gebhart/patrepeval huggingface dataset:
Biodegradability of Disulfide-Organosilica Nanoparticles Evaluated by Soft X-ray Photoelectron Spectroscopy: Cancer Therapy Implications (2018)

Two kinds of organosilica nanoparticles (NPs) that were fabricated from thiol-containing precursors, (3-mercaptopropyl)trimethoxysilane (MPMS) and (3-mercaptopropyl)methyldimethoxysilane (MPDMS), are potential delivery vehicles of anticancer drugs. MPMS can form three siloxane bonds, but MPDMS forms two siloxane bonds as the maximum limit. Hence, disulfide bonds can be involved in the three-dimensional morphology of MPDMS NPs. In addition, NPs containing disulfide bonds are potentially degraded by a reduced form of glutathione (GSH). To examine reactions between the organosilica NPs and GSH, the NPs were incubated in 10 mM GSH aqueous solution at 37 °C for 7 d and the products were analyzed using field-emission scanning electron microscopy (FE-SEM), Raman spectroscopy, and soft X-ray photoelectron spectroscopy (XPS). The Raman spectra showed the presence of disulfide bonds in the MPDMS NPs and the absence of disulfide bonds in MPMS NPs. The results of XPS measurements suggested that the disulfide bonds in the outer layer of MPDMS NPs were reduced to thiol groups. FE-SEM observations of MPDMS NPs detected changes in NP morphology after the GSH incubation. These results support the idea that MPDMS NPs contain disulfide bonds and are degradable by GSH. Therefore, MPDMS NPs possess a biodegradable feature that is advantageous for clinical translation, that is, nanomedicine.
Epidemiologic and Clinical Characteristics of Optic Neuritis in Japan (2019)

The present large-scale cohort study revealed the clinicoepidemiologic features of noninfectious optic neuritis in Japan. Anti-aquaporin-4 antibody-positive optic neuritis has poor visual outcome. In contrast, MOG-Ab positive cases manifested severe clinical findings of optic neuritis before treatment, but few showed concurrent lesions in sites other than the optic nerve and generally showed good treatment response with favorable visual outcome. These findings indicate that autoantibody measurement is useful for prompt diagnosis and proper management of optic neuritis that tends to become refractory.
Self-similarity in the web (2002)

Algorithmic tools for searching and mining the Web are becoming increasingly sophisticated and vital. In this context, algorithms that use and exploit structural information about the Web perform better than generic methods in both efficiency and reliability.We present an extensive characterization of the graph structure of the Web, with a view to enabling high-performance applications that make use of this structure. In particular, we show that the Web emerges as the outcome of a number of essentially independent stochastic processes that evolve at various scales. A striking consequence of this scale invariance is that the structure of the Web is "fractal"---cohesive subregions display the same characteristics as the Web at large. An understanding of this underlying fractal nature is therefore applicable to designing data services across multiple domains and scales.We describe potential applications of this line of research to optimized algorithm design for Web-scale data analysis.
Boom chameleon (2002)

We introduce the Boom Chameleon, a novel input/output device consisting of a flat-panel display mounted on a tracked mechanical boom. The display acts as a physical window into 3D virtual environments, through which a one-to-one mapping between real and virtual space is preserved. The Boom Chameleon is further augmented with a touch-screen and a microphone/speaker combination. We present a 3D annotation application that exploits this unique configuration in order to simultaneously capture viewpoint, voice and gesture information. Design issues are discussed and results of an informal user study on the device and annotation software are presented. The results show that the Boom Chameleon annotation facilities have the potential to be an effective, easy to learn and operate 3D design review system.
Transformation of Brucella Species with Suicide and Broad Host-Range Plasmids (2003)

The six species that make up the genus Brucella infect a wide variety of animals and humans (1). This bacterial species is gram-negative and classified as a facultative intracellular pathogen (reviewed in ref. 2). In the livestock industry of the United States and numerous countries throughout the world, the major economic impact of Brucella is its ability to induce abortions in cattle (3). B. abortus is able to infect and replicate within macrophages (4–6), trophoblasts (7–9), and a variety of other cells (10–12). It is not clearly understood how virulent strains of B. abortus survive in the bovine host for extended periods of time in the face of a detectable cell-mediated immunity (3). In order to determine the genetic basis of the virulence of Brucella, i.e., to replicate and live inside professional and nonprofessional phagocytic cells, it is necessary to identify virulence genes as well as characterize these genes by complementation and mutational studies. Thus, the ability to transform Brucella with suicide plasmids (to introduce transposons or cause allelic exchanges) or replicating plasmids (to perform complementation studies) is paramount in implementing molecular approaches to unravel the genetic basis for Brucella virulence determinants.
Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians (2011)

FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.
Fiber spinning and rheology of liquid-crystalline polymers (1994)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1994.
Optical Pumping of Molecules (1969)

A technique is described for the optical pumping of gas-phase molecules based on the orientation dependence of their absorption cross section. It is shown that when the rate of excitation exceeds the relaxation rate of a ground-state (υ″, J″) level, the magnetic sublevels are preferentially “burned away” and the steady-state M-level population is altered appreciably. An experiment to demonstrate molecular alignment has proved successful using the 4880-Å line of a cw argon-ion laser to cause the transition (υ″ = 3, J″ = 43)→(υ′ = 6, J′ = 43) in the B 1Σu − X 1Σg+ blue-green band system of the Na2 molecule. The establishment of an unequal magnetic sublevel population is detected by monitoring the degree of polarization P of the fluorescence as a function of laser intensity. It is found that P first remains constant then decreases by about 50% as the laser-beam power increases from 0.1 to 150 mW. In addition, the absorption becomes nonlinear with a power threshold corresponding to the onset of the decrease in P. This optical pumping technique is applicable to a wide class of molecules, and both simple classical and quantum mechanical theories of the pumping process have been formulated. These theories relate the degree of polarization to both the pumping rate and the relaxation time of the pumped level. The time-dependent as well as steady-state behavior of P is examined. Under conditions of strong optical pumping it is predicted that the degree of polarization as a function of time will overshoot its steady-state value, and as the pumping rate increases large negative transients in P will appear.
Design Rules for Template-Confined DNA-Mediated Nanoparticle Assembly* (2020)

Template-based strategies are becoming increasingly important for controlling the position of nanoparticle-based (NP-based) structures on surfaces for a wide variety of encoding and device fabrication strategies. Thus, there is an increasing need to understand the behavior of NPs in confined spaces. Herein, a systematic investigation of the diffusion and adsorption properties of DNA-modified NPs is presented in lithographically defined, high-aspect-ratio pores using a template-confined, DNA-mediated assembly. Leveraging 1210the sequence-specific binding affinity of DNA, it is discovered that although NP adsorption in deep polymer pores follows a traditional Langmuir adsorption model when under thermodynamic control, such NPs kinetically follow Fick’s classical law of diffusion. Importantly, these observations allow one to establish design rules for template-confined, DNA-mediated NP assembly on substrates based on pore dimensions, NP size and shape, NP concentration, temperature, and time. As a proof-of-concept example, these design rules are used to engineer a vertical, four-layer assembly consisting of individual octahedral NPs stacked on top of one another, with in-plane positioning defined by pores generated by e-beam lithography.
Fabrication of Optically Active Er3+-Doped Bi2O3–SiO2 Glass Thin Films by Pulsed Laser Deposition (2006)

We examined the fabrication conditions of optically active Er 3+ -doped Bi 2 O 3 –SiO 2 glass thin films prepared by pulsed laser deposition using a glass target with a nominal composition (mol %) of 41Bi 2 O 3 ·57SiO 2 ·2Er 2 O 3 . The transparent glass films were obtained at 200 °C under 5 ×10 -2 Torr O 2 . The glass films were found to possess a composition and a refractive index close to those of the bulk glass used as the target. The films exhibited a broad emission of Er 3+ ions at around 1.5–1.6 µm as well as Er 3+ upconversion-pumped fluorescence in the 500–700 nm range.
Abstract 2771: KSQ-4279 mediated USP1 inhibition induces replication associated DNA gaps that contribute to cell death (2023)

