Prediction of the Spectrum of a Digital Delta–Sigma Modulator Followed by a Polynomial Nonlinearity

This paper presents a mathematical analysis of the power spectral density of the output of a nonlinear block driven by a digital delta-sigma modulator. The nonlinearity is a memoryless third-order polynomial with real coefficients. The analysis yields expressions that predict the noise floor caused by the nonlinearity when the input is constant

Transcriptional regulation of multiciliated cell differentiation

Multiciliated cells (MCC) project dozens to hundreds of motile cilia from the cell surface to generate fluid flow across epithelial surfaces or turbulence to promote the transport of gametes. The MCC differentiation program is initiated by GEMC1 and MCIDAS, members of the geminin family, that activate key transcription factors, including p73 and FOXJ1, to control the multiciliogenesis program. To support the generation of multiple motile cilia, MCCs must undergo massive centriole amplification to generate a sufficient number of basal bodies (modified centrioles). This transcriptional program involves the generation of deuterosomes, unique structures that act as platforms to regulate centriole amplification, the reactivation of cell cycle programs to control centriole amplification and release, and extensive remodeling of the cytoskeleton. This review will focus on providing an overview of the transcriptional regulation of MCCs and its connection to key processes, in addition to highlighting exciting recent developments and open questions in the field

Genesis and Propagation of Fractal Structures During Photoelectrochemical Etching of n-Silicon

The genesis, propagation, and dimensions of fractal-etch patterns that form anodically on front- or back-illuminated n-Si(100) photoelectrodes in contact with 11.9 M NH₄F(aq) has been investigated during either linear-sweep voltammetry or when the electrode was held at a constant potential (E = +6.0 V versus Ag/AgCl). Optical images collected in situ during electrochemical experiments revealed the location and underlying mechanism of initiation and propagation of the structures on the surface. X-ray photoelectron spectroscopic (XPS) data collected for samples emersed from the electrolyte at varied times provided detailed information about the chemistry of the surface during fractal etching. The fractal structure was strongly influenced by the orientation of the crystalline Si sample. The etch patterns were initially generated at points along the circumference of bubbles that formed upon immersion of n-Si(100) samples in the electrolyte, most likely due to the electrochemical and electronic isolation of areas beneath bubbles. XPS data showed the presence of a tensile-stressed silicon surface throughout the etching process as well as the presence of SiO_xF_y on the surface. The two-dimensional fractal dimension D_(f,2D) of the patterns increased with etching time to a maximum observed value of D_(f,2D)=1.82. Promotion of fractal etching near etch masks that electrochemically and electronically isolated areas of the photoelectrode surface enabled the selective placement of highly branched structures at desired locations on an electrode surface

Surgical treatment of acute limb iscahemia in the presence of malignancy

AbstractObjectivesThe aim of this study was to examine the outcome of surgical treatment of acute limb ischaemia (ALI) developing in the presence of malignancy.MethodsPatients undergoing emergency surgery were identified from theatre registers, notes were reviewed, and data collected in relation to indications for, and outcome following operation. All patients with a current or past medical history of histologically confirmed malignant disease were identified and their notes specifically reviewed to determine the staging of their tumours. The results of the malignancy cohort were compared to a group of patients undergoing surgery for ALI of other aetiologies.ResultsFourteen patients with a malignancy were identified with ALI and in addition there were 102 without malignancy. The cohort with a malignancy contained a higher proportion of males (p=0.0305), and a greater number of smokers (p=0.037) than those with other aetiologies for ALI. The peri-operative management of the 2 groups was similar. Histological examination revealed tumour thrombus in only 1 case. The recurrence (29% versus 18%; p=0.328) and amputation rates (29% versus 17%; p=0.278) were similar, however, the 30-day (50% versus 30%; p=0.038) and 60-day mortality rates (100% versus 35%; p<0.001) were significantly higher in the malignancy group.ConclusionsThe development of ALI in patients with malignant disease may be regarded as a terminal event despite comparable performance status at the time of surgery to those with other cause for ALI. The role of surgery in patients with known advanced malignancies appears to be of dubious benefit with little survival benefit

The ASD Living Biology: from cell proliferation to clinical phenotype.

Autism spectrum disorder (ASD) has captured the attention of scientists, clinicians and the lay public because of its uncertain origins and striking and unexplained clinical heterogeneity. Here we review genetic, genomic, cellular, postmortem, animal model, and cell model evidence that shows ASD begins in the womb. This evidence leads to a new theory that ASD is a multistage, progressive disorder of brain development, spanning nearly all of prenatal life. ASD can begin as early as the 1st and 2nd trimester with disruption of cell proliferation and differentiation. It continues with disruption of neural migration, laminar disorganization, altered neuron maturation and neurite outgrowth, disruption of synaptogenesis and reduced neural network functioning. Among the most commonly reported high-confidence ASD (hcASD) genes, 94% express during prenatal life and affect these fetal processes in neocortex, amygdala, hippocampus, striatum and cerebellum. A majority of hcASD genes are pleiotropic, and affect proliferation/differentiation and/or synapse development. Proliferation and subsequent fetal stages can also be disrupted by maternal immune activation in the 1st trimester. Commonly implicated pathways, PI3K/AKT and RAS/ERK, are also pleiotropic and affect multiple fetal processes from proliferation through synapse and neural functional development. In different ASD individuals, variation in how and when these pleiotropic pathways are dysregulated, will lead to different, even opposing effects, producing prenatal as well as later neural and clinical heterogeneity. Thus, the pathogenesis of ASD is not set at one point in time and does not reside in one process, but rather is a cascade of prenatal pathogenic processes in the vast majority of ASD toddlers. Despite this new knowledge and theory that ASD biology begins in the womb, current research methods have not provided individualized information: What are the fetal processes and early-age molecular and cellular differences that underlie ASD in each individual child? Without such individualized knowledge, rapid advances in biological-based diagnostic, prognostic, and precision medicine treatments cannot occur. Missing, therefore, is what we call ASD Living Biology. This is a conceptual and paradigm shift towards a focus on the abnormal prenatal processes underlying ASD within each living individual. The concept emphasizes the specific need for foundational knowledge of a living child's development from abnormal prenatal beginnings to early clinical stages. The ASD Living Biology paradigm seeks this knowledge by linking genetic and in vitro prenatal molecular, cellular and neural measurements with in vivo post-natal molecular, neural and clinical presentation and progression in each ASD child. We review the first such study, which confirms the multistage fetal nature of ASD and provides the first in vitro fetal-stage explanation for in vivo early brain overgrowth. Within-child ASD Living Biology is a novel research concept we coin here that advocates the integration of in vitro prenatal and in vivo early post-natal information to generate individualized and group-level explanations, clinically useful prognoses, and precision medicine approaches that are truly beneficial for the individual infant and toddler with ASD

