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Observation of a single protein by ultrafast X-ray diffraction

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light(Science & Applications) 2024年第1期13卷 80-90页

作者： Tomas Ekeberg Dameli Assalauova Johan Bielecki rebecca Boll Benedikt J.Daurer lutz A.Eichacker linda E.Franken Davide E.Galli luca Gelisio lars Gumprecht laura H.Gunn Janos Hajdu Robert Hartmann Dirk Hasse Alexandr Ignatenko Jayanath Koliyadu Olena Kulyk Ruslan Kurta Markus Kuster Wolfgang lugmayr Jannik lübke Adrian P.Mancuso Tommaso Mazza Carl Nettelblad Yevheniy Ovcharenko Daniel E.Rivas Max Rose Amit K.Samanta Philipp Schmidt Egor Sobolev Nicusor Timneanu Sergey Usenko Daniel Westphal Tamme Wollweber lena Worbs Paul lourdu Xavier Hazem Yousef Kartik Ayyer Henry N.Chapman Jonas A.Sellberg Carolin Seuring Ivan A.Vartanyants Jochen Küpper Michael Meyer Filipe R.N.C.Maia laboratory of Molecular Biophysics Department of Cell and Molecular BiologyUppsala UniversityHusargatan 3(Box 596)SE-75124 UppsalaSweden Deutsches Electronen-Synchrotron DESY Notkestrasse 8522607 HamburgGermany European XFEl Holzkoppel 422869 SchenefeldGermany Diamond light Source Harwell Science&Innovation CampusDidcot OX110DEUK University of Stavanger Centre Organelle ResearchRichard-Johnsensgate 44021 StavangerNorway leibniz Institute for Experimental Virology(HPI) Centre for Structural Systems BiologyNotkestraße 8522607 HamburgGermany Dipartimento di Fisica“Aldo Pontremoli” Universitàdegli Studi di Milanovia Celoria 1620133 MilanoItaly Center for Free-Electron laser Science DESY22607 HamburgGermany Plant Biology Section School of Integrative Plant ScienceCornell UniversityIthacaNY 14853USA PNSensor GmbH Otto-Hahn-Ring 6D-81739 MünchenGermany Biomedical and X-Ray Physics Department of Applied PhysicsAlbaNova University CenterKTH Royal Institute of TechnologySE-10691 StockholmSweden ElI Beamlines/IoP Institute of Physics AS CR v.v.i.Na Slovance 218221 Prague 8Czech Republic Multi-User CryoEM Facility Centre for Structural Systems BiologyNotkestr.8522607 HamburgGermany University Medical Center Hamburg-Eppendorf(UKE) Martinistrasse 5220246 HamburgGermany The Hamburg Center for Ultrafast Imaging Universität HamburgLuruper Chaussee 14922761 HamburgGermany Department of Physics Universität HamburgLuruper Chaussee 14922761 HamburgGermany Department of Chemistry and Physics La Trobe Institute for Molecular ScienceLa Trobe UniversityMelbourneVIC 3086Australia Division of Scientific Computing Science for Life LaboratoryDepartment of Information TechnologyUppsala UniversityBox 337SE-75105 UppsalaSweden European Molecular Biology laboratory c/o DESYNotkestrasse 8522607 HamburgGermany Department of Physics and Astronomy Uppsala UniversityBox 516SE-75120 UppsalaSweden Max Planck Institute for the Structure and Dynamics of Matter Luruper Chaussee 14922761 HamburgGe

The idea of using ultrashort X-ray pulses to obtain images of single proteins frozen in time has fascinated and inspired *** was one of the arguments for building X-ray free-electron *** to theory,the extremely intense pulses provide sufficient signal to dispense with using crystals as an amplifier,and the ultrashort pulse duration permits capturing the diffraction data before the sample inevitably *** was first demonstrated on biological samples a decade ago on the giant *** then,a large collaboration has been pushing the limit of the smallest sample that can be *** ability to capture snapshots on the timescale of atomic vibrations,while keeping the sample at room temperature,may allow probing the entire conformational phase space of *** we show the first observation of an X-ray diffraction pattern from a single protein,that of Escherichia coli GroEl which at 14 nm in diameter is the smallest biological sample ever imaged by X-rays,and demonstrate that the concept of diffraction before destruction extends to single *** the pattern,it is possible to determine the approximate orientation of the *** experiment demonstrates the feasibility of ultrafast imaging of single proteins,opening the way to single-molecule time-resolved studies on the femtosecond timescale.

