Vector Bin Packing with Multiple-Choice

We consider a variant of bin packing called multiple-choice vector bin packing. In this problem we are given a set of items, where each item can be selected in one of several $D$-dimensional incarnations. We are also given $T$ bin types, each with its own cost and $D$-dimensional size. Our goal is to pack the items in a set of bins of minimum overall cost. The problem is motivated by scheduling in networks with guaranteed quality of service (QoS), but due to its general formulation it has many other applications as well. We present an approximation algorithm that is guaranteed to produce a solution whose cost is about $\ln D$ times the optimum. For the running time to be polynomial we require $D=O(1)$ and $T=O(\log n)$. This extends previous results for vector bin packing, in which each item has a single incarnation and there is only one bin type. To obtain our result we also present a PTAS for the multiple-choice version of multidimensional knapsack, where we are given only one bin and the goal is to pack a maximum weight set of (incarnations of) items in that bin

The balance of power: accretion and feedback in stellar mass black holes

In this review we discuss the population of stellar-mass black holes in our galaxy and beyond, which are the extreme endpoints of massive star evolution. In particular we focus on how we can attempt to balance the available accretion energy with feedback to the environment via radiation, jets and winds, considering also possible contributions to the energy balance from black hole spin and advection. We review quantitatively the methods which are used to estimate these quantities, regardless of the details of the astrophysics close to the black hole. Once these methods have been outlined, we work through an outburst of a black hole X-ray binary system, estimating the flow of mass and energy through the different accretion rates and states. While we focus on feedback from stellar mass black holes in X-ray binary systems, we also consider the applicability of what we have learned to supermassive black holes in active galactic nuclei. As an important control sample we also review the coupling between accretion and feedback in neutron stars, and show that it is very similar to that observed in black holes, which strongly constrains how much of the astrophysics of feedback can be unique to black holes.Comment: To be published in Haardt et al. Astrophysical Black Holes. Lecture Notes in Physics. Springer 201

Large-eddy simulation of low-frequency unsteadiness in a turbulent shock-induced separation bubble

The need for better understanding of the low-frequency unsteadiness observed in shock wave/turbulent boundary layer interactions has been driving research in this area for several decades. We present here a large-eddy simulation investigation of the interaction between an impinging oblique shock and a Mach 2.3 turbulent boundary layer. Contrary to past large-eddy simulation investigations on shock/turbulent boundary layer interactions, we have used an inflow technique which does not introduce any energetically significant low frequencies into the domain, hence avoiding possible interference with the shock/boundary layer interaction system. The large-eddy simulation has been run for much longer times than previous computational studies making a Fourier analysis of the low frequency possible. The broadband and energetic low-frequency component found in the interaction is in excellent agreement with the experimental findings. Furthermore, a linear stability analysis of the mean flow was performed and a stationary unstable global mode was found. The long-run large-eddy simulation data were analyzed and a phase change in the wall pressure fluctuations was related to the global-mode structure, leading to a possible driving mechanism for the observed low-frequency motions

Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844–848

Neurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000–3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p.Arg1809 and a single amino acid deletion p.Met922del. Both variants predispose to a distinct mild NF1 phenotype with neither externally visible cutaneous/plexiform neurofibromas nor other tumors. Here, we report 162 individuals (129 unrelated probands and 33 affected relatives) heterozygous for a constitutional missense mutation affecting one of five neighboring NF1 codons—Leu844, Cys845, Ala846, Leu847, and Gly848—located in the cysteine-serine-rich domain (CSRD). Collectively, these recurrent missense mutations affect ∼0.8% of unrelated NF1 mutation-positive probands in the University of Alabama at Birmingham (UAB) cohort. Major superficial plexiform neurofibromas and symptomatic spinal neurofibromas were more prevalent in these individuals compared with classic NF1-affected cohorts (both p < 0.0001). Nearly half of the individuals had symptomatic or asymptomatic optic pathway gliomas and/or skeletal abnormalities. Additionally, variants in this region seem to confer a high predisposition to develop malignancies compared with the general NF1-affected population (p = 0.0061). Our results demonstrate that these NF1 missense mutations, although located outside the GAP-related domain, may be an important risk factor for a severe presentation. A genotype-phenotype correlation at the NF1 region 844–848 exists and will be valuable in the management and genetic counseling of a significant number of individuals

Etnobotânica e medicina popular no tratamento de malária e males associados na comunidade ribeirinha Julião – baixo Rio Negro (Amazônia Central)

RESUMO A utilização de plantas medicinais para o tratamento de doenças tropicais como a malária na Amazônia Central é de suma importância, principalmente em locais onde o sistema único de saúde não se encontra presente como na maioria das comunidades ribeirinhas desta região. Sendo assim, investigar e resgatar o conhecimento popular a respeito de plantas medicinais utilizadas no tratamento de malária e males associados pelos moradores da comunidade Julião situada na Reserva de Desenvolvimento Sustentável do Tupé, Manaus-AM, torna-se importante no registro de como as populações locais se previnem e tratam essa doença tão prevalente e perigosa na região. O trabalho foi conduzido na forma de oficinas participativas, segregadas por gênero e complementadas com entrevistas semiestruturadas aliadas à técnica da turnê-guiada nos quintais e floresta adjacente à comunidade. Foram calculados os índices de diversidade de Shannon-Wiener, equitabilidade e concordância quanto ao uso principal (CUP). A partir da colaboração efetiva de 13 comunitários foram registradas 62 espécies vegetais pertencentes a 53 gêneros e 34 famílias botânicas que resultaram em índice de diversidade (H’) de 1,62 decits e equitabilidade de 0,9. As famílias mais representativas foram: Fabaceae (7 espécies), Asteraceae e Lamiaceae (4 espécies cada) e Solanaceae e Rutaceae (3 espécies cada). Vale destacar que 16 espécies (25,8%) foram citadas para tratamento de malária e males associados pela primeira vez em estudos etnobotânicos realizados na América Latina

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials