Structured soils are characterized by the presence of inter- and intra-aggregate pore systems and aggregates, which show varying chemical, physical, and biological properties depending on the aggregate type and land u...Structured soils are characterized by the presence of inter- and intra-aggregate pore systems and aggregates, which show varying chemical, physical, and biological properties depending on the aggregate type and land use system. How far these aspects also affect the ion exchange processes and to what extent the interaction between the carbon distribution and kind of organic substances affect the internal soil strength as well as hydraulic properties like wettability are still under discussion. Thus, the objective of this research was to clarify the effect of soil aggregation on physical and chemical properties of structured soils at two scales: homogenized material and single aggregates. Data obtained by sequentially peeling off soil aggregates layers revealed gradients in the chemical composition from the aggregate surface to the aggregate core. In aggregates from long term untreated forest soils we found lower amounts of carbon in the external layer, while in arable soils the differentiation was not pronounced. However, soil aggregates originating from these sites exhibited a higher concentration of microbial activity in the outer aggregate layer and declined towards the interior. Furthermore, soil depth and the vegetation type affected the wettability. Aggregate strength depended on water suction and differences in tillage treatments.展开更多
In neonates, persistent hyperinsulinemic hypoglycemia (PHH) is associated with nesidioblastosis. In adults, PHH is usually caused by solitary benign insulinomas. We report on an adult patient who suffered from insulin...In neonates, persistent hyperinsulinemic hypoglycemia (PHH) is associated with nesidioblastosis. In adults, PHH is usually caused by solitary benign insulinomas. We report on an adult patient who suffered from insulin-de- pendent diabetes mellitus, and subsequently developed PHH caused by diffuse nesidioblastosis. Mutations of the MEN1 and Mody 2/3 genes were ruled out. Preoperative diagnostic procedures, the histopathological criteria and the surgical treatment options of adult nesidioblastosis are discussed. So far only one similar case of adult nesidioblastosis subsequent to diabetes mellitus Ⅱ has been reported in the literature. In case of conversion of diabetes into hyperinsulinemic hypoglycemia syndrome, nesidioblastosis in addition to insulinoma should be con- sidered.展开更多
Subcutaneous panniculitis-like T cell lymphoma(SPTCL) is a very rare variant of non-Hodgkin's lymphoma. Currently, there is no standard imaging method for staging of SPTCL nor for assessment of treatment response....Subcutaneous panniculitis-like T cell lymphoma(SPTCL) is a very rare variant of non-Hodgkin's lymphoma. Currently, there is no standard imaging method for staging of SPTCL nor for assessment of treatment response. Here, we describe our use of fluorine-18 fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(PET/CT) for staging and monitoring of treatment response in 3 cases of SPTCL. Primary staging by PET/CT showed that all 3 patients had multiple foci in the subcutaneous fat tissue, with SUVmax from 10.5 to 14.6. Involvement of intra-abdominal fat with high SUVmax was identified in 2 of the patients. Use of the triple drug regimen of gemcitabine, cisplatin and methylprednisolone(commonly known as "GEM-P") as first-line therapy or second-line therapy facilitated complete metabolic response for all 3 cases. FDG PET/CT provides valuable information for staging and monitoring of treatment response and can reveal occult involvement of the intraabdominal visceral fat. High FDG uptake on pre-treatment PET can identify patients with aggressive disease and help in selection of first-line therapy.展开更多
The contribution redefines the concept of “terra-forming” and the basically technical term “water works” from a sociological interpretation of metabolism: since human reproduction emancipated from mere participati...The contribution redefines the concept of “terra-forming” and the basically technical term “water works” from a sociological interpretation of metabolism: since human reproduction emancipated from mere participation from nature, it became, at least, a systematic transformation of nature. Irrigation and drainage became the twin brothers of agriculture and mining, the most important modifiers of both metabolism and nature itself. From the early “hydraulic” toward modern “industrial” societies, the systemic conditions of reproduction evolved hand in hand with accompanying social dynamics.展开更多
Two novel copper complexes (<strong>1,2</strong>) with N,O-donor ligands were synthesized by reaction of copper(II) malonates with 3,3’-bis(pyrazolyl)pentane and 4,4’-trimethylenedipyridine in methanol a...Two novel copper complexes (<strong>1,2</strong>) with N,O-donor ligands were synthesized by reaction of copper(II) malonates with 3,3’-bis(pyrazolyl)pentane and 4,4’-trimethylenedipyridine in methanol at moderate temperature. These compounds were characterized by elemental analysis, UV-VIS, IR spectroscopies and powder X-ray diffraction analyses. Compound (<strong>1</strong>) melts at higher temperature (202°C) than compound (<strong>2</strong>) (100<span style="white-space:normal;">°</span>C). The IR spectra showed typical vibrations related to C=N and C=C, characteristic of pyrazolyl and pyridine ligands.展开更多
