gebhart/patrepeval huggingface dataset:
Microfluidic solvent extraction of poly(vinyl alcohol) droplets: effect of polymer structure on particle and capsule formation (2018)

We investigate the formation of poly(vinyl alcohol) microparticles by the selective extraction of aqueous polymer solution droplets, templated by microfluidics and subsequently immersed in a non-solvent bath. The role of polymer molecular mass (18-105 kg mol-1), degree of hydrolysis (88-99%) and thus solubility, and initial solution concentration (0.01-10% w/w) are quantified. Monodisperse droplets with radii ranging from 50 to 500 μm were produced at a flow-focusing junction with carrier phase hexadecane and extracted into ethyl acetate. Solvent exchange and extraction result in droplet shrinkage, demixing, coarsening and phase-inversion, yielding polymer microparticles with well-defined dimensions and internal microstructure. Polymer concentration, varied from below the overlap concentration c* to above the concentrated crossover c**, as estimated by viscosity measurements, was found to have the largest impact on the final particle size and extraction timescale, while polymer mass and hydrolysis played a secondary role. These results are consistent with the observation that the average polymer concentration upon solidification greatly exceeds c**, and that the internal microparticle porosity is largely unchanged. However, reducing the initial polymer concentration to well below c* (approximately 100×) and increasing droplet size yields thin-walled (100's of nm) capsules which controllably crumple upon extraction. The symmetry of the process can be readily broken by imposing extraction conditions at an impermeable surface, yielding large, buckled, cavity morphologies. Based on these results, we establish robust design criteria for polymer capsules and particles, demonstrated here for poly(vinyl alcohol), with well-defined shape, dimensions and internal microstructure.
Dynamic band unblocking and leakage two-photon absorption in InSb (1997)

An experimental demonstration of a dynamic decrease of the optical band gap of bulk $n$-InSb induced by picosecond, midinfrared laser pulses is reported. This occurs as a result of laser heating of the quiescent electron distribution by free-carrier absorption. The hot electrons vacate low-energy states near the conduction-band minimum, unblocking terminal states for two-photon absorption across the band gap. This ``leakage'' two-photon absorption is detected as a consequence of changes to the refractive index and absorption coefficient of the semiconductor caused by photocarriers. The onset of dynamic band unblocking agrees with a calculation of laser-induced electron heating.
Digoxigenin-Labeled Probes Amplified from Genomic DNA Detect T-Cell Gene Rearrangements (1992)

The detection of clonal rearrangements of the human T-cell receptor by Southern hybridization is a useful tool to diagnose morphologically difficult lymphoid proliferations. Widespread application of this method has been facilitated by the advent of sensitive nonradiolabeled probes. Although a limited number of nonradiolabeled DNA probes are commercially available, other probes must be obtained through a time-consuming and technically difficult procedure of amplification, isolation, and labeling of plasmid-cloned DNA sequences. A simple and time-saving procedure to simultaneously amplify and nonradioactively label DNA probes for use in gene rearrangement studies is described. Specifically, a method using the polymerase chain reaction to amplify and label with digoxigenin large quantities of probe to the constant region of the T-cell receptor directly from genomic DNA is described. The resultant probes are specific for the T-cell receptor-constant region, detect the appropriate germline configuration in placental DNA, and identify rearranged clonal T-cell proliferations. The polymerase chain reaction digoxigenin-labeled probes are suitable for detection by conventional colorimetric methods or by chemiluminescent detection schemes.
Supplementary Figure 1 from Combining a PI3K Inhibitor with a PARP Inhibitor Provides an Effective Therapy for BRCA1-Related Breast Cancer (2023)

&lt;p&gt;PDF file - 319K, Target inhibition after treatments with NVP-BKM120 in vivo. Tumor-bearing MMTV-CreBRCA1f/fp53+/- mice were biopsied before treatment, and tumor tissues harvested within 3 hours after the last treatment. Tissues were fixed and processed for immunohistochemistry with anti-phospho AKT (S473) antibodies. 400 x magnification&lt;/p&gt;
Defining the role of ICOS and CD28 costimulation in TH17 cell activation, differentiation and tumor immunity (46.29) (2012)

