Multiscale molecular simulation of membranes

Fundamental advances in the understanding of the molecular mechanisms enable a guided strategy towards analysis, modeling, and design of nanoscale structures. An essential difficulty in molecular modeling is that relevant system sizes of interest are very large. Although molecular mechanics has developed accurate models of interactions between individual molecules, the difficulty is that it is simply infeasible to solve these models on existing – or even conceived – computers. Although accurate models of the individual interactions between the molecules are available, the engineered materials typically consist of well over a billion such molecules. However, multiscale methods are well-suited to such problems: near the region of activity, e.g., an indenter pushing through the substrate, we can use molecular resolution to understand the critical features of indenter/substrate interactions; away from the active region, we can coarse-grain to retain only the effective influence. On the other hand, existing molecular multiscale methods, such as Quasi-continuum, Bridging-scales, and Bridging-domain methods, are only suitable for crystalline materials. They rely on the Cauchy–Born rule to relate the lattice vectors to the deformation gradient tensor which is a continuum description. The main feature of crystals is the translational symmetry. However, several structures such as nanotubes, bended graphene sheets, biological structures, and animal cell membranes do not exhibit translational symmetry. In our study, a unique molecular multiscale method for noncrystalline, but highly symmetric structures, is developed. Our method is based on the Objective Structures framework. In other words our method not only exploits the translational symmetry, but also uses other symmetries such as rotational and screw symmetries. Our strategy is to approximate the energy of full atomistic system by the energy of coarse-grained particles. We incorporate the symmetries of the structure to find the neighborhood around the coarse-grained particles. We then use finite element analysis to minimize the energy

ELICITATION OF FORSKOLIN IN CULTURES OF RHIZACTONIA BATATICOLA-A PHYTOCHEMICAL SYNTHESIZING ENDOPHYTIC FUNGI

Objective: Coleus forskohlii is the only known source of forskolin-a labdanediterpene and a highly valuable phytochemical. Coleus forskohlii has been listed as endangered plant; therefore, efforts have been made to find novel sources of forskolin production.Methods: Endophytic fungi were isolated from Coleus forskohlii tissue and screened for forskolin production by using thin layer chromatography (TLC) method. Further, 16 different elicitation media combinations were used to enhance the forskolin content.Results: In this study, out of 38 strains of endophytic fungi from Coleus forskohlii only 2 strains EF1 and EF2 were found to synthesize forskolin in mycelium, whereas EF2 was found to release the forskolin into the broth. Further, EF2 was identified as Rhizactonia bataticola accession no. NFCCI 2028. Further, T2S1 media showed dramatic effects on enhanced forskolin production in mycelium. However, there was a significant increase about four folds in broth which corresponded to 0.5 mg compared to T1S1 media where it was 0.09 mg.Conclusion: The present study suggests that the forskolin producing Rhizactonia bataticola and T2S1 media can serve as potential materials for large scale enhancement of forskolin production. Â

Spinal Cord Compression Secondary to Metastatic Sinonasal Undifferentiated Carcinoma

Sinonasal undifferentiated carcinoma (SNUC) is a rare malignancy of the upper airways and anterior skull base that carries a poor prognosis. The tumor is known to be invasive into the surrounding structures of the skull base and brain. To date, there is only one existing case report documenting drop metastasis to the intradural extramedullary spinal cord. To the best of our knowledge, we present the second case of metastatic SNUC to the spine. This report describes a 59-year-old male with a history of head and neck SNUC who presented with thoracic back pain and bilateral lower extremity paresis. Neuroimaging demonstrated an extradural thoracic mass with severe spinal cord compression. The patient underwent thoracic laminectomy and fusion for decompression of the spinal cord and internal stabilization. The pathology returned as SNUC. The patient was subsequently lost to follow-up from our institution. Metastatic SNUC is rare. We discuss the relevant clinical imaging and review the literature. Such a malignancy portends a very poor prognosis