Background & Aims: To investigate the efficacy and safety of certolizumab pegol (a polyethylene-glycolated Fab’ frag-ment of anti-tumor necrosis factor, CDP870) in Crohn’ s disease. Methods: In a placebo-control...Background & Aims: To investigate the efficacy and safety of certolizumab pegol (a polyethylene-glycolated Fab’ frag-ment of anti-tumor necrosis factor, CDP870) in Crohn’ s disease. Methods: In a placebo-controlled, phase II study, 292 patients with moderate to severe Crohn’ s disease received subcutaneous certolizumab 100, 200, or 400 mg or placebo at weeks 0, 4, and 8. The primary end point was the percentage of patients with a clinical response at week 12 (a Crohn’ s Disease Activity Index decrease of < 100 points or remission [Crohn’ s Disease Activity Index ≤ 150 points]) in the intent-to-treat population. Results: All certolizumab doses produced significant clinical benefit over placebo at week 2 (placebo, 15.1% ; certolizumab 100 mg, 29.7% [P = .033]; 200 mg, 30.6% [P = .026]; 400 mg, 33.3% [P = .010]). At all time points, the clinical response rates were highest for certolizumab 400 mg, greatest at week 10 (certolizumab 400 mg, 52.8% ; placebo, 30.1% ; P = .006) but not significant at week 12 (certolizumab 400 mg, 44.4% ; placebo, 35.6% ; P = .278). Patients with baseline Creactive protein levels of 10 mg/L or greater (n = 119) showed clearer separation between active treatment and placebo (week 12 clinical res-ponse: certolizumab 400 mg, 53.1% ; placebo, 17.9% ; P = .005; post hoc analysis) owing to a lower placebo response rate than patients with C-reactive protein levels of less than 10 mg/L. Adverse events were similar among groups. Conclusions: Certolizumab 400mg may be effective and iswell tolerated in patients with active Crohn’ s disease. High placebo response rates in the large patient subgroup with low C-reactive protein levels may have obscured statistical separation between certolizumab and placebo. Ongoing phase III trials are necessary to establish the clinical efficacy of certolizumab.展开更多
The early fixation of bone screws after surgical implantation still remains a challenge in the field of traumatology. Whilst hydroxyapatite (HA) coatings are known to enhance the fixation of implants;their removal at ...The early fixation of bone screws after surgical implantation still remains a challenge in the field of traumatology. Whilst hydroxyapatite (HA) coatings are known to enhance the fixation of implants;their removal at a later time-point may be problematic. An HA coating has been developed to demonstrate that both implant fixation and safe removal are feasible in the same design. Accordingly the aim of this study was to compare the In-Vivo performance of thin biomimetic HA coated titanium screws to uncoated counterparts used as control after bilateral implantation in the femoral condyle of 36 New Zealand White Rabbits. The screws were analysed macroscopically, by histology, micro-CT and biomechanically at both two and six weeks post-implantation. The HA coated screws demonstrated excellent biocompatibility. At two weeks the HA coated screws demonstrated a significant increase in removal torque values as well as a strong trend towards higher pull-out forces. In addition histology confirmed a higher degree of osseointegration and direct bone to implant contact. At six weeks no difference in pull-out force and removal torque could be detected. SEM images confirmed the absence of any residual HA coating indicating a fast coating degradation In-Vivo. The low level of removal torque after full osseointegration at 6 weeks supports the feasibility of safe and easy removal of the implant. The HA coating under study appears to offer a unique characteristic of enhanced fixation with a minimal increase in removal torque after full osseointegration. This may be of value in clinical applications where it is necessary to assure both screw fixation and later removal.展开更多
In a recent article published in Science,Sharma et al.describes the essential role of saposins in cross-presentation of tumor membraneassociated antigens by dendritic cells(DC)to CD8^(+)T cells.1 However,antigen cross...In a recent article published in Science,Sharma et al.describes the essential role of saposins in cross-presentation of tumor membraneassociated antigens by dendritic cells(DC)to CD8^(+)T cells.1 However,antigen cross-presentation,which is fundamental in cancer cell elimination,is hindered in tumor DC by hyperglycosylation of the common saposin precursor prosaposin(pSAP)leading to impaired T cell tumor immunity-yet,the potential of recombinant pSAP to re-establish T cell responses may offer a novel way to counteract immune evasion in a therapeutic approach.展开更多
In a recent article published in Science,Dart and colleagues reported that colonic T cells expressing the Vγ4 T-cell receptor(TCR)interact with epithelial butyrophilin-like(BTNL)proteins BTNL3 and BTNL8 in healthy in...In a recent article published in Science,Dart and colleagues reported that colonic T cells expressing the Vγ4 T-cell receptor(TCR)interact with epithelial butyrophilin-like(BTNL)proteins BTNL3 and BTNL8 in healthy individuals,and they observed a depletion of Vγ4 T cells in inflammatory bowel diseases with renormalization associated with disease remission.1 This paper identifies the BTNL/Vγ4 axis as a new disease modifier in IBD.展开更多
