gebhart/patrepeval huggingface dataset:
Data from Synthetic DNA-Encoded Monoclonal Antibody Delivery of Anti–CTLA-4 Antibodies Induces Tumor Shrinkage <i>In Vivo</i> (2023)

&lt;div&gt;Abstract&lt;p&gt;Antibody-based immune therapies targeting the T-cell checkpoint molecules CTLA-4 and PD-1 have affected cancer therapy. However, this immune therapy requires complex manufacturing and frequent dosing, limiting the global use of this treatment. Here, we focused on the development of a DNA-encoded monoclonal antibody (DMAb) approach for delivery of anti–CTLA-4 monoclonal antibodies &lt;i&gt;in vivo&lt;/i&gt;. With this technology, engineered and formulated DMAb plasmids encoding IgG inserts were directly injected into muscle and delivered intracellularly by electroporation, leading to &lt;i&gt;in vivo&lt;/i&gt; expression and secretion of the encoded IgG. DMAb expression from a single dose can continue for several months without the need for repeated administration. Delivery of an optimized DMAb encoding anti-mouse CTLA-4 IgG resulted in high serum levels of the antibody as well as tumor regression in Sa1N and CT26 tumor models. DNA-delivery of the anti-human CTLA-4 antibodies ipilimumab and tremelimumab in mice achieved potent peak levels of approximately 85 and 58 μg/mL, respectively. These DMAb exhibited prolonged expression, with maintenance of serum levels at or above 15 μg/mL for over a year. Anti-human CTLA-4 DMAbs produced &lt;i&gt;in vivo&lt;/i&gt; bound to human CTLA-4 protein expressed on stimulated human peripheral blood mononuclear cells and induced T-cell activation in a functional assay &lt;i&gt;ex vivo&lt;/i&gt;. In summary, direct &lt;i&gt;in vivo&lt;/i&gt; expression of DMAb encoding checkpoint inhibitors serves as a novel tool for immunotherapy that could significantly improve availability and provide broader access to such therapies.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Significance:&lt;/b&gt; DNA-encoded monoclonal antibodies represent a novel technology for delivery and expression of immune checkpoint blockade antibodies, thus expanding patient access to, and possible clinical applications of, these therapies. &lt;i&gt;Cancer Res; 78(22); 6363–70. ©2018 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
PIK3CA Genotype and a PIK3CA Mutation-Related Gene Signature and Response to Everolimus and Letrozole in Estrogen Receptor Positive Breast Cancer (2013)

The phosphatidylinositol 3' kinase (PI3K) pathway is commonly activated in breast cancer and aberrations such as PI3K mutations are common. Recent exciting clinical trial results in advanced estrogen receptor-positive (ER) breast cancer support mTOR activation is a major means of estrogen-independent tumor growth. Hence the means to identify a responsive breast cancer population that would most benefit from these compounds in the adjuvant or earlier stage setting is of high interest. Here we study PIK3CA genotype as well as a previously reported PI3K/mTOR-pathway gene signature (PIK3CA-GS) and their ability to estimate the level of PI3K pathway activation in two clinical trials of newly diagnosed ER-positive breast cancer patients- a total of 81 patients- one of which was randomized between letrozole and placebo vs letrozole and everolimus. The main objectives were to correlate the baseline PIK3CA genotype and GS with the relative change from baseline to day 15 in Ki67 (which has been shown to be prognostic in breast cancer) and phosphorylated S6 (S240) immunohistochemistry (a substrate of mTOR). In the randomized dataset, the PIK3CA-GS could identify those patients with the largest relative decreases in Ki67 to letrozole/everolimus (R = -0.43, p = 0.008) compared with letrozole/placebo (R = 0.07, p = 0.58; interaction test p = 0.02). In a second dataset of pre-surgical everolimus alone, the PIK3CA-GS was not significantly correlated with relative change in Ki67 (R = -0.11, p = 0.37) but with relative change in phosphorlyated S6 (S240) (R = -0.46, p = 0.028). PIK3CA genotype was not significantly associated with any endpoint in either datasets. Our results suggest that the PIK3CA-GS has potential to identify those ER-positive BCs who may benefit from the addition of everolimus to letrozole. Further evaluation of the PIK3CA-GS as a predictive biomarker is warranted as it may facilitate better selection of responsive patient populations for mTOR inhibition in combination with letrozole.
A new Fc receptor on mouse macrophages binding IgG3. (1981)

