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Surgical brain injury (SBI) is unavoidable during many neurosurgical procedures intrinsically linked to postoperative neurological deficits. We have previously demonstrated that implantation of collagen glycosaminoglycan (CG) following surgical brain injury could significantly promote functional recovery and neurogenesis. In this study we further hypothesized that this scaffold may provide a microenvironment by promoting angiogenesis to favor neurogenesis and subsequent functional recovery. Using the rodent model of surgical brain injury as we previously established, we divided Sprague-Dawley male rats (weighting 300-350 g) into three groups: (1) sham (2) surgical injury with a lesion (L), and (3) L with CG matrix implantation (L + CG). Our results demonstrated that L + CG group showed a statistically significant increase in the density of vascular endothelial cells and blood vessels over time. In addition, tissue concentrations of angiogenic growth factors (such as VEGF, FGF2, and PDGF) significantly increased in L + CG group. These results suggest that implantation of a CG scaffold can promote vascularization accompanied by neurogenesis. This opens prospects for use of CG scaffolds in conditions such as brain injury including trauma and ischemia.

A series of 2,7-diamidofluorenones were designed, synthesized, and screened by SRB assay. Some synthesized compounds exhibited antitumor activities in submicromolar range. Ten compounds (3a, 3b, 3c, 3g, 3j, 3l, 4a, 4h, 4i, and 4j) were also selected by NCI screening system and 3c (GI50=1.66 μM) appeared to be the most active agent of this series. Furthermore, 3c attenuated topoisomerase I-mediated DNA relaxation at low micromolar concentrations. These results indicated that fluorenones have potential to be further developed into anticancer drugs., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Two new receptors 1 and 2 were prepared, and their chromogenic and fluorogenic behaviors toward various anions were investigated. Receptors 1 and 2 show exclusive response toward HSO4(-) ion and also distinguish HSO4(-) from other anions by different color changes in aqueous solution (CH3CN/H2O=4/1, v/v). Between them receptor 1 selectively exhibits a pronounced HSO4(-)-induced fluorescence enhancement. The detection limit for the HSO4(-) ion was determined as (0.24±0.03μM). Thus, the receptor 1 can be used as a colorimetric and fluorescent sensor for the determination of HSO4(-) ion. The sensing mechanism has been suggested to proceed via a hydrolysis process. The hydrolysis product has been isolated and further identified by (1)H NMR spectroscopy, ESI-MS analysis and X-ray diffraction., (Copyright © 2013 Elsevier B.V. All rights reserved.)

By using fragment-based design strategies, a series of 2-thio-substituted anthra[1,2-d]imidazole-6,11-diones were synthesized and evaluated for hTERT repressing activities, cell proliferations, and NCI 60-cell panel assay. Compounds 2, 3, 4, 11, 15 and 35 were selected by the NCI and 3, 4, 11 and 15 represent the GI₅₀, TGI and LC₅₀, respectively. Among them, all were moderate selectivity toward leukemia cancer except for 4 exhibited distinctive selectivity of CNS and renal cancer with 7.403 and 6.475. The overall of test compounds exhibited different cytostatic and cytotoxic activities for further developing potential application as anticancer drugs., (Crown Copyright © 2013. Published by Elsevier Masson SAS. All rights reserved.)

The Lon protease is ubiquitous in nature. Its proteolytic activity is associated with diverse cellular functions ranging from maintaining proteostasis under normal and stress conditions to regulating cell metabolism. Although Lon was originally identified as an ATP-dependent protease with fused AAA+ (ATPases associated with diverse cellular activities) and protease domains, analyses have recently identified LonC as a class of Lon-like proteases with no intrinsic ATPase activity. In contrast to the canonical ATP-dependent Lon present in eukaryotic organelles and prokaryotes, LonC contains an AAA-like domain that lacks the conserved ATPase motifs. Moreover, the LonC AAA-like domain is inserted with a large domain predicted to be largely α-helical; intriguingly, this unique Lon-insertion domain (LID) was disordered in the recently determined full-length crystal structure of Meiothermus taiwanensis LonC (MtaLonC). Here, the crystal structure of the N-terminal AAA-like α/β subdomain of MtaLonC containing an intact LID, which forms a large α-helical hairpin protruding from the AAA-like domain, is reported. The structure of the LID is remarkably similar to the tentacle-like prong of the periplasmic chaperone Skp. It is shown that the LID of LonC is involved both in Skp-like chaperone activity and in recognition of unfolded protein substrates. The structure allows the construction of a complete model of LonC with six helical hairpin extensions defining a basket-like structure atop the AAA ring and encircling the entry portal to the barrel-like degradation chamber of Lon.

The crystal structure of TM-1, a P-I class snake-venom metalloproteinase (SVMP) from the Trimeresurus mucrosquamatus venom, was determined at 1.8-Å resolution. The structure exhibits the typical feature of SVMPs and is stabilized by three disulfide linkages. The active site shows a deep S1' substrate-binding pocket limited by the non-conserved Pro174 at the bottom. Further comparisons with other SVMPs suggest that the deep S1' site of TM-1 correlates with its high inhibition sensitivity to the endogenous tripeptide inhibitors. Proteolytic specificity analysis revealed that TM-1 prefers substrates having a moderate-size and hydrophobic residue at the P1' position, consistent with our structural observation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The Lon proteases are a unique family of chambered proteases with a built-in AAA+ (ATPases associated with diverse cellular activities) module. Here, crystal structures of a unique member of the Lon family with no intrinsic ATPase activity in the proteolytically active form are reported both alone and in complexes with three covalent inhibitors: two peptidomimetics and one derived from a natural product. This work reveals the unique architectural features of an ATP-independent Lon that selectively degrades unfolded protein substrates. Importantly, these results provide mechanistic insights into the recognition of inhibitors and polypeptide substrates within the conserved proteolytic chamber, which may aid the development of specific Lon-protease inhibitors.

