gebhart/patrepeval huggingface dataset:
Design and Synthesis of Orexin 1 Receptor-Selective Agonists (2023)

Orexins are a family of neuropeptides that regulate various physiological events, such as sleep/wakefulness as well as emotional and feeding behavior, and that act on two G-protein-coupled receptors, i.e., orexin 1 (OX<sub>1</sub>R) and orexin 2 receptors (OX<sub>2</sub>R). Since the discovery that dysfunction of the orexin/OX<sub>2</sub>R system causes the sleep disorder narcolepsy, several OX<sub>2</sub>R-selective and OX<sub>1/2</sub>R dual agonists have been disclosed. However, an OX<sub>1</sub>R-selective agonist has not yet been reported, despite the importance of the biological function of OX<sub>1</sub>R. Herein, we report the discovery of a potent OX<sub>1</sub>R-selective agonist, (<i>R</i>,<i>E</i>)-3-(4-methoxy-3-(<i>N</i>-(8-(2-(3-methoxyphenyl)-<i>N</i>-methylacetamido)-5,6,7,8-tetrahydronaphthalen-2-yl)sulfamoyl)phenyl)-<i>N</i>-(pyridin-4-yl)acrylamide [(<i>R</i>)-YNT-3708; EC<sub>50</sub> = 7.48 nM for OX<sub>1</sub>R; OX<sub>2</sub>R/OX<sub>1</sub>R EC<sub>50</sub> ratio = 22.5]. The OX<sub>1</sub>R-selective agonist (<i>R</i>)-YNT-3708 exhibited antinociceptive and reinforcing effects through the activation of OX<sub>1</sub>R in mice.
Fluid-induced pattern-formation in 3D photonic crystals with spatially varying surface functionalization (2010)

We introduce a 3D porous photonic crystal whose inner surfaces are chemically functionalized in arbitrary spatial patterns with micro-scale resolution. We use this platform to demonstrate pattern-formation.
Proteomic Analysis Reveals Autophagy as Pro-Survival Pathway Elicited by Long-Term Exposure with 5-Azacitidine in High-Risk Myelodysplasia (2017)

Azacytidine (5-AZA) is the standard first-choice treatment for high-risk myelodysplasia (MDS) patients. However, the clinical outcome for those patients who interrupt treatment or whose disease failed to respond is very poor. In order to identify the cellular pathways that are modified by long-term exposure to 5-AZA, we evaluated key proteins associated with the autophagy pathway by reverse-phase microarray (RPPA). Comparing bone marrow mononucleated cells (BMMCs) obtained from 20 newly-diagnosed patients and after four 5-AZA cycles we found an increased autophagy signaling. We then evaluated <i>ex-vivo</i> the effect of the combination of 5-AZA with autophagy inhibitors chloroquine (CQ) and leupeptin. Since 5-AZA and CQ showed synergism due to an increase of basal autophagy after 5-AZA exposure, we adopted a sequential treatment treating BMMCs with 5 μM 5-AZA for 72 h followed by 10 μM CQ for 24 h and found increased apoptosis, associated to a reduction of G2M phase and increase in G0-G1 phase. Long-term exposure to 5-AZA induced the reduction of the autophagic marker SQSTM1/p62, reversible by CQ or leupeptin exposure. In conclusion, we identified autophagy as a compensatory pathway occurring in MDS-BM after long-term exposure to 5-AZA and we provided evidences that a sequential treatment of 5-AZA followed by CQ could improve 5-AZA efficacy, providing novel insight for tailored therapy in MDS patients progressing after 5-AZA therapy.
ChemInform Abstract: PROCEDURE FOR DIETHOXYMETHYLATION OF KETONES (1981)

Abstract Orthoameisensäureester (I) liefert mit BF 3 ein Kation (II), das mit Cyclohexanon (III) zum Substitutionsprodukt (IV) als Hauptprodukt führt.
Mechanisms of Microtubule Guiding on Microfabricated Kinesin-Coated Surfaces:  Chemical and Topographic Surface Patterns (2003)

