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State-of-the-art silicon interposer technology of chip-on-wafer-on-substrate (CoWoS) containing the second-generation high bandwidth memory (HBM) has been applied for the first time in fabricating high-performance wafer-level system-in-package. An ultralarge Si interposer up to 1200mm2 made by a two-mask stitching process is used to form the basis of the second-generation CoWoS (CoWoS-2) to accommodate chips of logic and memory and achieve the highest possible performance. Yield challenges associated with the high warpage of such a large heterogeneous system are resolved to achieve high package yield. Compared to alternative interposer integration approaches such as chip-on-substrate, CoWoS offers more competitive design rule which results in better power consumption, transmission loss, and eye diagram. CoWoS-2 has positioned itself as a flexible 3-D IC platform for logic-memory heterogeneous integration between logic system-on-chip and HBM for various high-performance computing applications. [ABSTRACT FROM PUBLISHER]

In the present work we report on the synthesis of type-I clathrates Sr8Ga16Sn xGe30 − x (0 ≤ x ≤ 12). To find out how the substitution of Sn for Ge affects structural stability and electronic structure, the structural and electronic properties for Sr8Ga16Sn xGe30 − x (0 ≤ x ≤ 30) have been investigated by a first-principles method based on the density-functional theory (DFT). We found that the lattice constants of Sr8Ga16Sn xGe30 − x series increase with increasing Sn content, which is consistent with X-ray diffraction (XRD) results. Calculations indicate that the substitution of Sn for Ge leads to the change of the bulk modulus and the decrease of stability of the structure. It is found that these alloys are all indirect-gap semiconductors and the bandgap decreases from about 0.36 eV in Sr8Ga16Ge30 to about 0.03 eV in Sr8Ga16Sn30 with increasing Sn content. The decrease of the bandgap is attributed to the increase of the free space for the Sr guest motion, which is accompanied by the guest's low-energy modes and larger anharmonicity. These mean that an increase in the ratio of Sn-to-Ge can not only control the electrical properties of the materials, but also may reduce their thermal conductivity, suggesting that cage-size tuning is one of the useful means to obtain high-performance thermoelectric (TE) materials. [ABSTRACT FROM AUTHOR]

This study addresses the poorly explored issue of the control of false positive rate (FPR) in the mapping of pair-wise epistatic quantitative trait loci (QTL). A nested test framework was developed to (1) allow pre-identified QTL to be used directly to detect epistasis in one-dimensional genome scans, (2) to detect novel epistatic QTL pairs in two-dimensional genome scans and (3) to derive genome-wide thresholds through permutation and handle multiple testing. We used large-scale simulations to evaluate the performance of both the one- and two-dimensional approaches in mapping different forms and levels of epistasis and to generate profiles of FPR, power and accuracy to inform epistasis mapping studies. We showed that the nested test framework and genome-wide thresholds were essential to control FPR at the 5% level. The one-dimensional approach was generally more powerful than the two-dimensional approach in detecting QTL-associated epistasis and identified nearly all epistatic pairs detected from the two-dimensional approach. However, only the two-dimensional approach could detect epistatic QTL with weak main effects. Combining the two approaches allowed effective mapping of different forms of epistasis, whereas using the nested test framework kept the FPR under control. This approach provides a good search engine for high-throughput epistasis analyses. [ABSTRACT FROM AUTHOR]

Syphilis testing guidelines in China are usually based on symptomatic criteria, overlooking risk assessment and ultimately opportunities for disease detection and control. We used data from 10,695 sexually transmitted disease (STD) clinic patients in Guangxi, China, to assess the efficacy of a potential screening tool inquiring about behavioural and health risk factors in identifying the STD patients who should not be triaged for syphilis testing under current guidelines, but on the contrary receive such testing. Validity testing of the screening tool was performed and receiver-operating characteristic curves were plotted to determine an optimal total risk score cut-off for testing. About 40.9% of patients with positive toluidine red unheated serum test and Treponema pallidum particle agglutination test did not show hallmark signs of syphilis. The screening tool was more sensitive in detecting infection in non-triaged male versus female patients (highest sensitivity = 90% vs. 55%) and the cut-off score to warrant testing was lower in non-triaged female patients than in non-triaged male patients (cut-off = 1 vs. 2). Most of the cases were missed among female STD patients. In spite of selective testing based on behavioural and health indicators that improve case detection, cases were still missed. Our study supports universal testing for syphilis in the STD population. [ABSTRACT FROM AUTHOR]

By intergeneric sexual hybridization between Sinapis alba and Brassica oleracea, F1, F2 and BC1 progeny plants were produced. S. alba plants (genome SS, 2n = 24) were pollinated with B. oleracea (genome CC, 2n = 18), and the fertile F1 plants were pollinated with B. oleracea to obtain BC1 plants. GISH analysis showed that 10 out of 12 F1 plants had 12 S. alba chromosomes (one full S chromosome set) and nine B. oleracea chromosomes (one C chromosome sets), representing the expected hybrids. However, two F1 plants had 12 S chromosomes and 18 C chromosomes (two C chromosome sets), indicating unexpected hybrids. A maximum of three trivalents between C and S chromosomes were identified at metaphase I of semi-fertile F1 pollen mother cells (PMCs), which indicates homology and chromosome pairing between these two genomes. The C genome had obviously been doubled in two F2 plants from selfed semi-fertile F1 plants. BC1 plants consisted of 18 C chromosomes and different numbers of one, five and six additional S chromosomes, respectively. Monosomic alien addition lines developed in the present study can be used for B. oleracea breeding and Sinapis alba gene mapping. [ABSTRACT FROM AUTHOR]

In the present work we report on the synthesis of type-I clathrates Sr8Ga16Sn xGe30 − x (0 ≤ x ≤ 12). To find out how the substitution of Sn for Ge affects structural stability and electronic structure, the structural and electronic properties for Sr8Ga16Sn xGe30 − x (0 ≤ x ≤ 30) have been investigated by a first-principles method based on the density-functional theory (DFT). We found that the lattice constants of Sr8Ga16Sn xGe30 − x series increase with increasing Sn content, which is consistent with X-ray diffraction (XRD) results. Calculations indicate that the substitution of Sn for Ge leads to the change of the bulk modulus and the decrease of stability of the structure. It is found that these alloys are all indirect-gap semiconductors and the bandgap decreases from about 0.36 eV in Sr8Ga16Ge30 to about 0.03 eV in Sr8Ga16Sn30 with increasing Sn content. The decrease of the bandgap is attributed to the increase of the free space for the Sr guest motion, which is accompanied by the guest's low-energy modes and larger anharmonicity. These mean that an increase in the ratio of Sn-to-Ge can not only control the electrical properties of the materials, but also may reduce their thermal conductivity, suggesting that cage-size tuning is one of the useful means to obtain high-performance thermoelectric (TE) materials. [ABSTRACT FROM AUTHOR]

We conducted a hospital-based case-control study to investigate the associations of dietary intake of folate and MTHFR C677T and A1298C polymorphisms with breast cancer in a Chinese population. A 1:1-matched case-control study was conducted. Two hundred and thirty patients who were newly diagnosed and histologically confirmed breast cancer and 230 controls were enrolled from Xinxiang Central Hospital. Folate intake was calculated by standard portion size and relative size for each food item in the questionnaire. Genotyping of MTHFR C677T and A1298C was performed by PCR-RFLP. MTHFR 677TT (OR = 2.26, 95%CI = 1.09-4.87, P = 0.02) and T allele (OR = 1.40, 95%CI = 1.03-1.90, P = 0.03) had an increased risk of laryngeal cancer when compared with the CC genotype. We found any interaction between MTHFR C677T and folate intake (P for interaction = 0.02). In conclusion, our study demonstrated that MTHFR C677T polymorphism and folate are associated with risk of breast cancer.

Influence measures based on the pairwise deletion approach and the differentiation approach are developed for unmasking observations masked by other observations in the proportional hazards model. These influential observations might have substantial impact on statistical inference and might provide important information for model adequacy. One numerical example based on real data is presented and discussed.

