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Surface lipids on pathogenic mycobacteria modulate infection outcomes by regulating host immune responses. Phenolic glycolipid (PGL) is a host-modulating surface lipid that varies among clinical Mycobacterium tuberculosisstrains. PGL is also found in Mycobacterium marinum, where it promotes infection of zebrafish through effects on the innate immune system. Given the important role this lipid plays in the host–pathogen relationship, tools for profiling its abundance, spatial distribution, and dynamics are needed. Here, we report a strategy for imaging PGL in live mycobacteria using bioorthogonal metabolic labeling. We functionalized the PGL precursor p-hydroxybenzoic acid (pHB) with an azide group (3-azido pHB). When fed to mycobacteria, 3-azido pHB was incorporated into the cell surface, which could then be visualized viathe bioorthogonal conjugation of a fluorescent probe. We confirmed that 3-azido pHB incorporates into PGL using mass spectrometry methods and demonstrated selectivity for PGL-producing M. marinumand M. tuberculosisstrains. Finally, we applied this metabolic labeling strategy to study the dynamics of PGL within the mycobacterial membrane. This new tool enables visualization of PGL that may facilitate studies of mycobacterial pathogenesis.

In this work, in-situ experimental tests are first performed to investigate the powder spreading process of additive manufacturing, where different kinds of scrapers and spreading speeds are employed. Detailed kinetic behaviours of individual powder particles are discussed by discrete element method simulations. It is found that the decrease of inclination angle of the scraper improves the powder pressure and compaction in the spreading process, leading to a denser powder flow and thus a denser powder bed. The increase of spreading speed also improves the powder pressure and compaction in the spreading process. However, the powder flow becomes looser due to the volume dilation, and thus the quality of the paved powder bed decreases. In industrial applications, if the higher powder spreading speed is employed to improve the processing efficiency, the scraper with a smaller inclination angle can be used to ensure the powder bed quality.

Expressed on epidermal Langerhans cells, CD1a presents a range of self-lipid antigens found within the skin; however, the extent to which CD1a presents microbial ligands from bacteria colonizing the skin is unclear. Here we identified CD1a-dependent T cell responses to phosphatidylglycerol (PG), a ubiquitous bacterial membrane phospholipid, as well as to lysylPG, a modified PG, present in several Gram-positive bacteria and highly abundant in Staphylococcus aureus. The crystal structure of the CD1a–PG complex showed that the acyl chains were buried within the A′- and F′-pockets of CD1a, while the phosphoglycerol headgroup remained solvent exposed in the F′-portal and was available for T cell receptor contact. Using lysylPG and PG-loaded CD1a tetramers, we identified T cells in peripheral blood and in skin that respond to these lipids in a dose-dependent manner. Tetramer+CD4+T cell lines secreted type 2 helper T cell cytokines in response to phosphatidylglycerols as well as to co-cultures of CD1a+dendritic cells and Staphylococcusbacteria. The expansion in patients with atopic dermatitis of CD4+CD1a–(lysyl)PG tetramer+T cells suggests a response to lipids made by bacteria associated with atopic dermatitis and provides a link supporting involvement of PG-based lipid-activated T cells in atopic dermatitis pathogenesis.

Monometallic yttrium β-diketiminate complexes are active and controlled catalysts for perfectly alternating ring-opening copolymerization of 1-butene oxide and phthalic anhydride under mild conditions. β-Diketiminate ligands with pendant neutral donors were targeted to identify both the impact of donor strength and number of donors on rates of polymerization and the presence of undesirable side reactions. Initiating groups were also varied between alkyls, chlorides, and alkoxides. In the presence of a cocatalyst, the catalysts studied were active for polymerization with minimal side reactions, whereas lack of cocatalysts led to competing homopolymerization of epoxides. While a greater donor strength and a larger number of donors both increase the rate of polymerization, donor strength generally had a bigger impact when a cocatalyst was used. Additionally, alkoxide and chloride initiators proved to be the fastest, with alkyls being more sluggish. These subtle ligand changes significantly impacting polymerization activity lend promise to the facile tunability of rare earth metal complexes to be highly active for the target copolymerization, which renders further research in this area attractive and timely.

