gebhart/patrepeval huggingface dataset:
Caracterización funcional de receptores de quimioquinas : activación y desensibilización del CCR2 y sus implicaciones en la infección por HIV-1 (2012)

Las quimioquinas son una familia de proteinas de bajo peso molecular caracterizada por su capacidad de inducir la migracion y activacion de diferentes poblaciones leucocitarias. En los ultimos anos ha cobrado importancia el papel que juegan en otros procesos como son la hematopoyesis, angiogenesis, rechazo de tumores o la infeccion por HIV-1. Las quimioquinas ejercen sus efectos mediante su interacion con receptores de siete dominios transmembrana acoplados a proteinas G. Estos receptores constan de un extremo amino terminal y tres bucles extracelulares, implicados en la interaccion con el ligando, y de un extremo carboxilo terminal y tres bucles intracelulares que colaboran en la traduccion de la senal. La activacion de los receptores de quimioquinas por sus respectivos ligandos induce la activacion de las vias de senalizacion aclopadas a proteinas del tipo Gi. Tomando como modelo la quimioquina MCP-1 y su receptor, CCR2, nos hemos planteado identificar los mecanismos que se activan tras la union de la quimioquina a su receptor. Para ello, se han obtenido anticuerpos monoclonales especificos frente al CCR2. Estos anticuerpos nos han permitido detectar la presencia de dicho receptor en poblaciones linfocitarias. De especial interes es la presencia de CCR2 funcional en la superficie de los linfocitos B. El hecho de que alguno de los anticuerpos obtenidos presente actividad inhibitoria de algunas cepas del virus HIV-1,asi como actividad agonista o antagonista del MCP-1, nos ha permitido definir aquellas regiones del CCR2 que juegan un papel importante en la interaccion con el MCP-1 y con la proteina gp120 del HIV-1. En lo que se refiere a la activacion del CCR2, hemos identificado que el MCP-1 induce la fosforilacion en tirosinas del CCR2 y la activacion de quinasas de la familia JANUS, que incluye la asociacion y fosforilacion de JAK2 y de factores de transcripcion de la familia STAT. Tras este paso previo en el cual juega un papel critico la tirosina 139 del receptor, se producen los cambios conformacionales que posibilitan la asociacion de la proteina Gi y la consiguiente activacion de las vias con ella relacionadas. En el estudio tambien se han identificado las senales implicadas en la desensibilizacion de dichos receptores. En este sentido, la activacion con MCP-1 conduce a la formacion de un complejo macromolecular formado por el propio receptor, la GRK2 y la arrestina que desacopla la proteina G. El CCR2 es finalmente internalizado en vesiculas de clatrina, proceso en el que juega un papel fundamental la dinamina
Cerebral granulomatosis as a manifestation of Crohn’s disease (2018)

Cerebral manifestation of CD is a possibly underreported entity that may respond well to immunosuppressive treatment. In contrast to earlier reports of cerebral manifestations in CD, our patient showed no coincident gastrointestinal symptoms indicating an activity of CD during the progression of cortical lesion load, suggesting that similar to other extra-intestinal manifestations in CD, the activity of gastrointestinal symptoms does not necessarily reflect the activity of CD associated cerebral vasculitis. Therefore, diagnosis and therapy of cerebral manifestation may be delayed when focusing on gastrointestinal symptoms alone.
Abstract IA08: Therapeutic resistance and feedback loops (2017)

Abstract Therapeutic resistance is a major obstacle in the clinic. Utilizing our novel genetically engineered mouse models (GEMMs) of breast cancer driven by inducible expression of PIK3CAH1047R or a wildtype HER2, coupled with pharmacological approaches, we identified a number of significant resistance mechanisms to PI3K- or HER2-targeted therapy. For example, we found spontaneous focal amplification of Met and Myc, recurrent mutations in Ras and β-catenin, and compensatory activation of the MAPK pathway render resistance to PI3K inhibition. We recently identified Cyclin D1-CDK4 mediated resistance to HER2-targeted therapy through a signaling feedback loop. More importantly, our results led to the design of a randomized phase II trial examining a CDK4/6 inhibitor plus trastuzumab as a regimen for patients with metastatic, refractory HER2+ breast cancer. In addition to GEMMs, we have led the efforts at DFCI to establish and characterize novel breast cancer patient-derived xenograft (PDX) models, with an emphasis on brain metastases, an emerging clinical challenge. I will discuss how we have used these models to discover a therapeutic strategy that overcomes resistance and yields durable remission of brain metastases of HER2+ breast cancer in animals. Citation Format: Jean J. Zhao. Therapeutic resistance and feedback loops. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr IA08.
Object Class Recognition by Boosting a Part-Based Model (2005)