Deletion diagnostics are developed for identifying observations that influence the estimates of regression parameters and the mixture parameter in the families of relative risk functions for failure time data. The diagnostic for the regression parameters is a generalization of Cain and Lange's (1984, Biometrics 40, 493-499) measure of individual influence. The generalizations of martingale residuals, Schoenfeld's partial residuals (1982, Biometrika 69, 239-241), and score residuals by Therneau, Grambsch, and Fleming (1990, Biometrika 77, 147-160) are also obtained. The influence of some observations on regression parameters can be drastically modified as the mixture parameter changes, even for a very small change. In addition, adding or deleting some observations might result in choosing different models. The diagnostics are applied to a family proposed by Guerrero and Johnson (1982, Biometrika 69, 309-314). One illustrative example is presented.

We develop a statistical model for estimating cystic fibrosis (CF) incidence among infants born in the U.S.A. that accounts for under-diagnosis due to death prior to diagnosis and we apply it to the Cystic Fibrosis Foundation Patient Registry data for the years 1989 to 1991. The resulting estimate of incidence relative to live births among whites is 1:3419 while that among non-whites is 1:12,163. As a by-product of the modelling approach, estimates of the underlying average diagnosis age given survival to diagnosis are 4.09 years for whites and 4.55 years for non-whites, but this difference was not statistically significant and appears to demonstrate that diagnosis efforts may be approximately the same for whites and non-whites. Also, as another by-product of the modelling approach, CF mortality was estimated as more severe for females than males and marginally more severe for non-whites than whites. A variety of statistical methods underlie achievement of these results, including semi-parametric maximum likelihood, survival analysis, multiple imputation and bootstrap techniques.

In this experiment, we used morgrel dogs to study the effect of trauma on the neuro-endocrine and metabolic organs and the effects of hormones on metabolism by determining the levels of intracellular cAMP, cGMP and DNA. From the changes in intracellular nucleotides, we learned that many neuro-endocrine organs and the main metabolic organs are characteristic of predominance in alpha-adrenoreceptor after trauma, thereby leading to high blood sugar.

In this study, we have developed two latex agglutination tests (LATs) with phenolic glycolipid-I (PGL-I) and natural disaccharide-octyl-bovine serum albumin (ND-O-BSA) as antigens in 110 leprosy patients (LL = 30, BL = 30, BT = 30, and TT = 20), 50 tuberculosis cases, and 30 normal controls. These two LATs were compared with corresponding ELISAs (ND-O-BSA ELISA and PGL-I ELISA) and analyzed by the chi-squared test. There were no significant differences between the two LATs (PGL-I LAT and ND-O-BSA LAT) and their corresponding ELISAs. There was an increase in the proportion of positive cases detectable which coincided with the clinical classification of leprosy, i.e., lepromatous cases were more likely to be positive than tuberculoid cases. LATs are more simple and rapid than ELISAs and have high sensitivity (77% in ND-O-BSA LAT, 80.5% in PGL-I LAT) and specificity (99% in both LATs). LATs may become useful tools for the immunodiagnosis of leprosy in the field. The stability and repeatability of LATs are discussed in detail.

We systematically conducted comparative studies on the validity, reliability and practicality of FLA-ABS.T/PGI-ELISA in large samples. Namely, 284 leprosy patients, 20 tuberculosis patients, 172 normal controls (from nonendemic area of leprosy), 425 leprosy household contacts (HC) and 2573 random samples from the general population (RS) were involved. The results indicated that FLA-ABS.T/PGI-ELISA are highly sensitive and specific for detecting antibodies against M. leprae. Their Youden's indexes (YI) are greater than 90%, and the positive predicative and negative values are 90%. The test results agreed with immuno-epidemiological studies: 1. The positive rates using FLA-ABS.T/PGI-ELISA increased gradually from TT to LL leprosy patients (in HC, the positive rates of PGI-ELISA were much higher in contacts of multibacillary patients than in contacts of paucibacillary patients); 2. The positive rates detected by FLA-ABS.T were identical to those of PGI-ELISA both in HC and in RS; 3. Among RS, the positive rates detected by FLA-ABS. T/PGI-ELISA were similar in each district and were in concordance with the general prevalence rates. Thus, both FLA-ABS.T and PGI-ELISA are useful tests in diagnosing leprosy and detecting subclinical infection with M. leprae. However, because the PGI-ELISA is simple, it will be more practical than FLA-ABS.T in the future. The authors emphasize that the methodology of obtaining dried blood from ear lobes is important for the immuno-epidemiological study of leprosy on a large scale.