Microtubule length distributions in the presence of protein-induced severing

Microtubules are highly regulated dynamic elements of the cytoskeleton of eukaryotic cells. One of the regulation mechanisms observed in living cells is the severing by the proteins katanin and spastin. We introduce a model for the dynamics of microtubules in the presence of randomly occurring severing events. Under the biologically motivated assumption that the newly created plus end undergoes a catastrophe, we investigate the steady state length distribution. We show that the presence of severing does not affect the number of microtubules, regardless of the distribution of severing events. In the special case in which the microtubules cannot recover from the depolymerizing state (no rescue events) we derive an analytical expression for the length distribution. In the general case we transform the problem into a single ODE that is solved numerically.Comment: 9 pages, 4 figure

The Effect of Electronic Cigarette User Modifications and E-liquid Adulteration on the Particle Size Profile of an Aerosolized Product

Electronic cigarettes (e-cigarettes) are an alternate nicotine delivery system that generate a condensation aerosol to be inhaled by the user. The size of the droplets formed in the aerosol can vary and contributes to drug deposition and ultimate bioavailability in the lung. The growing popularity of e-cigarette products has caused an increase in internet sources promoting the use of drugs other than nicotine (DOTNs) in e-cigarettes. The purpose of this study was to determine the effect of various e-cigarette and e-liquid modifications, such as coil resistance, battery voltage, and glycol and drug formulation, on the aerosol particle size. E-liquids containing 12 mg/mL nicotine prepared in glycol compositions of 100% propylene glycol (PG), 100% vegetable glycerin (VG), or 50:50 PG:VG were aerosolized at three voltages and three coil resistances. Methamphetamine and methadone e-liquids were prepared at 60 mg/mL in 50:50 PG:VG and all e-liquids were aerosolized onto a 10 stage Micro-Orifice Uniform Deposit Impactor. Glycol deposition correlated with drug deposition, and the majority of particles centered between 0.172–0.5 μm in diameter, representing pulmonary deposition. The 100% PG e-liquid produced the largest aerosol particles and the 100% VG and 50:50 PG:VG e-liquids produced ultra-fine particles \u3c0.3 μm. The presence of ultrafine particles indicates that drugs can be aerosolized and reach the pulmonary alveolar regions, highlighting a potential for abuse and risk of overdose with DOTNs aerosolized in an e-cigarette system

Inflammatory mediators in children with protein-energy malnutrition1-3

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Magnetic-film atom chip with 10 μ\mum period lattices of microtraps for quantum information science with Rydberg atoms

We describe the fabrication and construction of a setup for creating lattices of magnetic microtraps for ultracold atoms on an atom chip. The lattice is defined by lithographic patterning of a permanent magnetic film. Patterned magnetic-film atom chips enable a large variety of trapping geometries over a wide range of length scales. We demonstrate an atom chip with a lattice constant of 10 $\mu$m, suitable for experiments in quantum information science employing the interaction between atoms in highly-excited Rydberg energy levels. The active trapping region contains lattice regions with square and hexagonal symmetry, with the two regions joined at an interface. A structure of macroscopic wires, cut out of a silver foil, was mounted under the atom chip in order to load ultracold $^{87}$Rb atoms into the microtraps. We demonstrate loading of atoms into the square and hexagonal lattice sections simultaneously and show resolved imaging of individual lattice sites. Magnetic-film lattices on atom chips provide a versatile platform for experiments with ultracold atoms, in particular for quantum information science and quantum simulation.Comment: 7 pages, 7 figure

Endovascular treatment for acute ischaemic stroke in routine clinical practice:prospective, observational cohort study (MR CLEAN Registry)

