Distributional hypothesis as isomorphism between word-word co-occurrence and analogical parallelograms.

Most of the modern natural language processing (NLP) techniques are based on the vector space models of language, in which each word is represented by a vector in a high dimensional space. One of the earliest successes was demonstrated by the four-term analogical reasoning task: what is to C as B is to A? The trained word vectors form "parallelograms" representing the quadruple of words in analogy. This discovery in NLP offers us insight into our understanding of human semantic representation of words via analogical reasoning.

Polymeric nanocapsules loaded with poly(I:C) and resiquimod to reprogram tumor-associated macrophages for the treatment of solid tumors.

Background: In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play a key immunosuppressive role that limits the ability of the immune system to fight cancer. Toll-like receptors (TLRs) ligands, such as poly(I:C) or resiquimod (R848) are able to reprogram TAMs towards M1-like antitumor effector cells. The objective of our work has been to develop and evaluate polymeric nanocapsules (NCs) loaded with poly(I:C)+R848, to improve drug stability and systemic toxicity, and evaluate their targeting and therapeutic activity towards TAMs in the TME of solid tumors.

Pathological and genomic features of myeloproliferative neoplasms associated with splanchnic vein thrombosis in a single-center cohort.

Here, we reviewed clinical-morphological data and investigated mutational profiles by NGS in a single-center series of 58 consecutive MPN-SVT patients admitted to our hospital between January 1979 and November 2021. We identified 15.5% of PV, 13.

In Vitro Methods to Evaluate Macrophage Polarization and Function in Cancer.

Tumor-associated macrophages (TAMs) play a key immunosuppressive role that limits the ability of the immune system to fight cancer and hinder the anti-tumoral efficacy of most treatments currently applied in the clinic. However, a key feature of macrophages is their phenotypical and functional plasticity, which called their attention as promising targets for therapeutic intervention based on their elimination or reprogramming toward M1-like cytotoxic effector cells, with anti-tumor functions. This polarization status of macrophages can be studied in terms of molecular markers and functional activities, using an appropriate combination of experimental methodologies, both in vitro and in vivo.

Single-Cell RNA Sequencing for the Detection of Clonotypic V(D)J Rearrangements in Multiple Myeloma.

Multiple myeloma (MM) has a highly heterogeneous genetic background, which complicates its molecular tracking over time. Nevertheless, each MM patient's malignant plasma cells (PCs) share unique V(D)J rearranged sequences at immunoglobulin loci, which represent ideal disease biomarkers. Because the tumor-specific V(D)J sequence is highly expressed in bulk RNA in MM patients, we wondered whether it can be identified by single-cell RNA sequencing (scRNA-seq).

Mannose-modified hyaluronic acid nanocapsules for the targeting of tumor-associated macrophages.

Tumor-associated macrophages (TAMs), a class of immune cells that play a key role in tumor immunosuppression, are recognized as important targets to improve cancer prognosis and treatment. Consequently, the engineering of drug delivery nanocarriers that can reach TAMs has acquired special relevance. This work describes the development and biological evaluation of a panel of hyaluronic acid (HA) nanocapsules (NCs), with different compositions and prepared by different techniques, designed to target macrophages.

Functional Impact of Genomic Complexity on the Transcriptome of Multiple Myeloma.

Purpose: Multiple myeloma is a biologically heterogenous plasma-cell disorder. In this study, we aimed at dissecting the functional impact on transcriptome of gene mutations, copy-number abnormalities (CNA), and chromosomal rearrangements (CR). Moreover, we applied a geno-transcriptomic approach to identify specific biomarkers for personalized treatments.

A Journey Through Myeloma Evolution: From the Normal Plasma Cell to Disease Complexity.

The knowledge of cancer origin and the subsequent tracking of disease evolution represent unmet needs that will soon be within clinical reach. This will provide the opportunity to improve patient's stratification and to personalize treatments based on cancer biology along its life history. In this review, we focus on the molecular pathogenesis of multiple myeloma (MM), a hematologic malignancy with a well-known multi-stage disease course, where such approach can sooner translate into a clinical benefit.