Background: Current evidence from epidemiologic studies suggested that phthalate metabolites might be associated with blood pressure (BP) changes. However, the special relationship between phthalate metabolites and BP changes in children has not been clearly elucidated in existing researches. Objectives: We investigated the links between phthalate metabolites and various BP parameters, including systolic/diastolic BP, mean arterial pressure (MAP), and the presence of hypertension. Methods: The population sample consisted of 1036 children aged 8 to 17 years from the 2013–2018 NHANES in the United States. High performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used to measure urinary concentrations of 19 phthalate metabolites. Systolic/diastolic BP were derived from the average of three valid measurements, and MAP was calculated as (systolic BP + 2 × diastolic BP)/3. Hypertension was defined as mean systolic BP and/or diastolic BP that was ≥ 95th percentile for gender, age, and height reference. Linear regression, logistic regression, and weighted quantile sum (WQS) regression models were employed to assess the associations between phthalate exposure and systolic/diastolic BP, MAP, and hypertension. Results: Ten of 19 phthalate metabolites including MCNP, MCOP, MECPP, MBP, MCPP, MEP, MEHHP, MiBP, MEOHP, and MBzP had detection frequencies > 85% with samples more than 1000. MCNP, MCOP, MECPP, MBP, MCPP, MEHHP, MiBP, MEOHP, and MBzP were generally negatively associated with systolic/diastolic BP and MAP, but not protective factors for hypertension. These associations were not modified by age (8–12 and 13–17 years) or sex (boys and girls). The above-mentioned associations were further confirmed by the application of the WQS analysis, and MCOP was identified as the chemical with the highest weight. Conclusion: Phthalate metabolites were associated with modest reductions in systolic/diastolic BP, and MAP in children, while appeared not protective factors for hypertension. Given the inconsistent results among existing studies, our findings should be confirmed by other cohort studies.

Conventional scanning approaches with fixed laser parameters are prone to causing localized defects and in-homogeneous performance when forming parts with complicated geometries using the laser powder bed fusion (LPBF) process. While online monitoring of the forming process using thermal cameras allows the identification of abnormal infrared radiation intensity values of the scanning line to pinpoint regions of potential defects, it fails to proactively prevent defects from occurring. To solve this problem, this study constructed a back propagation (BP) neural network to predict the infrared radiation intensity of the current layer before scanning. In the meantime, this study designed a parameter optimization algorithm to adjust the local scanning parameters with a view to avoiding defects and thus enhancing the performance consistency of the formed parts. This study drew on the idea of the divide-and-conquer method to divide the parts into multiple units for data acquisition by thermal camera, and has collected 500,000 pieces of experimental data through 15 experiments. By utilizing these data, this study trained a BP neural network to predict the infrared radiation intensity, and its mean absolute error (MAE) of the prediction results was 25, the coefficient of determination (R2) was 0.708, and the F1 score (abnormal radiation intensity identification and classification) was 0.802. Subsequently, the study optimized the scanning parameters of the unit by using particle swarm optimization (PSO), and performed practical application and validation on spherical gear parts of 316 L stainless steel and blade parts of DZ125 nickel-based superalloy. Findings indicated that the automatic optimization strategy can effectively prevent abnormal infrared radiation intensity values during the scanning process and enhance the performance consistency of the LPBF process for complicated parts in both different materials and structures.

The first asymmetric total synthesis of three structures proposed for mycobacterial diacyl trehaloses, DAT1, DAT2, and DAT3is reported. The presence of two of these glycolipids, DAT1and DAT3, within different strains of pathogenic M. tuberculosis was confirmed, and it was shown that their abundance varies significantly. In mass spectrometry, synthetic DAT2possessed almost identical fragmentation patterns to presumptive DAT2from Mycobacterium tuberculosisH37Rv, but did not coelute by HPLC, raising questions as the precise relationship of the synthetic and natural materials. The synthetic DATs were examined as agonists for signaling by the C-type lectin, Mincle. The small differences in the chemical structure of the lipidic parts of DAT1, DAT2, and DAT3led to drastic differences of Mincle binding and activation, with DAT3showing similar potency as the known Mincle agonist trehalose dimycolate (TDM). In the future, DAT3could serve as basis for the design of vaccine adjuvants with simplified chemical structure.

