Low noise, self-referenced all polarization maintaining Ytterbium fiber laser frequency comb.

We report the implementation of a self-referenced optical frequency comb generated by a passively mode-locked all polarization maintaining (PM) Yb fiber laser based on a nonlinear amplifying loop mirror (NALM). After spectral broadening the optical spectrum spans from 650 nm to 1400 nm, allowing for the generation of an optical octave and carrier envelope offset frequency (f) stabilization through a conventional f-2f interferometer. We demonstrate for the first time the stabilization of the f of such a PM Yb system with an in-loop fractional frequency stability scaled to an optical frequency of low 10 at 1 second averaging time, offering a great potential for applications in optical atomic clock metrology.

Single allele Lmbrd1 knockout results in cardiac hypertrophy.

Background/purpose: LMBD1 protein, a type IV-B plasma membrane protein possessing nine putative trans-membrane domains, was previously demonstrated at cellular level to play a critical part in the signaling cascade of insulin receptor through its involvement in regulating clathrin-mediated endocytosis. However, at physiological level, the significance of LMBD1 protein in cardiac development remains unclear.

Methods: To understand the role of Lmbrd1 gene involved in the cardiac function, heterozygous knockout mice were used as an animal model system.

Characteristics of intrabony nerve canals in mandibular interforaminal region by using cone-beam computed tomography and a recommendation of safe zone for implant and bone harvesting.

Background: Cone-beam computed tomography can accurately show anatomic structure of intrabony nerve canals in mandibular interforaminal region.

Purpose: The aim was to evaluate the characteristics of intrabony nerve canals in mandibular interforaminal region by using cone-beam computed tomography (CBCT) and determine a safe zone for implant and bone harvesting.

Materials And Methods: Hemimandibles (824) CBCT images were obtained.

11,670 whole-genome sequences representative of the Han Chinese population from the CONVERGE project.

The China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology (CONVERGE) project on Major Depressive Disorder (MDD) sequenced 11,670 female Han Chinese at low-coverage (1.7X), providing the first large-scale whole genome sequencing resource representative of the largest ethnic group in the world. Samples are collected from 58 hospitals from 23 provinces around China.

Clinical Evaluation of Bone Strength and Fracture Risk.

Purpose Of Review: This paper seeks to evaluate and compare recent advances in the clinical assessment of the changes in bone mechanical properties that take place as a result of osteoporosis and other metabolic bone diseases and their treatments.

Recent Findings: In addition to the standard of DXA-based areal bone mineral density (aBMD), a variety of methods, including imaging-based structural measurements, finite element analysis (FEA)-based techniques, and alternate methods including ultrasound, bone biopsy, reference point indentation, and statistical shape and density modeling, have been developed which allow for reliable prediction of bone strength and fracture risk. These methods have also shown promise in the evaluation of treatment-induced changes in bone mechanical properties.

Adaptations in the Microarchitecture and Load Distribution of Maternal Cortical and Trabecular Bone in Response to Multiple Reproductive Cycles in Rats.

Pregnancy, lactation, and weaning result in dramatic changes in maternal calcium metabolism. In particular, the increased calcium demand during lactation causes a substantial degree of maternal bone loss. This reproductive bone loss has been suggested to be largely reversible, as multiple clinical studies have found that parity and lactation history have no adverse effect on postmenopausal fracture risk.

The Genetic Architecture of Major Depressive Disorder in Han Chinese Women.

Importance: Despite the moderate, well-demonstrated heritability of major depressive disorder (MDD), there has been limited success in identifying replicable genetic risk loci, suggesting a complex genetic architecture. Research is needed to quantify the relative contribution of classes of genetic variation across the genome to inform future genetic studies of MDD.

Objectives: To apply aggregate genetic risk methods to clarify the genetic architecture of MDD by estimating and partitioning heritability by chromosome, minor allele frequency, and functional annotations and to test for enrichment of rare deleterious variants.

Understanding the diverse functions of Huatan Tongluo Fang on rheumatoid arthritis from a pharmacological perspective.

Huatan Tongluo Fang (HTTLF) is a traditional herbal formula that can resolve phlegm and dredge collaterals. HTTLF has also been used to treat rheumatoid arthritis (RA); however, the mechanism underlying the therapeutic effects of HTTLF on RA has not been clearly elucidated at the molecular level. In the present study, an integrated model of system pharmacology containing chemical space analysis, potential active compound prediction and compound-target-disease network was constructed to investigate the molecular mechanisms of HTTLF.

[Anti-aging traditional Chinese medicine： potential mechanisms involving AMPK pathway and calorie restriction based on "medicine-food homology" theory].

There have been many reports about the anti-aging effect of traditional Chinese medicine (TCM), but the material basis and mechanism of action have not been clearly elucidated. AMP-activated protein kinase (AMPK) is the receptor of energy metabolism and its life extending effect has been confirmed in different experiments. Over expression or activation with metform in of AAK-2/AMPK has been shown to extend life expectancy in nematodes and Drosophila.

Genetic Control over mtDNA and Its Relationship to Major Depressive Disorder.

Control over the number of mtDNA molecules per cell appears to be tightly regulated, but the mechanisms involved are largely unknown. Reversible alterations in the amount of mtDNA occur in response to stress suggesting that control over the amount of mtDNA is involved in stress-related diseases including major depressive disorder (MDD). Using low-coverage sequence data from 10,442 Chinese women to compute the normalized numbers of reads mapping to the mitochondrial genome as a proxy for the amount of mtDNA, we identified two loci that contribute to mtDNA levels: one within the TFAM gene on chromosome 10 (rs11006126, p value = 8.

