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A first example of a manganese pincer complex for synthesis of δ-hydroxynitriles through formal conjugate addition of nitriles with allylic alcohols with 100% atom economy.

A novel method of gas concentration calibration for tunable diode laser absorption spectroscopy, in which spectral analysis and harmonic signal intensity ratio measurement are combined, is proposed in this study. A harmonic signal is extracted from a transmitted light intensity by spectral analysis. The ratio of the second harmonic to the first harmonic is proportional to the gas concentration. The noise caused by electronics and environment is filtered out via frequency-domain filtering, and the harmonic ratio measurement eliminates the effects of light intensity fluctuations. The accuracy and effectiveness of the proposed method are verified by simulation and experiment. Experimental results show that the relative error of measurement is less than 3% and the correlation coefficient between measurement and calibration line is 0.9991.

Purpose Phosphatidylinositol 3-kinase (PI3K) signaling is critical for the proliferation and survival of malignant B cells. Copanlisib, a pan-class I PI3K inhibitor with predominant activity against PI3K-α and -δ isoforms, has demonstrated efficacy and a manageable safety profile in patients with indolent lymphoma. Patients and Methods In this phase II study, 142 patients with relapsed or refractory indolent lymphoma after two or more lines of therapy were enrolled to receive copanlisib 60 mg intravenously on days 1, 8, and 15 of a 28-day cycle. The primary end point was objective response rate; secondary end points included duration of response, progression-free survival, and overall survival. In addition, safety and gene expression were evaluated. Results Median age was 63 years (range, 25 to 82 years), and patients had received a median of three (range, two to nine) prior regimens. The objective response rate was 59% (84 of 142 patients); 12% of patients achieved a complete response. Median time to response was 53 days. Median duration of response was 22.6 months, median progression-free survival was 11.2 months, and median overall survival had not yet been reached. The most frequent treatment-emergent adverse events were transient hyperglycemia (all grades, 50%; grade 3 or 4, 41%) and transient hypertension (all grades, 30%; grade 3, 24%). Other grade ≥3 events included decreased neutrophil count (24%) and lung infection (15%). High response rates to copanlisib were associated with high expression of PI3K/B-cell receptor signaling pathway genes. Conclusion PI3K-α and -δ inhibition by copanlisib demonstrated significant efficacy and a manageable safety profile in heavily pretreated patients with relapsed or refractory indolent lymphoma.

The quadrature demodulation algorithm used for all-fiber self-mixing sensors is applied to displacement measurements. A fiber electro-optic modulator is used to introduce phase modulation, which can improve the accuracy of measurements. Although phase modulation is easily affected by the polarization state of light, this method can process signals by sampling the interference signals at specific time points. Such signals are insensitive to polarization, and thus, the calculation process and experimental devices are simplified. The feasibility of the algorithm is validated via a series of experiments under nonpolarization-maintaining conditions.

The present experiment was carried out to assess the effects of reconstituted milk (RM), acidified reconstituted milk (ARM), and acidified fresh milk (AFM) on growth performance, diarrhea rate, and hematological parameters of preweaning dairy calves. For this purpose, a total of 27 Holstein female calves (one month of age) with initial body weight of (67.46 &plusmn, 4.08) kg were divided into three groups in such a way that each group contained nine calves. Calves were housed individually, and starter was offered ad libitum to each calf. The dietary treatments were RM, ARM, and AFM. The highest milk intake was observed in calves receiving AFM as compared to other treatments (p &lt, 0.01). Calves fed AFM had more feed intake than those fed ARM and RM (p &lt, 0.01). Feed efficiency was significantly lower for calves offered ARM than those offered RM and AFM (p &lt, 0.01). A lower withers height growth was found for calves fed RM than those fed ARM and AFM (p &lt, 0.05). Diarrhea rate and white blood cell (WBC) and lymphocytes (LYM) counts were greater for calves fed RM than those fed ARM and AFM (p &lt, 0.05). These findings suggested that ARM and AFM had positive effects on growth performance and health status of the preweaning dairy calves.

