135 research outputs found
New encouraging developments in contact prediction: Assessment of the CASP11 results
This article provides a report on the state-of-the-art in the prediction of intra-molecular residue-residue contacts in proteins
based on the assessment of the predictions submitted to the CASP11 experiment. The assessment emphasis is placed on the
accuracy in predicting long-range contacts. Twenty-nine groups participated in contact prediction in CASP11. At least eight
of them used the recently developed evolutionary coupling techniques, with the top group (CONSIP2) reaching precision of
27% on target proteins that could not be modeled by homology. This result indicates a breakthrough in the development of
methods based on the correlated mutation approach. Successful prediction of contacts was shown to be practically helpful
in modeling three-dimensional structures; in particular target T0806 was modeled exceedingly well with accuracy not yet
seen for ab initio targets of this size (>250 residues
Si-Based Electrodes for Potentiometric Measurements of Aqueous Solutions, Journal of Telecommunications and Information Technology, 2009, nr 4
Three sensors for chemical and physical examination of aqueous solutions were presented in the paper. An Au potentiometric electrode, an AgCl chlorine ion sensor and a p-n junction thermometer were developed. Their layout and internal structure were explained in the light of the manufacturing process. The device characteristics were measured in conditions corresponding to normal operation of the devices. Basic electrical parameters of the developed structures, as well as their sensitivity to environmental parameter variation were estimated
Program of early detection of pulmonary neoplasms by the computed tomography - preliminary Szczecin experience
Wstęp: Rak płuca (RP) stanowi jeden z najpoważniejszych problemów epidemiologicznych i klinicznych w Polsce i na
świecie. Wyniki leczenia RP są niezadowalające. Jedną z przyczyn wysokiej umieralności z powodu RP jest niski odsetek pacjentów identyfikowanych we wczesnym stadium choroby. Obecnie na świecie prowadzi się kilka programów przesiewowych
RP opartych na tomografii komputerowej (TK). W Polsce dotychczas nie przeprowadzono tego typu badań.
Materiał i metody: Badaniami przesiewowymi objęto mieszkańców Szczecina znajdujących się w grupie podwyższonego
ryzyka zachorowania na raka płuca: wiek 55-65 lat, obie płcie, osoby palące tytoń lub mające w wywiadzie przynajmniej
20 paczkolat palenia. Program zaplanowano na minimum 3 kolejne lata i rozpoczęto 1 maja 2008 roku. Do 31 grudnia 2008 roku
przebadano 3647 osób. Algorytm dalszego postępowania z pacjentami w zależności od rodzaju wykrytych zmian oparto na
protokole International Early Lung Cancer Action Program (IELCAP) oraz na programie NELSON.
Wyniki: Wykryto 25 nowotworów złośliwych, w tym 21 niedrobnokomórkowych RP (17 kobiet, 4 mężczyzn), z tego 70%
w stadium I. W porównywalnej grupie wiekowej diagnozowanej na podstawie objawów odsetek RP w stadium IA wynosił
jedynie 16,8%. Pięćdziesięciu siedmiu chorych operowano, wykonując radykalne wycięcie płata lub płuca z limfadenektomią
śródpiersia w 16 przypadkach. U 3 osób przeprowadzono resekcję brzeżną, u 2 kolejnych segmentektomię. Śmiertelność
okołooperacyjna wyniosła 0%. Usunięto również 3 przerzuty do płuc oraz pobrano wycinki międzybłoniaka złośliwego.
W 32 przypadkach usunięto zmiany łagodne (gruźliczaki, odpryskowiaki, zmiany zapalne, grzybicze, sarkoidalne i inne)
o różnym znaczeniu klinicznym. U 996 osób stwierdzono ogółem 1365 zmian w obrębie klatki piersiowej, które były diagnozowane
zgodnie z przyjętym algorytmem.
