gebhart/patrepeval huggingface dataset:
Abstract A13: Siglec-7/9-sialic acid interactions inhibit T cell immune response in prostate cancer (2022)

Abstract Immunotherapy has rapidly expanded in the care of patients with cancer with the discovery of immune checkpoints like PD-1 and CTLA-4. However, current immune checkpoint inhibitors are largely ineffective for prostate cancer. Recent studies suggest an alternative immune evasion pathway through the interactions between Sialic acid-binding immunoglobulin-type lectin proteins (Siglec) and their ligands, sialylated glycoprotein. Siglec-7/9-sialic acid interactions are reported to inhibit the immune cell response in several cancer types including leukemia, melanoma, and non-small cell lung cancer. Here, we demonstrated that Siglec-7/9 ligands were expressed in both prostate cancer tumor tissues and cell lines. We promoted T cell-mediated cytotoxicity of cancer cells by disrupting the interactions between Siglec-7/9 and their ligands. We discovered that FXYD5 and CD59 are potential Siglec-7 and Siglec-9 ligands, respectively, with CRISPRi screen. We then found that FXYD5 and CD59 knockout cells had reduced Siglec-7/9 binding capacity and enhanced T cells mediated killing effects on prostate cancer cells. These results provide a rationale for novel immune checkpoints and potential approaches for targeting Siglec-7/FXYD5 and Siglec-9/CD59 immune checkpoints for prostate cancer. Citation Format: Ru M Wen, Jessica C. Stark C Stark, Fernando García-Marqués, Hongjuan Zhao, Rosie Nolley, Carolyn R Bertozzi, Sharon J Pitteri, James D. Brooks. Siglec-7/9-sialic acid interactions inhibit T cell immune response in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A13.
Cyclooxygenase-2 is Essential for the Optimal Differentiation of Human Antibody Secreting Cells: Implications for Vaccination (84.11) (2009)

Abstract Generation of optimal humoral immunity in response to vaccination is essential in order to protect the public from potentially devastating infectious agents. Cyclooxygenase inhibitors are amongst the most widely used and commonly prescribed medications. However, relatively little is understood about their influence on human immune responses. Herein, we report that non-steroidal anti-inflammatory drugs (NSAIDs) and small molecule Cox-2 selective inhibitors attenuated human B cell immunoglobulin production in a Cox-2-dependent manner. We further demonstrated that the Cox-2 selective inhibitors SC-58125 and NS-398 non-selectively blunt the production of human antibody isotypes including IgM, IgG1, IgG2, IgG3 and IgG4. This correlated with a significant reduction in the generation of CD38+ IgM+ and CD38+IgG+ antibody secreting plasma cell precursors. Interestingly, we discovered that inhibition of Cox-2 activity with SC-58125 severely reduced the mRNA and protein levels of the essential plasma cell transcription factors, Blimp-1 and Xbp-1 in normal human B cells. These new results demonstrate an essential role for Cox-2 in the terminal differentiation of human B lymphocytes to antibody secreting cells. Our findings suggest that the use of drugs that attenuate Cox-2 activity can reduce the generation of plasma cells and ultimately optimal antibody responses to vaccines and pathogenic infections. This research was supported by DE011390, ES01247, AI071064 and T32-DE007202.
Boosting of HIV-1 Neutralizing Antibody Responses by a Distally Related Retroviral Envelope Protein (2014)

Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycoprotein (Env). In this article, we report an immunization strategy composed of a trivalent HIV-1 (clade B envs) DNA prime, followed by a SIVmac239 gp140 Env protein boost that aimed to focus the immune response to structurally conserved parts of the HIV-1 and simian immunodeficiency virus (SIV) Envs. Heterologous NAb titers, primarily to tier 1 HIV-1 isolates, elicited during the trivalent HIV-1 env prime, were significantly increased by the SIVmac239 gp140 protein boost in rabbits. Epitope mapping of Ab-binding reactivity revealed preferential recognition of the C1, C2, V2, V3, and V5 regions. These results provide a proof of concept that a distally related retroviral SIV Env protein boost can increase pre-existing NAb responses against HIV-1.
Discovery of chemical inhibitors of the selective transfer of lipids mediated by the HDL receptor SR-BI (2002)