A Windmill-Shaped Molecule with Anthryl Blades to Form Smooth Hole-Transport Layers via a Photoprecursor Approach.

Preparation of high-performance organic semiconductor devices requires precise control over the active-layer structure. To this end, we are working on the controlled deposition of small-molecule semiconductors through a photoprecursor approach wherein a soluble precursor compound is processed into a thin-film form and then converted to a target semiconductor by light irradiation. This approach can be applied to layer-by-layer solution deposition, enabling the preparation of p-i-n-type photovoltaic active layers by wet processing.

PLGA Based Nanoparticles for the Monocyte-Mediated Anti-Tumor Drug Delivery System.

Together with the development of new therapeutic agents, innovation in the delivery system of anti-tumor drugs is required to increase tumor-specificity and avoid unexpected toxicity. To achieve higher efficiency, we combined a live cell-mediated drug delivery system with nanotechnology, with the aim to prove that blood monocytes can be a cargo to deliver antitumor drugs encapsulated in Polymeric poly(D, L-lactide-co-glycolide) acid based nanoparticles (PLGA NPs). In this study, we have characterized how isolated purified monocytes efficiently internalize PLGA-NPs and have imaged their trafficking upon intravenous injection in tumor-bearing mice.

Poly(I:C) stimulation is superior than Imiquimod to induce the antitumoral functional profile of tumor-conditioned macrophages.

Macrophage plasticity is the ability of mononuclear phagocytes to change phenotype, function, and genetic reprogramming upon encounter of specific local stimuli. In the tumor microenvironment, Tumor-Associated Macrophages (TAMs) acquire an immune-suppressive and tumor-promoting phenotype. With the aim to re-educate TAMs to antitumor effectors, in this study, we used two immunestimulatory compounds: the TLR7 agonist Imiquimod (IMQ) and the TLR3 agonist Poly(I:C).

Targeting Cancer Cells and Tumor Microenvironment in Preclinical and Clinical Models of Hodgkin Lymphoma Using the Dual PI3Kδ/γ Inhibitor RP6530.

Purpose: Tumor-associated macrophages (TAMs) and the hyperactivation of the PI3K/AKT pathway are involved in the pathogenesis of Hodgkin lymphoma and affect disease outcome. Because the δ and γ isoforms of PI3K are overexpressed in Hodgkin/Reed-Sternberg (HRS) cells and the tumor microenvironment (TME), we propose that the PI3Kδ/γ inhibitor RP6530 might affect both HRS cells and TME, ultimately leading to an enhanced antitumor response.

Experimental Design: Hodgkin lymphoma cell lines (L-540, KM-H2, and L-428) and primary human macrophages were used to investigate the activity of RP6530 and in Hodgkin lymphoma cell line xenografts.

High-Mobility p-Type and n-Type Copper Nitride Semiconductors by Direct Nitriding Synthesis and In Silico Doping Design.

Thin-film photovoltaics (PV) have emerged as a technology that can meet the growing demands for efficient and low-cost large-scale cells. However, the photoabsorbers currently in use contain expensive or toxic elements, and the difficulty in bipolar doping, particularly in a device structure, requires elaborate optimization of the heterostructures for improving the efficiency. This study shows that bipolar doping with high hole and electron mobilities in copper nitride (Cu N), composed solely of earth-abundant and environmentally benign elements, is readily available through a novel gaseous direct nitriding reaction applicable to uniform and large-area deposition.

Establishment of a Direct-Injection Electron Ionization-Mass Spectrometry Metabolomics Method and Its Application to Lichen Profiling.

Direct-injection electron ionization-mass spectrometry (DI-EI-MS) is a multivariate analysis method useful for characterizing biological materials. We demonstrated the use of DI-EI-MS for metabolic profiling using several closely related lichen species: Cladonia krempelhuberi, C. gracilis, C.

