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We seek to transform how new and emergent variants of pandemiccausing viruses, specifically SARS-CoV-2, are identified and classified. By adapting large language models (LLMs) for genomic data, we build genome-scale language models (GenSLMs) which can learn the evolutionary landscape of SARS-CoV-2 genomes. By pretraining on over 110 million prokaryotic gene sequences and finetuning a SARS-CoV-2-specific model on 1.5 million genomes, we show that GenSLMs can accurately and rapidly identify variants of concern. Thus, to our knowledge, GenSLMs represents one of the first whole genome scale foundation models which can generalize to other prediction tasks. We demonstrate scaling of GenSLMs on GPU-based supercomputers and AI-hardware accelerators utilizing 1.63 Zettaflops in training runs with a sustained performance of 121 PFLOPS in mixed precision and peak of 850 PFLOPS. We present initial scientific insights from examining GenSLMs in tracking evolutionary dynamics of SARS-CoV-2, paving the path to realizing this on large biological data.
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Objective: To investigate the representability and etiological diagnostic value of myocardium samples obtained from patients with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography-guided percutaneous intramyocardial septal biopsy (myocardial biopsy of Liwen procedure). Methods: This study was a retrospective case-series analysis. Patients with HCM, who underwent myocardial biopsy of Liwen procedure and radiofrequency ablation in Xijing Hospital, Air Force Military Medical University from July to December 2019, were included. Demographic data (age, sex), echocardiographic data and complications were collected through electronic medical record system. The histological and echocardiographic features, pathological characteristics of the biopsied myocardium of the patients were analyzed. Results: A total of 21 patients (aged (51.2±14.5) years and 13 males (61.9%)) were enrolled. The thickness of ventricular septum was (23.3±4.5)mm and the left ventricular outflow tract gradient was (78.8±42.6)mmHg (1 mmHg=0.133 kPa). Eight patients (38.1%) were complicated with hypertension, 1 patient (4.8%) had diabetes, and 2 patients (9.5%) had atrial fibrillation. Hematoxylin-eosin staining of myocardial samples of HCM patients before radiofrequency ablation evidenced myocytes hypertrophy, myocytes disarray, nuclear hyperchromatism, hypertrophy, atypia, coronary microvessel abnormalities, adipocyte infiltration, inflammatory cell infiltration, cytoplasmic vacuoles, lipofuscin deposition. Interstitial fibrosis and replacement fibrosis were detected in Masson stained biopsy samples. Hematoxylin-eosin staining of myocardial samples of HCM patients after radiofrequency ablation showed significantly reduced myocytes, cracked nuclear in myocytes, coagulative necrosis, border disappearance and nuclear fragmentation. Quantitative analysis of myocardial specimens of HCM patients before radiofrequency ablation showed that there were 9 cases (42.9%) with mild myocardial hypertrophy and 12 cases (57.1%) with severe myocardial hypertrophy. Mild, moderate and severe fibrosis were 5 (23.8%), 9 (42.9%) and 7 (33.3%), respectively. Six cases (28.6%) had myocytes disarray. There were 11 cases (52.4%) of coronary microvessel abnormalities, 4 cases (19.0%) of adipocyte infiltration, 2 cases (9.5%) of inflammatory cell infiltration,6 cases (28.5%) of cytoplasmic vacuole, 16 cases (76.2%) of lipofuscin deposition. The diameter of cardiac myocytes was (25.2±2.8)μm, and the percentage of collagen fiber area was 5.2%(3.0%, 14.6%). One patient had severe replacement fibrosis in the myocardium, with a fibrotic area of 67.0%. The rest of the patients had interstitial fibrosis. The myocardial specimens of 13 patients were examined by transmission electron microscopy. All showed increased myofibrils, and 9 cases had disorder of myofibrils. All patients had irregular shape of myocardial nucleus, partial depression, mild mitochondrial swelling, fracture and reduction of mitochondrial crest, and local aggregation of myofibrillary interfascicles. One patient had hypertrophy of cardiomyocytes, but the arrangement of muscle fibers was roughly normal. There were vacuoles in the cytoplasm, and Periodic acid-Schiff staining was positive. Transmission electron microscopy showed large range of glycogen deposition in the cytoplasm, with occasional double membrane surround, which was highly indicative of glycogen storage disease. No deposition of glycolipid substance in lysozyme was observed under transmission electron microscope in all myocardial specimens, which could basically eliminate Fabry disease. No apple green substance was found under polarized light after Congo red staining, which could basically exclude cardiac amyloidosis. Conclusion: Myocardium biopsied samples obtained by Liwen procedure of HCM patients are representative and helpful for the etiological diagnosis of HCM.
