Miracle-dz/UniFAR-FTUs huggingface dataset:
Shape of the particulate beam attenuation spectrum and its inversion to obtain the shape of the particulate size distribution.

The link between the spectral shape of the beam attenuation spectrum and the shape of the particle size distribution (PSD) of oceanic particles is revisited to evaluate the extent to which one can be predicted from the other. Assuming a hyperbolic (power-law) PSD, N(D) ? D(-xi), past studies have found for an infinite distribution of nonabsorbing spheres with a constant index of refraction that the attenuation spectrum is hyperbolic and that the attenuation spectral slope gamma is related to the PSD slope xi by xi = gamma + 3. Here we add a correction to this model because of the finite size of the biggest particle in the population. This inversion model is given by xi = gamma + 3 - 0.5 exp(-6gamma). In most oceanic observations xi > 3, and the deviation between these two models is negligible. To test the robustness of this inversion, we perturbed its assumptions by allowing for populations of particles that are nonspherical, or absorbing, or with an index of refraction that changes with wavelength. We found the model to provide a good fit for the range of parameters most often encountered in the ocean. In addition, we found that the particulate attenuation spectrum, c(p)(lambda), is well described by a hyperbolic relation to the wavelength c(p) ? lambda(-gamma) throughout the range of the investigated parameters, even when the inversion model does not apply. This implies that knowledge of the particulate attenuation at two visible wavelengths could provide, to a high degree of accuracy, the particulate attenuation at other wavelengths in the visible spectrum.
ACAT2 deficiency limits cholesterol absorption in the cholesterol‐fed mouse: Impact on hepatic cholesterol homeostasis

Acyl CoA:cholesterol acyltransferase (ACAT) 2 is the major cholesterol‐esterifying enzyme in mouse enterocytes and hepatocytes. Male ACAT2+/+ and ACAT2−/ − mice were fed chow containing added cholesterol (0%‐0.500% w/w) for 24 days. Over this range, fractional cholesterol absorption in the ACAT2+/+ mice fell from 41.4% ± 6.6% to 21.0% ± 5.2%, and in their ACAT2−/− counterparts it fell from 35.1% ± 4.5% to 7.9% ± 0.8%. The mass of dietary cholesterol absorbed (mg/d per 100 g body weight) increased from 1.2 ± 0.2 to 14.7 ± 4.4 in the ACAT2+/+ mice and from 1.0 ± 0.2 to 5.5 ± 0.6 in those without ACAT2. In the ACAT2+/+ mice, hepatic cholesterol concentrations increased as a function of intake despite compensatory changes in cholesterol and bile acid synthesis and in the expression of adenosine triphosphate–binding cassette transporter G5 (ABCG5) and ABC transporter G8 (ABCG8). In contrast, in ACAT2−/− mice in which the amount of cholesterol absorbed at the highest intake was only 37% of that in the ACAT2+/+ mice, suppression of synthesis was a sufficient adaptive response; there was no change in bile acid synthesis, ABCG5/G8 expression, or hepatic cholesterol concentration. The expression of adenosine triphosphate–binding cassette transporter A1 (ABCA1) in the jejunum was markedly elevated in the ACAT2−/− mice, irrespective of dietary cholesterol level. In conclusion, although ACAT2 deficiency limits cholesterol absorption, the extent to which it impacts hepatic cholesterol homeostasis depends on cholesterol intake. Loss of ACAT2 activity may result in unesterified cholesterol being absorbed via an ABCA1‐mediated basolateral efflux pathway. (HEPATOLOGY 2004;40:1088–1097.)
Role of complement and perspectives for intervention in ischemia-reperfusion damage

