From the microbiome to the central nervous system, an update on the epidemiology and pathogenesis of bacterial meningitis in childhood [version 1; referees: 3 approved]

In the past century, advances in antibiotics and vaccination have dramatically altered the incidence and clinical outcomes of bacterial meningitis. We review the shifting epidemiology of meningitis in children, including after the implementation of vaccines that target common meningitic pathogens and the introduction of intrapartum antibiotic prophylaxis offered to mothers colonized with Streptococcus agalactiae. We also discuss what is currently known about the pathogenesis of meningitis. Recent studies of the human microbiome have illustrated dynamic relationships of bacterial and viral populations with the host, which may potentiate the risk of bacterial meningitis

The effect of tantalum on the structure/properties of two polycrystalline nickel-base superalloys: B-1900 + Hf MAR-M247

The microstructure, phase compositions, and phase fractions were studied in conventionally cast B-1900 + Hf and both conventionally cast and directionally solidified MAR-M247 as a function of tantalum concentration. The hot tensile and creep rupture properties of the solutionized and aged MAR-M247-type alloys were also determined as a function of tantalum level. The effects of tantalum on the microstructure and phase compositions of B-1900 + Hf and MAR-M247 (conventionally cast and directionally solidified) were found to be very similar. The addition of tantalum to the as cast and heat treated alloys was shown to cause the partial replacement of the Hf in the MC carbides by Ta, although the degree of replacement was decreased by the solutionizing and aging heat treatment. The gamma prime and minor phase fractions (primarily MC type carbides) both increased approximately linearly with tantalum concentration. The gamma prime phase compositions were relatively insensitive to tantalum variations with the exception of the tantalum and/or hafnium levels. Bulk tantalum additions increased the tantalum, chromium, and cobalt levels of the gamma phase in both alloy series. The increase in the concentrations of the latter two elements in the gamma phase was a result of the decrease in the gamma phase fraction with increasing bulk tantalum concentration and constant gamma/gamma prime partitioning ratio. Tantalum additions increased the yield stress and ultimate tensile strength of the directionally solidified MAR-M247 type alloys and had no significant effect on ductility

Effect of environmental weathering on flexural creep behavior of long fiber-reinforced thermoplastic composites

Flexural creep behavior of nylon 6/6 (NY66)- and polypropylene (PP)- based long fiber (l/d = 2000-10 000) thermoplastic (LFT) composites was investigated as a function of ultraviolet irradiation and moisture absorption. Extrusion/compression-molded panels were prepared according to ASTM D-2990 and conditioned according to ASTM D-618. NY66 and PP LFTs were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier-transform infrared (FTIR) spectroscopy in the unexposed condition, and as-exposed to 253.7 nm UV radiation. The creep compliance of PP LFT increased with increasing UV exposure, whereas the creep compliance of NY66 LFT showed a moderate decrease with increasing UV exposure. Moisture absorption experiments were performed in boiling water until saturation on NY66 and its LFT composites. Characterization of desorbed moisture absorption specimens suggested slight variation in the structure, and an analysis of creep compliances showed minimal changes as compared to the dry/unexposed specimens

Promoter targeted small RNAs induce long-term transcriptional gene silencing in human cells

Small RNAs targeted to gene promoters in human cells can mediate transcriptional gene silencing (TGS) by directing silent state epigenetic modifications to targeted loci. Many mechanistic details of this process remain poorly defined, and the ability to stably modulate gene expression in this manner has not been explored. Here we describe the mechanisms of establishment and maintenance of long-term transcriptional silencing of the human ubiquitin C gene (UbC). Sustained targeting of the UbC promoter with a small RNA for a minimum of 3 days resulted in long-term silencing which correlated with an early increase in histone methylation and a later increase in DNA methylation at the targeted locus. Transcriptional silencing of UbC required the presence of a promoter-associated RNA. The establishment and maintenance of the TGS were shown to require distinct protein factors. Argonaute 1 (Ago1), DNA methyltransferase 3a (DNMT3a) and histone deacetylase 1 (HDAC1) were required for the initiation of silencing, and DNA methyltransferase 1 (DNMT1) was necessary for maintenance. Taken together the data presented here highlight the cellular pathway with which noncoding RNAs interact to epigenetically regulate gene expression in human cells

Domain wall QCD with physical quark masses

We present results for several light hadronic quantities ($f_\pi$, $f_K$, $B_K$, $m_{ud}$, $m_s$, $t_0^{1/2}$, $w_0$) obtained from simulations of 2+1 flavor domain wall lattice QCD with large physical volumes and nearly-physical pion masses at two lattice spacings. We perform a short, O(3)%, extrapolation in pion mass to the physical values by combining our new data in a simultaneous chiral/continuum `global fit' with a number of other ensembles with heavier pion masses. We use the physical values of $m_\pi$, $m_K$ and $m_\Omega$ to determine the two quark masses and the scale - all other quantities are outputs from our simulations. We obtain results with sub-percent statistical errors and negligible chiral and finite-volume systematics for these light hadronic quantities, including: $f_\pi$ = 130.2(9) MeV; $f_K$ = 155.5(8) MeV; the average up/down quark mass and strange quark mass in the $\bar {\rm MS}$ scheme at 3 GeV, 2.997(49) and 81.64(1.17) MeV respectively; and the neutral kaon mixing parameter, $B_K$, in the RGI scheme, 0.750(15) and the $\bar{\rm MS}$ scheme at 3 GeV, 0.530(11).Comment: 131 pages, 30 figures. Updated to match published versio