Subject(s)
Humans , Male , Biopsy/adverse effects , Cardiomegaly/pathology , Cardiomyopathy, Hypertrophic/diagnosis , Eosine Yellowish-(YS) , Fibrosis , Heart Defects, Congenital , Hematoxylin , Lipofuscin , Myocardium/pathology , Retrospective StudiesABSTRACT
We seek to completely revise current models of airborne transmission of respiratory viruses by providing never-before-seen atomic-level views of the SARS-CoV-2 virus within a respiratory aerosol. Our work dramatically extends the capabilities of multiscale computational microscopy to address the significant gaps that exist in current experimental methods, which are limited in their ability to interrogate aerosols at the atomic/molecular level and thus ob-scure our understanding of airborne transmission. We demonstrate how our integrated data-driven platform provides a new way of exploring the composition, structure, and dynamics of aerosols and aerosolized viruses, while driving simulation method development along several important axes. We present a series of initial scientific discoveries for the SARS-CoV-2 Delta variant, noting that the full scientific impact of this work has yet to be realized. ACM Reference FormatAbigail Dommer1{dagger}, Lorenzo Casalino1{dagger}, Fiona Kearns1{dagger}, Mia Rosenfeld1, Nicholas Wauer1, Surl-Hee Ahn1, John Russo,2 Sofia Oliveira3, Clare Morris1, AnthonyBogetti4, AndaTrifan5,6, Alexander Brace5,7, TerraSztain1,8, Austin Clyde5,7, Heng Ma5, Chakra Chennubhotla4, Hyungro Lee9, Matteo Turilli9, Syma Khalid10, Teresa Tamayo-Mendoza11, Matthew Welborn11, Anders Christensen11, Daniel G. A. Smith11, Zhuoran Qiao12, Sai Krishna Sirumalla11, Michael OConnor11, Frederick Manby11, Anima Anandkumar12,13, David Hardy6, James Phillips6, Abraham Stern13, Josh Romero13, David Clark13, Mitchell Dorrell14, Tom Maiden14, Lei Huang15, John McCalpin15, Christo- pherWoods3, Alan Gray13, MattWilliams3, Bryan Barker16, HarindaRajapaksha16, Richard Pitts16, Tom Gibbs13, John Stone6, Daniel Zuckerman2*, Adrian Mulholland3*, Thomas MillerIII11,12*, ShantenuJha9*, Arvind Ramanathan5*, Lillian Chong4*, Rommie Amaro1*. 2021. #COVIDisAirborne: AI-Enabled Multiscale Computational Microscopy ofDeltaSARS-CoV-2 in a Respiratory Aerosol. In Supercomputing 21: International Conference for High Perfor-mance Computing, Networking, Storage, and Analysis. ACM, New York, NY, USA, 14 pages. https://doi.org/finalDOI
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The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replication transcription complex (RTC) is a multi-domain protein responsible for replicating and transcribing the viral mRNA inside a human cell. Attacking RTC function with pharmaceutical compounds is a pathway to treating COVID-19. Conventional tools, e.g., cryo-electron microscopy and all-atom molecular dynamics (AAMD), do not provide sufficiently high resolution or timescale to capture important dynamics of this molecular machine. Consequently, we develop an innovative workflow that bridges the gap between these resolutions, using mesoscale fluctuating finite element analysis (FFEA) continuum simulations and a hierarchy of AI-methods that continually learn and infer features for maintaining consistency between AAMD and FFEA simulations. We leverage a multi-site distributed workflow manager to orchestrate AI, FFEA, and AAMD jobs, providing optimal resource utilization across HPC centers. Our study provides unprecedented access to study the SARS-CoV-2 RTC machinery, while providing general capability for AI-enabled multi-resolution simulations at scale.
