A collector cart includes a body having an open rear end, which is closed by a canopy pivotally mounted adjacent its front end on the body adjacent its front end. The body has a support pivotally connected to caster wheel supports and a tow bar attached to a riding lawn mower hitch bar. Telescoping chutes connect the mower outlet with a canopy port to fill the cart with debris. When the cart is to be dumped, a linkage mechanism is activated by an operator, who remains on the mower, raising a lift handle to initially cause rearward shifting of the canopy relative to the body to release a locking connection of the rear of the canopy to the rear of the body. The body is released from its tow bar at the same time so that continued raising of the lift handle by the operator causes the body to pivot to a dumping position while the canopy pivots away from the body due to a rope of a fixed length connecting the front of the canopy to the mower.
A laminated, cylindrical, metal screen or molding element for vacuum perforation of plastic film or sheets, comprising two or more relatively thin cylindrical metal screens, each having a predetermined inside and outside diameter and each having a plurality of openings or holes therein of a predetermined size and geometrical shape, and said relatively thin screens stacked and bonded together, diametrically one inside the other thereby providing a screen of a desired thickness and a desired hole geometry wherein the holes in the screen have substantially straight walls perpendicular to the surface of the screen.;A method of producing a relatively thick cylindrical metal screen for
A rotatable perforated molding element for embossing and/or perforating thermoplastic sheet or film, the molding element including a series of perforated strips having two parallel sides and two parallel ends, the sides being perpendicular to the ends, each of the strips being welded at the end prior to placing the strips on a supporting drum. Additional strips are placed on the drum until the desired area of the drum is covered with the strips.
A perforated thermoplastic film with less than ideally shaped tapered capillaries which has an increased liquid flow rate through the tapered capillaries and a method for making such a film. The method includes forming a perforated thermoplastic film having tapered capillaries from a resin into which an effective amount of a polarizable, migrating surfactant has been blended therewith and then treating the perforated thermoplastic film with a corona discharge treatment sufficient to increase the flow rate of liquid through said perforated film and provide a film having a percent run off of from about zero to ten percent.;The perforated film made in accordance with the invention has a much higher
Eugenics, the attempt to improve the genetic quality of the humanspecies by `better breeding', developed as a worldwide movement between 1900and 1940. It was particularly prominent in the United States, Britain andGermany, and in those countries was based on the then-new science ofMendelian genetics. Eugenicists developed research programs to determine thedegree to which traits such as Huntington's chorea, blindness, deafness,mental retardation (feeblemindedness), intelligence, alcoholism,szhiophrenia, manic depression, rebelliousness, nomadism, prostitution andfeeble-inhibition were genetically determined. Eugenicists were also activein the political arena, lobbying in the United States for immigrationrestriction and compulsory sterilization laws for those deemed geneticallyunfit; in Britain they lobbied for incarceration of genetically unfit and inGermany for sterilization and eventually euthanasia. In all these countriesone of the major arguments was that of efficiency: that it was inefficientto allow genetic defects to be multiplied and then have to try and deal withthe consequences of state care for the offspring. National Socialists calledgenetically defective individuals `useless eaters' and argued forsterilization or euthanasia on economic grounds. Similar arguments appearedin the United States and Britain as well. At the present time (1997) muchresearch and publicity is being given to claims about a genetic basis forall the same behaviors (alcoholism, manic depression, etc), again in aneconomic context – care for people with such diseases is costing toomuch. There is an important lesson to learn from the past: genetic argumentsare put forward to mask the true – social and economic – causesof human behavioral defects.
The pharmaceutical industry has become highly efficient at synthesizing and testing very large numbers of drug-like molecules, typically through the application of automation in high-throughput screening and combinatorial chemistry. This has yielded something of a “data explosion“, as a result of which it can be challenging simply to manage and store the results, let alone analyze them in any detail. However, for drug discovery to be truly effective, it is important to do just that. Transformation of data into information and information into knowledge can help yield the substantial improvements being demanded of the industry. The scale of the problem is further magnified through the inclusion of vast swathes of genomic data that have become available in recent years (and which have also been generated through the application of automated methodologies). Furthermore, whilst the impact in the GPCR arena is so far modest, we can also anticipate that advances in protein crystallography will yield substantial amounts of structural data that should be very valuable. Chemogenomics is the application of computational methods to make sense of the huge amount of data that sits at this interface between genetics, pharmacology, structural biology and medicinal chemistry. In an attempt to introduce one level of simplification, for this special issue we have chosen to focus on chemogenomics as applied to a single protein family, namely the G-Protein-Coupled Receptors (GPCRs). In its truest sense, however, the technique extends to the prediction of activity for all drug-like molecules at all biological targets and there are elements of that in some of the papers that follow. Given the well-known importance of GPCRs as drug targets, it is perhaps natural to focus there, although the methods described have gained significant traction in other areas as well. This is most notable for the protein kinases where the high levels of similarity in the orthosteric site lend them to such analyses, although results in a somewhat unusual focus on selectivity issues. GPCRs provide an interesting test-bed for chemogenomic methods due to the amount of data available, the relatively diverse nature of their binding site(s) and their on-going importance as drug targets through, for example, the exploitation of targets with hitherto limited chemical tractability, orphan receptors, alternative signaling mechanisms (e.g. beta-arrestin or functional selectivity) and targeted polypharmacology profiles. The principles learned should, however, be applied quite readily to other protein families. Gloriam and Garland have looked at how the available crystal structures can be used to define a reference set of amino acid residues that are accessible for ligand binding in the GPCR transmembrane helical bundle. This set has been used to cluster the receptors to reflect ligand-binding preferences without the “evolutionary noise“ associated with non-ligand-binding portions of the sequence. However, the authors show that to achieve high-resolution relationships it is necessary to cluster receptors using a further reduced residue set defined on a per ligand (binding site/mode) basis. This style of analysis has been applied to 3 privileged structures and yields both a rationale for the privileged status as well as predictions for the activity profile across the whole of Family A, with clear applications for ligand/drug design. Frimurer and Hogberg have developed an efficient “physicogenetic“ protocol for relating GPCRs with respect to the physicochemical nature of binding sites as well as a “site-directed drug discovery“ approach to target- and ligand-based drug design. In one study, a small diverse library directed towards GPR44 (aka CRTh2) generated several useful hit series which were further converted into drug-like lead series. They show the value of including the GPR44 receptor homology model in the design rather than just relying on those targets i