Objectives: This study describes a novel carrier, the ethosome-based system, which is composed of non-ionic surfactants, ethanol, and water., Methods: Brij(®) 52 (non-ionic surfactants), soya phosphatidylcholine (PC), cholesterol, and the major compounds (caffeine and gallic acid) of black tea extracts were dissolved in the ethanolic phase. The aqueous phase containing Paragon III was heated to 60 °C and mixed with the previous solution. Finally, 3.4 ml NaOH (6.5 N) was added to adjust the pH level to 4.05. The mixture was centrifuged at 2000 g for two minutes, and the precipitate was taken as the end product. Black tea extracts were applied in ethosome-based formulations, and the efficacy of these formulations in penetrating nude mouse skin and in dyeing white hairs was investigated., Results: Compared with an ethanolic solution and black tea extracts, the non-ionic ethosomal delivery system dramatically enhanced the adsorption of black tea extracts onto hair surfaces in vitro. The non-ionic ethosomal system was much more efficient in delivering and facilitating the adsorption of black tea extracts to the hair surface than hydroalcoholic black tea extracts., Conclusions: This formulation may have potential for development as a hair dye and protective agent., (© 2013 The International Society of Dermatology.)

A series of anthra[1,2-d]imidazole-6,11-dione derivatives were synthesized and evaluated for telomerase inhibition, hTERT expression and suppression of cancer cell growth in vitro. All of the compounds tested, except for compounds 4, 7, 16, 24, 27 and 28 were selected by the NCI screening system. Among them, compounds 16, 39, and 40 repressed hTERT expression without greatly affecting cell growth, suggesting for the selectivity toward hTERT expression. Taken together, our findings indicated that the analysis of cytotoxicity and telomerase inhibition might provide information applicable for further developing potential telomerase and polypharmacological targeting strategy., (Crown Copyright © 2012. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: The primary objective of this study was to investigate the feasibility of using niosomes as a delivery vehicle for the dermal administration in vitro of black tea extract (BTE) as a sunscreen., Methods: Multi-lamellar niosomes were obtained by means of a previously reported method of lipid hydration films. In vitro penetration experiments through nude mouse skin were carried out to evaluate the potential of niosomes as a dermal formulation. The nude mouse skin membrane allowed the effects of penetration with a niosome formulation to be evaluated. Penetration rates of caffeine- and gallic acid-loaded niosomes in a steady state were higher than dispersion in aqueous solutions., Results: For skin permeation, higher transdermal absorption rates were seen with solutions of caffeine and gallic acid., Conclusions: In the near future, BTE as a sunscreen agent will be dermally delivered by niosomes., (© 2012 The International Society of Dermatology.)

Poly (ADP-ribose) polymerase-1 (PARP-1) and telomerase, as well as DNA damage response pathways are targets for anticancer drug development, and specific inhibitors are currently under clinical investigation. The purpose of this work is to evaluate anticancer activities of anthraquinone-derived tricyclic and tetracyclic small molecules and their structure-activity relationships with PARP-1 inhibition in non-small cell lung cancer (NSCLC) and NSCLC-overexpressing Oct4 and Nanog clone, which show high-expression of PARP-1 and more resistance to anticancer drug. We applied our library selected compounds to NCI's 60 human cancer cell-lines (NCI-60) in order to generate systematic profiling data. Based on our analysis, it is hypothesized that these drugs might be, directly and indirectly, target components to induce mitochondrial permeability transition and the release of pro-apoptotic factors as potential anti-NSCLC or PARP inhibitor candidates. Altogether, the most active NSC747854 showed its cytotoxicity and dose-dependent PARP inhibitory manner, thus it emerges as a promising structure for anti-cancer therapy with no significant negative influence on normal cells. Our studies present evidence that telomere maintenance should be taken into consideration in efforts not only to overcome drug resistance, but also to optimize the use of telomere-based therapeutics. These findings will be of great value to facilitate structure-based design of selective PARP inhibitors, in general, and telomerase inhibitors, in particular. Together, the data presented here expand our insight into the PARP inhibitors and support the resource-demanding lead optimization of structurally related small molecules for human cancer therapy.

We experimentally observe an intriguing phenomenon of complex spatio-temporal dynamics in a commercial optically pumped semiconductor laser with intracavity second harmonic generation. We numerically verify that the experimental results come from the total mode locking of transverse electromagnetic modes (TEM 00 ) and higher-order modes with significant astigmatism. The scenarios of the spatio-temporal dynamics are quite similar to the phenomena in soft-aperture Kerr-lens mode locked Ti:sapphire lasers.

We experimentally confirm that diamond surface cooling can significantly enhance the output performance of a sub-nanosecond diode-end-pumped passively Q-switched Yb:YAG laser. It is found that the pulse energy obtained with diamond cooling is approximately 1.5 times greater than that obtained without diamond cooling, where a Cr(4+):YAG absorber with the initial transmission of 84% is employed. Furthermore, the standard deviation of the pulse amplitude peak-to-peak fluctuation is found to be approximately 3 times lower than that measured without diamond cooling. Under a pump power of 3.9 W, the passively Q-switched Yb:YAG laser can generate a pulse train of 3.3 kHz repetition rate with a pulse energy of 287 μJ and with a pulse width of 650 ps.

