text:
|Publication number||US6437012 B1|
|Application number||US 09/428,162|
|Publication date||Aug 20, 2002|
|Filing date||Oct 27, 1999|
|Priority date||Oct 27, 1999|
|Publication number||09428162, 428162, US 6437012 B1, US 6437012B1, US-B1-6437012, US6437012 B1, US6437012B1|
|Original Assignee||Agilent Technologies, Inc.|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (9), Non-Patent Citations (3), Referenced by (5), Classifications (10), Legal Events (8)|
|External Links: USPTO, USPTO Assignment, Espacenet|
This invention relates to the use of low-swelling, highly crosslinked, macroporous styrene polymers as scavengers for removing unreacted compounds and side products from a reaction medium. The styrene polymers of this invention can be functionalized with one or more groups which are designed to be reactive with functional groups contained on the compounds to be removed form the reaction mixture. Typically, such functional groups include isocyanate groups, thiol groups, aldehyde groups, amino groups, and hydrazine groups. The styrene polymers of this invention can be used in purification schemes involving the high throughput parallel synthesis of combinatorial chemical libraries of potential lead drug compounds.
Parallel synthesis, as referred to herein, describes a technology for high throughput organic synthesis characterized by the preparation of a large number of compounds simultaneously and discretely (in parallel). Parallel synthesis generally involves the use of a large number of reaction vessels, such as an array of multi-well plates, which may contain different combinations of a number of reactants of interest. The reactions are allowed to proceed simultaneously and in parallel in each vessel to produce a diverse collection or library of product molecules. The individual compounds in the library can be screened against a suitable target to determine the probability of biological activity. Automation of synthesis and screening procedures is desired to provide high throughput operation using mechanical devices, such as laboratory robots. In this way, many thousands of compounds can be prepared and screened in a relatively short time.
One of the bottlenecks in automated processes such as these is product purification. Ideally, these reactions proceed to completion, and only a single reaction product will be generated in each reaction vessel. However, in many instances the reaction medium may contain unreacted reactants and/or reaction by-products as impurities after a reaction has occurred. These substances represent impurities which must be efficiently removed from the reaction mixture as part of the purification procedure to obtain the desired product. Traditionally, the purification can be accomplished by chromatographic separation, using plain silica or reverse phase silica, such as C18 modified silica, as a stationary phase. The traditional chromatographic separation is both time and labor intensive, and cannot be run in parallel for a relatively large number of compounds.
Two purification strategies have generally been adapted for high throughput parallel synthesis: a solid phase synthesis; and a solid reagent assisted solution phase synthesis, including the use of soluble polymer reagents that can be precipitated out of the reaction mixture by solvent switching.
In solid phase synthesis, a reactant is first linked with a cleavable linkage to a solid support. The subsequent reaction of the support-anchored reactant with another reactant in solution produces an expected chemical identity anchored to the support. A selective cleavage releases the expected compound from the solid support with relatively high purity. Unreacted reactants and by-products are easily removed from products anchored to the support by washing or filtering the support after the reaction. However, the majority of the well-documented organic reactions is performed in solution phase, and many of these reactions cannot be carried out using a solid phase synthesis without substantial changes to the reaction procedure, if at all. Other drawbacks of solid phase synthesis include the required tolerance of the linker towards the reaction mixture, the required tolerance of the linker against premature cleavage, unnecessary by-products generated from the cleavage reaction, and the presence of trace of the linker in the final product.
The other approach, solid-reagent assisted solution phase synthesis, involves the use of solid-phase reagents, either participating in the synthesis reactions, or removing excess reactants and by-products from the reaction mixture. In the former case, the solid-support reagents, often termed “solid reagents”, are a part of the organic synthesis reaction, and this approach differs from solid phase synthesis by forming and removing by-products in solid form, leaving desired compounds in the solution. In the latter case, the solid-supported reagents, often termed “scavengers”, are not part of the synthesis reactions, and are applied to selectively remove excess reactants and/or by-products in the reaction mixture by ion-pairing or covalent bonding these impurities, leaving the desired compounds in the solution.