The high-density lipoprotein (HDL) receptor, scavenger receptor, class B, type I (SR-BI), mediates both the selective uptake of lipids, mainly cholesterol esters, from HDL to cells and the efflux of cholesterol from cells to lipoproteins. The mechanism underlying these lipid transfers is distinct from classic receptor-mediated endocytosis, but it remains poorly understood. To investigate SR-BI's mechanism of action and in vivo function, we developed a high-throughput screen to identify small molecule inhibitors of SR-BI-mediated lipid transfer in intact cells. We identified five compounds that in the low nanomolar to micromolar range block lipid transport (BLTs), both selective uptake and efflux. The effects of these compounds were highly specific to the SR-BI pathway, because they didn't interfere with receptor-mediated endocytosis or with other forms of intracellular vesicular traffic. Surprisingly, all five BLTs enhanced, rather than inhibited, HDL binding by increasing SR-BI's binding affinity for HDL (decreased dissociation rates). Thus, the BLTs provide strong evidence for a mechanistic coupling between HDL binding and lipid transport and may serve as a starting point for the development of pharmacologically useful modifiers of SR-BI activity and, thus, HDL metabolism.
Fast algorithm for chirp transforms with zooming-in ability and its applications (2000)

A general fast numerical algorithm for chirp transforms is developed by using two fast Fourier transforms and employing an analytical kernel. This new algorithm unifies the calculations of arbitrary real-order fractional Fourier transforms and Fresnel diffraction. Its computational complexity is better than a fast convolution method using Fourier transforms. Furthermore, one can freely choose the sampling resolutions in both x and u space and zoom in on any portion of the data of interest. Computational results are compared with analytical ones. The errors are essentially limited by the accuracy of the fast Fourier transforms and are higher than the order 10(-12) for most cases. As an example of its application to scalar diffraction, this algorithm can be used to calculate near-field patterns directly behind the aperture, 0 < or = z < d2/lambda. It compensates another algorithm for Fresnel diffraction that is limited to z > d2/lambdaN [J. Opt. Soc. Am. A 15, 2111 (1998)]. Experimental results from waveguide-output microcoupler diffraction are in good agreement with the calculations.
Formal Convergent Synthesis of Ivermectin Aglycone - A Synthetic Approach to the C10-C25 Subunit of Avermectins 2b (2009)

International audience
Tricyclic-Carbocyclic RORγt Inverse Agonists—Discovery of BMS-986313 (2021)

SAR efforts directed at identifying RORγt inverse agonists structurally different from our clinical compound <b>1</b> (BMS-986251) led to tricyclic-carbocyclic analogues represented by <b>3</b>-<b>7</b> and culminated in the identification of <b>3d</b> (BMS-986313), with structural differences distinct from <b>1</b>. The X-ray co-crystal structure of <b>3d</b> with the ligand binding domain of RORγt revealed several key interactions, which are different from <b>1</b>. The in vitro and in vivo PK profiles of <b>3d</b> are described. In addition, we demonstrate robust efficacy of <b>3d</b> in two preclinical models of psoriasis-the IMQ-induced skin lesion model and the IL-23-induced acanthosis model. The efficacy seen with <b>3d</b> in these models is comparable to the results observed with <b>1</b>.
Shannon-based capacity estimations of future microcellular wireless communication systems (2002)

This paper presents a Shannon-based approach towards estimating the multi-user uplink and downlink transmission capacities of future microcellular communication systems exhibiting high user densities and application-dependent broadband data rates.
Electrothermal Launcher and PDV used for calibration of Polyvinylidene Fluoride (PVDF) pressure gauges (2011)

Slides presented at the 6th Annual Photonic Doppler Velocimetry (PDV) Workshop held at Lawrence Livermore National Laboratory, Livermore, California, November 3-4, 2011.
Both Overlapping and Distinct Signaling Pathways for Somatostatin Receptor Subtypes SSTR1 and SSTR2 in Pituitary Cells (1997)