We theoretically explore the eigenstates of a coupled p:q commensurate harmonic oscillator with SU(2) coupling interactions under the canonical transformation. The spatial patterns of the high-order eigenstates are found to be markedly localized on Lissajous figures from single to multiple periodic orbits. Controlling the pumping size in large-Fresnel-number degenerate cavities, we have experimentally observed the laser transverse modes that display the wave patterns to be analogous to the derived eigenstates.

A series of symmetrical disubstituded 1,8-diamidoanthraquinones were synthesized and evaluated for anti-proliferation, telomerase inhibitory by TRAP assay, and hTERT expression by SEAP assay. All of the compounds tested, except for compounds 3a and 3s were selected by the NCI screening system. In addition, compounds 4e and 4k exhibited inhibitory effects on telomerase activity. Taken together, our findings indicated that the analysis of cytotoxicity and telomerase inhibition might provide information applicable for further developing potential telomerase targeting strategy., (Crown Copyright © 2012. Published by Elsevier Masson SAS. All rights reserved.)

Surgical or traumatic brain injury often leads to loss of cerebral parenchyma but there is as yet no clinically effective strategy for neural regeneration. Collagen glycosaminoglycan (collagen-GAG, CG) scaffolds have previously been used in many tissues in vivo but have never been utilized in the brain. Using an animal model, we investigated the effects of the implantation of CG scaffold matrix following surgical brain trauma. Results indicated that implantation of CG scaffold could significantly promote functional recovery following surgical brain trauma. The CG scaffold was found to facilitate proliferation, differentiation and migration of endogenous neural precursor cells (NPCs) both in the intra-matrix zone (IMZ) and lesion boundary zone (LBZ). The tissue concentration of brain-derived neurotrophic factor (BDNF) and glia-derived neurotrophic factor (GDNF) in the cortex demonstrated a sustained increase after implantation of CG scaffold following surgical brain trauma. These results suggest that the utilization of CG scaffolds can be considered as a potential clinical strategy for tissue regeneration and functional recovery after brain injury., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

QC (glutaminyl cyclase) catalyses the formation of N-terminal pGlu (pyroglutamate) in peptides and proteins. pGlu formation in chemoattractants may participate in the regulation of macrophage activation and migration. However, a clear molecular mechanism for the regulation is lacking. The present study examines the role of QC-mediated pGlu formation on MCPs (monocyte chemoattractant proteins) in inflammation. We demonstrated in vitro the pGlu formation on MCPs by QC using MS. A potent QC inhibitor, PBD150, significantly reduced the N-terminal uncyclized-MCP-stimulated monocyte migration, whereas pGlu-containing MCP-induced cell migration was unaffected. QC small interfering RNA revealed a similar inhibitory effect. Lastly, we demonstrated that inhibiting QC can attenuate cell migration by lipopolysaccharide. These results strongly suggest that QC-catalysed N-terminal pGlu formation of MCPs is required for monocyte migration and provide new insights into the role of QC in the inflammation process. Our results also suggest that QC could be a drug target for some inflammatory disorders.