Cells regulate active transport of intracellular cargo using motor proteins. Recent nanobiotechnology efforts aim to adapt motor proteins to power the movement and assembly of synthetic materials. A motor-protein-based nanoscale transport system (molecular shuttle) requires that the motion of the shuttles be guided along tracks. This study investigates the principles by which microtubules, serving as shuttle units, are guided along micrometer-scale kinesin-coated chemical and topographical tracks, where the efficiency of guidance is determined by events at the track boundary. Thus, we measure the probability of guiding as microtubules reach the track boundary of (1) a chemical edge between kinesin-coated and kinesin-free surfaces, (2) a topography-only wall coated completely with kinesin, and (3) a kinesin-free wall next to a kinesin-coated bottom surface (topography and chemistry combined). We present a guiding mechanism for each surface type that takes into account the physical properties of microtubule filaments and the surface properties (geometry, chemistry), and elucidate the contributions of surface topography and chemistry. Our experimental and theoretical results show that track edges that combine both topography and chemistry guide microtubules most frequently (approximately 90% of all events). By applying the principles of microtubule guidance by microfabricated surfaces, one may design and build motor-protein-powered devices optimized for transport.
FT-1101: A Structurally Distinct Pan-BET Bromodomain Inhibitor with Activity in Preclinical Models of Hematologic Malignancies (2015)

Abstract Members of the Bromodomain and Extra-Terminal (BET) family of bromodomain-containing proteins (BRD2, BRD3, BRD4, and BRDT) bind to acetylated lysine residues on histone tails and act as epigenetic readers to regulate chromatin structure and gene expression. In particular, BET family member BRD4 has been shown to positively regulate the expression of MYC and other critical cancer-associated genes through the localization of BRD4 to super-enhancer regulatory elements. Results from preclinical studies conducted using the small molecule tool BET inhibitor (+)-JQ1, and emerging data from clinical trials of BET inhibitors in leukemia and lymphoma patients, have provided support for the therapeutic potential of BET inhibitors in hematologic malignancies. A protein structure-guided drug design approach was employed to explore small molecule acetyl lysine mimetics and led to the identification of the BET inhibitor FT-1101, which is structurally unrelated to reported clinical-stage BET inhibitors in the (+)-JQ1 class. In biochemical binding assays, FT-1101 displayed equipotent inhibition of binding of both bromodomains in all four BET family members to a known bromodomain ligand (Kd ≤ 20 nM). In vitro, FT-1101 displayed potent anti-proliferative activity across a broad panel of human leukemia, lymphoma, and multiple myeloma cell lines, with 66 out of 123 cell lines having IC50 values &lt; 500 nM. For the MV-4-11 acute myeloid leukemia cell line, the anti-proliferative activity of FT-1101 (IC50 = 40 nM) correlated with down-regulation of MYC gene and protein expression, suggesting that its anti-proliferative activity was at least in part due to suppression of MYC. Additionally, genome-wide mapping of BRD4 super-enhancer binding sites in MV-4-11 cells by ChIP-sequencing identified several potential pharmacodynamic biomarkers outside of the MYC signaling network. In vivo, in the MV-4-11 xenograft model, oral treatment with FT-1101 at its maximum tolerated dose resulted in significant tumor growth inhibition, including tumor regressions, on schedules ranging from once daily to once weekly, and similar activity was also observed in the THP-1 AML xenograft model. Superior in vivo efficacy in the MV-4-11 model was observed for FT-1101 relative to BET inhibitors of the (+)-JQ1 class. In vivo efficacy was associated with prolonged drug exposure and a &gt;75% decrease in MYC gene expression in tumors that was sustained for at least 12 hours. FT-1101 also crossed the blood-brain barrier in mice, achieving a pharmacologically relevant free drug concentration in the brain. The promising preclinical profile of FT-1101 warranted its rapid progression into human clinical trials, and a Phase 1 study in patients with relapsed refractory acute leukemia or high-risk myelodysplastic syndrome is currently underway. Disclosures No relevant conflicts of interest to declare.
Potent Inactivation of Human Respiratory Viruses Including SARS-CoV-2 by a Photoactivated Self-Cleaning Regenerative Antiviral Coating (2022)