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{beta}-coronaviruses alone have been responsible for three major global outbreaks in the 21st century. The current crisis has led to an urgent requirement to develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components are required as a back-up against the emergence of lethal viral variants. One such target is the main protease (Mpro) that plays an indispensible role in viral replication. The availability of over 270 Mpro X-ray structures in complex with inhibitors provides unique insights into ligand-protein interactions. Herein, we provide a comprehensive comparison of all non-redundant ligand-binding sites available for SARS-CoV2, SARS-CoV and MERS-CoV Mpro. Extensive adaptive sampling has been used to explore conformational dynamics employing convolutional variational auto encoder-based deep learning, and investigates structural conservation of the ligand binding sites using Markov state models across {beta}-coronavirus homologs. Our results indicate that not all ligand-binding sites are dynamically conserved despite high sequence and structural conservation across {beta}-coronavirus homologs. This highlights the complexity in targeting all three Mpro enzymes with a single pan inhibitor.
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Despite the recent availability of vaccines against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the search for inhibitory therapeutic agents has assumed importance especially in the context of emerging new viral variants. In this paper, we describe the discovery of a novel non-covalent small-molecule inhibitor, MCULE-5948770040, that binds to and inhibits the SARS-Cov-2 main protease (Mpro) by employing a scalable high throughput virtual screening (HTVS) framework and a targeted compound library of over 6.5 million molecules that could be readily ordered and purchased. Our HTVS framework leverages the U.S. supercomputing infrastructure achieving nearly 91% resource utilization and nearly 126 million docking calculations per hour. Downstream biochemical assays validate this Mpro inhibitor with an inhibition constant (Ki) of 2.9 {micro}M [95% CI 2.2, 4.0]. Further, using room-temperature X-ray crystallography, we show that MCULE-5948770040 binds to a cleft in the primary binding site of Mpro forming stable hydrogen bond and hydrophobic interactions. We then used multiple {micro}s-timescale molecular dynamics (MD) simulations, and machine learning (ML) techniques to elucidate how the bound ligand alters the conformational states accessed by Mpro, involving motions both proximal and distal to the binding site. Together, our results demonstrate how MCULE-5948770040 inhibits Mpro and offers a springboard for further therapeutic design. O_TEXTBOXSignificance StatementThe ongoing novel coronavirus pandemic (COVID-19) has prompted a global race towards finding effective therapeutics that can target the various viral proteins. Despite many virtual screening campaigns in development, the discovery of validated inhibitors for SARS-CoV-2 protein targets has been limited. We discover a novel inhibitor against the SARS-CoV-2 main protease. Our integrated platform applies downstream biochemical assays, X-ray crystallography, and atomistic simulations to obtain a comprehensive characterization of its inhibitory mechanism. Inhibiting Mpro can lead to significant biomedical advances in targeting SARS-CoV-2 treatment, as it plays a crucial role in viral replication. C_TEXTBOX
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Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation by activating nuclear factor-κB (NF-κB). Sirtuin 2 (SIRT2) is a key modulator in inflammation. However, the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied. Therefore, this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues. Subsequently, SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway. The activation of p65 triggered airway inflammation, increment of mucus secretion by goblet cells, and acceleration of tracheal stenosis. Meanwhile, p65 phosphorylation and acetylation, airway inflammation, and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5. Triptolide (a specific p65 inhibitor) reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure. Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.
