Characterizing the degradation of alginate hydrogel for use in multilumen scaffolds for spinal cord repair

Alginate was studied as a degradable nerve guidance scaffold material in vitro and in vivo. In vitro degradation rates were determined using rheology to measure the change in shear modulus vs time. The shear modulus decreased from 155 kPa to 5 kPa within 2 days; however, alginate samples maintained their superficial geometry for over 28 days. The degradation behavior was supported by materials characterization data showing alginate consisted of high internal surface area (400 m2/g), which likely facilitated the release of cross‐linking cations resulting in the rapid decrease in shear modulus. To assess the degradation rate in vivo, multilumen scaffolds were fabricated using a fiber templating technique. The scaffolds were implanted in a 2‐mm‐long T3 full transection rodent spinal cord lesion model for 14 days. Although there was some evidence of axon guidance, in general, alginate scaffolds degraded before axons could grow over the 2‐mm‐long lesion. Enabling alginate‐based scaffolds for nerve repair will likely require approaches to slow its degradation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 611–619, 2016.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137597/1/jbma35600.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137597/2/jbma35600_am.pd

Separation of Crocin/Betanin Using Aqueous Two-phase Systems Containing Ionic Liquid and Sorbitol

Betanin and crocin, two food additives with attractive colors, are bioactive compounds of plants that are widely used in food, pharmaceutical, and medical industries. These bioactive pigments are sensitive to light, heat, organic solvents, and pH. It seems that a benign economic method is needed to extract these biomolecules, especially for industrial applications. The aqueous two-phase system (ATPS) is a liquid-liquid extraction technique that has shown its potential in recent years to extract and separate biomolecules. In this study, an ATPS consisting of carbohydrate (sorbitol) and ionic liquid (tetrabutyl phosphonium bromide) has been proposed as a new separation system with unique properties to study the partition coefficient of crocin and betanin. The results indicated that crocin and betanin had more tendency to the ionic liquid (IL)-rich phase and carbohydrate-rich phase, respectively. The influence of the concentration of IL and sorbitol on the partition coefficient was studied. The results showed that an increase in the tie-line length (concentrations) increased the partition coefficient of crocin and betanin. Enhancement in temperature increased the partition coefficient of crocin. The highest values of crocin recovery (97.55 %) and partition coefficient (39.85) at 308 K show that our proposed ATPS can be considered for crocin separation in one step

Diagnostic accuracy of coronary calcium score less than 100 in excluding coronary artery disease

Background: Coronary artery calcium score (CACS) is a quantitative assessment of calcifications and an established predictor of cardiovascular events. Objectives: In this study, we evaluated the diagnostic accuracy, negative predictive value (NPV), positive predictive value (PPV), specificity and sensitivity of CACS less than 100 in predicting significant coronary artery stenosis in patients with risk of coronary artery disease (CAD) in a vessel-based analysis. Patients and Methods: A cross sectional study was carried out on a study population of 2527 consecutive stable patients with symptoms suggestive of CAD who were referred for coronary computed tomographic angiography (CCTA). We performed 1343 studies with 256 slice machine in Shahid Rajaee hospital and the other studies were carried out with 64 slice machine in Imam Khomeini hospital and the calcium score was quantified according to the Agatston method. Results: At the cutoff point of 100 for coronary calcium scoring, therewashigh specificity (87), high sensitivity (79), high efficiency (84), high PPV (79), and high NPV (87) in the diagnosis of significant stenosis in the whole heart. The frequency of zero calcium scoring was 59 in normal or nonsignificant stenosis and 7.6 in significant stenosis in the whole heart. Calcium scoring increased with greater severity of the arterial stenosis (P values < 0.001). Conclusion: We conclude that coronary calcium scoring provided useful information in the management of patients. In CACS less than 100, it has a NPV of 87 in excluding significant stenosis in patients with the risk of CAD but it does not have enough diagnostic accuracy for surely excluding coronary stenosis, so we should perform a combination of CACS and coronary CT angiography for patients. � 2016, Tehran University of Medical Sciences and Iranian Society of Radiology

Peripheral nerve growth within a hydrogel microchannel scaffold supported by a kink‐resistant conduit