Acellular dermal matrix (ADM) shows promise for cartilage regeneration and repair. However, an effective decellularization technique that removes cellular components while preserving the extracellular matrix, the transformation of 2D-ADM into a suitable 3D scaffold with porosity and the enhancement of bioactive and biomechanical properties in the 3D-ADM scaffold are yet to be fully addressed. In this study, we present an innovative decellularization method involving 0.125% trypsin and 0.5% SDS and a 1% Triton X-100 solution for preparing ADM and converting 2D-ADM into 3D-ADM scaffolds. These scaffolds exhibit favorable physicochemical properties, exceptional biocompatibility and significant potential for driving cartilage regeneration in vitroand in vivo. To further enhance the cartilage regeneration potential of 3D-ADM scaffolds, we incorporated porcine-derived small intestinal submucosa (SIS) for bioactivity and calcium sulfate hemihydrate (CSH) for biomechanical reinforcement. The resulting 3D-ADM+SIS scaffolds displayed heightened biological activity, while the 3D-ADM+CSH scaffolds notably bolstered biomechanical strength. Both scaffold types showed promise for cartilage regeneration and repair in vitroand in vivo, with considerable improvements observed in repairing cartilage defects within a rabbit articular cartilage model. In summary, this research introduces a versatile 3D-ADM scaffold with customizable bioactive and biomechanical properties, poised to revolutionize the field of cartilage regeneration.

Mycobacterium tuberculosis(Mtb) is the world’s most deadly pathogen. Unlike less virulent mycobacteria, Mtbproduces 1-tuberculosinyladenosine (1-TbAd), an unusual terpene nucleoside of unknown function. In the present study 1-TbAd has been shown to be a naturally evolved phagolysosome disruptor. 1-TbAd is highly prevalent among patient-derived Mtbstrains, where it is among the most abundant lipids produced. Synthesis of TbAd analogs and their testing in cells demonstrate that their biological action is dependent on lipid linkage to the 1-position of adenosine, which creates a strong conjugate base. Furthermore, C20 lipid moieties confer passage through membranes. 1-TbAd selectively accumulates in acidic compartments, where it neutralizes the pH and swells lysosomes, obliterating their multilamellar structure. During macrophage infection, a 1-TbAd biosynthesis gene (Rv3378c) confers marked phagosomal swelling and intraphagosomal inclusions, demonstrating an essential role in regulating the Mtbcellular microenvironment. Although macrophages kill intracellular bacteria through phagosome acidification, Mtbcoats itself abundantly with antacid.

Salmonella species are among the world’s most prevalent pathogens. Because the cell wall interfaces with the host, we designed a lipidomics approach to reveal pathogen-specific cell wall compounds. Among the molecules differentially expressed between Salmonella Paratyphi and S. Typhi, we focused on lipids that are enriched in S. Typhi, because it causes typhoid fever. We discovered a previously unknown family of trehalose phospholipids, 6,6′-diphosphatidyltrehalose (diPT) and 6-phosphatidyltrehalose (PT). Cardiolipin synthase B (ClsB) is essential for PT and diPT but not for cardiolipin biosynthesis. Chemotyping outperformed clsB homology analysis in evaluating synthesis of diPT. DiPT is restricted to a subset of Gram-negative bacteria: large amounts are produced by S. Typhi, lower amounts by other pathogens, and variable amounts by Escherichia coli strains. DiPT activates Mincle, a macrophage activating receptor that also recognizes mycobacterial cord factor (6,6′-trehalose dimycolate). Thus, Gram-negative bacteria show convergent function with mycobacteria. Overall, we discovered a previously unknown immunostimulant that is selectively expressed among medically important bacterial species.

AbstractWe study an important paper of Bustince and Burillo to generalize their derivations. Our findings will provide some theoretical extensions for interval-valued intuitionistic fuzzy sets.

