gebhart/patrepeval huggingface dataset:
Threatened OHSS in a long GnRH agonist protocol (2015)

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Myeloid Cell-Mediated Trained Innate Immunity in Mucosal AIDS Vaccine Development (2020)

Trained innate immunity has recently emerged as a novel concept of innate immune cells, such as myeloid cells, exhibiting immune memory, and nonspecific heterologous immunity to protect against infections. The memory and specificity are mediated by epigenetic, metabolic, and functional reprogramming of the myeloid cells and myeloid progenitors (and/or NK cells) in the bone marrow and peripheral tissues such as gut and lung mucosa. A variety of agents, such as BCG, viruses, and their components, as well as TLR agonists, and cytokines have been shown to be involved in the induction of trained immunity. Since these agents have been widely used in AIDS vaccine development as antigen delivery vectors or adjuvants, myeloid cell mediated trained immunity might also play an important role in protecting against mucosal AIDS virus transmission or in control of virus replication in the major gut mucosal reservoir. Here we review the trained innate immunity induced by these vectors/adjuvants that have been used in AIDS vaccine studies and discuss their role in mucosal vaccine efficacy and possible utilization in AIDS vaccine development. Delineating the protective effect of the trained innate immunity mediated by myeloid cells will guide the design of novel AIDS vaccines.
T cell landscape within primary melanoma as a biomarker of survival after cancer vaccination in patients with metastatic disease (2015)

Meeting abstracts Melanoma is a highly malignant melanocyte-derived tumor and its incidence is increasing at outstanding rate. Despite different types of immunotherapy became available for the treatment of melanoma, including adoptive T cell transfer, immune checkpoint blockade, and vaccines such
An Investigation of Turbine Wheelspace Cooling Flow Interactions With a Transonic Hot Gas Path—Part II: CFD Simulations (2011)

A computational model has been developed to study the mechanisms responsible for hot gas ingestion into the wheel-space cavity of a stationary high pressure turbine (HPT) cascade rig. Simulations were undertaken for the stationary rig described by Bunker et al. (2009, “An Investigation of Turbine Wheelspace Cooling Flow Interactions With a Transonic Hot Gas Path—Part I: Experimental Measurements,” ASME Paper No. GT2009-59237) in a companion paper. The rig consists of five vanes, a wheel-space cavity, and five cylinders that represent the blockage due to the leading edge of the rotor airfoils. The experimental program investigated two cylinder diameters and three clocking positions for a nominal coolant flow rate. Comparisons are made between the computed and measured flow-fields for the smaller of the two cylinders. It is demonstrated that the circumferential variation of pressure established by the vane wake and leading edge bow wave results in an unstable shear layer over the rim seal axial gap (trench) that causes hot gases to ingest for a nominal coolant flow. Steady-state computational fluid dynamics (CFD) simulations did not capture this effect and it was determined that an unsteady analysis was required in order to match the experimental data. Favorable agreement is noted between the time-averaged computed and measured pressure distributions in the circumferential direction both upstream and downstream of the trench, as well as within the trench itself. Furthermore, it is noted that time-averaged buffer cavity effectiveness agrees to within 5% of the experimental data for the cases studied. The validated CFD model is then used to simulate the effect of rotation by rotating the cylinders and disk at rotational rate that scales with a typical engine. A sliding mesh interface is utilized to communicate data between the stator and rotor domains. The stationary cases tend to ingest past the first angel-wing for a nominal coolant flow condition, whereas the effect of rotation helps pressurize the cavity and is responsible for preventing hot gas from entering the buffer cavity.
Abstract 6794: SETD2 loss in renal cell carcinoma generates peptides from aberrantly translated retained introns (2023)

