The economic burden of chronic neurological disease

Figure S2. Forest plots of the 5 studies evaluating the association between EP and endometriosis according to the endometriosis stage (stage 4 versus stage 1, and stages 3–4 versus stages 1–2). (TIFF 2134 kb

Sulfur-doped graphene with iron pyrite (FeS 2 ) as an efficient and stable electrocatalyst for the iodine reduction reaction in dye-sensitized solar cells

As an alternative to platinum (Pt), hybrid electrocatalysts based on sulfur-doped graphene with FeS2 microspheres (SGN-FeS2) were used as a counter electrode (CE) in dye-sensitized solar cells (DSSCs). Benefiting from the high conductivity of SGN and excellent electrocatalytic activity of the FeS2, the bifunctional hybrid electrocatalyst-based device displays a power conversion efficiency (PCE) of 8.1%, which is comparable to that (8.3%) of traditional Pt CE-based DSSC, while also exhibiting excellent stability in ambient conditions. These characteristics, in addition to its low-cost and facile preparation, make the SGN–FeS2 hybrid an ideal CE material for DSSCs

Padronização da pesquisa de linfonodos sentinelas em estômago por métodos combinados

Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Pós-Graduação em Ciências da Cirurgia, Campinas, 2012.Introdução - Com os estudos de Gould et al. (1960), Cabanas (1977) e Morton et al. (1992), estabeleceu-se o conceito da pesquisa do linfonodo sentinela. Esse se baseia na teoria de que ao identificar a presença ou ausência de metástase no primeiro linfonodo que recebe a drenagem linfática a partir do tumor (sentinela), poderia representar o estado de acometimento dos outros linfonodos. Isto evitaria a realização desnecessária de linfadenectomias. Com o passar dos anos, foi consagrada para ser aplicada em casos de melanoma e câncer de mama. Nesta última década, tenta-se estender os princípios da utilização da pesquisa de linfonodo sentinela para os cânceres do aparelho digestivo. Entretanto, no caso do estômago, existem algumas dificuldades, como: presença de sistema de drenagem linfática multidirecional, ocorrência de metástases saltatórias e identificação de mais de um linfonodo sentinela por indivíduo. Objetivo - Criar e padronizar um modelo animal para o treinamento de pesquisa de linfonodos sentinelas em estômago. Método - Trinta e dois coelhos, saudáveis, foram submetidos à anestesia exclusivamente intramuscular. Por meio de laparotomia, foi injetado na subserosa da parede anterior do corpo gástrico, 0,1 ml de fitato marcado com tecnécio-99m (0,2 mCi), em seguida pelo mesmo orifício, de 0,2 ml de Azul Patente V® 2,5%. A cavidade abdominal foi avaliada, in vivo , para pesquisa de suspeitas de linfonodos azuis (corados em azul) e com detector manual de radiação gamma aos 5, 10 e 20 minutos para detecção de suspeitas de linfonodos radioativos (radioatividade identificada superior a 10X o valor apresentado pelo fundo). Após 20 minutos, realizou-se ressecção e exérese total do estômago, baço e suspeitas de linfonodos, para posterior avaliação da radioatividade ex vivo . A seguir, encaminharam-se as suspeitas de linfonodos para estudo histológico para identificação de tecido linfóide. Resultados - Foram identificados linfonodos em 30 coelhos (93,75%) com média de 2,2 por animal. Das 90 suspeitas de linfonodos detectadas, em 70 casos (77,77%) obteve-se confirmação histológica para tecido linfóide. Dessas, a maioria foi identificada e localizada na região entre o esôfago e o fundo gástrico durante a avaliação in vivo aos 5 minutos. Dois coelhos faleceram durante os experimentos (Taxa de mortalidade = 6,25%). Conclusão - O modelo experimental em coelhos para pesquisa de linfonodos sentinelas em estômago por métodos combinados foi factível, de fácil execução e baixa mortalidade, podendo ser usado para treinamento.Abstract : Introduction - The concept of sentinel lymph node was established by the studies of Gould et al. (1960), Cabanas (1977) and Morton et al. (1992). It is based on the theory that, whenever the presence or absence of metastasis is identified in the first lymph node that receives the lymphatic drainage from the tumor (sentinel) the status of involvement of other lymph nodes might be infered. This could avoid the performance of unnecessary lymphadenectomies. Over the years, its use was consecrated by its application in melanoma and breast cancer. In the last decade, attempts have been made to extend the principles of sentinel lymph node investigation to cancers of the digestive tract. In the case of stomach cancer, additional difficulties were found, such as multiple and aberrant lymphatic routes, the occurrence of skip metastasis and the possible identification of more than one sentinel lymph node in the same patient. Aim - To develop and evaluate an animal model for training sentinel lymph node navigation in the stomach. Methods - Thirtytwo healthy rabbits, were prepped and given intramuscular anesthesia. Through a formal laparotomy, they received a subserosal injection of 0.1 ml of phytate labeled with technetium-99m (0.2 mCi) in the anterior wall of the gastric corpus, followed by 0.2 ml of Blue Patent ® V 2.5%, through the same puncture site. Suspicious lymph nodes were searched in-vivo at 5, 10 and 20 minutes, both visually (Blue Patent stained lymph nodes) and with a manual gamma radiation detector (to detect suspected radioactive lymph nodes, displaying radioactivity levels over 10X the value displayed by the background). En-block resection of the stomach, spleen, visible limph nodes and local fat tissue was then performed and the specimen was assessed "ex vivo" for radioactivity. Suspected lymph nodes were sent for histological study to evaluate the presence of lymphoid tissue. Results Radiolabeled or stained lymph nodes were identified in 30 rabbits (93.75%) with an average of 2.2 specimens per animal; of the 90 suspicious lymph nodes detected, histology confirmed lymphoid tissue in 70 cases (77.77%). Most lymph nodes were identified at the 5-minute in-vivo evaluation and their most common location was found to be in the region between the esophagus and the gastric fundus. Two rabbits died during the procedure resulting in a 6.25% mortality. Conclusion - The rabbit model proved adequate for training in sentinel node navigation in the stomach by combined methods (dye and radiocolloid) being easy to execute and associated with low mortality

