXCs) (2012)

We evaluated the consumption of hydrogen gas at the anode of a microbial electrolysis cell (MEC) and characterized the significance of new interactions between anode respiring bacteria (ARB) and homo-acetogens. We demonstrated the significance of biofilm limitation for direct consumption of H(2) over acetate by ARB, using the deep biofilm model. Selective inhibition of the major competing hydrogen sink at the biofilm anode, methanogenesis, resulted in significant increase in electron recovery as electric current (∼10-12 A/m(2)). The presence of acetate at high concentration in the anode compartment and detection of formate, a known intermediate of the acetyl-CoA pathway, provide evidence towards the role of homoacetogenic bacteria. We also assessed the activity of homoacetogens with reverse transcription quantitative PCR targeting formyltetrahydrofolate synthetase (FTHFS) transcripts, and observed a comparable decrease in the FTHFS transcript numbers with current density and acetate concentrations as we decreased the HRT below 4.5 h. The biofilm anode community was predominated by Deltaproteobacteria (70% of total readouts) along with a fraction of the homoacetogenic genus, Acetobacterium (4% of total readouts), established by pyrosequencing targeting the V6 region of the 16S rRNA. Homoacetogens seem to play a major role as syntrophic members of the biofilm anode community when electron recovery is high.
Hydrolysis of Lactose and Transglycosylation of Selected Sugar Alcohols by LacA β-Galactosidase from Lactobacillus plantarum WCFS1 (2020)

The production, biochemical characterization, and carbohydrate specificity of LacA β-galactosidase (locus <i>lp_3469</i>) belonging to the glycoside hydrolase family 42 from the probiotic organism <i>Lactobacillus plantarum</i> WCFS1 are addressed. The β-d-galactosidase activity was maximal in the pH range of 4.0-7.0 and at 30-37 °C. High hydrolysis capacity toward the β(1 → 4) linkages between galactose and glucose (lactose) or fructose (lactulose) was found. High efficiency toward galactosyl derivative formation was observed when lactose and glycerol, xylitol, or erythritol were used. Galactosyl derivatives of xylitol were characterized for the first time as 3-<i>O</i>-β-d-galactopyranosyl-xylitol and 1-<i>O</i>-β-d-galactopyranosyl-xylitol, displaying high preference of LacA β-galactosidase for the transfer of galactosyl residues from lactose to the C1 or C3 hydroxyl group of xylitol. These results indicate the feasibility of using LacA β-galactosidase for the synthesis of different galactosyl-polyols, which could be promising candidates for beneficial and appealing functional and technological applications such as novel prebiotics or hypocaloric sweeteners.
Speechreading supplemented with frequency-selective sound-pressure information and formant-frequency information (1984)

The benefit of supplementing speechreading with frequency-selective sound-pressure information or formant-frequency information was studied by auditorily presenting this information to normal-hearing listeners without experience in speechreading. In a first experiment the sound-pressure levels in one or two, octave or 1/3-octave bands were used to amplitude-modulate pure-tone carriers with frequencies equal to the center frequencies of the filterbands (500, 1600, or 3160 Hz). Eighteen listeners scored 65.7% correct syllables (from totally unknown sentences) for speechreading with sound-pressure information in a single one-octave band at 500 Hz, and 86.7% correct syllables for speechreading with two one-octave bands at 500 and 3160 Hz, respectively. Speechreading-only scored 22.8%. In a second experiment the frequencies of the first and second formant from voiced speech were presented either as pure tones, or as a complex speechlike signal. In this experiment 18 (other) listeners scored 82.0% correct syllables on speechreading with formant-frequency information. No significant difference was found between presenting this information as pure tones or as a complex speechlike signal. Speechreading-only scored again 22.8% correct syllables.
Hydroxypropylation of Guar Splits: Kinetics and Rheology (2019)