Abstract TH17 cells play an essential role in regulating host defense and exacerbating various autoimmune diseases, but their role in tumor immunity remains incompletely elucidated. We found that CD28 abrogates TH17 expansion and function, while the inducible costimulator (ICOS) augments the generation of polyfunctional TH17 cells. Of clinical importance, ICOS-expanded TH17 cells were superior at killing human tumors compared to cells expanded with CD28. Our objective is to identify how ICOS regulates the differentiation and optimal expansion of TH17 cells that mediate tumor regression. We have polarized human CD4+ T cells towards TH17 with beads expressing anti-CD3 and CD28 and/or ICOS agonists. ICOS costimulation promotes the long-term generation of TH17 cells, determined by CD161 and CCR6 expression and IL-17A production. By sorting peripheral blood cells based on these two receptors, we identified a subset of cells that nearly all produce IL-17 when stimulated with an ICOS agonist. This innovative approach allows us to study the basic biology of IL-17-producing cells and affords us the ease of exclusively enriching them for adoptive immunotherapy for cancer. We are now uncovering new transcription factors uniquely regulated by ICOS that distinctly impact TH17 cells’ phenotype and functional fate. Understanding how ICOS signaling and optimal culture conditions promote TH17 cell function will be instrumental in advancing T cell-based therapies for cancer and infectious diseases.
1-Semibullvalenylcarbinyl cation (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT1-Semibullvalenylcarbinyl cationGary H. Birnberg and Leo A. PaquetteCite this: J. Org. Chem. 1980, 45, 26, 5379–5381Publication Date (Print):December 1, 1980Publication History Published online1 May 2002Published inissue 1 December 1980https://doi.org/10.1021/jo01314a038Request reuse permissionsArticle Views29Altmetric-Citations2LEARN 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 InReddit PDF (368 KB) Get e-Alertsclose Get e-Alerts
Impact of enhanced metabolic stability on pharmacokinetics and pharmacodynamics of GalNAc–siRNA conjugates (2017)

Covalent attachment of a synthetic triantennary N-acetylagalactosamine (GalNAc) ligand to chemically modified siRNA has enabled asialoglycoprotein (ASGPR)-mediated targeted delivery of therapeutically active siRNAs to hepatocytes in vivo. This approach has become transformative for the delivery of RNAi therapeutics as well as other classes of investigational oligonucleotide therapeutics to the liver. For efficient functional delivery of intact drug into the desired subcellular compartment, however, it is critical that the nucleic acids are stabilized against nucleolytic degradation. Here, we compared two siRNAs of the same sequence but with different modification pattern resulting in different degrees of protection against nuclease activity. In vitro stability studies in different biological matrices show that 5'-exonuclease is the most prevalent nuclease activity in endo-lysosomal compartments and that additional stabilization in the 5'-regions of both siRNA strands significantly enhances the overall metabolic stability of GalNAc-siRNA conjugates. In good agreement with in vitro findings, the enhanced stability translated into substantially improved liver exposure, gene silencing efficacy and duration of effect in mice. Follow-up studies with a second set of conjugates targeting a different transcript confirmed the previous results, provided additional insights into kinetics of RISC loading and demonstrated excellent translation to non-human primates.
Effects of deoxyadenosine on the activation of ADA inhibited T & B cells. (1982)

