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The energy landscapes of proteins are highly complex and can be influenced by changes in physical and chemical conditions under which the protein is studied. The redox enzyme cytochrome P450cam undergoes a multistep catalytic cycle wherein two electrons are transferred to the heme group and the enzyme visits several conformational states. Using paramagnetic NMR spectroscopy with a lanthanoid tag, we show that the enzyme bound to its redox partner, putidaredoxin, is in a closed state at ambient temperature in solution. This result contrasts with recent crystal structures of the complex, which suggest that the enzyme opens up when bound to its partner. The closed state supports a model of catalysis in which the substrate is locked in the active site pocket and the enzyme acts as an insulator for the reactive intermediates of the reaction. [ABSTRACT FROM AUTHOR]

Paramagnetic lanthanides ions are broadly used in NMR spectroscopy. The effects of unpaired electrons on NMR spectral parameters provide a powerful tool for the characterization of macromolecular structures and dynamics. Here, a new lanthanide-chelating NMR probe, Caged Lanthanide NMR Probe-7 (CLaNP-7), is presented. It can be attached to protein surfaces via two disulfide bridges, yielding a probe that is rigid relative to the protein backbone. CLaNP-7 extends the application range of available probes. It has a yellow color, which is helpful for sample preparation. Its effects are comparable to those of CLaNP-5, but its charge is two units lower (+1) than that of CLaNP-5 (+3), reducing the change in surface potential after probe attachment. It also has a different magnetic susceptibility tensor, so by using both tags, two sets of structural restraints can be obtained per engineered cysteine pair. Moreover, it was found that the orientation of the magnetic susceptibility tensor is pH dependent (pKa ≈ 7) when a histidine residue is located in the neighborhood of the probe attachment site. The results show that the His imidazole group interacts with the CLaNP-7 tag. It is proposed that the histidine residue forms a hydrogen bond to a water/hydroxyl molecule that occupies the ninth coordination position on the lanthanide, thus breaking the two-fold symmetry of the CLaNP tag in a pH-dependent way. [ABSTRACT FROM AUTHOR]

MicroRNAs interact with multiple mRNAs resulting in their degradation and/or translational repression. This report used the delayed implantation model to determine the role of miRNAs in blastocysts. Dormant blastocysts in delayed implanting mice were activated by estradiol. Differential expression of 45 out of 238 miRNAs examined was found between the dormant and the activated blastocysts. Five of the nine members of the microRNA lethal-7 (let-7) family were downregulated after activation. Human blastocysts also had a low expression of let-7 family. Forced-expression of a family member, let-7a in mouse blastocysts decreased the number of implantation sites (let-7a: 1.160.4; control: 3.860.4) in vivo, and reduced the percentages of blastocyst that attached (let-7a: 42.068.3%; control: 79.065.1%) and spreaded (let-7a: 33.562.9%; control: 67.363.8%) on fibronectin in vitro. Integrin-b3, a known implantation-related molecule, was demonstrated to be a target of let-7a by 39-untranslated region reporter assay in cervical cancer cells HeLa, and Western blotting in mouse blastocysts. The inhibitory effect of forced-expression of let-7a on blastocyst attachment and outgrowth was partially nullified in vitro and in vivo by forced-expression of integrin-b3. This study provides the first direct evidence that let [ABSTRACT FROM AUTHOR]

In mammals, the sperm deliver mRNA of unknown function into the oocytes during fertilization. The role of sperm microRNAs (miRNAs) in preimplantation development is unknown. miRNA profiling identified six miRNAs expressed in the sperm and the zygotes but not in the oocytes or preimplantation embryos. Sperm contained both the precursor and the mature form of one of these miRNAs, miR-34c. The absence of an increased level of miR-34c in zygotes derived from a-amanitin-treated oocytes and in parthenogenetic oocytes supported a sperm origin of zygotic miR-34c. Injection of miR-34c inhibitor into zygotes inhibited DNA synthesis and significantly suppressed first cleavage division. A 3' IJTR luciferase assay and Western blotting demonstrated that miR-34c regulates B-cell leukemia/lymphoma 2 (Bcl-2) expression in the zygotes. Coinjection of anti-Bcl-2 antibody in zygotes partially reversed but injection of Bcl-2 protein mimicked the effect of miR-34c inhibition. Oocyte activation is essential for the miR-34c action in zygotes, as demonstrated by a decrease in 3' UTR luciferase reporter activity and Bcl-2 expression after injection of precursor miR-34c into parthenogenetic oocytes. Our findings provide evidence that sperm-borne miR-34c is important for the first cell division via modulation of Bcl-2 expression. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules capable of regulating transcription and translation. Previously, a cluster of miRNAs that are specifically expressed in mouse zygotes but not in oocytes or other preimplantation stages embryos are identified by multiplex real-time polymerase chain reaction-based miRNA profiling. The functional role of one of these zygote-specific miRNAs, miR-135a, in preimplantation embryo development was investigated. Methodology/Principal Findings: Microinjection of miR-135a inhibitor suppressed first cell cleavage in more than 30% of the zygotes. Bioinformatics analysis identified E3 Ubiquitin Ligase Seven In Absentia Homolog 1A (Siah1a) as a predicted target of miR-135a. Western blotting and 39UTR luciferase functional assays demonstrated that miR-135a down-regulated the expression of Siah1 in HeLa cells and in mouse zygotes. Siah1a was expressed in preimplantation embryos and its expression pattern negatively correlated with that of miR-135a. Co-injection of Siah1a-specific antibody with miR-135a inhibitor partially nullified the effect of miR-135a inhibition. Proteasome inhibition by MG-132 revealed that miR-135a regulated proteasomal degradation and potentially controlled the expression of chemokinesin DNA binding protein (Kid). Conclusions/Significance: The present study demonstrated for the first time that zygotic specific miRNA modulates the first cell cleavage through regulating expression of Siah1a. [ABSTRACT FROM AUTHOR]