Monoclonal antibodies to sheep erythrocytes (SRBC) have proved useful in identifying two Fc receptors on mouse macrophages, one for IgG2a, and one for IgG1 and IgG2b. We have used monoclonal IgG3 anti-SRBC to identify a third Fc receptor on mouse macrophages which binds IgG3 uniquely. This receptor is present on primary resident and thioglycolate-induced peritoneal macrophages and on some macrophage cell lines. The binding of IgG3-coated SRBC is inhibited by aggregated byt not monomeric IgG3, and not by IgG1, IgG2a, and IgG2b aggregates. It is unaffected by treating the macrophages with trypsin or cytochalasin B and occurs at both 4 degrees and 37 degrees C. IgG3, like all other IgG subclasses, mediates phagocytosis. We have also generated a variant macrophage line which bears the receptors for IgG1 and IgG2b and for IgG2a, but not for IgG3.
Profils d’expression des gènes dans le cancer du sein (2001)

Al'origine, l'etude moleculaire des voies de la carcinogenese s'est penchee sur un seul gene a la fois. De nouvelles techniques vont permettre de mesurer simultanement le niveau d'expression de milliers de genes dans un fragment tumoral (profil transcriptionnel). Des travaux recents ont montre l'interet de ces techniques dans la classification des leucemies, des lymphomes, des melanomes et des cancers du sein. Une proportion importante des cas familiaux de cancer du sein a debut precoce sont dus a une mutation du gene BRCA1 ou BRCA2, mutations tres rares dans les formes sporadiques. On peut imaginer que ces formes proviennent d'une perturbation des voies moleculaires auxquelles participent BRCA1 et BRCA2. Hedenfalk et al. [1] ont utilise des chips d'ADN complementaires contenant les sondes de 5361 genes afin de comparer les profils transcriptionnels de 22 tumeurs du sein avec ou sans mutation des genes BRCA1 ou BRCA2. Leur methode comportait la comparaison de l'intensite de liaison d'un ADNc fluorescent genere par un ARN messager issu d'un tissu de reference et de la tumeur, a une rangee comportant des milliers d'ADNc clones sur une lame de verre. Cette technique permet d'identifier les genes actifs et silencieux dans les deux tissus. Pour visualiser les 22 fragments tumoraux dans un espace a 5361 dimensions, les auteurs ont utilise une forme de reduction des donnees (echelonnage multidimensionnel) permettant d'en diminuer la complexite. Cela leur a permis de demontrer que les profils d'expression des trois types de tumeurs (BRCA1, BRCA2 ou aucun des deux) etaient clairement distincts. Ce travail illustre la possibilite d'une vision a l'echelle du genome dans le diagnostic de cancer. Des profils d'expressions genetiques complexes peuvent etre utilises pour identifier les anomalies de toute une voie moleculaire, sans qu'il soit necessaire de rechercher le gene en cause. Cette etude illustre aussi la facon dont les difficultes representees par le sequencage de grands genes comme BRCA1 peuvent etre partiellement contournees par l'utilisation du profil transcriptionnel. D'autres applications sont imaginables, par exemple l'utilisation de cette technique pour predire la reponse d'une tumeur a la chimiotherapie, dans le cas des lymphomes par exemple [2]1. Hedenfalk I., et al. 2001. Gene-expression profiles in hereditary breast cancer. N Engl J Med 344 : 539-548.2. Golub T.R. 2001. Genome-wide views of cancer. N Engl J Med 344 : 601-602.
The 5q- abnormality (1987)