Using an in vitro model of adenosine deaminase deficiency, we have shown that the triggering of T lymphocyte proliferation by PHA is inhibited by concentrations of deoxyadenosine likely to occur in the plasma of ADA deficient children with severe combined immunodeficiency (ADA-SCID). Prostaglandin E1 increases the sensitivity of T cells to this inhibition, suggesting that derangement of cyclic nucleotide metabolism underlies the profound T lymphopaenia seen in ADA-SCID and in patients treated with the ADA inhibitor, deoxycoformycin. The proliferation and Ig synthesis of ADA inhibited B cells stimulated with protein A and EBV is in general less sensitive to the inhibitory effects of deoxyadenosine. However, this sensitivity varies widely between experiments suggesting that other cells present in the cultures may modify the inhibitory effect of deoxyadenosine. This may help explain the variability in B cell numbers and function in patients with ADA-SCID.
Supplementary Data from Efficacy and Determinants of Response to HER Kinase Inhibition in <i>HER2</i>-Mutant Metastatic Breast Cancer (2023)

&lt;p&gt;Supplementary data&lt;/p&gt;
Picosecond ultrasonic study of localized phonon surface modes in Al/Ag superlattices (1994)

We present the results of picosecond ultrasonic studies of localized acoustic-phonon surface modes in Al/Ag superlattices. By making measurements on a series of superlattices with different periods, we have been able to study surface modes with frequencies in the range from 110 to 670 GHz. The experiment reveals interesting variations in the surface-mode structure as the geometry of the cap layers is varied. We compare these results with the predictions of a transfer-matrix theory of the localized modes. The measured damping rate of the modes varies linearly with frequency and is nearly independent of temperature in the temperature range from 70 to 300 K. This variation of the attenuation with frequency and the order of magnitude of the attenuation are consistent with the assumption that the attenuation rises from an interaction between the phonon mode and the electrons, but the damping rate is about a factor of 5 larger than expected based upon Pippard's theory for bulk materials. It is likely that the enhancement in the damping rate is primarily due to losses occurring at the free surface of the structure.
Whole Exome Sequencing of HIV-1 long-term non-progressors identifies rare variants in genes encoding innate immune sensors and signaling molecules (2018)

Common CCR5-∆32 and HLA alleles only explain a minority of the HIV long-term non-progressor (LTNP) and elite controller (EC) phenotypes. To identify rare genetic variants contributing to the slow disease progression phenotypes, we performed whole exome sequencing (WES) on seven LTNPs and four ECs. HLA and CCR5 allele status, total HIV DNA reservoir size, as well as variant-related functional differences between the ECs, LTNPs, and eleven age- and gender-matched HIV-infected non-controllers on antiretroviral therapy (NCARTs) were investigated. Several rare variants were identified in genes involved in innate immune sensing, CD4-dependent infectivity, HIV trafficking, and HIV transcription mainly within the LTNP group. ECs and LTNPs had a significantly lower HIV reservoir compared to NCARTs. Furthermore, three LTNPs with variants affecting HIV nuclear import showed integrated HIV DNA levels below detection limit after in vitro infection. HIV slow progressors with variants in the TLR and NOD2 pathways showed reduced pro-inflammatory responses compared to matched controls. Low-range plasma levels of fibronectin was observed in a LTNP harboring two FN1 variants. Taken together, this study identified rare variants in LTNPs as well as in one EC, which may contribute to understanding of HIV pathogenesis and these slow progressor phenotypes, especially in individuals without protecting CCR5-∆32 and HLA alleles.
Understanding Relationships between Free Volume and Oxygen Absorption in Ionic Liquids (2022)

Understanding the factors that govern gas absorption in ionic liquids is critical to the development of high-capacity solvents for catalysis, electrochemistry, and gas separations. Here, we report experimental probes of liquid structure that provide insights into how free volume impacts the O<sub>2</sub> absorption properties of ionic liquids. Specifically, we establish that isothermal compressibility─measured rapidly and accurately through small-angle X-ray scattering─reports on the size distribution of transient voids within a representative series of ionic liquids and is correlated with O<sub>2</sub> absorption capacity. Additionally, O<sub>2</sub> absorption capacities are correlated with thermal expansion coefficients, reflecting the beneficial effect of weak intermolecular interactions in ionic liquids on free volume and gas absorption capacity. Molecular dynamics simulations show that the void size distribution─in particular, the probability of forming larger voids within an ionic liquid─has a greater impact on O<sub>2</sub> absorption than the total free volume. These results establish relationships between the ionic liquid structure and gas absorption properties that offer design strategies for ionic liquids with high gas solubilities.
Cortical indices of sound localization mature monotonically in early infancy (2014)