Abstract Tumors with defects in DNA double strand break (DSB) repair pathways, including those with mutations in BRCA1/2, are often treated with either poly (ADP-ribose) polymerase-1 (PARP1) inhibitors or platinum-based chemotherapy. Despite their clinical benefits, many patients develop resistance leading to the need for novel therapeutic approaches. To address this unmet clinical need, we applied our CRISPRomics® platform to identify novel therapeutic targets for DNA damage and repair deficient cancers. One of the top ranked targets was the deubiquitinating enzyme, USP1, with known functions in DNA damage repair pathways of translesion synthesis (TLS) and fanconi anemia (FA). We developed a novel small molecule inhibitor, KSQ-4279, that selectively inhibits USP1 and leads to accumulation of mono-ubiquitinated USP1 substrates such as proliferating nuclear antigen (PCNA). In addition to KSQ-4279’s activity in BRCA mutant tumors with known homologous recombination deficiencies (HRD), KSQ-4279 also exhibits synergistic activity in combination with PARP inhibitors and re-sensitizes PARP refractory tumors. Mechanistically, we show that in sensitive cell lines, treatment with KSQ-4279 alters the replication fork dynamics resulting in replication stress via induction of replication associated single stranded DNA gaps and subsequent fork degradation. Additionally, KSQ-4279 leads to loss of the essential DNA replication and repair protein, PCNA, which can be rescued by blocking PCNA ubiquitination either through Rad18 knockout or by ectopic expression of a PCNA K164R mutant. This loss of PCNA and sensitizing ssDNA lesions eventually lead to DNA double strand breaks (DSBs) and wide-spread DNA damage accumulation that contributes to cell death. This mechanistic insight supports the ongoing clinical trial of KSQ-4279 in patients with tumors harboring BRCA1/2 or other HRD mutations, both as a single agent and in combination with PARP inhibitors. Citation Format: Sumeet Nayak, Pamela Sullivan, Yuji Mishina, Anne Dodson, Pei-Lun Kao, Hugh Gannon, Chris Middleton, Sol Shenker, Morgan Murray, Michael Schlabach, Frank Stegmeier, Erica Tobin, Louise Cadzow, Andrew Wylie. KSQ-4279 mediated USP1 inhibition induces replication associated DNA gaps that contribute to cell death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2771.
Dynamic stress-strain behavior of filled natural rubber under combined axial and shear straining (2017)

As success is achieved in modeling individual aspects of rubber's stress strain response such as nonlinear elasticity, the Mullins effect, the Fletcher/Gent/Payne effect, and viscoelasticity, it is becoming possible to contemplate increasingly realistic models that simultaneously embody many aspects. This chapter presents the results of an experiment involving combined axial and shear cyclic straining. A typical material element of the test specimen is shown in the original and deformed states. The deformation history applied to the specimen features events that probe a number of different aspects of rubber's behavior. The first two events involve purely axial loading, first in the compressive direction, then in the tensile. The stress and strain states on the mid-plane can be inferred for the specimen from measurements of the applied force, torque, axial displacement, and twist, via relatively simple calculations. The values of the apparent stiffness and loss factor depend strongly on mean deformation.
Neck Displacements of Volunteers, BioRID P3 and Hybrid III in Rear Impacts: Implications to Whiplash Assessment by a Neck Displacement Criterion (NDC) (2002)

