Coagulation and fragmentation processes with evolving size and shape profiles : a semigroup approach

We investigate a class of bivariate coagulation-fragmentation equations. These equations describe the evolution of a system of particles that are characterised not only by a discrete size variable but also by a shape variable which can be either discrete or continuous. Existence and uniqueness of strong solutions to the associated abstract Cauchy problems are established by using the theory of substochastic semigroups of operators

Cover Crop Effect on Subsequent Wheat Yield in the Central Great Plains

Crop production systems in the water-limited environment of the semiarid central Great Plains may not have potential to profitably use cover crops because of lowered subsequent wheat (Triticum asestivum L.) yields following the cover crop. Mixtures have reportedly shown less yield-reducing effects on subsequent crops than single-species plantings. This study was conducted to determine winter wheat yields following both mixtures and single-species plantings of spring-planted cover crops. The study was conducted at Akron, CO, and Sidney, NE, during the 2012–2013 and 2013–2014 wheat growing seasons under both rainfed and irrigated conditions. Precipitation storage efficiency before wheat planting, wheat water use, biomass, and yield were measured and water use efficiency and harvest index were calculated for wheat following four single-species cover crops (flax [Linum usitatissimum L.], oat [Avena sativa L.], pea [Pisum sativum ssp. arvense L. Poir], rapeseed [Brassica napus L.]), a 10-species mixture, and a fallow treatment with proso millet (Panicum miliaceum L.) residue. There was an average 10% reduction in wheat yield following a cover crop compared with following fallow, regardless of whether the cover crop was grown in a mixture or in a single-species planting. Yield reductions were greater under drier conditions. The slope of the wheat water use–yield relationship was not significantly different for wheat following the mixture (11.80 kg ha–1 mm–1) than for wheat following single-species plantings (12.32–13.57 kg ha–1 mm–1). The greater expense associated with a cover crop mixture compared with a single species is not justified

Los Alamos National Laboratory`s Mobile Real Time Radiography System

A 450-KeV Mobile Real Time Radiography (RTR) System was delivered to Los Alamos National Laboratory (LANL) in January 1996. It was purchased to inspect containers of radioactive waste produced at (LANL). Since its delivery it has been used to radiograph greater than 600 drums of radioactive waste at various LANL sites. It has the capability of inspecting waste containers of various sizes. It has three independent X-Ray acquisition formats. The primary system used is a 12 in. image intensifier, the second is a 36 in. linear diode array (LDA) and the last is an open system. It is fully self contained with on board generator, HVAC and a fire suppression system. It is on a 53 ft long X 8 ft. wide X 14 ft. high trailer that can be moved over any highway requiring only a easily obtainable overweight permit because it weighs approximately 38 tons. It was built to conform to industry standards for a cabinet system which does not require an exclusion zone. The fact that this unit is mobile has allowed us to operate where the waste is stored, rather than having to move the waste to a fixed facility

Borderline Aggregation Kinetics in ``Dry'' and ``Wet'' Environments

We investigate the kinetics of constant-kernel aggregation which is augmented by either: (a) evaporation of monomers from finite-mass clusters, or (b) continuous cluster growth -- \ie, condensation. The rate equations for these two processes are analyzed using both exact and asymptotic methods. In aggregation-evaporation, if the evaporation is mass conserving, \ie, the monomers which evaporate remain in the system and continue to be reactive, the competition between evaporation and aggregation leads to several asymptotic outcomes. For weak evaporation, the kinetics is similar to that of aggregation with no evaporation, while equilibrium is quickly reached in the opposite case. At a critical evaporation rate, the cluster mass distribution decays as $k^{-5/2}$, where $k$ is the mass, while the typical cluster mass grows with time as $t^{2/3}$. In aggregation-condensation, we consider the process with a growth rate for clusters of mass $k$, $L_k$, which is: (i) independent of $k$, (ii) proportional to $k$, and (iii) proportional to $k^\mu$, with $0<\mu<1$. In the first case, the mass distribution attains a conventional scaling form, but with the typical cluster mass growing as $t\ln t$. When $L_k\propto k$, the typical mass grows exponentially in time, while the mass distribution again scales. In the intermediate case of $L_k\propto k^\mu$, scaling generally applies, with the typical mass growing as $t^{1/(1-\mu)}$. We also give an exact solution for the linear growth model, $L_k\propto k$, in one dimension.Comment: plain TeX, 17 pages, no figures, macro file prepende

Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway.