The concept and practice of “scavenging”, referring to the selective removal of organic compounds from solution by binding them onto a solid surface, is known in the art. As an example, U.S. Pat. No. 3,576,870 describes the purification of N, N-dimethylacetamide by removing excess acetic anhydride with a basic ion exchange resin. It is also known in the art that organic compounds can be selectively scavenged by covalently bonding them onto a solid surface. Examples of such types of “scavenging” are found in U.S. Pat. Nos. 5,087,671 and 5,244,582, which describe the use of various reactive groups immobilized on inorganic substrates to remove carcinogenic nitrosating agents from liquids. Another example, published in J. Am. Chem. Soc., 97, page 4407 (1975), shows the use of an amine bound to a lightly cross-linked polystyrene gel for removing organic anhydrides from an organic solution. While the application of “scavengers” in organic parallel synthesis reactions is relatively new, there have been many recent publications directed to this emerging technology. U.S. Pat. No. 5,767,238 describes the general application of functionalized solid particles for removing impurities in a so-called “inverse solid-phase synthesis” process by either ionic or covalent binding. Scavenger-assisted combinatorial libraries are described in the following European patent publications: EP 816309, for preparing ureas or thioureas; EP 818431, for scavenging secondary amines; EP 825164, for scavenging amides, carbamates and sulfonamides. The scavengers used include amines, isocyantes, and acid chloride functionalities bound to certain polymers and inorganic substrates.
Many functionalized polymer-based particles have been used as scavenger materials, and some commonly used scavengers, based on lightly cross-linked (1% or 2%) polystyrene/divinylbenzene particles, are commercially available from several sources (e.g. Novabiochem, Laufelfingen, Switzerland). However, most of the polymer-based scavengers in the prior art are based on lightly cross-linked (1% or 2%) polystyrene/divinylbenzene, particularly for covalent-bonding scavengers. These materials have some distinct disadvantages. First, these materials can be used only with solvents that produce significant amounts of swelling, such as THF and methylene chloride, which allow accessibility of the functional sites to reactants in solution. Many common solvents, such as methanol and acetonitrile, may result in poor scavenging performance of the materials due to insufficient swelling. Second, using those compatible solvents, the materials may swell greatly, e.g. up to 5-10 fold of the original volume of the dry polymers. The high degree of swelling limits the amount of scavengers which can be put in a small vessel, such as 96 well microtiters which are commonly used in high throughput parallel synthesis reactions. Due to the large volume of absorbed solvent, the amount of solvent required for rinsing the particles must be high, raising concerns over volume constraints of collectors and processing equipment. The swelling also makes the materials unsuitable for being pre-packed in certain desired formats, such as columns, membranes or cartridges.
Although highly cross-linked porous polymer materials have long been used for ion-exchange, catalysis and organic absorption, the application of these materials in organic synthesis was not extensively explored until recently. A few examples given below show the application of such highly cross-linked porous polymers for ion-exchange, solid phase extraction, column chromatography, and solid phase synthesis. U.S. Pat. No. 5,230,806 describes the use of functionalized polystyrene-divinylbenzene adsorbent resins in solid-phase extraction. In particular, the reference describes the use of polystyrene-divinylbenzene resins containing such functionality as hydroxymethyl, acetyl or cyanomethyl groups for removing phenols from aqueous solutions by adsorption with minimal selectivity. U.S. Pat. No. 4,871,824 describes azlactone-functional polymer beads which can be used as complexing agents and chromatographic support materials.
In U.S. Pat. No. 5,656,707, new highly cross-linked polymer materials are disclosed. In one embodiment, the highly crosslinked polymer can be prepared from a styrene monomer and an acrylic cross-linking agent. The materials are characterized by their good mechanical stability, due to their high degree of crosslinking, and relatively higher swelling, due to the cross-linking structure. These properties are particularly desirable when the polymers are used for solid phase synthesis. Some macroporous polymer resins are also commercially available for solid phase synthesis (e.g., Argonaut Technologies, San Carlos, Calif.).