The COVID-19 pandemic marks an inflection point in the perception and treatment of human health. Substantial resources have been reallocated to address the direct medical effects of COVID-19 and to curtail the spread of the virus. Thereby, shortcomings of traditional disinfectants, especially their requirement for regular reapplication and the related complications (e.g., dedicated personnel and short-term activity), have become issues at the forefront of public health concerns. This issue became especially pressing when infection-mitigating supplies dwindled early in the progression of the pandemic. In consideration of the constant threat posed by emerging novel viruses, we report a platform technology for persistent surface disinfection to combat virus transmission through nanomaterial-mediated, localized UV radiation emission. In this work, two formulations of Y<sub>2</sub>SiO<sub>5</sub>-based visible-to-UV upconversion nanomaterials were developed using a facile sol-gel-based synthesis. Our formulations have shown substantial antiviral activities (4 × 10<sup>4</sup> to 0 TCID<sub>50</sub> units in 30 min) toward an enveloped, circulating human coronavirus strain (OC43) under simple white light exposure as an analogue to natural light or common indoor lighting. Additionally, we have shown that our two formulations greatly reduce OC43 RNA recovery from surfaces. Antiviral activities were further demonstrated toward a panel of structurally diverse viruses including enveloped viruses, SARS-CoV-2, vaccinia virus, vesicular stomatitis virus, parainfluenza virus, and Zika virus, as well as nonenveloped viruses, rhinovirus, and calicivirus, as evidence of the technology's broad antiviral activity. Remarkably, one formulation completely inactivated 10<sup>5</sup> infectious units of SARS-CoV-2 in only 45 min. The detailed technology has implications for the design of more potent, long-lived disinfectants and modified/surface-treated personal protective equipment targeting a wide range of viruses.
A MICROMACHINED STAINLESS STEEL CUFF FOR ELECTROMAGNETIC MEASUREMENT OF FLOW IN BLOOD VESSELS (2004)

This paper reports a micromachined cuff that senses blood flow velocity inside a blood vessel. Utilizing two electrically isolated electrodes in the cuff, the sensor produces a voltage proportional to the flow rate in the presence of a magnetic flux, which is to be externally read out by an implanted circuit chip. The cuff structure is fabricated from planar stainless steel foil using batch-compatible micro-electro-discharge machining and subsequently plastically reshaped into a ring by inflating a cylindrical balloon inside a blood vessel. The cuff has a pair of electrodes which are separated from each other by insulating links. A dielectric layer coats all surfaces except the electrodes. Devices deployed inside 3-mm i.d. silicone tubes demonstrate linear and symmetric responses of 3.1-4.3 V per cm/sec over 180 cm/sec with fields of about 0.25 T created by a local permanent magnet of 25x25x9 mm 3 .
HCIR 2012 (2012)

This report describes the 2012 Symposium on Human-Computer Interaction and Information Retrieval. Now in its sixth year, the two-day symposium (formerly a one-day workshop) was held in October in Cambridge, MA. The event brought together researchers and practitioners from academia, industry, and government and a range of disciplines for in-depth discussions in an informal atmosphere. The symposium attracted 75 attendees, over a third of which were from industry. New for this year, we accepted full papers that will be archived and published in the ACM Digital Library. We continued the HCIR Challenge, this year focusing on the problem of people and expertise finding, five in-depth system demonstrations, and audience selection of a challenge winner.
ChemInform Abstract: Double Oxidation of D‐Xylose to D‐glycero‐pentos‐2,3‐diulose (2,3‐Diketo‐D‐xylose) by Pyranose Dehydrogenase from the Mushroom Agaricus bisporus. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A New Approach to Teaching Thermofluids Dimensional Analysis (2000)

A new method of dimensional analysis is presented by demonstrating its application to a range of problems in fluid flow and heat transfer. The technique is a development of a previously published and accepted method of inspectional analysis. This new technique is shown to give the correct results on both simple equations with solutions, and on more complex sets of partial differential equations without solutions. This development of a single method from the simple to the complex has obvious teaching advantages.
Structure of a Bis-Amidinium Derivative of Hoechst 33258 Complexed to Dodecanucleotide D(CGCGAATTCGCG)2: The Role of Hydrogen Bonding in Minor Groove Drug-DNA Recognition (1997)

The crystal structure is reported of a complex between the dodecanucleotide sequence d(CGCGAATTCGCG)2and an analogue of the DNA binding drug Hoechst 33258, in which the piperazine ring has been replaced by an amidinium group and the phenol ring by a phenylamidinium group. The structure has been refined to an R factor of 19.5% at 2.2 A resolution. The drug is held in the minor groove by five strong hydrogen bonds, together with bridging water molecules at both ends. There are few other contacts with the floor of the groove, indicating a lack of isohelicity with the groove and suggesting (i) that the observed high DNA affinity of this drug is primarily due to the array of hydrogen bonds and (ii) that these more than compensate for its poor isohelicity.
Progress in the Function and Regulation of ADP-RibosylationA report on the 18th International Conference on ADP-Ribosylation, Zurich, Switzerland, 18 to 21 August 2010. (2011)