Gastrointestinal tract size, total-tract digestibility, and rumen microflora in different dairy cow genotypes

peer-reviewedThe superior milk production efficiency of Jersey (JE) and Jersey × Holstein-Friesian (JE × HF) cows compared with Holstein-Friesian (HF) has been widely published. The biological differences among dairy cow genotypes, which could contribute to the milk production efficiency differences, have not been as widely studied however. A series of component studies were conducted using cows sourced from a longer-term genotype comparison study (JE, JE × HF, and HF). The objectives were to (1) determine if differences exist among genotypes regarding gastrointestinal tract (GIT) weight, (2) assess and quantify whether the genotypes tested differ in their ability to digest perennial ryegrass, and (3) examine the relative abundance of specific rumen microbial populations potentially relating to feed digestibility. Over 3 yr, the GIT weight was obtained from 33 HF, 35 JE, and 27 JE × HF nonlactating cows postslaughter. During the dry period the cows were offered a perennial ryegrass silage diet at maintenance level. The unadjusted GIT weight was heavier for the HF than for JE and JE × HF. When expressed as a proportion of body weight (BW), JE and JE × HF had a heavier GIT weight than HF. In vivo digestibility was evaluated on 16 each of JE, JE × HF, and HF lactating dairy cows. Cows were individually stalled, allowing for the total collection of feces and were offered freshly cut grass twice daily. During this time, daily milk yield, BW, and dry matter intake (DMI) were greater for HF and JE × HF than for JE; milk fat and protein concentration ranked oppositely. Daily milk solids yield did not differ among the 3 genotypes. Intake capacity, expressed as DMI per BW, tended to be different among treatments, with JE having the greatest DMI per BW, HF the lowest, and JE × HF being intermediate. Production efficiency, expressed as milk solids per DMI, was higher for JE than HF and JE × HF. Digestive efficiency, expressed as digestibility of dry matter, organic matter, N, neutral detergent fiber, and acid detergent fiber, was higher for JE than HF. In grazing cows (n = 15 per genotype) samples of rumen fluid, collected using a transesophageal sampling device, were analyzed to determine the relative abundance of rumen microbial populations of cellulolytic bacteria, protozoa, and fungi. These are critically important for fermentation of feed into short-chain fatty acids. A decrease was observed in the relative abundance of Ruminococcus flavefaciens in the JE rumen compared with HF and JE × HF. We can deduce from this study that the JE genotype has greater digestibility and a different rumen microbial population than HF. Jersey and JE × HF cows had a proportionally greater GIT weight than HF. These differences are likely to contribute to the production efficiency differences among genotypes previously reported

Enrollment of adolescents and young adults onto SWOG cancer research network clinical trials: A comparative analysis by treatment site and era.

BackgroundFew adolescents and young adults (AYAs, 15-39 years old) enroll onto cancer clinical trials, which hinders research otherwise having the potential to improve outcomes in this unique population. Prior studies have reported that AYAs are more likely to receive cancer care in community settings. The National Cancer Institute (NCI) has led efforts to increase trial enrollment through its network of NCI-designated cancer centers (NCICC) combined with community outreach through its Community Clinical Oncology Program (CCOP; replaced by the NCI Community Oncology Research Program in 2014).MethodsUsing AYA proportional enrollment (the proportion of total enrollments who were AYAs) as the primary outcome, we examined enrollment of AYAs onto SWOG therapeutic trials at NCICC, CCOP, and non-NCICC/non-CCOP sites from 2004 to 2013 by type of site, study period (2004-08 vs 2009-13), and patient demographics.ResultsOverall, AYA proportional enrollment was 10.1%. AYA proportional enrollment decreased between 2004-2008 and 2009-2013 (13.1% vs 8.5%, P &lt; .001), and was higher at NCICCs than at CCOPs and non-NCICC/non-CCOPs (14.1% vs 8.3% and 9.2%, respectively; P &lt; .001). AYA proportional enrollment declined significantly at all three site types. Proportional enrollment of AYAs who were Black or Hispanic was significantly higher at NCICCs compared with CCOPs or non-NCICC/non-CCOPs (11.5% vs 8.8, P = .048 and 11.5% vs 8.6%, P = .03, respectively).ConclusionNot only did community sites enroll a lower proportion of AYAs onto cancer clinical trials, but AYA enrollment decreased in all study settings. Initiatives aimed at increasing AYA enrollment, particularly in the community setting with attention to minority status, are needed