The hallmark function of αβ T cell antigen receptors (TCRs) involves the highly specific co-recognition of a major histocompatibility complex molecule and its carried peptide. However, the molecular basis of the interactions of TCRs with the lipid antigen–presenting molecule CD1c is unknown. We identified frequent staining of human T cells with CD1c tetramers across numerous subjects. Whereas TCRs typically show high specificity for antigen, both tetramer binding and autoreactivity occurred with CD1c in complex with numerous, chemically diverse self lipids. Such extreme polyspecificity was attributable to binding of the TCR over the closed surface of CD1c, with the TCR covering the portal where lipids normally protrude. The TCR essentially failed to contact lipids because they were fully seated within CD1c. These data demonstrate the sequestration of lipids within CD1c as a mechanism of autoreactivity and point to small lipid size as a determinant of autoreactive T cell responses. CD1 molecules present diverse lipid ligands to TCRs expressed by NKT cells. Rossjohn, Moody and colleagues show a unique form of autoreactivity with human CD1c molecules, whereby TCRs recognize a closed conformation of CD1c molecules, which are loaded with a diverse array of ‘headless’ glycolipids.

During laser powder bed fusion (LPBF) additive manufacturing of components with complex geometries, short scanning lines easily induce localized excessive heat accumulation, resulting in poor manufacturing qualities, e.g., rough surface and low hardness, etc. An optimized scanning strategy was proposed to mitigate this heat accumulation to be consistent with the standard case. In the proposed strategy, a specific length of scanning line without laser energy was added to each short scanning line, making each scanning line of the same length. The temperature simulation results of 1 mm thin-walled specimen indicated that the conventional scanning strategy could easily drive a harsh increase in peak temperature, further leading to a harsh increase in melt pool size. After applying the optimized scanning strategy, the peak temperature and melt pool size of the 1 mm thin-walled specimen were almost similar to those of the standard specimen. Meanwhile, the corresponding experiments indicated that the average surface roughness and hardness of 1 mm thin-walled case processed by conventional scanning was Ra70 and 320 HV10. The deformation and bumpy area could be observed on the surface, the porosity was high, and the grain size tended to be larger. After optimization, the average surface roughness was decreased to Ra37 and the hardness was increased to 370 HV10. In addition, the above metallurgical defects were greatly reduced. The above scanning strategy was integrated into the self-developed LPBF equipment and manufacturing process, and the thin-walled blade model was processed to verify the feasibility of the optimized scanning strategy for complex parts. Since the scanning strategy is independent of material and process parameters, it is beneficial to improve the process and quality stability of LPBF manufacturing complex parts.

AbstractWe examine Imam (1998) for a traffic model with a rectangular bus service zone and without a capacity constraint to discover that his traffic model will be degenerated to an infinite long zone with one service route. We provide revision for his solution approach and then explain the shortcoming of his traffic model without a capacity constraint. Our finding will be a first but crucial step to develop a more robust traffic design network system.

AbstractSzmidt and Kacprzyk (2005) defined a new similarity measure for two intuitionistic fuzzy sets to incorporate the difference between intuitionistic fuzzy set and its complement. However, we have found a counter example to demonstrate that sometimes the similarity measure they defined is not reasonable. Moreover, we offered a comprehensive study for their application, which will help future researchers apply similarity measures to application problems.

Venoms frequently co-opt host immune responses, so study of their mode of action can provide insight into novel inflammatory pathways. Using bee and wasp venom responses as a model system, we investigated whether venoms contain CD1-presented antigens. Here, we show that venoms activate human T cells via CD1a proteins. Whereas CD1 proteins typically present lipids, chromatographic separation of venoms unexpectedly showed that stimulatory factors partition into protein-containing fractions. This finding was explained by demonstrating that bee venom–derived phospholipase A2 (PLA2) activates T cells through generation of small neoantigens, such as free fatty acids and lysophospholipids, from common phosphodiacylglycerides. Patient studies showed that injected PLA2 generates lysophospholipids within human skin in vivo, and polyclonal T cell responses are dependent on CD1a protein and PLA2. These findings support a previously unknown skin immune response based on T cell recognition of CD1a proteins and lipid neoantigen generated in vivo by phospholipases. The findings have implications for skin barrier sensing by T cells and mechanisms underlying phospholipase-dependent inflammatory skin disease.

AbstractDong and Wong (1987) developed an algorithm derive the fuzzy weighted average for fuzzy numbers with fuzzy weights. Liou and Wang (1992) provided an improved method for Dong and Wong (1987) to reduce the computation. Guh et al. (2001) proposed a linear programming approach and then they mentioned that their approach is much more powerful then the original nonlinear one. In this note, we will analysis their approach to point out that their approach is interesting but tedious. The same example of Dong and Wong (1987) and Guh et al. (2001) are examined to support out findings.

