gebhart/patrepeval huggingface dataset:
Glutathione-Sensitive Hyaluronic Acid-SS-Mertansine Prodrug with a High Drug Content: Facile Synthesis and Targeted Breast Tumor Therapy (2016)

Low tolerability and tumor selectivity restricts many potent anticancer drugs including mertansine from wide clinical use. Here, glutathione-activatable hyaluronic acid-SS-mertansine prodrug (HA-SS-DM1) was designed and developed to achieve enhanced tolerability and targeted therapy of CD44+ human breast tumor xenografts. DM1 was readily conjugated to HA using 2-(2-pyridyldithio)-ethylamine as a linker. Notably, HA-SS-DM1 with a high DM1 content of 20 wt % had a mean size of ∼170 nm at concentrations above 0.2 mg/mL while transformed into unimers upon dilution to 0.04 mg/mL. HA-SS-DM1 exhibited a superior targetability to MCF-7 cancer cells with an exceptionally low IC<sub>50</sub> of 0.13 μg DM1/mL. The pharmacokinetic studies displayed that Cy5-labeled HA-SS-DM1 had an elimination half-life of 2.12 h. Notably, HA-SS-DM1 displayed better tolerability with a maximum-tolerated dose 4-fold higher than free DM1. Cy5-labeled HA-SS-DM1 quickly accumulated in the MCF-7 tumor, the fluorescence intensity of which was maximized at 24 h post injection and kept strong in 48 h. The tumor Cy5 level reached 8.17%ID/g at 24 h. The therapeutic results demonstrated that HA-SS-DM1 effectively inhibited tumor growth at 800 μg DM1 equiv/kg while causing reduced side effects as compared to free DM1. Glutathione-cleavable HA-SS-DM1 prodrug with superior drug content, excellent targetability, enhanced tolerability, and easy large-scale synthesis appears to be a highly promising alternative to clinically used Trastuzumab emtansine (T-DM1) for targeted breast tumor therapy.
A Decellularized Skeletal Muscle-Derived Extracellular Matrix (ECM) for In Situ Muscle Regeneration (2020)

Lee, Hyeongjin PhD; Min Ju, Young PhD; Jackson, John D. PhD; Yoo, James J. MD, PhD; Atala, Anthony MD, FACS Author Information
Processing JPEG-compressed images (2002)

We present techniques that allow the processing of an image in the "JPEG-compressed" domain. The goal is to reduce memory requirements while increasing the speed by avoiding decompression and space domain operations. An effort is made to implement the minimum number of JPEG basic operations. Techniques are presented for scaling, previewing, rotating, mirroring, cropping, recompressing, and segmenting JPEG-compressed data.
Renewal, regeneration and ‘race’: Issues in urban policy (1992)

Abstract This article examines the impact of urban policy on Britain's inner city areas, and specifically on the various communities living within them. It is suggested that policies need to address the issue of ‘racial’ inequality directly, rather than relying on trickle‐down effects from conventional economic regeneration models. Problems with current urban renewal service delivery policies are highlighted, and proposals are put forward for models of ‘good practice’.
Active Thermal Controlof Distributed Parameter Systems Excited at MultipleFrequencies (2005)

Abstract In testing packaged high-power integrated circuits, active thermal control is useful in providing die-level temperature stability. A time-varying heat load is applied to the surface of the package to compensate for the time-varying test power sequence applied to the die. An earlier study determined the proper control heat load for a single-frequency sinusoidal variation in die power subject to a finite allowed temperature variation on the die. Actual test power sequences contain many frequencies at various phase angles, each contributing to the temperature variation of the die. In the present study, we develop a method of controlling multiple frequency test sequences subject to a finite temperature tolerance. It is shown that the total control power may be minimized assigning temperature tolerances to the highest frequencies in the test power sequence.
Total Synthesis of (±)-Sceptrin (2020)

