Hit to lead account of the discovery of a new class of inhibitors of Pim kinases and crystallographic studies revealing an unusual kinase binding mode.

A series of inhibitors of Pim-2 kinase identified by high-throughput screening is described. Details of the hit validation and lead generation process and structure-activity relationship (SAR) studies are presented. Disclosure of an unconventional binding mode for 1, as revealed by X-ray crystallography using the highly homologous Pim-1 protein, is also presented, and observed binding features are shown to correlate with the Pim-2 SAR.

Highly thermostable anatase titania-pillared clay for the photocatalytic degradation of airborne styrene.

Airborne styrene is a suspected human carcinogen, and traditional ways of mitigation include the use of adsorption technologies (activated carbon or zeolites) or thermal destruction. These methods presenttheir own shortcomings, i.e.

Advanced glycation end products impair function of late endothelial progenitor cells through effects on protein kinase Akt and cyclooxygenase-2.

Endothelial progenitor cells (EPCs) exhibit impaired function in the context of diabetes, and advanced glycation end products (AGEs), which accumulate in diabetes, may contribute to this. In the present study, we investigated the mechanism by which AGEs impair late EPC function. EPCs from human umbilical cord blood were isolated, and incubated with AGE-modified albumin (AGE-albumin) at different concentrations found physiologically in plasma.

Up-regulation of D-serine might induce GABAergic neuronal degeneration in the cerebral cortex and hippocampus in the mouse pilocarpine model of epilepsy.

Epilepsy is a serious neurological disorder with neuronal loss and spontaneous recurrent seizures, but the neurochemical basis remains largely unclear. We hypothesize that D-serine, a newly identified endogenous co-agonist of N-methyl-D-aspartate (NMDA) receptor, may trigger excitotoxicity and neuronal damage in epileptogenesis. By using a mouse pilocarpine model, immunohistochemistry, Fluoro-Jade staining and double-labeling, the present study revealed up-regulation of D-serine expression in a proportion (41%) of neurons in the cerebral cortex and hippocampus.

Association of reproductive performance with SNPs of FOXL2 gene by SSCP in Japanese flounder (Paralichthys olivaceus).

FOXL2 which is a putative winged helix/forkhead transcription factor gene and a sexually dimorphic marker of ovarian differentiation plays an important role in ovarian development, granulosa cell differentiation, and thus the proper maintenance of ovarian function. The aims of this study were to characterize polymorphisms within the FOXL2 gene in a population of 52 female Japanese flounder and analyze the association of FOXL2 polymorphisms with reproductive performance by polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP). Results indicated that five single nucleotide polymorphisms (SNPs), which were SNP1 [c.

Antitumor efficacy of combination of interferon-gamma-inducible protein 10 gene with gemcitabine, a study in murine model.

Background: Interferon-gamma-inducible protein 10 (IP-10) is a potent inhibitor of tumor angiogenesis. It has been reported that the antiangiogenic therapy combined with chemotherapy has synergistic effects.

Methods: To elucidate the mechanisms of IP-10 gene combined with a chemotherapy agent, we intramuscularly injected pBLAST-IP-10 expression plasmid combined with gemcitabine into tumor-bearing mice.

Losartan, an antagonist of AT1 receptor for angiotensin II, attenuates lipopolysaccharide-induced acute lung injury in rat.

Angiotensin II (Ang II) plays an important role in inflammatory process. Acute lung injury (ALI), an inflammatory disorder of the lung, is commonly associated with endotoxemia; however, the mechanism that endotoxin (lipopolysaccharide, LPS) induces the inflammatory response in ALI is not well defined. Here, we showed, in LPS-induced ALI rat model, that Ang II and Ang II type 1 (AT(1)) receptor were significantly increased in lung tissues, compared with those in controls.

Reendothelialization of tubular scaffolds by sedimentary and rotative forces: a first step toward tissue-engineered venous graft.

Purpose: Uniform and tubular surface seeding is a prerequisite for tissue-engineered blood vessels to mature properly in a bioreactor. Our objective was to investigate reendothelialization of tubular scaffolds by the synergistic forces of sedimentation and rotation, so as to fabricate tissue-engineered venous grafts in vitro.

Materials And Methods: Canine bone-marrow-derived endothelial progenitor cells were expanded in vitro.

Time-course of neuronal death in the mouse pilocarpine model of chronic epilepsy using Fluoro-Jade C staining.

