The FAIR principles have been widely cited,endorsed and adopted by a broad range of stakeholders since their publication in 2016.By intention,the 15 FAIR guiding principles do not dictate specific technological implem...The FAIR principles have been widely cited,endorsed and adopted by a broad range of stakeholders since their publication in 2016.By intention,the 15 FAIR guiding principles do not dictate specific technological implementations,but provide guidance for improving Findability,Accessibility,Interoperability and Reusability of digital resources.This has likely contributed to the broad adoption of the FAIR principles,because individual stakeholder communities can implement their own FAIR solutions.However,it has also resulted in inconsistent interpretations that carry the risk of leading to incompatible implementations.Thus,while the FAIR principles are formulated on a high level and may be interpreted and implemented in different ways,for true interoperability we need to support convergence in implementation choices that are widely accessible and(re)-usable.We introduce the concept of FAIR implementation considerations to assist accelerated global participation and convergence towards accessible,robust,widespread and consistent FAIR implementations.Any self-identified stakeholder community may either choose to reuse solutions from existing implementations,or when they spot a gap,accept the challenge to create the needed solution,which,ideally,can be used again by other communities in the future.Here,we provide interpretations and implementation considerations(choices and challenges)for each FAIR principle.展开更多
AIM： To assess the effects of Sb on fecal flora and shortchain fatty acids （SCFA） in patients on long-term TEN. METHODS： Ten patients （3 females, 7 males, 59±5.5 years）, on TEN for a median of 13 mo （1-125...AIM： To assess the effects of Sb on fecal flora and shortchain fatty acids （SCFA） in patients on long-term TEN. METHODS： Ten patients （3 females, 7 males, 59±5.5 years）, on TEN for a median of 13 mo （1-125）, and 15 healthy volunteers （4 females, 11 males, 32±2.0 years） received Sb （0.5 g bid PO） for 6 d. Two stool samples were taken before, on the last 2 d and 9-10 d after treatment, for SCFA measurement and for culture and bacterial identification. Values （mean4-SE） were compared using sign tests and ANOVA. RESULTS： Fecal butyrate levels were lower in patients （10.1±2.9 mmol/kg） than in controls （19.2±3.9, P= 0.02）. Treatment with Sb increased total fecal SCFA levels in patients （150.2＋27.2 vs 107.5±18.2 mmol/kg, P= 0.02） but not in controls （129.0±28.6 vs 113.0±15.2 mmol/kg, NS）. At the end of treatment with Sb, patients had higher fecal butyrate（16.0±4.4 vs 10.1 [2.9] mmol/kg, P= 0.004）. Total SCFAs remained high 9 d after treatment was discontinued. Before the treatment, the anaerobe to aerobe ratio was lower in patients compared to controls （2.4±2.3 vs 69.8±1.8, P= 0.003）. There were no significant changes in the fecal flora of TEN patients. CONCLUSION： Sb-induced increase of fecal SCFA concentrations （especially butyrate） may explain the preventive effects of this yeast on TEN-induced diarrhea.展开更多
AIM： To evaluate the long-term outcome and prognostic factors of patients with hilar cholangiocarinoma. METHODS： Ninety-six consecutive patients underwent treatment for malignant hilar bile duct tumors during 1995-2...AIM： To evaluate the long-term outcome and prognostic factors of patients with hilar cholangiocarinoma. METHODS： Ninety-six consecutive patients underwent treatment for malignant hilar bile duct tumors during 1995-2005. Of the 96 patients, 20 were initially treated with surgery （n = 2 R0 / n = 18 R1）. In non-operated patients, data analysis was performed retrospectively. RESULTS： Among the 96 patients, 76 were treated with endoscopic transpapillary （ERC, n = 45） and/or percutaneous transhepatic biliary drainage （PTBD, n = 31）. The mean survival time of these 76 patients undergoing palliative endoscopic and/or percutaneous drainage was 359 ± 296 d. The mean survival time of patients with initial bilirubin levels 〉 10 mg/dL was significantly lower （P 〈 0.001） than patients with bilirubin levels 〈 10 mg/dL. The mean survival time of patients with Bismuth stage Ⅱ （n = 8）, Ⅲ （n = 28） and Ⅳ （n = 40） was 496 =1= 300 d, 441 ± 385 d and 274 ± 218 d, respectively. Thus, patients with advanced Bismuth stage showed a reduced mean survival time, but the difference was not significant. The type of biliary drainage had no significant benefidal effect on the mean survival time （ERC vs PTBD, P = 0.806）. CONCLUSION： Initial bilirubin level is a significant prognostic factor for survival of patients. In contrast, age, tumor stage according to the Bismuth-Corlette classification, and types of intervention are not significant prognostic parameters for survival. Palliative treatment with endoscopic or percutaneous biliary drainage is still suboptimal, new diagnostic and therapeutic tools need to be evaluated.展开更多