Abstract Reperfusion of an organ following prolonged ischemia instigates the pro-inflammatory and pro-coagulant response of ischemia / reperfusion (IR) injury. IR injury is a wide-spread pathology, observed in many clinically relevant situations, including myocardial infarction, stroke, organ transplantation, sepsis and shock, and cardiovascular surgery on cardiopulmonary bypass. Activation of the classical, alternative, and lectin complement pathways and the generation of the anaphylatoxins C3a and C5a lead to recruitment of polymorphonuclear leukocytes, generation of radical oxygen species, up-regulation of adhesion molecules on the endothelium and platelets, and induction of cytokine release. Generalized or pathway-specific complement inhibition using protein-based drugs or low-molecular-weight inhibitors has been shown to significantly reduce tissue injury and improve outcome in numerous in-vitro, ex-vivo, and in-vivo models. Despite the obvious benefits in experimental research, only few complement inhibitors, including C1-esterase inhibitor, anti-C5 antibody, and soluble complement receptor 1, have made it into clinical trials of IR injury. The results are mixed, and the next objectives should be to combine knowledge and experience obtained in the past from animal models and channel future work to translate this into clinical trials in surgical and interventional reperfusion therapy as well as organ transplantation.
A Dielectric Rod Waveguide for Hyperthermia Application

In this paper, an applicator of dielectric rod waveguide for the microwave heating is described. The applicator consists of acrylic cylinder filled with deionized water as dielectric. By circulating the deionized water, the dielectric rod applicator acts as the surface cooling device, so that it doesn't need any bolus, and useful pattern of the effective heating region measured by heating experiment was obtained, which was circular or spheroidal shape and axially symmetric. This surface cooling function enables dielectric rod applicator to control the site of effective heating regions along the depth axis.
Inhibition of mTOR Kinase by AZD8055 Can Antagonize Chemotherapy-induced Cell Death through Autophagy Induction and Down-regulation of p62/Sequestosome 1*

Background: The dual mTORC1/mTORC2 inhibitor AZD8055 can induce autophagy. Results: Autophagy induction by AZD8055 antagonizes chemotherapy-induced cell death in association with inhibition of ULK1 phosphorylation at Ser757 and down-regulation of p62/sequestosome 1. Conclusion: AZD8055 induces pro-survival autophagy that attenuates cell death by down-regulating p62. Significance: mTOR kinase inhibition may reduce the efficacy of cytotoxic chemotherapy. AZD8055 is an ATP-competitive inhibitor of mammalian target of rapamycin (mTOR) that forms two multiprotein complexes, mTORC1 and mTORC2, and negatively regulates autophagy. We demonstrate that AZD8055 stimulates and potentiates chemotherapy-mediated autophagy, as shown by LC3I-II conversion and down-regulation of the ubiquitin-binding protein p62/sequestosome 1. AZD8055-induced autophagy was pro-survival as shown by its ability to attenuate cell death and DNA damage (p-H2AX), and to enhance clonogenic survival by cytotoxic chemotherapy. Autophagy inhibition by siRNA against Beclin 1 or LC3B, or by chloroquine, partially reversed the cytoprotective effect of AZD8055 that was independent of cell cycle inhibition. The pro-survival role of autophagy was confirmed using ectopic expression of Beclin 1 that conferred cytoprotection. To determine whether autophagy-mediated down-regulation of p62/sequestosome 1 contributes to its pro-survival role, we generated p62 knockdown cells using shRNA that showed protection from chemotherapy-induced cell death and DNA damage. We also overexpressed wild-type (wt) p62 that promoted chemotherapy-induced cell death, whereas mutated p62 at functional domains (PB1, UBA) failed to do so. The ability of ectopic wt p62 to promote cell death was blocked by AZD8055. AZD8055 was shown to inhibit phosphorylation of the autophagy-initiating kinase ULK1 at Ser757 and inhibited known targets of mTORC1 (p-mTOR Ser2448, p70S6K, p-S6, p4EBP1) and mTORC2 (p-mTOR Ser2481, p-AKT Ser473). Knockdown of mTOR, but not Raptor or Rictor, reduced p-ULK1 at Ser757 and enhanced chemotherapy-induced autophagy that resulted in a similar cytoprotective effect as shown for AZD8055. In conclusion, AZD8055 inhibits mTOR kinase and ULK1 phosphorylation to induce autophagy whose pro-survival effect is due, in part, to down-regulation of p62.
Telomere attrition and growth: a life‐history framework and case study in common terns