Objective: To investigate alterations of integrin αv, survival and apoptosis signaling pathways in uterine leiomyomas. Materials and Methods: In a prospective study of 50 women with uterine leiomyomas that had been pathologically confirmed, specimens were obtained laparoscopically from 2007 to 2009. The expressions of integrin αv signaling pathways (Ras/Raf/ERK1/2, Akt and cleaved caspase-3), surface microstructures by surface electron microscopy and immunohistochemical findings were assessed. Results: The study yielded novel results: (1) the integrin αv expression approached a low level (mRNA 0.39 ± 0.06, protein 0.47 ± 0.08) with coherent alterations of its downstream signaling molecules (Ras, p-c-Raf, p-ERK1/2) (p < 0.001); (2) smoother surface microstructures of uterine leiomyomas were correlated with low integrin αv expressions, and (3) survival signaling and apoptosis signaling were significantly down- and upregulated respectively (p < 0.001). Conclusion: Integrin αv and related survival signaling pathways were downregulated, but the apoptosis was upregulated in uterine leiomyomas. Benign smooth-contoured tumors may have low integrin expressions and cancer invasion potentials. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A new sensing mechanism based on CN isomerization, which shows a very significant fluorescence enhancement to the metal cations in a simple and efficient way, is demonstrated. A coumarin derivative (L) containing a CN group was designed as an example for illustration. The free ligand Lis almost nonfluorescent due to the isomerization of CN double bond in the excited state. However, the solution of ligand shows about a 200-fold increase of fluorescence quantum yield (about 30%) upon addition of Zn(ClO4)2. [ABSTRACT FROM AUTHOR]

A novel method for the construction of 2,3-dihydro-5-iodopyran-4-one through a domino cyclization/migration reaction of 1-alkynyl-2,3-epoxy alcohol was developed. Wet solvent is essential for this reaction. The resulting iodine- containing product can be readily elaborated to more complex products by using known organopalladium chemistry. [ABSTRACT FROM AUTHOR]

It has been shown that the rate of angular momentum loss (AML) in cataclysmic variables (CVs) below the period gap is about 2.47 times that caused by gravitational radiation (GR), suggesting an extra AML mechanism aside from GR. Several potential mechanisms have been proposed but none of them has been verified. In this work, we examine whether AML caused by friction between the expanding nova envelope and the donor star can account for the required AML rate. By adopting various expanding velocities of the envelope, we have calculated the evolution of CVs with typical initial parameters. Our results show that this friction interaction unlikely solves the extra AML problem unless the expanding velocities are extremely low. Thus, there should be a more efficient AML mechanism that plays a role in CV evolution. [ABSTRACT FROM AUTHOR]

Accretion-induced collapse (AIC) is widely accepted to be one of the formation channels for millisecond pulsars (MSPs). Since the MSPs have high spin-down luminosities, they can immediately start to evaporate their companion stars after birth. In this paper, we present a detailed investigation on the evolution of the post-AIC binaries, taking into account the effect of evaporation both before and during the Roche-lobe overflow process. We discuss the possible influence of the input parameters including the evaporation efficiency, the initial spin period, and the initial surface magnetic field of the newborn neutron star. We compare the calculated results with the traditional low-mass X-ray binary evolution and suggest that they may reproduce at least part of the observed redbacks and black widows in the companion mass–orbital period plane depending on the mechanisms of angular momentum loss associated with evaporation. [ABSTRACT FROM AUTHOR]