Epilepsy is a serious neurological disorder in human beings and the long-term pathological events remain largely obscure. We are interested in elucidating long-term brain injury that may occur in the temporal lobe epilepsy, and time-course of neuronal death was examined in a mouse pilocarpine model of chronic epilepsy by Fluoro-Jade C (FJC) dye that can specifically stain the degenerative neurons in the central nervous system. The FJC stain combined with immunohistochemistry to neuronal nuclear specific protein revealed that pilocarpine-induced status epilepticus (SE) resulted in massive degenerative death of neuronal cells in brains with their dense distribution in the cerebral cortex and hippocampus.

Mechanisms of lumbrokinase in protection of cerebral ischemia.

The present study was designed to explore the mechanisms involved in the anti-ischemic action of lumbrokinase (LK) in brain. The enzyme immunoassay, spectrofluorimeter and flow cytometry were used to detect the level of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP), the Ca(2+) mobilization, and human platelet surface antigen expression in order to elucidate the anti-platelet action involved in LK cerebroprotection. RT-PCR and western blot were used to identify the role of Intercellular adhesion molecule-1 (ICAM-1) and Janus Kinase1/Signal Transducers and Activators of Transcription1 (JAK1/STAT1) pathway in protecting brain against ischemic injury by anti-thrombosis and anti-apoptosis.

A Bayesian regression approach to the prediction of MHC-II binding affinity.

Peptide-major histocompatibility complex (MHC) binding is an important prerequisite event and has immediate consequences to immune response. Those peptides binding to MHC molecules can activate the T-cell immunity, and they are useful for understanding the immune mechanism and developing vaccines for diseases. Recently, researchers are interested in making prediction about binding affinity instead of differentiating the peptides as binder or non-binder.

Synthesis, characterization, and transistor response of semiconducting silole polymers with substantial hole mobility and air stability. Experiment and theory.

Realizing p-channel semiconducting polymers with good hole mobility, solution processibility, and air stability is an important step forward in the chemical manipulation of charge transport in polymeric solids and in the development of low-cost printed electronics. We report here the synthesis and full characterization of the dithienosilole- and dibenzosilole-based homopolymers, poly(4,4-di-n-hexyldithienosilole) (TS6) and poly(9,9-di-n-octyldibenzosilole) (BS8), and their mono- and bithiophene copolymers, poly(4,4-di-n-hexyldithienosilole-alt-(bi)thiophene) (TS6T1, TS6T2) and poly(9,9-di-n-octyldibenzosilole-alt-(bi)thiophene) (BS8T1, BS8T2), and examine in detail the consequences of introducing dithienosilole and dibenzosilole cores into a thiophene polymer backbone. We demonstrate air-stable thin-film transistors (TFTs) fabricated under ambient conditions having hole mobilities as large as 0.

Characterization of transparent conducting oxide surfaces using self-assembled electroactive monolayers.

The electronic properties of various transparent conducting oxide (TCO) surfaces are probed electrochemically via self-assembled monolayers (SAMs). A novel graftable probe molecule having a tethered trichlorosilyl group and a redox-active ferrocenyl functionality (Fc(CH2) 4SiCl3) is synthesized for this purpose. This molecule can be self-assembled via covalent bonds to form monolayers on various TCO surfaces.

Identification of estrogen receptor alpha gene polymorphisms by SSCP and its effect on reproductive traits in Japanese flounder (Paralichthys olivaceus).

Estrogen receptor (ERalpha) modifies the expression of genes involved in cell growth, proliferation and differentiation through binding to estrogen response elements (EREs) located in a number of gene promoters, so the ERalpha gene is considered as an important factor affecting reproductive endocrinology in Japanese flounder (Paralichthys olivaceus). In this study, twelve single nucleotide polymorphisms (SNPs) within eight CDS exons and 1 kb of 3'-UTR of the ERalpha gene were tested to association with four reproductive traits in a population of 119 Japanese flounder individuals with polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP). The association analysis of SNPs within Japanese flounder ERalpha gene with the reproductive traits was carried out using General Linear Model (GLM) estimation.

Augmenter of liver regeneration: an important intracellular survival factor for hepatocytes.

Background/aims: Augmenter of liver regeneration (ALR), a protein synthesized and stored in hepatocytes, is associated with mitochondria, and possesses sulfhydryl oxidase and cytochrome c reductase activities. We sought to determine the effects of ALR depletion in hepatocytes by antisense oligonucleotide transfection.

Methods: Rat hepatocytes in primary culture were transfected with antisense oligonucleotide for ALR mRNA (ALR-AS) or scrambled oligonucleotide.

