Cytosine-guanine-guanine repeats of FMR1 gene negatively affect ovarian reserve and response in Chinese women.

RESEARCH QUESTION: Do cytosine-guanine-guanine (CGG) repeats of the FMR1 gene affect ovarian function, ovarian response and assisted reproductive technology (ART) outcomes in Chinese women? DESIGN: A retrospective cohort study of 5869 women who underwent 8932 ART cycles at Women's Hospital, School of Medicine, Zhejiang University between January 2018 and June 2021. Basic hormone level, oocyte yield, embryo quality and the rate of live birth were considered as main outcome measures to evaluate the effects of CGG repeats on ovarian function, ovarian response and ART outcomes. RESULTS: The CGG repeats were negatively related to serum anti-Müllerian hormone (AMH), oestradiol, antral follicle count (AFC) and oocyte yield. A significant association was found between serum AMH, oestradiol and AFC even after age was controlled for. No statistically significant association, however, was found between CGG repeats and embryo quality or live birth rate. Ovarian function mediated the association between CGG repeats and ovarian response. CONCLUSION: Increased CGG repeats on the FMR1 gene were associated with diminished ovarian function and poor ovarian response, and ovarian function played an intermediary role in the relationship between CGG repeats and ovarian response.

Comparison of MIB-1-Specific Membrane Staining in Hyalinising Trabecular Tumor Using Mainstream Automated Immunohistochemical Staining Platforms.

BACKGROUND: MIB-1, a monoclonal antibody against Ki-67, exhibits specific membrane staining in the immunohistochemistry of hyalinising trabecular tumor (HTT). This specific staining pattern is crucial in diagnosing HTT. Although manual immunohistochemical staining remains the established method for MIB-1 staining, this process is complicated, inconsistent, and prone to false negatives. METHODS: This study aimed to explore whether the classical reaction pattern can be replicated by utilizing the current mainstream automated immunohistochemical staining platforms. Furthermore, we examined the effect of different conditions on staining efficiency and their value in clinical diagnosis assistance. RESULTS: Specimens obtained from eight and six cases of HTT and non-HTT, respectively, from a single center were stained using the manual staining method and the Dako Autostainer Link 48 (AS48), Dako Omnis, Ventana BenchMark ULTRA, and Leica BOND-III automated immunohistochemical staining platforms. The Autostainer Link 48 was found to be the most stable staining platform, while the BenchMark ULTRA with primary antibody incubation at room temperature (RT) and the Omnis platform with antigen retrieval at pH 9.0 were able to reproduce membrane-positive staining for MIB-1 in the HTT specimens. CONCLUSIONS: Our results offer crucial reference value for clinical diagnostic assistance.

Understanding adherence to continuous positive airway pressure in patients with obstructive sleep apnea post-stroke: A prospective study based on the Andersen model.

Adherence to continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) post-stroke is often problematic, despite potential benefits. This study aimed to evaluate CPAP adherence in patients with OSA post-stroke based on the Andersen behavioral model of health services utilization. A total of 227 eligible participants were recruited from a Chinese hospital. After baseline assessment, participants were followed for 6 months to determine short-term CPAP adherence. Those with good short-term adherence were followed for an additional 6 months to explore long-term adherence and influencing factors. Short-term CPAP adherence rate was 33%. Being married or living with a partner, having an associate degree or baccalaureate degree or higher, and stronger health beliefs independently predicted short-term CPAP adherence. Only 25% of participants from the adherent group showed good long-term adherence. The factor associated with long-term CPAP adherence was participants not using alcohol. Adherence to CPAP is suboptimal among patients having OSA post-stroke. Addressing unfavorable predisposing factors and modifying health beliefs are suggested.

Noninvasive Prenatal Screening for Common Fetal Aneuploidies Using Single-Molecule Sequencing.