学会抄録

DMPs on chromosome X. The location data: Illumina probe ID, chromosome, position, strand, UCSC gene symbol, UCSC genetic feature and regulatory feature, are shown alongside the methylation statistics: mean difference in beta, the p values and the BH-adjusted p values. DMPs associated to either PABPC5 or MIR223 are indicated in bold. (XLSX 12 kb

Quality Assurance and Efficiency Enhancement for Stereolithography-based 3D and 4D Printing

The emergence of additive manufacturing (AM), also referred to as 3D printing, has provided the potential to revolutionize the manufacturing sectors with shorter product development cycles, fewer materials wastes, and more product design and fabrication freedom. Recently, an increasing interest has been closely associated with AM and made it a mainstream manufacturing process leading to rapid growth in the global AM market. Consequently, extensive research efforts have been dedicated to advancing the development of AM and supporting its deployment. Particularly, recent advancement in AM has broadened its applications from rapid prototyping and tooling to rapid manufacturing of functional parts used in a wide range of industries such as aerospace, automobile, and consumer products. The current AM applications are mainly limited to small-sized, low-volume production. To further increase the utilization of AM technologies, it is critical to investigate and improve the fabrication quality and process efficiency. To facilitate the wide adoption of AM techniques for various potential applications and provide valuable insights to AM users and manufacturers, this dissertation is conducted to promote quality assurance of AM products and efficiency improvement for AM systems. More specifically, mathematical models are established to quantify the impacts of printing and post-curing parameters on the resulting mechanical behavior. The established models can be applied to aid the selection of process parameters in 3D printing and associated post-curing processes. In addition, the emerging shape memory property is theoretically modeled and characterized under cyclic thermo-mechanical conditions, when the thermo-responsive material is adopted for printing. Adopting the established models can improve the shape memory quality and aid enhance the cyclic durability of the 4D printed parts. Moreover, an efficiency-aware curing approach is proposed to predict and reduce the total build time considering several quality aspects. The proposed method is experimentally examined for its effectiveness in enhancing printing efficiency while ensuring product quality in terms of geometric dimensions, mechanical property, and surface finish. The outcomes of this dissertation will positively contribute to AM process planning and strengthen the understanding of quality assurance and efficiency enhancement in AM

