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Pendubot is a popular single input-multi output (SIMO) in laboratories to test control algorithms. In this paper, we focus on a developed model of pendubot – linear triple-linked pendubot (LTLP) and propose LQR to control this model. Through simulation, link 1 is kept balanced, kept following trajectories when link 2, 3 is kept upward under LQR control. Thence, besides balancing well this model at TOP position, our algorithm also makes system tracking sine and pulse trajectories well.

Summary: ADP-ribosylation is a post-translational modification involving the transfer of one or more ADP-ribose units from NAD+ to target proteins. Dysregulation of ADP-ribosylation is implicated in neurodegenerative diseases. In this study, genetic testing via exome sequencing was used to identify the underlying disease in two siblings with developmental delay, seizures, progressive muscle weakness, and respiratory failure following an episodic course. This identified a novel homozygous variant in the ADPRS gene (c.545A>G, p.His182Arg) encoding the mono(ADP-ribosyl) hydrolase ARH3, confirming the diagnosis of childhood-onset neurodegeneration with stress-induced ataxia and seizures (CONDSIAS) in these two children. Mechanistically, the ARH3H182R variant affects a highly conserved residue in the active site of ARH3, leading to protein instability, degradation, and, subsequently, reduced protein expression. The ARH3H182R mutant additionally fails to localize to the nucleus, which further resulted in accumulated mono-ADP ribosylated species in cells. The children’s clinical course combined with the biochemical characterization of their genetic variant develops our understanding of the pathogenic mechanisms driving CONDSIAS and highlights a critical role for ARH3-regulated ADP-ribosylation in nervous system integrity.

Abstract Inertial electrostatic confinement fusion (IECF) devices often use two concentric spherical electrodes to converge ions in a plasma electrostatically. Using a highly transparent inner cathode, the ions can move through the cathode and collide at the center to undergo fusion reactions. This is a simple method to build a neutron source. Past research has focused chiefly on cathode “grids” manufactured by joining metal wire loops or disc-shaped elements via spot welding. There are two common geometries: “Globe” grids with a distinct latitude-longitude structure and “symmetric” grids with even-sized triangular-shaped apertures. Recent advances in additive manufacturing have opened the way to manufacturing a third class of grids in which the apertures are evenly distributed over the grid surface and have either circular or polygonal shaped apertures - here called “regular” grids. These three types are analyzed and compared based on a set of metrics, including transparency, homogeneity of aperture size, and the regularity of aperture distribution. It is shown that every type of grid comes with different advantages and disadvantages. The analysis focuses on grid geometries with 6 to 120 apertures.

Context: The Piper species was studied several potential properties such as anti-tumor, anti-inflammatory and antioxidant activity. However, the specific anti-inflammatory activity of the extract from the fruits of P. longum L. has not been investigated. Objectives: Our study want to examine the anti-inflammatory effects of P. longum L. fruit methanolic extracts (PLE) on lipopolysachharide (LPS)-stimulated RAW 264.7 murine macrophages to understand the mechanism of this effect. Method: This study examined the chemical profiling of PLE by LC-HRMS analysis and measured the presence of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the supernatant using the Griess reagent assay and enzyme-linked immunosorbent assay (ELISA), respectively. The mRNA expression of IL-6, TNF-α, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) were evaluated by using real-time quantitative polymerase chain reaction (RT-qPCR). Furthermore, the protein expression of COX-2, iNOS and the phosphorylation of MAPK family, c-Jun N-terminal kinase (JNK), p38 in protein level were observed by western blotting. Result: PLE have detected 66 compounds which belong to different classes such as alkaloids, flavonoids, terpenoids, phenolics, lactones, and organic acids inhibited nitric oxide products with the IC50 = 28.5 ± 0.91 μg/mL. Moreover, PLE at 10–100 μg/mL up-regulate HO-1 protein expression from 3 to 10 folds at 3 h. It also downregulated the mRNA and protein expression of iNOS, COX-2, decreased IL-6 and TNF-α secretion by modulating the mitogen-activated protein kinase (MAPK) signaling pathway, specifically by decreasing the phosphorylation of p38 and JNK. Conclusion: These results shown chemical profiling of PLE and demonstrated that PLE exhibits anti-inflammatory effects by regulating the MAPK family and could be a potential candidate for the treatment of inflammatory diseases.

Using polysystem theory, the article examines the conceptions of literary researchers in Vietnam in establishing main standards in the process of literary evaluation. As a result, researchers often choose two basic and common standards: political and humanity. In particular, since the Renew (1986) until now, humanity standards have been considered by some researchers as a valuable category in the literary studies in Vietnam.