Abstract LOSS OF A PORTION of the long arm of chromosome 5 is seen predominantly in therapy-related myelodysplastic syndromes and acute leukemias, as well as in a unique clinical disorder known as the 5q– syndrome. Recently, many growth factor and growth factor receptor genes have been localized to the long arm of chromosome 5, and several of these genes have been found to be deleted in patients with a 5q– chromosomal abnormality. These findings raise the possibility that alteration of expression of these genes may play a pathogenetic role in these hematologic disorders. In this review, we discuss the clinical and molecular biological findings associated with the 5q– abnormality.
Investigations on Physical Random Access Channel Structure in Evolved UTRA Uplink (2009)

This paper presents the optimum physical random access channel (PRACH) structure in terms of the number of control signaling bits accommodated and the transmission bandwidth based on the link budget in order to satisfy the coverage requirement for the single-carrier (SC)-FDMA based E-UTRA uplink. First, we present the design concept of the PRACH structure considering the purposes of the random access procedure in the E-UTRA. Simulation evaluations including a system-level simulation show that a PRACH comprising a 0.5-msec preamble sequence can convey a 6-bit control signal at the cell edge when the inter-site distance (ISD) is 500m under full channel load conditions with one-cell frequency reuse. It is also shown, however, that a PRACH longer than one-sub-frame, e.g., 1.0msec, is necessary to support the ISD of 1732m assuming the same conditions. We also show that the best transmission bandwidth for the PRACH is approximately 1.08-4.5MHz from the viewpoint of the misdetection probability, and a 1.08-MHz transmission bandwidth is suitable considering other aspects such as flexible resource assignment in the time domain and a small number of options in the transmission bandwidth.
N-Pyridyl and Pyrimidine Benzamides as KCNQ2/Q3 Potassium Channel Openers for the Treatment of Epilepsy (2011)

A series of N-pyridyl benzamide KCNQ2/Q3 potassium channel openers were identified and found to be active in animal models of epilepsy and pain. The best compound 12 [ICA-027243, N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide] has an EC50 of 0.38 μM and is selective for KCNQ2/Q3 channels. This compound was active in several rodent models of epilepsy and pain but upon repeated dosing had a number of unacceptable toxicities that prevented further development. On the basis of the structure-activity relationships developed around 12, a second compound, 51, [N-(2-chloro-pyrimidin-5-yl)-3,4-difluoro-benzamide, ICA-069673], was prepared and advanced into a phase 1 clinical study. Herein, we describe the structure-activity relationships that led to the identification of compound 12 and to the corresponding pyrimidine 51.
Utilizing 3D Printing Technology to Merge MRI with Histology: A Protocol for Brain Sectioning (2016)

Magnetic resonance imaging (MRI) allows for the delineation between normal and abnormal tissue on a macroscopic scale, sampling an entire tissue volume three-dimensionally. While MRI is an extremely sensitive tool for detecting tissue abnormalities, association of signal changes with an underlying pathological process is usually not straightforward. In the central nervous system, for example, inflammation, demyelination, axonal damage, gliosis, and neuronal death may all induce similar findings on MRI. As such, interpretation of MRI scans depends on the context, and radiological-histopathological correlation is therefore of the utmost importance. Unfortunately, traditional pathological sectioning of brain tissue is often imprecise and inconsistent, thus complicating the comparison between histology sections and MRI. This article presents novel methodology for accurately sectioning primate brain tissues and thus allowing precise matching between histology and MRI. The detailed protocol described in this article will assist investigators in applying this method, which relies on the creation of 3D printed brain slicers. Slightly modified, it can be easily implemented for brains of other species, including humans.
Site-Specific Generation of Protein-Protein Conjugates Using Native Amino Acids (2019)

Chimeric protein-protein conjugates provide platforms for immunotherapy, targeted drug delivery, and vaccine development. However, many desirable constructs cannot be produced through direct expression, and the targeted coupling of two proteins is chemically challenging. Here we present a new approach for the rapid and site-specific coupling of proteins using native amino acids. Tyrosinase oxidizes exposed tyrosine residues on polypeptides, generating ortho-quinones that react rapidly with strategically placed cysteine residues in other proteins. This approach was used to modify CRISPR-Cas9 and other substrates with small molecules, peptides and even intact proteins. The conjugation of cell penetrating peptides to CRISPR-Cas9 was shown to increase cellular genome editing efficiency by 20-fold relative to unmodified Cas9. This technology represents a new paradigm for biomolecular coupling, and paves the way to an unprecedented range of multifunctional bioconjugates.
RECFMM: Recursive Parallelization of the Adaptive Fast Multipole Method for Coulomb and Screened Coulomb Interactions (2016)

