An interactive visualization tool to explore the biophysical properties of amino acids and their contribution to substitution matrices

BACKGROUND: Quantitative descriptions of amino acid similarity, expressed as probabilistic models of evolutionary interchangeability, are central to many mainstream bioinformatic procedures such as sequence alignment, homology searching, and protein structural prediction. Here we present a web-based, user-friendly analysis tool that allows any researcher to quickly and easily visualize relationships between these bioinformatic metrics and to explore their relationships to underlying indices of amino acid molecular descriptors. RESULTS: We demonstrate the three fundamental types of question that our software can address by taking as a specific example the connections between 49 measures of amino acid biophysical properties (e.g., size, charge and hydrophobicity), a generalized model of amino acid substitution (as represented by the PAM74-100 matrix), and the mutational distance that separates amino acids within the standard genetic code (i.e., the number of point mutations required for interconversion during protein evolution). We show that our software allows a user to recapture the insights from several key publications on these topics in just a few minutes. CONCLUSION: Our software facilitates rapid, interactive exploration of three interconnected topics: (i) the multidimensional molecular descriptors of the twenty proteinaceous amino acids, (ii) the correlation of these biophysical measurements with observed patterns of amino acid substitution, and (iii) the causal basis for differences between any two observed patterns of amino acid substitution. This software acts as an intuitive bioinformatic exploration tool that can guide more comprehensive statistical analyses relating to a diverse array of specific research questions

The Interconnections of the LHC Cryomagnets

The main components of the LHC, the next world-class facility in high-energy physics, are the twin-aperture high-field superconducting cryomagnets to be installed in the existing 26.7-km long tunnel. After installation and alignment, the cryomagnets have to be interconnected. The interconnections must ensure the continuity of several functions: vacuum enclosures, beam pipe image currents (RF contacts), cryogenic circuits, electrical power supply, and thermal insulation. In the machine, about 1700 interconnections between cryomagnets are necessary. The interconnections constitute a unique system that is nearly entirely assembled in the tunnel. For each of them, various operations must be done: TIG welding of cryogenic channels (~ 50 000 welds), induction soldering of main superconducting cables (~ 10 000 joints), ultrasonic welding of auxiliary superconducting cables (~ 20 000 welds), mechanical assembly of various elements, and installation of the multi-layer insulation (~ 200 000 m2). Defective junctions could be very difficult and expensive to detect and repair. Reproducible and reliable processes must be implemented together with a strict quality control. The interconnection activities are optimized taking into account several constraints: limited space availability, tight installation schedule, high level of quality, high reliability and economical aspects. In this paper, the functions to be fulfilled by the interconnections and the various technologies selected are presented. Quality control at different levels (component/ interconnect, subsystem, system) is also described. The interconnection assembly sequences are summarized. Finally, the validation of the interconnection procedures is presented, based in particular on the LHC prototype cell assembly (STRING2)

Spinalni epiduralni hemangiom pješčanog sata: jednokratna 2-stupanjska posteriorna mikrokiruška i transtorakalna endoskopska resekcija - prikaz slučaja i pregled literature

Spinal dumbbell tumors are defined by a narrowing at the point where they penetrate the intervertebral foramina or dura mater, assuming an hourglass or dumbbell shape. Dumbbell-shaped spinal hemangiomas are extremely rare. We describe a dumbbell spinal tumor (epidural cavernous hemangioma) resected by a 2-stage single-sitting combined approach. We also conduct a substantial literature review of the subject. We present a case of a 78-year-old male who was found to have a homogeneously enhancing, dumbbell-shaped, intraspinal, extradural tumor mass extending into the left chest cavity. The tumor was resected with a single-sitting 2-stage posterior technique: a microsurgical approach, followed by endoscopic resection via a thoracoscopic approach. There are several reports in the literature on the combined approach for dumbbell tumors of the spinal cord. Our case is the first to describe 2-stage combined surgery in 1 sitting for dumbbell hemangioma with the patient in the lateral decubitus position for the thoracoscopic part of the surgery; and the use of a fat pad, which was applied in the neuroforamen via the posterior route, as a marker for resection during the transthoracic procedure.Spinalni tumori pješčanog sata definirani su suženjem na mjestu gdje prodiru u intervertebralni foramen ili dura mater, uz pretpostavku da imaju oblik pješčanog sata ili bućice. Spinalni hemangiomi u obliku bućice su iznimno rijetki. Opisuje se spinalni tumor pješčanog sata (epiduralni kavernozni hemangiom) reseciran dvostupanjskim kombiniranim pristupom, uz opsežan pregled literature. Prikazuje se slučaj 78-godišnjeg muškarca za kojeg je utvrđeno da ima homogeno pojačanu intraspinalnu, ekstraduralnu masu u obliku bućice koja se širi u lijevu prsnu šupljinu. Tumor je reseciran jednokratnom 2-stupanjskom posteriornom tehnikom: mikrokirurški pristup, nakon čega slijedi endoskopska resekcija putem torakoskopskog pristupa. U literaturi postoji nekoliko izvješća o kombiniranom pristupu za tumore bućice kralježnične moždine. Naš je slučaj prvi koji opisuje 2-stupanjsku kombiniranu kirurgiju u 1 sjedenju za hemangiom pješčanog sata u bolesnika u lateralnom dekubitusnom položaju za torakoskopski dio operacije; i uporabu masnog jastučića koji je primijenjen u neuroforamenu preko stražnjeg puta, kao marker za resekciju tijekom transtorakalnog postupka

SGDB: a database of synthetic genes re-designed for optimizing protein over-expression