A chiral Rh catalyst was immobilized on the surface of glass slide, and the heterogeneous catalyst exhibited good catalytic efficiency for asymmetric transfer hydrogenation (ATH) of aromatic ketones in aqueous medium.

AbstractReview of “Interregional Recognition and Enforcement of Civil and Commercial Judgments” by Professor Jie Huang (Oxford and Portland, Oregon: Hart Publishing, 2014) which analyses the status quo of judgment recognition and enforcement in the Mainland China, Macao and Hong Kong under the ‘One Country, Two Systems’ regime. The book also presents a comparative study of the interregional recognition and enforcement of judgments in the US and EU.

A rapid growth in the number of vehicles contributes to more and more attention on vehicular ad hoc network (VANET) recently, and ensuring security plays a significant role in maintaining its stable operation. Because of some variable environmental factors, its impossible to evaluate a precise value of packets transmission success rate. To reduce the influence of errors on detection, we develop a novel two-person zero-sum intrusion detection game model for formulating confrontation behavior between intrusion detection system (IDS) and malicious node.

CD1c is expressed with high density on human dendritic cells (DCs) and B cells, yet its antigen presentation functions are the least well understood among CD1 family members. Using a CD1c-reactive T cell line (DN6) to complete an organism-wide survey of M. tuberculosis lipids, we identified C32 phosphomycoketide (PM) as a previously unknown molecule and a CD1c-presented antigen. CD1c binding and presentation of mycoketide antigens absolutely required the unusual, mycobacteria-specific lipid branching patterns introduced by polyketide synthase 12 (pks12). Unexpectedly, one TCR responded to diversely glycosylated and unglycosylated forms of mycoketide when presented by DCs and B cells. Yet cell-free systems showed that recognition was mediated only by the deglycosylated phosphoantigen. These studies identify antigen processing of a natural bacterial antigen in the human CD1c system, indicating that cells act on glycolipids to generate a highly simplified neoepitope composed of a sugar-free phosphate anion. Using knowledge of this processed antigen, we generated human CD1c tetramers, and demonstrate that CD1c–PM complexes stain T cell receptors (TCRs), providing direct evidence for a ternary interaction among CD1c-lipid-TCR. Furthermore, PM-loaded CD1c tetramers detect fresh human T cells from peripheral blood, demonstrating a polyclonal response to PM antigens in humans ex vivo.

Aggregation structure and properties such as crystallinity, orientation, mechanical properties, boiling water shrinkage of high-shrinkage component, low-shrinkage component, and the bi-shrinkage yarns which are spun at different process conditions are characterized and tested. The high-shrinkage component and low-shrinkage component spin individually, the bi-shrinkage yarns spun by one-step spinning process. The research indicates that with the spinning speed increases, the degree of crystallinity and orientation of the high-shrinkage component increases, and its tensile strength increases, elongation at break decreases, boiling water shrinkage attain the highest value when the spinning speed is 3,000 m/min; With draft ratio decreased, the orientation, crystallinity, tensile strength, initial modulus of the low shrinkage component decrease, and its elongation at break, boiling water shrinkage increases; as the draft ratio decrease, BSY crystallinity decreased, orientation first increases, then decreases, strength, initial modulus decrease slightly, boiling water shrinkage increases; H1 increases from 80 oC to 95 oC, BSY crystallinity gradually increased; degree of orientation decrease, strength, initial modulus increases and elongation decreases, boiling water shrinkage increases firstly,and decreases slightly afterwards; with the H2 temperature increases, BSY crystallinity increase, orientation first increased and then decreased slightly,the tensile strength reduce a little, elongation at break increase, initial modulus decreased, boiling water shrinkage decreased.