The purpose of this work was to assess the evidence for effectiveness of acupuncture （AC） treatment in gastrointestinal diseases. A systematic review of the Medline-cited literature for clinical trials was performed...The purpose of this work was to assess the evidence for effectiveness of acupuncture （AC） treatment in gastrointestinal diseases. A systematic review of the Medline-cited literature for clinical trials was performed up to May 2006. Controlled trials assessing acupuncture point stimulation for patients with gastrointestinal diseases were considered for inclusion. The search identified 18 relevant trials meeting the inclusion criteria. Two irritable bowel syndrome （IBS） trials, 1 Crohn＇s disease and 1 colitis ulcerosa trial had a robust random controlled trial （RCT） design. In regard to other gastrointestinal disorders, study quality was poor. In all trials, quality of life （QoL） improved significantly independently from the kind of acupuncture, real or sham. Real AC was significantly superior to sham acupuncture with regard to disease activity scores in the Crohn and Colitis trials. Efficacy of acupuncture related to QoL in IBS may be explained by unspecific effects. This is the same for QoL in inflammatory bowel diseases （IBD）, whereas specific acupuncture effects may be found in clinical scores. Further trials for IBDs and in particular for all other gastrointestinal disorders would be necessary to evaluate the efficacy of acupuncture treatment. However, it must be discussed on what terms patients benefit when this harmless and obviously powerful therapy with regard to QoL is demystified by further placebo controlled trials.展开更多
AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS: Brush cytology and forceps biopsy were routinely performed in patients with s...AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS: Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures. Fifty-eight consecutive patients undergoing endoscopic retrograde cholangio-pancreatography (ERCP) including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005.RESULTS: Positive results for malignancy were obtained in 24/58 patients (41.4%) by brush cytology and in 31/58 patients (53.4%) by forceps biopsy. The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% (35/58 patients). In 20/58 patients (34.5%), diagnosis were obtained by both positive cytology and positive histology, in 11/58 (19%) by positive histology (negative cytology) and only 4/58 patients (6.9%) were confirmed by positive cytology (negative histology).CONCLUSION: Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings.展开更多
AIM: To evaluate the role of CDX2 homeobox protein as a predictor for cancer progression and prognosis as well as its correlation with MUC2 expression. CDX2 represents a transcription factor for various intestinal gen...AIM: To evaluate the role of CDX2 homeobox protein as a predictor for cancer progression and prognosis as well as its correlation with MUC2 expression. CDX2 represents a transcription factor for various intestinal genes (including MUC2) and thus an important regulator of intestinal differentiation, which could previously be identified in gastric carcinomas and intestinal metaplasia. METHODS: Formalin-fixed and paraffin-embedded tissues from 190 gastric carcinoma patients were stained with monodonal antibodies recognizing CDX2 and MUC2, respectively. Immunoreactivity was evaluated semiquantitatively and statistical analyses including x2 tests, uni- and multi-variate survival analyses were performed. RESULTS: CDX2 was mostly expressed in a nuclear or supranuclear pattern,whereas MUC2 showed an almost exclusive supranuclear reactivity.Both antigens were present in >80% of areas exhibiting intestinal