Eucommia ulmoides Oliv.(EuO),also known as Duzhong,native to China,has been reported to have antioxidative function,but its cellular mechanism is not fully examined yet.We investigated inhibitory effects of EuO leaf e...Eucommia ulmoides Oliv.(EuO),also known as Duzhong,native to China,has been reported to have antioxidative function,but its cellular mechanism is not fully examined yet.We investigated inhibitory effects of EuO leaf ethanol extracts on H2O2-induced apoptosis in rat osteoblastic MC3T3-E1 cells and underlying mechanisms.Locally-grown Duzhong leaves were extracted with ethanol.MC3T3-E1 cells were treated with EuO (6.25,12.5,25,50,and 100 μg/ml) for 24 h,and then H2O2 (800 μmol/L) for an additional 24 h.Cell survival rate,percentage of apoptosis,and expressions of caspases 3,6,7,and 9 were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay,microscopic analysis,Western blotting,and reverse transcription polymerase chain reaction (RT-PCR).The final EuO leaf ethanol extract powder was detected to contain caffeotannic acid at 58 mg/g and geniposide at 3.45 mg/g by high performance liquid chromatography (HPLC).EuO remarkably restrained cell oxidative damage and increased cell survival rate in a dose-dependent manner: 0 μg/ml,0.21;6.25 μg/ml,0.28;12.5 μg/ml,0.31;25 μg/ml,0.48;50 μg/ml,0.54;and 100 μg/ml,0.66 (P<0.05),with the half-effective concentration being around 25 μg/ml.MTT results were confirmed by microscopic analysis.Western blotting and RT-PCR analyses showed that the expressions of caspases 3,6,7,and 9 were significantly decreased in the EuO-treated cells compared with the control (EuOand H2O2-free) (P<0.05),with the half-effective concentration of EuO ranging from 12.5 to 25 μg/ml.We conclude that the ethanol-extracted EuO leaf extracts promoted the growth of MC3T3-E1 cells,and suppressed the H2O2-induced apoptosis in a rat MC3T3-E1 osteogenic cell model,likely due to the inhibition of caspases’ activities.The results indicate that EuO is a potent antioxidant,which may contribute to its many cellular protective functions,including the promotion of bone growth.展开更多
The elusive task of defining the character of 76 T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and p T cell receptor genes o...The elusive task of defining the character of 76 T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and p T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, 76 T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and ap T cells are particularly well equipped to respond to the 'missing self' and the 'dangerous non-self', respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the 'safe non-self' and dealing with the inevitable 'distressed self', and it is within this more complex realm 76 T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human 76 T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life's many stresses.展开更多
As a typical biometric cue with great diversities, smile is a fairly influential signal in social interaction, which reveals the emotional feeling and inner state of a person. Spontaneous and posed smiles initiated by...As a typical biometric cue with great diversities, smile is a fairly influential signal in social interaction, which reveals the emotional feeling and inner state of a person. Spontaneous and posed smiles initiated by different brain systems have differences in both morphology and dynamics. Distinguishing the two types of smiles remains challenging as discriminative subtle changes need to be captured, which are also uneasily observed by human eyes. Most previous related works about spontaneous versus posed smile recognition concentrate on extracting geometric features while appearance features are not fully used, leading to the loss of texture information. In this paper, we propose a region-specific texture descriptor to represent local pattern changes of different facial regions and compensate for limitations of geometric features. The temporal phase of each facial region is divided by calculating the intensity of the corresponding facial region rather than the intensity of only the mouth region. A mid-level fusion strategy of support vector machine is employed to combine the two feature types. Experimental results show that both our proposed appearance representation and its combination with geometry-based facial dynamics achieve favorable performances on four baseline databases: BBC, SPOS, MMI, and UvA-NEMO.展开更多
Solid lithium ion conducting electrochemical cells using LiSiPO as solid electrolyte and Li2CO3 mixed with Au as electrodes were prepared and employed as chemical sensors for the detection of CO2 gas.The EMF of the ce...Solid lithium ion conducting electrochemical cells using LiSiPO as solid electrolyte and Li2CO3 mixed with Au as electrodes were prepared and employed as chemical sensors for the detection of CO2 gas.The EMF of the cell depends on the concentration of CO2 in air according to the partial pressure dependence of Nernst's law in the investigated range from 100 to 2000 ppm over the temperature range from 473 K to 673 K.展开更多
The aim of this study is to evaluate the influence of Tooth Mousse (TM) application, smear layer removal, and storage time on resin-dentin microtensile bond strength (pTBS). Dentin specimens were divided into two ...The aim of this study is to evaluate the influence of Tooth Mousse (TM) application, smear layer removal, and storage time on resin-dentin microtensile bond strength (pTBS). Dentin specimens were divided into two groups: (1) smear layer covered; (2) smear layer removed using 15% EDTA for 90 s. In each group, half the specimens were treated once with TM for 60 min. After bonding procedures using a two-step self-etching adhesive (Clearfil SE Bond (CSE); Kuraray Medical, Tokyo, Japan), an all-in-one adhesive (G-Bond (GB); GC Corp, Tokyo, Japan), and a total-etch adhesive (Adper Single Bond 2 (SB); 3M ESPE, St. Paul, MN, USA), the specimens were stored for 3 d or 6 months in deionized water at 37 ℃, and pTBS was tested and analyzed. With the exception of SB (no TM application) and GB, the pTBS was significantly increased for CSE and SB using EDTA pre-conditioning and 3 d of storage (P≤0.001). Bond strength of GB decreased significantly when using EDTA (3 d storage, P〈0.05). TM application only increased the pTBS of GB (no EDTA) and SB (with EDTA) after 3 d (P≤0.02). Comparing the adhesives after 3 d of storage, CSE exhibited the greatest pTBS values followed by GB and SB (P≤0.02). The factors of adhesive, EDTA, and TM did not show any significant impact on pTBS when specimens were stored for 6 months (P〉0.05). The additional application of TM and EDTA for cavity preparation seems only to have a short-term effect, and no influence on pTBS of dentin bonds after a period of 6 months.展开更多