Dichotomous roles for externalized cardiolipin in extracellular signaling: Promotion of phagocytosis and attenuation of innate immunity.

Among the distinct molecular signatures present in the mitochondrion is the tetra-acylated anionic phospholipid cardiolipin, a lipid also present in primordial, single-cell bacterial ancestors of mitochondria and multiple bacterial species today. Cardiolipin is normally localized to the inner mitochondrial membrane; however, when cardiolipin becomes externalized to the surface of dysregulated mitochondria, it promotes inflammasome activation and stimulates the elimination of damaged or nonfunctional mitochondria by mitophagy. Given the immunogenicity of mitochondrial and bacterial membranes that are released during sterile and pathogen-induced trauma, we hypothesized that cardiolipins might function as "eat me" signals for professional phagocytes.

Determination of trace iron in the boiler water used in power generation plants by solid-phase spectrophotometry.

A sensitive, simple and low-cost determination method for the total iron concentration in boiler water systems of power generation plants was developed by solid phase spectrometry (SPS) using 2,4,6-tris(2-pyridyl)-1,3,5-triazine (TPTZ) as a coloring agent. The reagents and 0.08 cm(3) of a cation exchanger were added to a 50-cm(3) boiler water sample, then mixed for 30 min to adsorb/concentrate the produced Fe(TPTZ)2(2+) colored complex on the solid beads, resulting in a 625 times concentration of the target analyte without any other procedure.

Time-resolved IR spectroscopy of 1,3-dicyanophenylcyclopentane-1,3-diyl diradicals: CN stretching wavenumber as a vibrational signature of radical character.

CN stretch bands of singlet and triplet cyclopentane-1,3-diyl diradicals (1,3-di(4-cyanophenyl)-2,2-dimethoxyoctahydropentalene-1,3-diyl and 1,3-di(4-cyanophenyl)-2,2-dimethyloctahydropentalene-1,3-diyl) were observed by time-resolved IR spectroscopy. CN stretching wavenumbers of the singlet and triplet diradicals were downshifted by 10 and 19 cm(-1) from those of their corresponding ring-closed compounds, which are in closed-shell electronic states, respectively. The observed downshifts are attributed to the bond-order decrease in the CN bonds due to the contribution from a resonance structure that has cumulative double bonds (C ═ C ═ N(•)) at the para-positions of the radical carbons.

Hepatic arterial embolization for unresectable hepatocellular carcinomas: do technical factors affect prognosis?

Purpose: To evaluate retrospectively whether technical factors of hepatic arterial embolization affect the prognosis of patients with hepatocellular carcinoma (HCC).

Materials And Methods: Inclusion criteria of this study were the following: (1) patients received embolization as the initial treatment during 2003-2004, (2) Child A or B liver profile, (3) five or fewer HCCs with maximum diameter of 7 cm or smaller, and (4) no extrahepatic metastasis. Patient data were gathered from 43 centers.

A mitochondria-targeted inhibitor of cytochrome c peroxidase mitigates radiation-induced death.

The risk of radionuclide release in terrorist acts or exposure of healthy tissue during radiotherapy demand potent radioprotectants/radiomitigators. Ionizing radiation induces cell death by initiating the selective peroxidation of cardiolipin in mitochondria by the peroxidase activity of its complex with cytochrome c leading to release of haemoprotein into the cytosol and commitment to the apoptotic program. Here we design and synthesize mitochondria-targeted triphenylphosphonium-conjugated imidazole-substituted oleic and stearic acids that blocked peroxidase activity of cytochrome c/cardiolipin complex by specifically binding to its haem-iron.

Are mitochondrial reactive oxygen species required for autophagy?

Reactive oxygen species (ROS) are said to participate in the autophagy signaling. Supporting evidence is obscured by interference of autophagy and apoptosis, whereby the latter heavily relies on ROS signaling. To dissect autophagy from apoptosis we knocked down expression of cytochrome c, the key component of mitochondria-dependent apoptosis, in HeLa cells using shRNA.