Kinematics of the neck are important biomechanical responses to whiplash in rear impacts. This study evaluates neck displacements of 10 volunteers, BioRID P3 and Hybrid III from JARI sled tests at 8.6 km/h with a standard seat and 9.3 km/h with a rigid seat. Film analysis determined the rotation, and x- and z-displacement of the occipital condyles (OC) with respect to T1. For the volunteers, average and standard deviations were determined and cross-plotted as OC rotation versus x-displacement, and z-versus x-displacement of OC-T1. These responses provide corridors for the natural range of neck motion in rear impacts. For these parameters, BioRID P3 and Hybrid III closely simulate the volunteer neck kinematics. Tests of the Saab SAHR and standard head restraints showed differences in neck displacements that are consistent with field whiplash rates. A Neck Displacement Criterion (NDC) has been proposed to assess whiplash risks. By using the BioRID P3 and Hybrid III responses in sled tests and knowing the field whiplash rates for the Saab SAHR and standard head restraints, initial working targets for NDC are proposed for consideration.
Class B Scavenger Receptor Types I and II and CD36 Mediate Bacterial Recognition and Proinflammatory Signaling Induced by Escherichia coli, Lipopolysaccharide, and Cytosolic Chaperonin 60 (2011)

Class B scavenger receptors (SR-B) are lipoprotein receptors that also mediate pathogen recognition, phagocytosis, and clearance as well as pathogen-induced signaling. In this study we report that three members of the SR-B family, namely, CLA-1, CLA-2, and CD36, mediate recognition of bacteria not only through interaction with cell wall LPS but also with cytosolic chaperonin 60. HeLa cells stably transfected with any of these SR-Bs demonstrated markedly (3- to 5-fold) increased binding and endocytosis of Escherichia coli, LPS, and chaperonin 60 (GroEL) as revealed by both FACS analysis and confocal microscopy imaging. Increased pathogen (E. coli, LPS, and GroEL) binding to SR-Bs was also associated with the dose-dependent stimulation of cytokine secretion in the order of CD36 > CLA-2 > CLA-1 in HEK293 cells. Pathogen-induced IL-6-secretion was reduced in macrophages from CD36- and SR-BI/II-null mice by 40-50 and 30-40%, respectively. Intravenous GroEL administration increased plasma IL-6 and CXCL1 levels in mice. The cytokine responses were 40-60% lower in CD36(-/-) relative to wild-type mice, whereas increased cytokine responses were found in SR-BI/II(-/-) mice. While investigating the discrepancy of in vitro versus in vivo data in SR-BI/II deficiency, SR-BI/II(-/-) mice were found to respond to GroEL administration without increases in either plasma corticosterone or aldosterone as normally seen in wild-type mice. SR-BI/II(-/-) mice with mineralocorticoid replacement demonstrated an ∼40-50% reduction in CXCL1 and IL-6 responses. These results demonstrate that, by recognizing and mediating inflammatory signaling of both bacterial cell wall LPS and cytosolic GroEL, all three SR-B family members play important roles in innate immunity and host defense.
Temperature Dependence of Charge and Spin Transfer in Azurin (2021)

The steady-state charge and spin transfer yields were measured for three different Ru-modified azurin derivatives in protein films on silver electrodes. While the charge-transfer yields exhibit weak temperature dependences, consistent with operation of a near activation-less mechanism, the spin selectivity of the electron transfer improves as temperature increases. This enhancement of spin selectivity with temperature is explained by a vibrationally induced spin exchange interaction between the Cu(II) and its chiral ligands. These results indicate that distinct mechanisms control charge and spin transfer within proteins. As with electron charge transfer, proteins deliver polarized electron spins with a yield that depends on the protein's structure. This finding suggests a new role for protein structure in biochemical redox processes.
Redox-dependent Igfbp2 signaling controls Brca1 DNA damage response to govern neural stem cell fate (2023)