Objective: The aim of the current study was to evaluate the effect of ultraviolet(UV) photofunctionalization of dental titanium implants with exposure to the oral cavity on osseointegration in an animal model. Meth...Objective: The aim of the current study was to evaluate the effect of ultraviolet(UV) photofunctionalization of dental titanium implants with exposure to the oral cavity on osseointegration in an animal model. Methods: Forty-eight titanium implants(Camlog~? Conelog~? 4.3 mmx9.0 mm) were placed epicrestally into the edentulous jaws of three minipigs and implant stability was assessed by measuring the implant stability quotient(ISQ). Prior to implantation half of the implants were photofunctionalized with intense UV-light. After three months, the implants were exposed and ISQ was measured again. After six months of implant exposure, the minipigs were sacrificed and the harvested specimens were analyzed using histomorphometric, light, and fluorescence microscopy. Main results: Forty-two of 48 implants osseointegrated. The overall mean bone-implant contact area(BIC) was(64±22)%. No significant differences were found in BIC or ISQ value(multivariate analysis of variance(MANOVA), P〉0.05) between implants with and without exposure to UV photofunctionalization. Conclusions: No significant effects were observed on osseointegration of dental titanium implants nine months after exposure of UV photofunctionalization.展开更多
Last year,we published a paper in this journal in which we described the effects of vitamin C and its phospho-modified version(phospho-vitamin C,pVC)on the in vitro activation,proliferation,and effector function of hu...Last year,we published a paper in this journal in which we described the effects of vitamin C and its phospho-modified version(phospho-vitamin C,pVC)on the in vitro activation,proliferation,and effector function of humanγδT cells.^(1)We were delighted to see that our study was recently highlighted in a Comment in this journal by Meraviglia and Dieli,2 underscoring the potential interest in using vitamin C to promoteγδT cell activity for use in cancer immunotherapy.Our study was a joint publication with our Chinese collaborators,headed by Prof.Zhinan Yin,with whom we share an interest in exploring the beneficial effects of vitamin C on boosting the cellular immune response.In fact,Yin and colleagues initiated clinical studies on the adoptive transfer of allogeneicγδT cells expanded in the presence of vitamin C into cancer patients.A report of a clinical phase I study demonstrating the safety of allogeneicγδT cell transfer has recently been published in this journal,another collaborative effort of our two groups.^(3)展开更多
The differentiation and functional plasticity of T cells are transcriptionally and epigenetically regulated by signals imposed by the local cytokine milieu and a variety of additional factors,including vitamins.Vitami...The differentiation and functional plasticity of T cells are transcriptionally and epigenetically regulated by signals imposed by the local cytokine milieu and a variety of additional factors,including vitamins.Vitamin C has pleiotropic functions in the immune system.It exerts antioxidant activity,can directly kill selected tumor targets,promotes early T-cell differentiation,and enhances Th1 cytokine production in mature T cells[1,2].展开更多
Emerging antibiotic resistance is a major global health threat. The analysis of nucleic acid sequences linked to susceptibility phenotypes facilitates the study of genetic antibiotic resistance determinants to inform ...Emerging antibiotic resistance is a major global health threat. The analysis of nucleic acid sequences linked to susceptibility phenotypes facilitates the study of genetic antibiotic resistance determinants to inform molecular diagnostics and drug development. We collected genetic data (11,087 newly-sequenced whole genomes) and culture-based resistance profiles (10,991 out of the 11,087 isolates comprehensively tested against 22 antibiotics in total) of clinical isolates including 18 main species spanning a time period of 30 years. Species and drug specific resistance patterns were observed including increased resistance rates for Acinetobacter baumannii to carbapenems and for Escherichia coli to fluoroquinolones. Species-level pan-genomes were constructed to reflect the genetic repertoire of the respective species,including conserved essential genes and known resis-tance factors. Integrating phenotypes and genotypes through species-level pan-genomes allowed to infer gene–drug resistance associations using statistical testing. The isolate collection and the analysis results have been integrated into GEAR-base,a resource available for academic research use free of charge at https://gear-base.com.展开更多
基金Project supported by the fund of the DFG (Deutsche Forschung Gemeinschaft) as part of the DFG priority program 1090: 'Soils as source and sink for CO2-mechanisms and regulation of organic matter stabilization in soils' (No. DFG SPP 1090).