Wnioski: Program wczesnego wykrywania nowotworów płuc zainicjowany w Szczecinie pozwolił istotnie zwiększyć liczbę
pacjentów zidentyfikowanych we wczesnym stadium choroby, a następnie leczonych radykalnie. Wykryto znaczną liczbę
zmian o zróżnicowanym znaczeniu klinicznym, podlegających dalszej ocenie.Introduction: Lung cancer (LC) remains one of the most serious epidemiological and clinical challenges both in the world
and Poland. Results of LC therapy are far from satisfaction. One of the reasons of high LC mortality is its late detection.
Currently, few centers in the world conduct LC screening programs based on low-dose spiral computed tomography (CT) of
the chest. There have been no such programs in Poland up to date.
Material and methods: The program of LC early detection based on CT for citizens of Szczecin aged 55-65, who smoked at
least 20 pack/years, was introduced on May 1st 2008 and was planned for 3 years. There were 3647 subjects examined till
December 31st 2008. Algorithm of further action for detected lesions was based on the IELCAP and NELSON trial protocols.
Results: There were 25 malignancies detected, including 21 LC (17 females and 4 males) up to date (70% were in stage I
TNM). In contrast - there was only 16.8% stage IA LC detected in the comparable group diagnosed on the symptoms basis.
Fifty seven patients were treated surgically, of whom 16 underwent lobectomy or pneumonectomy coupled with radical
mediastinal lymphadenectomy. There were 3 wedge resections and 2 segmentectomies performed, too. Perioperative
mortality was 0%. There were 32 benign lesions of different clinical importance resected as well (tuberculoma, hamartoma,
inflammatory, mycotic and sarcoidal lesions). In our group 1365 lesions were detected in 996 persons — they are followed
up in accordance with the IELCAP algorithm.
Conclusions: Early LC detection program initiated in Szczecin resulted in significant increase of stage IA TNM detected
patients subsequently treated radically. There was also a large number of small non malignant lesions detected
Electrical characterization of ISFETs, Journal of Telecommunications and Information Technology, 2007, nr 3
Methodology of electrical characterization of ISFETs has been described. It is based on a three-stage approach. First, electrical measurements of ISFET-like MOSFETs and extraction of basic parameters of the MOSFET compact model are performed. Next, mapping of the ISFET channel conductances and a number of other characteristic parameters is carried out using a semi-automatic testing setup. Finally, ISFET sensitivity to solution pH is evaluated. The methodology is applied to characterize ISFETs fabricated in the Institute of Electron Technology (IET)
The European Registry for Patients with Mechanical Circulatory Support (EUROMACS)
OBJECTIVES: A second paediatric report has been generated from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). The purpose of EUROMACS, which is operated by the European Association for Cardio-Thoracic Surgery, is to gather data related to durable mechanical circulatory support for scientific purposes and to publish reports with respect to the course of mechanical circulatory support therapy. Since the first report issued, efforts to increase compliance and participation have been extended. Additionally, the data provided the opportunity to analyse patients of younger age and lower weight.
METHODS: Participating hospitals contributed pre-, peri- and long-term postoperative data on mechanical circulatory support implants to the registry. Data for all implants in paediatric patients (≤19 years of age) performed from 1 January 2000 to 1 July 2019 were analysed. This report includes updates of patient characteristics, implant frequency, outcome (including mortality rates, transplants and recovery rates) as well as adverse events including neurological dysfunction, device malfunction, major infection and bleeding.
RESULTS: Twenty-nine hospitals contributed 398 registered implants in 353 patients (150 female, 203 male) to the registry. The most frequent aetiology of heart failure was any form of cardiomyopathy (61%), followed by congenital heart disease and myocarditis (16.4% and 16.1%, respectively). Competing outcomes analysis revealed that a total of 80% survived to transplant or recovery or are ongoing; at the 2-year follow-up examination, 20% died while on support. At 12 months, 46.7% received transplants, 8.7% were weaned from their device and 18.5% died. The 3-month adverse events rate was 1.69 per patient-year for device malfunction including pump exchange, 0.48 for major bleeding, 0.64 for major infection and 0.78 for neurological events.
