Spectro-temporal modulations of speech encode speech structures and speaker characteristics. An algorithm which distinguishes speech from non-speech based on spectro-temporal modulation energies is proposed and evaluated in robust text-independent closed-set speaker identification simulations using the TIMIT and GRID corpora. Simulation results show the proposed method produces much higher speaker identification rates in all signal-to-noise ratio (SNR) conditions than the baseline system using mel-frequency cepstral coefficients. In addition, the proposed method also outperforms the system, which uses auditory-based nonnegative tensor cepstral coefficients [Q. Wu and L. Zhang,"Auditory sparse representation for robust speaker recognition based on tensor structure," EURASIP J. Audio, Speech, Music Process. 2008, 578612 (2008)], in low SNR (≤ 10 dB) conditions.

Context Over half of cancer patients in Singapore use some form of complementary or alternative medicine (CAM) to improve their immunity and general health status. The effectiveness of CAM, however, in reducing acute complications is currently unknown. Concerns also exist as to whether CAM may cause toxic effects in patients with cancer. Objective To investigate the changes in general health status, immunity, and organ function over a 6-month period in CAM and non-CAM users with cancer. Design The authors designed a single-center, retrospective cohort study. The patients had participated previously in a cross-sectional prevalence survey about the types of oral CAM they were using in addition to chemotherapy. The authors used the data from the survey and clinical and medication-use information from patients' medical and pharmaceutical records to complete the current study. Setting The study occurred at the National Cancer Centre Singapore (NCCS), which is the largest ambulatory cancer center in Singapore and treats two-thirds of the solid-tumor patients in Singapore. The study excluded patients if their medical records were incomplete and/or if the patients had not received any cytotoxic or targeted therapies at the time of survey. Participants The authors reviewed the records of a total of 403 patients and excluded 46 patients because their records were missing (n=20) or because they had not received any form of anticancer treatment at the time of survey (n=26). They included 357 patients in the current study. The authors did not contact patients for this follow-up study. Outcome Measures The authors collected data on clinical characteristics for each patient and assessed the differences between each characteristic at baseline (at the time of the survey) and at 6 months after baseline measurement. The authors evaluated clinical characteristics using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3. Results As a whole, CAM use provided an absolute reduction of infection episodes by 11.9%(P=.045) and of antibiotic use by 10.3%(P=.022). Subgroup analysis showed a reduction of documented infection by 17.9%(P=.02) and a 13% decrease in hospitalizations due to infections (P=.043) among metastatic cancer patients who used CAM. CAM usage was not associated with significant changes of hepatic and renal function. Conclusion CAM use in patients with cancer was associated with a reduction in hospitalizations and requirements for antibiotics. CAM use was not associated with significant changes in hepatic and renal function. There is a need for well-designed, prospective clinical studies to confirm these findings.(Altern Ther Health Med. 2012;18(1):12-17.).

Nephroblastoma overexpressed (NOV or CCN3) is a secreted, matrix-associated protein that belongs to the CCN gene family and is involved in many cellular functions, including growth, differentiation, and adhesion. The effect of CCN3 on human prostate cancer cells, however, is unknown. Here, we have shown that CCN3 increased cell migration and intercellular adhesion molecule-1 (ICAM-1) expression in prostate cancer cells. In addition, expression of CCN3 was positively correlated with both cell migration and ICAM-1 expression in human prostate cancer cells. CCN3 activated a signal transduction pathway that included αvβ3 integrin, integrin-linked kinase (ILK), Akt, and NF-κB. Reagents that inhibit specific components of this pathway each diminished the ability of CCN3 to effect cell migration and ICAM-1 expression. Moreover, CCN3 increased binding of p65 to an NF-κB binding element in the ICAM-1 promoter. Finally, knockdown of CCN3 expression markedly inhibited cell migration, tumor growth in bone, and bone metastasis. Taken together, our results indicate that CCN3 enhances the migration of prostate cancer cells by increasing ICAM-1 expression through a signal transduction pathway that involves αvβ3 integrin, ILK, Akt, and NF-κB. CCN3 thus represents a promising new target for treating prostate cancer.

