Cross-validation in nonparametric regression with outliers

A popular data-driven method for choosing the bandwidth in standard kernel regression is cross-validation. Even when there are outliers in the data, robust kernel regression can be used to estimate the unknown regression curve [Robust and Nonlinear Time Series Analysis. Lecture Notes in Statist. (1984) 26 163--184]. However, under these circumstances standard cross-validation is no longer a satisfactory bandwidth selector because it is unduly influenced by extreme prediction errors caused by the existence of these outliers. A more robust method proposed here is a cross-validation method that discounts the extreme prediction errors. In large samples the robust method chooses consistent bandwidths, and the consistency of the method is practically independent of the form in which extreme prediction errors are discounted. Additionally, evaluation of the method's finite sample behavior in a simulation demonstrates that the proposed method performs favorably. This method can also be applied to other problems, for example, model selection, that require cross-validation.Comment: Published at http://dx.doi.org/10.1214/009053605000000499 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Androgen receptor phosphorylation status at serine 578 predicts poor outcome in prostate cancer patients

Purpose: Prostate cancer growth is dependent upon androgen receptor (AR) activation, regulated via phosphorylation. Protein kinase C (PKC) is one kinase that can mediate AR phosphorylation. This study aimed to establish if AR phosphorylation by PKC is of prognostic significance. Methods: Immunohistochemistry for AR, AR phosphorylated at Ser-81 (pARS81), AR phosphorylated at Ser-578 (pARS578), PKC and phosphorylated PKC (pPKC) was performed on 90 hormone-naïve prostate cancer specimens. Protein expression was quantified using the weighted histoscore method and examined with regard to clinico-pathological factors and outcome measures; time to biochemical relapse, survival from biochemical relapse and disease-specific survival. Results: Nuclear PKC expression strongly correlated with nuclear pARS578 (c.c. 0.469, p=0.001) and cytoplasmic pARS578 (c.c. 0.426 p=0.002). High cytoplasmic and nuclear pARS578 were associated with disease-specific survival (p<0.001 and p=0.036 respectively). High nuclear PKC was associated with lower disease-specific survival when combined with high pARS578 in the cytoplasm (p=0.001) and nucleus (p=0.038). Combined high total pARS81 and total pARS578 was associated with decreased disease-specific survival (p=0.005) Conclusions: pARS578 expression is associated with poor outcome and is a potential independent prognostic marker in hormone-naïve prostate cancer. Furthermore, PKC driven AR phosphorylation may promote prostate cancer progression and provide a novel therapeutic target

Fine-grained Spatio-Temporal Distribution Prediction of Mobile Content Delivery in 5G Ultra-Dense Networks

The 5G networks have extensively promoted the growth of mobile users and novel applications, and with the skyrocketing user requests for a large amount of popular content, the consequent content delivery services (CDSs) have been bringing a heavy load to mobile service providers. As a key mission in intelligent networks management, understanding and predicting the distribution of CDSs benefits many tasks of modern network services such as resource provisioning and proactive content caching for content delivery networks. However, the revolutions in novel ubiquitous network architectures led by ultra-dense networks (UDNs) make the task extremely challenging. Specifically, conventional methods face the challenges of insufficient spatio precision, lacking generalizability, and complex multi-feature dependencies of user requests, making their effectiveness unreliable in CDSs prediction under 5G UDNs. In this paper, we propose to adopt a series of encoding and sampling methods to model CDSs of known and unknown areas at a tailored fine-grained level. Moreover, we design a spatio-temporal-social multi-feature extraction framework for CDSs hotspots prediction, in which a novel edge-enhanced graph convolution block is proposed to encode dynamic CDSs networks based on the social relationships and the spatio features. Besides, we introduce the Long-Short Term Memory (LSTM) to further capture the temporal dependency. Extensive performance evaluations with real-world measurement data collected in two mobile content applications demonstrate the effectiveness of our proposed solution, which can improve the prediction area under the curve (AUC) by 40.5% compared to the state-of-the-art proposals at a spatio granularity of 76m, with up to 80% of the unknown areas

Assessment of Extracts from Red Yeast Rice for Herb-Drug Interaction by in-vitro and in-vivo assays

Red yeast rice (RYR) is made by fermenting the yeast Monascus purpureus over rice. It is a source of natural red food colorants, a food garnish and a traditional medication. Results of the current study demonstrated that polar fractions of the RYR preparations contained herbal-drug interaction activity, which if left unremoved, enhanced P-glycoprotein activity and inhibited the major drug metabolizing cytochromes P450, i,e, CYP 1A2, 2C9 and 3A4. The data from Caco-2 cell absorption and animal model studies further demonstrated that the pharmacokinetic modulation effect by RYR preparations containing the polar fractions (“untreated” preparation) was greater than that from RYR preparations with the polar fractions removed (“treated” preparation). The data indicates a potential for herb-drug interactions to be present in RYR commonly sold as nutritional supplements when the polar fractions are not removed and this should be taken into consideration when RYR is consumed with medications, including verapamil

A review of the pharmacological effects of Arctium lappa (burdock)