A four-step synthesis of the dimeric pyrrole-imidazole alkaloid sceptrin is reported. The brevity of the route is based on a simple solution developed for selective assembly of the cyclobutane core of the natural product. The photochemical intermolecular [2 + 2] dimerization of a useful hymenidin surrogate enables direct entry to this enigmatic class of biologically active marine secondary metabolites.
Catalytic Asymmetric Hydrogenation of N‐Iminopyridinium Ylides: Expedient Approach to Enantioenriched Substituted Piperidine Derivatives. (2005)

We have developed an efficient catalytic enantioselective hydrogenation of pyridine derivatives. Enhanced reactivity was possible by an optimization of the electronic properties of the catalyst through ligand modification. This methodology shows the particular reactivity of &lt;i&gt;N&lt;/i&gt;-iminopyridinium ylides that provides access to substituted piperidines in good enantiomeric excesses.
Topology Adaptive Graph Convolutional Networks (2017)

Spectral graph convolutional neural networks (CNNs) require approximation to the convolution to alleviate the computational complexity, resulting in performance loss. This paper proposes the topology adaptive graph convolutional network (TAGCN), a novel graph convolutional network defined in the vertex domain. We provide a systematic way to design a set of fixed-size learnable filters to perform convolutions on graphs. The topologies of these filters are adaptive to the topology of the graph when they scan the graph to perform convolution. The TAGCN not only inherits the properties of convolutions in CNN for grid-structured data, but it is also consistent with convolution as defined in graph signal processing. Since no approximation to the convolution is needed, TAGCN exhibits better performance than existing spectral CNNs on a number of data sets and is also computationally simpler than other recent methods.
Abstract IA15: Genetic screens to study cancer (2017)

Abstract We will describe our efforts to use the CRISPR/Cas9 system to systematically identify the genetic liabilities of cancer cells and the synthetic lethal relationships of common oncogenes. Citation Format: David M. Sabatini. Genetic screens to study cancer [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr IA15.
Nanocrystals with linear and branched topology (2023)

Disclosed herein are nanostructures comprising distinct dots and rods coupled through potential barriers of tuneable height and width, and arranged in three dimensional space at well defined angles and distances. Such control allows investigation of potential applications ranging from quantum information processing to artificial photosynthesis.
Continuing rearrangement of immunoglobulin and T-cell receptor genes in a Ha-ras-transformed lymphoid progenitor cell line. (1987)

The arrangement of immunoglobulin genes has been examined in a series of lymphoid cell lines transformed with the Harvey murine sarcoma virus. One cell line, HAFTL-1, expresses antigenic markers characteristic of B-lymphoid cells and undergoes frequent rearrangement at the JH locus (where J = joining and H = heavy chain) during propagation in culture. By molecular cloning and nucleotide sequence determination, these rearrangements were found to represent the earliest postulated step in heavy chain gene assembly: the joining of a diversity (D) segment to a JH segment. The HAFTL-1 cell line also undergoes infrequent D beta-to-J beta joining at the T-cell receptor beta locus in culture. The observations presented here suggest that the HAFTL-1 cell line represents the early stage of B-cell differentiation at which immunoglobulin gene rearrangement is initiated.
Development of a Multimaterial Optical Fiber for Fully Distributed Magnetic Sensing Applications (2021)

A novel multimaterial fiber optic magnetic sensing design is presented and evaluated in this letter. The multimaterial optical fiber has demonstrated <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$ &lt; 0.2\ n\epsilon $</tex-math></inline-formula> sensitivity to external magnetic fields over a 2-m gauge length. Intended for immediate use in unconventional oil and gas (UOG) and measuring while drilling (MWD), this instrument could have wide-ranging subsurface sensing applications. Composed of fused silica cladding, internally distributed ferromagnetic nickel, and a series of fiber Bragg gratings, the multimaterial structure has been consistently drawn to over 1 km of length on a fiber draw tower. Due to the consistency of manufacturability and high magnetic sensitivities over long lengths, the proposed design may be considered a competitive magnetic sensor in UOG and MWD applications.
Gibberellin-to-abscisic acid balances govern development and differentiation of the nucellar projection of barley grains (2014)