To elucidate the signaling events mediated by specific somatostatin receptor (SSTR) subtypes, we expressed SSTR1 and SSTR2 individually in rat pituitary GH12C1 and F4C1 cells, which lack endogenous somatostatin receptors. In transfected GH12C1 cells, both SSTR1 and SSTR2 coupled to inhibition of Ca2+ influx and hyperpolarization of membrane potential via a pertussis toxin (PTx)-sensitive mechanism. These effects reflected modulation of ion channel activities which are important for regulation of hormone secretion. Somatostatin analogs MK678 and CH275 acted as subtype selective agonists as expected. In transfected F4C1 cells, both SSTR1 and SSTR2 mediated somatostatin-induced inhibition of adenylyl cyclase via a PTx-sensitive pathway. In addition, activation of SSTR2 in F4C1 cells, but not SSTR1, stimulated phospholipase C (PLC) activity and an increase in [Ca2+]i due to release of Ca2+ from intracellular stores. Unlike adenylyl cyclase inhibition, the PLC-mediated response was only partially sensitive to PTx. To determine the structural determinants in SSTR2 necessary for activation of PLC, we constructed chimeric receptors in which domains of SSTR2 were introduced into SSTR1. Chimeric receptors containing only the third intracellular loop, or all three intracellular loops from SSTR2, mediated inhibition of adenylyl cyclase, but failed to stimulate PLC activity as did wild-type SSTR2. Furthermore, the C-terminal tail of SSTR2 was not required for coupling to PLC. Thus, by expressing individual somatostatin receptor subtypes in pituitary cells, we have identified both overlapping and distinct signaling pathways for SSTR1 and SSTR2, and have shown that sequences other than simply the intracellular domains are required for SSTR2 to couple to the PLC signaling pathway.
Atomic transport on one-dimensional optical lattices (1997)

We carry out quantum and semiclassical numerical simulations of the dynamics, particularly diffusion, of atoms in an optical lattice. We consider specifically the situation of a $J=1/2\ensuremath{\leftrightarrow}J=3/2$ atomic transition, whose experimental counterpart can be realized in ${\mathrm{Mg}}^{+}$ experiments. The semiclassical results, which cover a larger range of parameters than would be practical for fully quantum calculations, confirm and extend the work of Marksteiner et al. [Phys. Rev. A 53, 3409 (1996)], characterize the transition from normal to anomalous diffusion and the atomic trajectories which give rise to it, and provide a physical explanation for the difference between these two regimes. The full quantum calculations reveal uniquely quantum features of individual atomic trajectories, and in addition, predict significantly lower diffusion, by a factor of 1.2 to 2, than their semiclassical counterparts.
A cytotoxic factor for glial cells: a new avenue of research for multiple sclerosis? (1997)

A novel retrovirus, provisionally called Multiple Sclerosis RetroVirus (MSRV), was recently described in multiple sclerosis (MS). We report here that monocyte/macrophage culture supernatants from MS patients containing reverse transcriptase activity secrete a cytotoxin which induces death of primary mouse cortical glial cells. This cytotoxin, which was also found in MS cerebrospinal fluid, specifically causes death of mouse immortalized astrocytes and oligodendrocytes in vitro and seems to be associated to MSRV-specific RNA. This toxic factor, called gliotoxin, is present only in active cases of MS and is a stable glycosylated protein of 17 kDa, in CSF as well as in monocyte/macrophage culture supernatants. Since this gliotoxin is highly toxic for glial cells, it may represent an initial pathogenic factor, leading to the neuropathological features of MS, like blood brain barrier disruption and demyelination.
Apical and Basolateral Endocytic Pathways of MDCK Cells Meet in Acidic Common Endosomes Distinct from a Nearly‐Neutral Apical Recycling Endosome (2000)

Quantitative confocal microscopic analyses of living, polarized MDCK cells demonstrate different pH profiles for apical and basolateral endocytic pathways, despite a rapid and extensive intersection between the two. Three-dimensional characterizations of ligand trafficking demonstrate that the apical and basolateral endocytic pathways share early, acidic compartments distributed throughout the medial regions of the cell. Polar sorting for both pathways occurs in these common endosomes as IgA is sorted from transferrin to alkaline transcytotic vesicles. While transferrin is directly recycled from the common endosomes, IgA is transported to a downstream apical compartment that is nearly neutral in pH. By several criteria this compartment appears to be equivalent to the previously described apical recycling endosome. The functional significance of the abrupt increase in lumenal pH that accompanies IgA sorting is not clear, as disrupting endosome acidification has no effect on polar sorting. These studies provide the first detailed characterizations of endosome acidification in intact polarized cells and clarify the relationship between the apical and basolateral endocytic itineraries of polarized MDCK cells. The extensive mixing of apical and basolateral pathways underscores the importance of endocytic sorting in maintaining the polarity of the plasma membrane of MDCK cells.
The design and technology requirements of a 9-channel RS485 transceiver for ultra-SCSI applications (2002)

