Hydrodynamic Impeller Stiffness, Damping, and Inertia in the Rotordynamics of Centrifugal Flow Pumps

Measurements were made of the lateral hydrodynamic forces experienced by a centrifugal pump impeller performing circular whirl motions within several volute geometries. Experiments were conducted for various flow coefficients, [phi], impeller rotating speeds or angular frequencies, w, and the angular frequency of the whirl motion, [omega], was varied from zero to nearly synchronous (equation) and to nearly antisynchronous (equation). The lateral forces were decomposed into (i) time averaged lateral forces and (ii) hydrodynamic force matrices representing the variation of the lateral forces with position of the impeller center. No assumptions concerning the form of these matrices need to be made. The latter can be further decomposed according to the variation with whirl frequency, the result being "stiffness", "damping", and "fluid inertial" rotordynamic force matrices. It was found that these force matrices essentially consist of equal diagonal terms and skew-symmetric off-diagonal terms. One consequence of this is that during its whirl motion the impeller experiences forces acting normal and tangential to the locus of whirl. Data on these normal and tangential forces are presented; in particular it is shown that there exists a region of positive reduced whirl frequencies, [omega/w], within which the hydrodynamic forces can be destabilizing with respect to whirl

Synthesis and structural characterization of a mimetic membrane-anchored prion protein

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP

Anti-prion drug mPPIg5 inhibits PrP(C) conversion to PrP(Sc).

Prion diseases, also known as transmissible spongiform encephalopathies, are a group of fatal neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. The 'protein only hypothesis' advocates that PrP(Sc), an abnormal isoform of the cellular protein PrP(C), is the main and possibly sole component of prion infectious agents. Currently, no effective therapy exists for these diseases at the symptomatic phase for either humans or animals, though a number of compounds have demonstrated the ability to eliminate PrPSc in cell culture models. Of particular interest are synthetic polymers known as dendrimers which possess the unique ability to eliminate PrP(Sc) in both an intracellular and in vitro setting. The efficacy and mode of action of the novel anti-prion dendrimer mPPIg5 was investigated through the creation of a number of innovative bio-assays based upon the scrapie cell assay. These assays were used to demonstrate that mPPIg5 is a highly effective anti-prion drug which acts, at least in part, through the inhibition of PrP(C) to PrP(Sc) conversion. Understanding how a drug works is a vital component in maximising its performance. By establishing the efficacy and method of action of mPPIg5, this study will help determine which drugs are most likely to enhance this effect and also aid the design of dendrimers with anti-prion capabilities for the future

Measuring perinatal complications: methodologic issues related to gestational age

<p>Abstract</p> <p>Background</p> <p>Perinatal outcomes differ by week of gestational age. However, it appears that how measures to examine these outcomes vary among various studies. The current paper explores how perinatal complications are reported and how they might differ when different denominators, numerators, and comparison groups are utilized.</p> <p>Conclusion</p> <p>One issue that can clearly affect absolute rates and trends is how groups of women are categorized by their gestational age. Since most perinatal outcomes can only occur in women and neonates who have delivered, using the number of pregnancies delivered (PD) as the denominator of outcomes is appropriate. However, for an outcome such as antepartum stillbirth, all women who are pregnant at a particular gestational age are at risk. Thus, the denominator should include all ongoing pregnancies (OP). When gestational age is used by week this means using both deliveries during a particular week plus those women who deliver beyond the particular week of gestation in the denominator. Researchers should be careful to make sure they are utilizing the appropriate measure of perinatal complications so they do not report findings that would be misleading to clinicians, patients, and policy makers.</p

Skin-derived dendritic cells acquire and degrade the scrapie agent following in vitro exposure