In cereal grains, the maternal nucellar projection (NP) constitutes the link to the filial organs, forming a transfer path for assimilates and signals towards the endosperm. At transition to the storage phase, the NP of barley (Hordeum vulgare) undergoes dynamic and regulated differentiation forming a characteristic pattern of proliferating, elongating, and disintegrating cells. Immunolocalization revealed that abscisic acid (ABA) is abundant in early non-elongated but not in differentiated NP cells. In the maternally affected shrunken-endosperm mutant seg8, NP cells did not elongate and ABA remained abundant. The amounts of the bioactive forms of gibberellins (GAs) as well as their biosynthetic precursors were strongly and transiently increased in wild-type caryopses during the transition and early storage phases. In seg8, this increase was delayed and less pronounced together with deregulated gene expression of specific ABA and GA biosynthetic genes. We concluded that differentiation of the barley NP is driven by a distinct and specific shift from lower to higher GA:ABA ratios and that the spatial-temporal change of GA:ABA balances is required to form the differentiation gradient, which is a prerequisite for ordered transfer processes through the NP. Deregulated ABA:GA balances in seg8 impair the differentiation of the NP and potentially compromise transfer of signals and assimilates, resulting in aberrant endosperm growth. These results highlight the impact of hormonal balances on the proper release of assimilates from maternal to filial organs and provide new insights into maternal effects on endosperm differentiation and growth of barley grains.
Insecticidal 1-Cyclopropyl-1,4-diarylbutenes and 1,4-Diarylbutanes (1995)

Our investigations into pyrethroid insecticides in which various isosteric groups replaced the ester functionality have yielded a number of novel structures with insecticidal activity equal or superior to commercial standards. Some of these molecules also have miticidal activity. This chapter describes the synthesis and biological activity of compounds containing an alkene or epoxide linker group in place of the ester. We discuss spectrum and residual activity for several of these compounds. We selected one of the alkenes, 1-cyclopropyl-1-(4-chlorophenyl)-4-(4-fluoro-3-phenoxyphenyl)-2-butene, for further testing and showed it to have excellent activity against rice pests, low mammalian toxicity, and very low toxicity to fish.
Analysis of Retinol Binding Protein 4 and ABCA4 Gene Variation in Non-Neovascular Age-Related Macular Degeneration (2023)

Age-related macular degeneration (AMD) may be associated with <i>ABCA4</i> variants and is characterized by the accumulation of visual cycle-byproduct lipofuscin. Reducing retinol-binding protein 4 (RBP4), a retinol transporter protein, may reduce lipofuscin production. This study aims to assess the associations between plasma RBP4, the <i>ABCA4</i> variation, and AMD severity. Sixty-seven participants were grouped into healthy/mild AMD (<i>n</i> = 32) and severe AMD (<i>n</i> = 35) groups. The latter group was older than the former group and had higher levels of RBP4 (36.8 ± 8.3 vs. 30.4 ± 7.0 μg/mL, <i>p</i> = 0.0012). The ten participants with six <i>ABCA4</i> linked-variants had higher RBP4 than those without (37.8 ± 7.7 vs. 32.4 ± 7.9 μg/mL; <i>p</i> = 0.026), and eight of them had severe AMD. Univariate analyses showed that severe AMD was related to older age (OR, 1.26; 95% CI, 1.13-1.40; <i>p</i> < 0.0001) and to higher RBP4 levels (OR, 1.12; 95% CI, 1.04-1.20; <i>p</i> = 0.003), whereas the linked <i>ABCA4</i> variants had no associations. After adjustment, however, only age remained significantly associated with severe AMD. This pilot study shows a trend of higher plasma RBP4 levels in severe AMD or the <i>ABCA4</i>-linked variants, and further age-matched studies are warranted.
28.2: Genuinely Wearable Display with a Flexible Battery, a Flexible Display Panel, and a Flexible Printed Circuit (2014)

Abstract To fabricate a genuinely flexible and wearable display with a flexible battery together with a flexible OLED panel and a flexible printed circuit, a flexible lithium ion battery has been developed, and a prototype of a wrist‐wearable display has been fabricated.
Frequency Comb Fourier Transform Spectroscopy with kHz Optical Resolution (2009)