Recent observations show that white dwarfs (WDs) in cataclysmic variables (CVs) have an average mass significantly higher than isolated WDs and WDs in post-common envelope binaries (PCEBs), which are thought to be the progenitors of CVs. This suggests that either the WDs have grown in mass during the PCEB/CV evolution or the binaries with low-mass WDs are unable to evolve to be CVs. In this paper, we calculate the evolution of accreting WD binaries with updated hydrogen accumulation efficiency and angular momentum loss (AML) prescriptions. We show that thermal-timescale mass transfer is not effective in changing the average WD mass distribution. The WD mass discrepancy is most likely related to unstable mass transfer in WD binaries, in which an efficient mechanism of AML is required. [ABSTRACT FROM AUTHOR]

High-performance pervaporation membranes have potential in industrial separation applications, but overcoming the permeability-selectivity trade-off is a challenge. We report a strategy to create highly flexible metal-organic framework nanosheet (MOF-NS) membranes with a faveolate structure on polymer substrates for alcohol-water separation. The controlled growth followed by a surface-coating method effectively produced flexible and defect-free superhydrophobic MOF-NS membranes. The reversible deformation of the flexible MOF-NS and the vertical interlamellar pathways were captured with electron microscopy. Molecular simulations confirmed the structure and revealed transport mechanism. The ultrafast transport channels in MOF-NS exhibited an ultrahigh flux and a separation factor of 8.9 in the pervaporation of 5 weight % ethanol-water at 40°C, which can be used for biofuel recovery. MOF-NS and polydimethylsiloxane synergistically contribute to the separation performance. [ABSTRACT FROM AUTHOR]

In the title compound, C14H15ClN2O, the benzene and pyrimidine rings are nearly perpendicular, the dihedral angle between them being 84.7 (2)°. [ABSTRACT FROM AUTHOR]

In the crystal structure of the title compound, C9H9ClN4, there are non-classical intramolecular C—H⋯N hydrogen bonds and intermolecular C—H⋯π interactions. [ABSTRACT FROM AUTHOR]

Well-defined, stereospecific states in protein complexes are often in exchange with an ensemble of more dynamic orientations: the encounter states. The structure of the stereospecific complex between cytochrome P450cam and putidaredoxin was solved recently by X-ray diffraction as well as paramagnetic NMR spectroscopy. Other than the stereospecific complex, the NMR data clearly show the presence of additional states in the complex in solution. In these encounter states, populated for a small percentage of the time, putidaredoxin assumes multiple orientations and samples a large part of the surface of cytochrome P450cam. To characterize the nature of the encounter states, an extensive paramagnetic NMR dataset has been analyzed using the Maximum Occurrence of Regions methodology. The analysis reveals the location and maximal spatial extent of the additional states needed to fully explain the NMR data. Under the assumption of sparsity of the size of the conformational ensemble, several minor states can be located quite precisely. The distribution of these minor states correlates with the electrostatic potential map around cytochrome P450cam. Whereas some minor states are on isolated positively charged patches, others are connected to the stereospecific site via positively charged paths. The existence of electrostatically favorable pathways between the stereospecific interaction site and the different minor states or lack thereof suggests a means to discriminate between productive and futile encounter states. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of this study is to evaluate perioperative complications related to robotic-assisted laparoscopic surgery for management of gynaecologic disorders. MATERIALS AND METHODS: Eight hundred and fifty-one women who underwent robotic procedures between December 2011 and April 2015 were retrospectively included for analysis. Patient demographics, surgical outcomes and complications were evaluated. RESULTS: The overall complication rate was 5.5%, whereas the rate of complications for oncologic cases was 8.4%. Intra-operative complications (n = 7, 0.8%) consisted of five cases of bowel lacerations, one case of ureter laceration and one case of bladder injury. Early and late post-operative complications were 4.0% (n = 34) and 0.8% (n = 6), respectively. Six patients (0.7%) experienced Grade III complications based on the Clavien-Dindo classification and required further surgical intervention. CONCLUSION: Robotic-assisted laparoscopic surgery is a feasible approach for management of gynaecologic disorders; the complication rates for this type of procedure are acceptable. [ABSTRACT FROM AUTHOR]

Determining the three-dimensional structure of a small molecule–protein complex with weak affinity can be a significant challenge. We present a paramagnetic NMR method to determine intermolecular structure restraints based on pseudocontact shifts (PCSs). Since the ligand must be in fast exchange between free and bound states and the fraction bound can be as low as a few percent, the method is ideal for ligands with high micromolar to millimolar dissociation constants. Paramagnetic tags are attached, one at a time, in a well-defined way via two arms at several sites on the protein surface. The ligand PCSs were measured from simple 1D ¹H spectra and used as docking restraints. An independent confirmation of the complex structure was carried out using intermolecular NOEs. The results show that structures derived from these two approaches are similar. The best results are obtained if the magnetic susceptibility tensors of the tags are known, but it is demonstrated that with two-armed probes, the magnetic susceptibility tensor can be predicted with sufficient accuracy to provide a low-resolution model of the ligand orientation and the location of the binding site in the absence of isotope-labeled protein. This approach can facilitate fragment-based drug discovery in obtaining structural information on the initial fragment hits. [ABSTRACT FROM AUTHOR]

