Temperature Controlled 3D Bio-printing Using Bio-polymeric Ink

Bio-Printing 3D organs, tissues & scaffolds is advancing everyday, with various methods being introduces to mimic a perfect working organ or tissue which can be functional at the same time. We have developed a method to print bio-polymer in liquid state using them as bio-inks to prints scaffolds, while maintaining their temperatures. The design is cheap and efficient to print 3d scaffolds. Our Bio-Printer is also aided with a robotic arm to induce any bio-active ingredient in the 3d structures once it is printed without deforming or altering the structure of the scaffold. The main printer can be paused to allow the robotic arm to continue embedding and make repairs to the scaffold from any angle

Cellular Automata Applications in Shortest Path Problem

Cellular Automata (CAs) are computational models that can capture the essential features of systems in which global behavior emerges from the collective effect of simple components, which interact locally. During the last decades, CAs have been extensively used for mimicking several natural processes and systems to find fine solutions in many complex hard to solve computer science and engineering problems. Among them, the shortest path problem is one of the most pronounced and highly studied problems that scientists have been trying to tackle by using a plethora of methodologies and even unconventional approaches. The proposed solutions are mainly justified by their ability to provide a correct solution in a better time complexity than the renowned Dijkstra's algorithm. Although there is a wide variety regarding the algorithmic complexity of the algorithms suggested, spanning from simplistic graph traversal algorithms to complex nature inspired and bio-mimicking algorithms, in this chapter we focus on the successful application of CAs to shortest path problem as found in various diverse disciplines like computer science, swarm robotics, computer networks, decision science and biomimicking of biological organisms' behaviour. In particular, an introduction on the first CA-based algorithm tackling the shortest path problem is provided in detail. After the short presentation of shortest path algorithms arriving from the relaxization of the CAs principles, the application of the CA-based shortest path definition on the coordinated motion of swarm robotics is also introduced. Moreover, the CA based application of shortest path finding in computer networks is presented in brief. Finally, a CA that models exactly the behavior of a biological organism, namely the Physarum's behavior, finding the minimum-length path between two points in a labyrinth is given.Comment: To appear in the book: Adamatzky, A (Ed.) Shortest path solvers. From software to wetware. Springer, 201

Effect of welding energy on microstructure and strength of ultrasonic spot welded dissimilar joints of aluminum to steel sheets

Two dissimilar ultrasonic spot welded joints of aluminum to commercial steel sheets at different levels of welding energy were investigated. The tensile lap shear tests were conducted to evaluate the failure strength in relation to microstructural changes. The main intermetallics at the weld interface in both joints was θ (FeAl3), along with ɳ (Fe2Al5) phase in Al-to-AISI 304 stainless steel joint and Fe3Al phase in Al-to-ASTM A36 steel joint, respectively. The welding strength of Al-to-AISI 304 stainless steel weld samples was slightly higher than Al-to-ASTM A36 steel weld samples, whereas the fracture energies of Al-to-AISI 304 stainless steel weld samples were significantly higher as compared with Al-to-ASTM A36 steel weld samples. The welding strength of both Al-to-Steel welds were higher than other reported dissimilar USW joints in literature. The fracture surfaces of both weld joints exhibits the growth of IMC layer with increasing welding energy or time, whose inherent brittleness compromises the integrity of joints. In both cases, the lap shear tensile fracture occurred from the Al/Fe interface at lower energy inputs and the failure mode at higher welding energy inputs became the “transverse through-thickness crack growth” at the edge of the nugget zone on the softer Al side

Microstructure, tensile and fatigue properties of ultrasonic spot welded aluminum to galvanized high-strength-low-alloy and low-carbon steel sheets

The microstructure evolution, tensile lap shear strength and fatigue properties of dissimilar ultrasonic spot welded (USWed) joints of aluminum to two commercial steel sheets at different welding energies were investigated. The main intermetallics at the weld interface were θ (FeAl3) in both joints along with eutectic Al-Zn in Al-to-galvanized high-strength-low-alloy (HSLA) steel joints and Fe3Al in Al-to-ASTM A36 steel joints. The welding strengths of both joints were higher than those of other dissimilar joints reported in the literature. With increasing welding energy, the maximum tensile lap shear strength increased in the Al-to-galvanized HSLA steel joints, while the lap shear strength increased up to a peak value and then decreased in the Al-to-ASTM A36 steel joints. Both the average peak welding strength and fracture energy of the Al-to-galvanized HSLA steel joints were higher than those of the Al-to-ASTM A36 steel joints. The fatigue lives of both welded joints were in agreement with or somewhat longer than other Al-to-steel USWed joints in the literature. The fatigue fracture mode changed with increasing cyclic loads in both welded joints. Fatigue crack growth was mainly characterized by the formation of fatigue striations perpendicular to the fatigue crack propagation direction