Michelson-less Fourier spectra, comprising 500,000,000 spectral elements spanning 1 nm with 2.3 kHz (7.7 10−8 cm−1) resolution, are recorded within 6s. Moving mirror of equivalent interferometers should cover 130 km at 78,000 km/hour velocity.
Filtering Ground Reaction Force Data Affects the Calculation and Interpretation of Joint Kinetics and Energetics During Drop Landings (2013)

An inverse dynamic analysis and subsequent calculation of joint kinetic and energetic measures is widely used to study the mechanics of the lower extremity. Filtering the kinematic and kinetic data input to the inverse dynamics equations affects the calculated joint moment of force (JMF). Our purpose was to compare selected integral values of sagittal plane ankle, knee, and hip joint kinetics and energetics when filtered and unfiltered GRF data are input to inverse dynamics calculations. Six healthy, active, injury-free university student (5 female, 1 male) volunteers performed 10 two-legged landings. JMFs were calculated after two methods of data filtering. Unfiltered: marker data were filtered at 10 Hz, GRF data unfiltered. Filtered: both GRF and marker data filtered at 10 Hz. The filtering of the GRF data affected the shape of the knee and hip joint moment-time curves, and the ankle, knee and hip joint mechanical power-time curves. We concluded that although the contributions of individual joints to the support moment and to total energy absorption were not affected, the attenuation of high-frequency oscillations in both JMF and JMP time curves will influence interpretation of CNS strategies during landing.
Narrow-band topology optimization on a sparsely populated grid (2018)

A variety of structures in nature exhibit sparse, thin, and intricate features. It is challenging to investigate these structural characteristics using conventional numerical approaches since such features require highly refined spatial resolution to capture and therefore they incur a prohibitively high computational cost. We present a novel computational framework for high-resolution topology optimization that delivers leaps in simulation capabilities, by two orders of magnitude, from the state-of-the-art approaches. Our technique accommodates computational domains with over one billion grid voxels on a single shared-memory multiprocessor platform, allowing automated emergence of structures with both rich geometric features and exceptional mechanical performance. To achieve this, we track the evolution of thin structures and simulate its elastic deformation in a dynamic narrow-band region around high-density sites to avoid wasted computational effort on large void regions. We have also designed a mixed-precision multigrid-preconditioned iterative solver that keeps the memory footprint of the simulation to a compact size while maintaining double-precision accuracy. We have demonstrated the efficacy of the algorithm through optimizing a variety of complex structures from both natural and engineering systems.
Integrated Omic Analysis of Oropharyngeal Carcinomas Reveals Human Papillomavirus (HPV)–dependent Regulation of the Activator Protein 1 (AP-1) Pathway (2014)

HPV-positive oropharyngeal carcinoma (OPC) patients have superior outcomes relative to HPV-negative patients, but the underlying mechanisms remain poorly understood. We conducted a proteomic investigation of HPV-positive (n = 27) and HPV-negative (n = 26) formalin-fixed paraffin-embedded OPC biopsies to acquire insights into the biological pathways that correlate with clinical behavior. Among the 2,633 proteins identified, 174 were differentially abundant. These were enriched for proteins related to cell cycle, DNA replication, apoptosis, and immune response. The differential abundances of cortactin and methylthioadenosine phosphorylase were validated by immunohistochemistry in an independent cohort of 29 OPC samples (p = 0.023 and p = 0.009, respectively). An additional 1,124 proteins were independently corroborated through comparison to a published proteomic dataset of OPC. Furthermore, utilizing the Cancer Genome Atlas, we conducted an integrated investigation of OPC, attributing mechanisms underlying differential protein abundances to alterations in mutation, copy number, methylation, and mRNA profiles. A key finding of this integration was the identification of elevated cortactin oncoprotein levels in HPV-negative OPCs. These proteins might contribute to reduced survival in these patients via their established role in radiation resistance. Through interrogation of Cancer Genome Atlas data, we demonstrated that activation of the β1-integrin/FAK/cortactin/JNK1 signaling axis and associated differential regulation of activator protein 1 transcription factor target genes are plausible consequences of elevated cortactin protein levels.
Imeglimin amplifies glucose-stimulated insulin release from diabetic islets via a distinct mechanism of action (2021)