metaplasia. An immunoreactivity in >5% of the tumor area was observed in 57% (CDX2) or in 21% (MUC2) of the carcinomas.The presence of both molecules did not correlate with WHO, Lauren and Goseki classification (with the exception of a significantly stronger MUC2 expression in mucinous tumors). CDX2 correlated with a lower pT and pN stage in the subgroups of intestinal and stage I cancers and was associated with MUC2 positivity.A prognostic impact of CDX2 or MUC2 was not observed. CONCLUSION: CDX2 and MUC2 play an important role in the differentiation of normal, inflamed, and neoplastic gastric tissues. According to our results, loss of CDX2 may represent a marker of tumor progression in early gastric cancer and carcinomas with an intestinal phenotype.展开更多
Super-resolution structured illumination microscopy(SR-SIM) provides an up to twofold enhanced spatial resolution of fluorescently labeled samples. The reconstruction of high-quality SR-SIM images critically depends o...Super-resolution structured illumination microscopy(SR-SIM) provides an up to twofold enhanced spatial resolution of fluorescently labeled samples. The reconstruction of high-quality SR-SIM images critically depends on patterned illumination with high modulation contrast. Noisy raw image data(e.g., as a result of low excitation power or low exposure time), result in reconstruction artifacts. Here, we demonstrate deep-learning based SR-SIM image denoising that results in high-quality reconstructed images. A residual encoding–decoding convolutional neural network(RED-Net) was used to successfully denoise computationally reconstructed noisy SR-SIM images.We also demonstrate the end-to-end deep-learning based denoising and reconstruction of raw SIM images into high-resolution SR-SIM images. Both image reconstruction methods prove to be very robust against image reconstruction artifacts and generalize very well across various noise levels. The combination of computational image reconstruction and subsequent denoising via RED-Net shows very robust performance during inference after training even if the microscope settings change.展开更多
The sandfish is a lizard having the remarkable ability to move in desert sand in a swimming-like fashion. The most outstanding adaptations to this mode of life are the low friction behaviour and the extensive abrasion...The sandfish is a lizard having the remarkable ability to move in desert sand in a swimming-like fashion. The most outstanding adaptations to this mode of life are the low friction behaviour and the extensive abrasion resistance of the sandfish skin against sand, outperforming even steel. We investigated the topography, the composition and the mechanical properties of sandfish scales. These consist of glycosylated keratins with high amount of sulphur but no hard inorganic material, such as silicates or lime. Remarkably, atomic force microscopy shows an almost complete absence of attractive forces between the scale surface and a silicon tip, suggesting that this is responsible for the unusual tribological properties. The unusual glycosylation of the keratins was found to be absolutely necessary for the described phenomenon. The scales were dissolved and reconstituted on a polymer surface resulting in properties similar to the original scale. Thus, we provide a pathway towards exploitation of the reconstituted scale material for future engineering applications.展开更多
Acute pancreatitis is a necro-inflammatory disease of the exocrine pancreas that is characterized by inappropriate activation of zymogens, infiltration of the pancreas by inflammatory cells, and destruction of the pan...Acute pancreatitis is a necro-inflammatory disease of the exocrine pancreas that is characterized by inappropriate activation of zymogens, infiltration of the pancreas by inflammatory cells, and destruction of the pancreatic exocrine cells. Acute pancreatitis can progress to a severe life-threatening disease. Currently there is no pharmacotherapy to prevent or treat acute pancreatitis. One of the more common factors associated with acute pancreatitis is alcohol abuse. Although commonly associated with pancreatitis alcohol alone is unable to cause pancreatitis. Instead, it appears that alcohol and its metabolic by-products predispose the pancreas to damage from agents that normally do not cause pancreatitis, or to more severe disease from agents that normally cause mild pancreatic damage. Over the last 10 to 20 years, a tremendous amount of work has defined a number of alcohol-mediated biochemical changes in pancreatic cells. Among these changes are: Sustained levels of intracellular calcium, activation of the mitochondrial permeability transition pore, endoplasmic reticulum stress, impairment in autophagy, alteration in the activity of transcriptional activators, and colocalization of lysosomal and pancreatic digestive enzymes. Elucidation of these changes has led to a deeper understanding of the mechanisms by which ethanol predisposes acinar cells to damage. This greater understanding has revealed a number of promising targets for therapeutic intervention. It is hoped that further investigation of these targets will lead to the development of pharmacotherapy that is effective in treating and preventing the progression of acute pancreatitis.展开更多
基金The work of A.Jacobsen,C.Evelo,M.Thompson,R.Cornet,R.Kaliyaperuma and M.Roos is supported by funding from the European Union’s Horizon 2020 research and innovation program under the EJP RD COFUND-EJP N°825575.The work of A.Jacobsen,C.Evelo,C.Goble,M.Thompson,N.Juty,R.Hooft,M.Roos,S-A.Sansone,P.McQuilton,P.Rocca-Serra and D.Batista is supported by funding from ELIXIR EXCELERATE,H2020 grant agreement number 676559.R.Hooft was further funded by NL NWO NRGWI.obrug.2018.009.N.Juty and C.Goble were funded by CORBEL(H2020 grant agreement 654248)N.Juty,C.Goble,S-A.Sansone,P.McQuilton,P.Rocca-Serra and D.Batista were funded by FAIRplus(IMI grant agreement 802750)+12 种基金N.Juty,C.Goble,M.Thompson,M.Roos,S-A.Sansone,P.McQuilton,P.Rocca-Serra and D.Batista were funded by EOSClife H2020-EU(grant agreement number 824087)C.Goble was funded by DMMCore(BBSRC BB/M013189/)M.Thompson,M.Roos received funding from NWO(VWData 400.17.605)S-A.Sansone,P.McQuilton,P.Rocca-Serra and D.Batista have been funded by grants awarded to S-A.Sansone from the UK BBSRC and Research Councils(BB/L024101/1,BB/L005069/1)EU(H2020-EU 634107H2020-EU 654241,IMI(IMPRiND 116060)NIH Data Common Fund,and from the Wellcome Trust(ISA-InterMine 212930/Z/18/ZFAIRsharing 208381/A/17/Z)The work of A.Waagmeester has been funded by grant award number GM089820 from the National Institutes of Health.M.Kersloot was funded by the European Regional Development Fund(KVW-00163).The work of N.Meyers was funded by the National Science Foundation(OAC 1839030)The work of M.D.Wilkinson is funded by Isaac Peral/Marie Curie cofund with the Universidad Politecnica de Madrid and the Ministerio de Economia y Competitividad grant number TIN2014-55993-RMThe work of B.Magagna,E.Schultes,L.da Silva Santos and K.Jeffery is funded by the H2020-EU 824068The work of B.Magagna,E.Schultes and L.da Silva Santos is funded by the GO FAIR ISCO grant of the Dutch Ministry of Science and CultureThe work of G.Guizzardi is supported by the OCEAN Project(FUB).M.Courtot received funding from the I
文摘The FAIR principles have been widely cited,endorsed and adopted by a broad range of stakeholders since their publication in 2016.By intention,the 15 FAIR guiding principles do not dictate specific technological implementations,but provide guidance for improving Findability,Accessibility,Interoperability and Reusability of digital resources.This has likely contributed to the broad adoption of the FAIR principles,because individual stakeholder communities can implement their own FAIR solutions.However,it has also resulted in inconsistent interpretations that carry the risk of leading to incompatible implementations.Thus,while the FAIR principles are formulated on a high level and may be interpreted and implemented in different ways,for true interoperability we need to support convergence in implementation choices that are widely accessible and(re)-usable.We introduce the concept of FAIR implementation considerations to assist accelerated global participation and convergence towards accessible,robust,widespread and consistent FAIR implementations.Any self-identified stakeholder community may either choose to reuse solutions from existing implementations,or when they spot a gap,accept the challenge to create the needed solution,which,ideally,can be used again by other communities in the future.Here,we provide interpretations and implementation considerations(choices and challenges)for each FAIR principle.
基金Supported by a research grant from Laboratoires Biocodex,Montrouge, France, EU
文摘AIM： To assess the effects of Sb on fecal flora and shortchain fatty acids （SCFA） in patients on long-term TEN. METHODS： Ten patients （3 females, 7 males, 59±5.5 years）, on TEN for a median of 13 mo （1-125）, and 15 healthy volunteers （4 females, 11 males, 32±2.0 years） received Sb （0.5 g bid PO） for 6 d. Two stool samples were taken before, on the last 2 d and 9-10 d after treatment, for SCFA measurement and for culture and bacterial identification. Values （mean4-SE） were compared using sign tests and ANOVA. RESULTS： Fecal butyrate levels were lower in patients （10.1±2.9 mmol/kg） than in controls （19.2±3.9, P= 0.02）. Treatment with Sb increased total fecal SCFA levels in patients （150.2＋27.2 vs 107.5±18.2 mmol/kg, P= 0.02） but not in controls （129.0±28.6 vs 113.0±15.2 mmol/kg, NS）. At the end of treatment with Sb, patients had higher fecal butyrate（16.0±4.4 vs 10.1 [2.9] mmol/kg, P= 0.004）. Total SCFAs remained high 9 d after treatment was discontinued. Before the treatment, the anaerobe to aerobe ratio was lower in patients compared to controls （2.4±2.3 vs 69.8±1.8, P= 0.003）. There were no significant changes in the fecal flora of TEN patients. CONCLUSION： Sb-induced increase of fecal SCFA concentrations （especially butyrate） may explain the preventive effects of this yeast on TEN-induced diarrhea.
文摘AIM： To evaluate the long-term outcome and prognostic factors of patients with hilar cholangiocarinoma. METHODS： Ninety-six consecutive patients underwent treatment for malignant hilar bile duct tumors during 1995-2005. Of the 96 patients, 20 were initially treated with surgery （n = 2 R0 / n = 18 R1）. In non-operated patients, data analysis was performed retrospectively. RESULTS： Among the 96 patients, 76 were treated with endoscopic transpapillary （ERC, n = 45） and/or percutaneous transhepatic biliary drainage （PTBD, n = 31）. The mean survival time of these 76 patients undergoing palliative endoscopic and/or percutaneous drainage was 359 ± 296 d. The mean survival time of patients with initial bilirubin levels 〉 10 mg/dL was significantly lower （P 〈 0.001） than patients with bilirubin levels 〈 10 mg/dL. The mean survival time of patients with Bismuth stage Ⅱ （n = 8）, Ⅲ （n = 28） and Ⅳ （n = 40） was 496 =1= 300 d, 441 ± 385 d and 274 ± 218 d, respectively. Thus, patients with advanced Bismuth stage showed a reduced mean survival time, but the difference was not significant. The type of biliary drainage had no significant benefidal effect on the mean survival time （ERC vs PTBD, P = 0.806）. CONCLUSION： Initial bilirubin level is a significant prognostic factor for survival of patients. In contrast, age, tumor stage according to the Bismuth-Corlette classification, and types of intervention are not significant prognostic parameters for survival. Palliative treatment with endoscopic or percutaneous biliary drainage is still suboptimal, new diagnostic and therapeutic tools need to be evaluated.
文摘The purpose of this work was to assess the evidence for effectiveness of acupuncture （AC） treatment in gastrointestinal diseases. A systematic review of the Medline-cited literature for clinical trials was performed up to May 2006. Controlled trials assessing acupuncture point stimulation for patients with gastrointestinal diseases were considered for inclusion. The search identified 18 relevant trials meeting the inclusion criteria. Two irritable bowel syndrome （IBS） trials, 1 Crohn＇s disease and 1 colitis ulcerosa trial had a robust random controlled trial （RCT） design. In regard to other gastrointestinal disorders, study quality was poor. In all trials, quality of life （QoL） improved significantly independently from the kind of acupuncture, real or sham. Real AC was significantly superior to sham acupuncture with regard to disease activity scores in the Crohn and Colitis trials. Efficacy of acupuncture related to QoL in IBS may be explained by unspecific effects. This is the same for QoL in inflammatory bowel diseases （IBD）, whereas specific acupuncture effects may be found in clinical scores. Further trials for IBDs and in particular for all other gastrointestinal disorders would be necessary to evaluate the efficacy of acupuncture treatment. However, it must be discussed on what terms patients benefit when this harmless and obviously powerful therapy with regard to QoL is demystified by further placebo controlled trials.