Pricing foreign currency options under stochastic interest rates

In this paper, we build a general framework to price contingent claims on foreign currencies using the Heath et al. (1987) model of the term structure. Closed form solutions are obtained for European options on currencies and currency futures assuming that the volatility functions determining the term structure are deterministic. As such, this paper provides an example of a bond price process (for both the domestic and foreign economies) consistent with Grabbe's (1983) formulation of the same problem.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29151/1/0000193.pd

Symmetry-Adapted Phonon Analysis of Nanotubes

The characteristics of phonons, i.e. linearized normal modes of vibration, provide important insights into many aspects of crystals, e.g. stability and thermodynamics. In this paper, we use the Objective Structures framework to make concrete analogies between crystalline phonons and normal modes of vibration in non-crystalline but highly symmetric nanostructures. Our strategy is to use an intermediate linear transformation from real-space to an intermediate space in which the Hessian matrix of second derivatives is block-circulant. The block-circulant nature of the Hessian enables us to then follow the procedure to obtain phonons in crystals: namely, we use the Discrete Fourier Transform from this intermediate space to obtain a block-diagonal matrix that is readily diagonalizable. We formulate this for general Objective Structures and then apply it to study carbon nanotubes of various chiralities that are subjected to axial elongation and torsional deformation. We compare the phonon spectra computed in the Objective Framework with spectra computed for armchair and zigzag nanotubes. We also demonstrate the approach by computing the Density of States. In addition to the computational efficiency afforded by Objective Structures in providing the transformations to almost-diagonalize the Hessian, the framework provides an important conceptual simplification to interpret the phonon curves.Comment: To appear in J. Mech. Phys. Solid

A Case of Novel Coronavirus Disease 19 in a Chronic Hemodialysis Patient Presenting with Gastroenteritis and Developing Severe Pulmonary Disease.

Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease with an alarming case fatality rate up to 5%. The risk factors for severe presentations are concentrated in patients with chronic kidney disease, particularly patients with end-stage renal disease (ESRD) who are dialysis dependent. We report the first US case of a 56-year-old nondiabetic male with ESRD secondary to IgA nephropathy undergoing thrice-weekly maintenance hemodialysis for 3 years, who developed COVID-19 infection. He has hypertension controlled with angiotensin receptor blocker losartan 100 mg/day and coronary artery disease status-post stent placement. During the first 5 days of his febrile disease, he presented to an urgent care, 3 emergency rooms, 1 cardiology clinic, and 2 dialysis centers in California and Utah. During this interval, he reported nausea, vomiting, diarrhea, and low-grade fevers but was not suspected of COVID-19 infection until he developed respiratory symptoms and was admitted to the hospital. Imaging studies upon admission were consistent with bilateral interstitial pneumonia. He was placed in droplet-eye precautions while awaiting COVID-19 test results. Within the first 24 h, he deteriorated quickly and developed acute respiratory distress syndrome (ARDS), requiring intubation and increasing respiratory support. Losartan was withheld due to hypotension and septic shock. COVID-19 was reported positive on hospital day 3. He remained in critical condition being treated with hydroxychloroquine and tocilizumab in addition to the standard medical management for septic shock and ARDS. Our case is unique in its atypical initial presentation and highlights the importance of early testing

Multilevel effects in the Rabi oscillations of a Josephson phase qubit

We present Rabi oscillation measurements of a Nb/AlOx/Nb dc superconducting quantum interference device (SQUID) phase qubit with a 100 um^2 area junction acquired over a range of microwave drive power and frequency detuning. Given the slightly anharmonic level structure of the device, several excited states play an important role in the qubit dynamics, particularly at high power. To investigate the effects of these levels, multiphoton Rabi oscillations were monitored by measuring the tunneling escape rate of the device to the voltage state, which is particularly sensitive to excited state population. We compare the observed oscillation frequencies with a simplified model constructed from the full phase qubit Hamiltonian and also compare time-dependent escape rate measurements with a more complete density-matrix simulation. Good quantitative agreement is found between the data and simulations, allowing us to identify a shift in resonance (analogous to the ac Stark effect), a suppression of the Rabi frequency, and leakage to the higher excited states.Comment: 14 pages, 9 figures; minor corrections, updated reference

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe