gebhart/patrepeval huggingface dataset:
Modeling and Synthesis of Breast Cancer Optical Property Signatures With Generative Models (2021)

Is it possible to find deterministic relationships between optical measurements and pathophysiology in an unsupervised manner and based on data alone? Optical property quantification is a rapidly growing biomedical imaging technique for characterizing biological tissues that shows promise in a range of clinical applications, such as intraoperative breast-conserving surgery margin assessment. However, translating tissue optical properties to clinical pathology information is still a cumbersome problem due to, amongst other things, inter- and intrapatient variability, calibration, and ultimately the nonlinear behavior of light in turbid media. These challenges limit the ability of standard statistical methods to generate a simple model of pathology, requiring more advanced algorithms. We present a data-driven, nonlinear model of breast cancer pathology for real-time margin assessment of resected samples using optical properties derived from spatial frequency domain imaging data. A series of deep neural network models are employed to obtain sets of latent embeddings that relate optical data signatures to the underlying tissue pathology in a tractable manner. These self-explanatory models can translate absorption and scattering properties measured from pathology, while also being able to synthesize new data. The method was tested on a total of 70 resected breast tissue samples containing 137 regions of interest, achieving rapid optical property modeling with errors only limited by current semi-empirical models, allowing for mass sample synthesis and providing a systematic understanding of dataset properties, paving the way for deep automated margin assessment algorithms using structured light imaging or, in principle, any other optical imaging technique seeking modeling. Code is available.
A phase I study of the oral mTOR inhibitor ridaforolimus (RIDA) in combination with the IGF-1R antibody dalotozumab (DALO) in patients (pts) with advanced solid tumors. (2010)

3008 Background: RIDA is a non-prodrug rapamycin analog mTOR inhibitor, and DALO is a humanized monoclonal antibody targeting the IGF-1R receptor. In preclinical models, dual mTOR/IGF1-R inhibition results in synergistic antitumor activity and inhibits feedback AKT activation due to TORC1 inhibition by rapamycin analogs. Methods: Pts with advanced cancers who failed standard therapy received RIDA at escalating doses of 10-40 mg/day QD×5/week combined with DALO at 10 mg/kg/week or 7.5 mg/kg every other week. RIDA was administered for one week prior to starting DALO to enable PK/PD assessment with and without DALO. PD parameters were assessed from PBMCs, skin biopsies, and tumor biopsies. Two dose levels were expanded to determine the optimal dose for future study. Results: 62 pts have been enrolled. During dose escalation, only one pt experienced a DLT (prolonged G2 stomatitis at dose level 1). RIDA 40 mg plus DALO 10 mg/kg/week (recommended doses for RIDA and DALO as single agents) was declared MTD. In an expansion cohort at the declared MTD, 4 DLTs were observed in 9 DLT-evaluable patients (G3 stomatitis, 3 pts; G3 fatigue, 1 pt) and cumulatively 4 of 15 (27%) pts at the declared MTD had DLTs. A 2nd expansion cohort at the next lower dose level (RIDA 30 mg plus DALO 10 mg/kg/week) is being evaluated, and there was 1 DLT in 17 DLT-evaluable pts so far. The most frequent treatment-related adverse events included stomatitis, fatigue, and hyperglycemia, mostly grade 1-2. Efficacy signals included 3 confirmed PRs (2 breast cancer [BCa], 1 parotid adenocarcinoma), 2 partial metabolic responses (PMRs) on FDG-PET scan (2 BCa), 2 prolonged SD > 6 months (1 BCa and 1 endometrial ca), and 3 pts with ≥50% decline in CA-125 (2 ovarian and 1 endometrial Ca). Of 23 BCa pts enrolled by December 1, 5 pts had efficacy signals (2 PRs, 1 SD for 9 months, and 2 PMRs); all 5 pts were ER+, and 4 had high Ki67 breast tumors. PK/PD assessments are currently underway and will be presented at the meeting. Conclusions: The combination of ridaforolimus and dalotuzumab is tolerable and has promising antitumor activity in heavily pretreated advanced cancer, particularly in ER+/high proliferation breast cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck Merck Merck, Novartis
Generalization of analytical numerical matching for structural acoustic scattering with discontinuities using a composite Green’s function approach (1996)