文摘AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS: Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures. Fifty-eight consecutive patients undergoing endoscopic retrograde cholangio-pancreatography (ERCP) including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005.RESULTS: Positive results for malignancy were obtained in 24/58 patients (41.4%) by brush cytology and in 31/58 patients (53.4%) by forceps biopsy. The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% (35/58 patients). In 20/58 patients (34.5%), diagnosis were obtained by both positive cytology and positive histology, in 11/58 (19%) by positive histology (negative cytology) and only 4/58 patients (6.9%) were confirmed by positive cytology (negative histology).CONCLUSION: Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings.
基金Supported by Chongqing Natural Science Foundation Projects (CSTC-2008BA7032,CSTC-2010BB7003)the Fundamental Research Funds for the Central Universities (XDJK2009B032)+2 种基金the Doctoral Research Fund of Southwest University (SWU109020)the 948 Program of State Forestry Administration (2008-4-45)Chongqing Key Laboratory for the Protection and Restoration of Forest Ecology of the Three Gorges Reservoir Region (2008-01)
文摘AIM: To evaluate the role of CDX2 homeobox protein as a predictor for cancer progression and prognosis as well as its correlation with MUC2 expression. CDX2 represents a transcription factor for various intestinal genes (including MUC2) and thus an important regulator of intestinal differentiation, which could previously be identified in gastric carcinomas and intestinal metaplasia. METHODS: Formalin-fixed and paraffin-embedded tissues from 190 gastric carcinoma patients were stained with monodonal antibodies recognizing CDX2 and MUC2, respectively. Immunoreactivity was evaluated semiquantitatively and statistical analyses including x2 tests, uni- and multi-variate survival analyses were performed. RESULTS: CDX2 was mostly expressed in a nuclear or supranuclear pattern,whereas MUC2 showed an almost exclusive supranuclear reactivity.Both antigens were present in >80% of areas exhibiting intestinal metaplasia. An immunoreactivity in >5% of the tumor area was observed in 57% (CDX2) or in 21% (MUC2) of the carcinomas.The presence of both molecules did not correlate with WHO, Lauren and Goseki classification (with the exception of a significantly stronger MUC2 expression in mucinous tumors). CDX2 correlated with a lower pT and pN stage in the subgroups of intestinal and stage I cancers and was associated with MUC2 positivity.A prognostic impact of CDX2 or MUC2 was not observed. CONCLUSION: CDX2 and MUC2 play an important role in the differentiation of normal, inflamed, and neoplastic gastric tissues. According to our results, loss of CDX2 may represent a marker of tumor progression in early gastric cancer and carcinomas with an intestinal phenotype.
基金Deutsche Forschungsgemeinschaft(415832635)H2020 Marie Sk?odowska-Curie Actions(752080)Bundesministerium für Bildung und Forschung(01IS18041C)。
文摘Super-resolution structured illumination microscopy(SR-SIM) provides an up to twofold enhanced spatial resolution of fluorescently labeled samples. The reconstruction of high-quality SR-SIM images critically depends on patterned illumination with high modulation contrast. Noisy raw image data(e.g., as a result of low excitation power or low exposure time), result in reconstruction artifacts. Here, we demonstrate deep-learning based SR-SIM image denoising that results in high-quality reconstructed images. A residual encoding–decoding convolutional neural network(RED-Net) was used to successfully denoise computationally reconstructed noisy SR-SIM images.We also demonstrate the end-to-end deep-learning based denoising and reconstruction of raw SIM images into high-resolution SR-SIM images. Both image reconstruction methods prove to be very robust against image reconstruction artifacts and generalize very well across various noise levels. The combination of computational image reconstruction and subsequent denoising via RED-Net shows very robust performance during inference after training even if the microscope settings change.