Background: Menopausal experience differs among women with different cultural and ethnic backgrounds and may impact quality of life. Some women with severe menopausal symptoms seek medical help to alleviate menopause-related symptoms. Purpose: This study examined the demographic characteristics and health-related quality of life (HRQOL) of Taiwanese women experiencing menopausal symptoms and examined associations between menopausal symptoms and, respectively, poor HRQOL and healthcare resource utilization. Methods: This cross-sectional study used data from the 2005 National Health Interview Survey in Taiwan, which used a multistaged stratified systematic sampling scheme. A total of 4,437 women aged 35-64 years were analyzed. We used multivariable logistic regression models to identify variables significantly and independently associated with the presence of menopausal symptoms. We also used the model to assess the odds of poor HRQOL and healthcare resource utilization in women with menopausal symptoms compared with those without. Results: Eight hundred and forty-six women (19.1 %) reported experiencing menopausal symptoms. Age, religion, smoking, exercise, and comorbidity were independently associated with the presence of such symptoms. The propensity score-adjusted odds ratio of poor physical HRQOL, poor mental HRQOL, use of outpatient, traditional Chinese medicine and emergency room services, and hospitalization for women with menopausal symptoms were 1.85 (95% CI [1.54, 2.21]), 1.66 (95% CI [1.40, 1.97]), 1.39 (95% CI [1.18,1.63]), 1.73 (95% CI [1.37, 2.18]), 1.44 (95% CI [1.15, 1.81]), and 1.36 (95% CI [1.02, 1.81]), respectively, compared with those without symptoms. Conclusions: Nearly one fifth of women aged 35-64 years in Taiwan experience menopausal symptoms. The presence of menopausal symptoms increases the likelihood of poor HRQOL and healthcare resource utilization even after controlling for possible confounders. [ABSTRACT FROM AUTHOR]

Two novel amphiphilic l-proline derivatives bearing long alkyl chain on the 4-position via ether bonds, 1a and 1b, have been synthesized and evaluated for the asymmetric direct aldol reaction in organic solvents as well as in water. The catalytic activities with 5 mol% of 1a are better than that of 30 mol% of proline itself being used. Especially, high yields (up to 99%), excellent enantioselectivities (up to 99% ee) and anti-diastereoselectivities (up to 99:1) are achieved in the reactions of aromatic aldehydes and cyclic ketones at room temperature with 5 mol% of 1a in water. [InlineMediaObject not available: see fulltext.] [ABSTRACT FROM AUTHOR]

It is shown that in density functional theory (DFT), Koopmans' theorem for a large molecular system can be stated as follows:  The ionization energy of the system equals the negative of the highest occupied molecular orbital (HOMO) energy plus the Coulomb electrostatic energy of removing an electron from the system, or equivalently, the ionization energy of an N-electron system is the negative of the arithmetic average of the HOMO energy of this system and the lowest unoccupied molecular orbital (LUMO) energy of the (N− 1)-electron system. Relations between this DFT Koopmans' theorem and its existing counterparts in the literature are discussed. Some of the previous results are generalized and some are simplified. DFT calculation results of a fullerene molecule, a finite single-walled carbon nanotube and a finite boron nitride nanotube are presented, indicating that this Koopmans' theorem approximately holds, even if the orbital relaxation is taken into consideration. [ABSTRACT FROM AUTHOR]

A new growing method for simplex-based endmember extraction algorithms (EEAs), called simplex growing algorithm (SGA), is presented in this paper. It is a sequential algorithm to find a simplex with the maximum volume every time a new vertex is added. In order to terminate this algorithm a recently developed concept, virtual dimensionality (VD), is implemented as a stopping rule to determine the number of vertices required for the algorithm to generate. The SGA improves one commonly used EEA, the N-finder algorithm (N-FINDR) developed by Winter, by including a process of growing simplexes one vertex at a time until it reaches a desired number of vertices estimated by the VD, which results in a tremendous reduction of computational complexity. Additionally, it also judiciously selects an appropriate initial vector to avoid a dilemma caused by the use of random vectors as its initial condition in the N-FINDR where the N-FINDR generally produces different sets of final endmembers if different sets of randomly generated initial endmembers are used. In order to demonstrate the performance of the proposed SGA, the N-FINDR and two other EEAs, pixel purity index, and vertex component analysis are used for comparison. [ABSTRACT FROM AUTHOR]