To investigate the structure-function relationships and geographic variations of L-amino acid oxidase (LAAO) from Daboia venoms, a single LAAO (designated as DrLAO) was purified from eastern Indian Daboia russelii venom and characterized. The purified DrLAO showed subunit molecular mass of 60-64kDa; its N-terminal sequence (1-20) was identical to those of several true viper LAAOs. Its preferred substrates were hydrophobic l-amino acids and the kinetic specificities were ordered as follows: Phe, Tyr, Met, Leu, and Trp. Enzyme assay and Western blotting showed that the venom LAAO contents of D. russelii were higher than those of Daboia siamensis. DrLAO dose-dependently inhibited ADP- and collagen-induced platelet aggregation with IC(50) values of 0.27 and 0.82μM, respectively. Apparently, DrLAO may synergize with other venom components to prolong and enhance bleeding symptoms after Daboia envenoming. The full sequence of DrLAO was deduced from its cDNA sequence and then confirmed by peptide mass fingerprinting. Molecular phylogenetic analysis revealed that SV-LAAO family members could be differentiated not only by snake taxonomy but also by the variations at position 223, and they divided into H223, S223, N223, and D223 subclasses. We have further prepared recombinant DrLAO and mutants by the Pichia expression system. Mutagenic analyses of DrLAO His223 revealed that this residue bound substrates instead of serving as an essential base in the catalytic steps. Our results suggest a direct hydride transfer from substrate to FAD as the mechanism for SV-LAAOs., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Four series of compounds containing an anthraquinone-linked moiety and symmetrical or asymmetrical aminoacyl residues in side chains at positions 1,4-, 1,5-, 2,6-, and 2,7- were synthesized and evaluated for their inhibitory effects toward telomerase and hTERT expression. Of these, only compound B11 showed selective inhibition of telomerase activity. Although it is not as competent as several of the anthraquinones we identified previously, nevertheless, the result is consistent with that the general structure moiety at the 1,5-position of diaminoanthraquinone-linked compound is important for the telomerase inhibitory activity. Interestingly, compounds A6, A8, C8, and D8 exhibited selective repressing activities toward hTERT expression and showed less effect toward proliferation of the treated cancer cells. Although it is not apparent which structure moiety is responsible for the telomerase repression effects of these compounds, they could be further developed as potential anti-tumor agents., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Wogonin, one of flavonoid compounds isolated from Chinese herbal plants Scutellaria baicalensis Georgi, has been recognized as a potent anti-cancer agent acting through control of growth, differentiation and apoptosis. However, the underlying molecular mechanism of its anti-cancer activity remains to be further elucidated. In this study, we investigated the potential role of wogonin in the induced-apoptosis of human breast cancer cells MCF-7. Wogonin was found to inhibit the proliferation of MCF-7 in a concentration and time-dependent manner, notably wogonin could induce G1 phase arrest of MCF-7 cells. Wogonin-induced apoptosis was accompanied by a significant decrease of the Bcl-2 and survivin and increase of Bax and p53. Wogonin also increased active apoptosis forms of caspases-3, -8, -9 significantly. Z-DEVD-fmk, a specific caspase-3 inhibitor, significantly inhibited wogonin-induced cell apoptosis. Wogonin also suppressed the phosphorylation of PI3K/Akt and induced phosphorylation of ERK. PD98059, a specific ERK inhibitor, significantly blocked wogonin-induced apoptosis. On the other hand, LY294002, a specific PI3K inhibitor, significantly increased wogonin-induced cell apoptosis. Further study indicated that LY294002 not only down-regulated the expression of survivin alone, but also enhanced the inhibition of survivin expression combined with wogonin. In conclusion, the pro-apoptotic effect of wogonin is mediated through the activation of ERK and the activation of caspases, and is correlated with the block of the PI3K/Akt/survivin signal pathways in MCF-7 cells., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We thoroughly analyze the level statistics and eigenfunctions in concentric as well as nonconcentric square torus billiards. We confirm the characteristics of quantum and classical correspondence and the existence of scarred and superscarred modes in concentric square torus billiards. Furthermore, we not only verify that the transition from regular to chaotic behaviors can be manifested in nonconcentric square torus billiards, but also develop an analytical distribution to excellently fit the numerical level statistics. Finally, we intriguingly observe that numerous eigenstates commonly exhibit the wave patterns to be an ensemble of classical diamond trajectories, as the effective wavelengths are considerably shorter than the size of internal hole.

Mammalian MDC1 interacts with CHK2 in the regulation of DNA damage-induced S-phase checkpoint and apoptosis, which is directed by the association of MDC1-FHA and CHK2-pThr68. However, different ligand specificities of MDC1-FHA have been reported, and no structure is available. Here we report the crystal structures of MDC1-FHA and its complex with a CHK2 peptide containing pThr68. Unlike other FHA domains, MDC1-FHA exists as an intrinsic dimer in solution and in crystals. Structural and binding analyses support pThr+3 ligand specificity and provide structural insight into MDC1-CHK2 interaction.

The non-traditional stable strontium (Sr) isotopes have received increasing attention recently as new geochemical tracers for studying Sr isotopic fractionation and source identification. This has been attributed to the advancement in multiple-collector inductively coupled plasma mass spectrometry (MC-ICP-MS), allows to determine precisely and simultaneously of the triple Sr isotopes. In this study, we applied a modified empirical external normalization (EEN) MC-ICPMS procedure for mass bias correction in Sr isotopic measurement using (92)Zr/(90)Zr. High-purity Zr Standard was spiked into sample solutions and the degree of fractionation was calculated off-line using an exponential law. The long-term external reproducibility for NIST SRM 987 δ(87)Sr and δ(88)Sr was better than 0.040‰ and 0.018‰ (2SD), respectively. The IAPSO standard seawater was used as a secondary standard to validate the analytical protocol and the absolute ratios measured were 0.709161±0.000018 for (87)Sr/(86)Sr, 0.177±0.021‰ for δ(87)Sr, and 0.370±0.026‰ for δ(88)Sr (2SD, n=7). These values are in good agreement with the literature data analyzed by thermal ionization mass spectrometry (TIMS) double spike technique. Rock standards, BHVO-2, BCR-2 and AGV-2 were also analyzed to validate the robustness of the methodology and showed identical results with literature data. Compared to previous (91)Zr/(90)Zr correction, we obtained improved results based on (92)Zr/(90)Zr, probably due to similar mass difference between (92)Zr/(90)Zr and measured Sr isotopes. The new analytical protocol presented in this study not only improves the analytical precision but also increases sample efficiency by omitting the use of the standard-sample bracketing (SSB) procedure., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Protein-protein interactions are critical determinants in biological systems. Engineered proteins binding to specific areas on protein surfaces could lead to therapeutics or diagnostics for treating diseases in humans. But designing epitope-specific protein-protein interactions with computational atomistic interaction free energy remains a difficult challenge. Here we show that, with the antibody-VEGF (vascular endothelial growth factor) interaction as a model system, the experimentally observed amino acid preferences in the antibody-antigen interface can be rationalized with 3-dimensional distributions of interacting atoms derived from the database of protein structures. Machine learning models established on the rationalization can be generalized to design amino acid preferences in antibody-antigen interfaces, for which the experimental validations are tractable with current high throughput synthetic antibody display technologies. Leave-one-out cross validation on the benchmark system yielded the accuracy, precision, recall (sensitivity) and specificity of the overall binary predictions to be 0.69, 0.45, 0.63, and 0.71 respectively, and the overall Matthews correlation coefficient of the 20 amino acid types in the 24 interface CDR positions was 0.312. The structure-based computational antibody design methodology was further tested with other antibodies binding to VEGF. The results indicate that the methodology could provide alternatives to the current antibody technologies based on animal immune systems in engineering therapeutic and diagnostic antibodies against predetermined antigen epitopes.