The design aspects of a 9-channel ultra-SCSI transceiver chip are discussed including improvements to speed, power consumption and die size over a previous generation chip, Discussion of the enabling linear BiCMOS technology and an ESD strategy, critical to the function of this class of chip, are presented. Finally, the results of prototype silicon are reviewed.
Precise Control of Osteogenesis for Craniofacial Defect Repair (2012)

We have previously shown that inkjet-based bioprinting has the potential to significantly enhance the role of regenerative therapies in craniofacial surgery. This technology affords the precise control of osteogenesis necessary to reconstruct this region's intricate anatomical architecture. In the present study, we demonstrate that direct apposition of BMP-2-printed ADM to a source of osteoprogenitor cells (in this case dura mater) is necessary for bio-ink-directed osteogenesis to occur. These results have important implications for the design of more complex bioprinted osseous structures.
Linear Predic 7. Linear Prediction (2008)

Linear prediction plays a fundamental role in all aspects of speech. Its use seems natural and obvious in this context since for a speech signal the value of its current sample can be well modeled as a linear combination of its past values. In this chapter, we attempt to present the most important ideas on linear prediction. We derive the principal results, widely recognized by speech experts, in a very intuitive way without sacrificing mathematical rigor.
Sequential growth factor exposure of human Ad‑MSCs improves chondrogenic differentiation in an osteochondral biphasic implant (2021)

Joint cartilage damage affects 10-12% of the world's population. Medical treatments improve the short-term quality of life of affected individuals but lack a long-term effect due to injury progression into fibrocartilage. The use of mesenchymal stem cells (MSCs) is one of the most promising strategies for tissue regeneration due to their ability to be isolated, expanded and differentiated into metabolically active chondrocytes to achieve long-term restoration. For this purpose, human adipose-derived MSCs (Ad-MSCs) were isolated from lipectomy and grown in xeno-free conditions. To establish the best differentiation potential towards a stable chondrocyte phenotype, isolated Ad-MSCs were sequentially exposed to five differentiation schemes of growth factors in previously designed three-dimensional biphasic scaffolds with incorporation of a decellularized cartilage matrix as a bioactive ingredient, silk fibroin and bone matrix, to generate a system capable of being loaded with pre-differentiated Ad-MSCs, to be used as a clinical implant in cartilage lesions for tissue regeneration. Chondrogenic and osteogenic markers were analyzed by reverse transcription-quantitative PCR and cartilage matrix generation by histology techniques at different time points over 40 days. All groups had an increased expression of chondrogenic markers; however, the use of fibroblast growth factor 2 (10 ng/ml) followed by a combination of insulin-like growth factor 1 (100 ng/ml)/TGFβ1 (10 ng/ml) and a final step of exposure to TGFβ1 alone (10 ng/ml) resulted in the most optimal chondrogenic signature towards chondrocyte differentiation and the lowest levels of osteogenic expression, while maintaining stable collagen matrix deposition until day 33. This encourages their possible use in osteochondral lesions, with appropriate properties for use in clinical patients.
Wavelength-tunable and thermally stable Li-α-sialon:Eu2+ oxynitride phosphors for white light-emitting diodes (2006)

Eu 2 + -activated Li-α-sialon is a promising yellow phosphor for white light-emitting diodes (LEDs). This letter reports that the emission of Eu2+ in Li-α-sialon can be tuned widely (563–586nm) by tailoring the composition or controlling the Eu2+ concentration. The thermal stability of Li-α-sialon:Eu2+, relying a little on the composition and the Eu2+ concentration, remains high in a wide temperature range (25–200°C). Moreover, the chromaticity of Li-α-sialon:Eu2+ does not shift with changes in temperature. Using a single Li-α-sialon:Eu2+ phosphor, highly efficient white LEDs (46–55lm∕W) with different color temperatures (3000–5200K) can be fabricated.
Thermo-optic characterization of GaAs for quasi-phase-matched nonlinear-optical applications (2003)