Despite the many applications for macroporous polymers which have developed in a number of areas, the use of functionalized macroporous polymer materials as scavengers in solution phase parallel synthesis has not been well explored. Only a few commercial macroreticular polymer ion-exchange resins (e.g. Amberlites) have been used to remove amines or acids by ion-pairing. It would be desirable to overcome the difficulties in scavenging processes related to the high swelling and narrow solvent compatibility of current polymer scavengers, by developing and using functionalized highly cross-linked, macroporous polymer materials with specific functionality.
It will be readily appreciated that a need exists for improved scavenging reagents which have a relatively low degree of swellability while maintaining the capacity, reactivity and broad solvent compatibility desired in these applications. Such materials would be particularly useful in high throughput synthesis reactions, particularly in easy use formats such as columns, membranes, beds and cartridges.
The present invention features a scavenging reagent for use in chemical synthesis procedures, devices incorporating such reagents, and methods for using the reagent in such procedures. The scavenging reagent comprises a low-swelling, highly crosslinked, macroporous polymers, and preferably polystyrene resins, which contain functional groups designed to bind to, and remove impurities from, reaction mixtures containing products of interest. The products of interest can result from the combinatorial chemical synthesis of a large number of compounds in a chemical library. These chemical entities are purified using high speed techniques.
In one aspect, the polymers of this invention are highly crosslinked, low-swelling macroporous resins. The resins contain at least 8% mole of cross-linking agent, compared to the 1% or 2% crosslinking generally used for polystyrene divinylbenzene polymers. The highly crosslinked structures typically result in a polymer which swells less than about 100% in THF or dichloromethane, compared to 500% to 1000% swelling for 1% or 2% crosslinked polymers. The low degree of swelling produces a polymer reagent having a much higher scavenging capacity within a limited volume when used to remove compounds of interest from organic solutions. The broader solvent compatability results from the porous structure of the polymer. The porous characteristics of the polymer eliminate polymer swelling to permit the compounds to be scavenged to gain access to the functional sites of the polymer.
In another aspect, the polymers of this invention are macroporous and have a porosity ranging from about 0.15 cc/g to about 1.5 cc/g, with an average pore size of at least about 30 Å. The diameter of the polymer particles is preferably between about 10 microns and about 400 microns. This gives good reaction kinetics while also permitting a reasonable flow rate of reaction solution when using vacuum filtration.
In yet another aspect, the preferred polymers of this invention are macroporous polystyrene divinylbenzene polymers, and derivatives thereof, such as chloromethylated-polystyrene divinylbenzene and aminomethylated-polystyrene divinylbenzene polymers having specific surface areas of from about 15 M2/g to about 600 M2/g. However, many other low-swelling, highly crosslinked polymers are also suitable for the practice of this invention, so long as they function to selectively remove impurities from reaction mixtures without interfering with the reaction. These polymers, in general, can be copolymers of styrene or substituted styrenes, such as chlorostyrene, methyl styrene, chloromethyl styrene, aminomethyl styrene, and the like, cross-linked with a suitable cross-linker, such as an organic molecule having at least two vinyl groups that may be co-polymerized with styrene monomers, such as (but not exclusively) divinylbenzenes, triallyl isocyanurate, ethylene dimethacrylate, and the like. Such polymers are available from a number of commercial suppliers, such as the Rohm & Haas Company.
Polymer reagents, or scavenging reagents, having different functional groups are preferably prepared by functionalizing the low-swelling, highly crosslinked macroporous polymers described herein. Alternatively, the polymers of this invention can also be prepared by co-polymerizing functional monomers with other suitable monomers and/or crosslinking agents in appropriate amounts.