Subject(s)
Animals , Mice , Inflammation , NF-kappa B/metabolism , Particulate Matter/toxicity , Signal Transduction , Sirtuin 2/metabolism , Transcription Factor RelA/metabolismABSTRACT
We develop a generalizable AI-driven workflow that leverages heterogeneous HPC resources to explore the time-dependent dynamics of molecular systems. We use this workflow to investigate the mechanisms of infectivity of the SARS-CoV-2 spike protein, the main viral infection machinery. Our workflow enables more efficient investigation of spike dynamics in a variety of complex environments, including within a complete SARS-CoV-2 viral envelope simulation, which contains 305 million atoms and shows strong scaling on ORNL Summit using NAMD. We present several novel scientific discoveries, including the elucidation of the spikes full glycan shield, the role of spike glycans in modulating the infectivity of the virus, and the characterization of the flexible interactions between the spike and the human ACE2 receptor. We also demonstrate how AI can accelerate conformational sampling across different systems and pave the way for the future application of such methods to additional studies in SARS-CoV-2 and other molecular systems. ACM Reference FormatLorenzo Casalino1{dagger}, Abigail Dommer1{dagger}, Zied Gaieb1{dagger}, Emilia P. Barros1, Terra Sztain1, Surl-Hee Ahn1, Anda Trifan2,3, Alexander Brace2, Anthony Bogetti4, Heng Ma2, Hyungro Lee5, Matteo Turilli5, Syma Khalid6, Lillian Chong4, Carlos Simmerling7, David J. Hardy3, Julio D. C. Maia3, James C. Phillips3, Thorsten Kurth8, Abraham Stern8, Lei Huang9, John McCalpin9, Mahidhar Tatineni10, Tom Gibbs8, John E. Stone3, Shantenu Jha5, Arvind Ramanathan2*, Rommie E. Amaro1*. 2020. AI-Driven Multiscale Simulations Illuminate Mechanisms of SARS-CoV-2 Spike Dynamics. In Supercomputing 20: International Conference for High Performance Computing, Networking, Storage, and Analysis. ACM, New York, NY, USA, 14 pages. https://doi.org/finalDOI
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Objective The influenza A (H1N1) virus has the characteristic of strong infectiousness and variation. It can threaten the lives of patients. In this paper,we investigated the expression of programmed cell death molecule 5 (PDCD5) in peripheral blood of patients with influenza A (H1N1) and its correlation with the severity of disease. Methods The data of 104 patients with influenza A (H1N1) treated in Affiliated Hospital of Hebei University from January 2015 to December 2017 were analyzed retrospectively. The 104 patients were divided into the mild H1N1 group (n=78) and the severe H1N1 group (n=26). At the same time,104 healthy physical examination subjects were selected as control group. The blood routine,lymphocyte count and PDCD level were observed in three groups. Results The number of leukocytes,neutrophils and lymphocytes of the mild H1N1 group and severe H1N1 group were significantly lower than those of the control group (P<0.05). The number of leukocytes,neutrophils and lymphocytes of the severe H1N1 group were significantly lower than those of the mild H1N1 group (P<0.05). There was no significant difference in mononuclear cells between three groups (P>0.05). The levels of PDCD5 and lymphocyte apoptosis rate of the mild H1N1 group and severe H1N1 group were significantly higher than those of the control group (P<0.05) ,the severe H1N1 group was significantly higher than the mild H1N1 group (P<0.05). The total T cells,CD4+T cells and CD8+T cells of the mild H1N1 group and severe H1N1 group were significantly lower than those of the control group (P<0.05). The total T cells,CD4+T cells and CD8+T cells of the severe H1N1 group were significantly lower than those of the mild H1N1 group and con-trol group (P<0.05). The level of PDCD5 was positively correlated with the severity of disease and the rate of lymphocyte apoptosis (r=0.872,0.904,P<0.05),and negatively correlated with total T cells,CD4+T cells and CD8+T cells (r=-0.842,-0.805,-0.877,P<0.05). The sensitivity,specificity and area under the curve of PDCD5 to prediction of severe type H1N1 were 92.31%,97.25% and 0.941,respectively. Conclusion The level of peripheral blood PDCD5 in patients with influenza A (H1N1) virus in-fection is associated with the severity of the disease,and it can be considered as an important biomarker to predict severe influenza A (H1N1).
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Agonists of peroxisome proliferator-activated receptor gamma (PPARgamma) are of interest as a treatment of type II diabetes, and indenone derivatives are a new class of non-TZD PPARgamma agonists. Based on existing indenone derivatives, a series of novel ones have been designed and synthesized. Meanwhile the structures have been comfirmed with 1H NMR and MS. Among them, 17b and 19 showed higher agonistic activities than rosiglitazone.