The relationship between growth and age‐specific telomere length, as a proxy of somatic state, is increasingly investigated, but observed patterns vary and a predictive framework is lacking. We outline expectations based on the assumption that telomere maintenance is costly and argue that individual heterogeneity in resource acquisition is predicted to lead to positive covariance between growth and telomere length. However, canalization of resource allocation to the trait with a larger effect on fitness, rendering that trait relatively invariant, can cause the absence of covariance. In a case study of common tern (Sterna hirundo) chicks, in which hatching order is the main determinant of variation in resource acquisition within broods, we find that body mass, but not telomere length or attrition, varies with hatching order. Moreover, body mass and growth positively predict survival to fledging, whereas telomere length and attrition do not. Using a novel statistical method to quantify standardized variance in plasticity, we estimate between‐individual variation in telomere attrition to be only 12% of that of growth. Consistent with the relative invariance of telomere attrition, we find no correlation between age‐specific body mass or growth and telomere attrition. We suggest that common tern chicks prioritize investment in long‐term somatic state (as indicated by canalization of telomere maintenance) over immediate survival benefits of growth as part of an efficient brood reduction strategy that benefits the parents. As such, interspecific variation in the growth–telomere length relationship may be explained by the extent to which parents benefit from rapid mortality of excess offspring.
Tag SNP selection using particle swarm optimization

Single nucleotide polymorphisms (SNPs) are the most abundant form of genetic variations amongst species. With the genome‐wide SNP discovery, many genome‐wide association studies are likely to identify multiple genetic variants that are associated with complex diseases. However, genotyping all existing SNPs for a large number of samples is still challenging even though SNP arrays have been developed to facilitate the task. Therefore, it is essential to select only informative SNPs representing the original SNP distributions in the genome (tag SNP selection) for genome‐wide association studies. These SNPs are usually chosen from haplotypes and called haplotype tag SNPs (htSNPs). Accordingly, the scale and cost of genotyping are expected to be largely reduced. We introduce binary particle swarm optimization (BPSO) with local search capability to improve the prediction accuracy of STAMPA. The proposed method does not rely on block partitioning of the genomic region, and consistently identified tag SNPs with higher prediction accuracy than either STAMPA or SVM/STSA. We compared the prediction accuracy and time complexity of BPSO to STAMPA and an SVM‐based (SVM/STSA) method using publicly available data sets. For STAMPA and SVM/STSA, BPSO effective improved prediction accuracy for smaller and larger scale data sets. These results demonstrate that the BPSO method selects tag SNP with higher accuracy no matter the scale of data sets is used. © 2009 American Institute of Chemical Engineers Biotechnol. Prog. , 2010
Immunopharmacology and in fl ammation Anti-in fl ammatory effects of a triple-bond resveratrol analog : Structure and function relationship

Resveratrol is a polyphenol found in grapes and red wine, showing well-characterized anti-inflammatory and antiproliferative activities. In order to exceed resveratrol's biological effects and to reveal the structural determinants of the molecule's activity, numerous derivatives were synthesized recently. Most of these resveratrol analogs vary from the original molecule in the number, position or identity of the phenolic functional groups. Investigation of the analogs provided important data regarding structure– activity relationship of the molecule. With the exception of cisand trans-resveratrol and the reduced form dihydroresveratrol, little is known about the molecular effects of the stilbene backbone. In the present study we investigated the anti-inflammatory properties of a new, triple-bond resveratrol analog, 3,40 ,5-trihydroxy-diphenylacetylene (TDPA) on lipopolysaccharide-stimulated RAW macrophages. We found that the analog had weaker antioxidant activity and stronger inhibitory effect on nuclear factorkappaB activation, and on cyclooxygenase-2, tumor necrosis factor α and interleukin-6 production. It also prevented lipopolysaccharide-induced depolarization of the mitochondrial membrane. In contrast to resveratrol, TDPA increased the phosphorylation of c-Jun N-terminal and p38 mitogen activated protein kinases. In summary, we identified a novel compound with better anti-inflammatory properties than resveratrol. Our results contributed to a better understanding of the structural determinants of resveratrol's biological activities. & 2014 Elsevier B.V. All rights reserved.
Combination chemoprophylaxis and immunoprophylaxis in reducing the incidence of leprosy