The functional groups impart the desired binding sites to the polystyrene to enable the selective removal of the impurities from the reaction mixture. This makes the polymers particularly useful as scavengers since these groups selectively bind to the impurities in the reaction mixture in an irreversible manner, permitting the scavenger to efficiently remove the impurities from the reaction mixture. Functional groups of particular interest include, by way of example, the following: —CH2NCO, —CH2NHCONArNCO (wherein Ar is phenylene or methyl phenylene), —CH2SH, —CHO, —CH2NHCH2CH2N(CH2CH2NH2)2, —CH2NHCH2CH2NH2, —CH2O—Ar—CHO (wherein Ar is 1,4 phenylene), —CH2N(R1)R2 (wherein R1 and R2 are ethyl, isopropyl or n-propyl), -piperidinomethyl, and -morpholinomethyl. The type of functionality encompassed by these specific compounds includes the broad classes of isocyanate, thiol, aldehyde, and amino groups.
In one embodiment, the particulate polymer reagents of this invention can be embedded in a macroporous sheet or film, such as, for example, a porous film through which a reaction mixture passes. In this embodiment, the film can be part of a larger structure which is also porous and is used to support the film. The reaction mixture is caused to flow through the film and the impurities adhere to the film, while the reaction mixture containing essentially only the product is collected. The impurities can be removed from the resin by washing the film.
In another embodiment, the polystyrene can be used in the form of macroporous beads or particles. Preferably, the particles will be present in a device for removing impurities from a reaction mixture. The device can comprise a chromatographic column, a bed, or a cartridge packed with the functionalized, highly crosslinked, macroporous polystyrene particles. The reaction mixture can be passed through the column or cartridge in a continuous flow procedure for maximum speed and efficiency.
It has now surprisingly been found that a low-swelling, highly crosslinked macroporous polystyrene resin can have sufficiently low swelling in organic solvents so as to be capable of being used in a cartridge or bed format, while also possessing excellent liquid diffusion within the macroporous structure to permit the binding of impurities, such as unreacted reactants, to the substrate.
The low-swelling, highly crosslinked, macroporous polymers of the present invention can be prepared by a variety of techniques which are well known in the art. In general, a styrene monomer is polymerized with a suitable crosslinking agent in a solvent under polymerization conditions which are well established in the art. Typical reaction conditions, solvents and catalysts can be found in many publications, such as U.S. Pat. No. 5,656,707, the pertinent disclosure of which is incorporated herein by reference. Suitable resins are available commercially from a variety of sources, including the Hecheng Science and Technology Development Co. (China).
Crosslinking agents which can be used to crosslink the polystyrene resin include divinylbenzene, acrylates, multi-olefinic monomers, and the like. Sufficient crosslinking agent, e.g. 8% mole or more, is used in the polymerization reaction to obtain a high level of crosslinking.
The polystyrene resin of this invention is primarily used as scavenger to remove reaction impurities from a reaction mixture. The impurities may include excess reactants, reaction by-products, or catalysts. The reaction impurities are removed from the reaction mixture by selectively binding to a reactive or functional site on the polystyrene resin. For example, primary or secondary amines may be removed by selectively binding to an isocyanate-modified polymer in the presence of amides or tertiary amines.
The functional groups are introduced into the polystyrene resin by reacting the resin with a reagent containing at least one functional group. Alternatively, the monomeric units comprising the resin, or the crosslinking agent, can be reacted with the reagent containing the functional groups, and the polymeric constituents can be subsequently polymerized using conditions as described previously.
Reagents containing functional groups which are suitable for use in this invention include, by way of example, low-swelling, porous polystyrene divinylbenzene which is chloromethylated with chloromethylethylether, and subsequently transformed into polymer-bound functionality's.
Suitable funtionalized polymers with functional amines include MP—CH2NHCH2CH2NH2, MP—CH2NHCH2CH2N(CH2CH2NH2)2, MP—CH2N(R1)R2 (wherein R1 and R2 are ethyl, isopropyl or n-propyl) CH2NHCH2CH2NH2, MP-piperidinomethyl, and MP-morpholinomethyl, using corresponding amines such as ethylene diamine, trisaminoethylamine, diethylamine, diisolpropylamine, dipropylamine, piperidine, and morpholine. In the above polymers, and those described below, the designation “MP” refers to a low-swelling, porous polymer, and preferably a polystyrene divinlybenzene copolymer. Other suitable functionalized polymers are described below. However, it will be readily appreciate by those skilled in the art that a variety of other functional groups can be appended to a low-swelling polymer, and that the particular functionalized polymers described below can be made in a variety of ways by those skilled in the art.