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Drug Design , Hypoglycemic Agents , Pharmacology , Indenes , Chemistry , Pharmacology , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Structure , PPAR gamma , Structure-Activity Relationship , Thiazolidinediones , PharmacologyABSTRACT
Ubiquitin-proteasome pathway (UPP) is one of the ways utilized for selective degradation of many proteins in cells, and the 20S proteasome takes the functional machinery where hydrolysis of targeted proteins takes place. Based on existing peptide inhibitors, a series of novel tripeptidic tetrazoles have been designed, synthesized, and the structures have been confirmed with 1H NMR, MS and elemental analysis. Among them, three compounds (6b, 6d and 6h) showed inhibitory activities of ChT-L of 20S proteasome.
Subject(s)
Biological Assay , Drug Design , Molecular Structure , Oligopeptides , Chemistry , Pharmacology , Proteasome Endopeptidase Complex , Chemistry , Proteasome Inhibitors , Chemistry , Pharmacology , Tetrazoles , Chemistry , PharmacologyABSTRACT
Objective To evaluate the diagnostic accuracy of 3.0 T contrast enhanced (CE) whole heart coronary MRA ( CE MRA ) using 32-channel coils with high acceleration factor. Methods Sixty patients with suspected coronary artery disease who were scheduled for coronary angiography (CAG)underwent CE CMRA at 3.0 T MRI scanner. A 32-channel receiver coil was used for data acquisition. For image acquisition, an ECG-triggered, navigator-gated, inversion-recovery prepared, segmented gradient-echo sequence was used with an acceleration factor of three in the phase-encoding direction using GRAPPA reconstruction. Gd-BOPTA (0.15 mmol/kg body weight) was intravenously administered at a rate of 0. 3 ml/s. The diagnostic accuracy in detecting significant stenoses ( ≥50% of vessel lumen) was evaluated using χ2 test with X-ray angiography as the reference. Results Whole-heart CE CMRA was successfully completed in 56 patients who were scheduled for CAG. The averaged imaging time was ( 6. 0 ± 1.3 ) min.3.0 T CE CMRA using 32 channel coils correctly identified significant CAD in 28 patients and correctly ruled out CAD in 23 patients. The sensitivity and specificity were 93. 3% and 88.5% respectively.Conclusion Combined with dedicated 32-channel coils, 3.0 T CE CMRA allows significant reduction in imaging speed and reduced dose of the contrast agent. These improvements resulted in substantially improved overall accuracy of CE CMRA in detecting coronary artery disease.
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Objective To evaluate the value of contrast-enhanced whole-heart coronary magnetic resonance angiography ( CE CMRA ) at 3.0 T in the delineation of cardiac venous anatomy. Methods Contrast-enhanced whole-heart CMRA at 3.0T was performed in 43 consecutive subjects using ECG-triggered, navigator-gated, inversion-recovery prepared, segmented gradient-echo sequence with a 32-channel cardiac coil. The visibility of the coronary veins was graded visually using a 4-point scale.Continuous variable was expressed as (-x)±s. The paired student t test was used to evaluate the differences of the coronary sinus (CS) ostium diameter in anteroposterior and superoinferior directions. Results CMRA examination was successfully completed in 40 subjects with acquisition time of ( 6. 9 ± 1.8 ) min. The cardiac veins were finally evaluated in 38 of 40 (95.0%) subjects. The mean distance of the posterior vein of the left ventricle (PVLV) and the left marginal vein (LMV) to the CS ostium were (3.34 ± 0. 90) and (6. 12 ± 1.02) cm, respectively. The mean visibility scores of CS, posterior interventricular vein (PIV),PVLV, LMV, and anterior interventricular vein (AIV) were 4.0 ± 0.0, 3.4 ± 0. 5, 3.4 ± 0. 5, 3.0 ± 0. 8,and 3. 3 ± 0. 5, respectively. The diameter of the CS ostium in the superoinferior direction ( 1.13 ±0. 26) cm was larger than that in the anteroposterior direction (0. 82 ± 0. 19) cm (t = -4. 31 ,P <0. 05).Conclusion Contrast-enhanced whole-heart CMRA at 3.0 T can clearly depict the cardiac venous anatomy.