BACKGROUND: The mammalian epidermis is maintained by the ongoing proliferation of a subpopulation of keratinocytes known as epidermal stem cells. Sonic hedgehog (Shh) can regulate morphogenesis of hair follicles and several types of skin cancer, but the effect of Shh on proliferation of human putative epidermal stem cells (HPESCs) is poorly understood. METHODS AND RESULTS: We first found that Shh, its receptors Patched1 (Ptc1) as well as Smoothened (Smo) and its downstream transcription factor Gli-1 were expressed in the basal layer of human fetal epidermis and freshly sorted HPESCs. Next, treatment of HPESCs with media conditioned by Shh-N-expressing cells promoted cell proliferation, whereas inhibition of Shh by cyclopamine, a specific inhibitor of Shh signalling, had an opposite effect. Interestingly, the mitogenic effect of epidermal growth factor (EGF) on HPESCs was efficiently abolished by cyclopamine. Finally, bone morphogenetic protein 4 (BMP-4), a potential downstream effector of Shh signalling, increased HPESC proliferation in a concentration-dependent manner. CONCLUSIONS: Shh is an important regulator of HPESC proliferation in the basal layer of human fetal epidermis and modulates the cell responsiveness to EGF, which will assist to unravel the mechanisms that regulate stem cell proliferation and neoplasia in the human epidermis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human epidermis, a continuously renewing tissue, is maintained throughout life by stem cells that proliferate and replenish worn‐out or damaged cells in the tissue. Cultured human epidermal stem cells have great potential in clinical application. However, isolating and culturing a pure population of epidermal stem cells has proven to be challenging. METHODS AND RESULTS: We show that p63, a new marker for epidermal stem cells, is expressed in the basal layer of human fetal epidermis using immunohistochemistry, and that keratinocytes with the characteristics of stem cells can be isolated from the epidermis of aborted human fetuses aged ≥20 weeks based on high expression of β1 integrins by fluorescence‐activated cell sorting. Furthermore, the enriched population showed the expression of molecular markers of putative human epidermal stem cells under a confocal microscope and a high colony formation efficiency when it was cultured at a clonal density. Under an electron microscope the sorted stem cells exhibited a high nuclear:cytoplasmic ratio and fewer organelles than the transit amplifying cells. The cultured epidermal stem cells can also be amplified and induced to terminal differentiation by suspension in vitro. CONCLUSIONS: Human ‘fetal’ epidermal stem cells have been successfully isolated and cultured in vitro. The cultured human epidermal stem cells could be used as a tool for studying stem cell biology and testing stem cell therapy. [ABSTRACT FROM AUTHOR]

It is shown from Kohn-Sham (KS) density-functional theory that in a large molecular system, the Coulomb potential, molecular electrostatic potential, and KS effective potential may exhibit an approximately homogeneous variation in space, in response to a small change of the electron number. The homogeneous variation of potentials underlies the constant interaction (CI) model of quantum dots (QDs) and is related to the delocalization and invariance of KS orbitals, the identical shift of KS levels, and a natural definition of the QD capacitance. Calculation results of a fullerene C60 and a single-walled carbon nanotube are presented. Although the homogeneity of the potential variation is not perfect, it seems to lead to fairly good approximation of the CI model to the addition energy spectra of these systems. [ABSTRACT FROM AUTHOR]

BACKGROUND: Currently, benefits of robotic surgery in patients with benign gynecological conditions remain unclear. In this study, we compared the surgical outcome of robotic and laparoscopic total hysterectomies and evaluated the feasibility of robotic surgery in cases with pelvic adhesions or large uterus. MATERIALS AND METHODS: A total of 216 patients receiving total hysterectomy via robotic or laparoscopic approach were included in this study. Of all 216 patients, 88 underwent robotic total hysterectomy and 128 underwent laparoscopic total hysterectomy. All cases were grouped by surgical type, adhesion score, and uterine weight to evaluate the interaction or individual effect to the surgical outcomes. The perioperative parameters, including operation time, blood loss, postoperative pain score, time to full diet resumption, length of hospital stay, conversion rate, and surgeryrelated complications were compared between the groups. RESULTS: Operation time and blood loss were affected by both surgical type and adhesion score. For cases with severe adhesions (adhesion score greater than 4), robotic surgery was associated with a shortened operation time (113.9 ± 38.4 min versus 164.3 ± 81.4 min, P = 0.007) and reduced blood loss (187.5 ± 148.7 mL versus 385.7 ± 482.6, P=0.044) compared with laparoscopy. Moreover, robotic group showed a lower postoperative pain score than laparoscopic group, as the effect was found to be independent of adhesion score or uterine weight. The grade-II complication rate was also found to be lower in the robotic group. CONCLUSIONS: Comparing to laparoscopic approach, robotic surgery is a feasible and potential alternative for performing total hysterectomy with severe adhesions. [ABSTRACT FROM AUTHOR]