MP—CHO, which can be prepared by oxidizing MP—CH2Cl with DMSO in the presence of a strong base, such as potassium bicarbonate.
MP—CH2O—Ar—CHO (wherein Ar is 1,4 phenylene), which can be prepared from MP—CH2Cl by the substitution of Cl with 4-hydroxybenzaldehyde in the presence of a base such as sodium hydroxide.
MP—CH2SH, which can be prepared by substituting MP—CH2Cl with thiourea (H2NC(═S)NH2), and the subsequent reaction with an amine such as morpholine.
MP—CH2NH2, which can be prepared by substituting MP—CH2Cl with a phthalimide salt, such as potassium phthalimide, followed by reaction with hydrazine.
MP—CH2NCO, which can be prepared by treating MP—CH2NH2 with phosgene, diphosgene or triphosgene.
MP—CH2NHCONArNCO (wherein Ar is phenylene or methyl phenylene), which can be prepared by reacting MP—CH2NH2 with 1,4 phenylene diisocyanate, 1,3 phenylene diisocyanate, tolylene 2,4-diisocyanate, or tolylene 2,6-diisocyanate.
These funtionalized polymers can be used in a variety of reaction mixtures and solutions to remove impurities containing groups reactive with the polymer as described below.
MP—CH2NHCH2CH2NH2 and MP—CH2NHCH2CH2N(CH2CH2NH2)2 can be used to selectively remove organic acid halides, including sulfonyl halides, organic anhydrides, chloroformates, isocyanates by the formation of a —N—CO—or —N—SO2— bond, aldehydes by forming a —N═C— bond, and acids by forming an ion pair. These polymers can be present, for instance, in reaction mixtures as excess reagents involved in condensation reactions with amines, organic hydrazines, alcohols, and other nucleophiles. These polymers do not bind to the desired products of these reactions, such as amides, substituted hydrazines, esters, imines, and possibly derivatives such as tertiaryamines.
MP—CH2N(R1)R2 (wherein R1 and R2 are ethyl, isopropyl or n-propyl), MP-piperidinomethyl, and MP-morpholinomethyl can be used, for instance, in condensation reactions, such as reactions involving an organic acid chloride with a primary or secondary amine, to scavenge the hydrogen chloride generated. These polymers can also be used as catalysts in such condensation reactions.
MP—CHO and MP—CH2O—Ar—CHO can be used to scavenge hydrazine, primary and secondary amines, hydroxylamine, Grignard reagents, organolithium reagents, and other strong nucleophiles. These polymers do not bind to desired products, such as amides, substituted hydrazines, tertiaryamines, alcohols, and urethanes, since they are not strong nucleophiles with active hydrogen.
MP—CH2SH can preferably be used to scavenge active organic halides, such as benzyl bromide, for example. In general, the polymer should first be converted to a salt form, such as MP—CH2SK, by reaction with a solution of potassium trimethylsilycate in THF, to effectively remove the organic halides from a reaction mixture. MP—CH2NCO and MP—CH2NHCONArNCO can be used to scavenge primary and secondary amines and hydrazines by the formation of a urethane bond. The polymers can selectively remove primary or secondary amines in the presence of alcohols, at a significantly different reaction rate, or tertiary amines (no active hydrogen). These polymers do not react with amides, urethanes, substituted hydrazines, or the expected condensation products from primary and secondary amines, and hydrazines, as the products are not nucleophiles with active hydrogen.