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<p><b>BACKGROUND</b>Non-cement femoral stems are recognized in clinical use, but there are still some problems. The aim of this research was to make non-cement femoral stems to be press-fit with the medullary cavity.</p><p><b>METHODS</b>Twenty-four healthy adult mongrel dogs were randomly divided into experimental and control groups. In the right hip joint, an artificial femoral bone replacement surgery was conducted. For the experimental group, the replacement surgery of hydroxyapatite (HA)-coated femoral stems was done, while autogeneous morselized bone was implanted into the medullary cavity. For the control group, morselized bone was not implanted. At postoperative 1, 3, 6 months, a test for interfacial shear characteristics was conducted in the MTS810 Tester. The comparison between the two groups' bone-prostheses in shear strength for their interface from shearing destruction was made. A histological observation to check prosthesis-bone interface contact ratios and bone growth was carried out.</p><p><b>RESULTS</b>For the experimental group, shear strength was 0.317 MPa in 1 month, 1.447 MPa in 3 months, and 1.621 MPa in 6 months. For the control group, shear strength was 0.195 MPa in 1 month, 1.023 MPa in 3 months, and 1.483 MPa in 6 months. The difference was statistically significant. Stereomicroscope-based observation showed that the number of trabecular bones in the experimental group was larger than that of the control group, and bone growth of the former group was better than that of the latter group. Inverted microscopic observation showed that the binding degree between the prosthesis and trabecular bone of the experimental group was higher than that of the control group. Comparatively, the experimental group's trabecular bone had more stromal cells.</p><p><b>CONCLUSIONS</b>The morselized bones can effectively improve the biological bonding strength and bone-contact ratios in the short term for the HA-coated femoral stem and accelerate the bonding process. The use of morselized autogenous bones played a good role in bone in-growth of the femoral bone stem surface.</p>
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Animals , Dogs , Female , Male , Biomechanical Phenomena , Coated Materials, Biocompatible , Chemistry , Durapatite , Chemistry , Femur , Pathology , General Surgery , Osseointegration , Random Allocation , Shear StrengthABSTRACT
Objective To describe MRI findings of acute spinal cord decompression sickness.Methods MRI findings of 5 cases with clinical definite acute spinal cord decompression sickness were retrospectively analyzed.The main clinical informations included underwater performance history against regulations,short-term complete or incomplete spinal cord injury symptoms after fast going out of water,sensory disability and urinary and fecal incontinence,etc.Results Spinal cord vacuole sign was found in all 5 cases.Iso-signal intensity(n=3),high signal intensity(n=1),and low signal intensity (n=1)was demonstrated on T1 WI,and high signal intensity(n=5)was found on T2 WI.Owl eye sign was detected in 3 cases,and lacune foci were seen in 2 cases.Conclusion MRI findings of acute spinal cord decompression sickness had some characteristics,and it was easy to diagnose by combining diving history with clinical manifestations.
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Objective To explore the imaging findings and diagnostic values of X-ray, CT, MR,and ultrasonography in traumatic knee joints hemarthrosis and lipohemarthrosis. Methods Traumatic knee joints hemarthrosis (12 knees) and lipohemarthrosis (18 knees) proved by operation (27 knees) or puncturation (3 knees) were included in the study. Horizontal-beam plain radiographs (16 knees), CT (30 knees), MRI (30 knees) and ultrasonography (24 knees) in supine position were investigated. Results (1)supine position horizontal-beam plain radiographs: Fat-liquid layer was found in 8 cases of lipohemarthrosis. Dense supragenual bursa was found in 1 case of lipohemarthrosis and 7 cases of hemarthrosis. Fracture (13 knees) was diagnosed correctly. (2) CT findings: double fluid-fluid layer was found in 11 of all 18 cases, and single fluid-fluid layer was found in 7 of 11 cases of lipohemarthrosis. Single fluid-fluid layer was found in 3 of 12 cases of hemarthrosis. Isodensity was detected in 9 cases, and high-density blood clot was found in 4 cases. Fracture (30 knees) was diagnosed correctly. (3) MRI findings: in 12 of 18 cases of lipohemarthrosis, double fluid-fluid layer was shown including supernatant layer as short T1, long T2signal and low signal after fat-suppression, middle layer as long T1, long T2 signal and high signal after fat-suppression, and dependent layer as iso-T1, iso-T2 and slight high signal after fat-suppression. Single fluid-fluid layer was seen in 6 cases, only had aforementioned upper and under layer.Only aforementioned supernatant layer and dependent layer were seen in 12 cases of hemarthrosis. 4 cases showed entire blood clot in fluid, T1WI showed middle signal or center iso-signal accompanied with peripheral high signal ring, and fat-suppression imaging showed high signal. T2WI and fat-suppressionimaging showed middling or high signal accompanied with peripheral low signal ring. Fracture (30 knees) was diagnosed correctly. (4) Ultrasound findings: In 10 of 14 cases of lipohemarthrosis, double fluid-fluid level was shown, supernatant layer as equal echo, middle layer as echoless, and dependent layer as cloudy echo. Four cases with single fluid-fluid level only showed aforementioned upper and under layer. Three of 10 cases of hemarthrosis showed single fluid-fluid level, only showing aforementioned upper and under layer,and 7 cases showed cloudy echo and float. In 3 cases the fluid blood clot showed irregular shape low-equal echo bolus. No fracture hne was found. Conclusions CT can clearly detect fracture line, hemarthrosis and lipohemarthresis, and can substitute plain radiography. MRI is the best way to diagnose hemarthresis and lipohemarthrosis. Ultrasonography can be used in diagnosing hemarthresis and lipohemarthrosis but not helpful in the diagnosis of fracture.