Amplification biases caused by next-generation sequencing (NGS) for noninvasive prenatal screening (NIPS) may be reduced using single-molecule sequencing (SMS), during which PCR is omitted. Therefore, the performance of SMS-based NIPS was evaluated. We used SMS-based NIPS to screen for common fetal aneuploidies in 477 pregnant women. The sensitivity, specificity, positive predictive value, and negative predictive value were estimated. The GC-induced bias was compared between the SMS- and NGS-based NIPS methods. Notably, a sensitivity of 100% was achieved for fetal trisomy 13 (T13), trisomy 18 (T18), and trisomy 21 (T21). The positive predictive value was 46.15% for T13, 96.77% for T18, and 99.07% for T21. The overall specificity was 100% (334/334). Compared with NGS, SMS (without PCR) had less GC bias, a better distinction between T21 or T18 and euploidies, and better diagnostic performance. Overall, our results suggest that SMS improves the performance of NIPS for common fetal aneuploidies by reducing the GC bias introduced during library preparation and sequencing.

Phosphorylated walnut protein/chitosan nanocomplexes as promising carriers for encapsulation of caffeic acid phenethyl ester.

BACKGROUND: Walnut proteins display poor solubility and dispersity under acidic pH conditions, which limits their application in acidic beverages and foods. This study aimed to fabricate stable nanocomplexes between phosphorylated walnut protein (PWPI) and chitosan (CS) in an acidic pH and to investigate the encapsulation capacity of the complexes. RESULTS: The PWPI/CS nanocomplexes prepared at a mass ratio of 2:1 showed small Z-average sizes (approximately 285 nm at pH 5.5 and 222 nm at pH 3.5) with a narrow particle distribution (polydispersity index <0.3). Caffeic acid phenethyl ester (CAPE) can be effectively encapsulated into PWPI/CS with improved solubility. Circular dichroism analysis indicated that PWPI/CS and CAPE-loaded PWPI/CS (PWPI/CS-CAPE) had reduced α-helical content and increased ß-sheet content. Fourier transform infrared spectroscopy analysis further identified the different driving forces for the complexation of PWPI and CS at pH 3.5 and 5.5 and confirmed the successful encapsulation of CAPE. The rheological results revealed that the PWPI/CS and PWPI/CS-CAPE formed at pH 3.5 (PWPI/CS-CAPE-3.5) had a higher apparent viscosity and better viscoelasticity than the complexes formed at pH 5.5. The PWPI/CS-CAPE-3.5 also showed good stability under heat treatment, salt treatment, and long-term storage. The PWPI/CS-CAPE complexes showed controlled release of CAPE. CONCLUSION: Walnut protein and chitosan nanocomplexes prepared at acidic pH levels were stable and promising carriers for CAPE, which could expand the application of walnut proteins in the food industry. © 2023 Society of Chemical Industry.

Insights into the Diffusion Behaviors of Water over Hydrophilic/Hydrophobic Catalysts During the Conversion of Syngas to High-Quality Gasoline.

Although considerable efforts towards directly converting syngas to liquid fuels through Fischer-Tropsch synthesis have been made, developing catalysts with low CO2 selectivity for the synthesis of high-quality gasoline remains a big challenge. Herein, we designed a bifunctional catalyst composed of hydrophobic FeNa@Si-c and HZSM-5 zeolite, which exhibited a low CO2 selectivity of 14.3 % at 49.8 % CO conversion, with a high selectivity of 62.5 % for gasoline in total products. Molecular dynamic simulations and model experiments revealed that the diffusion of water molecules through hydrophilic catalyst was bidirectional, while the diffusion through hydrophobic catalyst was unidirectional, which were crucial to tune the water-gas shift reaction and control CO2 formation. This work provides a new fundamental understanding about the function of hydrophobic modification of catalysts in syngas conversion.

Prenatal diagnosis of Walker-Warburg syndrome due to compound mutations in the B3GALNT2 gene.