关键词： smallest intense ultrafast

Immunotherapy as maintenance treatment in metastatic triple negative breast cancer

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 315-322页

作者： Tira J.Tan Jack J.Chan rebecca A.Dent Division of Medical Oncology National Cancer CentreSingapore 169610Singapore.

Metastatic triple negative breast cancer(mTNBC)is an aggressive disease associated with a poor prognosis as compared to other subtypes of breast *** advances have been made in recent years with new approvals for PARP inhibitors for those patients who harbor germline BRCA mutations and immune checkpoint inhibitors for patients with programmed death ligand-1(PD-l1)expressing *** therapies are associated with favorable toxicity profiles and improved health-related quality of life when compared with *** therapy,now recognized as the mainstay for patients with ovarian malignancies,takes advantage of the benefit of low-intensity therapies to suppress a disease over a prolonged period of time following maximal response to induction *** strategy has been little explored in the treatment of ***,we briefly discuss the evidence to date lending credence to this treatment paradigm and examine the potential role of immunotherapy as maintenance in the management of mTNBC.

关键词： Triple negative breast cancer maintenance therapy immunotherapy PARP inhibitor

Post-weaning and whole-of-life performance of pigs is determined by live weight at weaning and the complexity of the diet fed after weaning

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Animal Nutrition 2017年第4期3卷 372-379页

作者： Cherie l.Collins John R.Pluske rebecca S.Morrison Trevor N.McDonald Robert J.Smits David J.Henman Ingunn Stensland Frank R.Dunshea Rivalea Australia Pty ltd School of Veterinary and life Sciences Murdoch University Faculty of Veterinary and Agricultural Sciences The University of Melbourne

The production performance and financial outcomes associated with weaner diet complexity for pigs of different weight classes at weaning were examined in this experiment. A total of 720 weaner pigs(360 entire males and 360 females) were selected at weaning(27 ± 3 d) and allocated to pens of 10 based on individual weaning weight(light weaning weight: pigs below 6.5 kg; medium weaning weight: 6.5 to8 kg; heavy weaning weight: above 8.5 kg). Pens were then allocated in a 3 x 2 x 2 factorial arrangement of treatments with the respective factors being weaning weight(heavy, medium and light; H, M and l,respectively), weaner diet complexity(high complexity/cost, HC; low complexity/cost, lC), and gender(male and female). Common diets were fed to both treatment groups during the final 4 weeks of the weaner period(a period of 39 days). In the first 6 d after weaning, pigs offered the HC diets gained weight faster and used feed more efficiently than those offered the lC diets(P = 0.031). Pigs fed a HC diet after weaning tended to be heavier at the sale live weight of 123 d of age compared with pigs fed the lC diet(P = 0.056). There were no other main effects of the feeding program on growth performance through to slaughter. Weaning weight had a profound influence on lifetime growth performance and weight at 123 d of age, with H pigs at weaning increasing their weight advantage over the M and l pigs(101.3,97.1, 89.6 kg respectively, P lyses suggested there was a minimal benefit in terms of cost per unit live weight gain over lifetime when pigs were offered a HC feeding program to l,with a lower feed cost/kg gain. The results from this investigation confirm the impact of weaning weight on lifetime growth performance, and suggest that a HC feeding program should be focused on l weaner pigs(i.e., weaning weight less than 6.5 kg at 27 d of age) in order to maximise financial returns.

关键词： Pigs Performance Diet complexity Weaning weight Carcass characteristics Cost benefit analyses

Analysis for stress environment in the alveolar sac model

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Journal of Biomedical Science and Engineering 2013年第9期6卷 901-907页

作者： Ramana M. Pidaparti Matthew Burnette rebecca l. Heise Angela Reynolds Department of Applied Mathematics Virginia Commonwealth University Richmond USA Department of Biomedical Engineering Virginia Commonwealth University Richmond USA Department of Mechanical and Nuclear Engineering Virginia Commonwealth University Richmond USA

Better understanding of alveolar mechanics is very important in order to avoid lung injuries for patients undergoing mechanical ventilation for treatment of respiratory problems. The objective of this study was to investigate the alveolar mechanics for two different alveolar sac models, one based on actual geometry and the other an idealized spherical geometry using coupled fluid-solid computational analysis. Both the models were analyzed through coupled fluid-solid analysis to estimate the parameters such as pressures/ velocities and displacements/stresses under mechanical ventilation conditions. The results obtained from the fluid analysis indicate that both the alveolar geometries give similar results for pressures and velocities. However, the results obtained from coupled fluid-solid analysis indicate that the actual alveolar geometry results in smaller displacements in comparison to a spherical alveolar model. This trend is also true for stress/strain between the two models. The results presented indicate that alveolar geometry greatly affects the pressure/velocities as well as displacements and stresses/strains.