Nerve repair in several mm‐long nerve gaps often requires an interventional technology. Microchannel scaffolds have proven effective for bridging nerve gaps and guiding axons in the peripheral nervous system (PNS). Nonetheless, fabricating microchannel scaffolds at this length scale remains a challenge and/or is time consuming and cumbersome. In this work, a simple computer‐aided microdrilling technique was used to fabricate 10 mm‐long agarose scaffolds consisting of 300 µm‐microchannels and 85 µm‐thick walls in less than an hour. The agarose scaffolds alone, however, did not exhibit adequate stiffness and integrity to withstand the mechanical stresses during implantation and suturing. To provide mechanical support and enable suturing, poly caprolactone (PCL) conduits were fabricated and agarose scaffolds were placed inside. A modified salt‐leaching technique was developed to introduce interconnected porosity in PCL conduits to allow for tuning of the mechanical properties such as elastic modulus and strain to failure. It was shown that the PCL conduits were effective in stabilizing the agarose scaffolds in 10 mm‐long sciatic nerve gaps of rats for at least 8 weeks. Robust axon ingress and Schwann cell penetration were observed within the microchannel scaffolds without using growth factors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3392–3399, 2017.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139110/1/jbma36186_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139110/2/jbma36186.pd

Acute renal failure: A rare initial presentation of acute lymphoblastic leukemia

Acute lymphoblastic leukemia has several presentations associated with bone marrow and extramedullary involvement. The unusual presentation may be due to the infiltration of leukemic cells in any organ. An 11-year-old girl presented with fever and vomiting, since one day before admission after starfish biting during swimming. Her vital signs were: blood pressure 150/100 mmHg, pulse 98 beats per minute, respiration 18 breathes per minute, and temperature 37.2 °C (99 F). Laboratory work-up showed blood urea nitrogen 38 mg/dl and creatinine 2.8 mg/dl. In peripheral blood smear, few atypical cells, mild anemia (Hb: 9.2 g/dl), and mild thrombocytopenia (Platelet: 109,000/µL) were detected. Bone marrow aspiration and immunophenotyping were in favor of acute precursor B cell type lymphoblastic leukemia. The patient had a favorable response to treatment after initiating high-risk chemotherapy. Therefore, acute renal failure can be a rare initial presentation of acute lymphoblastic leukemia, and azotemia will improve with an early chemotherapy treatment

Disruption of the plant-specific CFS1 gene impairs autophagosome turnover and triggers EDS1-dependent cell death

Cell death, autophagy and endosomal sorting contribute to many physiological, developmental and immunological processes in plants. They are mechanistically interconnected and interdependent, but the molecular basis of their mutual regulation has only begun to emerge in plants. Here, we describe the identification and molecular characterization of CELL DEATH RELATED ENDOSOMAL FYVE/SYLF PROTEIN 1 (CFS1). The CFS1 protein interacts with the ENDOSOMAL SORTING COMPLEX REQUIRED FOR TRANSPORT I (ESCRT-I) component ELCH (ELC) and is localized at ESCRT-I-positive late endosomes likely through its PI3P and actin binding SH3YL1 Ysc84/Lsb4p Lsb3p plant FYVE (SYLF) domain. Mutant alleles of cfs1 exhibit auto-immune phenotypes including spontaneous lesions that show characteristics of hypersensitive response (HR). Autoimmunity in cfs1 is dependent on ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1)-mediated effector-triggered immunity (ETI) but independent from salicylic acid. Additionally, cfs1 mutants accumulate the autophagy markers ATG8 and NBR1 independently from EDS1. We hypothesize that CFS1 acts at the intersection of autophagosomes and endosomes and contributes to cellular homeostasis by mediating autophagosome turnover