A series of diversely asymmetrical mono- or disubstituted 1,2-diamidoanthraquinone derivatives were synthesized and evaluated for drug-induced cytotoxicity by SRB assay, telomerase inhibitory activity by TRAP assay, and hTERT expression by SEAP assay. Interestingly, compounds 4, 11, 21, 32 and 36 exhibited selective potent antiproliferative activities by NCI with IC(50) values in the micromolar range. Of these, only compound 8 showed an IC(50) value of 0.95 μM against PC-3 cell lines (human prostate cancer) by SRB assay. All the synthesized compounds exhibited a poor or modest telomerase inhibitory activity by TRAP assay suggesting another mode of action for these compounds. Compound 11 showed broad inhibition against different types of cancer cell lines in the micromolar and submicromolar range., (Crown Copyright © 2011. Published by Elsevier Masson SAS. All rights reserved.)

We realize a femtosecond high-power spontaneous mode-locked operation with gigahertz oscillation in a vertical-external cavity surface-emitting laser under the condition of eliminating the internal and external unwanted reflection. We find that the reflectivity of the output coupler has a significant influence not only on the output power but also on the output pulse duration. With an incident pump power of 20 W, we have achieved 2.35 W of average output power with 778 fs pulse duration at a repetition rate of 2.17 GHz. The shortest pulse duration was 654 fs at an average output power of 0.45 W., (© 2011 Optical Society of America)

We explore the lasing mode selection between the chaotic and scarred modes in stadium-shaped vertical-cavity surface-emitting lasers (VCSELs). Experimental results reveal that the spatial gain distribution in the active layer of a VCSEL can be modified via the aperture size to favor the generation of either the chaotic or the scarred modes. Experimentally obtained chaotic and scarred modes are further employed to perform statistical analysis of wave function intensities for making a comparison with predictions based on the nonlinear σ model. We verify that the scarring effect can be quantitatively relevant to the weak-localization correction in the intensity probability distribution.

Objectives: In Traditional Chinese Medicine (TCM), Qi maintains the physiologic function and indicates physiologic energy. Glucose provides energy to humans, thereby playing a role analogous to "nutritive Qi." This study aims to identify the correlations among blood glucose, Qi Vacuity (QV), and the electrical conductances of acupoints., Methods: Twenty (20) subjects who had ingested a glucose solution after a 10-hour overnight fast were divided into two groups based on QV score. Then their acupoint conductances were measured sequentially using a Ryodoraku instrument during the following 120 minutes. Data were analyzed using generalized estimating equations as a time-series model., Results: Eight (8) subjects were categorized into a Qi Vacuous group for QV score >6, and the other 12 subjects were categorized into a Qi non-Vacuous group for QV score ≤6. During the first 30 minutes, the acupoint conductances decreased on the left Pericardium, left Heart, right Liver, Kidney, and Gallbladder meridians in the Qi Vacuous group, and increased on the right Pericardium meridian and decreased on the right Gallbladder meridian in the Qi non-Vacuous group. From 30 to 60 and 60 to 90 minutes, the acupoint conductances decreased on the Gallbladder, Heart, left Pericardium, left Kidney, right Liver, and right Stomach meridians in the Qi Vacuous group, and increased on the Pericardium, Heart, left Small Intestine, and left Lung meridians in the Qi non-Vacuous group. During the last 30 minutes, more of the acupoint conductances were increased in the Qi non-Vacuous group, whereas only the acupoint conductance on the liver meridian was increased and that on the left gallbladder meridian was decreased in the Qi Vacuous group., Conclusions: The findings suggest that the energy distribution and transformation in meridian vessels present different patterns in QV and non-QV groups after glucose consumption.

Background: Necrotizing fasciitis (NF), a life-threatening soft tissue infection, requires early diagnosis, prompt and repeated surgical intervention, and broad-spectrum antibiotic therapy. The aim of this study was to identify the independent predictors of mortality among patients with NF in Taiwan., Methods: We retrospectively reviewed the medical records of all patients who were admitted to Chi-Mei Medical Center, Tainan, Taiwan, with a diagnosis of NF. The definitive diagnosis was confirmed by the surgical findings, including (1) dishwater or foul-smelling discharge, (2) presence of necrotic fascia or lack of fascial bleeding, and (3) lack of resistance of normally adherent muscular fascia to blunt dissection. To identify factors associated with mortality, variables including personal history and comorbidities, clinical symptoms and signs, laboratory data, and microbiological data were compared between survivors and nonsurvivors., Results: From January 2003 to December 2009, 472 patients treated for NF were included in the study. The overall mortality was 12.1% (n = 57) and the 30-day mortality was 11.0% (n = 52). Multivariate analysis revealed eight independent predictors of mortality for NF including liver cirrhosis, soft tissue air, Aeromonas infection, age older than 60 years, band polymorphonuclear neutrophils >10%, activated partial thromboplastin time >60 s, bacteremia, and serum creatinine >2 mg/dL., Conclusion: We identified eight independent predictors of mortality that provided useful information on the severity of NF and guidance for treatment. Prospective studies are required to examine the fitness and sufficiency of these variables as effective predictors of NF mortality.