Analytical numerical matching (ANM), when applied to structural acoustics, efficiently models structural discontinuities by superposing high-resolution local analytical solutions at discontinuities upon a low-resolution global numerical solution. This composite solution is very accurate and computationally efficient. Previously, ANM composite solutions have been developed for several specific problem geometries. A method for treating general constraint configurations using ANM is presented using the Green’s function concept, which models general structural constraints as an integration of point force solutions of the unconstrained structure. The general local solution is found by integration of the ANM local solution derived in the case of a point force. The point force local solution is analytic, known explicitly, and independent of overall geometry. The complementary global solution is far smoother than the original problem and, therefore, can be more efficiently calculated. In short, a general discretely constrained problem is replaced by a smoothed constrained problem, plus a local analytic correction. The method is demonstrated by application to scattering from an infinitely long cylindrical shell with periodic bulkheads. Accuracy and convergence of the structural response and scattered pressure are compared using a classical modal solution, a previous ANM modal solution, and the present general method. [Work supported by ONR.]
Sonochemical synthesis of nano-cocrystals (2013)

Cocrystals are multicomponent solids with organic molecules assembled in combination to form a crystalline solid with properties different than the individual components. A cocrystal typically consists of a target molecule crystallized with a second molecule, or cocrystal former, employed to influence properties of the target (e.g., solubility). The conformer interacts with the target via intermolecular forces (e.g., hydrogen bonds) that hold the components together. The modularity of a cocrystal makes such solids attractive for applications where fine-tuning of properties is important (e.g., optical). In this presentation, we describe the use of sonochemistry to form cocrystals of nanoscale dimensions. In contrast to single-component solids, cocrystals present a fundamentally different challenge with respect to those reprecipitation methods used to form nanocrystals since the components of a cocrystal will tend to exhibit different solubilities. We show that sonochemistry affords nano-cocrystals with properties (e.g., reactivity) that contrast solids of macroscale dimensions. Related applications of sonochemistry to afford single-component nanocrystals will also be presented.
Micro-reactors to Study the Reaction of Slag in Alkaline Media (2015)

A micro-reactor approach to study the hydration of cementitious materials has been developed in our laboratory. The method involves milling gaps that are a few microns in dimension in grains using a Focused Ion Beam. These gaps are then filled with solution, leading to dissolution, nucleation, and growth in the gaps. Hydration is stopped at selected time intervals, and a Scanning Electron Microscope is used to image the gaps. Information is obtained about dissolution-growth kinetics and hydrate morphology. Using this technique, we were able to obtain significant insights into the factors influencing early age hydration of tricalcium silicate and alite, and the effect of selected chemical admixtures on the same. In this study, we present the use of micro-reactors to study the alkaline activation of slag. The effects of solution pH and of the nature of the alkaline solution on the alkaline activation are discussed. Additionally, the dissolution of slag is studied, and we show that it is strongly affected by the presence of calcium and aluminum in solution. Results are compared and contrasted with those obtained with tricalcium silicate and alite. Originality The micro-reactor approach is probably the only method that offers the possibility of obtaining information about both dissolution and growth processes. We present ways in which factors affecting dissolution and growth may be understood, something that is very difficult or impossible using other techniques. Applying the micro-reactor technique to alkaline activation offers a way to better understand the reaction and the factors influencing it. Additionally, although we only present results with slag here, this technique may be used to study geopolymerization of several precursors with various solution compositions.
Diastereoselective Heteroatom-Directed Conjugate Addition of Silylcuprate Reagents to Unsaturated Carbonyls. A Stereoselective Route to .beta.-Carbonyl Siloxanes1 (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDiastereoselective Heteroatom-Directed Conjugate Addition of Silylcuprate Reagents to Unsaturated Carbonyls. A Stereoselective Route to .beta.-Carbonyl Siloxanes1Michael R. Hale and Amir H. HoveydaCite this: J. Org. Chem. 1994, 59, 16, 4370–4374Publication Date (Print):August 1, 1994Publication History Published online1 May 2002Published inissue 1 August 1994https://pubs.acs.org/doi/10.1021/jo00095a007https://doi.org/10.1021/jo00095a007research-articleACS PublicationsRequest reuse permissionsArticle Views496Altmetric-Citations31LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Identification of ubiquitinated repeats in human erythroid α‐spectrin (2000)