Sex determination in ratite and non ratite birds by molecular method

In spite of number of methods for sex determination in birds, it is very difficult to distinguish sex especially in ratite birds due to lack of sexual dimorphism. Chromodomain helicase DNA binding 1 gene (CHD 1) is the choice of gene for gender differentiation using PCR based molecular method. In present study, non ratite CHD gene specific primers viz. 1237L/1272H, 2550F/2718R, P2/P8, P2/P3 and ratite bird specific primers viz.W5/ W7 and W1/ K7 were used for gender differentiation in ratite birds. The ratite bird specific primer W5/W7 was the only primer, which determined the sex in emu as well as ostrich successfully, while 1237L/1272H, 2550F/2718R, P2/ P8, P2/P3 primers were unable to discriminate sex in emu and ostrich but ratite and non ratite primers can be used to discriminate the sex in non-ratite bird, primarily in chicken. In an alternative approach of PCR-RFLP, the high resolution melting curve (HRM) analysis showed conflicting pattern in both sexes of ratite birds but in chicken HRM analysis showed clear cut differential melting temperature in both sexes, hence HRM can be used for gender differentiation successfully

Kinetic-Ballooning-Bifurcation in Tokamak Pedestals Across Shaping and Aspect-Ratio

We use a new gyrokinetic threshold model to predict a bifurcation in tokamak pedestal width-height scalings that depends strongly on plasma shaping and aspect-ratio. The bifurcation arises from the first and second stability properties of kinetic-ballooning-modes that yields wide and narrow pedestal branches, expanding the space of accessible pedestal widths and heights. The wide branch offers potential for edge-localized-mode-free pedestals with high core pressure. For negative triangularity, low-aspect-ratio configurations are predicted to give steeper pedestals than conventional-aspect-ratio. Both wide and narrow branches have been attained in tokamak experiments.Comment: 7 pages, 7 figure

Simultaneous inhibition of Sirtuin 3 and cholesterol homeostasis targets acute myeloid leukemia stem cells by perturbing fatty acid β-oxidation and inducing lipotoxicity

Outcomes for patients with acute myeloid leukemia (AML) remain poor due to the inability of current therapeutic regimens to fully eradicate disease-initiating leukemia stem cells (LSC). Previous studies have demonstrated that oxidative phosphorylation (OXPHOS) is an essential process that is targetable in LSC. Sirtuin 3 (SIRT3), a mitochondrial deacetylase with a multi-faceted role in metabolic regulation, has been shown to regulate OXPHOS in cancer models; however, it has not yet been studied in the context of LSC. Thus, we sought to identify if SIRT3 is important for LSC function. Using RNAi and a SIRT3 inhibitor (YC8-02), we demonstrate that SIRT3 is a critical target for the survival of primary human LSC but is not essential for normal human hematopoietic stem and progenitor cell function. In order to elucidate the molecular mechanisms by which SIRT3 is essential in LSC we combined transcriptomic, proteomic, and lipidomic approaches, showing that SIRT3 is important for LSC function through the regulation of fatty acid oxidation (FAO) which is required to support OXPHOS and ATP production in human LSC. Further, we discovered two approaches to further sensitize LSC to SIRT3 inhibition. First, we found that LSC tolerate the toxic effects of fatty acid accumulation induced by SIRT3 inhibition by upregulating cholesterol esterification. Disruption of cholesterol homeostasis sensitizes LSC to YC8-02 and potentiates LSC death. Second, SIRT3 inhibition sensitizes LSC to the BCL-2 inhibitor venetoclax. Together, these findings establish SIRT3 as a regulator of lipid metabolism and potential therapeutic target in primitive AML cells

MHD activity induced coherent mode excitation in the edge plasma region of ADITYA-U Tokamak