OBJECTIVETo determine outcomes and safety of endovascular treatment for acute ischaemic stroke, due to proximal intracranial vessel occlusion in the anterior circulation, in routine clinical practice.DESIGNOngoing, prospective, observational cohort study.SETTING16 centres that perform endovascular treatment in the Netherlands.PARTICIPANTS1488 patients included in the Multicentre Randomised Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands (MR CLEAN) Registry who had received endovascular treatment, including stent retriever thrombectomy, aspiration, and all alternative methods for acute ischaemic stroke within 6.5 hours from onset of symptoms between March 2014 and June 2016.MAIN OUTCOME MEASURESThe primary outcome was the modified Rankin Scale (mRS) score, ranging from 0 (no symptoms) to 6 (death) at 90 days after the onset of symptoms. Secondary outcomes were excellent functional outcome (mRS score 0-1), good functional outcome (mRS score 0-2), and favourable functional outcome (mRS score 0-3) at 90 days; score on the extended thrombolysis in cerebral infarction scale at the end of the intervention procedure; National Institutes of Health Stroke Scale score 24-48 hours after intervention; and complications that occurred during intervention, hospital admission, or three months' follow up period. Outcomes and safety variables in the MR CLEAN Registry were compared with the MR CLEAN trial intervention and control arms.RESULTSA statistically significant shift was observed towards better functional outcome in patients in the MR CLEAN Registry compared with the MR CLEAN trial intervention arm (adjusted common odds ratio 1.30, 95% confidence interval 1.02 to 1.67) and the MR CLEAN trial control arm (1.85, 1.46 to 2.34). The reperfusion rate, with successful reperfusion defined as a score of 2B-3 on the extended thrombolysis in cerebral infarction score, was 58.7%, the same as for patients in the MR CLEAN trial. Duration from onset of stroke to start of endovascular treatment and from onset of stroke to successful reperfusion or last contrast bolus was one hour shorter for patients in the MR CLEAN Registry. Symptomatic intracranial haemorrhage occurred in 5.8% of patients in the MR CLEAN Registry compared with 7.7% in the MR CLEAN trial intervention arm and 6.4% in the MR CLEAN trial control arm.CONCLUSIONIn routine clinical practice, endovascular treatment for patients with acute ischaemic stroke is at least as effective and safe as in the setting of a randomised controlled trial.</p

VACUTAINER(® )CPT™ and Ficoll density gradient separation perform equivalently in maintaining the quality and function of PBMC from HIV seropositive blood samples

BACKGROUND: For immune monitoring studies during HIV vaccine clinical trials, whole blood specimens from HIV seropositive (HIV(+)) patients may be collected at multiple sites and sent to a central location for peripheral blood mononuclear cell (PBMC) isolation, cryopreservation and functional evaluation. In this study we show a comparison of two PBMC preparation options, Ficoll density gradient separation (Ficoll) and Cell Preparation Tubes (CPT) using shipped whole blood specimens from 19 HIV(+ )patients (CD4 > 350, viral load < 50). The pre- and post- cryopreservation performance of samples collected by these two methods were compared by assessment of antigen-specific IFNγ expression in CD8(+ )and CD8(- )T cells, cellular viability, and cellular recovery. RESULTS: The results indicate that cryopreserved PBMC samples tested for CMV- and HIV- specific interferon-gamma (IFNγ) expression performed equivalent to the respective fresh PBMC processed under both collection conditions. Compared to fresh PBMC, the viability was significantly lower for cryopreserved PBMC derived using Ficoll, although it was never less than 90%. There were no significant differences in the IFNγ response, viability, or recovery between cryopreserved PBMC derived by Ficoll and by CPT. CONCLUSION: These data suggest that CPT is an efficient system for the collection and cryopreservation of functionally active HIV(+ )PBMC, as well as a viable alternative to Ficoll gradient separation

Adult Attachment and Personal Recovery in Clients With a Psychotic Disorder

Background: Personal recovery has become a key objective in the treatment of clients with a psychotic disorder. So far it has been established that the two attachment dimensions, ie, anxious and avoidant, are negatively associated with subjective well-being, self-esteem and hope. This study is the first to explore whether attachment styles are related to personal recovery in this population. Aims: To study the effects of anxious and avoidant attachment on personal recovery in a population with a psychotic disorder. Method: This cross-sectional study is part of the UP's multicenter cohort study on recovery from psychotic disorders, in which 265 participants are currently included. Attachment was assessed using the Psychosis Attachment Measure, including the anxious and avoidant attachment dimensions. Personal recovery was measured using the Recovering Quality of Life-10 (ReQOL-10) and the Individual Recovery Outcomes Counter (I.ROC). Regression analysis was used to investigate the effect of attachment on personal recovery. Results: We found negative effects of the anxious attachment style on the total scores of the ReQoL-10 (b = -4.54, SE = 0.69, β = β0.37) and the I.ROC (b = -5.21, SE = 0.89, β = -0.32). Although there were also negative effects of the avoidant attachment style on the total scores of the ReQoL-10 (b = -3.08, SE = 0.93, β = -0.18) and the I.ROC (b = -4.24, SE = 1.24, β = -0.19), these were less pronounced. Conclusion: Results show that both forms of insecure attachment (anxious and avoidant) are related to poorer personal recovery in clients with a psychotic disorder.</p