关键词： Alveolar Sac Stress Analysis Modeling

2-Octyl Cyanoacrylate Skin Adhesive for Topical Skin Incision Closure in Female Pelvic Surgery

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Open Journal of Obstetrics and Gynecology 2015年第5期5卷 280-285页

作者： rebecca l. James Marilyn Alejandro-Rodriquez Elba Adriana Perez Jeffrey Mangel MetroHealth Medical Center Cleveland OH USA

Background: 2-octyl cyanoacrylate (2OCA) high viscosity tissue adhesive (Medline Industries, Inc., Mundelein, Il) is a liquid topical skin adhesive. 2OCA offers the same design features and clinical utility in terms of flexibility, strength, and low complication rate as the commercially available 2OCA tissue adhesives. Additionally, 2OCA features high viscosity allowing for better control during the application process, polymerization without the use of an external activator, and a distinctive violet color for ease of application visualization. Objective: The aim of this prospective case series is to descriptively report clinical data with the application of 2OCA as a topical incision closure system in female pelvic surgery. The primary outcomes included: incisional pain, incisional dehiscence, and post-operative bleeding. The secondary outcome included drying times of the adhesive with regard to incision length. Methods: A prospective open-label observational case series study was conducted to evaluate the use of 2OCA in surgical wound closure of the topical skin in adult patients undergoing gynecologic surgical procedures. A total of 50 adult women undergoing gynecologic surgery were enrolled. 2OCA was applied only by surgeons who had undergone product training to the incisions in a standardized, protocol-defined fashion. Drying times for the adhesive and photography were recorded intraoperatively. Post treatment follow-up was conducted with queries of pain level, incisional dehiscence, and incisional bleeding immediately post-operatively, 48 hours, 5 - 10 days and 14 days post-treatment. Adverse events were documented. Results: 2OCA was applied to a total of 154 incisions from the 50 patients enrolled to the study. The procedures included: 16 laparoscopic total hysterectomies, 4 diagnostic laparoscopies, 2 laparoscopic myomectomies, 2 laparoscopic bilateral or unilateral salpingo-oophorectomies, 5 total robotic-assisted laparoscopic surgeries (2 total hysterectom

关键词： Female Pelvic Surgery Gynecologic Surgery Octyl Cyanoacrylate Surgical Incision Skin Closure

Hepatic sarcoidosis complicating treatment-naive viral hepatitis

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World Journal of Hepatology 2012年第12期4卷 402-405页

作者： Aloysious Aravinthan William Gelso Anita limbu rebecca Brais Paul Richardson Department of Hepatology Cambridge University Hospitals NHS TrustCambridge CB2 0QQUnited Kingdom Department of Hepatology Cambridge University Hospitals NHS TrustCambridge CB2 0QQUnited Kingdom n Department of Histopathology Cambridge University Hospitals NHS TrustCambridge CB2 0QQUnited Kingdom Department of Hepatology The Royal Liverpool and Broadgreen University Hospitals NHS TrustLiverpool L7 8XPUnited Kingdom

Hepatic sarcoidosis is usually asymptomatic but rarely leads to adverse liver-related ***-existence of viral hepatitis and hepatic sarcoidosis is a rare,but recognised *** a balance between immune suppression and anti-viral therapy may be *** in the presence of viral hepatitis can lead to rapid deterioration of liver ***,anti-viral therapy may exacerbate granulomatous *** we present two cases of viral hepatitis co-existing with sarcoidosis that illustrate successful management *** one,hepatitis B replication was suppressed with oral antiviral therapy before commencing *** the second,remission of hepatic sarcoidosis was achieved with prednisolone,before treating hepatitis C and obtaining a sustained virological response with pegylated interferon and ribavirin therapy.