Abstract We present REC FMM, a program representation and implementation of a recursive scheme for parallelizing the adaptive fast multipole method (FMM) on shared-memory computers. It achieves remarkable high performance while maintaining mathematical clarity and flexibility. The parallelization scheme signifies the recursion feature that is intrinsic to the FMM but was not well exploited. The program modules of REC FMM constitute a map between numerical computation components and advanced architecture mechanisms. The mathematical structure is preserved and exploited, not obscured nor compromised, by parallel rendition of the recursion scheme. Modern software system—C ILK in particular, which provides graph-theoretic optimal scheduling in adaptation to the dynamics in parallel execution—is employed. REC FMM supports multiple algorithm variants that mark the major advances with low-frequency interaction kernels, and includes the asymmetrical version where the source particle ensemble is not necessarily the same as the target particle ensemble. We demonstrate parallel performance with Coulomb and screened Coulomb interactions.
CMOS‐compatible fabrication of porous silicon gas sensors and their readout electronics on the same chip (2007)

Abstract In this work, integration on the same chip of porous silicon gas sensors along with their driving/readout electronic circuits by using an industrial microelectronic process is demonstrated. To ensure maximum compatibility, the porous silicon formation is performed after the integrated circuit fabrication flow is completed. The chip contains three CMOS operational amplifiers, a band‐gap voltage reference, an integrated temperature sensor and several porous silicon‐based NO 2 sensors. The simultaneous functionality of the electronics and the sensor is demonstrated by using various circuit blocks to implement a simple driving/readout electronic interface for the sensor. (© 2007 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Supplementary Data from Changes in Bone Marrow Tumor and Immune Cells Correlate with Durability of Remissions Following BCMA CAR T Therapy in Myeloma (2023)

Supplementary Data from Changes in Bone Marrow Tumor and Immune Cells Correlate with Durability of Remissions Following BCMA CAR T Therapy in Myeloma
Mathematical Model of Macromolecular Drug Transport in a Partially Liquefied Vitreous Humor (2021)

The purpose of this study is to investigate the effect of partial liquefaction (due to ageing) of the vitreous humor on the transport of ocular drugs. In our model, the gel part of the vitreous is treated as a Darcy-type porous medium. A spherical region within the porous part of vitreous is in a liquid state which, for computational purposes, is also treated as a porous medium but with a much higher permeability. Using the finite element method, a time-dependent, three-dimensional model has been developed to computationally simulate (using the Petrov-Galerkin method) the transport of intravitreally injected macromolecules where both convection and diffusion are present. From a fluid physics and transport phenomena perspective, the results show many interesting features. For pressure-driven flow across the vitreous, the flow streamlines converge into the liquefied region as the flow seeks the fastest path of travel. Furthermore, as expected, with increased level of liquefaction, the overall flow rate increases for a given pressure drop. We have quantified this effect for various geometrical considerations. The flow convergence into the liquefied region has important implication for convective transport. One effect is the clear diversion of the drug as it reaches the liquefied region. In some instances, the entry point of the drug in the retinal region gets slightly shifted due to liquefaction. While the model has many approximations and assumptions, the focus is illustrating the effect of liquefaction as one of the building blocks toward a fully comprehensive model.
Quantum advantage for differential equation analysis (2022)

Quantum algorithms for differential equation solving, data processing, and machine learning potentially offer an exponential speedup over all known classical algorithms. However, there also exist obstacles to obtaining this potential speedup in useful problem instances. The essential obstacle for quantum differential equation solving is that outputting useful information may require difficult postprocessing, and the essential obstacle for quantum data processing and machine learning is that inputting the data is a difficult task just by itself. In this study, we demonstrate that, when combined, these difficulties solve one another. We show how the output of quantum differential equation solving can serve as the input for quantum data processing and machine learning, allowing dynamical analysis in terms of principal components, power spectra, and wavelet decompositions. To illustrate this, we consider continuous-time Markov processes on epidemiological and social networks. These quantum algorithms provide an exponential advantage over existing classical Monte Carlo methods.
Supplemental Table 1 from Response to Neoadjuvant Targeted Therapy in Operable Head and Neck Cancer Confers Survival Benefit (2023)

