Computational fluid dynamic modeling of 100ml and scaled-down 10ml stirred suspension bioreactors enables prediction of embryonic stem cell characteristics

There is a growing necessity for cell cultivation using bioreactors to translate laboratory based culture protocols into reproducible, scalable, and robust bioprocesses. Stirred suspension bioreactors offer several advantages over planar static cultures, including: reduced labour and operating costs, reduced space requirements, greater cellular homogeneity, and increased cell density per volume [1]. An important consideration when using stirred suspension bioreactors is mechanical stimulation. Fluid shear at the fluid-cell interface triggers cellular responses through mechanotransduction and can modulate stem cell proliferation and differentiation. However, if the shear stress caused by the impeller exceeds the tolerance limit of the cells, it causes cell damage and death, resulting in a lower quality and yield of cells. The shear rate distribution depends on bioreactor geometry, impeller agitation rate, cell density, and cell media viscosity [2]. Current scale-up protocols to predict agitation rates rely on maximum values of hydrodynamic variables, which occur only at the impeller tip. The volume averaged shear stress and maximum shear stress differ greatly, and cells dispersed within the liquid experience different local and global forces. This makes it difficult to predict how cells will respond to changes in bioreactor geometries and sizes. Profiling distributed and average forces in the bioreactor is critical to ensure quality and yield in cell manufacturing. Hydrodynamics, specifically velocities, shear rates, and energy dissipation rates, can be studied using computational fluid dynamic (CFD) modeling. Please click Additional Files below to see the full abstract

SURVEY OF THE DEPENDENCE ON TEMPERATURE OF THE COERCIVITY OF GARNET-FILMS

The temperature dependence of the domain-wall coercive field of epitaxial magnetic garnets films has been investigated in the entire temperature range of the ferrimagnetic phase, and has been found to be described by a set of parametric exponents. In subsequent temperature regions different slopes were observed, with breaking points whose position was found to be sample dependent. A survey ba.ed on literature Data as well as on a large number of our own samples shows the general existence of this piecewise exponential dependence and the presence of the breaking points. This type of domain-wall coercive field temperature dependence was found in all samples in the large family of the epitaxial garnets (about 30 specimens of more than ten chemical compositionsj and also in another strongly anisotropic material (TbFeCo)

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study protocol

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but \u3e95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity

Use of Self-Selected Postures to Regulate Multi-Joint Stiffness During Unconstrained Tasks

The human motor system is highly redundant, having more kinematic degrees of freedom than necessary to complete a given task. Understanding how kinematic redundancies are utilized in different tasks remains a fundamental question in motor control. One possibility is that they can be used to tune the mechanical properties of a limb to the specific requirements of a task. For example, many tasks such as tool usage compromise arm stability along specific directions. These tasks only can be completed if the nervous system adapts the mechanical properties of the arm such that the arm, coupled to the tool, remains stable. The purpose of this study was to determine if posture selection is a critical component of endpoint stiffness regulation during unconstrained tasks.Three-dimensional (3D) estimates of endpoint stiffness were used to quantify limb mechanics. Most previous studies examining endpoint stiffness adaptation were completed in 2D using constrained postures to maintain a non-redundant mapping between joint angles and hand location. Our hypothesis was that during unconstrained conditions, subjects would select arm postures that matched endpoint stiffness to the functional requirements of the task. The hypothesis was tested during endpoint tracking tasks in which subjects interacted with unstable haptic environments, simulated using a 3D robotic manipulator. We found that arm posture had a significant effect on endpoint tracking accuracy and that subjects selected postures that improved tracking performance. For environments in which arm posture had a large effect on tracking accuracy, the self-selected postures oriented the direction of maximal endpoint stiffness towards the direction of the unstable haptic environment.These results demonstrate how changes in arm posture can have a dramatic effect on task performance and suggest that postural selection is a fundamental mechanism by which kinematic redundancies can be exploited to regulate arm stiffness in unconstrained tasks

Geriatric pharmacotherapy : optimisation through integrated approach in the hospital setting

