bluuebunny/crossref_metadata_2025_split huggingface dataset:
pARIS-htt: an optimised expression platform to study huntingtin reveals functional domains required for vesicular trafficking
Authors: Pardo Raúl , Molina-Calavita Maria , Poizat Ghislaine , Keryer Guy , Humbert Sandrine , Saudou Frédéric 
Published: June 2010

Abstract

Background
Huntingtin (htt) is a multi-domain protein of 350 kDa that is mutated in Huntington's disease (HD) but whose function is yet to be fully understood. This absence of information is due in part to the difficulty of manipulating large DNA fragments by using conventional molecular cloning techniques. Consequently, few studies have addressed the cellular function(s) of full-length htt and its dysfunction(s) associated with the disease.

Results
We describe a flexible synthetic vector encoding full-length htt called pARIS-htt (A daptable, R NAi I nsensitive & S ynthetic). It includes synthetic cDNA coding for full-length human htt modified so that: 1) it is improved for codon usage, 2) it is insensitive to four different siRNAs allowing gene replacement studies, 3) it contains unique restriction sites (URSs) dispersed throughout the entire sequence without modifying the translated amino acid sequence, 4) it contains multiple cloning sites at the N and C-ter ends and 5) it is Gateway compatible. These modifications facilitate mutagenesis, tagging and cloning into diverse expression plasmids. Htt regulates dynein/dynactin-dependent trafficking of vesicles, such as brain-derived neurotrophic factor (BDNF)-containing vesicles, and of organelles, including reforming and maintenance of the Golgi near the cell centre. We used tests of these trafficking functions to validate various pARIS-htt constructs. We demonstrated, after silencing of endogenous htt, that full-length htt expressed from pARIS-htt rescues Golgi apparatus reformation following reversible microtubule disruption. A mutant form of htt that contains a 100Q expansion and a htt form devoid of either HAP1 or dynein interaction domains are both unable to rescue loss of endogenous htt. These mutants have also an impaired capacity to promote BDNF vesicular trafficking in neuronal cells.

Conclusion
We report the validation of a synthetic gene encoding full-length htt protein that will facilitate analyses of its structure/function. This may help provide relevant information about the cellular dysfunctions operating during the disease. As proof of principle, we show that either polyQ expansion or deletion of key interacting domains within full-length htt protein impairs its function in transport indicating that HD mutation induces defects on intrinsic properties of the protein and further demonstrating the importance of studying htt in its full-length context.
Some Problems Connected with High-Speed Compression-Ignition Engine Development
Authors: Dicksee C. B. 
Published: June 2010

This paper was read by Mr. Dicksee on the occasion of the second Joint iMeeting of eleven Scientific Institutions, as follows:— The Chemical Engineering Group, the Diesel Engine Users' Association, the Institute of Fuel, the Institute of Marine Engineers, the Institution of Automobile Engineers, the Institution of Mechanical Engineers, the Institution of Petroleum Technologists, the Junior Institution of Engineers, the North-East Coast Institution of Engineers and Shipbuilders, the Royal Aeronautical Society, and the Society of Engineers. Following last year's precedent, the Chair was taken by Mr. Tookey, President of the Institution of Automobile Engineers, who introduced Mr. A. E. L. Chorlton as Chairman for the meeting. Mr. Chorlton gave it as his opinion that meetings of this nature must be exceedingly valuable as a means of expressing to the nation a combined technical opinion which must have far more weight than an expression of more individual character. He suggested that a continuation of the practice might lead to the formation of something in the nature of a Technical Parliament, and asked those present to consider the possibility of some such result. Mr. Chorlton went on to emphasize the importance of research for all classes of mechanical engineering, laying special stress on the need for co-ordination of research among all parties.
Notes on Test Methods and Some Instruments
Authors: Stead E. B. 
Published: June 2010

To obtain true factual results from tests carried out on the test bed and on the road, instruments are necessary. The author describes his own experiences with various instruments and test methods, for example, the use of thermocouple sparking plugs for carrying out distribution tests, and the advantages of and characteristic results obtained from a smoke meter on a compression-ignition engine. After a brief comment on electronic instruments in general, he describes the balanced-pressure method of obtaining indicator diagrams at high speed, using a cathode-ray apparatus. Some typical results are given, and the methods by which the apparatus with a few additions can be used to measure torsional-vibration amplitudes of crankshafts (with practical examples), and by which a friction damper is adjusted to the correct condition, are shown. The final section deals with road testing; in this the author advocates the use of a recording accelerometer for obtaining greater accuracy in brake and acceleration tests, and shows how such an instrument can also be used for measuring cornering forces, assessing the riding qualities, or recording gradients. Some results are given, and the design of such an instrument is dealt with.
Basic Problems in the Engineering of a Modern All-Metal Motor Body
Authors: White E. S. 
Published: June 2010

Modern trends in car fashions are aggravating the problems of the body engineer and British designers are further hampered by the degree of economy which they must needs exercise in the use of expensive tools. The aim of this paper is to make such problems more widely known among those connected with other aspects of car design and production. Designing for reduced weight, air resistance, and easier cleaning is advocated and a warning is given against production complications and increased costs arising from changes made for reasons of fashion. The range of materials from which a body may be made is described in some detail and it becomes obvious that steel still shows considerable advantages over all others. The relative merits of different forms of construction are examined in the light of quantity production. The method of assembly of a body has now to be studied in relation to the present practice of exporting vehicles in a partly-dismantled condition and it is pointed out how components may be made self-locating in order to render the use of jigs unnecessary in overseas assembly centres. An example is given of the way in which multiple pressing operations can be facilitated by careful sequence planning. The inclusion of a section on corrosion prevention is of particular value in view of the increased period of life expected from cars at the present time.
Lubrication of Engines in Public Service Vehicles
Authors: Wilford A. T. 
Published: June 2010

In the course of use an engine lubricating oil becomes contaminated with the products of its own breakdown, and with others derived from incomplete combustion of the fuel, leading to objectionable deposits influenced not only by the characteristics of the lubricant but also by other factors such as engine design, operating conditions, and maintenance. Fuel characteristics—such as volatility, ignition quality, and sulphur content—affect lubricating oil behaviour. The effect of viscosity on fuel consumption is explained. Increase in engine output for a given weight and size, together with operation at high temperature and load, have an adverse effect. Results obtained from service tests with an oxidation-inhibited oil and with a fully-detergent (“heavy duty”) oil are described, and examples are given of the use of data obtained by examination of used oils, considered in conjunction with statistics derived from a study of the condition of the engines. Physical specifications for non-additive type lubricants can be compiled to define oils which have proved satisfactory. The present position in Great Britain regarding specifications for detergent (H.D.) oils is reviewed; conventional specifications are inadequate to describe this type of lubricant, the behaviour of which can be determined only by engine tests.
The Propeller Shaft or Hooke's Coupling and the Cardan Joint
Authors: Evernden H. I. F. 
Published: June 2010

The purpose of this paper is to review the problem of designing a satisfactory open shaft-coupling between the power unit and the rear axle of a motor car. The vogue for a low car and a low, flat floor coupled with the need for adequate ground clearance under the power unit demanded by export conditions, creates the need for a divided “propeller” shaft. The cyclic forces on the centre bearing of such a divided propeller shaft are determined mathematically, and the story is told of the development of a design of centre bearing intended to prevent these cyclic forces being felt by the occupants of the vehicle. The cyclic bending which is induced in the propeller shaft is shown to reduce its whirling speed below that of a freely revolving shaft.
Electrical Equipment for Passenger Cars
Authors: Kendall M. W. 
Published: June 2010

The paper sets out to consider the present-day practice in British automotive electrical equipment, comparing this frequently with British practice prior to 1939 or current American practice wherever appropriate. It commences by considering the generating and energy-storage part of the system, dealing briefly with the provision of A.C. or D.C. equipment and the relative merits of 12-volt and 6-volt equipment. It then goes on to consider the operating and power-consuming parts of the system in fairly considerable detail, making particular note of the reduction in size and weight of generators which has been made possible in recent years by the use of new insulating enamels and of light alloys where practicable. The use of higher speeds is generally possible only where maximum car speeds are not very high, due to limitations imposed by centrifugal forces on armatures and the need to provide the rated output at a fairly constant road speed. Voltage regulators are dealt with in some detail with a general description of the British compensated voltage-control system and the transatlantic current-voltage type using two separate regulating circuits in series. With regard to batteries, the main development has been an improved paste which was developed during the 1939–45 war for dealing with low temperatures and which is now in general production. The problems of noise, power, and premature pinion ejection concerning starter-motors are discussed, with a comparison of the performance of 6- and 12-volt machines and of the various types of pinion-engaging mechanisms of the positive-mesh and inertia-meshing types, together with a reference to the comparatively large amount of power required to start a small engine. Developments in ignition equipment have not been great in recent years, but the point is made that an improved system will need to be developed for the higher compression ratios which are impending. The paper deals briefly with windscreen wipers, heaters, demisters, horns, direction indicators of the semaphore and flashing signal type, instruments, actuating motors, relays and protective devices, and also touches briefly on the subject of radio suppression for car radio and television. The paper concludes with a discussion on head lighting and dazzle.
Some Factors Governing the Performance of Crankcase Lubricating Oils
Authors: Towle A. 
Published: June 2010