In human neonates, orienting behavior in response to an off-midline sound source disappears around the first postnatal month, only to re-emerge at ~4 months. To date, it is unclear whether sound localization processes continue to operate between postnatal months 1 and 3. Here, we used an event-related potential, reflecting change detection in the auditory cortices, to measure the cortical responses elicited by large (± 90° relative to midline), infrequent changes in sound source location in 2-, 5-, 8- and 13-month-old infants. Both fast-negative mismatch negativity (MMN) Näätänen et al. (2007) and slow-positive mismatch response (MMR) Trainor et al. (2003) were elicited from all age groups. However, both components were smaller and the fast-negative component occurred later in the 2-month-old group than in older age groups. Additionally, the slow-positive component tended to diminish in amplitude with increasing age, whereas the fast-negative component grew larger and tended to occur earlier with increasing age. These results suggest that the cortical representation of sound location matures similarly to representations of pitch and duration. A subsequent investigation of 2-month-old infants confirmed that the observed MMR and MMN were elicited by changes in sound source location, and were not merely attributable to changes in loudness cues. The presence of both MMR and MMN in the 2-month-old group indicates that the cortex is able to detect changes in sound location despite the behavioral insensitivity observed around 1-3 months of age.
Are We There Yet? The Value of Deep Learning in a Multicenter Setting for Response Prediction of Locally Advanced Rectal Cancer to Neoadjuvant Chemoradiotherapy (2022)

This retrospective study aims to evaluate the generalizability of a promising state-of-the-art multitask deep learning (DL) model for predicting the response of locally advanced rectal cancer (LARC) to neoadjuvant chemoradiotherapy (nCRT) using a multicenter dataset. To this end, we retrained and validated a Siamese network with two U-Nets joined at multiple layers using pre- and post-therapeutic T2-weighted (T2w), diffusion-weighted (DW) images and apparent diffusion coefficient (ADC) maps of 83 LARC patients acquired under study conditions at four different medical centers. To assess the predictive performance of the model, the trained network was then applied to an external clinical routine dataset of 46 LARC patients imaged without study conditions. The training and test datasets differed significantly in terms of their composition, e.g., T-/N-staging, the time interval between initial staging/nCRT/re-staging and surgery, as well as with respect to acquisition parameters, such as resolution, echo/repetition time, flip angle and field strength. We found that even after dedicated data pre-processing, the predictive performance dropped significantly in this multicenter setting compared to a previously published single- or two-center setting. Testing the network on the external clinical routine dataset yielded an area under the receiver operating characteristic curve of 0.54 (95% confidence interval [CI]: 0.41, 0.65), when using only pre- and post-therapeutic T2w images as input, and 0.60 (95% CI: 0.48, 0.71), when using the combination of pre- and post-therapeutic T2w, DW images, and ADC maps as input. Our study highlights the importance of data quality and harmonization in clinical trials using machine learning. Only in a joint, cross-center effort, involving a multidisciplinary team can we generate large enough curated and annotated datasets and develop the necessary pre-processing pipelines for data harmonization to successfully apply DL models clinically.
An Approach to the Synthesis of the Manzamine Alkaloids Via the Vinylogous Amide PHotocycloAddition/Retro‐Mannich Fragmentation/Mannich Closure Cascade (pharM) (1997)

Abstract The application of the vinylogous amide [2+2] photocycloaddition/retro‐Mannich fragmentation/ M annich closure cascade ( pharM ) to the synthesis of the pentacyclic ring system of the anti‐leukemic marine alkaloid manzamine A is presented. Two approaches to the synthesis of the requisite pentacycle are described: (a) the transannular photocycloaddition of an 18‐membered vinylogous amide; and (b) photocycloaddition of an acyclic vinylogous amide, followed by macrolactamization of the derived pharM closure product to generate the pentacyclic ring system.
Relationships of quantitative ultrasound parameters with cancellous bone microstructure in human calcaneus in vitro (2012)