In this paper, we report the excitation of coherent density and potential fluctuations induced by magnetohydrodynamic (MHD) activity in the edge plasma region of ADITYA-U Tokamak. When the amplitude of the MHD mode, mainly the m/n = 2/1, increases beyond a threshold value of 0.3-0.4 %, coherent oscillations in the density and potential fluctuations are observed having the same frequency as that of the MHD mode. The mode numbers of these MHD induced density and potential fluctuations are obtained by Langmuir probes placed at different radial, poloidal, and toroidal locations in the edge plasma region. Detailed analyses of these Langmuir probe measurements reveal that the coherent mode in edge potential fluctuation has a mode structure of m/n = 2/1 whereas the edge density fluctuation has an m/n = 1/1 structure. It is further observed that beyond the threshold, the coupled power fraction scales almost linearly with the magnitude of magnetic fluctuations. Furthermore, the rise rates of the coupled power fraction for coherent modes in density and potential fluctuations are also found to be dependent on the growth rate of magnetic fluctuations. The disparate mode structures of the excited modes in density and plasma potential fluctuations suggest that the underlying mechanism for their existence is most likely due to the excitation of the global high-frequency branch of zonal flows occurring through the coupling of even harmonics of potential to the odd harmonics of pressure due to 1/R dependence of the toroidal magnetic field

Safety, tolerability, and efficacy of subcutaneous efgartigimod in patients with chronic inflammatory demyelinating polyradiculoneuropathy (ADHERE): a multicentre, randomised-withdrawal, double-blind, placebo-controlled, phase 2 trial

Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system that can lead to severe disability from muscle weakness and sensory disturbances. Around a third of patients do not respond to currently available treatments, and many patients with a partial response have residual neurological impairment, highlighting the need for effective alternatives. Efgartigimod alfa, a human IgG1 antibody Fc fragment, has demonstrated efficacy and safety in patients with generalised myasthenia gravis. We evaluated the safety, tolerability, and efficacy of subcutaneous efgartigimod PH20 in adults with CIDP. Methods: ADHERE, a multistage, double-blind, placebo-controlled trial, enrolled participants with CIDP from 146 clinical sites from Asia-Pacific, Europe, and North America. Participants with evidence of clinically meaningful deterioration entered an open-label phase of weekly 1000 mg subcutaneous efgartigimod PH20 for no longer than 12 weeks (stage A). Those with confirmed evidence of clinical improvement (ECI; treatment responders) entered a randomised-withdrawal phase of 1000 mg subcutaneous efgartigimod PH20 weekly treatment versus placebo for a maximum of 48 weeks (stage B). Participants were randomised (1:1) through interactive response technology and stratified by their adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT) score change during stage A and their most recent CIDP medication within 6 months before screening. Investigators, the clinical research organisation, and participants were masked to the treatment. The primary endpoint in stage A, evaluated in the stage A safety population, was confirmed ECI (≥1 points aINCAT decrease, ≥4 points [centile metric] Inflammatory Rasch-built Overall Disability Scale increase, or ≥8 kPa grip strength increase after four injections and two consecutive visits). The primary endpoint in stage B, evaluated in the modified intention-to-treat population, was the risk of relapse (time to first aINCAT increase of ≥1 points). ADHERE is registered with ClinicalTrials.gov (NCT04281472) and EudraCT (2019-003076-39) and is completed. Findings: Between April 15, 2020, and May 11, 2023, 629 participants were screened; 322 (114 female, 208 male) entered stage A, of whom 214 (66%, 95% CI 61·0-71·6) had confirmed ECI. In stage B, 221 participants were randomised (79 female, 142 male; 111 to subcutaneous efgartigimod PH20, 110 to placebo). Subcutaneous efgartigimod PH20 significantly reduced the risk of relapse versus placebo (hazard ratio 0·39 [95% CI 0·25-0·61]; p<0·0001). 31 (27·9% [19·6-36·3]) participants given subcutaneous efgartigimod PH20 had a relapse versus 59 (53·6% [44·3-63·0]) given placebo. In stage A, treatment-emergent adverse events (TEAEs) occurred in 204 (63%) participants and serious TEAEs in 21 (7%). In stage B, TEAEs occurred in 71 (64%) participants on subcutaneous efgartigimod PH20 and 62 (56%) participants on placebo, and serious TEAEs in six (5%) on subcutaneous efgartigimod PH20 and six (5%) on placebo. Three deaths occurred: two in stage A (one non-related and one unlikely related to treatment) and one in stage B (placebo group). Interpretation: ADHERE showed the efficacy of subcutaneous efgartigimod PH20 in reducing the risk of relapse versus placebo in people with CIDP who responded to treatment. Further studies are needed to provide data on the longer-term effects of efgartigimod alfa and how it compares with currently available treatment options. Funding: argenx

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe