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A series of novel composite microfibers composed of β-cyclodextrin (β-CDs) functionalized POM (polyoxymethylene) were prepared using electrospining technology with a mixture of hexafluoroisopropanol (HFIP) and N,N-dimethylformamide (DMF) as solvent. The concentration of β-CDs with respect to the POM was varied from 0 to 50 wt.%. The effect of β-CDs content on the morphology of POM/β-CD composite microfiber was investigated. The results showed that the introduction of β-CDs reduced the surface roughness and porosity of the microfibers, and the morphology of the fibers was changed. The increase of β-CDs content from 10% to 50% has led to increased average diameter of POM/β-CD composite fiber from 2.1 μm to 6.4 μm. The mechanical properties of the blend fiber mats were further investigated. In addition, silver nanoparticles were introduced to the POM/β-CD composite microfiber matrices during electrospinning. The POM/β-CD composite fiber allows CDs to form host–guest complexes with various small molecules and macromolecules. The TEM, SEM, XRD, and XPS were utilized to characterize the prepared samples. The data suggest that Ag nanoparticles were homogeneously distributed within the POM/β-CD fibers, and no aggregation was observed. The catalytic activity of Ag nanoparticles was tracked by ultraviolet-visible (UV-vis) spectroscopy which showed excellent catalytic degradation performance of organic dyes in the presence of NaBH4. The Ag/POM/β-CD mats are promising for use in waste treatment, molecular recognition, catalysis, and so on.

BackgroundSystemic inflammatory or dysimmune diseases (SIDDs) are encountered in up to a quarter of patients with myelodysplastic syndromes (MDS). Recently identified VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, associated with somatic mutations in UBA1, encompasses a range of severe inflammatory conditions along with hematologic abnormalities, including myelodysplasia. Only limited data are available on the pathophysiology of MDS-associated SIDDs, and especially about the role of different myeloid cell subsets.ObjectivesThe aim of this study was to describe the phenotype of myeloid immune cells (dendritic cells and monocytes) in MDS patients with associated SIDDs, and to compare their distribution with MDS patients without SIDDs and controls.MethodsPhenotype analysis by flow cytometry from PBMCs of 14 MDS patients with SIDDs, 23 MDS patients without SIDDs and 7 controls without MDS and SIDDs. Eight of the 14 MDS/SIDDs patients (57%) had a somatic UBA1 mutation.ResultsIn this study analyzing peripheral blood myeloid immune cells in MDS patients with and without SIDDs, we observed a quantitative reduction of different DC and monocyte subsets in MDS/SIDDs patients, especially in patients with active SIDDs and above all in patients with newly described VEXAS syndrome.ConclusionFurther functional studies are warranted to better understand the mechanisms and the consequences of the phenotypic modulations of immune myeloid cells in the pathophysiology of MDS-associated SIDDs, especially in VEXAS syndrome.Disclosure of InterestsNone declared

The aim of this study was to explore the expression of GTPase protein Ras-related protein Rap-2a (Rap2A) in breast cancer (BC). Furthermore, the associations of Rap2A with clinicopathological parameters of BC patients were investigated.quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine Rap2A expression in BC tissues and cells. The association between Rap2A expression and clinicopathological characteristics was analyzed by Chi-square test. Low expression of Rap2A in BC cells was conducted by transfection of small interfering RNA (siRNA). Subsequently, colony formation assay and transwell assay were used to detect the proliferation and invasion abilities of BC cells, respectively.Rap2A was highly expressed in both BC tissues and cells (p0.05). Further analysis showed that tumor size, clinical stage, and distant metastasis were correlated with Rap2A expression (p0.05). Besides, inhibition of Rap2A significantly decreased the proliferation and invasion abilities of BC cells (p0.05).Rap2A acted as a promotor in the development of BC. Our findings suggested that Rap2A might be a new potential therapeutic target marker for BC treatment.

OBJECTIVE: To evaluate and to compare dimensional alterations of hard and soft tissues in molar extraction sites with irregular deficiency of bone plates due to advanced periodontitis receiving two different procedures, namely the flapped and flapless techniques with Bio-Gide® membrane covering the Bio-Oss® material for ridge preservation. METHODS: Twenty-three patients with 24 infected-molar extraction sites received ridge preservation procedure, the first consecutive 12 sites belonged to the flap group (a full thickness mucoperiosteal flap and primary soft tissue closure) and the following 12 sites belonged to the flapless group (minimal flap with a collagen sponge and a secondary soft tissue closure). Width of keratinized tissue was evaluated before tooth extraction and after 6-month healing. Parallel periapical radiographs were taken immediately and 6 months after extraction to evaluate vertical bone changes. The width of the ridge was measured in the center of the ridge at the time of tooth extraction and after 6 months at implant placement. RESULTS: After 6 months, width of keratinized tissue decreased (1.6±1.5) mm in the flap group (P=0.004) when compared with (0.3±1.6) mm in the flapless group (P>0.05). Both groups showed increases in ridge height from the central aspect, (5.53±4.20) mm for flap group and (7.70±4.35) mm for flapless group. These differences between the groups were not statistically significant (P=0.226). The ridge widths were (9.5±2.2) mm for flap group and (9.3±1.0) mm for flapless group at the time of implant insertion, and no statistical significance was observed between the flap and flapless groups. CONCLUSION: The study points out that both ridge preservation techniques were effective in increasing ridge height and minimizing ridge resorption after tooth extraction, and the ridge width allowed the placement of implants 6 months after ridge preservation. The flapless technique gave positive outcome in terms of the keratinized gingival width than that of the flap technique.

Climate change is expected to affect plant communities worldwide. However, less is known about the consequences of global warming-induced decrease of soil moisture on alpine wetland ecosystem in the Qinghai-Tibetan Plateau. To determine response of natural alpine wetland community to decrease of soil moisture, we did a gradient analysis of soil moisture by sequence space-series variation. We used sequence space-series variation of soil moisture to reflect potential time-series variation of soil moisture in alpine wetland community, by examining the effects of spatial heterogeneity of soil moisture on wetland community, as well as by determining how shifts in above- and below-ground properties of alpine wetland community. We found that vegetation aboveground biomass, cover and height all significantly increased with increase of soil moisture, but species richness was decreased. Soil organic carbon, total nitrogen, available nitrogen, total phosphorus and available phosphorus all significantly increased with increase of soil moisture, but soil pH value, total potassium and available potassium were significantly decreased. Meanwhile, species richness showed significantly positive correlations to aboveground biomass, covers and height. Aboveground biomass, vegetation covers and height were all significant positively related to soil organic carbon, total N, P, and available N, P, but negatively related to total K. But, species richness were significant negatively related to soil organic carbon, total N, P, and available N, P, but positively related to total K. Our observation indicates that decreasing of soil moisture may potentially negatively impact on the above- and below-ground properties in alpine wetland community.

To investigate the expression of long non-coding RNA ZNF667-AS1 in cervical cancer and its effect on the proliferation of cervical cancer cell line, SiHa cells.The expression level of ZNF667-AS1 from two microarray datasets (GSE63514 and GSE6791) and TCGA (The Cancer Genome Atlas) were selected to analyze the difference between cervical cancer tissues and normal cervical tissues with bioinformatics methods. Then, the prognosis of ZNF667-AS1 was calculated in TCGA. The expression of LncRNA ZNF667-AS1 in 30 normal cervical tissues and 60 cervical cancer tissue samples was explored using qRT-PCR. In addition, analysis of the clinical data found that the expression of LncRNA ZNF667-AS1 was correlated with the total survival, tumor size and International Federation of Gynecology and Obstetrics (FIGO) stage. At last, the proliferative ability was detected by CCK8 and colon formation assay.Search the relevant microarray datasets using the keywords "cervical cancer" and "GPL570" from the Gene Expression Omnibus (GEO) database. Afterwards, two microarray datasets (GSE63514 and GSE6791) were selected to analyze the differentially expressed genes in cervical cancer tissues and normal cervical tissues using bioinformatics methods. The results showed that the expression of LncRNA ZNF667-AS1 in cervical cancer was significantly lower than that in normal cervical tissues. 30 normal cervical tissues and 60 cervical cancer tissue samples were selected to extract total RNA for qRT-PCR experiment, and found that the expression of LncRNA ZNF667-AS1 in cervical cancer tissues was lower than that in normal cervical tissues, which was consistent with that of TCGA. Analysis of the clinical data found that the expression of LncRNA ZNF667-AS1 was correlated with the total survival, tumor size and FIGO stage. Compared with the negative control group, the proliferation ability and cell cloning ability of cells with over-expressed LncRNA ZNF667-AS1 were significantly decreased (p0.001), indicating that overexpression of ZNF667-AS1 inhibited the proliferation of SiHa cells.Expression of LncRNA ZNF667-AS1 was significantly lower in cervical cancer tissues, and its expression was negatively correlated with the overall survival, tumor size and FIGO stage. ZNF667-AS1 inhibited the proliferation of cervical cancer cells and was expected to be the biomarker and potential therapeutic target for predicting cervical cancer and determining its prognosis.

Celiac disease is associated with the HLA-DR3-DQA1*05:01-DQB1*02:01 and DR4-DQA1*03:01-DQB1*03:02 haplotypes. In addition, there are currently over 40 non-HLA loci associated with celiac disease. This study extends previous analyses on different HLA haplotypes in celiac disease using next generation targeted sequencing. Included were 143 patients with celiac disease and 135 non-celiac disease controls investigated at median 9.8 years (1.4-18.3 years). PCR-based amplification of HLA and sequencing with Illumina MiSeq technology were used for extended sequencing of the HLA class II haplotypes HLA-DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1, respectively. Odds ratios were computed marginally for every allele and haplotype as the ratio of allelic frequency in patients and controls as ratio of exposure rates (RR), when comparing a null reference with equal exposure rates in cases and controls. Among the extended HLA haplotypes, the strongest risk haplotype for celiac disease was shown for DRB3*01:01:02 in linkage with DQA1*05:01-DQB1*02:01 (RR = 6.34; P-value.0001). In a subpopulation analysis, DRB3*01:01:02-DQA1*05:01-DQB1*02:01 remained the most significant in patients with Scandinavian ethnicity (RR = 4.63; P .0001) whereas DRB1*07:01:01-DRB4*01:03:01-DQA1*02:01-DQB1*02:02:01 presented the highest risk of celiac disease among non-Scandinavians (RR = 7.94; P = .011). The data also revealed 2 distinct celiac disease risk DR3-DQA1*05:01-DQB*02:01 haplotypes distinguished by either the DRB3*01:01:02 or DRB3*02:02:01 alleles, indicating that different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease. The associated risk of celiac disease for DR3-DRB3*01:01:02-DQA1*05:01-DQB1*02:01 is predominant among patients of Scandinavian ethnicity.

For ideal implant rehabilitation, an adequate bone volume, optical implant position, and stable and healthy soft tissue are required. The reduction of alveolar bone and changes in its morphology subsequent to tooth extraction will result in insufficient amount of bone and adversely affect the ability to optimally place dental implants in edentulous sites. Preservation of alveolar bone volume through ridge preservation has been demonstrated to reduce the vertical and horizontal contraction of the alveolar bone crest after tooth extraction and reduce the need for additional bone augmentation procedures during implant placement. In this case, a patient presented with a mandible molar of severe periodontal disease, the tooth was removed as atraumatically as possible and the graft material of Bio-Oss was loosely placed in the alveolar socket without condensation and covered with Bio-Gide to reconstruct the defects of the alveolar ridge. Six months later, there were sufficient height and width of the alveolar ridge for the dental implant, avoiding the need of additional bone augmentation and reducing the complexity and unpredictability of the implant surgery. Soft tissue defects, such as gingival and connective tissue, played crucial roles in long-term implant success. Peri-implant plastic surgery facilitated development of healthy peri-implant structure able to withstand occlusal forces and mucogingival stress. Six months after the implant surgery, the keratinized gingiva was absent in the buccal of the implant and the vestibular groove was a little shallow. The free gingival graft technique was used to solve the vestibulum oris groove supersulcus and the absence of keratinized gingiva around the implant. The deepening of vestibular groove and broadening of keratinized gingiva were conducive to the long-term health and stability of the tissue surrounding the implant. Implant installation and prosthetic restoration showed favorable outcome after six months.

To explore the effects of rapamycin on the migration of human epidermal cell line HaCaT, and to analyze its molecular mechanism.HaCaT cells were conventionally cultured with RPMI 1640 culture medium containing 10% fetal calf serum (hereinafter referred to as culture medium). (1) According to the random number table, HaCaT cells in logarithmic phase were divided into control group and 1, 5, 50, 100, 200 nmol/L rapamycin groups, with 6 wells in each group. The cells in rapamycin groups were cultured with culture medium containing rapamycin in corresponding mass concentration, and the cells in control group were cultured with culture medium containing dimethyl sulfoxide (DMSO) instead. After being conventionally cultured for 4 hours, proliferative activity of cells was determined with microplate reader (denoted as absorbance value). (2) HaCaT cells in logarithmic phase were grouped and cultured as that in experiment (1), with 1 well in each group. After being conventionally cultured for 4 hours, range of movement of cells in 3 hours was observed under live cell imaging workstation, and their curvilinear movement speeds were calculated. Then the suitable concentration of rapamycin was selected for experiments (3) and (4). (3) HaCaT cells in logarithmic phase were divided into control group and rapamycin group according to the random number table, with 1 well in each group. The cells in rapamycin group were cultured with culture medium containing 50 nmol/L rapamycin, and the cells in control group were cultured with culture medium containing DMSO. After being conventionally cultured for 4 hours, cells were collected for scratch assay. Wound area was observed at post scratching hour (PSH) 0, 5, 10, and 15, and the migration rates of cells at PSH 5, 10, and 15 were calculated respectively. (4) HaCaT cells in logarithmic phase were grouped and cultured as that in experiment (3), with 1 well in each group. Activity of focal adhesion kinase (FAK) was determined with Western blotting (denoted as the ratio of gray value of phosphorylated FAK to that of FAK). Above-mentioned experiments were independently repeated for three or five times. Data were processed with one-way analysis of variance, LSD test, and t test.(1) Proliferative activity of cells in control group and 1, 5, 50, 100, 200 nmol/L rapamycin groups was respectively 1.22±0.28, 1.29±0.38, 1.12±0.27, 1.20±0.29, 1.15±0.30, 1.39±0.40, without statistically significant differences among these groups (F=2.112, P=0.068). (2) The ranges of movement of cells in 1, 5 nmol/L rapamycin groups were similar to the range of movement of cells in control group, while those of cells in 50, 100, 200 nmol/L rapamycin groups were obviously smaller than the range of movement of cells in control group. There were statistically significant differences in cell curvilinear movement speeds among the 6 groups (F=3.525, P=0.004). The curvilinear movement speeds of cells in 1, 5 nmol/L rapamycin groups were respectively (0.8±0.4) and (0.8±0.8) μm/min, and they were similar to the curvilinear movement speed of cells in control group [(0.9±0.5) μm/min, with P values above 0.05]. The curvilinear movement speeds of cells in 50, 100, 200 nmol/L rapamycin groups were respectively (0.7±0.5), (0.7±0.4), (0.7±0.4) μm/min, and they were significantly lower than the curvilinear movement speed of cells in control group (with P values below 0.01). Thus, 50 nmol/L rapamycin was selected for experiments (3) and (4). (3) Compared with those of control group, wound areas of rapamycin group showed no obvious change at PSH 0 and 5, while they were obviously increased at PSH 10 and 15. At PSH 5, migration rate of cells in control group [(17.5±2.6)%] was similar to that in rapamycin group [(15.8±3.5)%, t=1.951, P0.05]. Migration rates of cells of rapamycin group at PSH 10 and 15 [(42.5±4.0)% and (71.3±9.2)%, respectively] were obviously decreased as compared with those of control group [(46.9±6.7)% and (88.0±7.7)%, with t values respectively 2.732 and 6.746, P values below 0.01]. (4) Compared with that in control group (0.46±0.14), FAK activity of cells in rapamycin group (0.16±0.08) was significantly down-regulated (t=4.967, P0.01).FAK signal pathway is sensitive to rapamycin in HaCaT cells. Inhibition effects of rapamycin on migration of HaCaT cells may be mediated by down-regulated activity of FAK.

Overgrazing affects typical steppe community in ways similar to grasslands in other areas. Exclusion of livestock grazing is one of the main management practices used to protect grasslands. However, it is not known if longterm exclusion of livestock grazing has positive effect on above- and belowground community properties in typical steppe of the Loess Plateau. We studied the long-term (20-year) cumulative effects of exclusion of livestock grazing on above- and belowground community properties compared with that before exclusion of livestock grazing in a typical steppe of the Loess Plateau, NW China. Our results show that twenty-year exclusion of livestock grazing significantly increased above- and belowground biomass, species richness, cover and height for five different com munities. Most of belowground biomass was in the 0–20 cm horizon and grazing exclusion increased biomass especially at the depth of 0–10 cm. Our study suggests that long-term exclusion of livestock grazing can greatly improve community properties of typical steppe in the Loess Plateau.

Soil organic matter is a heterogeneous mixture of organic substances with different compositions and stabilities. To enhance soil organic carbon (SOC) sequestration, it is helpful to understand the distribution of SOC among the soil particle size fractions, the stabilities of the SOC within each fraction, and the influence of management practices, such as tillage, on SOC mineralization. Hence, the objectives of this study were to determine the distribution and mineralization rate of active SOC in the sand (53-2000 µm), silt (2-53 µm) and clay (-1) to a 1:4 soil:water suspension. The sand, silt and clay fractions of the three tillages were aerobically incubated at 20°C and 30% moisture (wt/wt), and the CO2-C emissions were measured over 103 d. The SOC contents followed the order clay > silt > sand for all three tillages. On a whole-soil basis and averaged over the tillage treatments, 55.8% of the SOC was in the clay size fraction, 37.2% was in the silt fraction and 7.0% was in the sand fraction. Carbon mineralization rate in the incubated samples decreased over time, and was related to both particle size fraction and tillage practice. There was very good agreement between a first-order decay model (Ct= C1 + C0 (1-e-kt)) and measured SOC mineralization rates for all size fractions and tillages. The C mineralization data indicated that: (1) the SOC in the clay and sand fractions was more decomposable than the SOC in the silt fraction; and (2) the SOC associated with the clay and silt fractions was more readily decomposable under no-till than under mouldboard plough.

Background Brain-derived neurotrophic factor (BDNF) plays an important role in the pathogenesis of atopic dermatitis (AD). Whether BDNF gene polymorphisms are associated with Chinese AD remains totally unknown. Objective The aim is to determine if BDNF gene C270T and G196A polymorphisms are associated with Chinese AD, and analyse the clinical relevance of BDNF gene polymorphisms and BDNF serum levels. Methods We conducted a case-control association analysis (160 patients and 169 controls) in Northern Chinese subjects. Genotyping was performed by restriction fragment length polymorphism, and serum levels of BDNF were measured using enzyme-linked immunosorbent assay. Results For C270T, there were significant differences in C/T genotype distribution (P = 0.003) and T allele frequencies (P = 0.004) between AD patients and controls in the whole dataset. Higher C/T genotype frequencies were found in male AD (10.6% vs. 1.1%, P = 0.018) and in intrinsic AD (IAD; 15.79% vs. 2.91%, P = 0.008). No association between G196A polymorphism and AD was observed in the whole cohort, while A allele was much more frequent in AD patients with atopy in first-degree relatives (65.8% vs. 34.2%, P = 0.038). Serum BDNF levels were correlated with IAD severity as measured by Scoring Atopic Dermatitis index (r = 0.576, P

A novel dual-mode bandpass filter based on conventional triangular structure is designed in this paper. The filter has the characteristics of compact structure, low insertion loss and so on. Several attenuation poles in the stopband are realized to improve the selectivity of the proposed bandpass filter. The experimented results were in good agreement with simulated results.

A novel type of dual-band microstrip structure and its equivalent circuit are investigated, which is composed of defected split-ring resonator and interdigital capacitor. The influence of design parameters on the frequency characteristics is discussed, then a dual-band microstrip filter, which has two passbands of 1.8–2.5 GHz and 5.5–5.9 GHz with a transmission zero, is designed and fabricated. © 2007 Wiley Periodicals, Inc. Microwave Opt Technol Lett 49: 2104–2106, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.22673

The completion of a preliminary human genome map and development of molecular methods have enabled researchers to assay a large number of polymorphic markers that are evenly spaced along the entire human genome. Among many applications, marker data are valuable for mapping complex traits through linkage or linkage-disequilibrium analysis, the former of which is the focus of this paper, the first in a series on this subject. Formalizing the concept and computation for linkage analysis, Elston and Stewart [1971; Human Heredity 21:523-542] introduced a likelihood function to capture relevant genetic information and a recursive algorithm for computing the likelihood function. However, the computing burden is prohibitive in processing complex pedigrees. Since that fundamental development, improving the computational algorithm and extending the method has been a dynamic area of research. The primary objective of this communication is to introduce a semiparametric method for linkage analysis. It is a particularly suitable approach with desirable properties for mapping complex traits that may be binary, continuous, and partially observed (i.e., censored). It incorporates candidate genes, environmental factors, and their interactions with the putative gene and is expected to be robust and efficient in comparison with likelihood-based methods. The properties of the estimates have been studied in finite samples with a limited simulation study. This method is illustrated with an application to family data contributed to the Breast Cancer Consortium.

The joint distribution of repeated binary observations is multinomial, and can be specified using a representation first suggested by Bahadur (in: H. Solomon (Ed.) Studies in item analysis and prediction (Stanford University Press, Stanford, 1961)), and later by Cox (Appl. Statist., 21 (1972) 113–120). Using the Bahadur representation, the marginal probabilities of success can be related to a set of covariates using the logistic link function, or any other suitable link function. If only the marginal parameters are of interest, the these can be estimated using the generalized estimating equations approach proposed by Liang and Zeger (Biometrica (1986)). However, often the joint probabilities are of scientific interest. For example, we may have interest in the probability of success on any of the repeated measures. This “union” probability can be specified in terms of the joint probabilities between the repeated measures, which can be expressed as functions of the marginal probabilities and the 2nd and higher-order correlations. We present the results of a simulation study designed to evaluate the small sample properties of several methods of estimating the parameters of the Bahadur model.

Defect in the SPINK5 gene is known to be implicated in Netherton syndrome (NS), and has been suggested to be a locus predisposing to atopy in general. Coding polymorphisms in SPINK5 exons 13, 14 and 26 have been reported to be associated with atopic dermatitis (AD), asthma and high level of IgE.To examine whether the SPINK5 gene polymorphisms are associated with AD in Northeast China, and to assess how variants influence selected phenotypic traits.A case-control study was conducted on four non-synonymous polymorphisms in the coding region of SPINK5 in AD and controls. The SPINK5 gene polymorphisms were analyzed using the PCR and RFLP methods.For the four non-synonymous SNPs, A1103G(Asn368Ser), G1156A(Asp386Asn), G1258A(Glu420Lys), G2475T(Glu825Asp) in SPINK5, the allelic frequencies in the AD cohort were 0.55 for 1103G, 0.57 for 1156A, 0.54for 1258A, 0.62 for 2475T, consistent with those already published in the original British and Japanese cohorts. The T allele of SNP 2475GT was found to be significantly associated with AD. There were significant differences in genotype frequencies for G1258A(Glu420Lys) and G2475T(Glu825Asp) but not for A1103G(Asn368Ser) and G1156A(Asp386Asn). Genotypes GA(420Glu/Lys), TT (2475Asp/Asp) and GT(2475Glu/Asp) were significantly more frequent in AD. However, the SPINK5 gene polymorphisms was found not to be associated with AD in regard to either serum IgE levels, concurrent allergic asthma or early onset of AD.Our study confirms the association between SPINK5 and AD.

There has been very limited study on the stability of a Shack-Hartmann wavefront sensor (SHWS) since its emergence in the early 1970s. In this paper, through experimental study of the system stability of a digital SHWS, a special lenslet array with long focal range is designed and implemented with a spatial light modulator to improve the system performance. Diffractive lenses with long focal length range can provide pseudo-nondiffracting beams and a long range of focusing plane. The performance and effect of the modified SHWS with this lenslet array are investigated, and the experimental results show that the system stability and measurement repeatability are not sensitive to the sensing distance and stay at an acceptable level.

When wavefront is reflected by a surface, the information of the surface profile is carried by the reflected wavefront. Measure the wavefront can extract the profile information. There are different kinds of pre-defined surface profile with various dimensions. While the size of particular wavefront sensor is fixed, the measurement range is limited. The design of optical system to bridge the work piece and wavefront sensor is critical. This paper presents a platform for the guidance of optical system design. The parameters of commercial available optical components are input to the platforms and the propagation of reflected wavefront is simulated. The relationship of part profile and the measurement wavefront is provided. The discussion is focused on the 2f+2f system for surface flatness measurement. The measurement of aspherical surface is also presented. Shack-Hartmann wavefront sensor (SHWS) is selected due to its simple structure, insensitivity to vibration etc, which is suitable for in-line application. Optical system is designed with the guidance of simulation platform. The experimental results shows the 2f+2f system is compatible to misalignments, can be used to monitor the deformations of parts. The measurement of aspherical surface is also presented with the comparison of simulation results.

In this study, the interaction performance of three light sources, namely white light, laser diode and He-Ne laser, with two wave-front sensing systems was investigated experimentally using different sensing distances and sampling apertures (two hole-apertures for a Hartmann system and a spatial-light-modulator lenslet-array for a digital Shack-Hartmann system). It was found that the white light source was the best for the Hartmann system, while the He-Ne laser was the most suitable light source for the digital Shack-Hartmann system. Geometrical accuracy of a hole-array aperture and the sensing distance are important to generate stable wave fronts.

Since its emergence in the early 1970s, Shack-Hartmann Wavefront Sensing technology has been investigated and explored world-widely by the researchers and engineers. However, there are few papers or reports to study the system performance and key factors to affect the performance of a Shack-Hartmann Wavefront Sensor (SHWS), in this paper, through experimental study of the system stability of a SHWS, it is found that the image sensor and detector, normally a CCD, should be placed exactly at the focal plane of the lenslet array, otherwise it will bring in significant wavefront measurement error. In order to improve the system performance, a special lenslet array with long focal range is designed, and it is functioned by a spatial light modulator for sampling wavefront in a SHWS. Diffractive lenses with long focal length range can provide pseudo-nondiffracting beams, and a long range of focusing plane. The performances and effects of the modified SHWS with such a special lenslet array generated by a programmable SLM, are investigated, and the experimental results show that the system stability and measurement repeatability are not sensitive to the sensing distance, and can keep at a good level in a long range.

Using a recently developed semiparametric method for combined linkage/linkage-disequilibrium analysis, we analyzed the Collaborative Study on the Genetics of Alcoholism data subset developed for Genetic Analysis Workshop 11 (GAW11). This semiparametric approach estimates recombination fractions for linkage, marker log odds ratios for linkage-disequilibrium, their product for combined linkage/linkage-disequilibrium, and corresponding z-scores. We used two outcomes: alcohol dependence and "alcoholism-free" and a genome-wide significance level of 4.1 (which corresponds to a genome-wide lod score of 3.6). For the alcohol dependence outcome, we observed significant linkage signals at D1S1588-D1S1631, D1S547, D2S399, D2S425, D4S2361, D7S1796, and D7S1824. We also found significant linkage-disequilibrium signals at D1S547 and D7S1795. For the "alcoholism-free" outcome, we found significant linkage signals at D4S2457, D41651 (both flank ADH3), D11S2359, and D16S47 and significant linkage-disequilibrium signals at D4S2361, FABP2, D11S2359, D19S431 and D19S47-D19S198-D19S601.

A genome-wide scan of a simulated data set for fictitious disease genes was conducted using both semiparametric and nonparametric methods. The semiparametric model-based method, which tests for linkage/linkage disequilibrium separately and together, correctly identified all three underlying disease loci along with two false positives through the linkage analysis. However, the nonparametric model-free method which tests combined linkage/linkage disequilibrium, failed to yield any results due to the lack of linkage disequilibrium information in the data.

Decreased age at onset in successive generations has been observed for a number of diseases. Two nonparametric matched and unmatched test statistics are proposed, taking into account not only current age or age at death for unaffected individuals and age at disease onset for affected individuals, but also possible correlations among family members. Both are asymptotically normal with readily estimated variances from the data. A simulation study is conducted to compare the proposed tests with the commonly used paired t-test and log-rank test. It has been shown that the proposed test statistics yield valid conclusions in assessing genetic anticipation under all situations considered. However, the paired t-test is valid only when the censoring distributions are comparable between two generations, whereas the log-rank test is valid when the correlation among family members is weak. As expected, the matched test is most powerful when the data are heterogeneous, and the unmatched and the log-rank tests are most powerful when the data are homogeneous and the correlation is weak. Lastly, a population-based family study of breast cancer conducted at the Fred Hutchinson Cancer Research Center is used for illustration of the proposed and the log-rank tests. The preliminary analysis suggests that there appears a decreased age at onset over the successive generations in breast cancer.

Most complex traits such as cancer and coronary heart diseases are attributed either to heritable factors or to environmental factors or to both. Dissecting the genetic and environmental etiology of complex traits thus requires an interdisciplinary research strategy. Genetic studies generally involve families and investigate familial aggregations of traits, segregation of major disease genes, and locations of disease genes on the human genome, the latter of which can be identified via linkage analysis. Epidemiologic studies often use population-based case-control studies to establish the role of specific environmental factors. Integrating both objectives, genetic epidemiology is to assess the associations of environmental factors with disease status, to quantify the aggregation of cases within families, to characterize putative disease genes via segregation analysis, and to localize disease genes via linkage analysis with genetic markers. To accomplish these objectives through designed studies, we propose a class of population-based family study designs, which are formed by choosing among sampling designs at three stages. The objectives of sampling at these three stages are 1) combined aggregation and association analysis, 2) combined segregation, aggregation, and association analysis, and 3) combined linkage, segregation, aggregation, and association analysis. These designs form an interdisciplinary research framework for genetic epidemiology. Our preliminary exploration of this framework and related analytic methods indicates that population-based family study designs retain the efficiency of linkage analysis for localizing disease genes without losing the property of being population-based, and they will therefore allow an assessment of a joint contribution of genetic and environmental factors to complex traits.