U-drawing of Fortiform 1050 third generation steels. Numerical and experimental results

Elasto–plastic behavior of the third generation Fortiform 1050 steel has been analysed using cyclic tension–compression tests. At the same time, the pseudo elastic modulus evolution with plastic strain was analysed using cyclic loading and unloading tests. From the experiments, it was found that the cyclic behavior of the steel is strongly kinematic and elastic modulus decrease with plastic strain is relevant for numerical modelling. In order to numerically analyse a U-Drawing process, strip drawing tests have been carried out at different contact pressures and Filzek model has been used to fit the experimental data and implement a pressure dependent friction law in Autoform software. Finally, numerical predictions of springback have been compared with the experimentally ones obtained using a sensorized UDrawing tooling. Different material and contact models have been examined and most influencing parameters have been identified to model the forming of these new steels

Investigation of translocation, DNA unwinding, and protein displacement by NS3h, the helicase domain from the Hepatitis C virus helicase

Helicases are motor proteins that are involved in DNA and RNA metabolism, replication, recombination, transcription and repair. The motors are powered by ATP binding and hydrolysis. Hepatitis C virus encodes a helicase called non-structural protein (NS3). NS3 possesses protease and helicase activities on its N-terminal and C-terminal domains respectively. The helicase domain of NS3 protein is referred as NS3h. In vitro, NS3h catalyzes RNA and DNA unwinding in a 3’ to -5’ direction. The directionality for unwinding is thought to arise in part from the enzyme's ability to translocate along DNA, but translocation has not been shown explicitly. We examined the DNA translocase activity of NS3h by using single-stranded oligonucleotide substrates containing a fluorescent probe on the 5’ end. NS3h can bind to the ssDNA and in the presence of ATP, move towards the 5’-end. When the enzyme encounters the fluorescent probe, a fluorescence change is observed that allows translocation to be characterized. Under conditions that favor binding of one NS3h per DNA substrate (100 nM NS3h, 200 nM oligonucleotide) we find that NS3h translocates on ssDNA at a rate of 46 ± 5 nt s−1 and that it can move for 230 ± 60 nt before dissociating from the DNA. The translocase activity of some helicases is responsible for displacing proteins that are bound to DNA. We studied protein displacement by using a ssDNA oligonucleotide covalently linked to biotin on the 5’-end. Upon addition of streptavidin, a ‘protein-block’ was placed in the pathway of the helicase. Interestingly, NS3h was unable to displace streptavidin from the end of the oligonucleotide, despite its ability to translocate along the DNA. The DNA unwinding activity of NS3h was examined using a 22 bp duplex DNA substrate under conditions that were identical to those used to study translocation. NS3h exhibited little or no DNA unwinding under single cycle conditions, supporting the conclusion that NS3h is a relatively poor helicase in its monomeric form, as has been reported. In summary, NS3h translocates on ssDNA as a monomer, but the translocase activity does not correspond to comparable DNA unwinding activity or protein-displacement activity under identical conditions

Vacuum String Field Theory with B field

We continue the analysis of Vacuum String Field Theory in the presence of a constant B field. In particular we give a proof of the ratio of brane tensions is the expected one. On the wake of the recent literature we introduce wedge-like states and orthogonal projections. Finally we show a few examples of the smoothing out effects of the B field on some of the singularities that appear in VSFT.Comment: 20 pages; v2: typos corrected, references added; final versio

Defining Advance Care Planning for Adults: A Consensus Definition From a Multidisciplinary Delphi Panel

Despite increasing interest in advance care planning (ACP) and prior ACP descriptions, a consensus definition does not yet exist to guide clinical, research, and policy initiatives

