Palladium-Catalyzed Atroposelective Suzuki-Miyaura Coupling to Construct Axially Chiral Tetra-Substituted α-Boryl Styrenes.

Palladium-catalyzed Suzuki-Miyaura (SM) coupling is a valuable method for forming C─C bonds, including those between aryl moieties. However, achieving atroposelective synthesis of axially chiral styrenes via SM coupling remains challenging. In this study, a palladium-catalyzed atroposelective Suzuki-Miyaura coupling between gem-diborylalkenes and aryl halides is presented. Using the monophosphine ligand Me-BI-DIME (L2), a range of axially chiral tetra-substituted acyclic styrenes with high yields and excellent enantioselectivities are successfully synthesized. Control experiments reveal that the gem-diboryl group significantly influences the product enantioselectivities and the coupling prefers to occur at sites with lower steric hindrance. Additionally, the alkenyl boronate group in the products proves versatile, allowing for various transformations while maintaining high optical purities.

Atroposelective Synthesis of Axially Chiral Styrenes by Platinum- Catalyzed Stereoselective Hydrosilylation of Internal Alkynes.

Hydrofunctionalization of alkynes is one of the most efficient ways to access axially chiral styrenes with open-chained olefins. While great advances have been achieved for 1-alkynylnaphthalen-2-ols and analogues, atroposelective hydrofunctionalization of unactivated internal alkynes lags. Herein we reported a platinum-catalyzed atroposelective hydrosilylation of unactivated internal alkynes for the first time. With monodentate TADDOL-derived phosphonite L1 used as a chiral ligand, various axially chiral styrenes were achieved in excellent enantioselectivities with high E-selectivities. Control experiments showed that the NH-arylamide groups have significant effects on both the yields and enantioselectivities and could act as directing groups. The potential utilities of the products were shown by the transformations of the amide motifs of the products.

Analysis of Cow-Calf Microbiome Transfer Routes and Microbiome Diversity in the Newborn Holstein Dairy Calf Hindgut.

Hindgut microorganisms in newborn calves play an important role in the development of immunity and metabolism, and optimization of performance. However, knowledge of the extent to which microbiome colonization of the calf intestine is dependent on maternal characteristics is limited. In this study, placenta, umbilical cord, amniotic fluid, colostrum, cow feces, and calf meconium samples were collected from 6 Holstein cow-calf pairs. Microbial composition was analyzed by 16S rRNA gene high-throughput sequencing, and maternal transfer characteristics assessed using SourceTracker based on Gibbs sampling to fit the joint distribution using the mean proportions of each sample with meconium as the "sink" and other sample types as different "sources." Alpha and beta diversity analyses revealed sample type-specific microbiome features: microbial composition of the placenta, umbilical cord, amniotic fluid, colostrum, and calf feces were similar, but differed from cow feces (p < 0.05). Compared with profiles of meconium vs. placenta, meconium vs. umbilical cord, and meconium vs. colostrum, differences between the meconium and amniotic fluid were most obvious. SourceTracker analysis revealed that 23.8 ± 2.21% of the meconium OTUs matched those of umbilical cord samples, followed by the meconium-placenta pair (15.57 ± 2.2%), meconium-colostrum pair (14.4 ± 1.9%), and meconium-amniotic fluid pair (11.2 ± 1.7%). The matching ratio between meconium and cow feces was the smallest (10.5 ± 1%). Overall, our data indicated that the composition of the meconium microflora was similar compared with multiple maternal sites including umbilical cord, placenta, colostrum, and amniotic fluid. The umbilical cord microflora seemed to contribute the most to colonization of the fecal microflora of calves. Bacteria with digestive functions such as cellulose decomposition and rumen fermentation were mainly transmitted during the maternal transfer process.

Effect of acidified milk feeding on the intake, average daily gain and fecal microbiological diversity of Holstein 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 (p<0.05), and the solid feed intake of calves fed AM was higher than that of calves fed PM at 61 to 90 days (p<0.05). The average daily gain of calves fed AM was also higher than that of calves fed PM at 31 to 60, 61 to 180, and 7 to 180 days (p<0.05). The calves fed AM tended to have a lower diarrhea rate than those fed PM (p = 0.059). Bacteroides 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.

Comparison of Reconstituted, Acidified Reconstituted Milk or Acidified Fresh Milk on Growth Performance, Diarrhea Rate, and Hematological Parameters in Preweaning Dairy Calves.

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 ± 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 < 0.01). Calves fed AFM had more feed intake than those fed ARM and RM (p < 0.01). Feed efficiency was significantly lower for calves offered ARM than those offered RM and AFM (p < 0.01). A lower withers height growth was found for calves fed RM than those fed ARM and AFM (p <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 < 0.05). These findings suggested that ARM and AFM had positive effects on growth performance and health status of the preweaning dairy calves.

Rotation velocity measurement based on self-mixing interference with a dual-external-cavity single-laser diode.

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%.

TDLAS-WMS second harmonic detection based on spectral analysis.

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 <3%. In contrast to lock-in amplification, the proposed method does not require reference signals and low-pass filtering algorithms. These characteristics simplify data processing in the proposed method.

Phosphatidylinositol 3-Kinase Inhibition by Copanlisib in Relapsed or Refractory Indolent Lymphoma.

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.

Variational mode decomposition denoising combined with the Hausdorff distance.

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.

Multiple self-mixing interference based on phase modulation and demodulation for vibration measurement.

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.

Combining biomarkers linearly and nonlinearly for classification using the area under the ROC curve.

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.

Deletion of a single-copy DAAM1 gene in congenital heart defect: a case report.

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.