The paper deals in turn with the basic requirements of a crankcase oil; chemical and physical tests on new and used oils; viscosity, S.A.E. numbers, and viscosity index; common problems arising in lubrication; ring sticking; engine wear; oil consumption; bearing failures; engine deposits; the grouping of oils; the influence of Diesel fuel and gasolene on engine deposits and wear; engine laboratory tests; the rating of oil performance on an engine test; and finally, the correlation between field and laboratory tests. It attempts to show that unsatisfactory engine life is not necessarily connected with the quality of the lubricating oil, and that many of the faults often attributed to the lubricant are, in fact, controlled by incorrect engine design, excessive operating conditions, or poor maintenance. Better results can usually be obtained by the use of additive treated oils. Reference is made to the Supplement 1 series of oils which effectively deal with high-sulphur Diesel fuels, and examples are given of bench and field tests carried out on straight and treated oils.
An Application of Petrol Injection to Automobile Engines
Authors: Barrington R. , Downing E. W. 
Published: June 2010

The paper recounts the results obtained in a series of experiments carried out with the object of examining the claims made for improved results, both in fuel consumption and maximum power, which could be obtained by substituting a petrol injection system for a carburettor. The experiments, carried out on four-cylinder engines of approximately 1·5 litres capacity, led to the development of a satisfactory system capable of giving equal fuel distribution to all cylinders with a tolerance of ±2 per cent at all loads. They showed that, for engines of this order of size, manifold injection was superior to direct injection and established that petrol injection will not give any better combustion efficiency than carburation. Hence any saving in fuel consumption obtained can only be due to better fuel distribution between cylinders, better matching of fuel/air ratio to a desired value, or increase in compression ratio made possible by the elimination of the hot spot. Under certain conditions the resultant saving in fuel at part load on bench tests could amount to some 10–15 per cent. Maximum power can be increased by some 15–20 per cent by elimination of the choke, and still more if the compression ratio is increased slightly to take advantage of the reduced temperature of the incoming charge. Road tests in general confirmed the results of bench tests, but brought out the effect of many other factors which affect fuel economy. In order to properly evaluate these a number of experiments were carried out which are of interest and value as affecting the problem of fuel economy in general. Starting at low temperatures requires very considerable over-fuelling with a petrol injection system, just as in the case of a carburettor, but such a system may be made to give better control during the process of warming up. In the authors' view an engine fitted with petrol injection is pleasanter to drive as a result of its inherently better idling, more uniform and smoother torque and increased power at full throttle. The results obtained, however, while attractive, do not bear out some of the more exaggerated claims sometimes made by advocates of petrol injection systems. No attempt is made to urge the introduction of petrol injection and it is left to the industry to decide whether, in view of the results obtained, it is felt that a petrol injection system with its concomitant increase in first cost is worth adoption.
Metal Transfer from Piston Rings to Cylinders during “Run-in”
Authors: Strang C. D. , Burwell J. T. 
Published: June 2010

Piston rings with radio-active wearing-surfaces were used to study the micro-welding between rings and cylinder wall during “run-in” in a small, water-cooled, internal combustion engine. The results indicated that micro-welding and the accompanying transfer of metal were present under the mildest conditions of engine operation, including motoring with the engine cylinder-head removed. The distribution of micro-welding along the ring-travel was found to correspond to the wear profile observed in engine cylinders by other workers. Such transferred material may play a part in the formation of the “glazed” layer which is said to be present on “run-in” cylinder walls and rings. The presence of transferred metal at all points along the ring-travel indicates that the piston ring was not fully supported by a hydrodynamic oil film of sufficient thickness to separate completely the surfaces of the ring and the cylinder wall.
Significant Contributions of the Diesel Research Laboratory
Authors: Rosen C. G. A. 
Published: June 2010