Objective: To evaluate the effect of feeding acidified milk on the growth and fecal microbial diversity of dairy calves.Methods: Twenty healthy 3-day-old female Holstein calves with similar body weights were selected and randomly divided into two groups. One group was fed pasteurized milk (PM, Control), while the other was fed acidified milk (AM) ad libitum until weaned (day 60). The experiment lasted until day 180.Results: There was no difference in the nutritional components between PM and AM. The numbers of Escherichia coli and total bacteria in AM were lower than in PM. At 31 to 40 and 41 to 50 days of age, the milk intake of calves fed AM was higher than that of calves fed PM (pBacteroides had the highest abundance in the feces of calves fed AM on day 50, while Ruminococcaceae_UCG_005 had the highest abundance in the feces of calves fed AM on day 90 and calves fed PM on days 50 and 90. At the taxonomic level, the linear discriminant analysis scores of 27 microorganisms in the feces of calves fed AM and PM on days 50 and 90 were higher than 4.0.Conclusion: Feeding AM increased calf average daily gain and affected fecal bacterial diversity.

In biomedical studies, it is often of interest to classify/predict a subject's disease status based on a variety of biomarker measurements. A commonly used classification criterion is based on area under the receiver operating characteristic curve (AUC). Many methods have been proposed to optimize approximated empirical AUC criteria, but there are two limitations to the existing methods. First, most methods are only designed to find the best linear combination of biomarkers, which may not perform well when there is strong nonlinearity in the data. Second, many existing linear combination methods use gradient-based algorithms to find the best marker combination, which often result in suboptimal local solutions. In this paper, we address these two problems by proposing a new kernel-based AUC optimization method called ramp AUC (RAUC). This method approximates the empirical AUC loss function with a ramp function and finds the best combination by a difference of convex functions algorithm. We show that as a linear combination method, RAUC leads to a consistent and asymptotically normal estimator of the linear marker combination when the data are generated from a semiparametric generalized linear model, just as the smoothed AUC method. Through simulation studies and real data examples, we demonstrate that RAUC outperforms smooth AUC in finding the best linear marker combinations, and can successfully capture nonlinear pattern in the data to achieve better classification performance. We illustrate our method with a dataset from a recent HIV vaccine trial. Copyright © 2016 John Wiley & Sons, Ltd.

To solve the problem of nondestructive leak detection and location of pipelines, this study proposes a pipeline leak detection algorithm based on the characteristic of acoustic propagation in the form of transverse and longitudinal waves. A two-dimensional acceleration sensor is utilized to detect transverse and longitudinal waves. Subsequently, the time difference between the transverse and longitudinal waves is obtained using a time delay estimation algorithm for the location of leak points. The accuracy and effectiveness of the proposed algorithm are verified in different situations through experiments.

A novel Doppler velocity measurement method based on laser self-mixing interference with two parallel optical external cavities is investigated. In this method, the target object rotation velocity can be measured by the sum of two Doppler frequency shifts, which can be extracted by fast Fourier transform without setting and measuring incident angles. This study highlights the validity of the proposed method through a theoretical model analysis. Experiments realized velocity measurement with a relative error of less than 0.6%.