基金美国国家科学基金会(The National Science Foundation)资助的美国West-ED公司学生学习的评价和测评中心(Center for Assessment and Evaluation of StudentLearning)的研究成果之一美国教育部(U.S.Department of Education)教育研究和发展中心项目(the Educational Research and Development Centers Program)资助资助编号为:R305B960002
文摘The sandfish is a lizard having the remarkable ability to move in desert sand in a swimming-like fashion. The most outstanding adaptations to this mode of life are the low friction behaviour and the extensive abrasion resistance of the sandfish skin against sand, outperforming even steel. We investigated the topography, the composition and the mechanical properties of sandfish scales. These consist of glycosylated keratins with high amount of sulphur but no hard inorganic material, such as silicates or lime. Remarkably, atomic force microscopy shows an almost complete absence of attractive forces between the scale surface and a silicon tip, suggesting that this is responsible for the unusual tribological properties. The unusual glycosylation of the keratins was found to be absolutely necessary for the described phenomenon. The scales were dissolved and reconstituted on a polymer surface resulting in properties similar to the original scale. Thus, we provide a pathway towards exploitation of the reconstituted scale material for future engineering applications.
基金Supported by Funds from the University of Nebraska Department of Internal Medicine,the Fred and Pamela Buffett Cancer Center,and the Nebraska Research Initiative(to Clemens DL)by NIH,NIAAA grant AA020818(to Arkfeld CK)
文摘Acute pancreatitis is a necro-inflammatory disease of the exocrine pancreas that is characterized by inappropriate activation of zymogens, infiltration of the pancreas by inflammatory cells, and destruction of the pancreatic exocrine cells. Acute pancreatitis can progress to a severe life-threatening disease. Currently there is no pharmacotherapy to prevent or treat acute pancreatitis. One of the more common factors associated with acute pancreatitis is alcohol abuse. Although commonly associated with pancreatitis alcohol alone is unable to cause pancreatitis. Instead, it appears that alcohol and its metabolic by-products predispose the pancreas to damage from agents that normally do not cause pancreatitis, or to more severe disease from agents that normally cause mild pancreatic damage. Over the last 10 to 20 years, a tremendous amount of work has defined a number of alcohol-mediated biochemical changes in pancreatic cells. Among these changes are: Sustained levels of intracellular calcium, activation of the mitochondrial permeability transition pore, endoplasmic reticulum stress, impairment in autophagy, alteration in the activity of transcriptional activators, and colocalization of lysosomal and pancreatic digestive enzymes. Elucidation of these changes has led to a deeper understanding of the mechanisms by which ethanol predisposes acinar cells to damage. This greater understanding has revealed a number of promising targets for therapeutic intervention. It is hoped that further investigation of these targets will lead to the development of pharmacotherapy that is effective in treating and preventing the progression of acute pancreatitis.
基金HaK was supported by the National Natural Science Foundation of China(92043301,82030103,and 91843302)and China Medical Board Collaborating Program(16-250)AG and FS were supported by the Medical Research Council,UK(MK/M022625/1)+10 种基金the Natural Environment Research Council,UK(NE/R009384/1)and the European Union's Horizon 2020 Project Exhaustion(820655)VH was supported by the Spanish Ministry of Science and Innovation(PCIN-2017-046)and the German Federal Ministry of Education and Research(01 LSI201A2)YH and MH were supported by the Environment Research and Technology Development Fund(JPMEERF15S11412)the Environmental Restoration and Conservation Agency,Japan.JK and AU were supported by the Czech Science Foundation(18-22125S)ST was supported by the Shanghai Municipal Science and Technology Commission(18411951600)Y-LLG was supported by a Career Development Fellowship of the Australian National Health and Medical Research Council(APP1163693)SL was supported by an Early Career Fellowship of the Australian National Health and Medical Research Council(APP1109193)JJKJJ and NR were supported by the Academy of Finland(310372)The funders had no role in considering the study design or in the collection,analysis,interpretation of data,writing of the report,or decision to submit the article for publication.