Kinetic Study of the Inhibition Mechanism of Dehaloperoxidase-Hemoglobin A by 4‑Bromophenol

The mechanism of dehaloperoxidase-hemoglobin (DHP) inhibition by 4-bromophenol (4-BP) was investigated using Michealis-Menten and transient-state kinetic analyses. Transient-state kinetics using the stopped-flow technique to mix DHP and H₂O₂ in the presence of inhibitor concentrations less than 10-fold greater than the enzyme concentration show that 4-BP does not fully impede H₂O₂ entering the distal pocket to activate DHP. It is not clear whether an oxoferryl intermediate is formed under these conditions and there may be alternative pathways for H₂O₂ reaction in the 4-BP bound form of DHP. Two new species have been identified during the reaction of 4-BP bound form of DHP in the transient-state kinetic experiment by using Singular Value Decomposition (SVD) and global-fitting analysis. Rather than forming Compound ES in the unbound form, an inhibitor bound intermediate that possesses blue-shifted Soret band and a double peaked Q-band is observed. This intermediate is subsequently converted to the end-point species that is distinguished from Compound RH formed in the uninhibited enzyme. Bench-top mixing kinetics of DHP were conducted in order to determine the inhibitor binding constant and to understand the enzyme inhibition mechanism from a thermodynamic perspective. It was found that the inhibition constant, <i>K</i>_<i>i</i>, decreased from 2.56 mM to 0.15 mM over the temperature range from 283 to 298 K, which permits determination of the enthalpy and entropy for inhibitor binding as −135.5 ± 20.9 kJ/mol and 526.1 ± 71.9 J/(mol·K), respectively, leading to the conclusion that inhibitor binding is entropically driven

Ba₂(BO₃)_1–<i>x</i>(CO₃)_<i>x</i>Cl_1+<i>x</i>: A Mixed Borate and Carbonate Chloride Crystallized from High-Temperature Solution

A mixed borate and carbonate chloride Ba₂(BO₃)_1–<i>x</i>(CO₃)_<i>x</i>Cl_1+<i>x</i> was obtained by spontaneous crystallization from a high-temperature melt in open air. It crystallizes in the trigonal crystal system with space group of <i>P</i>3<i>m̅</i>1 and lattice constants of <i>a</i> = 5.4708(8) Å and <i>c</i> = 10.640(2) Å. The structure can be viewed as an intergrowth of trigonal Ba₂Mg­(BO₃)₂ (001) slab and (111) slab of the cubic fluorite BaCl₂. During Fourier analysis of the single-crystal X-ray diffraction data, additional electron density was found locating at <i>1b</i> (0, 0, 1/2) site and attributed to chlorine surplus, which was confirmed by chemical titration. Charge balance of the compound was found, unexpectedly in an acidic borate containing high-temperature melt, by partial CO₃^2– group substituting the BO₃^3– group. The existence of CO₃^2– anion in the crystal was detected by thermogravimetry–mass spectrum analysis and Raman spectrum. The transmittance spectrum shows that the crystal is transparent from ultraviolet to infrared with short-wavelength absorption edge at about 220 nm

Two New Barium Borate Fluorides ABa₁₂(BO₃)₇F₄ (A = Li and Na)

Two new barium borate fluorides LiBa₁₂(BO₃)₇F₄ and NaBa₁₂(BO₃)₇F₄ are obtained by spontaneous crystallization from high-temperature flux. The two compounds are isostructural and crystallized into the tetragonal system, <i>I</i>4/<i>mcm</i> space group, with unit cell parameters of <i>a</i> = 13.5709(6) Å, <i>c</i> = 14.9908(13) Å for LiBa₁₂(BO₃)₇F₄ and <i>a</i> = 13.6443(9) Å, <i>c</i> = 15.021(2) Å for NaBa₁₂(BO₃)₇F₄. Isolated Li/NaF₄–BO₃ units formed by Li/NaF₄O square pyramids and B3O₃ groups sharing the O5 atom are found occupying the octagonal tunnels built by Ba and BO₃ groups along the <i>c</i> axis. High mobility of Li⁺ ion is observed in the LiBa₁₂(BO₃)₇F₄ single crystal by ac impedance measurements at different temperatures