Background: Retroperitoneoscopic lumbar sympathectomy is a safe and effective treatment for plantar hyperhidrosis., Objective: To evaluate the safety and feasibility of laparoendoscopic single-site retroperitoneal lumbar sympathectomy in plantar hyperhidrosis., Methods: Bilateral laparoendoscopic single-site retroperitoneal lumbar sympathectomy was performed in a 27-year-old man who suffered from excessive sweating from the soles of the feet. A homemade single port was created with an Alexis wound retractor through a 2.5-cm incision at the tip of the 12th rib. With conventional 5-mm laparoscopy and instruments, retroperitoneal lumbar sympathectomy was performed., Results: The procedure was completed successfully without any complications and with minimal blood loss. The operative time was 110 and 80 minutes for the procedure on the left and right sides. The perioperative course and postoperative course were uneventful. The patient had anhidrosis of both feet after surgery with Hyperhidrosis Disease Severity Scale score of 1 at the 1-month follow-up., Conclusion: Laparoendoscopic single-site retroperitoneal lumbar sympathectomy is a safe and feasible procedure according to our initial experience.

We develop a novel method of creating optical vortex array by the conversion of a standing-wave Laguerre-Gaussian (LG) mode. Theoretically, by employing the transformational relation, the standing-wave LG mode is verified to be transformed from a pair of crisscrossed Hermite-Gaussian (HG) modes, embedded with optical vortex array, consists of a TEM n,m mode and a TEM m,n mode. Due to close correspondence between the transformational relation and the mode conversion of astigmatic lenses, we successfully generate the optical vortex array by transforming a standing-wave LG mode into the crisscrossed HG modes via a π/2 cylindrical lens mode converter. The investigation may provide useful insight in the study of the vortex light beam and its further applications.

We investigate the performance of a hybrid Q-switched (HQS) fiber laser that is constructed with a low RF-power driven acousto-optic (AO) Q-switch and an AlGaInAs semiconductor saturable absorber. Compared to a pure passively Q-switched (PQS) fiber laser, the ratio of timing jitter to pulse period can be significantly reduced from 2% to 0.3% in the regime of far above threshold. On the other hand, the prelasing effect in a pure actively Q-switched fiber laser can be considerably improved. More importantly, the maximum pulse energy of the HQS fiber laser can be increased approximately 25% in comparison with the result of the PQS fiber laser. At a pump power of 24 W, the highest pulse energy is up to 0.56 mJ with the pulse duration of 50 ns at the repetition rate of 23 kHz., (© 2011 Optical Society of America)

In a recent directed-evolution study, Escherichia coli D-sialic acid aldolase was converted by introducing eight point mutations into a new enzyme with relaxed specificity, denoted RS-aldolase (also known formerly as L-3-deoxy-manno-2-octulosonic acid (L-KDO) aldolase), which showed a preferred selectivity toward L-KDO. To investigate the underlying molecular basis, we determined the crystal structures of D-sialic acid aldolase and RS-aldolase. All mutations are away from the catalytic center, except for V251I, which is near the opening of the (α/β)(8)-barrel and proximal to the Schiff base-forming Lys-165. The change of specificity from D-sialic acid to RS-aldolase can be attributed mainly to the V251I substitution, which creates a narrower sugar-binding pocket, but without altering the chirality in the reaction center. The crystal structures of D-sialic acid aldolase·l-arabinose and RS-aldolase·hydroxypyruvate complexes and five mutants (V251I, V251L, V251R, V251W, and V251I/V265I) of the D-sialic acid aldolase were also determined, revealing the location of substrate molecules and how the contour of the active site pocket was shaped. Interestingly, by mutating Val251 alone, the enzyme can accept substrates of varying size in the aldolase reactions and still retain stereoselectivity. The engineered D-sialic acid aldolase may find applications in synthesizing unnatural sugars of C(6) to C(10) for the design of antagonists and inhibitors of glycoenzymes.

Aberrant pyroglutamate formation at the N terminus of certain peptides and proteins, catalyzed by glutaminyl cyclases (QCs), is linked to some pathological conditions, such as Alzheimer disease. Recently, a glutaminyl cyclase (QC) inhibitor, PBD150, was shown to be able to reduce the deposition of pyroglutamate-modified amyloid-β peptides in brain of transgenic mouse models of Alzheimer disease, leading to a significant improvement of learning and memory in those transgenic animals. Here, we report the 1.05-1.40 Å resolution structures, solved by the sulfur single-wavelength anomalous dispersion phasing method, of the Golgi-luminal catalytic domain of the recently identified Golgi-resident QC (gQC) and its complex with PBD150. We also describe the high-resolution structures of secretory QC (sQC)-PBD150 complex and two other gQC-inhibitor complexes. gQC structure has a scaffold similar to that of sQC but with a relatively wider and negatively charged active site, suggesting a distinct substrate specificity from sQC. Upon binding to PBD150, a large loop movement in gQC allows the inhibitor to be tightly held in its active site primarily by hydrophobic interactions. Further comparisons of the inhibitor-bound structures revealed distinct interactions of the inhibitors with gQC and sQC, which are consistent with the results from our inhibitor assays reported here. Because gQC and sQC may play different biological roles in vivo, the different inhibitor binding modes allow the design of specific inhibitors toward gQC and sQC.