BACKGROUND: Congenital hydrocephalus is one of the symptoms of Walker-Warburg syndrome that is attributed to the disruptions of the genes, among which the B3GALNT2 gene is rarely reported. A diagnosis of the Walker-Warburg syndrome depends on the clinical manifestations and the whole-exome sequencing after birth, which is unfavorable for an early diagnosis. METHODS: Walker-Warburg Syndrome was suspected in two families with severe fetal congenital hydrocephalus. Whole-exome sequencing and Sanger sequencing were performed on the affected fetuses. RESULTS: The compound heterozygous variants c.1A>G p.(Met1Val) and c.1151+1G>A, and c.1068dupT p.(D357*) and c.1052 T>A p.(L351*) in the B3GALNT2 gene were identified, which were predicted to be pathogenic and likely pathogenic, respectively. Walker-Warburg syndrome was prenatally diagnosed on the basis of fetal imaging and whole-exome sequencing. CONCLUSIONS: Our findings expand the spectrum of pathogenic mutations in Walker-Warburg syndrome and provide new insights into the prenatal diagnosis of the disease.

Mercury in sediment reflecting the intensive coal mining activities: Evidence from stable mercury isotopes and Bayesian mixing model analysis.

Severe environmental issues are caused by long-term coal mining activities; however, the process of mercury (Hg) response in mining subsidence area sediments (MSAS) is still unclear, and direct evidence showing the relationship between Hg accumulation mechanism in sediments and mining activities is lacking. In this study, the characteristics of total mercury (THg) content in MSAS were investigated. Moreover, Hg isotopes were obtained to determine the main sources and environmental process of mercury in MSAS, and a MixSIAR mixing model was first used to estimate the potential Hg sources. The THg content ranged from 27.5 to 113.9 ng/g, with a mean of 65.8 ± 29.4 ng/g, exceeding the local soil background value (19.7 ng/g). The Hg in MSAS was affected by clay and organic matter. The Δ199Hg and Δ201Hg in the sediments varied from - 0.05-0.05‰ (mean: -0.01 ± 0.03‰) and - 0.07-0.01‰ (mean: -0.02 ± 0.03‰), respectively, with the fitting results suggesting that a photochemical reaction occurred in some of the Hg in the sediments prior to deposition. The results of the MixSIAR mixing model revealed that the Hg in MSAS was mainly derived from gangue, soil erosion, coal, fly ash, and feed, and their corresponding percentage contribution was 51.5 ± 9.6%, 23.8 ± 13.1%, 13.9 ± 7.9%, 8.1 ± 5.4%, and 3.1 ± 1.4%, respectively. Hg isotopes can be used to trace the transport and transformation of environmental pollutants, and this may provide an important reference for the assessment and prevention of Hg pollution in typical areas such as coal mining and coal-fired.

Phosphorylated walnut protein isolate as a nanocarrier for enhanced water solubility and stability of curcumin.

BACKGROUND: The low solubility and poor dispersion of alkaline-extracted walnut protein isolate (AWPI) limit its application as a protein-based carrier for the delivery of poorly soluble nutraceuticals, including curcumin. This work investigated the physicochemical characteristics of phosphorylated walnut protein isolate (PWPI) extracted using sodium tripolyphosphate (STP) and evaluated its encapsulation ability. RESULTS: The results of phosphorus determination, X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR) spectroscopy confirmed the phosphorylation of the extracted PWPI. Circular dichroism (CD) analysis indicated that PWPI contained higher α-helix and lower ß-sheet contents than AWPI. The PWPI prepared at pH 9.0 and 11.0 showed significantly improved solubility, similar surface hydrophobicity, and increased surface charges compared to the AWPI. Fluorescence quenching experiments indicated that the binding affinity of curcumin to PWPI was significantly higher than that of AWPI. When bound to PWPI, the solubility of curcumin in aqueous solution was greatly enhanced, with an 8700-fold increase at a nanocomplex concentration of 10 mg mL-1 . The complexation of curcumin with PWPI significantly improved the storage stability of curcumin. Additionally, the PWPI-curcumin nanocomplexes showed significantly increased antioxidant capacity. CONCLUSION: Phosphorylated walnut protein isolate showed greatly improved solubility and strong encapsulation ability, making it a promising nanocarrier for curcumin. © 2022 Society of Chemical Industry.