The spectrin role(s) is (are) very important for the shape and the physical properties of red cells, such as deformability and resistance to mechanical stresses. Moreover a variety of spectrin diseases are known. We have previously demonstrated [Corsi, D., Galluzzi, L., Crinelli, R. & Magnani, M. (1995) J. Biol. Chem. 270, 8928-8935] that human erythroid alpha-spectrin is ubiquitinated in vitro and in vivo. In order to define the ubiquitinated repeats of this long protein and find out a possible function, we have produced recombinant peptides encompassing the alphaIII-, alphaIV-, alphaV- and EF hand domains of alpha-spectrin chain. These peptides were tested in in vitro ubiquitin conjugation assays and two regions susceptibles to ubiquitination were found. The first one, in the alphaIV-domain, includes the repeat 17 and the second one, in the alphaV-domain, includes the repeat 20 and a part of repeat 21. We also demonstrated that the susceptibility to ubiquitination of the alphaV-domain is reduced by interaction with the corresponding portion of beta-spectrin chain (betaIV-domain). Thus, at least ubiquitination of alphaV-domain is susceptible to cytoskeleton assembly and spectrin dimerization.
Efficient addition of alcohols, amines and phenol to unactivated alkenes by AuIII or PdII stabilized by CuCl2 (2007)

The nucleophilic addition of alcohols, amines and phenol to unactivated alkenes catalyzed by cationic gold and palladium becomes limited due to the fast reduction into metallic gold under reaction conditions. The presence of CuCl2 retards the reduction of Au(III) and Pd", strongly increasing the turnover number of gold and palladium catalysts. It is shown that new Au(III)-CuCl2 and Pd(II)-CuCl2 catalysts are active and selective for the nucleophilic addition of alcohols, amines and phenol to unactivated alkenes.
Abstract 3458: Role of the EphB1 gene in mediating migration, proliferation, and radiosensitization of medulloblastoma cells (2014)

Abstract Eph/ephrin signaling in a variety of cancers has been reported to promote aspects of tumorigenesis, including proliferation, migration, and angiogenesis. Medulloblastoma is an aggressive primitive neuroectodermal tumor originating in the cerebellum. Recently performed integrative genomic approach to a large cohort of medulloblastomas has identified four subtypes (A-D) based on clinical presentation, transcription profiles, genetic abnormalities, and clinical outcome. We show high levels of EphB1 expression in tumors derived from children with group D medulloblastomas, which are known to exhibit a poorer response to current therapies. The purpose of this study is to examine the effect knockdown of EphB1 has on cellular migration, proliferation, and radiosensitization of medulloblastoma tumors. Using a human-derived medulloblastoma cell line (DAOY) and small interfering RNA (siRNA) targeting EphB1, we compared cell migration in an electrical impedance-based transwell Boyden chamber assay (xCELLigence RTCA DP system). We show that siRNA knockdown of EphB1 results in significantly decreased migration. Assessment of proliferation by MTT assay indicates that knockdown of EphB1 affects cell cycle progression in DAOY. Results from cell cycle and sub-G1 analysis by flow cytometry demonstrate that knockdown of EphB1 results in G1 arrest. Our previous systems analysis investigation of global gene expression regulated by an intact ATM gene product also identified EphB1 as a downstream signaling molecule correlating with enhanced cellular radiation resistance. Our data strongly support EphB1 as an unequivocal target for radiation sensitization in human fibroblasts as well as in vitro medulloblastoma cell lines. siRNA knockdown of EphB1 expression in human medulloblastoma cell lines known to express high levels of EphB1 results in sensitization to ionizing radiation by clonogenic survival assays. Preliminary data from an in vivo xenograft medulloblastoma animal model suggest an enhanced response to radiation in tumors lacking the EphB1 gene. Our data indicate that EphB1 is a potential molecular target for medulloblastoma cancer treatment and radiosensitization. The mechanisms and downstream signaling cascades underlying EphB1's action on cell migration, proliferation, and cellular radiosensitization are currently under investigation. Citation Format: Nimrah A. Baig*, Olga Timofeeva*, Anatoly Dritschilo, Elena Pasquale, Marcel Kool, Brian Rood, Olga Rodriguez, Christopher Albanese^, Sana Karam^. Role of the EphB1 gene in mediating migration, proliferation, and radiosensitization of medulloblastoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3458. doi:10.1158/1538-7445.AM2014-3458
Filtration of submicrometer particles by pelagic tunicates (2010)