文摘Structured soils are characterized by the presence of inter- and intra-aggregate pore systems and aggregates, which show varying chemical, physical, and biological properties depending on the aggregate type and land use system. How far these aspects also affect the ion exchange processes and to what extent the interaction between the carbon distribution and kind of organic substances affect the internal soil strength as well as hydraulic properties like wettability are still under discussion. Thus, the objective of this research was to clarify the effect of soil aggregation on physical and chemical properties of structured soils at two scales: homogenized material and single aggregates. Data obtained by sequentially peeling off soil aggregates layers revealed gradients in the chemical composition from the aggregate surface to the aggregate core. In aggregates from long term untreated forest soils we found lower amounts of carbon in the external layer, while in arable soils the differentiation was not pronounced. However, soil aggregates originating from these sites exhibited a higher concentration of microbial activity in the outer aggregate layer and declined towards the interior. Furthermore, soil depth and the vegetation type affected the wettability. Aggregate strength depended on water suction and differences in tillage treatments.
文摘In neonates, persistent hyperinsulinemic hypoglycemia (PHH) is associated with nesidioblastosis. In adults, PHH is usually caused by solitary benign insulinomas. We report on an adult patient who suffered from insulin-de- pendent diabetes mellitus, and subsequently developed PHH caused by diffuse nesidioblastosis. Mutations of the MEN1 and Mody 2/3 genes were ruled out. Preoperative diagnostic procedures, the histopathological criteria and the surgical treatment options of adult nesidioblastosis are discussed. So far only one similar case of adult nesidioblastosis subsequent to diabetes mellitus Ⅱ has been reported in the literature. In case of conversion of diabetes into hyperinsulinemic hypoglycemia syndrome, nesidioblastosis in addition to insulinoma should be con- sidered.
文摘Subcutaneous panniculitis-like T cell lymphoma(SPTCL) is a very rare variant of non-Hodgkin's lymphoma. Currently, there is no standard imaging method for staging of SPTCL nor for assessment of treatment response. Here, we describe our use of fluorine-18 fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(PET/CT) for staging and monitoring of treatment response in 3 cases of SPTCL. Primary staging by PET/CT showed that all 3 patients had multiple foci in the subcutaneous fat tissue, with SUVmax from 10.5 to 14.6. Involvement of intra-abdominal fat with high SUVmax was identified in 2 of the patients. Use of the triple drug regimen of gemcitabine, cisplatin and methylprednisolone(commonly known as "GEM-P") as first-line therapy or second-line therapy facilitated complete metabolic response for all 3 cases. FDG PET/CT provides valuable information for staging and monitoring of treatment response and can reveal occult involvement of the intraabdominal visceral fat. High FDG uptake on pre-treatment PET can identify patients with aggressive disease and help in selection of first-line therapy.
文摘The contribution redefines the concept of “terra-forming” and the basically technical term “water works” from a sociological interpretation of metabolism: since human reproduction emancipated from mere participation from nature, it became, at least, a systematic transformation of nature. Irrigation and drainage became the twin brothers of agriculture and mining, the most important modifiers of both metabolism and nature itself. From the early “hydraulic” toward modern “industrial” societies, the systemic conditions of reproduction evolved hand in hand with accompanying social dynamics.