Cu-15Ni-8Sn alloy with layer-by-layer periodic heterogeneous microstructures composed of ultrafine equiaxed (~2.6 μm) and coarse columnar (~12.8 μm) grains was successfully fabricated by laser powder bed fusion (LPBF) additive manufacturing. The microstructures were composed of Sn-depleted α-Cu (Ni, Sn) matrix and Sn-rich γ-(CuxNi1-x)3Sn nano-precipitates. The γ nano-precipitates were found to be mainly uniformly distributed at the melt pool boundaries due to Sn reverse segregation, as though the densely distributed seeds on the surface of a strawberry. The interesting periodic bi-modal microstructure exhibited a simultaneous positive effect on the enhancement of strength and ductility. The yield strength, ultimate tensile strength and elongation at break were (474.04±2.88) MPa, (584.36±4.74) MPa and (14.29±1.78)%, respectively. Remarkable improvements of 12% and 286% in the yield strength and elongation at break were achieved compared with those cast counterparts reported in the published literature. The high dislocations density (~6.78×1014m-2) were the dominant source of high strength and contributed ~49% to the yield strength according to the theoretical calculation. Massive dislocation cells were generated around the γ nano-precipitates during tensile deformation, improving the dislocation storage capacity and the work hardening ability. These findings validated the LPBF printability and the property enhancement of Cu-15Ni-8Sn and provided a promising strategy for the design of high strength and ductility copper alloys through layered precipitation microstructures.

The anti-inflammatory effects of pranlukast, an antagonist of cysteinyl leukotriene receptor 1, may be rendered not only by antileukotriene activity but also by other pharmacological activities. Previous studies indicate that pranlukast reduces ischemic tissue injury partially through decreasing vascular permeability, but its effect on ischemic injury in endothelial cells is not known. Thus, in this study, we investigated the effect of pranlukast on ischemia-like injury induced by oxygen-glucose deprivation (OGD) in EA.hy926 cells, a human endothelial cell line, and the possible mechanisms. We found that cell viability was reduced, lactate dehydrogenase release was increased 4-8 hours after OGD, and necrosis was induced 8 hours after OGD. Production of reactive oxygen species (ROS) increased by 211%, 176%, and 128%, respectively, 0.5, 1, and 2 hours after OGD. Nuclear factor-κB (NF-κB) was translocated to the nuclei 4-8 hours after OGD. Pranlukast ameliorated the reduced viability, the increased lactate dehydrogenase release, and necrosis after OGD. It also reduced ROS production and inhibited NF-κB nuclear translocation after OGD. The ROS scavenger, edaravone, inhibited OGD-induced nuclear translocation of NF-κB as well. Edaravone and pyrrolidine dithiocarbamate (a specific NF-κB inhibitor) protected endothelial cells from the OGD-induced injury. However, zileuton, a 5-lipoxygenase inhibitor, did not affect the cell injury, ROS production, and NF-κB nuclear translocation after OGD. The exogenous leukotriene D4 did not induce cell injury, ROS production, and NF-κB translocation. Thus, we conclude that pranlukast protects endothelial cells from ischemia-like injury via decreasing ROS production and inhibiting NF-κB activation, which is leukotriene independent.

The dynamic behaviors of short fiber/polymer composite powders in powder paving process of additive manufacturing are investigated by discrete element method simulations. Two typical forms of powder paving, counter-rolling and scraping, are performed with mixed carbon fibers/polyamide12 powders. It is found that the compaction of the mixed powders in the counter-rolling form powder paving is stronger than that in the scraping form. With the same paving speed and layer thickness, the powder layer obtained from the counter-rolling form powder paving is denser. For both forms of powder paving, the powder layer density decreases with the increasing of the paving speed. Finally, the increase of the fiber length will reduce the spreadability of the mixed powders, and hence decreases the packing density of the powder layer. The negative effect of the fiber length is relatively weak in the counter-rolling form powder paving due to the compaction of the roller.

Dendritic cells (DCs) process and present bacterial and endogenous lipid antigens in complex with CD1 molecules to T cells and invariant natural killer T (NKT) cells. However, different types of DCs, such as blood myeloid DCs and skin Langerhans cells, exhibit distinct patterns of CD1a, CD1b, CD1c, and CD1d expression. The regulation of such differences is incompletely understood. Here, we initially observed that monocyte-derived DCs cultured in an immunoglobulin-rich milieu expressed CD1d but not CD1a, CD1b, and CD1c, whereas DCs cultured in the presence of low levels of immunoglobulins had an opposite CD1 profile. Based on this, we tested the possibility that immunoglobulins play a central role in determining these differences. IgG depletion and intravenous immunoglobulin (IVIg) add-in experiments strongly supported a role for IgG in directing the CD1 expression profile. Blocking experiments indicated that this effect was mediated by FcγRIIa (CD32a), and quantitative polymerase chain reaction data demonstrated that regulation of the CD1 profile occurred at the gene expression level. Finally, the ability of DCs to activate CD1-restricted NKT cells and T cells was determined by this regulatory effect of IgG. Our data demonstrate an important role for FcγRIIa in regulating the CD1 antigen presentation machinery of human DCs.