The silahydrocarbons of tetraalkylsilanes with different substituted alkyl groups (named as SiCH) were synthesized and evaluated as lubricants for steel-steel contacts by a home-made vacuum four-ball tribometer (VFBT-4000) under atmospheric pressure and under vacuum pressure (5 × 10-4 Pa). The SiCH oils possess better thermal stability, low temperature fluidity, and lower saturated vapor pressure than those of multialkylatedcyclopentanes (MACs). The tribological performances of the SiCH oils are also superior to those ofMACs and PFPE-Z25 in terms of friction-reduction ability and antiwear capacity under sliding friction at vacuum. The SEM/EDS and XPS results reveal that the boundary lubricating filmconsisting of (-O-Si-R-)n compounds is formed by tribochemical reactions and serious adhesion wear under atmospheric pressure and the film consisting of (-Si-R-Si-)n compounds is formed on the worn surface under vacuum pressure. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes based on gene expression signatures. In this study, we analyzed 893 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). We show that MYC/BCL2 protein coexpression occurred significantly more commonly in the ABC subtype. Patients with the ABC or GCB subtype of DLBCL had similar prognoses with MYC/BCL2 coexpression and without MYC/BCL2 coexpression. Consistent with the . notion that the prognostic difference between the 2 subtypes is attributable to MYC/BCL2 coexpression, there is no difference in gene expression signatures between the 2 subtypes in the absence of MYC/BCL2 coexpression. DLBCL with MYC/BCL2 coexpression demonstrated a signature of marked downregulation of genes encoding extracellular matrix proteins, those involving matrix deposition/remodeling and cell adhesion, and upregulation of proliferation-associated genes. We conclude that MYC/BCL2 coexpression in DLBCL is associated with an aggressive clinical course, is more common in the ABC subtype, and contributes to the overall inferior prognosis of patients with ABC-DLBCL. In conclusion, the data suggest that MYC/BCL2 coexpression, rather than cell-of-origin classification, is a better predictor of prognosis in patients with DLBCL treated with R-CHOP. [ABSTRACT FROM AUTHOR]

CD30, originally identified as a cell-surface marker of Reed-Sternberg and Hodgkin cells of classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including a subset of diffuse large B-cell lymphoma (DLBCL). However, the prognostic and biological importance of CD30 expression in DLBCL is unknown. Here we report that CD30 expression is a favorable prognostic factor in a cohort of 903 de novo DLBCL patients. CD30 was expressed in ~14% of DLBCL patients. Patients with CD30+ DLBCL had superior 5-year overall survival (CD30+, 79% vs CD30-, 59%; P = .001) and progression-free - survival (P = .003). The favorable outcome of CD30 expression was maintained in born the germinal center B-cell and activated B-cell subtypes. Gene expression profiling revealed the upregulation of genes encoding negative regulators of nuclear factor κB activation and lymphocyte survival, and downregulation of genes encoding B-cell receptor signaling and proliferation, as well as prominent cytokine and stromal signatures in CD30+ DLBCL patients, suggesting a distinct molecular basis for its favorable outcome. Given the superior prognostic value, unique gene expression signature, and significant value of CD30 as a therapeutic target for brentuximab vedotin in ongoing successful clinical trials, it seems appropriate to consider CD30+ DLBCL as a distinct subgroup of DLBCL. [ABSTRACT FROM AUTHOR]

High-performance deep-blue emitting phenanthroimidazolederivativeswith a structure of donor–linker–acceptor were designedand synthesized. By using different linkers and different linkingpositions, four deep-blue emitters were obtained and used as emittersor bifunctional hole-transporting emitters in OLEDs. Such devicesshow low turn-on voltages (as low as 2.8 V), high efficiency (2.63cd/A, 2.53 lm/W, 3.08%), little efficiency roll-off at high currentdensities, and stable deep-blue emissions with CIEy< 0.10. Performances are among the best comparing to recentlyreported deep-blue emitting devices with similar structures. The resultssuggest that the combination of the phenanthroimidazole and the donor–linker–acceptorstructure can be an important approach for developing high performancedeep-blue emitters in particular for lighting applications. [ABSTRACT FROM AUTHOR]

Uterine rupture during near-term pregnancy is a life-threatening condition. A 31-year-old pregnant woman with a breech presentation at the gestation age of 35 weeks had complained of a dull abdominal pain for days. She was treated 2 years ago with bilateral uterine artery ligation and hysterotomy for removal of the retained placenta. An aggravation of abdominal pain occurred suddenly 4 h after hospitalization. The cardiotocogram showed a fetal heart beat with loss of variability, but increasing deceleration. An urgent cesarean section was performed because of suspected placenta abruption. After successful delivery of the fetus, a protruding placental tissue was found on the fundal uterine wall. We performed wedge resection of the ruptured uterine wall with the aid of an intrauterine muscle injection of 20 IU oxytocin, a local injection of diluted vasopressin (1:60) into the myometrium around and into the rupture site, an intramuscular injection of 0.2 mg methylergonovine, and primary repair of the defect, but in vain. Cesarean hysterectomy was used to control the intractable bleeding. The accumulated blood loss was more than 10 000 mL. The final pathology confirmed placenta percreta with uterine rupture. Luckily, both mother and fetus recovered well and were discharged 7 days later. We concluded that women with retained placenta and/or postpartum hemorrhage managed by previous hysterotomy and uterine artery ligation still need careful prenatal care, since the possibility of re-occurrence of the placenta percreta is easily overlooked and may result in a further life-threatening situation, such as the uterine rupture in this case. [ABSTRACT FROM AUTHOR]