Background: Two phase III trials have demonstrated the efficacy of eribulin monotherapy in patients with metastatic breast cancer (MBC) who have progressed after previous anthracycline and taxane chemotherapy. Capecitabine is also an effective agent in patients with MBC. A phase Ib dose-escalation study has investigated two dosing schedules of eribulin in combination with capecitabine to determine the recommended phase II dose. The aims of this open-label, non-randomized, phase II, dose-confirmation study were to determine efficacy and safety of this combination in patients with MBC. Interim data to April 2014 are provided here; final results will be presented at the meeting. Methods: Eligible patients were females with MBC who had received up to 3 previous chemotherapy regimens in any setting (including an anthracycline and a taxane, but excluding capecitabine), an ECOG performance status (PS) ≤1, and adequate hematological, renal and hepatic function (at study entry, 20 [47.6%] patients had liver metastases; 24 [57.1%] had lung metastases). Patients received 1.4 mg/m2 eribulin mesylate (equivalent to 1.23 mg/m2 eribulin [expressed as free base]) i.v. on days 1 and 8 plus oral capecitabine 1000 mg/m2 b.i.d. on days 1–14 (21-day cycles) until disease progression, unacceptable toxicity or death. Disease assessments (CT scans) were performed every 6 weeks. The primary outcome was the objective response rate (ORR); secondary outcomes included clinical benefit rate (CBR), progression-free survival (PFS), and safety and tolerability. Results: 42 females (median age: 52.5 years [range: 32–74]; ECOG-PS of 0: n = 18 [42.9%]) were enrolled; patients received study drug as a 1st-line (23.8% [n = 10]), 2nd-line (45.2% [n = 19]) or ≥3rd-line (31.0% [n = 13]) chemotherapy. A median of 8 (range: 1–30) treatment cycles were administered (59.5% of patients received ≥6 cycles), with 94.4% of eribulin doses and 94.5% of capecitabine doses given as planned. The ORR was 42.9% and the CBR was 57.1% (Table), with a median PFS of 7.1 months (95% CI: 4.4, 9.8). The most common grade 3/4 adverse events (AEs) were neutropenia (66.7%), leukopenia (14.3%), febrile neutropenia (7.1%) and anemia, fatigue, nausea and peripheral sensory neuropathy (each 4.8%). AEs of special interest (any grade) included: hand–foot syndrome (26.2%), peripheral neuropathy (23.8%), and diarrhea (21.4%). The incidences of AEs leading to study drug dose adjustment were: 47.6% of patients (dose interruption), 42.9% (dose reduction), and 2.4% (drug withdrawal). Table: Tumor response (investigator assessment)PatientsN = 42n (%)n (%)Complete response (CR)2 (4.8)Partial response (PR)16 (38.1)Stable disease (SD)16 (38.1)Progressive disease (PD)3 (7.1)Not evaluable5 (11.9)Objective response rate (CR + PR)18 (42.9)95% CI27.7, 59.0Clinical benefit rate (CR + PR + SD ≥ 6 months)24 (57.1)95% CI41.0, 72.3 Conclusions: This phase II study suggests that eribulin in combination with capecitabine is efficacious in patients with MBC, with a safety and tolerability profile consistent with previous data. Phase III studies of this combination in patients with MBC are warranted. Citation Format: Chris Twelves, Muhammad Y Nasim, Alan Anthoney, Claudio I Savulsky, Shuxin Yin, TR Jeffry Evans. Efficacy and safety of eribulin in combination with capecitabine in patients with metastatic breast cancer: an open-label, phase II dose-confirmation study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-13-04.

Variational mode decomposition (VMD) is a recently introduced adaptive signal decomposition algorithm with a solid theoretical foundation and good noise robustness compared with empirical mode decomposition (EMD). However, there is still a problem with this algorithm associated with the selection of relevant modes. To solve this problem, this paper proposes a novel signal-filtering method that combines VMD with Hausdorff distance (HD) in the VMD-HD method. A noisy signal is first decomposed into a given number K of band-limited intrinsic mode functions by VMD. The probability density function is then estimated for each mode. The aim of this method is to reconstruct the signal using the relevant modes, which are selected on the basis of noticeable similarities between the probability density function of the input signal and that of each mode. Various similarity measures are investigated and compared, and the HD is shown to offer the best performance. The results of filtering of simulation signals illustrate the validity of the proposed method when compared with EMD-based methods under comprehensive quantitative evaluation criteria. As a specific example, the proposed method is successfully used for filtering the pipeline leakage signal as evaluated by the de-trended fluctuation analysis algorithm.

A novel algorithm based on a phase modulation and demodulation technique for multiple self-mixing interferometry was proposed in this paper. This algorithm can measure nanoscale vibration in real time and enhance the measurement resolution of a multiple self-mixing interferometer twofold compared with that of a self-mixing interferometer. In this paper, the principles of the method were described in detail, and a phase equation for multiple self-mixing interferometry was derived. Experiments were confirmed by conducting a series of experiments with different amplitudes, different signal-to-noise ratios, and different vibration waveforms. The experimental results showed that the algorithm can rapidly demodulate vibration in real time and indicated good agreement between theory and experiment.

In this paper, a high-precision and effective method of multiple self-mixing interference (MSMI) modulation and demodulation is proposed. The MSMI signal is sinusoidal modulated by an electro-optic modulator. Then, the four-quadrant integral technique is used to demodulate the modulated MSMI signal and reconstruct displacement of the vibration object. The four-quadrant integral technique is within a modulation period; the signal is integrated four times; the integral system is operated by simple linear operations and can obtain the phase. This method not only can demodulate sinusoidal vibration but also can reconstruct an arbitrary wave. At the same time, without increasing the hardware equipment and the complexity of the algorithm, the measurement accuracy of MSMI is doubled that of self-mixing interference. The simulation tests and experimental measurements are confirmed by conducting a series of experiments.