Leprosy is a complex infectious disease caused by Mycobacterium leprae that is a leading cause of nontraumatic peripheral neuropathy. Current control strategies, with a goal of early diagnosis and treatment in the form of multidrug therapy, have maintained new case reports at ~225,000 per year. Diagnostic capabilities are limited and even with revisions to multidrug therapy regimen, treatment can still require up to a year of daily drug intake. Although alternate chemotherapies or adjunct immune therapies that could provide shorter or simpler treatment regimen appear possible, only a limited number of trials have been conducted. More proactive strategies appear necessary in the drive to elimination. As a prevention strategy, most chemoprophylaxis campaigns to date have provided about a 2-year protective window. Vaccination, in the form of a single bacillus Calmette–Guérin (BCG) immunization, generally provides ~50% reduction in leprosy cases. Adapting control strategies to provide both chemoprophylaxis and immunoprophylaxis has distinct appeal, with chemoprophylaxis theoretically buttressed by vaccination to generate immediate protection that can be sustained in the long term. We also discuss simple assays measuring biomarkers as surrogates for disease development or replacements for invasive, but not particularly sensitive, direct measures of M. leprae infection. Such assays could facilitate the clinical trials required to develop these new chemoprophylaxis, immunoprophylaxis strategies, and transition into wider use.
Characterization of the novel GlyT1 PET tracer [18F]MK‐6577 in humans

Decreased glutamatergic neurotransmission is hypothesized to be involved in the pathophysiology of schizophrenia. Inhibition of glycine transporter Type‐1 (GlyT1) reuptake is expected to increase the glutamatergic neurotransmission and may serve as treatment for cognitive and negative symptoms of schizophrenia. In this article, we present human data from a novel GlyT1 PET tracer, [18F]MK‐6577. In the process of developing a GlyT1 inhibitor therapeutic, a PET tracer can assist in determining the dose with a high probability of sufficiently testing the mechanism of action. This article reports the human PET studies with [18F]MK‐6577 for measuring GlyT1 receptor availability at baseline in normal human subjects and occupancy with a GlyT1 inhibitor, MK‐2637. Studies were also performed to measure radiation burden and the baseline test‐retest (T‐RT) variability of the tracer. The effective dose from sequential whole‐body dosimetry scans in three male subjects was estimated to be 24.5 ± 2.9 µSV/MBq (mean ± SD). The time–activity curves from T‐RT scans modeled satisfactorily using a two tissue compartmental model. The tracer uptake was highest in the pons (VT = 6.7 ± 0.9, BPND = 4.1 ± 0.43) and lowest in the cortex (VT = 2.1 ± 0.5, BPND = 0.60 ± 0.23). VT T‐RT variability measured in three subjects was <12% on average. The occupancy scans performed in a cohort of 15 subjects indicated absence of a reference region. The in vivo potency (Occ50) of MK‐2637 was determined using two methods: A: Lassen plot with a population input function (Occ50 = 106 nM, SE = 20 nM) and B: pseudo reference tissue model using cortex as the pseudo reference region (Occ50 = 141 nM, SE = 21 nM). Synapse 69:33–40, 2015. © 2014 Wiley Periodicals, Inc.
Ophthalmologic Observations in a Patient with Partial Mosaic Trisomy 8

Abstract Background: To carefully assess the phenotype and genotype of a patient with partial mosaic trisomy 8 with particular attention to ophthalmologic features. Methods: Ophthalmologic and neuro-ophthalmologic examination; neuroimaging; conventional karyotyping; and array comparative genomic hybridization (CGH). Results: The proband was the only affected child of a non-consanguineous family. At birth she was noted to have facial dysmorphism including telecanthus, low set ears, prominent nares, and an everted lower lip. She had an accommodative esotropia with otherwise normal globes, optic nerves, retinae, and orbits. She also had delayed motor milestones and mild mental retardation associated with agenesis of the corpus callosum. Both karyotyping and array CGH documented mosaic partial trisomy of chromosome 8 that included all of the “q” arm and part of the proximal “p” arm. Conclusions: This girl had a number of the classic features of mosaic trisomy 8, including an accommodative esotropia with none of the other ocular and orbital anomalies described in patients with mosaic trisomy 8. This report constitutes an initial effort to create a virtual database of patients with mosaic chromosome 8 in which careful phenotype-genotype correlation employing high resolution array CGH may help identify clues regarding the genetic etiology of ophthalmologic features of this syndrome.
New mouse genetic models for human contraceptive development