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Objective To explore MRI findings of intervertebral suppurative spondylitis. Methods MRI findings of intervertebral suppurative spondylitis in 12 cases proved by surgery and 6 cases defined by clinical features were retrospectively analyzed. The MRI protocol included un-enhanced conventional scan in 18 cases and contrast-enhanced scan in 11 cases. Results Of the 18 cases, single focus was found in 16 cases, and multiple loci were seen in 2 cases. MRI findings included (1) Disappearance sign of nuclear crevice in 17 cases, accumulated fluid sign of intervertebral disc in 15 cases, intervertebral disc perforation in 4 cases, and intervertebral space narrowing in 7 cases. (2) Bone destruction under end plate and marrow oedema were shown in 18 cases, 17 cases had end plate destruction, 16 cases had covered sign of end plate.(3) Paraspinal soft tissue swelling was shown in 18 cases, in which thick wall microabscess was formed in 4 cases. (4) Vertebral canal was involved in 12 cases, vertebral canal abscess was formed in 5 cases.(5) Lump enhancement was demonstrated in 4 cases, nodular enhancement in 2, and ring-like enhancement in 2, respectively. No enhancement was seen in 3 cases. Dural sac linear enhancement was shown in 6 cases, and patchy enhancement in the anterior dural sac was shown in 10 cases. Conclusion Intervertebral suppurative spondytitis had characteristic MRI findings, and the key to correct diagnosis was to combine MRI finding with clinical characteristics.
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Covellite oxidation was evaluated with two acidophilic thiobacilli that are important in bioleaching processes.The experiments were carried out in shake flasks in the absence and presence of 4 g/L Fe2+ (as ferrous sulphate) at pH 2.0, 150 rpm and 35 ℃. The tests showed that the copper extraction by the Acidithiobacillus ferrooxidans culture was nearly the same as that by the mixed culture of Acidithiobacillus ferrooxidans and Acidithiobacillus caldus. On the other hand, additional iron clearly improved Cu leaching.
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Covellite oxidation was evaluated with two acidophilic thiobacilli that are important in bioleaching processes.The experiments were carried out in shake flasks in the absence and presence of 4 g/L Fe2+ (as ferrous sulphate) at pH 2.0, 150 rpm and 35 ℃. The tests showed that the copper extraction by the Acidithiobacillus ferrooxidans culture was nearly the same as that by the mixed culture of Acidithiobacillus ferrooxidans and Acidithiobacillus caldus. On the other hand, additional iron clearly improved Cu leaching.
ABSTRACT
Covellite oxidation was evaluated with two acidophilic thiobacilli that are important in bioleaching processes.The experiments were carried out in shake flasks in the absence and presence of 4 g/L Fe2+ (as ferrous sulphate) at pH 2.0, 150 rpm and 35 ℃. The tests showed that the copper extraction by the Acidithiobacillus ferrooxidans culture was nearly the same as that by the mixed culture of Acidithiobacillus ferrooxidans and Acidithiobacillus caldus. On the other hand, additional iron clearly improved Cu leaching.