A novel method for the detection of the second-harmonic component of tunable laser diode absorption spectroscopy-wavelength-modulated absorption spectroscopy is proposed in this study. The proposed method is based on spectral analysis, and the second-harmonic component is obtained in the frequency domain through a rectangular window. The validity, correctness, and noise immunity of the proposed method are verified through simulations and experiments. Experimental results demonstrate that the relative detection error level of the proposed method is

Introduction: There are limited treatment options for patients with indolent B-cell lymphoma who have relapsed or are refractory to standard therapies. Copanlisib is an intravenously administered pan-Class I phosphatidylinositol 3-kinase (PI3K) inhibitor with predominant activity against PI3K-α and PI3K-δ isoforms. We report here the primary results from a pivotal phase II study (NCT01660451, part B). Methods: Patients with indolent B-cell non-Hodgkin lymphoma (4 subtypes: follicular [FL], marginal zone [MZL], small lymphocytic [SLL] and lymphoplasmacytoid/Waldenström macroglobulinemia [LPL-WM]) and relapsed after, or refractory to, ≥2 prior lines of treatment were eligible. Previous treatment had to include rituximab and an alkylating agent. Copanlisib (60 mg, I.V.) was intermittently administered on days 1, 8 and 15 of a 28-day cycle. The primary efficacy endpoint was objective tumor response rate (ORR) as assessed per independent radiologic review (Cheson et al., JCO 20:579, 2007). Results: The full analysis set comprised 142 patients, of which 141 patients had indolent lymphoma (FL/MZL/SLL/LPL-WM: 104/23/8/6). At the time of primary analysis, median duration of treatment was 22 weeks (range 1-105); 46 patients remained on treatment. The most common treatment-related AEs (all grade/grade 3+) were transient hyperglycemia (49%/40%) and hypertension (29%/23%). Other AEs of interest included neutropenia (25%/19%), diarrhea (18%/4%), lung infection (14%/11%), pneumonitis (7%/1.4%), and colitis (0.7%/0.7%). No colonic perforations occurred. There were two non-fatal opportunistic infections. Laboratory toxicities of interest were principally grade-1, including alanine aminotransferase (23% all-grade/19% grade-1) and aspartate aminotransferase (28%/25%). There were 6 deaths, 3 of which were attributed to copanlisib: lung infection, respiratory failure, and a thromboembolic event. The ORR was 59.2%, including 12.0% complete response (CR) and 47.2% partial response (PR), with stable disease in 29.6% of patients and progressive disease in 2.1% of patients. In the FL subset, the ORR was 58.7%, including 14.4% CR and 44.2% PR. In the MZL subset, the ORR was 69.6%, including 8.7% CR and 60.9% PR. The estimated Kaplan-Meier (KM) median duration of response in the full analysis set was 687 days (range 0-687) and 370 days (range 0-687) in the FL subset. The KM-estimate of median PFS was 340 days (range 0-736). Median overall survival had not yet been reached. Conclusions: Treatment of patients with relapsed or refractory indolent B-cell lymphoma with copanlisib resulted in durable tumor responses. Administration of copanlisib had a manageable safety profile, with low rates of severe hepatic enzymopathy, diarrhea or inflammatory events, as well as low rates of opportunistic infections, fatal infections or other fatal serious adverse events. Citation Format: Martin Dreyling, Armando Santoro, Luigina Mollica, Sirpa Leppä, George A. Follows, Georg Lenz, Won Seog Kim, Arnon Nagler, Panayiotis Panayiotidis, Judit Demeter, Muhit Özcan, Marina Kosinova, Krimo Bouabdallah, Franck Morschhauser, Don A. Stevens, David Trevarthen, Marius Giurescu, Lisa Kupit, Shuxin Yin, Florian Hiemeyer, Jose Garcia-Vargas, Barrett H. Childs, Pier Luigi Zinzani. Copanlisib in patients with relapsed or refractory indolent B-cell lymphoma: Primary results of the pivotal Chronos-1 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT149. doi:10.1158/1538-7445.AM2017-CT149