Aims: High glucose promotes macrophage-derived foam cell formation involved in increased influx or reduced efflux of lipids. The aim of this study is to investigate the influence of hyperglycaemia on foam cell transformation of vascular smooth muscle cells (VSMCs) and possible mechanisms contributing to these effects. Methods and results: The results showed that high glucose increased the expression of CD36, a regulator of lipid influx, and suppressed the expression and activity of the adenosine triphosphate-binding cassette (ABC) transporter ABCG1, a regulator of cholesterol efflux to high-density lipoprotein, in a dose- and time-dependent manner. However, cholesterol efflux tolipid-free apoAI was not impaired. VSMCs exposed to high glucose readily developed into lipid-loaded cells, as demonstrated by Oil Red O staining and cholesterol content analysis. In addition, high glucose-induced downregulation of ABCG1 was reversed by nuclear factor-κB (NF-κB) inhibitors BAY 11-7085 and tosyl-phenylalanine chloromethyl ketone and by the antioxidant N-acetyl-L-cysteine (NAC). This reversal was accompanied by reduced cellular lipid content. Also, NAC and NF-κB inhibitors can effectively block the high glucose-induced activity of NF-κB binding to DNA and/or peroxide production. Conclusion: These results suggested that hyperglycaemia-induced foam cell formation in VSMCs was related to the imbalanced lipid flux by increasing CD36-mediated modified low-density lipoprotein uptake and reducing ABCG1-regulated cellular cholesterol efflux. Moreover, this effect was associated with increased oxidative stress and activated NF-κB pathway signalling. [ABSTRACT FROM PUBLISHER]

Aim: To evaluate the efficacy of uterine artery occlusion and myomectomy (UAO+M) for pregnant women with uterine leiomyomas who are undergoing cesarean section (CS). Methods: Seventy-two women with uterine leiomyomas undergoing CS for obstetrical reasons were enrolled into this case–control study. Thirty-six patients underwent UAO+M during CS (UAO+M group), and 36 received CS alone (Control group). The UAO+M procedure was performed immediately after closure of the uterine incision wound. The outcome was measured by comparing surgical techniques, and future surgical intervention (myomectomy, uterine vessel occlusion or hysterectomy) for symptomatic leiomyoma. Results: The average follow-up time was 63 months. General characteristics of the patients were similar in both groups. There were no statistical differences in intraoperative blood loss, postoperative recovery, complications, or wound pain between the two groups. The operative time was significantly longer in the UAO+M group compared with that in the Control group, but the further surgical intervention rate was significantly lower in the UAO+M group than in the Control group (2.8% vs 41.7%, P < 0.001). Seven patients (19%) in the UAO+M group and five (14%) in the Control group had a repeat CS during the follow-up period. Conclusion: UAO+M could be considered for treating pregnant women with uterine leiomyomas who are undergoing CS, compared with observation, as this procedure can minimize the necessity for future surgery, with increased operative time for the UAO+M procedure, but without increased surgical morbidity. [ABSTRACT FROM AUTHOR]

Aim: Our aim was to assess the role of surgical intervention for symptom control and reproductive performance improvement in the management of subfertile women with symptomatic extensive uterine adenomyosis. Methods: Sixty-five subfertile women with pathology-proven extensive uterine adenomyosis, who were treated with conservative surgery or medical treatment with 6-month gonadotrophin-releasing hormone (GnRH) agonist or combination therapy, were retrospectively reviewed and their data analyzed. Twenty-eight women received conservative surgery with/without GnRH agonist (group A), and 37 received 6-month GnRH agonist therapy only (group B). Follow-up evaluations, including subjective symptoms (a self-reported 6-point verbal numeric rating scale and an analgesic usage score for dysmenorrhea) and objective parameters (serum CA125 level, and uterine size), and clinical pregnancy and successful delivery rates were made semi-annually over the ensuing 3 or more years. Results: The women in group A had higher serum CA125 levels, more infertile years, and a larger uterine size. Subjective symptom control and objective parameters were better in group A during the entire 36-month follow up compared with those in group B. Cumulative 3-year clinical pregnancy and successful delivery rates were significantly higher in group A, compared with those in group B (46.4% [13/28] versus 10.8% [4/37], P = 0.002, and 32.1% [9/28] versus 8.1% [3/37], P = 0.022, respectively). Conclusion: Conservative surgery or combination therapy provides more effective and longer durable symptom control in the management of symptomatic women with extensive uterine adenomyosis, compared with GnRH agonist alone. Reproductive performance was also better in patients treated with conservative surgery with/without GnRH agonist. [ABSTRACT FROM AUTHOR]