This review of Diesel engine development is based on the work carried out at the Diesel Research Laboratory of Caterpillar Tractor Co. under the sponsorship of the author as Director of Research. For many years intensive effort has been made to understand the combustion process in this type of engine by a better knowledge of the fundamentals of ignition and the mechanism of the combustion process, and this study has been developed in the laboratory on a competitive basis. Originally six combustion systems were put to trial and a modified precombustion-chamber engine won the palm of victory on the basis of its ability to maintain uniformity over extended periods of operation. Briefly, the character of the comparative combustion studies followed two general classifications: (1) visual combustion studies; (2) study of combustion-chamber deposits. In order to make extended studies of the combustion phenomena by visual means, a quartz window was designed to achieve maximum cleanliness without the distraction of soot condensation on the cold windows. The author describes the precombustion-chamber process, and deals with the composition of combustion gases, flame duration, temperature distribution, the mechanism of ignition, and combustion-chamber deposits. He also discusses the development of fuel-injection equipment, pretiming, precalibrating, and the evolution of the fuel pump; he describes the characteristics of several types of check valve and fuel valve, and the fuel-pump control of engine torque characteristics. Spray characteristics and the flow through the fuel-valve orifice are also examined. Comments are made upon materials for cylinder liners and piston rings, and the effect of fuel inclusions on cylinder wear; lubrication is also considered. It is believed that excellent performance has been achieved in the precombustion-chamber engine with a minimum of complication in the fuel-injection equipment, and that the development of this principle of combustion has not yet reached its limit of progress.
An Experimental Investigation into Pre-ignition in the Spark-ignition Engine
Authors: Downs D. , Pignéguy J. H. 
Published: June 2010

Pre-ignition and auto-ignition are uncontrolled ignition of combustible mixture in an engine by a hot surface. Pre-ignition is distinct from “knock” or “detonation” which is caused by the rapid combustion of the last part of the mixture following the initiation of flame by a spark. More work has been carried out on knock than pre-ignition because knock sets the primary limit to the possible power-output and fuel economy of an engine. Owing to increases in engine power in recent years, however, interest in pre-ignition has been revived, and this paper describes an investigation which was primarily directed to finding the pre-ignition ratings of various fuels. Two methods of obtaining pre-ignition ratings have been developed; with one a 500 c.c. single-cylinder water-cooled unit is used, having an electrically heated hot-spot to induce pre-ignition, and with the other a single-cylinder air-cooled aircraft engine with an air-cooled pre-igniter is used. A rating scale has been constructed in which iso-octane has been given the value of 100, and cumene zero. A large number of pure fuels from the paraffin, naphthene, aromatic, and alcohol groups have been rated for pre-ignition tendency using these methods. In addition, typical commercial motor-fuels, motor-racing fuels, and water-alcohol injection fluids have been tested. The relationship between pre-ignition tendency and the temperature of the hot-spot with normal running and with pre-ignition conditions has been established. The effects of engine variables, for example, mixture strength, speed, ignition advance, and air and cylinder temperatures, on pre-ignition, have been studied, in addition to the effects of important fuel additives such as tetraethyl lead and the aromatic amines. The additive tests include substances, such as formaldehyde and nitrogen peroxide, which are of interest from the chemical aspect and, based on the results, some information on the fundamental chemical processes involved in hot-spot ignition has been obtained.
An Analytical Approach to Automobile. Valve Gear Design
Authors: Bishop J. L. H. 
Published: June 2010

In the automotive field during the last decade, owing primarily to increases in maximum engine speed and the almost universal use of overhead valve gear, increasing attention has been focused upon improper valve functioning which causes noisy operation, excessive valve spring surge, valve seat pounding, and exhaust valve burning. With the conventional design of cams no allowance is made for the flexibility of the push rod and rocker, consequently in general the accelerations imparted to the valve are much greater than is necessary at high speeds when inertia effects build up. A general mathematical analysis of the conventional three-arc cam is presented, introducing the terms “eccentricity” and “instantaneous radius”, and this is followed by a similar analysis of the new cam profile using the same terms, together with the method of correcting the cam profile for highspeed operation. It is also shown how the new general equations can be used to deduce a variable eccentricity ramp, the purpose of which is to take up clearance at variable velocity. The effects of the new cam profile on horse-power and thermal efficiency are shown; the effect of the acceleration characteristic on valve spring design also is illustrated, and a comparison shows the reduction in spring weight made possible by the elimination of valve spring surge.
Shock Absorbers
Authors: Kinchin J. W. , Stock C. R. 
Published: June 2010

The progress made in suspension during recent years, especially with regard to forms of relatively frictionless springing, makes the shock absorber, now generally known as the suspension damper, an essential part of the suspension system. The simple friction type of damper has been displaced from universal popularity by some form of hydraulic control, and it is to the hydraulic damper that the paper is devoted. The three main types of hydraulic damper mentioned are the vane type, the lever-operated piston type, and the direct-acting telescopic type. Design requirements for recuperating, transfer, and pressure valves are stated, and types of seals, and sealing problems, are given. Reference is made to the desirable characteristics of damper fluids, together with a summary of tests on various fluids. The causes of noise—the most common being knock, swish, and squeak—are investigated, and remedies for their elimination are discussed. Various tests on dampers are described, and work diagrams, from which it is possible to analyse the various common faults, are given. Ride determination is mentioned and a damper calibration chart illustrated. A review of the use of dampers for auxiliary purposes is made, and the type of damping that is required is considered.