We propose a new technique for object class recognition, which learns a generative appearance model in a discriminative manner. The technique is based on the intermediate representation of an image as a set of patches, which are extracted using an interest point detector. The learning problem becomes an instance of supervised learning from sets of unordered features. In order to solve this problem, we designed a classifier based on a simple, part based, generative object model. Only the appearance of each part is modeled. When learning the model parameters, we use a discriminative boosting algorithm which minimizes the loss of the training error directly. The models thus learnt have clear probabilistic semantics, and also maintain good classification performance. The performance of the algorithm has been tested using publicly available benchmark data, and shown to be comparable to other state of the art algorithms for this task; our main advantage in these comparisons is speed (order of magnitudes faster) and scalability.
ZD6474, a Novel Tyrosine Kinase Inhibitor of Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor, Inhibits Tumor Growth of Multiple Nervous System Tumors (2005)

In conclusion, ZD6474 shows significant activity against xenograft models of several primary human CNS tumor types. Consideration for clinical development in this disease setting seems warranted.
L’utilisation d’un antagoniste non stéroïdien du récepteur minéralocorticoïde (BR-4628) prévient les lésions rénales induites par l’ischémie-reperfusion (2015)

L’ischémie-reperfusion (I/R) représente la principale cause d’insuffisance rénale aiguë (IRA). L’IRA est associée au développement d’une insuffisance rénale chronique. Il a été montré chez le rat que l’administration d’antagonistes du récepteur minéralocorticoïde (RM) comme la spironolactone, prévenait les lésions rénales aiguës et chroniques induites par l’I/R. Malgré leurs bénéfices, ces antagonistes présentent un risque d’hyperkaliémie. Ceci favorise donc la recherche de nouveaux antagonistes avec une meilleure balance bénéfice/risque. L’objectif était de tester l’efficacité d’un antagoniste non stéroïdien du RM, BR-4628, sur la prévention des lésions rénales induites par l’I/R. Vingt rats Wistar mâles sont répartis en 4 groupes : sham (S), un groupe I/R rénale bilatérale pendant 25 minutes (I/R), et deux groupes traités avec l’antagoniste, BR-4628 (10 mg/kg), soit 3 jours avant l’I/R (B10-pré), soit 3 heures après l’I/R (B10-post). Les études sont faites 24 heures après la reperfusion. On a mesuré la créatinine et l’urée plasmatique. Nous avons réalisé des analyses moléculaires et histologiques dans le rein. Les rats qui ont subi l’I/R développent des lésions rénales, caractérisées par une dysfonction rénale, une augmentation de l’expression de marqueurs de lésions tubulaires (Hsp72 et Kim-1) et de cytokines pro-inflammatoires. Ces modifications sont absentes dans les groupes B10-pré et B10-post. L’I/R induit une augmentation de l’expression de marqueurs macrophagiques spécifique du phénotype M1 : iNOS, CCL3, TNF-alpha et MCP1 (phénotype pro-inflammatoire). Ces variations sont entièrement prévenues par l’administration du BR-4628. Enfin, nous observons dans les groupes traités avec le BR-4628 une augmentation importante de l’expression de marqueurs macrophagiques spécifiques du phénotype M2 : IL4r, FIZZ1 et IGFR2 (phénotype de réparation tissulaire). Nous croyons que l’effet bénéfique du BR-4628 est lié à la favorisation de la polarisation des macrophages vers un phénotype de réparation tissulaire. Nous montrons pour la première fois les bénéfices apportés par un antagoniste non stéroïdien, BR-4628, dans la prévention des lésions rénales induites par l’I/R.
Alphavirus E1 Glycoprotein-Liposome-Nucleic Acid Complexes Protect Mice from Lethal Challenge with Multiple Alphaviruses (2015)