Several cases in which uteruses have been preserved in women with placenta percreta have been reported. We herein report a 38-year-old woman with a history of previous cesarean section who was admitted with lower abdominal pain and vaginal bleeding at 31 weeks of gestation. An urgent exploratory laparotomy revealed active bleeding from the uterine rupture on the posterior uterine wall. A female infant weighing 1560 g, with Apgar scores of 1, 1, and 3 at 1, 5, and 10 min, respectively, was delivered, and the placenta was removed. We performed bilateral uterine vessel occlusion, followed by wedge resection of the ruptured uterine wall with the aid of an intrauterine muscle injection of 20 IU oxytocin, a local injection of diluted vasopressin (1:60) into the myometrium around and into the rupture site, and an intramuscular injection of 0.2 mg methylergonovine, primary repair of the defect, and an additional 24-h postoperative oxytocin infusion (30 IU in 5% dextrose 500 mL) to preserve the uterus successfully. Although the overall blood loss was 3700 mL, no disseminated intravascular coagulopathy occurred after the patient had received adequate blood transfusion. The postoperative pathological diagnosis was placenta percreta with uterine rupture. The patient and her baby were discharged uneventfully. In some cases of spontaneous uterine rupture secondary to placenta percreta, we can preserve the uterus by performing bilateral uterine vessel occlusion and wedge resection of the ruptured uterine wall. [ABSTRACT FROM AUTHOR]

Background: Microarray gene expression (MAGE) signatures allow insights into the transcriptional processes of leukemias and may evolve as a molecular diagnostic test. Introduction of MAGE into clinical practice of leukemia diagnosis will require comprehensive assessment of variation due to the methodologies. Here we systematically assessed the impact of three different total RNA isolation procedures on variation in expression data: method A: lysis of mononuclear cells, followed by lysate homogenization and RNA extraction; method B: organic solvent based RNA isolation, and method C: organic solvent based RNA isolation followed by purification. Results: We analyzed 27 pediatric acute leukemias representing nine distinct subtypes and show that method A yields better RNA quality, was associated with more differentially expressed genes between leukemia subtypes, demonstrated the lowest degree of variation between experiments, was more reproducible, and was characterized with a higher precision in technical replicates. Unsupervised and supervised analyses grouped leukemias according to lineage and clinical features in all three methods, thus underlining the robustness of MAGE to identify leukemia specific signatures. Conclusion: The signatures in the different subtypes of leukemias, regardless of the different extraction methods used, account for the biggest source of variation in the data. Lysis of mononuclear cells, followed by lysate homogenization and RNA extraction represents the optimum method for robust gene expression data and is thus recommended for obtaining robust classification results in microarray studies in acute leukemias. [ABSTRACT FROM AUTHOR]

A new three-component cyclization—coupling reaction catalyzed by palladium was developed, producing polysubstituted furans in good yields from readily available substrates. The reaction conditions and the scope of the process were examined, and a possible mechanism is proposed. [ABSTRACT FROM AUTHOR]

Reports on the utilization of the analysis of single nucleotide polymorphisms in investigating the genetic cause of complex human disease in the U.S. Risk factor for developing chronic mucocutaneous candidiasis and thyroid disease; Feasibility of locus-specific amplification in terms of oligonucleotide synthesis; Complexity of the one-primer amplification assay; Accuracy of the genotype-calling algorithm.

Genetic studies aimed at understanding the molecular basis of complex human phenotypes require the genotyping of many thousands of single-nucleotide polymorphisms (SNPs) across large numbers of individuals. Public efforts have so far identified over two million common human SNPs; however, the scoring of these SNPs is labor-intensive and requires a substantial amount of automation. Here we describe a simple but effective approach, termed whole-genome sampling analysis (WGSA), for genotyping thousands of SNPs simultaneously in a complex DNA sample without locus-specific primers or automation. Our method amplifies highly reproducible fractions of the genome across multiple DNA samples and calls genotypes at >99% accuracy. We rapidly genotyped 14,548 SNPs in three different human populations and identified a subset of them with significant allele frequency differences between groups. We also determined the ancestral allele for 8,386 SNPs by genotyping chimpanzee and gorilla DNA. WGSA is highly scaleable and enables the creation of ultrahigh density SNP maps for use in genetic studies. [ABSTRACT FROM AUTHOR]

The title compound, C11H9ClN2O2, crystallizes with weak inter­molecular N—H⋯O hydrogen-bond inter­actions. The dihedral angle between the pyrimidine and benzene rings is 86.82 (7)°. [ABSTRACT FROM AUTHOR]