Monte carlo estimation of electron contamination in a 18 MV clinical photon beam

Background: The electron contamination may reduce or even diminish the skin sparing property of the megavoltage beam. The detailed characteristics of contaminant electrons are presented for different field sizes and cases. Materials and Methods: The Monte Carlo code, MCNPX, has been used to simulate 18 MV photon beam from a Varian Linac-2300 accelerator. All dose measurements were carried out using a PTW-MP2 scanner with an ionization chamber (0.6 CC) at the water phantom. Results: The maximum electron contaminant dose at the surface ranged from 6.1 for 5 � 5 cm2 to 38.8 for 40 � 40 cm2 and at the depth of maximum dose was 0.9 up to 5.77 for the 5 � 5 cm2 to the 40 � 40 cm2 field sizes, respectively. The additional contaminant electron dose at the surface for the field with tray increased 2.3 for 10 � 10 cm2, 7.3 for 20 � 20 cm2, and 21.4 for 40 � 40 cm2 field size comparing to the standard field without any accessories. This increase for field with tray and shaping block was 5.3 and 13.3 for 10 � 10 and 20 � 20 cm2, respectively, while, the electron contamination decreased for the fields with wedge, i.e. 2.2 for the 10 � 10 cm2 field. Conclusion: The results have provided more comprehensive knowledge of the high-energy clinical beams and may be useful to develop the accurate treatment planning systems capable of taking the electron contamination in to account

On Multi-objective Policy Optimization as a Tool for Reinforcement Learning

Many advances that have improved the robustness and efficiency of deep reinforcement learning (RL) algorithms can, in one way or another, be understood as introducing additional objectives, or constraints, in the policy optimization step. This includes ideas as far ranging as exploration bonuses, entropy regularization, and regularization toward teachers or data priors when learning from experts or in offline RL. Often, task reward and auxiliary objectives are in conflict with each other and it is therefore natural to treat these examples as instances of multi-objective (MO) optimization problems. We study the principles underlying MORL and introduce a new algorithm, Distillation of a Mixture of Experts (DiME), that is intuitive and scale-invariant under some conditions. We highlight its strengths on standard MO benchmark problems and consider case studies in which we recast offline RL and learning from experts as MO problems. This leads to a natural algorithmic formulation that sheds light on the connection between existing approaches. For offline RL, we use the MO perspective to derive a simple algorithm, that optimizes for the standard RL objective plus a behavioral cloning term. This outperforms state-of-the-art on two established offline RL benchmarks

A novel frame-shift deletion in FANCF gene causing autosomal recessive Fanconi anemia: A case report

Background: Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by congenital anomalies, early-onset bone marrow failure, and a high predisposition to cancers. Up to know, different genes involved in the DNA repair pathway, mainly FANCA genes, have been identified to be affected in patients with FA. Case presentation: Here, we report clinical, laboratory and genetic findings in a 3.5-year-old Iranian female patient, a product of a consanguineous marriage, who was suspicious of FA, observed with short stature, microcephaly, skin hyperpigmentation, anemia, thrombocytopenia and hypo cellular bone marrow. Therefore, Next Generation Sequencing was performed to identify the genetic cause of the disease in this patient. Results revealed a novel, private, homozygous frameshift mutation in the FANCF gene (NM-022725: c. 534delG, p. G178 fs) which was confirmed by Sanger sequencing in the proband. Conclusion: Such studies may help uncover the exact pathomechanisms of this disorder and establish the genotype-phenotype correlations by identification of more mutations in this gene. It is the first report of a mutation in the FANCF gene in Iranian patients with Fanconi anemia. This new mutation correlates with a hematological problem (pancytopenia), short stature, and microcephaly and skin hyperpigmentation. Until now, no evidence of malignancy was detected

A Suite of Computationally Expensive Shape Optimisation Problems Using Computational Fluid Dynamics

This is the author accepted manuscript. The final version is available from Springer via the DOI in this record.PPSN2018: 15th International Conference on Parallel Problem Solving from Nature, 8-12 September 2018, Coimbra, PortugalIn many product design and development applications, Computational Fluid Dynamics (CFD) has become a useful tool for analysis. This is particularly because of the accuracy of CFD simulations in predicting the important flow attributes for a given design. On occasions when design optimisation is applied to real-world engineering problems using CFD, the implementation may not be available for examination. As such, in both the CFD and optimisation communities, there is a need for a set of computationally expensive benchmark test problems for design optimisation using CFD. In this paper, we present a suite of three computationally expensive real-world problems observed in different fields of engineering. We have developed Python software capable of automatically constructing geometries from a given decision vector, running appropriate simulations using the CFD code OpenFOAM, and returning the computed objective values. Thus, users may easily evaluate a decision vector and perform optimisation of these design problems using their optimisation methods without developing custom CFD code. For comparison, we provide the objective values for the base geometries and typical computation times for the test cases presented here.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC) grant (reference number: EP/M017915/1)