Tachyon Dynamics in Open String Theory

In this review we describe our current understanding of the properties of open string tachyons on an unstable D-brane or brane-antibrane system in string theory. The various string theoretic methods used for this study include techniques of two dimensional conformal field theory, open string field theory, boundary string field theory, non-commutative solitons etc. We also describe various attempts to understand these results using field theoretic methods. These field theory models include toy models like singular potential models and p-adic string theory, as well as more realistic version of the tachyon effective action based on Dirac-Born-Infeld type action. Finally we study closed string background produced by the `decaying' unstable D-branes, both in the critical string theory and in the two dimensional string theory, and describe the open string completeness conjecture that emerges out of this study. According to this conjecture the quantum dynamics of an unstable D-brane system is described by an internally consistent quantum open string field theory without any need to couple the system to closed strings. Each such system can be regarded as a part of the `hologram' describing the full string theory.Comment: LaTex file, 169 pages, based on lectures at various schools; v2: references adde

Sex-Specific Growth and Reproductive Dynamics of Red Drum in the Northern Gulf of Mexico

The Red Drum Sciaenops ocellatus stock is heavily targeted in the Gulf of Mexico (GOM) by recreational fishers and supports a small commercial fishery in Mississippi. Despite their popularity, little recent work has been done to describe their life history. In this work, we describe sex‐specific growth and reproductive dynamics of Red Drum collected from the northern GOM from September 2016 through October 2017. We evaluated seven candidate growth models and found that the three‐parameter von Bertalanffy growth function (VBGF) was the best candidate length‐at‐age model. No significant difference in growth between sexes was observed with the three‐parameter VBGF, despite the female‐specific curve having a larger mean asymptotic length than the male‐specific curve. All seven candidate growth models predicted similar mean length‐at‐age estimates, and four of them exhibited significant differences in sex‐specific mean length at age, with females reaching a larger length at age than males after age 5. There was no significant difference between the sex‐specific weight‐at‐length relationships. Red Drum are batch spawners that spawn in northern GOM coastal waters during August and September. We estimated 3.7 d between spawns and 10.5 spawning events per female in 2017. Nearly 20% of fish collected during the spawning season were sexually mature but reproductively inactive, indicating the possibility of skipped spawning. The age at 50% maturity was around 3 years (length at 50% maturity = 670 mm TL) in both sexes, but fish were not spawning capable until age 4.5 (703 mm TL) in males and age 5.8 (840 mm TL) in females. Furthermore, elevated gonadosomatic indices were not observed until around age 5–6. The updated life history information presented in this work helps to address current data limitations and provides critical information for future assessments of Red Drum stocks in the northern GOM

Probabilistic modeling of personalized drug combinations from integrated chemical screen and molecular data in sarcoma

BACKGROUND: Cancer patients with advanced disease routinely exhaust available clinical regimens and lack actionable genomic medicine results, leaving a large patient population without effective treatments options when their disease inevitably progresses. To address the unmet clinical need for evidence-based therapy assignment when standard clinical approaches have failed, we have developed a probabilistic computational modeling approach which integrates molecular sequencing data with functional assay data to develop patient-specific combination cancer treatments. METHODS: Tissue taken from a murine model of alveolar rhabdomyosarcoma was used to perform single agent drug screening and DNA/RNA sequencing experiments; results integrated via our computational modeling approach identified a synergistic personalized two-drug combination. Cells derived from the primary murine tumor were allografted into mouse models and used to validate the personalized two-drug combination. Computational modeling of single agent drug screening and RNA sequencing of multiple heterogenous sites from a single patient's epithelioid sarcoma identified a personalized two-drug combination effective across all tumor regions. The heterogeneity-consensus combination was validated in a xenograft model derived from the patient's primary tumor. Cell cultures derived from human and canine undifferentiated pleomorphic sarcoma were assayed by drug screen; computational modeling identified a resistance-abrogating two-drug combination common to both cell cultures. This combination was validated in vitro via a cell regrowth assay. RESULTS: Our computational modeling approach addresses three major challenges in personalized cancer therapy: synergistic drug combination predictions (validated in vitro and in vivo in a genetically engineered murine cancer model), identification of unifying therapeutic targets to overcome intra-tumor heterogeneity (validated in vivo in a human cancer xenograft), and mitigation of cancer cell resistance and rewiring mechanisms (validated in vitro in a human and canine cancer model). CONCLUSIONS: These proof-of-concept studies support the use of an integrative functional approach to personalized combination therapy prediction for the population of high-risk cancer patients lacking viable clinical options and without actionable DNA sequencing-based therapy