Environmental geochemical characteristics of rare-earth elements in surface waters in the Huainan coal mining area, Anhui Province, China.

This study investigated the environmental geochemical characteristics of rare-earth elements (REEs) in surface waters in the Huainan mining area, Anhui Province, China. The REEs concentrations were determined by ICP-MS, and the inorganic species of dissolved REEs in the river and coal mining subsidence area water samples were calculated by using the Visual MINTEQ (version 3.1) code. On this basis, the distribution and geochemical characteristics of REEs in the surface waters were systematically analyzed, and the main inorganic species of REEs were investigated. The results showed the following: (1) The REEs concentrations in the surface waters were relatively low, ranging from 0.1361 to 0.3536 µg/L, and the average ∑REEs concentration was 0.2062 µg/L. Compared with light rare-earth elements (LREEs), heavy rare-earth elements (HREEs) were significantly enriched, with an average enrichment factor of 1.4642. Due to the interaction of high pH values and high cation concentrations, the ∑REEs content in the subsidence area water was significantly lower than that in the river water. (2) The distribution pattern of REEs in the surface waters normalized against the North American Shale Composite (NASC) showed that the REEs in the study area had different degrees of cerium (Ce) and europium (Eu) anomalies. The negative Ce anomalies were probably closely related to the pH conditions, whereas the positive Eu anomalies were mainly attributed to preferential chemical weathering and the dissolution of feldspar minerals. (3) The simulation results obtained by using Visual MINTEQ code showed that the dominant and typically inorganic complex form of REEs in the surface waters was carbonate complexes, and this form was one of the reasons for the enrichment of HREEs in the surface water.

Nitrate sources and transformations in surface water of a mining area due to intensive mining activities: Emphasis on effects on distinct subsidence waters.

The increase in NO3- content in surface water caused by intensive mining activities in Huainan City, China, has attracted considerable attention owing to the deterioration of water quality and the degradation of ecosystems in recent years. The Huainan mining area, which is highly disturbed by anthropogenic activities, was selected as a typical observation area, and the surface water was classified as open subsidence water (OSW), closed subsidence water (CSW), and river water (RW). Moreover, the hydrochemical parameters and the δ15N and δ18O values of nitrate were employed to quantitatively trace the sources and biochemical transformation of NO3-, and the contribution ratios of different NO3- sources were estimated using the stable isotope analysis in R based on the Bayesian model. There was evident nitrification in the study area, but no significant denitrification has occurred. A substantial portion of δ15N-NO3- demonstrated complex sources of NO3-. Compared with those of CSW, the NO3- compositions of the OSW approached to those of the RW due to river recharge and discharge, and were greatly affected by anthropogenic activities. The proportional contribution of manure and sewage in the OSW was found to be the highest with a mean value of 39.5 % ± 12.3 %, which was followed by that of mine drainage (mean: 22.1 % ± 13.1 %), chemical fertilizer (mean: 17.5 % ± 10.6 %), and soil organic nitrogen (mean: 17.5 % ± 11.6 %). In the RW, the highest mean contribution of manure sewage was 35.2 % ± 9.7 %, which was followed by that of chemical fertilizer (mean: 29.3 % ± 7.2 %), mine drainage (mean: 23.4 % ± 13.0 %), and soil organic nitrogen (mean: 10.9 % ± 8.3 %). In contrast, the contribution of chemical fertilizer to the CSW was the highest with a mean value of 33.9 % ± 13.6 %, which was followed by that of soil organic nitrogen (mean: 26.5 % ± 13.8 %), mine drainage (mean: 18.1 % ± 11.6 %). Therefore, NO3- in the surface water of the mining area primarily originates from chemical fertilizers and manure sewage. In addition, the contribution of mine drainage to nitrate in the study area indicates the potential impact of mining activities on surface water. These findings highlight the value of classifying different types of surface water in tracing NO3- contamination sources, and provide relevant theoretical basis for tracing nitrate sources in other areas.

A prospective evaluation of clinical and genetic predictors of weight changes in breast cancer survivors.