Dendritic cells (DCs) process and present bacterial and endogenous lipid antigens in complex with CD1 molecules to T cells and invariant natural killer T (NKT) cells. However, different types of DCs, such as blood myeloid DCs and skin Langerhans cells, exhibit distinct patterns of CD1a, CD1b, CD1c, and CD1d expression. The regulation of such differences is incompletely understood. Here, we initially observed that monocyte-derived DCs cultured in an immunoglobulin-rich milieu expressed CD1d but not CD1a, CD1b, and CD1c, whereas DCs cultured in the presence of low levels of immunoglobulins had an opposite CD1 profile. Based on this, we tested the possibility that immunoglobulins play a central role in determining these differences. IgG depletion and intravenous immunoglobulin (IVIg) add-in experiments strongly supported a role for IgG in directing the CD1 expression profile. Blocking experiments indicated that this effect was mediated by FcγRIIa (CD32a), and quantitative polymerase chain reaction data demonstrated that regulation of the CD1 profile occurred at the gene expression level. Finally, the ability of DCs to activate CD1-restricted NKT cells and T cells was determined by this regulatory effect of IgG. Our data demonstrate an important role for FcγRIIa in regulating the CD1 antigen presentation machinery of human DCs.

CD1c-mediated T cells are activated by a mycobacterial phospholipid antigen whose carbohydrate structure precisely corresponds to mammalian mannosyl β-1-phosphodolichol (MPD), but contains an unusual lipid moiety. Here, we show that this T cell antigen is a member of a family of branched, alkane lipids that vary in length (C30-34) and are produced by medically important mycobacteria such as M. tuberculosis and M. bovis Bacille-Calmette-Guerin. The alkane moiety distinguished these mycobacterial lipid antigens from mammalian MPDs and was necessary for activation of CD1c-restricted T cells, but could not be accounted for by any known lipid biosynthetic pathway. Metabolic labeling and mass spectrometric analyses suggested a mechanism for elongating lipids using alternating C2 and C3 units, rather than C5 isopentenyl pyrophosphate. Inspection of the M. tuberculosis genome identified one candidate gene, pks12, which was predicted to encode the largest protein in M. tuberculosis, consisting of 12 catalytic domains that correspond to key steps in the proposed pathway. Genetic deletion and complementation showed that Pks12 was necessary for antigen production, but did not affect synthesis of true isoprenols. These studies establish the genetic and enzymatic basis for a previously unknown type of polyketide, designated mycoketide, which contains a lipidic pathogen-associated molecular pattern.

The ß chain of high-affinity IgE receptor (Fc?RIß) has been proposed as a candidate gene for asthma and atopic diseases.

T cells recognize microbial glycolipids presented by CD1 proteins, but there is no information regarding the generation of natural glycolipid antigens within infected tissues. Therefore, we determined the molecular basis of CD1b-restricted T cell recognition of mycobacterial glycosylated mycolates, including those produced during tissue infection in vivo. Transfection of the T cell receptor (TCR) α and β chains from a glucose monomycolate (GMM)-specific T cell line reconstituted GMM recognition in TCR-deficient T lymphoblastoma cells. This TCR-mediated response was highly specific for natural mycobacterial glucose-6-O-(2R, 3R) monomycolate, including the precise structure of the glucose moiety, the stereochemistry of the mycolate lipid, and the linkage between the carbohydrate and the lipid. Mycobacterial production of antigenic GMM absolutely required a nonmycobacterial source of glucose that could be supplied by adding glucose to media at concentrations found in mammalian tissues or by infecting tissue in vivo. These results indicate that mycobacteria synthesized antigenic GMM by coupling mycobacterial mycolates to host-derived glucose. Specific T cell recognition of an epitope formed by interaction of host and pathogen biosynthetic pathways provides a mechanism for immune response to those pathogenic mycobacteria that have productively infected tissues, as distinguished from ubiquitous, but innocuous, environmental mycobacteria.