Neural stem cell (NSC) maintenance and functions are regulated by reactive oxygen species (ROS). However, the mechanisms by which ROS control NSC behavior remain unclear. Here we report that ROS-dependent Igfbp2 signaling controls DNA repair pathways which balance NSC self-renewal and lineage commitment. Ncf1 or Igfbp2 deficiency constrains NSCs to a self-renewing state and prevents neurosphere formation. Ncf1-dependent oxidation of Igfbp2 promotes neurogenesis by NSCs in vitro and in vivo while repressing Brca1 DNA damage response genes and inducing DNA double-strand breaks (DDSBs). By contrast, Ncf1<sup>-/-</sup> and Igfbp2<sup>-/-</sup> NSCs favor the formation of oligodendrocytes in vitro and in vivo. Notably, transient repression of Brca1 DNA repair pathway genes induces DDSBs and is sufficient to rescue the ability of Ncf1<sup>-/-</sup> and Igfbp2<sup>-/-</sup> NSCs to lineage-commit to form neurospheres and neurons. NSC lineage commitment is dependent on the oxidizable cysteine-43 residue of Igfbp2. Our study highlights the role of DNA damage/repair in orchestrating NSC fate decisions downstream of redox-regulated Igfbp2.
Benign Fasciculation Syndrome (2015)

Questions from patients about pain conditions, analgesic pharmacotherapy, and responses from authors are presented to help educate patients and make them more effective self-advocates. In reply to a question about benign fasciculation syndrome, the presentation, causes, treatment, and chances of developing amyotrophic lateral sclerosis will be discussed.
Figure S5 from Computational Staining of Pathology Images to Study the Tumor Microenvironment in Lung Cancer (2023)

&lt;p&gt;Supplemental Figure S5 Validation of lymphocyte detection results in whole-slide image nuclei segmentation and classification by HD-Staining model.&lt;/p&gt;
On the influence of non-individual binaural cues and the impact of level normalization on auditory distance estimation of nearby sound sources (2021)

Nearby sound sources provide distinct binaural cues, mainly in the form of interaural level differences, which vary with respect to distance and azimuth. However, there is a long-standing controversy regarding whether humans can actually utilize binaural cues for distance estimation of nearby sources. Therefore, we conducted three experiments using non-individual binaural synthesis. In Experiment 1, subjects had to estimate the relative distance of loudness-normalized and non-normalized nearby sources in static and dynamic binaural rendering in a multi-stimulus comparison task under anechoic conditions. Loudness normalization was used as a plausible method to compensate for noticeable intensity differences between stimuli. With the employed loudness normalization, nominal distance did not significantly affect distance ratings for most conditions despite the presence of non-individual binaural distance cues. In Experiment 2, subjects had to judge the relative distance between loudness-normalized sources in dynamic binaural rendering in a forced-choice task. Below chance performance in this more sensitive task revealed that the employed loudness normalization strongly affected distance estimation. As this finding indicated a general issue with loudness normalization for studies on relative distance estimation, Experiment 3 directly tested the validity of loudness normalization and a frequently used amplitude normalization. Results showed that both normalization methods lead to remaining (incorrect) intensity cues, which subjects most likely used for relative distance estimation. The experiments revealed that both examined normalization methods have consequential drawbacks. These drawbacks might in parts explain conflicting findings regarding the effectiveness of binaural cues for relative distance estimation in the literature.
Proctorship and mentoring: Its backbone and application in robotic surgery (2016)

In pursuit of continuing medical education in robotic surgery, several forms of training have been implemented. This variable application of curriculum has brought acquisition of skills in a heterogeneous and unstandardized fashion from different parts of the world. Recently, efforts have been made to provide cost effective and well-structured curricula with the aim of bridging the gap between formal fellowship training and short courses. Proctorship training has been implicated on some curriculum to provide excellent progression during the learning curve while ensuring patient safety.
Serverless Programming with Swift (2017)

This chapter covers how the Swift language is used in one of these cloud environments, namely event-driven, or server-less, environments. There are many other advantages to using microservices. Because the ideally designed microservice is small and focused in function, it is easier for developers to understand and troubleshoot. Inter-module communication can be more challenging, or at least require more careful consideration, in a microservices application. Monolithic applications can rely on fast in-process method invocations between modules, and they frequently evolve into rather “chatty- implementations. The key thing about serverless computing that makes it attractive to developers is that they can concentrate solely on application business logic development and avoid spending any time whatsoever dealing with infrastructure or application environment provisioning or deployment. OpenWhisk is an open source project that provides a distributed compute service to execute application logic in response to events. It delivers an event-driven platform within which one can execute code in response to the occurrence of some event.