Abstract Arctium lappa, commonly known as burdock, is being promoted/recommended as a healthy and nutritive food in Chinese societies. Burdock has been used therapeutically in Europe, North America and Asia for hundreds of years. The roots, seeds and leaves of burdock have been investigated in view of its popular uses in traditional Chinese medicine (TCM). In this review, the reported therapeutic effects of the active compounds present in the different botanical parts of burdock are summarized. In the root, the active ingredients have been found to "detoxify" blood in terms of TCM and promote blood circulation to the skin surface, improving the skin quality/texture and curing skin diseases like eczema. Antioxidants and antidiabetic compounds have also been found in the root. In the seeds, some active compounds possess anti-inflammatory effects and potent inhibitory effects on the growth of tumors such as pancreatic carcinoma. In the leaf extract, the active compounds isolated can inhibit the growth of micro-organisms in the oral cavity. The medicinal uses of burdock in treating chronic diseases such as cancers, diabetes and AIDS have been reported. However, it is also essential to be aware of the side effects of burdock including contact dermatitis and other allergic/inflammatory responses that might be evoked by burdock

Association between body mass index and risk of total knee replacement, the Singapore Chinese Health Study

SummaryPurposeData on the association between body mass index (BMI) and risk of knee osteoarthritis (KOA) are sparse for Asian populations who are leaner than Western populations. We evaluated the association between BMI and risk of total knee replacement (TKR) due to severe KOA among Chinese in Singapore.MethodsWe used data from the Singapore Chinese Health Study (SCHS), a population-based prospective cohort of 63,257 Chinese men and women, aged 45–74 years at enrollment from 1993 to 1998. Information on height, weight, diet and lifestyle factors were obtained via in-person interviews. TKR cases for severe KOA were identified via linkage with the nationwide hospital discharge database through 2011. Cox regression and weighted least squares regression were used in the analysis.ResultsThe mean BMI among cohort participants was 23.1 kg/m2, and more than two-thirds had BMI below 25 kg/m2. A total of 1649 had TKR attributable to severe KOA. Risk of TKR increased in a strong dose-dependent manner with increasing BMI throughout the 15–32 kg/m2 range and became less clear at BMI >32 kg/m2. In the BMI range 16–27 kg/m2, there was a 27% increase in TKR risk for each unit increase in BMI (P for trend < 0.001). Compared to BMI 19–20 kg/m2, the risk estimates of TKR were all statistically significant with increasing unit of BMI ≥21 kg/m2. Results were similar for men and women.ConclusionOur results provided evidence for a constant mechanical mechanism underlying BMI and KOA initiation and/or progression

Androgen receptor phosphorylation at serine 515 by Cdk1 predicts biochemical relapse in prostate cancer patients

&lt;br&gt;Background:Prostate cancer cell growth is dependent upon androgen receptor (AR) activation, which is regulated by specific kinases. The aim of the current study is to establish if AR phosphorylation by Cdk1 or ERK1/2 is of prognostic significance.&lt;/br&gt; &lt;br&gt;Methods: Scansite 2.0 was utilised to predict which AR sites are phosphorylated by Cdk1 and ERK1/2. Immunohistochemistry for these sites was then performed on 90 hormone-naive prostate cancer specimens. The interaction between Cdk1/ERK1/2 and AR phosphorylation was investigated in vitro using LNCaP cells.&lt;/br&gt;&lt;br&gt;Results:Phosphorylation of AR at serine 515 (pAR(S515)) and PSA at diagnosis were independently associated with decreased time to biochemical relapse. Cdk1 and pCdk1(161), but not ERK1/2, correlated with pAR(S515). High expression of pAR(S515) in patients with a PSA at diagnosis of &#8804;20 ng ml(-1) was associated with shorter time to biochemical relapse (P=0.019). This translated into a reduction in disease-specific survival (10-year survival, 38.1% vs 100%, P&#60;0.001). In vitro studies demonstrated that treatment with Roscovitine (a Cdk inhibitor) caused a reduction in pCdk1(161) expression, pAR(S515)expression and cellular proliferation.&lt;/br&gt; &lt;br&gt;Conclusion: In prostate cancer patients with PSA at diagnosis of &#8804;20 ng ml(-1), phosphorylation of AR at serine 515 by Cdk1 may be an independent prognostic marker.&lt;/br&gt

Anti-inflammatory effect of gallic acid on HaCaT keratinocytes through the inhibition of MAPK-, NF-kB-, and Akt-dependent signaling pathways

The objectives of the present study were to evaluate the antioxidant and anti-inflammatory effects of gallic acid, a naturally occurring triphenolic compound, on HaCaT keratinocytes and study its mechanisms of action. The results showed that gallic acid at concentrations lower than 30 µM was non-toxic to HaCaT cells, reduced the intracellular level of reactive oxygen species, and suppressed the release of chemokines interleukin-8 and monocyte chemoattractant protein-1 in tumor necrosis factor-α- and interferon-γ-stimulated HaCaT keratinocytes. In addition, gallic acid reduced the total protein expression of NF-κB and inhibited the phosphorylation of ERK1/2, p38 MAPK, and Akt in stimulated HaCaT keratinocytes. In conclusion, our study revealed that gallic acid exhibited antioxidant and anti-inflammatory effects on keratinocytes, probably through the inhibition of MAPK-, NF-κB-, and Akt-dependent signaling pathways