BACKGROUND: Postdiagnosis weight gain in patients with breast cancer has been associated with increased cancer recurrence and mortality. This study was designed to identify risk factors for weight gain and create a predictive model to identify a high-risk population for targeted interventions. METHODS: The weight of 393 patients with breast cancer from the Northwestern Robert H. Lurie Cancer Center was measured over a 2-year period from diagnosis, with body mass index (BMI) change over 18 months as the primary endpoint. Demographics, clinical factors, treatment methods, as well as tumor characteristics were also recorded; and a lifestyle questionnaire was conducted. Blood samples were genotyped for 16 single nucleotide polymorphisms in FTO, adiponectin pathway genes (ADIPOQ, ADIPOR1), and FNDC5. Serum leptin, adiponectin, and irisin levels also were measured. RESULTS: Mean ± standard deviation 18-month BMI changes were 0.68 ± 1.42, 0.98 ± 1.62, 0.79 ± 1.74, and -0.44 ± 1.58 kg/m2 for patients ages <40, 40 to 49, 50 to 59, and ≥60 years, respectively. The optimal multivariable model for 18-month BMI change contained the predictors age, height, and endocrine therapy, but only age was statistically significant, with a 0.04 kg/m2 increase in 18-month BMI change per younger year of age. Single nucleotide polymorphisms in ADIPOR1, FTO, and FNDC5 were associated with 18-month BMI change, and the first 2 remained significant after adjusting for the optimal clinical model (all P < .05). CONCLUSIONS: Women age 60 years and younger at the time of breast cancer diagnosis who have an obesity genetic risk model are at increased risk for weight gain after treatment and should be targeted for weight-maintenance interventions. Cancer 2017;123:2413-21. © 2017 American Cancer Society.

4-1BB ligand signaling to T cells limits T cell activation.

4-1BB ligand (4-1BBL) and its receptor, 4-1BB, are both induced on T cells after activation, but little is known about the role of 4-1BBL. In this study we show that 4-1BBL can transmit signals that limit T cell effector activity under tolerogenic conditions. Cross-linking 4-1BBL inhibited IL-2 production in vitro, primarily with suboptimal TCR stimulation. Furthermore, naive 4-1BBL-deficient OT-II transgenic T cells displayed a greater conversion to effector T cells in vivo when responding to soluble OVA peptide in wild-type hosts, whereas development of Foxp3(+) regulatory T cells was not altered. A greater number of effector T cells also differentiated from naive wild-type OT-II T cells when transferred into 4-1BB-deficient hosts, suggesting that APC-derived 4-1BB is likely to trigger 4-1BBL. Indeed, effector T cells that could not express 4-1BBL accumulated in larger numbers in vitro when stimulated with 4-1BB-expressing mesenteric lymph node dendritic cells. 4-1BBL was expressed on T cells when Ag presentation was limiting, and 4-1BBL was aberrantly expressed at very high levels on T cells that could not express 4-1BB. Trans-ligation, Ab capture, and endocytosis experiments additionally showed that T cell-intrinsic 4-1BB regulated internalization of membrane 4-1BBL, implying that the strong induction of 4-1BB on T cells may counteract the suppressive function of 4-1BBL by limiting its availability. These data suggest that 4-1BBL expressed on T cells can restrain effector T cell development, creating a more favorable regulatory T cell to effector cell balance under tolerogenic conditions, and this may be particularly active in mucosal barrier tissues where 4-1BB-expressing regulatory dendritic cells present Ag.

Morphological and molecular control of chemical vapor deposition (CVD) polymerized polythiophene thin films.