CONCLUSIONS: The overall survival rate was 81.5% at 12 months following ventricular assist device implant. The comparison of survival rates of the early and later eras shows no significant difference. A focus on specific subgroups showed that survival was less in patients of younger age (<1 year of age) (P = 0.01) and lower weight (<20 kg) (P = 0.015). Transplant rates at 6 months contin
NERO: a biomedical named-entity (recognition) ontology with a large, annotated corpus reveals meaningful associations through text embedding.
Machine reading (MR) is essential for unlocking valuable knowledge contained in millions of existing biomedical documents. Over the last two decades1,2, the most dramatic advances in MR have followed in the wake of critical corpus development3. Large, well-annotated corpora have been associated with punctuated advances in MR methodology and automated knowledge extraction systems in the same way that ImageNet4 was fundamental for developing machine vision techniques. This study contributes six components to an advanced, named entity analysis tool for biomedicine: (a) a new, Named Entity Recognition Ontology (NERO) developed specifically for describing textual entities in biomedical texts, which accounts for diverse levels of ambiguity, bridging the scientific sublanguages of molecular biology, genetics, biochemistry, and medicine; (b) detailed guidelines for human experts annotating hundreds of named entity classes; (c) pictographs for all named entities, to simplify the burden of annotation for curators; (d) an original, annotated corpus comprising 35,865 sentences, which encapsulate 190,679 named entities and 43,438 events connecting two or more entities; (e) validated, off-the-shelf, named entity recognition (NER) automated extraction, and; (f) embedding models that demonstrate the promise of biomedical associations embedded within this corpus
TSSOI as an efficient tool for diagnostics of SOI technology in Institute of Electron Technology, Journal of Telecommunications and Information Technology, 2005, nr 1
This paper reports a test structure for characterization of a new technology combining a standard CMOS process with pixel detector manufacturing technique. These processes are combined on a single thick-_lm SOI wafer. Preliminary results of the measurements performed on both MOS SOI transistors and dedicated SOI test structures are described in detail
DNA conformations and their sequence preferences
The geometry of the phosphodiester backbone was analyzed for 7739 dinucleotides from 447 selected crystal structures of naked and complexed DNA. Ten torsion angles of a near-dinucleotide unit have been studied by combining Fourier averaging and clustering. Besides the known variants of the A-, B- and Z-DNA forms, we have also identified combined A + B backbone-deformed conformers, e.g. with α/γ switches, and a few conformers with a syn orientation of bases occurring e.g. in G-quadruplex structures. A plethora of A- and B-like conformers show a close relationship between the A- and B-form double helices. A comparison of the populations of the conformers occurring in naked and complexed DNA has revealed a significant broadening of the DNA conformational space in the complexes, but the conformers still remain within the limits defined by the A- and B- forms. Possible sequence preferences, important for sequence-dependent recognition, have been assessed for the main A and B conformers by means of statistical goodness-of-fit tests. The structural properties of the backbone in quadruplexes, junctions and histone-core particles are discussed in further detail
Cell-active Small Molecule Inhibitors of the DNA-damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG) : Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides
DNA
damage repair enzymes are promising targets in the development
of new therapeutic agents for a wide range of cancers and potentially
other diseases. The enzyme poly(ADP-ribose) glycohydrolase (PARG)
plays a pivotal role in the regulation of DNA repair mechanisms; however,
the lack of potent drug-like inhibitors for use in cellular and in
vivo models has limited the investigation of its potential as a novel
therapeutic target. Using the crystal structure of human PARG in complex
with the weakly active and cytotoxic anthraquinone <b>8a</b>, novel quinazolinedione sulfonamides PARG inhibitors have been identified
by means of structure-based virtual screening and library design.
1-Oxetan-3-ylmethyl derivatives <b>33d</b> and <b>35d</b> were selected for preliminary investigations in vivo. X-ray crystal
structures help rationalize the observed structure–activity
relationships of these novel inhibitors
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