Immunity against tumor angiogenesis induced by a fusion vaccine with murine beta-defensin 2 and mFlk-1.

Purpose: Previous studies indicated that humoral or cellular immunity against murine vascular endothelial growth factor 2 (mFlk-1) was elicited to inhibit tumor growth. Here we describe a genetic fusion vaccine, pMBD2-mFlk-1, based on the targeting of a modified mFlk-1 to antigen-presenting cells by a murine beta-defensin 2 (MBD2) protein to induce both humoral and cellular immunity against mFlk-1, with the targeting especially focused on immature dendritic cells.

Experimental Design: The protective and therapeutic antitumor immunity of the fusion vaccine was investigated in mouse models.

Evaluation of oxidative stress in a group of adolescents exposed to a high level of aflatoxin B1--a multi-center and multi-biomarker study.

The association between aflatoxin B1 (AFB1) exposure and oxidative stress was extensively examined in 84 adolescents from an area at high risk for hepatocellular carcinoma in China. Plasma level of aflatoxin B1-albumin adducts (AAAs) was associated with AFB1 excretion in urine (r = 0.394, P < 0.

Stereoselective construction of fluorinated indanone derivatives via a triple cascade Lewis acid-catalyzed reaction.

A one-pot three-component cascade reaction proceeds by way of a Lewis acid-catalyzed Knoevenagel condensation/Nazarov cyclization/electrophilic fluorination sequence to afford fluorinated 1-indanone derivatives in moderate to good yields with high diastereoselectivities.

[Short and long-term efficacy of focused ultrasound therapy for vulva dystrophy].

Objective: To investigate the short and long-term efficacy and complications, as well as the influential factors of focused ultrasound for the treatment of vulva dystrophy.

Methods: Seventy-six eligible patients with vulva dystrophy were randomized and treated with focused ultrasound between 1999 and 2002. Among them, 45 patients were with squamous hyperplasia (SH) and 31 patients were with lichen sclerosus (LS).

Pim kinase substrate identification and specificity.

The Pim family of Ser/Thr kinases has been implicated in the process of lymphomagenesis and cell survival. Known substrates of Pim kinases are few and poorly characterized. In this study we set out to identify novel Pim-2 substrates using the Kinase Substrate Tracking and Elucidation (KESTREL) approach.

Organic light-emitting diodes having carbon nanotube anodes.

Single-walled carbon nanotube (SWNT) films on flexible PET (polyethyleneterephthalate) substrates are used as transparent, flexible anodes for organic light-emitting diodes (OLEDs). For polymer-based OLEDs having the structure: SWNT/PEDOT-PSS:MeOH/TFB (poly(9,9-dioctylfluorene-co-N-(4-butylphenyl)diphenylamine)) + TPD-Si(2) (4,4'-bis[(p-trichlorosilylpropylphenyl)phenylamino]biphenyl) /BT (poly(9,9-dioctylfluorene-co-benzothiadiazole))/CsF/Al, a maximum light output of 3500 cd/m(2) and a current efficiency of 1.6 cd/A have been achieved.

High-performance transparent inorganic-organic hybrid thin-film n-type transistors.

High-performance thin-film transistors (TFTs) that can be fabricated at low temperature and are mechanically flexible, optically transparent and compatible with diverse substrate materials are of great current interest. To function at low biases to minimize power consumption, such devices must also contain a high-mobility semiconductor and/or a high-capacitance gate dielectric. Here we report transparent inorganic-organic hybrid n-type TFTs fabricated at room temperature by combining In2O3 thin films grown by ion-assisted deposition, with nanoscale organic dielectrics self-assembled in a solution-phase process.

[Effect of lenti-mCCL20 on the growth of mouse tumor].

Objects: We aim at inducing a potent antitumor immune response via CCL20 expressing in situ tumor.

Methods: We constructed a recombinant lentivirus encoding mouse CCL20 cDNA and transduced the mouse mesenchymal stem cells (mMSCs) in vitro, and then selected the transfected cells to get a stable mixed mCCL20-expressing pool (named as lenti-mCCL20-mMSCs) with blasticidin. By the same means, we produced another pool named as lenti-null-mMSCs.

[Cloning and analyzing of the female-specific marker in the dioecious species Asparagus officinalis L].

Sex-linked molecular markers are being obtained, which would be essential to be used in the screening of different sex of dioecious plants at the seedling stage. Furthermore, it is important in cloning the gene related to the sex. In this study the random amplified polymorphic DNA (RAPD) technique was employed with the objective to find markers linked to sex determination in Asparagus.