Please cite this paper as: Lee C, Lin S, Lin C, Shih J, Lin T, Su Y. Clinical utility of array comparative genomic hybridisation for prenatal diagnosis: a cohort study of 3171 pregnancies. BJOG 2012; DOI: 10.1111/j.1471-0528.2011.03279.x Objective  To evaluate the clinical value of prenatal array comparative genomic hybridisation (CGH) in screening for submicroscopic genomic imbalances. Design  Cross-sectional study. Setting  Tertiary referral centre. Population  From June 2008 to February 2011, 3171 fetuses underwent prenatal array CGH testing and karyotyping at the National Taiwan University Hospital. Indications for invasive prenatal diagnosis included abnormal karyotype, abnormal ultrasound, advanced maternal age and parental anxiety. Methods  In all, 2497 fetuses were screened with 1-Mb resolution bacterial artificial chromosome array-based CGH, and 674 fetuses with 60-K oligonucleotide array-based CGH. Multiplex ligation-dependent probe amplification, fluorescence in situ hybridization, or 105-K oligonucleotide array CGH provided further confirmation. Main outcome measure  Copy number variations identified by array CGH. Results  Array CGH detected numerical chromosome anomalies in 37 (1.2%) fetuses, microdeletion/duplication in 34 (1.1%) fetuses, large deletion/duplication in 13 (0.4%) fetuses, benign copy number changes in 13 (0.4%) fetuses and variation of unknown clinical significance in five (0.2%) fetuses. Array CGH was effective in identifying submicroscopic genomic imbalance in fetuses with de novo balance translocations (2/17, 1.8%), supernumerary marker chromosomes (3/6, 50%), and abnormal prenatal ultrasound findings (33/194, 17.0%). Array CGH detected microdeletions/duplications in 12 fetuses with normal karyotype. Conclusion  Prenatal array CGH is effective in screening for submicroscopic genomic imbalance. Array CGH may add 8.2% to the diagnostic field, compared with conventional karyotyping, for fetuses with abnormal ultrasound results, and is particularly useful in fetuses with karyotypic balanced translocation or marker chromosomes. There is a 0.52% baseline risk of submicroscopic genomic imbalance, even in women with an uneventful prenatal examination.

Abstract Proper subcellular localization is critical for proteins to perform their roles in cellular functions. Proteins are transported by different cellular sorting pathways, some of which take a protein through several intermediate locations until reaching its final destination. The pathway a protein is transported through is determined by carrier proteins that bind to specific sequence motifs. In this article, we present a new method that integrates protein interaction and sequence motif data to model how proteins are sorted through these sorting pathways. We use a hidden Markov model (HMM) to represent protein sorting pathways. The model is able to determine intermediate sorting states and to assign carrier proteins and motifs to the sorting pathways. In simulation studies, we show that the method can accurately recover an underlying sorting model. Using data for yeast, we show that our model leads to accurate prediction of subcellular localization. We also show that the pathways learned by our model recover many known sorting pathways and correctly assign proteins to the path they utilize. The learned model identified new pathways and their putative carriers and motifs and these may represent novel protein sorting mechanisms. Supplementary results and software implementation are available from http://murphylab.web.cmu.edu/software/2010_RECOMB_pathways/.

A base catalyzed hydrolysis reaction of thiolester has been studied in both gas and solution phases using two ab initio quantum mechanics calculations such as Gaussian09 and CPMD. The free energy surface along the reaction path is also constructed using a configuration sampling technique namely the metadynamics method. While there are two different reaction paths obtained for the potential profile of the base-catalyzed hydrolysis reaction for thiolester in gas phase, a triple-well reaction path is computed for the reaction in solution phase by both two quantum mechanics calculations. Unlike a SN2 mechanism (a concerted mechanism) found for the gas-phase reaction, a nucleophilic attack from the hydroxide ion on the carbonyl carbon to yield a tetrahedral intermediate (a stepwise mechanism) is observed for the solution phase reaction. Moreover, the energy profiles computed by these two theoretical calculations are found to be well comparable with those determined experimentally.