Alphaviruses are globally distributed, mosquito borne pathogens that cause death and disease in vertebrates, including humans. Therapeutics to combat alphaviral disease are non-existant and only a handful of IND status vaccines are available. Of the available vaccines most are associated with a poor immunological response and a high rate of reactivity, and none protects against more than a single alphavirus species. We designed and tested novel alphavirus vaccines comprised of the E1 glycoproteins of western equine encephalitis virus (WEEV) or Venezuelan equine encephalitis virus (VEEV). Immunization with cationic lipid nucleic acid complexes (CLNCs) and alphavirus E1ecto mixture (lipid-antigen-nucleic acid complexes:LANACs) provided significant protection in mice challenged with either WEEV, VEEV or eastern equine encephalitis virus (EEEV) regardless of challenge route. LANAC immunized mice mount a strong humoral immune response lacking neutralizing antibody. Passive transfer of immune sera from LANAC immunized mice to non-immunized mice confers protection to challenge, indicating that non-neutralizing antibody is sufficient for protection. In summary, our LANAC vaccine has both therapeutic and prophylactic potential and is able to offer protection against distinct alphavirus species irrespective of the route of infection.
Electromagnetic wave absorption properties of carbon nanocoil composites in the millimeter waveband (2018)

Carbon nanocoil (CNC) is a carbon nanofiber with helical shape. In this study, we fabricated CNC-based composites endowed with electromagnetic wave absorption property. CNCs were synthesized by chemical vapor deposition using acetylene as a precursor and Fe and SnO2 particles as catalysts. The composites were produced by dispersing CNCs into epoxy resin or paraffin by ultrasonication, and then hardening a droplet of the solution on an aluminum substrate with ca. 2mm in specimen thickness. Paraffin was used as a solvent when producing the composites with the CNC concentration higher than or equal to 5wt.%; otherwise epoxy was used. The reflection ratio of the composites with different concentrations were measured by the free space method using lens antennas in frequency ranges of 5.6–40 and 67–110 GHz. The CNCs/epoxy composites of 0.1–1.0 wt.% showed poor reflection losses. The 10 wt.% CNCs/paraffin composite achieved a reflection loss of −32 dB at 79.2 GHz. Its bandwidth corresponding to the reflection loss below −20 dB was 4.85 GHz. The CNCs/paraffin composite also turned out to show a good absorption property in W band frequencies (75– 110 GHz).
Visible laser and laser array sources for projection displays (2006)

Laser-based projection displays have long attracted interest because of the multiple advantages (expanded color gamut, high resolution, longer lifetime, etc.) expected from lasers as compared to lamps. However, most of these advantages have been largely negated by the significant cost, size, and cooling requirements associated with lasers, and their inability to produce red, green, and blue colors in the same platform. In this paper, we review a new, laser array technology based of frequency-doubled, semiconductor, surface-emitting lasers. The key features of this technology, such as demonstrated multi-Watt output for rear-projection TVs, power levels scalable with the number of emitters, speckle suppression due to multi-emitter array, and a low-cost and compact design are discussed in detail.
Low-Cost, Long-Cycle-Life Sodium-Ion Battery to Enable Grid Scale Energy Storage (2014)

Large-capacity, cost-effective energy storage is the transformational technology needed to enable large scale integration of renewable energy (e.g. wind, solar). The rechargeable battery offers efficient electrical energy storage (EES). The Li-ion battery has been the leading option based on its performance, but it is too expensive for large-scale EES. Unlike Li, Na is readily available worldwide and therefore much less costly than Li. Sodium-ion batteries (SIBs) based on a hexacyanometallate (HCM) cathode are good options for the purpose of a low cost battery for EES. These materials correspond to the general chemical formula, A x M 1 [M 2 (CN) 6 ] y ·zH 2 O, consisting of a cubic framework with cyanide (C≡N) - ligands bridging metal-ions, M 1 and M 2 , thus forming large lattice interstitial spaces to facilitate efficient alkali-ion, “A”, intercalation. Electronic configurations of M 1 and M 2 are strongly affected by the cyanide ligands. In particular, ligand field splitting energy is higher for M 2 -ions associated with carbon than for M 1 -ions associated with nitrogen, which results in a low spin (LS) electron configuration for M 2 , but a high spin (HS) electron configuration for M 1 . We will present our study on HCM-based cathode materials, including their bulk and surface structures as well as their electrochemical performance. We will demonstrate that the HCM-based cathodes provide promising low-cost and long-cycle life SIBs of high specific energy density and efficient EES. References: 1. Long Wang, Yuhao Lu, Jue Liu, Maowen Xu, Jinguang Cheng, Dawei Zhang, and John B. Goodenough. Angew. Chem. Int. Ed., 2013, 52, 1964 –1967. 2. Yuhao Lu, Long Wang, Jinguang Cheng and John B. Goodenough . Chem. Commun. , 2012, 48, 6544–6546.
"Keynote CIO/CTO perspectives panel" with panelists (2010)