Hydroxypropyl guar (HPG) is one of the most important derivatives of natural guar gum. In this paper, we describe the hydroxypropylation kinetics when these functional groups are added to guar splits, which are the form of guar gum typically modified in an industrial process. NMR spectroscopy was applied to quantify the amount of reacted propylene as a function of reaction time. A kinetic model was then established, enabling the derivation of a reaction rate law for the hydroxypropylation of guar. Finally, we investigated the rheological properties of aqueous-phase HPG and its cross-linked derivatives as a function of propylene content and cross-linker amount.
Photonic Crystals: Enabling Ideal Selective Solar Absorption with 2D Metallic Dielectric Photonic Crystals (Adv. Mater. 47/2014) (2014)

A metallic dielectric photonic crystal (MDPhC) is capable of selectively absorbing the entire solar spectrum via cavity modes, shown in red, while reflecting light at longer wavelengths. By doing so, the MDPhC can efficiently convert solar energy into heat for solar thermo-photovoltaic applications. On page 8041, J. B. Chou, S.-G. Kim, and co-workers demonstrate a fabricated wafer-scale, omnidirectional, selective solar absorber that is stable at high temperature.
Pharmacokinetic evaluation of two HFA pMDI formulations of salmeterol xinafoate administered through a spacer in healthy subjects (2011)

Background: No pharmacokinetic studies of salmeterol HFA pMDI with a spacer device have been published. In this study comparative bioavailability of two salmeterol HFA pMDI formulations administered through a spacer device was evaluated using pharmacokinetic endpoints.

Aim: To compare the rate and extent of absorption of the test product Salmeterol xinafoate HFA pMDI (Cipla Ltd.) with that of the reference product Serevent Evohaler (supplied by Allen & Hanburys, UK), both administered using a spacer.

Methods: This was a balanced, open label, randomised, two-period, single dose, crossover comparative bioavailability study in 24 healthy subjects. Eligible subjects were randomly assigned to receive a single dose of 100μg of both test and reference product administered with a spacer in a crossover manner on two treatment days. The two treatment days were separated with a washout period of 1 week. The blood samples were collected upto 24 hrs. Safety assessments including ECG, tremor assessment, serum potassium and blood glucose were also done at predefined time points. The primary endpoints were Cmax and AUC0-t.

Results: The plasma concentration–time profile of the test product (T) was similar in shape to that of the reference product (R). The T/R ratio of the geometric mean for Cmax and AUC0-t was 94.54 (90% CI 87.11-102.61) and 90.68 (90% CI 83.87–98.03) respectively. The CI limits for Cmax and AUC0-t was well within the bioequivalence range of 80 – 125%.

Conclusion: The bioavailability of the two HFA formulations of salmeterol when administered with a spacer was comparable and both the treatments were safe and well tolerated.
Modelling risk factors for fatal pedestrian crashes in Kolkata, India (2020)

In developing countries, pedestrian safety is an issue of major concern. Although an extensive body of literature is available on the identification of elements related to the pedestrian's risk; the studies are primarily conducted in urban areas of developed countries. The findings from these studies may only be partially relevant to the cities of an emerging country such as India. The present study analyzes historical crash records obtained from the "Kolkata Police" and identifies the risk factors at the road network level for the hazardous corridors posing a high risk to the pedestrians. The study findings reveal that pedestrians' fatalities at intersections are associated with a high vehicular volume, higher pedestrian-vehicular interaction, high approach speed, overtaking tendency of vehicles, certain land-use type, encroachment of footpath, inadequate sight distance, inaccessible pedestrian crosswalk, wider minor carriageway, the absence of a pedestrian signal head, and lack of enforcement. On the other hand, the models outcomes reveal that pedestrians' fatalities at midblock road segments are associated with low pedestrian volume, high approach speed, overtaking tendency of the vehicle, encroachment of footpath, on-street parking, wider road width, certain land-use type, inadequate sight distance, insufficient lighting, and inadequate pavement markings.
Keys for Unlocking Photolabile Metal‐Containing Cages (2010)

Photolabile metal-containing cages are metal complexes that undergo a change in coordination environment upon exposure to light of an appropriate wavelength. The light-responsive functionality can either be a component of the encapsulating ligand or a property of the metal complex itself. The altered coordination properties of light-responsive complexes can result in release of the coordinated metal ion into its surroundings, a differential reactivity of the metal center, or the liberation of a reactive molecule that had been passivated by binding to the metal center. These triggerable agents can be useful tools for manipulating the bioavailability of metals or their coordinating ligands in order to study biological pathways or for potential therapeutic purposes.
Observation of few-cycle, strong-field phenomena in surface plasmon fields (2011)