文摘Two novel copper complexes (<strong>1,2</strong>) with N,O-donor ligands were synthesized by reaction of copper(II) malonates with 3,3’-bis(pyrazolyl)pentane and 4,4’-trimethylenedipyridine in methanol at moderate temperature. These compounds were characterized by elemental analysis, UV-VIS, IR spectroscopies and powder X-ray diffraction analyses. Compound (<strong>1</strong>) melts at higher temperature (202°C) than compound (<strong>2</strong>) (100<span style="white-space:normal;">°</span>C). The IR spectra showed typical vibrations related to C=N and C=C, characteristic of pyrazolyl and pyridine ligands.
文摘Background & Aims: To investigate the efficacy and safety of certolizumab pegol (a polyethylene-glycolated Fab’ frag-ment of anti-tumor necrosis factor, CDP870) in Crohn’ s disease. Methods: In a placebo-controlled, phase II study, 292 patients with moderate to severe Crohn’ s disease received subcutaneous certolizumab 100, 200, or 400 mg or placebo at weeks 0, 4, and 8. The primary end point was the percentage of patients with a clinical response at week 12 (a Crohn’ s Disease Activity Index decrease of < 100 points or remission [Crohn’ s Disease Activity Index ≤ 150 points]) in the intent-to-treat population. Results: All certolizumab doses produced significant clinical benefit over placebo at week 2 (placebo, 15.1% ; certolizumab 100 mg, 29.7% [P = .033]; 200 mg, 30.6% [P = .026]; 400 mg, 33.3% [P = .010]). At all time points, the clinical response rates were highest for certolizumab 400 mg, greatest at week 10 (certolizumab 400 mg, 52.8% ; placebo, 30.1% ; P = .006) but not significant at week 12 (certolizumab 400 mg, 44.4% ; placebo, 35.6% ; P = .278). Patients with baseline Creactive protein levels of 10 mg/L or greater (n = 119) showed clearer separation between active treatment and placebo (week 12 clinical res-ponse: certolizumab 400 mg, 53.1% ; placebo, 17.9% ; P = .005; post hoc analysis) owing to a lower placebo response rate than patients with C-reactive protein levels of less than 10 mg/L. Adverse events were similar among groups. Conclusions: Certolizumab 400mg may be effective and iswell tolerated in patients with active Crohn’ s disease. High placebo response rates in the large patient subgroup with low C-reactive protein levels may have obscured statistical separation between certolizumab and placebo. Ongoing phase III trials are necessary to establish the clinical efficacy of certolizumab.
基金part of the 7^(th) Framework programme—BIODESIGN as well as the Swedish Science Council is gratefully acknowledged for financial support
文摘The early fixation of bone screws after surgical implantation still remains a challenge in the field of traumatology. Whilst hydroxyapatite (HA) coatings are known to enhance the fixation of implants;their removal at a later time-point may be problematic. An HA coating has been developed to demonstrate that both implant fixation and safe removal are feasible in the same design. Accordingly the aim of this study was to compare the In-Vivo performance of thin biomimetic HA coated titanium screws to uncoated counterparts used as control after bilateral implantation in the femoral condyle of 36 New Zealand White Rabbits. The screws were analysed macroscopically, by histology, micro-CT and biomechanically at both two and six weeks post-implantation. The HA coated screws demonstrated excellent biocompatibility. At two weeks the HA coated screws demonstrated a significant increase in removal torque values as well as a strong trend towards higher pull-out forces. In addition histology confirmed a higher degree of osseointegration and direct bone to implant contact. At six weeks no difference in pull-out force and removal torque could be detected. SEM images confirmed the absence of any residual HA coating indicating a fast coating degradation In-Vivo. The low level of removal torque after full osseointegration at 6 weeks supports the feasibility of safe and easy removal of the implant. The HA coating under study appears to offer a unique characteristic of enhanced fixation with a minimal increase in removal torque after full osseointegration. This may be of value in clinical applications where it is necessary to assure both screw fixation and later removal.
文摘In a recent article published in Science,Sharma et al.describes the essential role of saposins in cross-presentation of tumor membraneassociated antigens by dendritic cells(DC)to CD8^(+)T cells.1 However,antigen cross-presentation,which is fundamental in cancer cell elimination,is hindered in tumor DC by hyperglycosylation of the common saposin precursor prosaposin(pSAP)leading to impaired T cell tumor immunity-yet,the potential of recombinant pSAP to re-establish T cell responses may offer a novel way to counteract immune evasion in a therapeutic approach.
基金Open Access funding enabled and organized by Projekt DEAL.
文摘In a recent article published in Science,Dart and colleagues reported that colonic T cells expressing the Vγ4 T-cell receptor(TCR)interact with epithelial butyrophilin-like(BTNL)proteins BTNL3 and BTNL8 in healthy individuals,and they observed a depletion of Vγ4 T cells in inflammatory bowel diseases with renormalization associated with disease remission.1 This paper identifies the BTNL/Vγ4 axis as a new disease modifier in IBD.