Salps are common in oceanic waters and have higher per-individual filtration rates than any other zooplankton filter feeder. Although salps are centimeters in length, feeding via particle capture occurs on a fine, mucous mesh (fiber diameter d approximately 0.1 microm) at low velocity (U = 1.6 +/- 0.6 cmxs(-1), mean +/- SD) and is thus a low Reynolds-number (Re approximately 10(-3)) process. In contrast to the current view that particle encounter is dictated by simple sieving of particles larger than the mesh spacing, a low-Re mathematical model of encounter rates by the salp feeding apparatus for realistic oceanic particle-size distributions shows that submicron particles, due to their higher abundances, are encountered at higher rates (particles per time) than larger particles. Data from feeding experiments with 0.5-, 1-, and 3-microm diameter polystyrene spheres corroborate these findings. Although particles larger than 1 microm (e.g., flagellates, small diatoms) represent a larger carbon pool, smaller particles in the 0.1- to 1-microm range (e.g., bacteria, Prochlorococcus) may be more quickly digestible because they present more surface area, and we find that particles smaller than the mesh size (1.4 microm) can fully satisfy salp energetic needs. Furthermore, by packaging submicrometer particles into rapidly sinking fecal pellets, pelagic tunicates can substantially change particle-size spectra and increase downward fluxes in the ocean.
Design and implementation of a cylindrical array for passive mapping of cavitation fields produced by clinical high intensity focused ultrasound transducers. (2010)

Key to the success of high-intensity focused ultrasound (HIFU) as a clinical tool is the development of standardized quality assessment procedures to assess the safety and efficacy of HIFU transducers. The present work details the development of a cylindrical sensor array to be positioned around the HIFU focus during pre-treatment quality assessment of clinical transducers, which is designed to localize cavitation activity in three dimensions by passive mapping of the broadband emissions arising from inertial cavitation. The propagation of sound from a collection of broadband sources was first modeled to determine the optimum size, number and distribution of array elements for accurate mapping, and characterization of the cavitation dynamics produced during HIFU exposure. The optimal array configuration was then manufactured from PVDF using a novel printed circuit board technique, and theoretical predictions of the spatial resolution that it could achieve were validated experimentally. Because inertial cavitation is a pressure driven phenomenon, the ability to map cavitation activity using this array could provide a novel tool for rapid mapping of pressure fields produced by clinical HIFU transducers, in addition to providing invaluable information about the evolution of cavitation dynamics during HIFU exposure.
Basolateral chloride current in human airway epithelia (2007)

Electrolyte transport by airway epithelia regulates the quantity and composition of liquid covering the airways. Previous data indicate that airway epithelia can absorb NaCl. At the apical membrane, cystic fibrosis transmembrane conductance regulator (CFTR) provides a pathway for Cl(-) absorption. However, the pathways for basolateral Cl(-) exit are not well understood. Earlier studies, predominantly in cell lines, have reported that the basolateral membrane contains a Cl(-) conductance. However, the properties have varied substantially in different epithelia. To better understand the basolateral Cl(-) conductance in airway epithelia, we studied primary cultures of well-differentiated human airway epithelia. The basolateral membrane contained a Cl(-) current that was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). The current-voltage relationship was nearly linear, and the halide selectivity was Cl(-) > Br(-) >> I(-). Several signaling pathways increased the current, including elevation of cellular levels of cAMP, activation of protein kinase C (PKC), and reduction of pH. In contrast, increasing cell Ca(2+) and inducing cell swelling had no effect. The basolateral Cl(-) current was present in both cystic fibrosis (CF) and non-CF airway epithelia. Likewise, airway epithelia from wild-type mice and mice with disrupted genes for ClC-2 or ClC-3 all showed similar Cl(-) currents. These data suggest that the basolateral membrane of airway epithelia possesses a Cl(-) conductance that is not due to CFTR, ClC-2, or ClC-3. Its regulation by cAMP and PKC signaling pathways suggests that coordinated regulation of Cl(-) conductance in both apical and basolateral membranes may be important in controlling transepithelial Cl(-) movement.
Mixing colored LED sources (2003)