As used in the context of this invention, the term “highly crosslinked” is intended to denote a degree of crosslinking greater than about 8% mole. A polymer which is highly crosslinked will also generally be a “low-swelling” polymer, i.e. a polymer which swells less than about 100% in an organic solvent, such as THF or dichloromethane. The use of a smaller amount of crosslinking agent will generally result in a polymer which swells excessively, i.e., more than about 300%.
By “macroporous” or “porous” is generally meant a porosity ranging from about 0.15 cc/g to about 1.5 cc/g, with an average pore size of at least about 30 Å. The degree of porosity refers to the total pore volume within the solid support. Porosity increases with increasing pore volume.
By “impurity” is meant an unreacted reactant, or excess reactant, a reaction by-product, or a catalyst left after the reaction in a reaction mixture, but not including a desired reaction product.
By “selectively” or “selectively removed” is meant that the functionalized polymer binds to the compound to be removed from the reaction mixture, but does not substantially bind to the desired reaction product. Preferably, the funtionalized polystyrene resin will bind less than about 10% of the desired reaction product, and most preferably less than about 5%.
Although this invention is preferably directed to polystyrene resins, it also encompasses other polymers which have the requisite low-swelling properties and porous structure.
The low-swelling, highly crosslinked, macroporous, funtionalized polymer can be embedded in a film or sheet material in contact with the reaction mixture. For instance, the film or sheet can act as a filter, and the reaction mixture can flow through the film. The impurities in the reaction mixture bind or adhere to the film, while the reaction mixture containing the desired product flows through the film. The product can then be separated from the liquid phase using conventional separation technology. The film can be cleaned of impurities by removing the film from the reaction mixture, and washing it with an aqueous solution or a solvent, as appropriate. The polystyrene resin can also be supported by, or contained within, a porous, insoluble support matrix which is inert to the reaction medium.
The polystyrene resin can also be used in the form of particles or beads. The particles can have any desired shape, and preferably will be sized in the range from about 10 microns to about 400 microns in diameter. The particles can be placed in a container, such as a packed bed, in a chromatography column, in a cartridge, or embedded in a porous film or sheet. The reaction mixture flows through the container and contacts the resin particles where the impurities are retained on the particles. The advantage of using the resin particles in a container is that the effective surface area can be maximized, and the system can be configured for high throughput and automated operation. These features are useful for purifying compounds produced as a result of the combinatorial synthesis of libraries of compounds. The minimal swelling characteristics of the polystyrene resin due to the high degree of crosslinking enables the resin to be used in confined spaces at a much higher loading than conventional polymers.
Further advantages of the highly crosslinked, macroporous polystyrene resin of this invention include the high rate of reaction of the resin with the target impurity in a wide array of solvents, making the performance of the resin essentially independent of the solvent used in the reaction. In addition, the relatively low swelling of the resin reduces the amount of organic solvents used in the reaction, as well as the amount of solvent used for rinsing the product. This, in turn, reduces the volume of reactors, collectors, and associated equipment used to produce a given amount of a targeted product.
The following examples are intended to illustrate the various aspects of the invention without limiting it thereby. As will be appreciated by those skilled in the art, various changes can be made to the procedures, methods and materials employed in the examples without departing from the spirit and scope of the present invention. The present invention is intended to encompass all such variations.
Preparation of MP—CH2O—Ar—CHO (Ar=1,4 phenylene)
Under argon, 4 grams of sodium hydroxide and 50 ml of dry DMSO were placed in a flask, then 15 grams of hydroxybenzaldehyde was added at room temperature. The mixture was heated to 50° C.-60° C. and kept under stirring at this temperature for about 1 hour until the sodium hydroxide was consumed almost completely. The mixture was cooled to room temperature, and 20 grams of macroporous chloromethyl polystyrene divinylbenzene (average diameter 70 microns, 1.7 mmol/g, 15% crosslinking; obtained from Hecheng Science and Technology, Inc.) was added under nitrogen. The mixture was kept under stirring for 60 hours at 90° C. under argon. An off-white solid (MP—CH2OArCHO) was obtained by filtration and washed subsequently with DMSO, methanol, THF and pentane, then dried in a vacuum oven for 5 hours with mild heating. The structure of the product MP—CH2OArCHO was confirmed by its IR. spectrum, and the degree of functionality was about 1.4 mmol/g, determined by the uptake of phenylhydrazine.