基金Project (No.2007C33030) supported by the Science and Technology Program of Zhejiang Province,China
文摘Eucommia ulmoides Oliv.(EuO),also known as Duzhong,native to China,has been reported to have antioxidative function,but its cellular mechanism is not fully examined yet.We investigated inhibitory effects of EuO leaf ethanol extracts on H2O2-induced apoptosis in rat osteoblastic MC3T3-E1 cells and underlying mechanisms.Locally-grown Duzhong leaves were extracted with ethanol.MC3T3-E1 cells were treated with EuO (6.25,12.5,25,50,and 100 μg/ml) for 24 h,and then H2O2 (800 μmol/L) for an additional 24 h.Cell survival rate,percentage of apoptosis,and expressions of caspases 3,6,7,and 9 were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay,microscopic analysis,Western blotting,and reverse transcription polymerase chain reaction (RT-PCR).The final EuO leaf ethanol extract powder was detected to contain caffeotannic acid at 58 mg/g and geniposide at 3.45 mg/g by high performance liquid chromatography (HPLC).EuO remarkably restrained cell oxidative damage and increased cell survival rate in a dose-dependent manner: 0 μg/ml,0.21;6.25 μg/ml,0.28;12.5 μg/ml,0.31;25 μg/ml,0.48;50 μg/ml,0.54;and 100 μg/ml,0.66 (P<0.05),with the half-effective concentration being around 25 μg/ml.MTT results were confirmed by microscopic analysis.Western blotting and RT-PCR analyses showed that the expressions of caspases 3,6,7,and 9 were significantly decreased in the EuO-treated cells compared with the control (EuOand H2O2-free) (P<0.05),with the half-effective concentration of EuO ranging from 12.5 to 25 μg/ml.We conclude that the ethanol-extracted EuO leaf extracts promoted the growth of MC3T3-E1 cells,and suppressed the H2O2-induced apoptosis in a rat MC3T3-E1 osteogenic cell model,likely due to the inhibition of caspases’ activities.The results indicate that EuO is a potent antioxidant,which may contribute to its many cellular protective functions,including the promotion of bone growth.
文摘The elusive task of defining the character of 76 T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and p T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, 76 T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and ap T cells are particularly well equipped to respond to the 'missing self' and the 'dangerous non-self', respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the 'safe non-self' and dealing with the inevitable 'distressed self', and it is within this more complex realm 76 T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human 76 T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life's many stresses.
基金the National Natural Science Foundation of China (No. 60675025), the National High-Tech R&D Program (863) of China (No. 2006AA04Z247), the Scientific and Tech- nical Innovation Commission of Shenzhen Municipality, China (Nos. JCYJ20130331144631730 and JCYJ20130331144716089), and the Specialized Research Fund for the Doctoral Program of Higher Education, China (No. 20130001110011)
文摘As a typical biometric cue with great diversities, smile is a fairly influential signal in social interaction, which reveals the emotional feeling and inner state of a person. Spontaneous and posed smiles initiated by different brain systems have differences in both morphology and dynamics. Distinguishing the two types of smiles remains challenging as discriminative subtle changes need to be captured, which are also uneasily observed by human eyes. Most previous related works about spontaneous versus posed smile recognition concentrate on extracting geometric features while appearance features are not fully used, leading to the loss of texture information. In this paper, we propose a region-specific texture descriptor to represent local pattern changes of different facial regions and compensate for limitations of geometric features. The temporal phase of each facial region is divided by calculating the intensity of the corresponding facial region rather than the intensity of only the mouth region. A mid-level fusion strategy of support vector machine is employed to combine the two feature types. Experimental results show that both our proposed appearance representation and its combination with geometry-based facial dynamics achieve favorable performances on four baseline databases: BBC, SPOS, MMI, and UvA-NEMO.
文摘Solid lithium ion conducting electrochemical cells using LiSiPO as solid electrolyte and Li2CO3 mixed with Au as electrodes were prepared and employed as chemical sensors for the detection of CO2 gas.The EMF of the cell depends on the concentration of CO2 in air according to the partial pressure dependence of Nernst's law in the investigated range from 100 to 2000 ppm over the temperature range from 473 K to 673 K.