Abstract Introduction: SETD2, a histone H3-K36 trimethyltransferase, is necessary for regulation of proper intron splicing. SETD2 is frequently inactivated in kidney cancer. We hypothesized that SETD2 deficiency would cause aberrant translation of retained introns (ATaRI) that could serve as potential immunotherapeutic targets in SETD2-mutant states. Methods and Results: We detected increased presence of retained introns in SETD2-mutant vs WT tumors in two publicly available renal cell carcinoma RNA-seq data sets. We hypothesized that if intronic sequences translated into proteins, accumulation of misfolded proteins would activate the Unfolded Protein Response (UPR). The UPR pathway was strongly transcriptionally enriched as measured by GSEA, as were several immunotherapy-relevant pathways, suggesting that tumors are inflamed, possibly related to the antigenic nature of translated introns. To investigate this further, we generated Setd2-isogenic mouse renal cancer cells using CRISPR in the RENCA cell line. RNAseq followed by GSEA confirmed upregulation of UPR pathway transcriptional signature in the Setd2-null condition, supporting our observation in human tumors. Indicators of UPR activation such as cleavage of ATF6 and increase in ATF4 and Xbp1 levels in Setd2 deficient vs. unedited RENCA cells, as well as nuclear translocation of ATF6 in SETD2-mutant human kidney cancer samples validates these findings. We then measured the presence of ATaRI-derived peptides in Setd2-mutant RENCA cells using mass spectrometry, detecting 47 such peptides. Using publicly available proteomics data from one human data set, we preliminarily identified peptides translated from 151 introns that are retained in SETD2-mutant cases. Applying netMHCpan to both the human and murine data, we found that detectable ATaRI peptides were predicted to generate multiple 10-amino acid-long peptides which strongly bind to the 8 murine MHC or to the 20 most common human HLA receptors. We propose that these presentable peptides might activate an immune response to SETD2-mutant renal cell carcinoma. Conclusions: We identified intron retention which may cause activation of the UPR as a feature of SETD2-mutant kidney cancer. ATaRI peptides are detectable and should be presented to the adaptive immune system. These features may represent a new therapeutic vulnerability for exploitation as a rationale for personalized medicine. Citation Format: Marya T. Kozinova, Alexander Metz, Robert Uzzo, Janusz Franco-Barraza, Michael Slifker, Jessica Peskin, Angel Fernández Sanromán, Samra Turajlic, Edna Cukierman, Phillip Phillip Abbosh. SETD2 loss in renal cell carcinoma generates peptides from aberrantly translated retained introns. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6794.
Florodeoxyglucose imaging: A method to assess the proliferative activity of human cancer in vivo. Comparison with DNA flow cytometry in head and neck tumors (1988)

Thirteen patients with malignant head and neck tumors were studied before they were treated with (18F) fluorodeoxyglucose (FDG) imaging and DNA flow cytometry (FCM). The nuclear DNA content and the percentage of proliferative cells (S + G2/M) were compared with the FDG uptake; FDG was retained in the primary tumor and/or neck metastasis in all patients. The accumulation of FDG did not correlate with histologic grade of the tumors, but there was a clear correlation (r = 0.86, P less than 0.001) between the proportion of the cells in S + G2/M phases of the cell cycle and the intensity of FDG accumulation. The uptake of FDG by the tumor also correlated with the percentage of S-phase cells (r = 0.82, P less than 0.001). The result suggests that enhanced glucose metabolism, measured by FDG uptake, is associated with the proliferative activity of the tumor. Thus, imaging with FDG may offer a new method to assess the aggressiveness of human cancer growth in vivo.
Oxygen sensing ability of positronium atom for tumor hypoxia imaging (2020)

Abstract Positronium (Ps), a hydrogen-like atom consisting of a positron and an electron, is efficiently formed in the human body during positron emission tomography (PET) examination, and its decay rate into gamma-ray photons is significantly influenced by the chemical environment, especially the dissolved oxygen concentration (pO 2 ) due to the unpaired electrons. However, the functionality of PET has been underestimated by neglecting the specific information provided by Ps. By comparing the decay rates in O 2 -, N 2 -, and air-saturated waters, here we show that Ps probes the absolute value of pO 2 with a good linearity and a resolution better than 10 mmHg. This is a sufficient sensitivity for discriminating a hypoxic region in a tumor at approximately 6 mmHg from healthy tissues at approximately 40 mmHg. This method depends only on the fundamental properties of Ps and is independent of specific radiopharmaceuticals. The applications of Ps spin states and reactions will greatly enhance PET functionalities in the next decade.
Effect of Steeping with Sulfite Salts and Adjunct Acids on Corn Wet‐Milling Yields and Starch Properties (2005)