Adenosine 5'-diphosphate (ADP)-ribosylation is a protein posttranslational modification that is catalyzed by ADP-ribosyltransferases (ARTs), using nicotinamide adenine dinucleotide (NAD(+)) as a substrate. Mono-ribosylation can be extended into polymers of ADP-ribose (PAR). Poly(ADP-ribosyl)polymerase (PARP) 1, the best-characterized cellular enzyme catalyzing this process, is the prototypical member of a family of mono- and poly(ADP-ribosyl)transferases. The physiological consequences of ADP-ribosylation are inadequately understood. PARP2010, the 18th International Conference on ADP-Ribosylation, attracted scientists from all over the world to Zurich, Switzerland. Highlights from this meeting include promising clinical trials with PARP inhibitors and new insights into cell, structural, and developmental biology of ARTs and the (glyco)hydrolase proteins that catalyze de-ADP-ribosylation of mono- or poly-ADP-ribosylated proteins. Moreover, potential links to the NAD-dependent sirtuin family were explored on the basis of a shared dependence on cellular NAD(+) concentrations and the relationship of ADP-ribosylation with intermediary metabolism and cellular energetics.
High-Performance Long-Wavelength ( 1.3 m) InGaAsPN Quantum-Well Lasers (1999)

We demonstrate high-performance InGaAsPN quan- tum well based long-wavelength lasers grown on GaAs substrates. Nitrogen containing lasers emitting in the = 1.2- to 1.3- m wavelength range were grown by gas source molecular beam epitaxy using a RF plasma nitrogen source. Under pulsed exci- tation, lasers emitting at = 1.295 m exhibited a record low threshold current density ( ) of 2.5 kA/cm . Lasers grown with less nitrogen in the quantum well exhibited significantly lower threshold current densities of = 1.9 kA/cm at = 1.27 m and = 1.27 kA/cm at = 1.2 m. We also report a slope efficiency of 0.4 W/A and an output power of 450 mW under pulsed operation for nitrogen containing lasers emitting at 1.2 m.
Evaluation of shielded enclosure leak detection system (SELDS) with non-conventional excitation for shield weld quality monitoring (2004)

In this paper, we describe laboratory evaluations of nonconventional shielded enclosure leak detection system (SELDS) test techniques for determining/monitoring welded seam quality for EMI/RFI shielded construction. These techniques involve a "transmission line" seam excitation rather than the usual "circuit" excitation. The method of evaluation and results are presented.
Two-Timescale Stochastic Dispatch of Smart Distribution Grids (2017)

Smart grids should efficiently integrate stochastic renewable resources while effecting voltage regulation. Energy management is challenging since it is a multistage problem where decisions are not all made at the same timescale and must account for the variability during real-time operation. The joint dispatch of slow- and fast-timescale controls in a smart distribution grid is considered here. The substation voltage, the energy exchanged with a main grid, and the generation schedules for small diesel generators have to be decided on a slow timescale; whereas optimal photovoltaic inverter setpoints are found on a more frequent basis. While inverter and looser voltage regulation limits are imposed at all times, tighter bus voltage constraints are enforced on the average or in probability, thus enabling more efficient renewable integration. Upon reformulating the two-stage grid dispatch as a stochastic convex-concave problem, two distribution-free schemes are put forth. An average dispatch algorithm converges provably to the optimal two-stage decisions via a sequence of convex quadratic programs. Its non-convex probabilistic alternative entails solving two slightly different convex problems and is numerically shown to converge. Numerical tests on real-world distribution feeders verify that both schemes yield lower costs over competing alternatives.
Ultrastable Complexes for in vivo Use: A Bifunctional Chelator Incorporating a Cross-Bridged Macrocycle. (2005)

For Abstract see ChemInform Abstract in Full Text.
A Monte Carlo approach to validation of FFF VMAT treatment plans for the TrueBeam linac (2013)

The authors have presented a method for making the Varian IAEA compliant 6 MV FFF phase space file of the TrueBeam linac compatible with BEAMnrc/DOSXYZnrc. After benchmarking the modified phase space against measurement, they have demonstrated its potential for use in MC based quality assurance of complex delivery techniques.
Endogenous interleukin-10 modulates fibrosis and regeneration in experimental chronic pancreatitis (2002)

