Medical devices and methods of using medical devices are disclosed. An example tissue retraction device includes a first engagement member having a first end and a second end, a second engagement member having a first end and a second end, a first elastic member attached to the second end of the first engagement member, and a first alignment member having a first end, a second end and a lumen extending therethrough. Further, the tissue retraction device has a first length, the first alignment member has a second length, the first elastic member extends within the lumen of the first alignment member and the second length of the first alignment member is less than or equal to the first length of the tissue retraction device.
The present disclosure relates to the field of tissue dissection. Specifically, the present disclosure relates to medical devices that lift and retract tissue during a dissection procedure to improve visualization of the target tissue and mitigate obstructions for dissection tools. In particular, the present disclosure relates to devices that transition from a constrained to an unconstrained bowed configuration to immobilize and retract the dissected portion of target tissue during a dissection procedure.
Lee, Matthew R.
Plewe, Michael B.
BRAF is among the most frequently mutated oncogenes in human cancers. Multiple small molecule BRAF kinase inhibitors have been approved for treating melanoma carrying BRAF-V600 mutations. However, the benefits of BRAF kinase inhibitors are generally short-lived. Small molecule-mediated targeted protein degradation has recently emerged as a novel pharmaceutical strategy to remove disease proteins through hijacking the cellular ubiquitin proteasome system (UPS). In this study, we developed thalidomide-based heterobifunctional compounds that induced selective degradation of BRAF-V600E, but not the wild-type BRAF. Downregulation of BRAF-V600E suppressed the MEK/ERK kinase cascade in melanoma cells and impaired cell growth in culture. Abolishing the interaction between degraders and cereblon or blocking the UPS significantly impaired the activities of these degraders, validating a mechanistic role of UPS in mediating targeted degradation of BRAF-V600E. These findings highlight a new approach to modulate the functions of oncogenic BRAF mutants and provide a framework to treat BRAF-dependent human cancers.
Tula, Anjan K.
Mansouri, Seyed Soheil
A number of powerful tools have been developed for process simulation, optimization, and design. However, the current software in Process Systems Engineering is mainly focused on processes without consideration of controller design or validation. Therefore, there is always a demand for integrated platforms for solving various process design and control problems. In this paper, an integrated software, ProCACD, developed for solution and analysis of control related problems is presented. Embedded within the software architecture are process design methods, analysis methods, integrated tools, and a library of process models that allow users to study a wide range of problems. With ProCACD, users can solve problems involving generation of process models, steady-state and/or dynamic simulations, analysis of process dynamics in open-loop and/or closed-loop, design of the controller structure, and solving integrated process-control design problems. The application of the software-tool is highlighted through four examples that illustrate the use of features available in ProCACD. (C) 2020 Elsevier Ltd. All rights reserved.
DNA is the carrier of genetic information. DNA modifications play a central role in essential physiological processes. Phosphorothioation (PT) modification involves the replacement of an oxygen atom on the DNA backbone with a sulfur atom. PT modification can cause genomic instability in Salmonella enterica under hypochlorous acid stress. This modification restores hydrogen peroxide (H2O2) resistance in the catalase-deficient Escherichia coli Hpx(-) strain. Here, we report biochemical characterization results for a purified PT modification protein complex (DndCDE) from S. enterica. We observed multiplex oligomeric states of DndCDE by using native PAGE. This protein complex bound avidly to PT-modified DNA. DndCDE with an intact iron-sulfur cluster (DndCDE-FeS) possessed H2O2 decomposition activity, with a V-max of 10.58 +/- 0.90 mM min(-1) and a half-saturation constant, K-0.5S, of 31.03 mM. The Hill coefficient was 2.419 +/- 0.59 for this activity. The protein's activity toward H2O2 was observed to be dependent on the intact DndCDE and on the formation of an iron-sulfur (Fe-S) cluster on the DndC subunit. In addition to cysteine residues that mediate the formation of this Fe-S cluster, other cysteine residues play a catalytic role. Finally, catalase activity was also detected in DndCDE from Pseudomonas fluorescens Pf0-1. The data and conclusions presented suggest that DndCDE-FeS is a short-lived catalase. Our experiments also indicate that the complex binds to PT sites, shielding PT DNA from H2O2 damage. This catalase shield might be able to extend from PT sites to the entire bacterial genome. IMPORTANCE DNA phosphorothioation has been reported in many bacteria. These PT-hosting bacteria live in very different environments, such as the human body, soil, or hot springs. The physiological function of DNA PT modification is still elusive. A remarkable property of PT modification is that purified genomic PT DNA is susceptible to oxidative cleavage. Among the oxidants, hypochlorous acid and H2O2 are of physiological relevance for human pathogens since they are generated during the human inflammation response to bacterial infection. However, expression of PT genes in the catalase-deficient E. coli Hpx(-) strain restores H2O2 resistance. Here, we seek to solve this obvious paradox. We demonstrate that DndCDE-FeS is a short-lived catalase that binds tightly to PT DNA. It is thus possible that by docking to PT sites the catalase activity protects the bacterial genome against H2O2 damage.