Preparation of Functionalized Polystyrene MP—CH2NCO
8.5 grams of macroporous aminomethylpolystyrene divinylbenzene (average dimeter 70 microns, 1.4 mmol/g, 15% crosslinking; obtained from Hecheng Science and Technology, Inc.) was suspended in about 20 mL of methylene chloride under argon in a reaction flask and 8.5 mL of tributylamine was added. A solution of triphosgene (1.8 grams, Aldrich) in 10 mL of dichloromethane was added dropwise into the flask at 0° C.-5° C. (cooled with an ice/water bath). Upon completion of the addition, the reaction mixture was kept at room temperature for 5 hours under argon, and an off-white solid (MP—CH2NCO) was obtained upon filtration and washed with dichloromethane, THF and pentane, respectively, and then dried in a vacuum oven at 40° C. for 5 hours. The structure of the product MP—CH2NCO was confirmed by its IR spectrum, and the degree of functionality was 1 mmol/g, determined by the uptake of benzylamine.
Preparation of Functionalized Polystyrene MP—CH2SH
20 grams of macroporous chloromethylpolystyrene divinylbenzene (average diameter 70 microns, 1.7 mmol/g, 15% crosslinking; obtained from Hecheng Science and Technology, Inc.) was mixed with 8 grams of thiourea (H2NC(═S)NH2, Aldrich) and about 40 mL of triethylene glycol in a reaction flask. The mixture was heated at 110° C. under argon for about 16 hours with magnetic stirring. Upon cooling off, the mixture was filtered, and the solid obtained was washed with methanol. The solid was replaced into a flask, and then mixed with 10 mL of morpholine and 40 mL of methanol. The mixture was refluxed for an extra 3 hours under argon. An off-white solid (MP—CH2SH) was obtained upon filtration and washed with methanol and acetonitrile until the pH of the eluant became 7. The product was dried in a vacuum oven at 50° C. for 4 hours. The mercaptane functionality was confirmed by its IR spectrum, and the degree of functionality was 1.7 mmol/g as determined by elemental analysis.
Preparation of Functionalized Polystyrene MP—CH2NHCH2CH2NH2
50 grams of macroporous chloromethylpolystyrene divinylbenzene (average diameter 70 microns, 1.5 mmol/g, 15% crosslinking; obtained from Hecheng Science and Technology, Inc.) was placed in a reaction flask, 130 mL of DMF and 35 mL of ethylene diamine were added. The mixture was kept at 80° C.-90° C. under N2 flow with magnetic stirring for 24 hours. Upon filtration, a white solid was obtained and washed successively with DMF, methanol, methanol/triethylamine (4:1), THF, Hexane. The expected product, MP—CH2NHCH2CH2NH2, was obtained upon drying in a vacuum oven at 70° C.-80° C. for 5 hours. The degree of functionality was 2.2 meq (NH and NH2), determined by elemental analysis, and confirmed by uptake of phenylisocyanate.
Scavenging of Benzylamine From a Reaction Mixture
0.6 mL of benzylamine in dichloromethane (0.5M) was mixed with 0.4 mL of phenyl isocyante in dichloromethane (0.5M) and extra 0.5 ml dichloromethane in a vial. The mixture was shaken at room temperature for 1 hour. 1 mL MeOH and 0.4 g MP—CH2NCO (1 mmol/g) was added. The mixture was shaken for 2 more hours at room temperature before filtration. GC analysis of the filtrate showed only peaks of phenyl benzyl urethane and internal standards. Upon evaporation of solvents, the phenyl benzyl urethane was obtained in 87% yield.