Bidirectional Transcription Directs Both Transcriptional Gene Activation and Suppression in Human Cells

Small RNAs targeted to gene promoters in human cells have been shown to modulate both transcriptional gene suppression and activation. However, the mechanism involved in transcriptional activation has remained poorly defined, and an endogenous RNA trigger for transcriptional gene silencing has yet to be identified. Described here is an explanation for siRNA-directed transcriptional gene activation, as well as a role for non-coding antisense RNAs as effector molecules driving transcriptional gene silencing. Transcriptional activation of p21 gene expression was determined to be the result of Argonaute 2–dependent, post-transcriptional silencing of a p21-specific antisense transcript, which functions in Argonaute 1–mediated transcriptional control of p21 mRNA expression. The data presented here suggest that in human cells, bidirectional transcription is an endogenous gene regulatory mechanism whereby an antisense RNA directs epigenetic regulatory complexes to a sense promoter, resulting in RNA-directed epigenetic gene regulation. The observations presented here support the notion that epigenetic silencing of tumor suppressor genes, such as p21, may be the result of an imbalance in bidirectional transcription levels. This imbalance allows the unchecked antisense RNA to direct silent state epigenetic marks to the sense promoter, resulting in stable transcriptional gene silencing

The social consequences of minor innovations in construction

Innovation studies in construction focus on a desire to increase economics and efficiency at a large scale. This has resulted in a skewed perspective that sees only major corporations with substantial R&D resources, complex projects, or national interests at the heart of innovation. By adopting anthropological methods, it becomes possible to examine the two aims of this paper: to demonstrate that an accumulation of minor innovations can have significant consequences; and to show that these are inherently social rather than purely economic. Results come from fieldwork studying the improvisatory house-building practices of the Kelabit people of rural Borneo, tracing changes to the technologies used for roofing and foundations, and describes how these are mutually entangled with new social structures. The conclusion is that we should think more broadly about the forms and effects of innovation in construction, and recognise the significance of improvisation at the level of the individual or small group

The cultural antiquity of rainforests: Human-plant associations during the mid-late Holocene in the interior highlands of Sarawak, Malaysian Borneo

© 2015 Elsevier Ltd and INQUA. Rainforests are often described as the world's last virgin landscapes; however hunter-gatherers may have been modifying these environments for over 50,000 years. Despite this, the antiquity of early tropical forest exploitation by hunter-gathers and the transition to farming are still poorly understood. Today globalization drives deforestation of rainforests at an unprecedented rate. The forest, the lives of its present-day inhabitants, and the archaeological evidence for their history are unlikely to survive for much longer in their present form. The 'Cultured Rainforest Project', an interdisciplinary project involving anthropologists, archaeologists and palaeoecologists, was set up in 2007 to investigate the long-term and present-day interactions between people and the rainforest in the Kelabit Highlands of central Borneo, so as to better understand past and present agricultural and hunter-gatherer lifestyles and landscapes. This paper examines the environmental evidence used to investigate initial signs of plant exploitation and the transition to agriculture, as well as to understand the wider significance of past plants in a changing cultural landscape. Results have shown that two pronounced cultural waves of human-plant interactions took place in the Kelabit Highlands during the late Holocene; although tentative marks may be present on the landscape ca.7000-6000 years ago. The first pronounced wave of human-plant interaction begins from at least 3000 cal BP. It seems to correspond with the appearance of stone mounds and open-air sites recorded in the archaeological record. The sago palm Eugeissona plays an important role during this period. A second wave of cultural activity, particularly in the last 450 years, is recorded in the southern Kelabit Highlands and is marked by rice becoming important. This may be linked to the construction of a wide range of different megaliths and earthworks, due to its inferred association with wealth and status in prehistoric and historic periods. It is perhaps also linked to a rise in trade between the coastal regions and highlands

Motion of a driven tracer particle in a one-dimensional symmetric lattice gas

We study the dynamics of a tracer particle subject to a constant driving force $E$ in a one-dimensional lattice gas of hard-core particles whose transition rates are symmetric. We show that the mean displacement of the driven tracer grows in time, $t$, as $\sqrt{\alpha t}$, rather than the linear time dependence found for driven diffusion in the bath of non-interacting (ghost) particles. The prefactor $\alpha$ is determined implicitly, as the solution of a transcendental equation, for an arbitrary magnitude of the driving force and an arbitrary concentration of the lattice gas particles. In limiting cases the prefactor is obtained explicitly. Analytical predictions are seen to be in a good agreement with the results of numerical simulations.Comment: 21 pages, LaTeX, 4 Postscript fugures, to be published in Phys. Rev. E, (01Sep, 1996