The Regulatory Implications of Hydroquinone for the Multifunctional Enzyme Dehaloperoxidase-Hemoglobin from <i>Amphitrite ornata</i>

Hydroquinone (H₂Q) has been observed to compete with the oxidation of substrates 2,4,6-tribromophenol (2,4,6-TBP) and 2,4,6-trichlorophenol (2,4,6-TCP) catalyzed by the dehaloperoxidase-hemoglobin (DHP) from <i>Amphitrite ornata</i> in the presence of H₂O₂. This competition is observed as a lag phase during which H₂Q is preferentially oxidized to 1,4-benzoquinone (1,4-BQ) while totally inhibiting either 2,4,6-TBP or 2,4,6-TCP oxidation. The inhibition by H₂Q is distinct from that of the native competitive inhibitor 4-bromophenol (4-BP) since H₂Q is itself oxidized and its product 1,4-BQ is not an inhibitor. Thus, once H₂Q is completely consumed, the inhibition is removed, and normal substrate turnover is initiated, which explains the lag phase. To probe the mechanism of lag phase, the reactions between H₂Q and DHP were both studied both in the presence and in the absence of H₂O₂. The reversible reactions between ferric/oxyferrous DHP A and H₂Q/1,4-BQ are shown to involve a proton-coupled electron transfer (PCET) mechanism, where the distal histidine His⁵⁵ serves as the proton acceptor. The p<i>K</i>_a of the distal histidine His⁵⁵ has been determined by resonance Raman spectroscopy in order to corroborate its involvement in this mechanism. Consistent with the proposed mechanism, kinetic assays have shown that H₂Q serves as a substrate for DHP that follows the Michaelis–Menten kinetics. Unlike H₂Q, the product 1,4-BQ has a relatively large <i>K</i>_i value and therefore has negligible inhibition. This study sheds light on understanding the difference between substrate and inhibitor binding sites and regulatory implication for the peroxidase and oxygen-transporter functions in DHP. It also provides information on PCET in DHP, which is important for resolving the switching between the ferric peroxidase catalytic function and the ferrous oxygen transport function

In-Depth Characterization of Sphingoid Bases via Radical-Directed Dissociation Tandem Mass Spectrometry

Sphingoid base (SPH) is a basic structural unit of all classes of sphingolipids. A sphingoid base typically consists of an aliphatic chain that may be desaturated between C4 and C5, an amine group at C2, and a variable number of OH groups located at C1, C3, and C4. Variations in the chain length and the occurrence of chemical modifications, such as methyl branching, desaturation, and hydroxylation, lead to a large structural diversity and distinct functional properties of sphingoid bases. However, conventional tandem mass spectrometry (MS/MS) via collision-induced dissociation (CID) faces challenges in characterizing these modifications. Herein, we developed an MS/MS method based on CID-triggered radical-directed dissociation (RDD) for in-depth characterization of sphingoid bases. The method involves derivatizing the sphingoid amine with 3-(2,2,6,6-tetramethylpiperidin-1-yloxymethyl)-picolinic acid 2,5-dioxopyrrolidin-1-yl ester (TPN), followed by MS2 CID to unleash the pyridine methyl radical moiety for subsequent RDD. This MS/MS method was integrated on a reversed-phase liquid chromatography–mass spectrometry workflow and further applied for in-depth profiling of total sphingoid bases in bovine heart and Caenorhabditis elegans. Notably, we identified and relatively quantified a series of unusual sphingoid bases, including SPH id17:2 (4,13) and SPH it19:0 in C. elegans, revealing that the metabolic pathways of sphingolipids are more diverse than previously known