| 1. |
- Agirre, Jon, et al.
(författare)
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The CCP4 suite: integrative software for macromolecular crystallography
- 2023
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Ingår i: Acta Crystallographica Section D. - : INT UNION CRYSTALLOGRAPHY. - 2059-7983. ; 79, s. 449-461
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Tidskriftsartikel (refereegranskat)abstract
- The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.
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| 2. |
- Rieke, Johanna Magdalena, et al.
(författare)
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SLC20A1Is Involved in Urinary Tract and Urorectal Development
- 2020
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Ingår i: Frontiers in Cell and Developmental Biology. - : FRONTIERS MEDIA SA. - 2296-634X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies in developingXenopusand zebrafish reported that the phosphate transporterslc20a1ais expressed in pronephric kidneys. The recent identification ofSLC20A1as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role ofSLC20A1in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish orthologslc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detectedSLC20A1in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequencedSLC20A1in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelicde novovariants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novelde novovariant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact ofSLC20A1variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggestSLC20A1is involved in urinary tract and urorectal development and implicateSLC20A1as a disease-gene for BEEC.
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| 3. |
- Ali, Tahir, et al.
(författare)
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Cellulose ether treatment inhibits amyloid beta aggregation, neuroinflammation and cognitive deficits in transgenic mouse model of Alzheimers disease
- 2023
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Ingår i: Journal of Neuroinflammation. - : BMC. - 1742-2094. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimers disease (AD) is an incurable, progressive and devastating neurodegenerative disease. Pathogenesis of AD is associated with the aggregation and accumulation of amyloid beta (A & beta;), a major neurotoxic mediator that triggers neuroinflammation and memory impairment. Recently, we found that cellulose ether compounds (CEs) have beneficial effects against prion diseases by inhibiting protein misfolding and replication of prions, which share their replication mechanism with A & beta;. CEs are FDA-approved safe additives in foods and pharmaceuticals. Herein, for the first time we determined the therapeutic effects of the representative CE (TC-5RW) in AD using in vitro and in vivo models. Our in vitro studies showed that TC-5RW inhibits A & beta; aggregation, as well as neurotoxicity and immunoreactivity in A & beta;-exposed human and murine neuroblastoma cells. In in vivo studies, for the first time we observed that single and weekly TC-5RW administration, respectively, improved memory functions of transgenic 5XFAD mouse model of AD. We further demonstrate that TC-5RW treatment of 5XFAD mice significantly inhibited A & beta; oligomer and plaque burden and its associated neuroinflammation via regulating astrogliosis, microgliosis and proinflammatory mediator glial maturation factor beta (GMF & beta;). Additionally, we determined that TC-5RW reduced lipopolysaccharide-induced activated gliosis and GMF & beta; in vitro. In conclusion, our results demonstrate that CEs have therapeutic effects against A & beta; pathologies and cognitive impairments, and direct, potent anti-inflammatory activity to rescue neuroinflammation. Therefore, these FDA-approved compounds are effective candidates for developing therapeutics for AD and related neurodegenerative diseases associated with protein misfolding.
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| 4. |
- Becket, Ralph, et al.
(författare)
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Spoken Language Translator: Phase Two Report
- 1997
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Spoken Language Translator (SLT) is a project whose long-term goal is the construction of practically useful systems capable of translating human speech from one language into another. The current SLT prototype, described in detail in this report, is capable of speech-to-speech translation between English and Swedish in either direction within the domain of airline flight inquiries, using a vocabulary of about 1500 words. Translation from English and Swedish into French is also possible, with slightly poorer performance.A good English-language speech recognizer existed before the start of the project, and has since been improved in several ways. During the project, we have constructed a Swedish-language recognizer, arguably the best system of its kind so far built. This has involved among other things collection of a large amount of Swedish training data. The recognizer is essentially domain-independent, but has been tuned to give high performance in the air travel inquiry domain.The main version of the Swedish recognizer is trained on the Stockholm dialect of Swedish, and achieves near-real-time performance with a word error rate of about 7%. Techniques developed partly under this project make it possible to port the recognizer to other Swedish dialects using only modest quantities of training data.On the language-processing side, we had at the start of the project a substantial domain-independent language-processing system for English, a preliminary Swedish version, and a sketchy set of rules to permit English to Swedish translation. We now have good versions of the language-processing system for English, Swedish and French, and fair to good support for translation in five of the six possible language- pairs. Translation is carried out using a novel robust architecture developed under the project. In essence, this translates as much of the input utterance as possible using a sophisticated grammar-based method, and then employs a much simpler set of word- to-word translation rules to fill in the gaps.The language-processing modules are all generic in nature, are based on large, linguistically motivated grammars, and can fairly easily be tuned to give good performance in new domains. Much of the work involved in the domain adaptation process can be carried out by non-experts using tools developed under the project.Formal comparisons are problematic, in view of the different domains and languages used and the lack of accepted evaluation criteria. None the less, the evidence at our disposal suggests that the current SLT prototype is no worse than the German Verbmobil demonstrator, in spite of a difference in project budget of more than an order of magnitude.
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| 5. |
- Zhuang, Xiahai, et al.
(författare)
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Evaluation of algorithms for Multi-Modality Whole Heart Segmentation : An open-access grand challenge.
- 2019
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Ingår i: Medical Image Analysis. - : Elsevier BV. - 1361-8415 .- 1361-8423. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of whole heart anatomy is a prerequisite for many clinical applications. Whole heart segmentation (WHS), which delineates substructures of the heart, can be very valuable for modeling and analysis of the anatomy and functions of the heart. However, automating this segmentation can be challenging due to the large variation of the heart shape, and different image qualities of the clinical data. To achieve this goal, an initial set of training data is generally needed for constructing priors or for training. Furthermore, it is difficult to perform comparisons between different methods, largely due to differences in the datasets and evaluation metrics used. This manuscript presents the methodologies and evaluation results for the WHS algorithms selected from the submissions to the Multi-Modality Whole Heart Segmentation (MM-WHS) challenge, in conjunction with MICCAI 2017. The challenge provided 120 three-dimensional cardiac images covering the whole heart, including 60 CT and 60 MRI volumes, all acquired in clinical environments with manual delineation. Ten algorithms for CT data and eleven algorithms for MRI data, submitted from twelve groups, have been evaluated. The results showed that the performance of CT WHS was generally better than that of MRI WHS. The segmentation of the substructures for different categories of patients could present different levels of challenge due to the difference in imaging and variations of heart shapes. The deep learning (DL)-based methods demonstrated great potential, though several of them reported poor results in the blinded evaluation. Their performance could vary greatly across different network structures and training strategies. The conventional algorithms, mainly based on multi-atlas segmentation, demonstrated good performance, though the accuracy and computational efficiency could be limited. The challenge, including provision of the annotated training data and the blinded evaluation for submitted algorithms on the test data, continues as an ongoing benchmarking resource via its homepage (www.sdspeople.fudan.edu.cn/zhuangxiahai/0/mmwhs/).
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