Summary form only given. We have measured the thermo-optic coefficient near room temperature as a function of wavelength throughout the GaAs spectral transmission window. We compare these results to measurements of the temperature dependence of frequency doubling of 4-/spl mu/m radiation in orientation patterned GaAs.
Microwave-Assisted Synthesis of Graphene-Coated Mn-Doped Lithium Iron Phosphate (LFMP/G) for Electrochemical Capacitor (2015)

Lithium Iron Phosphate (LFP) material is widely used to power commercial products such as torches, automotive vehicles and certain laptops. The material is relatively cheap, safe to use and longer life times than some of the other battery chemistry materials; however it suffers from poor electronic conductivity. In order to improve the electronic conductivity of LFP, the material can be doped with transition metals such as manganese (Mn) and coated with a carbon source such as graphene [1]. Various methods can be used to synthesize LFP materials with microwave synthesis being one of the examples [2]. Microwave irradiation allows for rapid synthesis. The experimental processes involved a one-pot design where all the starting materials were added together and underwent ultra-sonication, microwaving, washing, drying and annealing at 700°C. During the microwave irradiation process it was seen that crystalline LFP material was formed with a coating of graphene to form LFP/G and some of the material was doped with Mn to form LFMP/G. The LFP/G and doped LFMP/G material was made up into asymmetrical electrochemical capacitors (AEC). The LFP/G AEC had a much faster charge and discharge response time at 7mA relative to the LFMP/G AEC, however the LFMP/G AEC could be charged and discharged to higher voltages. The LFP/G AEC provided 1.43 mFcm -2 at a current density of 8.85 mAcm¯² over 30 h, whereas the LFMP/G provided 4.63 mFcm -2 at a current density of 12.4 mAcm¯² over 50 h. Both capacitors showed very little internal resistance once the testing was completed. In this presentation, we will discuss in detail our findings on the various microwave-based synthetic strategies adopted for the LFP/G and LFMP/G and their electrochemical properties for the development of efficient cathode materials for lithium ion batteries and asymmetric electrochemical capacitors. References (1) I. Bilecka, A. Hintennach, I. Djerdj, P. Novàk, M. Niederberger, J. Mater. Chem. 19 (2009) 5125. (2) D. Jugović, D. Uskoković, J. Power Sources 190 (2009) 538. Figure 1
Nanobiotechnology medical applications: Overcoming challenges through innovation (2018)

Abstract Biomedical Nanotechnology (BNT) has rapidly become a revolutionary force that is driving innovation in the medical field. BNT is a subclass of nanotechnology (NT), and often operates in cohort with other subclasses, such as mechanical or electrical NT for the development of diagnostic assays, therapeutic implants, nano-scale imaging systems, and medical machinery. BNT is generating solutions to many conventional challenges through the development of enhanced therapeutic delivery systems, diagnostic techniques, and theranostic therapies. Therapeutically, BNT has generated many novel nanocarriers (NCs) that each express specifically designed physiochemical properties that optimize their desired pharmacokinetic profile. NCs are also being integrated into nanoscale platforms that further enhance their delivery by controlling and prolonging their release profile. Nano-platforms are also proving to be highly efficient in tissue regeneration when combined with the appropriate growth factors. Regarding diagnostics, NCs are being designed to perform targeted delivery of luminescent tags and contrast agents that enhance the NC -aided imaging capabilities and resulting diagnostic accuracy of the presence of diseased cells. This technology has also been advancing the ability for surgeons to practice true precision surgical techniques. Incorporating therapeutic and diagnostic NC-components within a single NC can facilitate both functions, referred to as theranostics, which facilitates real-time in vivo tracking and observation of drug release events via enhanced imaging. Additionally, stimuli-responsive theranostic NCs are quickly developing as vectors for tumor ablation therapies by providing a model that facilitates the location of cancer cells for the application of an external stimulus. Overall, BNT is an interdisciplinary approach towards health care, and has the potential to significantly improve the quality of life for humanity by significantly decreasing the treatment burden for patients, and by providing non-invasive therapeutics that confer enhanced therapeutic efficiency and safety