Interleukin (IL)-10, a potent anti-inflammatory cytokine, limits the severity of acute pancreatitis and downregulates transforming growth factor (TGF)-beta release by inflammatory cells on stimulation. Proinflammatory mediators, reactive oxygen species, and TGF-beta can activate pancreatic stellate cells and their synthesis of collagen I and III. This study evaluates the role of endogenous IL-10 in the modulation of the regeneration phase following acute pancreatitis and in the development of pancreatic fibrosis. IL-10 knockout (KO) mice and their C57BL/6 controls were submitted to repeated courses (3/wk, during 6 wk, followed by 1 wk of recovery) of cerulein-induced acute pancreatitis. TGF-beta(1) release was measured on plasma, and its pancreatic expression was assessed by quantitative RT-PCR and immunohistochemistry. Intrapancreatic IL-10 gene expression was assessed by semiquantitative RT-PCR, and intrapancreatic collagen content was assessed by picrosirius staining. Activated stellate cells were detected by immunohistochemistry. S phase intrapancreatic cells were marked using tritiated thymidine labeling. After repeated acute pancreatitis, IL-10 KO mice had more severe histological lesions and fibrosis (intrapancreatic collagen content) than controls. TGF-beta(1) plasma levels, intrapancreatic transcription, and expression by ductal and interstitial cells, as well as the number of activated stellate cells, were significantly higher. IL-10 KO mice disclosed significantly fewer acinar cells in S phase, whereas the opposite was observed for pseudotubular cells. Endogenous IL-10 controls the regeneration phase and limits the severity of fibrosis and glandular atrophy induced by repeated episodes of acute pancreatitis in mice.
Supplementary Fig S3 from Gemcitabine Mechanism of Action Confounds Early Assessment of Treatment Response by 3′-Deoxy-3′-[<sup>18</sup>F]Fluorothymidine in Preclinical Models of Lung Cancer (2023)

&lt;p&gt;TS and hENT1 expression are not altered 6 h after gemcitabine.&lt;/p&gt;
On the origin of smallpox: Correlating variola phylogenics with historical smallpox records (2007)

Human disease likely attributable to variola virus (VARV), the etiologic agent of smallpox, has been reported in human populations for >2,000 years. VARV is unique among orthopoxviruses in that it is an exclusively human pathogen. Because VARV has a large, slowly evolving DNA genome, we were able to construct a robust phylogeny of VARV by analyzing concatenated single nucleotide polymorphisms (SNPs) from genome sequences of 47 VARV isolates with broad geographic distributions. Our results show two primary VARV clades, which likely diverged from an ancestral African rodent-borne variola-like virus either approximately 16,000 or approximately 68,000 years before present (YBP), depending on which historical records (East Asian or African) are used to calibrate the molecular clock. One primary clade was represented by the Asian VARV major strains, the more clinically severe form of smallpox, which spread from Asia either 400 or 1,600 YBP. Another primary clade included both alastrim minor, a phenotypically mild smallpox described from the American continents, and isolates from West Africa. This clade diverged from an ancestral VARV either 1,400 or 6,300 YBP, and then further diverged into two subclades at least 800 YBP. All of these analyses indicate that the divergence of alastrim and variola major occurred earlier than previously believed.
Integration of Solid Freeform Fabrication in Design (2001)

During the last few decades, designers have been educated to develop designs with restricted geometry so that parts can be made easily. The revolutionary aspect of Rapid Manufacturing will be that geometry will no longer be a limiting factor. The introduction of Rapid Manufacturing will have a number of effects on Design. It will be possible to have re-entrant shapes without complicating manufacturing, no draft angles, variable wall thickness, no split lines and fewer parts leading to easier assembly and lower stock. The individual designer’s method of working will change with the introduction of Rapid Manufacturing and also there will be changes to the overall design process. Examples will be the elimination of prototype and pre-production stages, as end part manufacture will occur as soon as the CAD is finished. This will affect project management practices and sign-off procedures.
Physics and performance of new solid-state laser gain media (1994)

Many new solid state laser media have been identified during the last decade, and it is now possible to usefully generate laser light from the ultraviolet region to the mid-infrared. These new laser media have become available in part because of the improved understanding of the solid state physics issues that impact the laser performance. The physics and performance of the new tunable ultraviolet-emitting laser crystal, Ce3+:LiSAF, will be discussed, as will the critical physics issues pertaining to the operation of 3 μm Er3− and Ho3+-based crystals.