Oxidative chemical vapor deposition (oCVD) has emerged as one of the most promising techniques for conjugated polymer deposition, especially for unsubstituted polythiophene thin films. oCVD overcomes the insolubility challenge that unsubstituted polythiophene (PT) presents and adds the ability to control morphological and molecular structure. This control is important for enhancing the performance of devices which incorporate organic conductors. In this work, Raman spectroscopy, UV-vis spectroscopy, and AFM reveal that the relative amount of distortion in the polymer chains, the conjugation length and the film roughness are all affected by the CVD deposition conditions, in particular the reactor pressure. PT films deposited at 150 mT and 300 mT are found to have lower chain distortion, longer conjugation lengths and lower surface roughness compared to other deposition pressures. The oCVD PT film is also directly grafted to the trichloro(phenylethyl)silane (PTS) treated substrates, where the effect of PTS grafting is observed to significantly affect film roughness. In addition, we report the first study of the effect of oCVD PT films on the performance of lithium-ion battery electrodes. These oCVD PT films are used to engineer a LiCoO2 cathode in lithium-ion batteries. The observed improvements are a 52% increase in the discharge capacity (67 mA h g-1 to 102 mA h g-1) at 10C and a 500% improvement in cycling stability tested at 5C within the voltage range of 3.0-4.5 V (capacity fading rate is reduced from 1.92%/cycle to 0.32%/cycle).

Effects of surface hydrophobization on the phase evolution behavior of iron-based catalyst during Fischer-Tropsch synthesis.

Iron-based Fischer-Tropsch synthesis (FTS) catalyst is widely used for syngas conversion, but its iron carbide active phase is easily oxidized into Fe3O4 by the water produced during reaction, leading to the deterioration of catalytic performance. Here, we show an efficient strategy for protecting the iron carbide active phase of FTS catalyst by surface hydrophobization. The hydrophobic surface can reduce the water concentration in the core vicinity of catalyst during syngas conversion, and thus inhibit the oxidation of iron species by water, which enhances the C - C coupling ability of catalyst and promotes the formation of long-chain olefins. More significantly, it is unraveled that appropriate shell thickness plays a crucial role in stabilizing the iron carbide active phase without Fe3O4 formation and achieving good catalytic performance.

Performance of noninvasive prenatal screening for fetal sex chromosome aneuploidies in a cohort of 116,862 pregnancies.

BACKGROUND: Noninvasive prenatal screening (NIPS) has shown good performance in screening common aneuploidies. However, its performance in detecting fetal sex chromosome aneuploidies (SCAs) needs to be evaluated in a large cohort. RESEARCH DESIGN AND METHODS: In this retrospective observation, a total of 116,862 women underwent NIPS based on DNA nanoball sequencing from 2015 to 2022. SCAs were diagnosed based on karyotyping or chromosomal microarray analysis (CMA). Among them, 2,084 singleton pregnancies received karyotyping and/or CMA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NIPS for fetal SCAs were evaluated. RESULTS: The sensitivity was 97.7% (95%CI, 87.7-99.9), 87.3% (95% CI, 76.5-94.4), 96.1% (95%CI, 86.5-99.5), and 95.7% (95% CI, 78.1-99.9), the PPV was 25.8% (95%CI, 19.2-33.2), 80.9% (95%CI, 69.5-89.4), 79.0% (95%CI, 66.8-88.3), and 53.7% (95%CI, 37.4-69.3) for 45,X, 47,XXY, 47,XXX, and 47,XYY, respectively. The specificity was 94.1% (95%CI, 93.0-95.1) for 45,X, and more than 99.0% for sex chromosome trisomy (SCT). The NPV was over 99.0% for all. CONCLUSIONS: NIPS screening for fetal SCAs has high sensitivity, specificity and NPV. The PPV of SCAs was moderate, but that of 45,X was lower than that of SCTs. Invasive prenatal diagnosis should be recommended for high-risk patients.

A randomized Phase I pre-operative window trial of transdermal endoxifen in women planning mastectomy: Evaluation of dermal safety, intra-mammary drug distribution, and biologic effects.