We present experimental evidence of the generation of few-cycle propagating surface plasmon polariton (SPP) wavepackets. Ultrashort plasmonic pulses were generated by few-cycle laser pulses of 5.5 fs to 6.5 fs duration on a thin silver film of 50 nm thickness coated on the face of a right-angle prism to enable Kretschmann-type SPP coupling. SPP pulses were characterized by an autocorrelation-type measurement based on fourth order, nonlinear electron photoemission induced by the SPP field. The evaluation of the measured ultrashort, fringe-resolved autocorrelation curve of the SPP wavepacket resulted in a retrieved SPP pulse length of 6.5 fs. This first demonstration of the generation of few-cycle propagating SPP wavepackets on a metal surface has important applications in ultrafast plasmonics.
A feasibility study on green biorefinery of high lignin content agro-food industry waste through supercritical water treatment (2021)

This work discusses hydrolysis of defatted grape in supercritical water (SCW) at 380 °C and 260 bar from 0.18 s to 1 s focusing attention to sugars recovery in the liquid phase of the product and detailed characterization of remaining solid phase enriched in polyaromatics (e.g. lignin, flavonoids, etc.). After the longest reaction time of 1 s, 56% of carbohydrates could be recovered in the liquid phase, as a result of carbohydrate hydrolysis. The high content of insoluble lignin in biomass (36%), acts as a mass transfer limitation and presents an important feature in the hydrolysis process, slowing down the conversion of carbohydrate fraction, as after the maximum time of 1s, 10% of carbohydrates still remained in the solid phase. Milled wood lignin, extracted from biomass and dioxane extract from the solid phase were characterized in order to understand the main structural changes during the SCW hydrolysis process. Dioxane (80%) extraction of solids produces a very complex mixture of lipophilic extractives, flavonoids and lignin with a certain amount of chemically linked carbohydrates. 2D NMR analysis of dioxane extract shows remarkably subtle changes in the amounts of main lignin moieties (β-O-4′, β-β’ (resinol) and β-5 (phenylcoumaran)). This subtle change of the main lignin structures is an important feature in the further valorisation of this sulfur-free lignin residue.
Subcapsular Splenic Urinoma and Splenorenal Fistula: A New Complication of Percutaneous Nephrolithotomy (2017)

<b><i>Background:</i></b> Splenic urinoma has not been previously reported as a complication of percutaneous nephrolithotomy (PNL). <b><i>Case Presentation:</i></b> A 46-year-old Caucasian male underwent PNL for two large left renal stones. Surgery was performed in prone split-leg position, with access obtained through combined fluoroscopic guidance and direct ureteroscopic observation of the targeted calix. The tract was dilated to 30F using a pressure balloon, and complete clearance of stones was obtained through a combination of rigid and flexible nephroscopy, as well as antegrade ureteroscopy. The patient was left with a Double-J ureteral stent on a string for removal in 1 week. After overnight observation, his hemoglobin, white blood cell count, and renal function were normal and thus he was discharged home. The day after stent removal, he presented to the emergency department with abdominal pain, was found to have mild left hydronephrosis on CT, and was discharged on 1 week of antibiotics. One week later he re-presented with worsening abdominal pain and was found to have an elevated creatinine and a white blood cell count of 21 × 10<sup>9</sup>/L. On contrasted CT with delayed images, an 18 cm splenic fluid collection was seen with a fistulous connection to the left kidney collecting system. He underwent emergent stent placement and improved clinically without drainage of the urinoma. A renal ultrasonography 1 month after stent placement confirmed resolution of the splenic urinoma, so the stent was removed at 1 month. Follow-up CT 1 month after stent removal was normal without any evidence of fistula or urinoma recurrence. <b><i>Conclusion:</i></b> This is the first report of a subcapsular splenic urinoma and splenorenal fistula post-PNL. Ureteral stent placement was sufficient for drainage and to resolve the complication.