&lt;p&gt;Comparison of clinical to pathologic stage migration between patients enrolled in 1 of 4 window trials compared to a control group&lt;/p&gt;
Identification of deoxyribonucleic acid sequences that bind retinoid-X receptor-gamma with high affinity. (1994)

The retinoid-X receptor (RXR) family (-alpha, -beta and -gamma) forms homodimers that bind to a number of retinoid-X response elements and trans-activate gene expression in a retinoid-dependent manner. Although, the RXRs are known to bind tandem direct repeats (DR) of the hexamer, RGGTCA, separated by 1 nucleotide, it is not known whether these represent the optimal and/or only recognition sequences. We, therefore, used a nonbiased strategy to identify sequences that efficiently bound RXR gamma, an isoform preferentially expressed in cardiac and skeletal muscle tissue. We performed binding site selection with bacterially expressed RXR gamma bound to glutathione-agarose and a pool of random sequences to derive a consensus DNA-binding site for RXR gamma. We analyzed a total of 41 individually selected oligonucleotides and found that RXR gamma bound with high affinity to motifs that were accommodated by the consensus AARGRNCAAAGGTCAA/cR. We observed that the majority of the sequences that formed complexes with RXR gamma in electrophoretic mobility shift analysis were DR-1 motifs; however, DR- motifs separated by 2, 4, and 8 nucleotides and a palindrome-0 motif were also demonstrated to interact with RXR gamma. Mutagenesis of the derived sequences indicated that both RGGTCA motifs were required for high affinity binding to RXR gamma. These derived sequences conferred appropriate 9-cis- and all-trans-retinoic acid (RA) responses to a thymidine kinase promoter. Furthermore, supershift experiments with a RXR antibody verified that these sequences specifically interacted with RXR in nuclear extracts derived from C2C12 muscle cells. In conclusion, this study rigorously defines the range of DR motifs that can recognize RXR and regulate gene expression in a RA-dependent fashion. The derived consensus accommodates retinoid-X response elements that have been identified in a diverse range of genes trans-activated by 9-cis-RA via the RXR family.
Cost-effective multi-camera array for high quality video with very high dynamic range (2014)

Temporal bracketing can create images with higher dynamic range than the underlying sensor. Unfortunately, moving objects cause disturbing artifacts. Moreover, the combination with high frame rates is almost unachiev­ able since a single video frame requires multiple sensor readouts. The combination of multiple synchronized side-by-side cameras equipped with different attenuation filters promises a remedy, since all exposures can be performed at the same time with the same duration using the playout video frame rate. However, a disparity correction is needed to compensate the spatial displacement of the cameras. Unfortunately, the requirements for a high quality disparity correction contradict the goal to increase dynamic range. When using two cameras, disparity correction needs objects to be properly exposed in both cameras. In contrast, a dynamic range in­crease needs the cameras to capture different luminance ranges. As this contradiction has not been addressed in literature so far, this paper proposes a novel solution based on a three camera setup. It enables accurate de­ termination of the disparities and an increase of the dynamic range by nearly a factor of two while still limiting costs. Compared to a two camera solution, the mean opinion score (MOS) is improved by 13.47 units in average for the Middleburry images.
Terahertz Vibrational Motions Mediate Gas Uptake in Organic Clathrates (2020)

Clathrates, supramolecular materials that contain guest molecules trapped within a framework of a host lattice, are important in many areas of science and technology. However, despite much research, fundamental questions concerning the mechanism and kinetics associated with the enclathration process remain unanswered. Here, through a combination of terahertz spectroscopy, density functional theory, and molecular dynamics simulations, we demonstrate that the gas-capture process is mediated by a single terahertz vibrational mode and then use this mode to track the uptake of gas. This result provides a critical molecular-level understanding of this key kinetic process in clathrate science.