A promising new compound class for treating human malaria is the imidazolopiperazines (IZP) class. IZP compounds KAF156 (Ganaplacide) and GNF179 are effective against Plasmodium symptomatic asexual blood-stage infections, and are able to prevent transmission and block infection in animal models. But despite the identification of resistance mechanisms in P. falciparum, the mode of action of IZPs remains unknown. To investigate, we here combine in vitro evolution and genome analysis in Saccharomyces cerevisiae with molecular, metabolomic, and chemogenomic methods in P. falciparum. Our findings reveal that IZP-resistant S. cerevisiae clones carry mutations in genes involved in Endoplasmic Reticulum (ER)-based lipid homeostasis and autophagy. In Plasmodium, IZPs inhibit protein trafficking, block the establishment of new permeation pathways, and cause ER expansion. Our data highlight a mechanism for blocking parasite development that is distinct from those of standard compounds used to treat malaria, and demonstrate the potential of IZPs for studying ER-dependent protein processing

Concizumab en pacientes con Hemofilia A/B: una revisión sistemática

Objective: We systematically assessed the efficacy of Concizumab in patients with Hemophilia A/B. Material and Methods: Five databases were searched up to May 2022 for randomized controlled trials in adults with severe Hemophilia A/B with or without inhibitors treated with Concizumab compared to standard care or placebo. Outcomes were bleeding episodes (ABRs), D - dimer, prothrombin fragment 1.2, fibrinogen levels, prothrombin time, nasopharyngitis, and upper respiratory tract infection. Results: Two RCTs (n = 86) were included. In both studies, decreased bleeding rates were observed at high levels of concizumab. Furthermore, both studies support the use of concizumab as a safe and well-tolerated prophylactic therapy administered subcutaneously in all haemophilia patients. Placebo was the comparator in one RCT, while Eptacog alfa (activated) rFVIIIa was the comparator in the other RCT. The dosing of concizumab in the RCTs ranged from 0.15, 0.20, 0.25, 0.5 and 0.8, mg/kg with follow-up times between 42 days and 24 weeks. Conclusion: The efficacy and safety of Concizumab for the treatment of patients with Hemophilia A/B cannot be estimated or recommended due to the weak evidence and low number of relevant studies supporting its use.Objetivo: Evaluamos sistemáticamente la eficacia de Concizumab en pacientes con Hemofilia A/B. Material y Métodos: Se buscaron en cinco bases de datos hasta mayo de 2022 ensayos controlados aleatorios en adultos con Hemofilia A/B grave con o sin inhibidores tratados con Concizumab en comparación con la atención estándar o el placebo. Los resultados fueron los episodios de hemorragia (ABRs), el dímero D, el fragmento de protrombina 1.2, los niveles de fibrinógeno, el tiempo de protrombina, la nasofaringitis y la infección del tracto respiratorio superior. Resultados: Se incluyeron dos ECA (n = 86). En ambos estudios, se observó una disminución de las tasas de hemorragia con niveles elevados de concizumab. Además, ambos estudios apoyan el uso de concizumab como terapia profiláctica segura y bien tolerada administrada por vía subcutánea en todos los pacientes con hemofilia. El placebo fue el comparador en un ECA, mientras que Eptacog alfa (activado) rFVIIIa fue el comparador en el otro ECA. La dosis de concizumab en los ECAs osciló entre 0,15, 0,20, 0,25, 0,5 y 0,8, mg/kg con tiempos de seguimiento entre 42 días y 24 semanas. Conclusiones: No se puede estimar ni recomendar la eficacia y seguridad de Concizumab para el tratamiento de pacientes con Hemofilia A/B debido a la débil evidencia y bajo número de estudios pertinentes que respalden su uso

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al