7535 Background: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (iNHL) subtype, yet treatment options in the relapsed/refractory (r/r) setting are limited. Copanlisib is a pan-Class I phosphatidylinositol 3-kinase (PI3K) inhibitor with predominant PI3K-α and PI3K-δ activity. We report results from the FL subset of a large phase II study (n=141) in iNHL patients (pts) (NCT01660451, part B). Methods: A total of 104 pts with indolent FL (grade 1-3a) relapsed/refractory to ≥2 prior lines of treatment were treated with copanlisib (60 mg IV infusion) administered on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was objective tumor response rate (ORR) per independent radiologic review (Cheson et al., JCO 20:579, 2007). Results: Of the 104 pts treated, 62% were refractory; median prior lines 3 (range 2-8), median time from progression 8 wks (range 1-73 wks). 52% were male, 83% white, median age 62 yrs, and 62% ECOG 0. At the time of primary analysis the ORR was 58.7%, comprising 15 pts (14.4%) with complete response (CR) and 46 (44.2%) with partial response. Stable disease was observed in 35 (33.7%) pts and progression of disease as best response in 2 pts. The median duration of response was 370 days (range 0-687), with 43 responders censored at data cut-off. Median duration of treatment was 22 wks (range 1-105); 33 (32%) pts remained on treatment. For all pts, the most common treatment-emergent AEs occurring in >25% of pts included (all grade/grade 3+): diarrhea (34%/5%), reduced neutrophil count (30%/24%), fatigue (30%/2%), and fever (25%/4%). Hyperglycemia (50%/41%) and hypertension (30%/24%) were transient. The incidence of pneumonitis (8%/1.4%), hepatic enzymopathy (AST 28%/1.4%; ALT 23%/1.4%), opportunistic infection (1.4%) and colitis (0.7%) were low. Six deaths were observed, 3 of which were attributed to copanlisib: one lung infection, one respiratory failure, and one thromboembolic event. Conclusions: Copanlisib was highly active as a single agent in heavily pretreated r/r FL pts and resulted in durable responses in the majority of pts. Toxicities were manageable, with a low incidence of severe AEs associated with other PI3K inhibitors, especially hepatic enzymopathy, opportunistic infections, and colitis. Clinical trial information: NCT01660451.

Background With an increasing incidence of congenital heart defects (CHDs) in recent years, genotype-phenotype correlation and array-based methods have contributed to the genome-wide analysis and understanding of genetic variations in the CHD population. Here, we report a copy number deletion of chromosomal 14q23.1 in a female fetus with complex congenital heart defects. This is the first description of DAAM1 gene deletion associated with congenital heart anomalies. Case Presentation Compared with the control population, one CHD fetus showed a unique copy number deletion of 14q23.1, a region that harbored DAAM1 and KIAA0666 genes. Conclusions Results suggest that the copy number deletion on chromosome 14q23.1 may be critical for cardiogenesis. However, the exact relationship and mechanism of how DAAM1 and KIAA0666 deletion contributes to the onset of CHD is yet to be determined.

This paper introduces a new method of video-compress based on H.264. The coding algorithm adopts 3-D wavelet transformation and Shape Coding. In hardware implement, DSP chips and FPGA chips is adopted, FPGA completes the task of multiply clock periods operate, while DSP chips accomplishes the function of both the single clock period operate and the control of FPGA relocated calculation. Experimental result indicates the design can improve coding efficiency and get a good tradeoff between bit-rate and distortion. The method is shown to be simple, efficient and suitable for hardware implementation.

In this paper, we present an efficient hybrid image compression method. According to Human eye sensitivity, It is not sensitive to gray-scale error, but the human eye is particularly sensitive to the image edge features, through we research strengths and weaknesses of the fractal image coding and SPIHT(set partitioning in hierarchical trees) algorithm, proposed a hybrid algorithm based on SPIHT and Fractal image compression algorithm, it makes full use of landscape features and human visual characteristics, the image is decompounded into low frequency sub-band and high frequency sub-band, then the low frequency sub-band is uses fractal coding, this could make the low-frequency information loss less who is sensitivity to human visual signal and the high frequency sub-band is uses SPIHT coding, so encoding time greatly reduced. Experimental results show that the Hybrid Image Compression Algorithm not only raises the coding efficiency and reconstructed image quality but also reduces the image encoding time.

With the growth of mobile and sensor devices, embedded systems, and communication technologies, we are moving towards an era of pervasive computing. Pervasive computing applications typically involve interactions between a large number of entities that span different organizations. Uncontrolled disclosure of information or unconstrained interaction among entities may have extremely grave consequences. Traditional security policies and mechanisms are inadequate for pervasive computing applications. Unlike traditional applications, pervasive computing applications have no definite security perimeters and are dynamic in nature. Pervasive computing applications may need to interact with entities that are not known a priori and therefore cannot be trusted. The traditional binary notion of trust where known entities are completely trusted and unknown entities are distrusted are not suitable for such applications. To fill this gap, we develop a trust model useful for pervasive computing applications and develop strategies for establishing trust between entities. The model must accommodate the notion of different degrees of trust, identify how to determine the trust value, and define how trust changes over time.