Here we present the Synthetic Gene Database (SGDB): a relational database that houses sequences and associated experimental information on synthetic (artificially engineered) genes from all peer-reviewed studies published to date. At present, the database comprises information from more than 200 published experiments. This resource not only provides reference material to guide experimentalists in designing new genes that improve protein expression, but also offers a dataset for analysis by bioinformaticians who seek to test ideas regarding the underlying factors that influence gene expression. The SGDB was built under MySQL database management system. We also offer an XML schema for standardized data description of synthetic genes. Users can access the database at , or batch downloads all information through XML files. Moreover, users may visually compare the coding sequences of a synthetic gene and its natural counterpart with an integrated web tool at , and discuss questions, findings and related information on an associated e-forum at

Update of the LHC Arc Cryostat Systems Layouts and Integration

Since the LHC Conceptual Design report's publication in October 1995 [1], and subsequent evolutions [2], the LHC Arc Cryostat System has undergone recently a number of significant changes, dictated by the natural evolution of the project. Most noteworthy are the recent decisions to route the large number of auxiliary circuits feeding the arc corrector magnets in a separate tube placed inside the cryostat with connections to the magnets every half-cell. Further decisions concern simplification of the baseline vacuum and cryogenic sectorization, the finalization of the design of the arc cryogenic modules and the layout of the arc electrical distribution feedboxes. The most recent features of the highly intricate cryogenics, magnetic, vacuum and electrical distribution systems of the LHC are presente

Beam Vacuum Interconnects for the LHC Cold Arcs

The design of the beam vacuum interconnect is described in this paper. Features include a novel RF bridge design to maximise lateral flexibility during cryostat Cold arcs of the LHC will consist of twin aperture dipole, quadrupole and corrector magnets in cryostats, operating at 1.9 K. Beam vacuum chambers, along with all connecting elements require flexible 'interconnects' between adjacent cryostats to allow for thermal and mechanical offsets foreseen during machine operation and alignment. In addition, the beam vacuum chambers contain perforated beam screens to intercept beam induced heat loads at an intermediate temperature. These must also be connected with low impedance RF bridges in the interconnect zones.alignment and so-called 'nested' bellows to minimise the required length of the assembly

The New Superfluid Helium Cryostats for the Short Straight Sections of the CERN Large Hadron Collider (LHC)

The lattice of the CERN Large Hadron Collider (LHC) contains 364 Short Straight Section (SSS) units, one in every 53 m long half-cell. An SSS consists of three major assemblies: the standard cryostat section, the cryogenic service module, and the jumper connection. The standard cryostat section of an SSS contains the twin aperture high-gradient superconducting quadrupole and two pairs of superconducting corrector magnets, operating in pressurized helium II at 1.9 K. Components for isolating cryostat insulation vacuum, and the cryogenic supply lines, have to be foreseen. Special emphasis is given to the design changes of the SSS following adoption of an external cryogenic supply line (QRL). A jumper connection connects the SSS to the QRL, linking all the cryogenic tubes necessary for the local full-cell cooling loop [at every second SSS]. The jumper is connected to one end of the standard cryostat section via the cryogenic service module, which also houses beam diagnostics, current feedthroughs, and instrumentation capillaries. The conceptual design fulfilling the tight requirements of magnet alignment precision and cryogenic performance are described. Construction details, aimed at minimizing costs of series manufacturing and assembly, while ensuring the high quality of this complex accelerator component, are given

Mechanical design and layout of the LHC standard half-cell

The LHC Conceptual Design Report issued on 20th October 1995 [1] introduced significant changes to some fundamental features of the LHC standard half-cell, composed of one quadrupole, 3 dipoles and a set of corrector magnets. A separate cryogenic distribution line has been adopted containing most of the distribution lines previously installed inside the main cryostat. The dipole length has been increased from 10 to 15 m and independent powering of the focusing and defocusing quadrupole magnets has been chosen. Individual quench protection diodes were introduced in magnet interconnects and many auxiliary bus bars were added to feed in series the various families of superconducting corrector magnets. The various highly intricate basic systems such as: cryostats and cryogenics feeders, superconducting magnets and their electrical powering and protection, vacuum beam screen and its cooling, support and alignment devices have been redesigned, taking into account the very tight space available. These space constraints are imposed by the desire to have maximum integral bending field strength for maximum LHC energy, in the existing LEP tunnel. Finally, cryogenic and vacuum sectorisation have been introduced to reduce downtimes and facilitate commissioning

Synthetic antibodies against BRIL as universal fiducial marks for single−particle cryoEM structure determination of membrane proteins

We propose the concept of universal fiducials based on a set of pre-made semi-synthetic antibodies (sABs) generated by customized phage display selections against the fusion protein BRIL, an engineered variant of apocytochrome b562a. These sABs can bind to BRIL fused either into the loops or termini of different GPCRs, ion channels, receptors and transporters without disrupting their structure. A crystal structure of BRIL in complex with an affinity-matured sAB (BAG2) that bound to all systems tested delineates the footprint of interaction. Negative stain and cryoEM data of several examples of BRIL-membrane protein chimera highlight the effectiveness of the sABs as universal fiducial marks. Taken together with a cryoEM structure of sAB bound human nicotinic acetylcholine receptor, this work demonstrates that these anti-BRIL sABs can greatly enhance the particle properties leading to improved cryoEM outcomes, especially for challenging membrane proteins

The Preparation of the Cryomagnets and the Assembly of the LHC Test String 2

The numerous complex activities required to prepare the cryomagnets for the installation in String 2 are described. These include the configuration of the mechanical interfaces, thee conditioning of the beam tubes, the installation of beam screens and the instrumentation as well as the final checks. The preparation of the cryomagnets for String 2 has been a dress rehearsal for the preparation that the cryomagnets will undergo before their installation in the tunnel. After a description of the interconnection procedures of the components for String 2, the tests carried-out to release the String for operation are described. A brief account of the lessons learnt is also given