The soil bacterium Bacillus subtilis can utilize exogenous proline as a sole nitrogen or carbon source. The proline-inducible putBCP (formerly ycgMNO) operon encodes proteins responsible for proline uptake and two-step oxidation of proline to glutamate. We now report that a gene (formerly ycgP, now designated prcR) located downstream of the putBCP operon is essential for B. subtilis cells to utilize proline as a sole nitrogen or carbon source. Disruption of the prcR gene also abolished proline induction of putB transcription. prcR expression is not subject to autoregulation and proline induction. The PrcR protein shows no significant amino acid sequence similarity to the known transcriptional activators for proline utilization genes of other bacteria, but it shows partial amino acid sequence similarity with the transcriptional regulator PucR for purine degradation genes of B. subtilis. PrcR orthologs with unknown function are present in some other Bacillus species. Primer extension analysis suggests that both putB and prcR are transcribed by a σ(A)-dependent promoter. Deletion and mutation analysis revealed that an inverted repeat (TTGTGG-N5-CCACAA) centered at position -76 relative to the transcriptional initiation site of putB is essential for putB expression. Electrophoretic mobility shift assays showed that the purified His-tagged PrcR was capable of binding specifically to this inverted repeat. Altogether, these results suggest that PrcR is a PucR-type transcriptional activator mediating expression of the B. subtilis putBCP operon in response to proline availability.

Although many clinical trials have showed that metformin improves non-alcoholic fatty liver disease, which is a common liver disease associated with hepatic enzyme abnormalities, an animal model is required to investigate the effects of altered gene expression and post-translational processing (proteins) in mediating the observed responses. Laying hens appear to develop fatty livers, as in the case in human beings, when ingesting energy in excess of maintenance, and they can be used as an animal model for observing hepatic steatosis. The aim of this study was to investigate whether metformin could improve the non-alcoholic fatty liver of laying hens and to examine the possible mechanisms of lipid-lowering effects. Forty-eight Leghorn laying hens of Hy-Line variety W-36 - 44weeks with 64.8% hen-day egg production - were randomly assigned into 4 treatments, each receiving 0, 10, 30, or 100mg of metformin with saline per kg body weight by daily wing vein injection. Results showed that, compared with the control, significant decreases existed in the laying rates; plasma triglyceride, cholesterol, and insulin levels; body weights; abdominal fat weights; hepatic lipid contents; and hepatic fatty acid synthase expression of layers receiving 30 or 100mg per kg body weight, whereas significant increases in their hepatic 5'adenosine monophosphate-activated protein kinase, acyl-CoA carboxylase phosphorylation, adipose triglyceride lipase, and carnitine palmitoyl transferase-1 expression were observed. These data suggest that metformin could reduce lipid deposits in the liver and that the laying hen is a valuable animal model for studying hepatic steatosis.

Der f 7 and Der p 7 are important house dust mite allergens with known structure and suggested biological function recently. However, their IgE-binding determinants remain unknown. The purpose of this study is to identify the IgE-reactive epitopes of Der f 7 and the determinants of IgE-mediated cross-reactivity between Der f 7 and Der p 7. IgE-reactive determinants were identified by immunodot blot inhibition using synthetic overlapping peptides, allergen mutants, and a Der f 7 structural model. Our results showed that synthetic peptides with sequence (156)SILDP(160) on Der f 7 bind IgE in two of the 30 asthmatic serum samples tested. Recombinant Der f 7 I157A, L158A, or D159A mutants have reduced IgE-binding activity. Inhibition experiments confirmed Asp159 as a critical core residue for IgE-binding. Among Der p 7, Der f 7 and Der f 7 mutants with single substitution between residues 156 and 160, only the D159A mutant cannot inhibit significantly IgE-binding against Der p 7. Therefore, Asp159 contributes to IgE-mediated cross-reactivity between Der f 7 and Der p 7. The structural model constructed for Der f 7 suggests that the IgE-binding epitope forms a loop-like structure on the surface of the molecule. In conclusion, Asp 159 is a critical core residue of an IgE-binding and IgE-mediated cross-reactive epitope (156)SILDP(160) of Der f 7. Results obtained from this study provide more information on molecular and structural features related to allergenicity, underlying basis of IgE cross-reactivity between allergens, and in designing safer immunotherapy.