The accumulation of the scrapie agent in lymphoid tissues following inoculation via the skin is critical for efficient neuroinvasion, but how the agent is initially transported from the skin to the draining lymph node is not known. Langerhans cells (LCs) are specialized antigen-presenting cells that continually sample their microenvironment within the epidermis and transport captured antigens to draining lymph nodes. We considered LCs probable candidates to acquire and transport the scrapie agent after inoculation via the skin. XS106 cells are dendritic cells (DCs) isolated from mouse epidermis with characteristics of mature LC cells. To investigate the potential interaction of LCs with the scrapie agent XS106 cells were exposed to the scrapie agent in vitro. We show that XS106 cells rapidly acquire the scrapie agent following in vitro exposure. In addition, XS106 cells partially degrade the scrapie agent following extended cultivation. These data suggest that LCs might acquire and degrade the scrapie agent after inoculation via the skin, but data from additional experiments demonstrate that this ability could be lost in the presence of lipopolysaccharide or other immunostimulatory molecules. Our studies also imply that LCs would not undergo maturation following uptake of the scrapie agent in the skin, as the expression of surface antigens associated with LC maturation were unaltered following exposure. In conclusion, although LCs or DCs have the potential to acquire the scrapie agent within the epidermis our data suggest it is unlikely that they become activated and stimulated to transport the agent to the draining lymph node

Global analysis of a buck regulator

Liapunov's direct stability method as applied to discrete systems and the method of paired systems due to Kaiman are used to obtain sufficient conditions for global stability. The global convergence of a buck regulator is also investigated

Pregnancy Intendedness by Maternal Disability Status and Type in the United States

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154611/1/psrh12130.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154611/2/psrh12130_am.pd

Detection of prions in skin punch biopsies of Creutzfeldt–Jakob disease patients

Prion real-time quaking-induced conversion (RT-QuIC) is an ultrasensitive assay detecting pathological aggregates of misfolded prion protein in biospecimens. We studied 71 punch biopsy skin samples of 35 patients with Creutzfeldt–Jakob disease (CJD), including five assessed in vitam. The results confirmed the high value of skin prion RT-QuIC for CJD diagnosis (89% sensitivity and 100% specificity) and support its use in clinical practice. Preliminary data based on a limited number of cases suggest that prion-seeding activity in the skin varies according to the prion strain, being higher in sporadic CJD subtypes linked to the V2 strain (VV2 and MV2K) than in typical CJDMM1

The Duration of Spontaneous Active and Pushing Phases of Labour among 75,243 US women when intervention is minimal: A prospective, observational cohort study

Background Friedman\u27s curve, despite acknowledged limitations, has greatly influenced labour management. Interventions to hasten birth are now ubiquitous, challenging the contemporary study of normal labour. Our primary purpose was to characterise normal active labour and pushing durations in a large, contemporary sample experiencing minimal intervention, stratified by parity, age, and body mass index (BMI). Methods This is a secondary analysis of the national, validated Midwives Alliance of North America 4·0 (MANA Stats) data registry (n = 75,243), prospectively collected between Jan 1, 2012 and Dec 31, 2018 to describe labour and birth in home and birth center settings where common obstetric interventions [i.e., oxytocin, planned cesarean] are not available. The MANA Stats cohort includes pregnant people who intended birth in these settings and prospectively collects labour and birth processes and outcomes regardless of where birth or postpartum care ultimately occurs. Survival curves were calculated to estimate labour duration percentiles (e.g. 10th, 50th, 90th, and others of interest), by parity and sub-stratified by age and BMI. Findings Compared to multiparous women (n = 32,882), nulliparous women (n = 15,331) had significantly longer active labour [e.g., median 7.5 vs. 3.3 h; 95th percentile 34.8 vs. 12.0 h] and significantly longer pushing phase [e.g., median 1.1 vs. 0.2 h; 95th percentile 5.5 vs. 1.1 h]. Among nulliparous women, maternal age \u3e35 was associated with longer active first stage of labour and longer pushing phase, and BMI \u3e30 kg/m² was associated with a longer active first stage of labour but a shorter pushing phase. Patterns among multiparous women were different, with those \u3e35 years of age experiencing a slightly more rapid active labour and no difference in pushing duration, and those with BMI \u3e30 kg/m² experiencing a slightly longer active labour but, similarly, no difference in pushing duration. Interpretation Nulliparous women had significantly longer active first stage and pushing phase durations than multiparous women, with further variation noted by age and by BMI. Contemporary US women with low-risk pregnancies who intended birth in settings absent common obstetric interventions and in spontaneous labour with a live, vertex, term, singleton, non-anomalous fetus experienced labour durations that were often longer than prior characterizations, particularly among nulliparous women. Results overcome prior and current sampling limitations to refine understanding of normal labour durations and time thresholds signaling ‘labour dystocia’