Breast cancer prevention only requires local exposure of the breast to active drug. However, oral preventive agents entail systemic exposure, causing adverse effects that limit acceptance by high-risk women. Drug-delivery through the breast skin is an attractive option, but requires demonstration of dermal safety and drug distribution throughout the breast. We formulated the tamoxifen metabolite (E/Z)-endoxifen for transdermal delivery and tested it in a placebo-controlled, double-blinded Phase I trial with dose escalation from 10 to 20 mg daily. The primary endpoint was dermal toxicity. Thirty-two women planning mastectomy were randomized (2:1) to endoxifen-gel or placebo-gel applied to both breasts for 3-5 weeks. Both doses of endoxifen-gel incurred no dermal or systemic toxicity compared to placebo. All endoxifen-treated breasts contained the drug at each of five sampling locations; the median per-person tissue concentration in the treated participants was 0.6 ng/g (IQR 0.4-1.6), significantly higher (p < 0.001) than the median plasma concentration (0.2 ng/mL, IQR 0.2-0.2). The median ratio of the more potent (Z)-isomer to (E)-isomer at each breast location was 1.50 (IQR 0.96-2.54, p < 0.05). No discernible effects of breast size or adiposity on tissue concentrations were observed. At the endoxifen doses and duration used, and the tissue concentration achieved, we observed a non-significant overall reduction of tumor proliferation (Ki67 LI) and significant downregulation of gene signatures known to promote cancer invasion (FN1, SERPINH1, PLOD2, PDGFA, ITGAV) (p = 0.03). Transdermal endoxifen is an important potential breast cancer prevention agent but formulations with better dermal penetration are needed.

Requirements for survivin in terminal differentiation of erythroid cells and maintenance of hematopoietic stem and progenitor cells.

Survivin, which is the smallest member of the inhibitor of apoptosis protein (IAP) family, is a chromosomal passenger protein that mediates the spindle assembly checkpoint and cytokinesis, and also functions as an inhibitor of apoptosis. Frequently overexpressed in human cancers and not expressed in most adult tissues, survivin has been proposed as an attractive target for anticancer therapies and, in some cases, has even been touted as a cancer-specific gene. Survivin is, however, expressed in proliferating adult cells, including human hematopoietic stem cells, T-lymphocytes, and erythroid cells throughout their maturation. Therefore, it is unclear how survivin-targeted anticancer therapies would impact steady-state blood development. To address this question, we used a conditional gene-targeting strategy and abolished survivin expression from the hematopoietic compartment of mice. We show that inducible deletion of survivin leads to ablation of the bone marrow, with widespread loss of hematopoietic progenitors and rapid mortality. Surprisingly, heterozygous deletion of survivin causes defects in erythropoiesis in a subset of the animals, with a dramatic reduction in enucleated erythrocytes and the presence of immature megaloblastic erythroblasts. Our studies demonstrate that survivin is essential for steady-state hematopoiesis and survival of the adult, and further, that a high level of survivin expression is critical for proper erythroid differentiation.

Statistical characterization of the nonlinear noise in 2.8 Tbit/s PDM-16QAM CO-OFDM system.

We show for the first time through comprehensive simulations under both uncompensated transmission (UT) and dispersion managed transmission (DMT) systems that the statistical distribution of the nonlinear interference (NLI) within the polarization multiplexed 16-state quadrature amplitude modulation (PM-16QAM) Coherent Optical OFDM (CO-OFDM) system deviates from Gaussian distribution in the absence of amplified spontaneous emission (ASE) noise. We also observe that the dependences of the variance of the NLI noise on both the launch power and the transmission distance (logrithm) seem to be in a simple linear way.

Transient thermal effect, nonlinear refraction and nonlinear absorption properties of graphene oxide sheets in dispersion.

The nonlinear refraction (NLR) properties of graphene oxide (GO) in N, N-Dimethylformamide (DMF) was studied in nanosecond, picosecond and femtosecond time regimes by Z-scan technique. Results show that the dispersion of GO in DMF exhibits negative NLR properties in nanosecond time regime, which is mainly attributed to transient thermal effect in the dispersion. The dispersion also exhibits negative NLR in picosecond and femtosecond time regimes, which are arising from sp(2)- hybridized carbon domains and sp(3)- hybridized matrix in GO sheets. To illustrate the relations between NLR and nonlinear absorption (NLA), NLA properties of the dispersion were also studied in nanosecond, picosecond and femtosecond time regimes.