关键词： Hepatic sarcoidosis Chronic hepatitis C infection Chronic hepatitis B infection Immune suppression Anti-viral therapy

Efficient hexane isomers separation in isoreticular bipyrazolate metal-organic frameworks:The role of pore functionalization

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Nano Research 2021年第2期14卷 532-540页

作者： rebecca Vismara Corrado Di Nicola Rodrigo Gil-San Millan Kostiantyn V.Domasevich Claudio Pettinari Jorge A.R.Navarro Simona Galli Dipartimento di Scienza e Alta Tecnologiay University delVInsubria 22100 ComoItaly School of Science and Technology University ofCamerino62032 Camerino(MC)Italy Departamento de Quimica Inorganica Universidad de Granada18071 GranadaSpain Taras Shevchenko National University of Kyiv 01601 KyivUkraine School of Pharmacy University of Camerino62032 Camerino(MC)Italy Istituto di Chimica dei Composti Organometallici(ICCOM-CNR) 50019 Sesto FiorentinoItaly Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali 50121 FirenzeItaly Department of Chemistry University of LiverpoolLiverpool L73NYUK

Hydrocarbons separation in petrochemical industries is a key,energy-consuming stage in the manufacture of high-quality added-value products—hence the need for more efficient materials and environmentally friendly methodologies to improve this *** this context,we have studied the effect of metal-organic frameworks(MOFs)pore functionalization in hexane isomers separation,isolating the robust isoreticular zinc(ll)bipyrazolates Zn(BPZ),showing no pore decoration,Zn(Me_(2)BPZ),the pores of which are decorated with apolar methyl groups,and Zn(BPZ(NH_(2))_(2)),the spacers of which possess polar lewis-basic functions(H_(2)BPZ=1H,1'H-4,4'-bipyrazole;H_(2)Me_(2)BPZ=3,3'-dimethyl-1H,1'H-4,4'-bipyrazole;H_(2)BPZ(NH_(2))_(2)=3,5-diamino-1H,1'H-4,4'-bipyrazole;DMF=dimethylformamide).After characterizing Zn(BPZ(NH_(2))_(2))as per its crystal structure and thermal behaviour,and all the three MOFs as per their textural properties,we investigated,from the experimental and computational points of view,the impact of the square one-dimensional channels decoration on the separation of the hexane isomers,demonstrating the relevance of pore constrictions in the resolution of the title alkanes mixture.

关键词： adsorption molecular sieving nitrogen-donor ligands gas separation pow der diffraction variable-tem perature pulse gas chromatography

Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse

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Cellular & Molecular Immunology 2010年第3期7卷 211-220页

作者： Paul l Bollyky Stephen P Evanko rebecca P Wu Susan Potter-Perigo S Alice long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight Benaroya Research Institute SeattleWAUSA

Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and *** hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC *** primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA ***,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA *** effects were seen upon the addition of exogenous Th1 cytokines,Il-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th *** data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell *** also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen *** data point to a pivotal role for HA in DC–T cell interactions at the IS.

关键词： dendritic cell hyaluronan immune synapse pericellular matrix Th1

The Potential Risk Associated with Foodborne Pathogens in Watersheds: <i>Salmonellap</i>spp. in Dairy Cattle

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Journal of Water Resource and Protection 2015年第6期7卷 476-484页

作者： rebecca Bordonaro Patrick l. McDonough Yung-Fu Chang Hussni O. Mohammed Section of Epidemiology Department of Population Medicine and Diagnostic Sciences College of Veterinary Medicine Cornell University Ithaca NY USA

Salmonella spp. is one of the most important food- and waterborne pathogens implicated in human and animal disease. A repeat cross-sectional study was performed to assess the occurrence of Salmonella in dairy herds in a watershed and determine the factors that play a role in the likelihood of perpetuation of this organism among animals on these farms. A convenience sample of herds in the Delaware County watershed was selected based on farmers’ willingness to participate. Fecal samples were collected per rectum from a representative sample of cattle in these herds and tested for the presence of Salmonella using a combination of culturing and molecular detection methods. The significance of association between the putative risk factors and the likelihood of Salmonella spp. was evaluated using the logistic regression analysis. A total of 34 dairy farms were enrolled in the study and 1987 samples were collected coinciding with seasonal variation. Salmonella spp. was detected in 44% (15/34) of the herds in the study population (i.e., from at least one animal in these herds). However, only a small fraction of the entire sampling population (1.7%) was found to be shedding Salmonella. Risk factors that were found to be associated with the presence of the pathogen on the farm in the final multivariable model included concrete flooring for calves, prevention of calf access to the dam, and the lack of a designated calving pen. Two serovars, Salmonella enterica serovar Infantis and Salmonella enterica serovar Oranienburg, were identified among the isolates recovered in this study. Our study demonstrated that there was a potential risk of watershed degradation from Salmonella associated with cattle.

关键词： Salmonellap Risk Dairy Cows Watershed Polymerase Chain Reaction (PCR)