Ultrasound parameters (attenuation, phase velocity, and backscatter), bone mineral density (BMD), and microarchitectural features were measured on 29 human cancellous calcaneus samples in vitro. Regression analysis was performed to predict ultrasound parameters from BMD and microarchitectural features. The best univariate predictors of the ultrasound parameters were the indexes of bone quantity: BMD and bone volume fraction (BV/TV). The most predictive univariate models for attenuation, phase velocity, and backscatter coefficient yielded adjusted squared correlation coefficients of 0.69-0.73. Multiple regression models yielded adjusted correlation coefficients of 0.74-0.83. Therefore attenuation, phase velocity, and backscatter are primarily determined by bone quantity, but multiple regression models based on bone quantity plus microarchitectural features achieve slightly better predictive performance than models based on bone quantity alone.
Dynamic manipulation (2002)

Dynamic manipulation is defined, and a brief survey of dynamic operations is given. The design, control, and planning of dynamic manipulation is addressed. An example of dynamic manipulation, club-throwing using dynamic closure, is described.
Musashi-2 (MSI2) supports TGF-β signaling and inhibits claudins to promote non-small cell lung cancer (NSCLC) metastasis (2016)

Non-small cell lung cancer (NSCLC) has a 5-y survival rate of ∼16%, with most deaths associated with uncontrolled metastasis. We screened for stem cell identity-related genes preferentially expressed in a panel of cell lines with high versus low metastatic potential, derived from NSCLC tumors of Kras(LA1/+);P53(R172HΔG/+) (KP) mice. The Musashi-2 (MSI2) protein, a regulator of mRNA translation, was consistently elevated in metastasis-competent cell lines. MSI2 was overexpressed in 123 human NSCLC tumor specimens versus normal lung, whereas higher expression was associated with disease progression in an independent set of matched normal/primary tumor/lymph node specimens. Depletion of MSI2 in multiple independent metastatic murine and human NSCLC cell lines reduced invasion and metastatic potential, independent of an effect on proliferation. MSI2 depletion significantly induced expression of proteins associated with epithelial identity, including tight junction proteins [claudin 3 (CLDN3), claudin 5 (CLDN5), and claudin 7 (CLDN7)] and down-regulated direct translational targets associated with epithelial-mesenchymal transition, including the TGF-β receptor 1 (TGFβR1), the small mothers against decapentaplegic homolog 3 (SMAD3), and the zinc finger proteins SNAI1 (SNAIL) and SNAI2 (SLUG). Overexpression of TGFβRI reversed the loss of invasion associated with MSI2 depletion, whereas overexpression of CLDN7 inhibited MSI2-dependent invasion. Unexpectedly, MSI2 depletion reduced E-cadherin expression, reflecting a mixed epithelial-mesenchymal phenotype. Based on this work, we propose that MSI2 provides essential support for TGFβR1/SMAD3 signaling and contributes to invasive adenocarcinoma of the lung and may serve as a predictive biomarker of NSCLC aggressiveness.
Nickel Ferrite Aerogels with Monodisperse Nanoscale Building Blocks—The Importance of Processing Temperature and Atmosphere (2008)

Using two-step (air/argon) thermal processing, sol-gel-derived nickel-iron oxide aerogels are transformed into monodisperse, networked nanocrystalline magnetic oxides of NiFe(2)O(4) with particle diameters that can be ripened with increasing temperature under argon to 4.6, 6.4, and 8.8 nm. Processing in air alone yields poorly crystalline materials; heating in argon alone leads to single phase, but diversiform, polydisperse NiFe(2)O(4), which hampers interpretation of the magnetic properties of the nanoarchitectures. The two-step method yields an improved model system to study magnetic effects as a function of size on the nanoscale while maintaining the particles within the size regime of single domain magnets, as networked building blocks, not agglomerates, and without stabilizing ligands capping the surface.