Predicting the transition from anxiety to depressive symptoms in early adolescence: Negative anxiety response style as a moderator of sequential comorbidity.

Background: Anxiety often precedes depression. The anxiety response styles theory of comorbidity suggests anxious individuals with a tendency to ruminate or make hopeless attributions about anxiety symptoms (negative anxiety response styles [NARS]) are more vulnerable to subsequent depressive symptoms. However, this theory has never been tested in adolescence, when the anxiety-depression transition may frequently occur, or using an extended (one-year) follow-up period.

On clinical trials with a high placebo response rate.

The basic problem that causes the frequent failure of a standard randomized parallel placebo-controlled clinical trial with a high placebo response rate is the underestimation of the treatment effect by the observed relative treatment difference. A two-period sequential parallel enrichment design has been proposed where the first period is a standard parallel design and at the end of the first period, the placebo non-responders are identified and re-randomized in the second period. Based on such a design, available methods have primarily focused on testing either the first period treatment null hypothesis or the global null hypothesis defined as the joint period 1 and period 2 treatment effect null hypothesis by a test statistic which is either derived from a combined statistic or defined directly as a weighted z-score where the weights are functions of some population and design parameters satisfying certain power optimality criterion.

Overview of multiple testing methodology and recent development in clinical trials.

Multiplicity control is an important statistical issue in clinical trials where strong control of the type I error rate is required. Many multiple testing methods have been proposed and applied to address multiplicity issues in clinical trials. This paper provides an application oriented and comprehensive overview of commonly used multiple testing procedures and recent developments in statistical methodology in multiple testing in clinical trials.

Molecular signatures of major depression.

Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual's somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.

Adenovirus-delivered PDCD5 counteracts adriamycin resistance of osteosarcoma cells through enhancing apoptosis and inhibiting Pgp.

In the present study, we investigated the roles of PDCD5 (programmed cell death 5) in multidrug re-sistance (MDR) of osteosarcoma cells and the possible lurking mechanisms. An adenovirus expression vector of PDCD5 was constructed and transfected into human adriamycin-resistant osteosarcoma cell line Saos-2/ADM. We found that up-regulation of PDCD5 could significantly enhance the sensitivity of Saos-2/ADM cells towards vincristine, methotrexate, cisplatin and arsenic trioxide (As2O3), and could decrease the capacity of cells to efflux adriamycin.

The feasibility study of non-invasive fetal trisomy 18 and 21 detection with semiconductor sequencing platform.

Objective: Recent non-invasive prenatal testing (NIPT) technologies are based on next-generation sequencing (NGS). NGS allows rapid and effective clinical diagnoses to be determined with two common sequencing systems: Illumina and Ion Torrent platforms. The majority of NIPT technology is associated with Illumina platform.

Smoking and major depressive disorder in Chinese women.

Objective: To investigate the risk factors that contribute to smoking in female patients with major depressive disorder (MDD) and the clinical features in depressed smokers.

Methods: We examined the smoking status and clinical features in 6120 Han Chinese women with MDD (DSM-IV) between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and smoking status and between risk factors for MDD and smoking status.

Meta-analysis based on weighted ordered P-values for genomic data with heterogeneity.

Background: Meta-analysis has become increasingly popular in recent years, especially in genomic data analysis, due to the fast growth of available data and studies that target the same questions. Many methods have been developed, including classical ones such as Fisher's combined probability test and Stouffer's Z-test. However, not all meta-analyses have the same goal in mind.

Ornithokinin (avian bradykinin) from the skin of the Chinese bamboo odorous frog, Odorrana versabilis.

One of the most widespread and abundant families of pharmacologically active peptides in amphibian defensive skin secretions is the bradykinins and related peptides. Despite retaining certain primary structural attributes that assign them to this peptide family, bradykinins and related peptides are unique among amphibian skin peptides in that they exhibit a wide range of primary structural variations, post-translational modifications and/or N-terminal or C-terminal extensions. Initially it was believed that their high degree of primary structural heterogeneity was reflective of random gene mutations within species, but latterly, there is an increasing body of evidence that the spectrum of structural modifications found within this peptide family is reflective of the vertebrate predator spectrum of individual species.

A two-step hierarchical hypothesis set testing framework, with applications to gene expression data on ordered categories.

Background: In complex large-scale experiments, in addition to simultaneously considering a large number of features, multiple hypotheses are often being tested for each feature. This leads to a problem of multi-dimensional multiple testing. For example, in gene expression studies over ordered categories (such as time-course or dose-response experiments), interest is often in testing differential expression across several categories for each gene.

Dose dependent cytotoxicity of pranoprofen in cultured human corneal endothelial cells by inducing apoptosis.

Pranoprofen (PPF), a non-steroidal anti-inflammatory drugs (NSAIDs), is often used in keratitis treatment in clinic. Several studies have assessed in vitro the cytotoxicity of topical NSAIDs to corneal epithelial cells due to its importance for predicting human corneal toxicity. Damage by cytotoxic drugs can result in excessive loss of human corneal endothelial (HCE) cells which lead to decompensation of the endothelium and eventual loss of visual acuity.

Optimizing capillary electrophoresis for top-down proteomics of 30-80 kDa proteins.

The direct analysis of intact proteins via MS offers compelling advantages in comparison to alternative methods due to the direct and unambiguous identification and characterization of protein sequences it provides. The inability to efficiently analyze proteins in the "middle mass range," defined here as proteins from 30 to 80 kDa, in a robust fashion has limited the adoption of these "top-down" methods. Largely, a result of poor liquid chromatographic performance, the limitations in this mass range may be addressed by alternative separations that replace chromatography.