基金Project supported by the National Natural Science Foundation of China(Nos.81271955 and 30973350)the Zhejiang Provincial Natural Science Foundation of China(No.Y2080338)
文摘The aim of this study is to evaluate the influence of Tooth Mousse (TM) application, smear layer removal, and storage time on resin-dentin microtensile bond strength (pTBS). Dentin specimens were divided into two groups: (1) smear layer covered; (2) smear layer removed using 15% EDTA for 90 s. In each group, half the specimens were treated once with TM for 60 min. After bonding procedures using a two-step self-etching adhesive (Clearfil SE Bond (CSE); Kuraray Medical, Tokyo, Japan), an all-in-one adhesive (G-Bond (GB); GC Corp, Tokyo, Japan), and a total-etch adhesive (Adper Single Bond 2 (SB); 3M ESPE, St. Paul, MN, USA), the specimens were stored for 3 d or 6 months in deionized water at 37 ℃, and pTBS was tested and analyzed. With the exception of SB (no TM application) and GB, the pTBS was significantly increased for CSE and SB using EDTA pre-conditioning and 3 d of storage (P≤0.001). Bond strength of GB decreased significantly when using EDTA (3 d storage, P〈0.05). TM application only increased the pTBS of GB (no EDTA) and SB (with EDTA) after 3 d (P≤0.02). Comparing the adhesives after 3 d of storage, CSE exhibited the greatest pTBS values followed by GB and SB (P≤0.02). The factors of adhesive, EDTA, and TM did not show any significant impact on pTBS when specimens were stored for 6 months (P〉0.05). The additional application of TM and EDTA for cavity preparation seems only to have a short-term effect, and no influence on pTBS of dentin bonds after a period of 6 months.
基金Project supported by the Camlog Foundation(No.CF 31401),Basel,Switzerland
文摘Objective: The aim of the current study was to evaluate the effect of ultraviolet(UV) photofunctionalization of dental titanium implants with exposure to the oral cavity on osseointegration in an animal model. Methods: Forty-eight titanium implants(Camlog~? Conelog~? 4.3 mmx9.0 mm) were placed epicrestally into the edentulous jaws of three minipigs and implant stability was assessed by measuring the implant stability quotient(ISQ). Prior to implantation half of the implants were photofunctionalized with intense UV-light. After three months, the implants were exposed and ISQ was measured again. After six months of implant exposure, the minipigs were sacrificed and the harvested specimens were analyzed using histomorphometric, light, and fluorescence microscopy. Main results: Forty-two of 48 implants osseointegrated. The overall mean bone-implant contact area(BIC) was(64±22)%. No significant differences were found in BIC or ISQ value(multivariate analysis of variance(MANOVA), P〉0.05) between implants with and without exposure to UV photofunctionalization. Conclusions: No significant effects were observed on osseointegration of dental titanium implants nine months after exposure of UV photofunctionalization.
文摘Last year,we published a paper in this journal in which we described the effects of vitamin C and its phospho-modified version(phospho-vitamin C,pVC)on the in vitro activation,proliferation,and effector function of humanγδT cells.^(1)We were delighted to see that our study was recently highlighted in a Comment in this journal by Meraviglia and Dieli,2 underscoring the potential interest in using vitamin C to promoteγδT cell activity for use in cancer immunotherapy.Our study was a joint publication with our Chinese collaborators,headed by Prof.Zhinan Yin,with whom we share an interest in exploring the beneficial effects of vitamin C on boosting the cellular immune response.In fact,Yin and colleagues initiated clinical studies on the adoptive transfer of allogeneicγδT cells expanded in the presence of vitamin C into cancer patients.A report of a clinical phase I study demonstrating the safety of allogeneicγδT cell transfer has recently been published in this journal,another collaborative effort of our two groups.^(3)
基金This work was supported by a grant from the Deutsche Forschungsgemeinschaft(Ka502/19-3 to DK).
文摘The differentiation and functional plasticity of T cells are transcriptionally and epigenetically regulated by signals imposed by the local cytokine milieu and a variety of additional factors,including vitamins.Vitamin C has pleiotropic functions in the immune system.It exerts antioxidant activity,can directly kill selected tumor targets,promotes early T-cell differentiation,and enhances Th1 cytokine production in mature T cells[1,2].
基金supported by Siemens Healthcare, the Curetis Groupparts by the Best Ageing Program from the European Union (Grant No. 306031)the Austrian Research Promotion Agency (Grant Nos 866389 and 863729)
文摘Emerging antibiotic resistance is a major global health threat. The analysis of nucleic acid sequences linked to susceptibility phenotypes facilitates the study of genetic antibiotic resistance determinants to inform molecular diagnostics and drug development. We collected genetic data (11,087 newly-sequenced whole genomes) and culture-based resistance profiles (10,991 out of the 11,087 isolates comprehensively tested against 22 antibiotics in total) of clinical isolates including 18 main species spanning a time period of 30 years. Species and drug specific resistance patterns were observed including increased resistance rates for Acinetobacter baumannii to carbapenems and for Escherichia coli to fluoroquinolones. Species-level pan-genomes were constructed to reflect the genetic repertoire of the respective species,including conserved essential genes and known resis-tance factors. Integrating phenotypes and genotypes through species-level pan-genomes allowed to infer gene–drug resistance associations using statistical testing. The isolate collection and the analysis results have been integrated into GEAR-base,a resource available for academic research use free of charge at https://gear-base.com.