Cardiac hypertrophy with maladjusted cardiac remodeling is the leading cause of heart failure. In the past decades, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been proved to exert multiple functions in cellular biological behaviors; however, their role in cardiac hypertrophy remains largely unclear. Presently, we first obtained hypertrophic H9c2 cells by treating with angiotensin II (Ang II) and uncovered upregulation of lncRNA taurine upregulated gene 1 (TUG1) in such H9c2 cells. Then, we demonstrated that silencing TUG1 attenuated Ang II-induced cardiac hypertrophy. Besides, a strong interactivity of TUG1 with miR-29b-3p at the putative sites was validated, suggesting that TUG1 was an endogenous sponge of miR-29b-3p in H9c2 cells. Additionally, the expression of miR-29b-3p was strikingly reduced by TUG1 upregulation and also inhibited under Ang II treatment, whereas it was restored after silencing TUG1 in hypertrophic cells. Also, we proved miR-29b-3p as a negative regulator in cardiac hypertrophy. Finally, miR-29b-3p inhibition abolished the anti-hypertrophy effect of TUG1 depletion in Ang II-treated H9c2 cells. Collectively, our findings confirmed that TUG1 functioned as a positive modulator of cardiac hypertrophy via sponging miR-29b-3p, indicating that TUG1 might serve as a potential target for the treatment of cardiac hypertrophy and even heart failure.
Introduction: Osteosarcoma is the most common bone tumor with high metastasis and recurrence rate. MicroRNA-19a (miR-19a) has been reported to act as tumor oncogene in multiple cancers. The objective of the study was to explore the molecular mechanisms of miR-19a in osteosarcoma cell migration and invasion. Materials and methods: Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting were employed to measure the levels of miR-19a and RhoB in osteosarcoma tissues and cell lines. Transwell assay was employed to analyze the tissues and cell lines' migratory and invasive abilities. Dual luciferase reporter assay was utilized to analyze the association between miR-19a and RhoB. Results: MiR-19a was overexpressed in osteosarcoma tissues and cell lines. MiR-19a promoted osteosarcoma cell migration and invasion in vitro. RhoB was thus confirmed as a direct and functional target of miR-19a, and it could partially reverse the function of miR-19a. Knockdown miR-19a inhibited osteosarcoma cell epithelial-mesenchymal transition (EMT) and suppressed osteosarcoma xenograft growth. Conclusion: MiR-19a enhanced cell migration, invasion and EMT through RhoB in osteosarcoma. The newly identified miR-19a/RhoB axis provides novel insight into the progression of osteosarcoma and offers a promising target for osteosarcoma therapy.
Provided are an electrolytic cathode assembly and an electrolytic cell. The electrolytic cathode assembly therein comprises a cathode plate; a wrapping strip, which seals a side of the cathode plate; and an insulating clamp, which is located above the wrapping strip on one side and which sealedly clamps on the cathode plate.
The present disclosure relates to the field of tissue dissection. Specifically, the present disclosure relates to medical devices which lift and retract tissue during a dissection procedure to improve visualization of the target tissue and mitigate obstruction of dissection tools. In particular, the present disclosure relates to a tissue retraction device which moves from a constrained to relaxed configuration to immobilize and retract the dissected portion of target tissue during a dissection procedure.
A method and a device for use in secondary text input, the method comprising: detecting a contact action; when the contact action conforms to a trigger condition for entering into a candidate result cutting mode, triggering to enter the candidate result cutting mode, and selecting and cutting a to-be-cut candidate result, thus forming an upper-screen portion and a re-acquisition portion; and performing an upper-screen operation on the upper-screen portion, and re-acquiring a secondary candidate result according to a character string corresponding to the re-acquisition portion. The method and device according to the present invention can streamline user operations, modify the candidate result at any time according to user input, and retain accurate parts in the candidate result, which provide users with more timely and efficient input feedback in the input process, and thereby providing a better user experience.