We optimized lipidomics methods to broadly detect endogenous lipids bound to cellular CD1a proteins. Whereas membrane phospholipids dominate in cells, CD1a preferentially captured sphingolipids, especially a C42, doubly unsaturated sphingomyelin (42:2 SM). The natural 42:2 SM but not the more common 34:1 SM blocked CD1a tetramer binding to T cells in all human subjects tested. Thus, cellular CD1a selectively captures a particular endogenous lipid that broadly blocks its binding to TCRs. Crystal structures show that the short cellular SMs stabilized a triad of surface residues to remain flush with CD1a, but the longer lipids forced the phosphocholine group to ride above the display platform to hinder TCR approach. Whereas nearly all models emphasize antigen-mediated T cell activation, we propose that the CD1a system has intrinsic autoreactivity and is negatively regulated by natural endogenous inhibitors selectively bound in its cleft. Further, the detailed chemical structures of natural blockers could guide future design of therapeutic blockers of CD1a response.

The development of two programs based upon a microcomputer system for simulation of dynamic systems is described. The usefulness of the two programs developed for educational and research purposes is demonstrated. Samples of results obtained are also included.

The masses of the light hadrons are calculated in terms of the cloudy bag model with self-energies due to both gluon and pion exchange. By use of a type of pion-quark interaction which incorporates the finite extent of the pion the convergent self-energy due to pion exchange is obtained. The difficulties in the bag models which only include one type of the self-energies can be removed by taking account of both and the baryon spectrum is reproduced well. It is found that these self-energies are large but have opposite effect on the masses of the hadrons.

Deuteron electrodisintegration cross section in threshold region has been calculated by using the Kisslinger's hybrid quark-hadron model, including isoscalar MEC. The appearance of the second maximum can be explained by the dependence of cross section on , and may be the signal of six-quark clusters.

A method for tuning PID controllers for a class of processes with dead time is presented. The controller settings are so determined that the overall system output satisfies a predefined control objective. Effectiveness of the proposed method for tuning controllers is illustrated by means of numerical examples.

The d6 tungsten phenyldiazene complex [trans, trans-W (NH=NPh) (CO)2(NO) (PPh3)2+][PF6−] (1a) reacted with ammonia, methylamine or hydrazine at −78°C giving [trans-W (NH=NPh) (CO) (NO) (NH2R) (PPh3)2+][PF6−] (2a, R = H; 2b, R = CH3; 2c, R = NH2) as purple salts in good yield, along with one equivalent of carbon monoxide. Sodium azide reacted with la or the p-tolyldiazene derivative [trans, trans-W(NH=NTol)(CO)2(NO)(PPh3)2+][PF6−] (1b) in the presence of a proton source giving CO and [trans, trans-W(NHNHR)(N3)2(NO) (PPh3)2] (3a, R = Ph, 3b, R = Tol), neutral bis (azido) complexes containing arylhydrazido ligands. These reactions involving nitrogen nucleophiles are in striking contrast with the known activity of 1a,b with Br− that gives [trans-W(Br)(CO)2(NO)(PPh3)2] and free NH = NPh.

LetU(x), xεℤd-|0}, be a nonnegative even function such that Σx≠0U(x)≦1. In this paper, we consider an infinite system of stochastic processξt(x); xεℤdwith the following mechanism: at each sitex, after mean 1 exponential waiting time,ξt(x) is replaced by a Gaussian random variable with meanΣy≠xξt(y) U(y-x)and variance 1. It is understood here that all the interactions are independent of one another. The behavior of this system will be investigated and some ergodic theorems will be derived. The results strongly depend whetherΣx≠0U(x)<1 or =1.

In this article the author discusses the scope of database copyright protection under the Database Directive citing the court case Football Dataco Ltd. v. Yahoo! UK Ltd. It mentions the dispute between Dataco and Yahoo on the exploitation of data and rights related to football matches which led to a trial confirming that database copyright does not subsist in Dataco's football fixtures lists. It also notes the questions referred to the European Court of Justice (ECJ) regarding the copyright.

A crystallographic study using synchrotron radiation shows that a C&z.dbd6;C bond of one phenyl group of a PPh3 ligand bonds to Mo in [Cp(CO)2(PPh3)Mo]+, resulting in an unusual bonding mode in which PPh3 functions as a chelating four-electron donor ligand.