Since older patients are more vulnerable to adverse drug-related events, there is a need to ensure appropriate prescribing in these patients in order to prevent misuse, overuse and underuse of drugs. Different tools and strategies have been developed to reduce inappropriate prescribing; the available measures can be divided into medication assessment tools, and specific interventions to reduce inappropriate prescribing. Implicit criteria of inappropriate prescribing focus on appropriate dosing, search for drug-drug interactions, and increase adherence. Explicit criteria are consensus-based standards focusing on drugs and diseases and include lists of drugs to avoid in general or lists combining drugs with clinical data. These criteria take into consideration differences between patients, and stand for a medication review, by using a systematic approach. Different types of interventions exist in order to reduce inappropriate prescribing in older patients, such as: educational interventions, computerized decision support systems, pharmacist-based interventions, and geriatric assessment. The effects of these interventions have been studied, sometimes in a multifaceted approach combining different techniques, and all types seem to have positive effects on appropriateness of prescribing. Interdisciplinary teamwork within the integrative pharmaceutical care is important for improving of outcomes and safety of drug therapy. The pharmaceutical care process consists offour steps, which are cyclic for an individual patient. These steps are pharmaceutical anamnesis, medication review, design and follow-up of a pharmaceutical care plan. A standardized approach is necessary for the adequate detection and evaluation of drug-related problems. Furthermore, it is clear that drug therapy should be reviewed in-depth, by having full access to medical records, laboratory values and nursing notes. Although clinical pharmacists perform the pharmaceutical care process to manage the patient’s drug therapy in every day clinical practice, the physician takes the ultimate responsibility for the care of the patient in close collaboration with nurses

Mössbauer mineralogy of rock, soil, and dust at Gusev crater, Mars: Spirit's journey through weakly altered olivine basalt on the plains and pervasively altered basalt in the Columbia Hills

The Mössbauer spectrometer on Spirit measured the oxidation state of Fe, identified Fe-bearing phases, and measured relative abundances of Fe among those phases for surface materials on the plains and in the Columbia Hills of Gusev crater. Eight Fe-bearing phases were identified: olivine, pyroxene, ilmenite, magnetite, nanophase ferric oxide (npOx), hematite, goethite, and a Fe3+-sulfate. Adirondack basaltic rocks on the plains are nearly unaltered (Fe3+/FeT < 0.2) with Fe from olivine, pyroxene (Ol > Px), and minor npOx and magnetite. Columbia Hills basaltic rocks are nearly unaltered (Peace and Backstay), moderately altered (WoolyPatch, Wishstone, and Keystone), and pervasively altered (e.g., Clovis, Uchben, Watchtower, Keel, and Paros with Fe3+/FeT ~ 0.6–0.9). Fe from pyroxene is greater than Fe from olivine (Ol sometimes absent), and Fe2+ from Ol + Px is 40–49% and 9–24% for moderately and pervasively altered materials, respectively. Ilmenite (Fe from Ilm 3–6%) is present in Backstay, Wishstone, Keystone, and related rocks along with magnetite (Fe from Mt 10–15%). Remaining Fe is present as npOx, hematite, and goethite in variable proportions. Clovis has the highest goethite content (Fe from Gt = 40%). Goethite (α-FeOOH) is mineralogical evidence for aqueous processes because it has structural hydroxide and is formed under aqueous conditions. Relatively unaltered basaltic soils (Fe3+/FeT ~ 0.3) occur throughout Gusev crater (60–80% Fe from Ol + Px, 10–30% from npOx, and 10% from Mt). PasoRobles soil in the Columbia Hills has a unique occurrence of high concentrations of Fe3+-sulfate (65% of Fe). Magnetite is identified as a strongly magnetic phase in Martian soil and dust.Additional co-authors: E Kankeleit, P Gütlich, F Renz, SW Squyres, RE Arvidso

Attenuated reovirus displays oncolysis with reduced host toxicity

Background: Although the naturally occurring reovirus causes only mild symptoms in humans, it shows considerable potential as an oncolytic agent because of its innate ability to target cancer cells. In immunocompromised hosts, however, wild-type reovirus can target healthy tissues, including heart, liver, pancreas and neural structures. Methods: We characterized an attenuated form of reovirus (AV) derived from a persistently infected cell line through sequence analysis, as well as western blot and in vitro transcription and translation techniques. To examine its pathogenesis and oncolytic potential, AV reovirus was tested on healthy embryonic stem cells, various non-transformed and transformed cell lines, and in severe combined immunodeficiency (SCID) mice with tumour xenografts. Results: Sequence analysis of AV reovirus revealed a premature STOP codon in its sigma 1 attachment protein. Western blot and in vitro translation confirmed the presence of a truncated ?1. In comparison to wild-type reovirus, AV reovirus did not kill healthy stem cells or induce black tail formation in SCID mice. However, it did retain its ability to target cancer cells and reduce tumour size. Conclusion: Despite containing a truncated attachment protein, AV reovirus still preferentially targets cancer cells, and compared with wild-type reovirus it shows reduced toxicity when administered to immunodeficient hosts, suggesting the potential use of AV reovirus in combination cancer therapy