ABSTRACT Two corn hybrids (3394 and 33R87) were steeped with three sulfite salts and five acids to test the effect of sulfur dioxide (SO 2 ) source and acid sources on wet‐milling yields and starch properties. Milling yields from each treatment were compared with a control sample that was steeped with 2,000 ppm of SO 2 (using sodium metabisulfite) and 0.55% lactic acid. Sulfur dioxide sources were potassium sulfite, sodium sulfite, and ammonium sulfite; acids were acetic, hydrochloric, oxalic, phosphoric, and sulfuric. Starch yields were affected by the SO 2 source and steep acids but the effects were hybrid‐dependent. Different steep acids gave different starch yields when wet milled at the same pH. Among the acids tested, weak acids (lactic and acetic) tended to give higher starch yields compared with strong acids (hydrochloric, sulfuric, phosphoric, and oxalic). Some differences were observed with different sulfite salts and acids on starch pasting properties; however, there were no clear trends.
Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a “Tail Switching” Strategy on a Piperazinyl Azetidine Skeleton (2019)

Monoacylglycerol lipase (MAGL) is a serine hydrolase that degrades 2-arachidonoylglycerol (2-AG) in the endocannabinoid system (eCB). Selective inhibition of MAGL has emerged as a potential therapeutic approach for the treatment of diverse pathological conditions, including chronic pain, inflammation, cancer, and neurodegeneration. Herein, we disclose a novel array of reversible and irreversible MAGL inhibitors by means of "tail switching" on a piperazinyl azetidine scaffold. We developed a lead irreversible-binding MAGL inhibitor 8 and reversible-binding compounds 17 and 37, which are amenable for radiolabeling with <sup>11</sup>C or <sup>18</sup>F. [<sup>11</sup>C]8 ([<sup>11</sup>C]MAGL-2-11) exhibited high brain uptake and excellent binding specificity in the brain toward MAGL. Reversible radioligands [<sup>11</sup>C]17 ([<sup>11</sup>C]PAD) and [<sup>18</sup>F]37 ([<sup>18</sup>F]MAGL-4-11) also demonstrated excellent in vivo binding specificity toward MAGL in peripheral organs. This work may pave the way for the development of MAGL-targeted positron emission tomography tracers with tunability in reversible and irreversible binding mechanisms.
The Use of Polymer Blends in the Treatment of Ocular Diseases (2022)

The eye is an organ with limited drug access due to its anatomical and physiological barriers, and the usual forms of ocular administration are limited in terms of drug penetration, residence time, and bioavailability, as well as low patient compliance. Hence, therapeutic innovations in new drug delivery systems (DDS) have been widely explored since they show numerous advantages over conventional methods, besides delivering the content to the eye without interfering with its normal functioning. Polymers are usually used in DDS and many of them are applicable to ophthalmic use, especially biodegradable ones. Even so, it can be a hard task to find a singular polymer with all the desirable properties to deliver the best performance, and combining two or more polymers in a blend has proven to be more convenient, efficient, and cost-effective. This review was carried out to assess the use of polymer blends as DDS. The search conducted in the databases of Pubmed and Scopus for specific terms revealed that although the physical combination of polymers is largely applied, the term polymer blend still has low compliance.
CD4-Specific Transgenic Expression of Human Cyclin T1 Markedly Increases Human Immunodeficiency Virus Type 1 (HIV-1) Production by CD4+T Lymphocytes and Myeloid Cells in Mice Transgenic for a Provirus Encoding a Monocyte-Tropic HIV-1 Isolate (2006)

Human immunodeficiency virus type 1 (HIV-1)-encoded Tat provides transcriptional activation critical for efficient HIV-1 replication by interacting with cyclin T1 and recruiting P-TEFb to efficiently elongate the nascent HIV transcript. Tat-mediated transcriptional activation in mice is precluded by species-specific structural differences that prevent Tat interaction with mouse cyclin T1 and severely compromise HIV-1 replication in mouse cells. We investigated whether transgenic mice expressing human cyclin T1 under the control of a murine CD4 promoter/enhancer cassette that directs gene expression to CD4(+) T lymphocytes and monocytes/macrophages (hu-cycT1 mice) would display Tat responsiveness in their CD4-expressing mouse cells and selectively increase HIV-1 production in this cellular population, which is infected primarily in HIV-1-positive individuals. To this end, we crossed hu-cycT1 mice with JR-CSF transgenic mice carrying the full-length HIV-1(JR-CSF) provirus under the control of the endogenous HIV-1 long terminal repeat and demonstrated that human cyclin T1 expression is sufficient to support Tat-mediated transactivation in primary mouse CD4 T lymphocytes and monocytes/macrophages and increases in vitro and in vivo HIV-1 production by these stimulated cells. Increased HIV-1 production by CD4(+) T lymphocytes was paralleled with their specific depletion in the peripheral blood of the JR-CSF/hu-cycT1 mice, which increased over time. In addition, increased HIV-1 transgene expression due to human cyclin T1 expression was associated with increased lipopolysaccharide-stimulated monocyte chemoattractant protein 1 production by JR-CSF mouse monocytes/macrophages in vitro. Therefore, the JR-CSF/hu-cycT1 mice should provide an improved mouse system for investigating the pathogenesis of various aspects of HIV-1-mediated disease and the efficacies of therapeutic interventions.
Rewiring a secondary metabolite pathway towards itaconic acid production in Aspergillus niger (2016)

Expression of the IA biosynthesis cluster in Aspergillus niger AB1.13 strain enables IA production. Moreover, in the AB1.13 CAD strain IA production resulted in overexpression of a putative cytosolic citrate synthase citB. Upon overexpression of citB we have achieved titers of up to 26.2 g/L IA with a productivity of 0.35 g/L/h in controlled batch cultivations. By overexpressing citB we have also diminished side product formation and optimized the production pathway towards IA.
ChemInform Abstract: Regio‐ and Stereocontrolled Syntheses of Cyclic Chiral cis‐Amino Alcohols from 1,2‐Diols or Epoxides. (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Immunodynamics: a cancer immunotherapy trials network review of immune monitoring in immuno-oncology clinical trials (2016)

The efficacy of PD-1/PD-L1 targeted therapies in addition to anti-CTLA-4 solidifies immunotherapy as a modality to add to the anticancer arsenal. Despite raising the bar of clinical efficacy, immunologically targeted agents raise new challenges to conventional drug development paradigms by highlighting the limited relevance of assessing standard pharmacokinetics (PK) and pharmacodynamics (PD). Specifically, systemic and intratumoral immune effects have not consistently correlated with standard relationships between systemic dose, toxicity, and efficacy for cytotoxic therapies. Hence, PK and PD paradigms remain inadequate to guide the selection of doses and schedules, both starting and recommended Phase 2 for immunotherapies. The promise of harnessing the immune response against cancer must also be considered in light of unique and potentially serious toxicities. Refining immune endpoints to better inform clinical trial design represents a high priority challenge. The Cancer Immunotherapy Trials Network investigators review the immunodynamic effects of specific classes of immunotherapeutic agents to focus immune assessment modalities and sites, both systemic and importantly intratumoral, which are critical to the success of the rapidly growing field of immuno-oncology.
Nuclear Inositide Signaling Via Phospholipase C (2017)

The existence of an independent nuclear inositide pathway distinct from the cytoplasmic one has been demonstrated in different physiological systems and in diseases. In this prospect we analyze the role of PI-PLCβ1 nuclear isoform in relation to the cell cycle regulation, the cell differentiation, and different physiopathological pathways focusing on the importance of the nuclear localization from both molecular and clinical point of view. PI-PLCβ1 is essential for G1/S transition through DAG and Cyclin D3 and plays also a central role in G2/M progression through Cyclin B1 and PKCα. In the differentiation process of C2C12 cells PI-PLCβ1 increases in both myogenic differentiation and osteogenic differentiation. PI-PLCβ1 and Cyclin D3 reduction has been observed in Myotonic Dystrophy (DM) suggesting a pivotal role of these enzymes in DM physiopathology. PI-PLCβ1 is also involved in adipogenesis through a double phase mechanism. Moreover, PI-PLCβ1 plays a key role in the normal hematopoietic differentiation where it seems to decrease in erythroid differentiation and increase in myeloid differentiation. In Myelodysplastic Syndromes (MDS) PI-PLCβ1 has a genetic and epigenetic relevance and it is related to MDS patients' risk of Acute Myeloid Leukemia (AML) evolution. In MDS patients PI-PLCβ1 seems to be also a therapeutic predictive outcome marker. In the central nervous system, PI-PLCβ1 seems to be involved in different pathways in both brain cortex development and synaptic plasticity related to different diseases. Another PI-PLC isozyme that could be related to nuclear activities is PI-PLCζ that is involved in infertility processes. J. Cell. Biochem. 118: 1969-1978, 2017. © 2017 Wiley Periodicals, Inc.
Modélisation des valeurs extrêmes des courants induits par des interférences électromagnétiques (2013)

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Chipless identification applied to human body (2014)

We report in this paper the study of the identification of persons using a Radio Frequency IDentification (RFID) chipless tag. Obtained results show that a robust identification is possible due to the capability of the tag to generate a cross polarization that is used for the identification. Simulations and measurements of a chipless tag placed on a body have been made. By this way, the tag could be easily designed to be an integral part of a clothing.
Crystal structures of two active proliferating cell nuclear antigens (PCNAs) encoded by Thermococcus kodakaraensis (2011)

Proliferating cell nuclear antigen (PCNA) is a ring-shaped protein that encircles duplex DNA and plays an essential role in many DNA metabolic processes in archaea and eukarya. The eukaryotic and euryarchaea genomes contain a single gene encoding for PCNA. Interestingly, the genome of the euryarchaeon Thermococcus kodakaraensis contains two PCNA-encoding genes (TK0535 and TK0582), making it unique among the euryarchaea kingdom. It is shown here that the two T. kodakaraensis PCNA proteins support processive DNA synthesis by the polymerase. Both proteins form trimeric structures with characteristics similar to those of other archaeal and eukaryal PCNA proteins. One of the notable differences between the TK0535 and TK0582 rings is that the interfaces are different, resulting in different stabilities for the two trimers. The possible implications of these observations for PCNA functions are discussed.
Over-expression and single-step purification of human IFNα8 and human IFNα2b reveals the highest antiviral activity of human IFNα8 (2006)

Hu IFN 8 gene one minor codon AUA (ATA triplet, that encodes for Ile) is present in the first cluster, while in the second one, the CUA (CTA triplet, that encodes for Leu) exists.
Simulation of computational ghost imaging: application for 3D measurement (2019)

Cameras are common imaging elements in optical measurement systems. A different approach to imaging utilizes only a single pixel sensor and is nevertheless capable of producing two-dimensional images: In computational ghost imaging (CGI) a projector illuminates the object with a known set of patterns and a single photodiode records the resulting radiation powers. These are passed on to a reconstruction algorithm. Such setups can be advantageous where classical camera systems might fail or be too expensive, but cannot currently compete with them in high speed imaging applications. Although the idea is not new, it represents a very different and rarely used paradigm compared to conventional approaches to two- and three-dimensional imaging. Three-dimensional reconstruction through CGI can be achieved through well-known techniques such as photogrammetric stereo reconstruction. Theoretical work has shown that for an actual setup having a single projector and two photodiodes arranged in a parallax is not sufficient. Instead, two projectors and a single photodiode in combination with a computer are necessary for the production of two images suitable for stereo reconstruction. Two characteristics of a CGI setup should play an important role in its technical implementation. These are the type of projected patterns and the sensor dynamic range. A two-dimensional simulation showed that the type of patterns, the sensor’s dynamic range and also the dynamic range of the projector are crucial design aspects. A threedimensional photometric simulation of the setup was designed. It adds a proof of concept to CGI with backscattered light and showed that it can be used for stereo reconstruction. Experiments in the future shall reveal more details about the technical implementation. In this submission we present the introduced novel 3D sensor approach and the most significant details of the simulation results.