This paper investigated the impact properties of reactive powder concrete modified with different types (nano-SiO2, nano-TiO2, and nano-ZrO2) and dosages (1.0% and 3.0%) of nanofillers. Three mechanical parameters (dynamic compressive strength, dynamic ultimate strain, and dynamic peak strain) and two toughness indicators (impact toughness and specific energy absorption) were used as the evaluation indexes of impact properties. Experimental results show that the incorporation of nanofillers significantly improves the impact properties of concrete. Composites with nano-SiO2 present the largest dynamic peak strain, whereas composites containing nano-ZrO2 and nano-TiO2 present higher dynamic ultimate strain and dynamic compressive strength. With the incorporation of nanofillers, the impact toughness of nanocomposites increased by 23.2%-39.9%, and the specific energy absorption increased by as high as 159.7%-246.9%. Among the three types of nanofillers, nano-SiO2 shows an obvious advantage on the toughening enhancement for concrete. The reinforcement mechanisms of nanofillers are attributed to three main aspects: (1) the small size effect and gap filling effect of nanofillers reduce the initial defects of concrete and increases the compactness; (2) the nucleation effect and core effect of nanofillers inhibit the crack propagation and improve the weak interface of concrete; and (3) the pozzolanic effect of nanofillers enhances the structural performance of concrete.
Additive manufacturing, also known as three-dimension printing (3DP), has the advantages of high building efficient, low labor cost and less construction wastes compared to traditional construction technology. 3D printed concrete is a special type of concrete, which can be deposited through a 3D printer layer by layer without any formwork support and vibration process. Its important performance indexes, including workability, setting and hardening time, and mechanical properties, can be optimized by materials selection and printing parameters. To date, many building structures have been successfully printed using 3D printed concrete technology, some of which have even achieved its real applications. The 3D printed concrete has a great potential on practical applications, such as the affordable housing construction in low-income countries, military bunkers when the soldiers fighting in the wild, and complex constructions where the formwork is difficult to manufacture. In order to comprehensively introduce 3D printed concrete, this paper reviews the progress of 3D printed concrete in terms of workability, mechanical properties and building plan design. In addition, the current applications and further developments of 3D printed concrete are also discussed.
Shea, Matthew J.
Flach, Jessica T.
Zanni, Martin T.
Arnold, Michael S.
Thin film semiconducting single walled carbon nanotube (s-SWCNT) photovoltaics suffer losses due to trapping and quenching of excitons by defects induced when dispersing s-SWCNTs into solution. We study these aspects by preparing photovoltaic devices from (6,5) carbon nanotubes isolated by different processes: extended ultrasonication, brief ultrasonication, and shear force mixing. Peak quantum efficiency increases from 28% to 38% to 49% as the processing harshness decreases and is attributed to both increasing s-SWCNT length and reducing sidewall defects. Fill-factor and open-circuit voltage also improve with shear force mixing, highlighting the importance of obtaining long, defect-free s-SWCNTs for efficient photoconversion devices. (C) 2018 Author(s).
Quick, Quincy A.
Genetic heterogeneity is recognized as a major contributing factor of glioblastoma resistance to clinical treatment modalities and consequently low overall survival rates. This genetic diversity results in variations in protein expression, both intratumorally and between individual glioblastoma patients. In this regard, the spectraplakin protein, microtubule actin cross-linking factor 1 (MACF1), was examined in glioblastoma. An expression analysis of MACF1 in various types of brain tumor tissue revealed that MACF1 was predominately present in grade III-IV astroctyomas and grade IV glioblastoma, but not in normal brain tissue, normal human astrocytes and lower grade brain tumors. Subsequent genetic inhibition experiments showed that suppression of MACF1 selectively inhibited glioblastoma cell proliferation and migration in cell lines established from patient derived xenograft mouse models and immortalized glioblastoma cell lines that were associated with downregulation of the Wnt-signaling mediators, Axinl and beta-catenin. Additionally, concomitant MACF1 silencing with the chemotherapeutic agent temozolomide (TMZ) used for the clinical treatment of glioblastomas cooperatively reduced the proliferative capacity of glioblastoma cells. In conclusion, the present study represents the first investigation on the functional role of MACF1 in tumor cell biology, as well as demonstrates its potential as a unique biomarker that can be targeted synergistically with TMZ as part of a combinatorial therapeutic approach for the treatment of genetically multifarious glioblastomas.