Pole-to-pole oscillations of the Min proteins in Escherichia coli are required for the proper placement of the division septum. Direct interaction of MinE with the cell membrane is critical for the dynamic behavior of the Min system. In vitro, this MinE-membrane interaction led to membrane deformation; however, the underlying mechanism remained unclear. Here we report that MinE-induced membrane deformation involves the formation of an amphipathic helix of MinE(2-9), which, together with the adjacent basic residues, function as membrane anchors. Biochemical evidence suggested that the membrane association induces formation of the helix, with the helical face, consisting of A2, L3, and F6, inserted into the membrane. Insertion of this helix into the cell membrane can influence local membrane curvature and lead to drastic changes in membrane topology. Accordingly, MinE showed characteristic features of protein-induced membrane tubulation and lipid clustering in in vitro reconstituted systems. In conclusion, MinE shares common protein signatures with a group of membrane trafficking proteins in eukaryotic cells. These MinE signatures appear to affect membrane curvature.

We report that the subthreshold emission spectra of vertical-cavity surface-emitting lasers (VCSELs) can be analogously used to manifest the quantum-billiard energy spectra. The Fourier-transformed distributions of the subthreshold emission spectra are demonstrated to display various peak structures that are in good agreement with the results of the quantum-billiard model. We also verify that the statistical analyses of the nearest-neighbor eigenvalue spacing distributions obey a Poisson distribution for an equilateral-triangular device and a Wigner distribution for a stadium-shaped device.

We report on a millijoule-level Yb-doped photonic crystal fiber (PCF) laser passively Q-switched with AlGaInAs quantum wells (QWs). Three types of AlGaInAs devices with different QW numbers are fabricated to investigate the performance. With 50 groups of three AlGaInAs QWs as a saturable absorber (SA), the PCF laser generates an average power of 7.1 W with a pulse repetition rate of 6.5 kHz at a pump power of 16 W, corresponding to the pulse energy of 1.1 mJ. The maximum peak power is up to 110 kW.

An improved technique for precise and accurate determination of boron isotopic composition in Na-rich natural waters (groundwater, seawater) and marine biogenic carbonates was developed. This study used a 'micro-sublimation' technique to separate B from natural sample matrices in place of the conventional ion-exchange extraction. By adjusting analyte to appropriate pH, quantitative recovery of boron can be achieved (>98%) and the B procedural blank is limited to <8 pg. An additional mass bias effect in MC-ICP-MS was observed which could not be improved via the standard-sample-standard bracketing or the 'pseudo internal' normalization by Li. Therefore a standard other than NBS SRM 951 was used to monitor plasma condition in order to maintain analytical accuracy. An isotope cross-calibration with results from TIMS shows that the space-charge mass bias on MC-ICP-MS can be successfully corrected using off-line mathematical manipulation. Several reference materials, including the seawater IAPSO and two groundwater standards IAEA-B-2 and IAEA-B-3, were used to validate this approach. We found that the delta(11)B of the reference coral JCp-1 was 24.22+/-0.28 per thousand, corresponding to seawater pH based on the coral delta(11)B-pH function., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Glutaminyl cyclases (QCs) (EC 2.3.2.5) catalyze the formation of pyroglutamate (pGlu) at the N-terminus of many proteins and peptides, a critical step for the maturation of these bioactive molecules. Proteins having QC activity have been identified in animals and plants, but not in bacteria. Here, we report the first bacterial QC from the plant pathogen Xanthomonas campestris (Xc). The crystal structure of the enzyme was solved and refined to 1.44-A resolution. The structure shows a five-bladed beta-propeller and exhibits a scaffold similar to that of papaya QC (pQC), but with some sequence deletions and conformational changes. In contrast to the pQC structure, the active site of XcQC has a wider substrate-binding pocket, but its accessibility is modulated by a protruding loop acting as a flap. Enzyme activity analyses showed that the wild-type XcQC possesses only 3% QC activity compared to that of pQC. Superposition of those two structures revealed that an active-site glutamine residue in pQC is substituted by a glutamate (Glu(45)) in XcQC, although position 45 is a glutamine in most bacterial QC sequences. The E45Q mutation increased the QC activity by an order of magnitude, but the mutation E45A led to a drop in the enzyme activity, indicating the critical catalytic role of this residue. Further mutagenesis studies support the catalytic role of Glu(89) as proposed previously and confirm the importance of several conserved amino acids around the substrate-binding pocket. XcQC was shown to be weakly resistant to guanidine hydrochloride, extreme pH, and heat denaturations, in contrast to the extremely high stability of pQC, despite their similar scaffold. On the basis of structure comparison, the low stability of XcQC may be attributed to the absence of both a disulfide linkage and some hydrogen bonds in the closure of beta-propeller structure. These results significantly improve our understanding of the catalytic mechanism and extreme stability of type I QCs, which will be useful in further applications of QC enzymes., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

We report our observation of the signature of photon periodic orbits in the spontaneous emission spectra of large-aperture vertical-cavity surface-emitting lasers (VCSELs). The high-resolution measurement clearly demonstrates that over a thousand cavity modes with a narrow linewidth can be perfectly exhibited in the spontaneous emission spectrum just below the lasing threshold. The Fourier-transformed spectrum is analyzed to confirm that the spontaneous emission spectra of large-aperture VCSELs can be exploited to analogously investigate the energy spectra of the 2D quantum billiards.