Given a set of available LEDs or other light sources with known spectrum, total luminous flux (lumen) and efficacy (lumen/Watt), price etc. we show how to select that combination which yields light of desired (photometric) color and, in addition, maximizes efficacy, luminous flux , color rendering index or other objectives.
Characterization of CD20 expression loss as a mechanism of resistance to mosunetuzumab in patients with relapsed/refractory B-cell non-Hodgkin lymphomas. (2022)

7526 Background: Mosunetuzumab (M) is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage and eliminate malignant B cells being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHL). CD20 is an optimal target, with uniform expression across B-NHL histologies and minimal receptor turnover. We characterized CD20 loss as a potential mechanism of resistance to M in patients (pts) on a Phase I/II trial (NCT02500407) receiving M monotherapy for the treatment (tx) of R/R B-NHL. Methods: Pts with R/R B-NHL received M intravenously in 3-week cycles, for eight to 17 cycles depending on tumor response. At baseline (BL), biomarker-evaluable (archival or fresh) biopsies were collected from 293 pts. Biopsies from 62 pts were collected at additional time points during tx with M and/or at disease progression (PD). The proportion of CD20+ and PAX5+ tumor cells was determined by immunohistochemistry (IHC) using dual-staining with anti-CD20 (clone L26, VENTANA) and anti-PAX5 (clone DAK-PAX5, DAKO) antibodies. Expression of MS4A1, the gene encoding CD20 , was measured by RNA-sequencing (RNA-seq); MS4A1 mutation profiling was performed by whole exome sequencing (WES). Levels of CD20 expression were assessed relative to response rates. Correlative analyses were performed and assessed centrally (IHC, RNA-seq, and WES) and locally (IHC). Results: CD20 levels were consistently high ( &gt; 75% CD20+PAX5+ cells) in the majority of BL biopsies and generally comparable across histologies (FL, DLBCL, tFL, MCL, and RT). BL CD20 loss (≤5% CD20+PAX5+ cells) was seen in 16/293 pts (5.5%), more commonly in aggressive NHL, and responses to M were not seen in these pts. Among 62 pts with BL and on-tx/at-PD biopsies, BL CD20 levels were ≤5% in 7/62 pts (11%) (6/7 pts [86%] progressed before completing Cycle 2). CD20 levels were maintained in on-tx biopsies from 23/24 pts (96%). At PD, biopsies showed CD20 loss in 7/26 pts (27%). For five pts with BL, on-tx and at-PD biopsies, all pts maintained CD20 while on-tx and 1/5 pts (20%) had CD20 loss at PD. There was no clear association between CD20 reduction and histology. Data from 185 BL biopsies showed generally concordant levels of CD20 gene and protein expression (r = 0.72). In 10/185 pts (5%), MS4A1 was expressed without detectable CD20 protein expression; DNA sequencing revealed novel mutations in MS4A1, including mutations leading to truncation of the protein. CD20 transmembrane and extra-cellular domain mutations were also observed but do not block CD20 expression. Conclusions: In pts with R/R B-NHL treated with M, low BL CD20 expression is associated with lack of response to M. During M tx, loss of tumor cell expression of CD20 is one mechanism of acquired resistance; however, CD20 expression is maintained in most pts with PD, implying alternative mechanisms for acquired M resistance. Clinical trial information: NCT02500407.