No abstract available.
Toxicological Assessment of ITER-Like Tungsten Nanoparticles Using an In Vitro 3D Human Airway Epithelium Model (2019)

The International Thermonuclear Experimental Reactor (ITER) is an international project aimed at the production of carbon-free energy through the use of thermonuclear fusion. During ITER operation, in case of a loss-of-vacuum-accident, tungsten nanoparticles (W-NPs) could potentially be released into the environment and induce occupational exposure via inhalation. W-NPs toxicity was evaluated on MucilAir™, a 3D in vitro cell model of the human airway epithelium. MucilAir™ was exposed for 24 h to metallic ITER-like milled W-NPs, tungstate (WO<sub>4</sub><sup>2-</sup>) and tungsten carbide cobalt particles alloy (WC-Co). Cytotoxicity and its reversibility were assessed using a kinetic mode up to 28 days after exposure. Epithelial tightness, metabolic activity and interleukin-8 release were also evaluated. Electron microscopy was performed to determine any morphological modification, while mass spectrometry allowed the quantification of W-NPs internalization and of W transfer through the MucilAir™. Our results underlined a decrease in barrier integrity, no effect on metabolic activity or cell viability and a transient increase in IL-8 secretion after exposure to ITER-like milled W-NPs. These effects were associated with W-transfer through the epithelium, but not with intracellular accumulation. We have shown that, under our experimental conditions, ITER-like milled W-NPs have a minor impact on the MucilAir™ in vitro model.
Multiple motion scene reconstruction from uncalibrated views (2002)

We describe a reconstruction method of multiple motion scenes, which are the scenes containing multiple moving objects, from uncalibrated views. Assuming that the objects are moving with constant velocities, the method recovers the scene structure, the trajectories of the moving objects, the camera motion and the camera intrinsic parameters (except skews) simultaneously. The number of the moving objects is automatically detected without prior motion segmentation. The method is based on a unified geometrical representation of the static scene and the moving objects. It first performs a projective reconstruction using a bilinear factorization algorithm, and then converts the projective solution to a Euclidean one by enforcing metric constraints. Experimental results on synthetic and real images are presented.
The Relation of Plasmacytoid Dendritic Cells (pDCs) and Regulatory T-Cells (Tregs) with HPV Persistence in HIV-Infected and HIV-Uninfected Women (2014)

Other than CD4+ count, the immunologic factors that underlie the relationship of HIV/AIDS with persistent oncogenic HPV (oncHPV) and cervical cancer are not well understood. Plasmacytoid dendritic cells (pDCs) and regulatory T-cells (Tregs) are of particular interest. pDCs have both effector and antigen presenting activity and, in HIV-positive patients, low pDC levels are associated with opportunistic infections. Tregs downregulate immune responses, and are present at high levels in HIV-positives. The current pilot study shows for the first time that low pDC and high Treg levels may be significantly associated with oncHPV persistence in both HIV-positive and HIV-negative women. Larger studies are now warranted.
C-106 Cancer vaccine strategies (2014)

We developed several cancer vaccine strategies and translated them from mice to humans. We used “epitope enhancement” to modify an epitope of the TARP prostate cancer antigen to increase affinity for HLA-A2 and immunogenicity in HLA-A2-transgenic mice. This and another high affinity TARP epitope elicited human T cells killing human tumor cells. We translated these into a vaccine trial in stage D0 prostate cancer, in which patients after primary disease treatment now have rising PSA. Patients received TARP peptides either in montanide or pulsed onto autologous DCs. No difference was seen between arms. Seventy-two percent of vaccinees at 24 wks and 74% at 48 wks had a decreased PSA velocity (P = 0.0004), a validated measure of tumor growth. Seventy-seven percent of vaccinees made a specific IFNg ELISpot response, but there was no correlation with clinical effect, suggesting that the quality of the T cells is critical. Accordingly, a phase II randomized placebo-controlled clinical trial is being opened. We also developed an adenovirus vaccine expressing the extracellular & transmembrane domains of HER2, which cured almost all mice with large (up to 2 cm) established tumors and lung metastases. The protection in mice is purely antibody-dependent. We translated this to a clinical trial with autologous DCs transduced with an adenovirus expressing human HER2 domains. The first part is a dose-escalation in patients with any type of cancer expressing 1+ to 3+ HER2 by IHC who are naive to HER2-targeted therapies. Of 3 patients so far at the 2nd dose level, we have an indication of a partial response in 1. Thus, translation of cancer vaccine strategies from mice to humans is beginning to show promising results.
A Thermomorphic Polyethylene‐Supported Imidazolium Salt for the Fixation of CO<sub>2</sub> into Cyclic Carbonates (2020)