Prostate cancer (PCa) remains the most diagnosed non-skin cancer amongst the American male population. Treatment for localized prostate cancer consists of androgen deprivation therapies (ADTs), which typically inhibit androgen production and the androgen receptor (AR). Though initially effective, a subset of patients will develop resistance to ADTs and the tumors will transition to castration-resistant prostate cancer (CRPC). Second generation hormonal therapies such as abiraterone acetate and enzalutamide are typically given to men with CRPC. However, these treatments are not curative and typically prolong survival only by a few months. Several resistance mechanisms contribute to this lack of efficacy such as the emergence of AR mutations, AR amplification, lineage plasticity, AR splice variants (AR-Vs) and increased kinase signaling. Having identified SRC kinase as a key tyrosine kinase enriched in CRPC patient tumors from our previous work, we evaluated whether inhibition of SRC kinase synergizes with enzalutamide or chemotherapy in several prostate cancer cell lines expressing variable AR isoforms. We observed robust synergy between the SRC kinase inhibitor, saracatinib, and enzalutamide, in the AR-FL+/AR-V+ CRPC cell lines, LNCaP95 and 22Rv1. We also observed that saracatinib significantly decreases AR Y534 phosphorylation, a key SRC kinase substrate residue, on AR-FL and AR-Vs, along with the AR regulome, supporting key mechanisms of synergy with enzalutamide. Lastly, we also found that the saracatinib-enzalutamide combination reduced DNA replication compared to the saracatinib-docetaxel combination, resulting in marked increased apoptosis. By elucidating this combination strategy, we provide pre-clinical data that suggests combining SRC kinase inhibitors with enzalutamide in select patients that express both AR-FL and AR-Vs.

OBJECTIVES/GOALS: This study investigates whether localization of high mobility group box 1 (HMGB1) controls inflammatory signaling and DNA damage response in human keratinocytes, the cell of origin for squamous cell carcinoma (SCC). SCC is especially metastatic in chronic wounds, burns, and in patients with recessive dystrophic epidermolysis bullosa (RDEB). METHODS/STUDY POPULATION: We used CRISPR/Cas9 gene-editing to knock out HMGB1 in a keratinocyte line, p16INK4a-negative keratinocytes immortalized by ectopic hTERT expression (N/TERT-2G [46,XY]). Following gene editing, clonal keratinocyte populations were screened for knockout by PCR followed by TIDE analysis (Tracking of Indels by Decomposition) to identify indels that would result in a frameshift mutation. Total cell lysates for each clonal population were analyzed by immunoblot and immunofluorescence for HMGB1 protein. These cells will be used to assay for DNA damage sensitivity in the presence of genotoxic agents (etoposide, ultraviolet radiation, γ-irradiation). A lentiviral vector will then be used to express mutant forms of HMGB1 that localize to the nucleus (C23/45S) or cytoplasm (C106S) and DNA damage assays repeated. RESULTS/ANTICIPATED RESULTS: We have confirmed by sequencing, immunoblot, and immunofluorescence that HMGB1 is knocked out in a clonal population of N/TERT-2G human keratinocyte cells. We anticipate that cells with a complete absence of HMGB1 will have high sensitivity to DNA damaging agents, but little change in inflammatory signaling. We also expect that cells expressing mutant HMGB1 that localizes exclusively to the cytoplasm will demonstrate an increased sensitivity to DNA damage relative to wild-type controls, while mutant HMGB1 that localizes exclusively to the nucleus will be protected from DNA damage caused by exposure to genotoxic agents. DISCUSSION/SIGNIFICANCE: HMGB1 is a nuclear protein and damage associated molecular pattern that is elevated systemically in patients with RDEB, many of whom will go on to develop metastatic squamous cell carcinoma. The experiments described here investigate whether HMGB1 plays a mechanistic role in skin carcinogenesis via regulation of the DNA damage response.

Abstract This work presents experiments about the transmission of electrons with an energy of around 15 keV with beam currents up to 20 µA through macroscopic glass capillaries. A systematic study was conducted to experimentally investigate the transmission of electrons through borosilicate glass capillaries with curve angles of 90°, 180°, 270° and 360° for the first time. The focus of the work was to identify the conditions under which the injected electron current is transmitted through the capillary. It was also shown that the transmission process in the macroscopic capillaries can be optically observed by cathodoluminescence—the interaction of electrons with the capillary surface causes locally a blue glow. Different distinctive “glow states” were observed and are found to correlate with different states of electron transmission.