Pancreatic islet β-cell dysfunction is characterized by defective glucose-stimulated insulin secretion (GSIS) and is a predominant component of the pathophysiology of diabetes. Imeglimin, a novel first-in-class small molecule tetrahydrotriazine drug candidate, improves glycemia and GSIS in preclinical models and clinical trials in patients with Type 2 diabetes; however, the mechanism by which it restores β-cell function is unknown. Here, we show that imeglimin acutely and directly amplifies GSIS in islets isolated from rodents with Type 2 diabetes via a mode of action that is distinct from other known therapeutic approaches. The underlying mechanism involves increases in the cellular nicotinamide adenine dinucleotide (NAD + ) pool—potentially via the salvage pathway and induction of nicotinamide phosphoribosyltransferase (NAMPT) along with augmentation of glucose-induced ATP levels. Further, additional results suggest that NAD + conversion to a second messenger, cyclic ADP ribose (cADPR), via ADP ribosyl cyclase/cADPR hydrolase (CD38) is required for imeglimin’s effects in islets, thus representing a potential link between increased NAD + and enhanced glucose-induced Ca 2+ mobilization which—in turn—is known to drive insulin granule exocytosis. Collectively, these findings implicate a novel mode of action for imeglimin that explains its ability to effectively restore—β-cell function and provides for a new approach to treat patients suffering from Type 2 diabetes.
Zur Herstellung von glasgekapselten superparamagnetischen Eisenoxidnanopartikeln für die Entfernung von Schwermetallionen aus Industrieabwässern (2003)

Die etablierten Techniken zur Aufarbeitung schwermetallbelasteter Industrieabwässer haben verschiedene Nachteile. Sie haben geringe Selektivitäten, produzieren große Mengen von Schlämmen oder sind nur schwer im Sinne eines Recyclings in den Produktionsprozeß integrierbar. Außerdem versagen sie oft bei geringen Schwermetallkonzentrationen. Durch die Kombination von gekapselten superparamagnetischen Eisenoxidpartikeln mit einer Oberflächenmodifikation durch Komplexbildner sollte ein Partikelsystem zur Abtrennung von Schwermetallionen aus wässrigen Systemen entwickelt werden. Diese Partikel sollten Metallionen komplexieren und anschließend magnetisch abgetrennt werden. Nach einer Aufarbeitung sollten die Partikel resuspendiert und wiederverwendet werden. Aus Gründen der chemischen Stabilität ebenso wie einer leichteren magnetischen Abtrennung und eines verbesserten Handlings war dazu die Entwicklung eines glasgekapselten Kompositpartikelsystems nötig.
Biodegradable Blends of Cellulose Acetate and Starch: Production and Properties (1995)

Abstract Blends of cellulose acetate (2.5 degree of substitution) and starch were melt processed and evaluated for mechanical properties, biodegradability during composting, and marine and soil toxicity. Formulations containing, on a weight basis, 57% cellulose acetate (CA), 25% corn starch (St) and 19% propylene glycol (PG) had mechanical properties similar to polystyrene. Increasing plasticizer or starch content lowered tensile strength. Simulated municipal composting of cellulose acetate alone showed losses of 2−3 and 90% dry weight after 30 and 90 days, respectively. CA/St/PG blends in both soil burial and composting experiments indicate that propylene glycol and starch are degraded first. Extended incubations are required to detect losses from cellulose acetate. Marine toxicity tests using polychaete worms and mussels showed no toxicity of cellulose acetate or starch. High doses had an adverse effect due to oxygen depletion in the marine water due to rapid biodegradation of the polymers. Preliminary plant toxicity tests of the CA/St blends showed no negative impact on growth and yield for sweet corn, butternut squash, and plum tomatoes. The results indicate that CA/St blends have acceptable properties for injection-molded applications and are biodegradable and nontoxic.