Abstract An imidazolium catalyst supported on thermomorphic polyethylene (PE) was prepared from 1‐methylimidazole and polyethylene iodide (PE−I). The catalyst was characterized by 1 H and 13 C NMR, SEC and MALDI‐ToF mass spectrometry. Its catalytic activity was evaluated in the ring‐opening of epoxides with carbon dioxide to give cyclic carbonates under solvent‐free conditions. The catalyst proved to be active at low catalyst loading (down to 0.1 mol%) and allows the reaction to occur at low CO 2 pressure (1–5 bar) and moderate temperature (100 °C). A range of terminal and internal epoxides was converted to the corresponding cyclic carbonates with high yields and selectivities. The recyclability of the catalyst was studied and no significant loss of activity was observed after 5 runs. magnified image
Molecular Basis for Histone Acetyltransferase Regulation by Binding Partners, Associated Domains, and Autoacetylation (2015)

Acetylation is a post-translational modification (PTM) that regulates chromatin dynamics and function. Dysregulation of acetylation or acetyltransferase activity has been correlated with several human diseases. Many, if not all, histone acetyltransferases (HATs) are regulated in part through tethered domains, association with binding partners, or post-translational modification, including predominantly acetylation. This review focuses on what is currently understood at the molecular level of HAT regulation as it occurs via binding partners, associated domains, and autoacetylation.
Remote Sensing Small Explosives With an Ionospheric Radar (2023)

Abstract Earth's ionosphere has long been targeted as a medium for remote sensing of explosive terrestrial events such as earthquakes, volcanic eruptions, and nuclear/conventional weapon detonations. Until now, the only confirmed ionospheric detections have been of very large events that were easily detectable through other traditional global sensor systems (e.g., seismic). We present the first clear, confirmed detections of relatively low yield 1‐ton TNT‐equivalent chemical explosions using pulsed Doppler radar observations of isodensity layers in the ionospheric E region. The shape and spectra of the detected waveforms closely match predictions from the acoustic ray tracing and weakly nonlinear waveform propagation models. The explosions were roughly three orders of magnitude lower yield than any previous confirmed ionospheric detection and represent the first conclusive evidence that explosions of this size can have clear impacts on the ionosphere. This technique could improve the remote detection of both anthropogenic and natural explosive events.
Elevated levels of insulin-like growth factor-binding protein-2 in the serum of prostate cancer patients. (1993)

We have previously documented the presence of specific insulin-like growth factor (IGF)-binding protein (IGFBPs) in seminal plasma and prostate epithelial cell-conditioned medium IGFBP-2 is the prevalent IGFBP in both fluids. To assess whether patients with prostate carcinoma have alterations in serum IGFP levels related to the production of IGFBPs by their tumors, we performed Western ligand blots (WLB) and IGFBP-2 RIA on serum samples from 32 patients with prostate carcinoma of various degrees of clinical severity and compared them to results in 16 healthy age-matched controls. We have also measured serum IGF-I and -II by RIA. The mean level of IGFBP-2 in the prostate cancer patients was 170% of control levels by WLB analysis and 195% of control levels by RIA (P < 0.01). The degree of elevation of IGFBP-2 was related to the stage of the tumor and the levels of the serum tumor marker, prostate-specific antigen. Serum IGFBP-3 levels determined by WLB and serum IGF-I and IGF-II levels measured by RIA after acid chromatography were not different among the subjects with cancer and the normal controls. We conclude that IGFBP-2, which is the main IGFBP produced by prostate epithelial cells, is elevated in the serum of patients with prostate carcinoma, and that the degree of this elevation is related to serum prostate-specific antigen levels and the stage of the tumor. We speculate that prostate-derived IGFBPs may be secreted by prostate tumors and could e of value in understanding the pathophysiology of prostatic tumor growth as well as provide potential diagnostic markers.