The Influence of Mineralization on Intratrabecular Stress and Strain Distribution in Developing Trabecular Bone

The load-transfer pathway in trabecular bone is largely determined by its architecture. However, the influence of variations in mineralization is not known. The goal of this study was to examine the influence of inhomogeneously distributed degrees of mineralization (DMB) on intratrabecular stresses and strains. Cubic mandibular condylar bone specimens from fetal and newborn pigs were used. Finite element models were constructed, in which the element tissue moduli were scaled to the local DMB. Disregarding the observed distribution of mineralization was associated with an overestimation of average equivalent strain and underestimation of von Mises equivalent stress. From the surface of trabecular elements towards their core the strain decreased irrespective of tissue stiffness distribution. This indicates that the trabecular elements were bent during the compression experiment. Inhomogeneously distributed tissue stiffness resulted in a low stress at the surface that increased towards the core. In contrast, disregarding this tissue stiffness distribution resulted in high stress at the surface which decreased towards the core. It was concluded that the increased DMB, together with concurring alterations in architecture, during development leads to a structure which is able to resist increasing loads without an increase in average deformation, which may lead to damage

N- and KRAS mutations in primary testicular germ cell tumors: Incidence and possible biological implications

Recently, conflicting results have been reported on the incidence of RAS mutations in primary testicular germ cell tumors of adults (TGCTs). In four studies a low incidence of mutations (less than 15%) in a variety of TGCTs or derived cell lines was found, whereas in two other studies a high incidence of N- or KRAS mutations (over 40%) was shown. A total of 62 testicular seminomas (SE) and 34 nonseminomatous TGCTs (NS) were studied thus far. The largest series consisted of 42 TGCTs, studied on paraffin embedded tissue. We present the results of analysis for the presence of N- and KRAS mutations, in codons 12, 13, and 61, in snap frozen samples of 100 primary TGCTs, comprising 40 SE and 60 NS. Using the polymerase chain reaction (PCR) and allele specific oligonucleotide hybridization (ASO), mutations were found in five SE (three in NRAS and two in KRAS, all codon 12), and in one NS (KRAS, codon 12). To exclude underestimation of the incidence of RAS mutations in TGCTs due to the presence of an excess of wild type alleles in the analyzed sample, a PCR technique preferentially ampli

Non-circular Gas Kinematics and Star Formation in the Ringed Galaxy NGC 4736

We analyze the gas kinematics and star formation properties of the nearby RSab galaxy NGC 4736 using interferometric and single-dish CO(1-0) data and previously published Halpha and HI data. The CO morphology is dominated by a central molecular bar and tightly wound spiral arms associated with a bright ring of star formation. Strong HI emission is also found in the ring, but HI is absent from the central regions. Comparison of the HI and Halpha distributions suggests that HI in the ring is primarily dissociated H$_2$. Modeling of the CO kinematics reveals gas motion in elliptical orbits around the central bar, and we argue that the ring represents both the OLR of the bar and the ILR of a larger oval distortion. The HI kinematics show evidence for axisymmetric inflow towards the ring and are inconsistent with streaming in aligned elliptical orbits, but the highly supersonic (~40 km/s) inflow velocities required, corresponding to mass inflow rates of ~2 Msol/yr, suggest that more sophisticated models (e.g., gas orbiting in precessed elliptical orbits) should be considered. The radial CO and Halpha profiles are poorly correlated in the vicinity of the nuclear bar, but show a better correlation (in rough agreement with the Schmidt law) at the ring. Even along the ring, however, the azimuthal correspondence between CO and Halpha is poor, suggesting that massive stars form more efficiently at some (perhaps resonant) locations than at others. These results indicate that the star formation rate per unit gas mass exhibits strong spatial variations and is not solely a function of the available gas supply. The localization of star formation to the ring is broadly consistent with gravitational instability theory, although the instability parameter $Q \sim 3$ on average in the ring, only falling below 1 in localized regions.Comment: Revised version accepted by ApJ, with new section on p-v diagrams. 24 pages with 24 figures (emulateapj5). Full resolution and color versions are available at http://astro.berkeley.edu/~twong/preprint