Genetic strategies for the post-genomic sequence age will be designed to provide information about gene function in a myriad of physiological processes. Here an ENU mutagenesis program (http://reprogenomics.jax.org) is described that is generating a large resource of mutant mouse models of infertility; male and female mutants with defects in a wide range of reproductive processes are being recovered. Identification of the genes responsible for these defects, and the pathways in which these genes function, will advance the fields of reproduction research and medicine. Importantly, this program has potential to reveal novel human contraceptive targets.
A Prospective Study of Ankle Injury Risk Factors

Many factors are thought to cause ankle ligament in juries. The purpose of this study was to examine injury risk factors prospectively and determine if an abnor mality in any one or a combination of factors identifies an individual, or an ankle, at risk for subsequent inver sion ankle injury. We examined 145 college-aged ath letes before the athletic season and measured gener alized joint laxity, anatomic foot and ankle alignment, ankle ligament stability, and isokinetic strength. These athletes were monitored throughout the season. Fifteen athletes incurred inversion ankle injuries. Statistical analyses were performed using both within-group (un injured versus injured groups) data and within-subject (injured versus uninjured ankles) data. No significant differences were found between the injured (N = 15) and uninjured (N = 130) groups in any of the param eters measured. However, the eversion-to-inversion strength ratio was significantly greater for the injured group compared with the uninjured group. Analysis of the within-subject data demonstrated that plantar flex ion strength and the ratio of dorsiflexion to plantar flex ion strength was significantly different for the injured ankle compared with the contralateral uninjured ankle. Individuals with a muscle strength imbalance as meas ured by an elevated eversion-to-inversion ratio exhib ited a higher incidence of inversion ankle sprains. Ankles with greater plantar flexion strength and a smaller dorsiflexion-to-plantar flexion ratio also had a higher incidence of inversion ankle sprains.
Injection Drug Users’ Access to a Supervised Injection Facility in Vancouver, Canada: The Influence of Operating Policies and Local Drug Culture

North America’s first supervised injection facility (SIF) was established in Vancouver, Canada, in 2003. Although evaluation research has documented reductions in risk behavior among SIF users, there has been limited examination of the influence of operational features on injection drug users’ access to these facilities. We conducted an ethnographic study that included observational research within the SIF, 50 in-depth individual interviews with SIF users, and analysis of the regulatory frameworks governing the SIF. The government-granted exemption allowing the facility to operate legally imposes key operating regulations, as well as a cap on capacity, which results in significant wait times to enter the injecting room. Regulations that prohibit practices that are common in the local drug culture also negatively affect SIF utilization. Restructuring policies that shape the operation of the SIF could enhance access to the facility and permit SIF services to better accommodate local drug use practices.
Nicotine regulates smoking patterns.

BACKGROUND Since 1953, the sales-weighted average "tar" and nicotine yields of commercial cigarettes in developed countries have significantly declined. However, the risk for chronic obstructive pulmonary disease (COPD) and for cancer of the lung has not decreased; adenocarcinoma incidence even continues to rise faster than the rate of squamous cell carcinoma of the lung. Undiminished risk of cigarette smokers for COPD and lung cancer is largely due to more intense smoking and deeper inhalation of the smoke of "low-yield" cigarettes and to significant changes in the smoke yields of certain lung carcinogens. METHODS Puff frequency, puff duration, and puff volume of cigarette smokers were determined by a microcomputer-assisted flow transducer. These parameters were then programmed into a smoking machine to generate mainstream smoke for quantifying nicotine and lung carcinogens. RESULTS Simulating the human smoking characteristics increases the yields of "tar" and nicotine per cigarette two- to threefold above Federal Trade Commission-reported levels. Smoke yields of lung carcinogens like benzo[alpha]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone parallel those of nicotine and "tar. " CONCLUSIONS The way people smoke and the total number of cigarettes consumed daily determine the uptake, i.e., the administered dose of nicotine, other toxic, and genotoxic smoke constituents. It is important to communicate this to consumers rather than letting the smokers believe that they are truly smoking a cigarette of lower smoke yields when they choose "light" or "ultralight" products.