We design a reliable linear three-element cavity to make a comparative study between the conventional and diffusion-bonded Nd:GdVO(4) crystals in the passively mode-locked operation. Experimental investigations reveal that the mode-locked pulse width obtained with the diffusion-bonded crystal is considerably broader than that obtained with the conventional crystal, even though the diffusion-bonded crystal can significantly reduce the thermal effects. The pulse broadening is experimentally verified to come from the length of the undoped part that brings in a reduction of the spatial-hole-burning (SHB) effect.

The present study was attempted to determine whether interleukin-1 receptor antagonist (IL-1ra) pretreatment exerts its antipyresis by reducing organum vasculosum laminae terminalis (OVLT) release of glutamate, hydroxyl radicals and prostaglandin E(2) in rabbits. It was found that systemic administration of lipopolysaccharide induced increased levels of both core temperature and OVLT levels of glutamate, hydroxyl radicals, and prostaglandin E(2). The rise in both the core temperature and OVLT glutamate, hydroxyl radicals and prostaglandin E(2) could also be induced by intracerebroventricular injection of interleukin-1beta. Pretreatment with an intracerebroventricular dose of IL-1ra significantly prevented the lipopolysaccharide or IL-1beta-induced overproduction of glutamate, hydroxyl radicals, and prostaglandin E(2) in OVLT of rabbit's brain. The febrile response caused by systemic administration of lipopolysaccharide or central injection of interleukin-1beta could also be IL-1ra pretreatment-ameliorated. These results indicate that IL-1ra pretreatment may exert its antipyresis by inhibiting the glutamate-hydroxyl radicals-prostaglandin E(2) pathways in the OVLT of rabbit's brain during lipopolysaccharide fever., (Copyright (c) 2009 Elsevier B.V. All rights reserved.)

Reconstruction of penile skin loss resulting from various causes is a challenge for clinician. Especially in a potent man, functional and cosmetic outcomes are demanded. Conservative treatment with topical agents is not enough for the full-thickness burn although hypertrophic scar and secondary contracture usually occurs. Resurfacing of total penile full-thickness burn after wound management with the Versajet hydrosurgery system (a water-jet powered debrider) is described for the first use in our hospital.

We investigate the lasing modes in large-Fresnel-number laser systems with astigmatism effects. Experimental results reveal that numerous lasing modes are concentrated on exotic patterns corresponding to intriguing geometries. We theoretically use the quantum operator algebra to construct the wave representation for manifesting the origin of the localized wave patterns.

NSC746364, NSC746365, and NSC746366 are structurally novel 2,7-diamidoanthraquinone derivatives compared with other clinically used anticancer agents and have exhibited a unique multilog differential pattern of activity in our earlier studies. To systematically evaluate their potential anticancer activity, three selected compounds were tested for their cytotoxicity in vitro against 60 human cancer lines in the National Cancer Institute's anticancer drug screen as well as for dose response curves and telomerase activity. Cell growth was analyzed by the MTT assay, with differences between dose-response curves analyzed nonparametrically. Telomerase activity was detected by a modified version of the PCR-based assay and telomere repeat amplification protocol assay. To elucidate the structure-activity relationships and in-vitro anticancer activity, we correlated their activity profile [GI(50), total growth inhibition (TGI), and LC(50)] in the screening system and also their effects on telomerase activity, human telomerase reverse transcriptase expression, cell proliferations, and cytotoxicity. As a result we found that NSC746364, NSC746365, and NSC746366 have potent activity with 50% net growth inhibition conferred by 0.23-16.0 micromol/l (2.08 micromol/l mean); 0.78-15.9 micromol/l (2.57 micromol/l mean); 1.38-63.1 micromol/l (3.89 micromol/l mean), respectively. Sensitive cell lines exhibit TGI and 50% lethality to NSC746364, exhibited an LC(50) with as little as 2.82 micromol/l and TGI with as little as 0.95 micromol/l; NSC746365, exhibited an LC(50) with as little as 3.30 micromol/l, and TGI with as little as 1.65 micromol/l; NSC746366, exhibited an LC(50) with as little as 8.80 micromol/l; and TGI with as little as 4.06 micromol/l, respectively. Results of the study extend the initial in-vitro observation reported in the data above and confirm the importance of anticancer activity and telomerase inhibition. The unique molecular characterization, cytotoxicity, and telomerase activity profiles warrant further investigation and indicate a potential novel mechanism of anticancer action involved.

We report on a gigahertz self-mode-locked high-order Hermite-Gaussian (HG) Nd:GdVO(4) laser. With a pump power of 2.2 W, the average output power for the TEM(0,m) modes from m=9 to m=0 are among 350-780 mW at a repetition rate of 3.5 GHz. The mode-locked pulse width is in the range of 20-25 ps for various HG TEM(0,m) modes. With a simple cylindrical-lens converter, the mode-locked HG beams are converted to generate picosecond optical vortex pulses.

We demonstrate comparative studies for Cr(4+):YAG crystal and AlGaInAs quantum-well (QW) used as a saturable absorbers in passively Q-switched Yb-doped fiber lasers. Both saturable absorbers were designed to be possessed of nearly the same initial transmission. Under a pump power of 24 W, the average output powers were up to 14.4 W and 13.8 W obtained with the AlGaInAs QWs and with the Cr(4+):YAG crystal, respectively. The maximum pulse energies obtained with the Cr(4+):YAG crystal and with the AlGaInAs QWs were found to be 0.35 mJ and 0.45 mJ, respectively.