Comparison of the Solvent Effect of Macroporous and Gel-type Polymer Scavengers
In the following Table, the use of highly cross-linked macroporous polystyrene (“MP”) was compared with lightly cross-linked gel-type polystyrene (“Gel”) with repect to the uptake of HCl, the uptake of benzylamine, the uptake of toluenesulfonyl hydrazine, and the scavenging capacity of the resin in methanol compared to THF. The resins included amounts of divinylbenzene (“DVB”) as shown.
1uptake of HCI
2uptake of benzylamine
3uptake of toluenesulfonyl hydrazide
4scavenging capacity of 1 gram resin in methanol compared to that in THF
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|U.S. Classification||521/32, 525/379, 525/377, 525/382, 525/350, 525/332.2|
|Cooperative Classification||C08F2810/20, C08F8/00|
|Mar 6, 2000||AS||Assignment|
|Apr 24, 2000||AS||Assignment|
|May 30, 2000||AS||Assignment|
|Feb 21, 2006||FPAY||Fee payment|
Year of fee payment: 4
|Jan 29, 2010||FPAY||Fee payment|
Year of fee payment: 8
|Mar 28, 2014||REMI||Maintenance fee reminder mailed|
|Aug 20, 2014||LAPS||Lapse for failure to pay maintenance fees|
|Oct 7, 2014||FP||Expired due to failure to pay maintenance fee|
Effective date: 20140820

domain: chemistry


text:
Is your shoulder pain making it difficult for you to perform your daily activities? Are you looking to avoid surgery if possible? Have you heard of Osteopathic Manipulative Treatment (OMT), the all-natural alternative to pain relief?
Studies have shown:
Shoulder injuries are caused due to the over usage or repetitive motion of the arms and are common in athletes participating in sports or can be work related. Other causes are listed below.Next section
In addition to pain, you may experience stiffness, restricted movements, difficulty in performing routine activities, and popping sensation.Next section
The cause of your shoulder pain is diagnosed by conducting a thorough medical and physical examination. Specific tests such as X-rays, CT and MRI scans, electromyography (to tests nerve function) and arthroscopy (shoulder joint is viewed with a camera inserted through a small incision) may be ordered to confirm the diagnosis.Next section
Early treatment is necessary to prevent serious shoulder injuries. The immediate mode of treatment recommended for shoulder injuries is R.I.C.E.:
Anti-inflammatory medications may also be prescribed to help reduce the swelling and pain for the first couple days. Following the first few days after an acute injury, Tylenol is a better pain medication so the body has the chance to start healing itself. Anti-inflammatories block the healing cascade the body naturally produces.
Certain exercises may be recommended to strengthen shoulder muscles and regain shoulder movement based on the type and severity of injury.
Osteopathic manipulative treatment (OMT) is a natural method of treating pain, which can be employed along with usual treatment methods to accelerate recovery of shoulder pain.
Prolotherapy is also options to consider in certain situations.
Surgery may be recommended when conservative treatments do not work, if there are full-thickness tears, or certain fractures/dislocations are present. OMT can also be used as an adjunct to accelerate the healing process post-operatively.Return to start
Osteopath treatment for Shoulder Pain
Frequently asked questions
What should I wear to my appointments?
Loose-fitting clothing or gym clothes
How many visits will I need?
This is variable depending upon what is being treated and how extensive your treatment needs to be. Our goal is to bring you to optimal health so that you won’t need to continually return.
What is the difference between licensing and board certification for a physician, and do you have any of these?
Physicians are required to be licensed to practice medicine in the U.S. by the licensing board in each state they wish to practice.
A board certified physician has completed an additional training program in a specialty and has passed a rigorous exam to assess his or her knowledge, skills and experience to provide quality patient care in that specialty.
In my case, I am licensed to practice medicine in Texas, and I have two board certifications. The first one is Family Medicine and the second one is Neuromusculoskeletal Medicine/Osteopathic Manipulative Medicine.
What our patients say
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domain: health


It sounds like you're stacking a pile of these to add your third dimension.
Make a sandwich of straight strips.
You can accomplish by breaking your shape up into two versions made of straight, ¾" strips. Take the following simple example. By stacking Alpha-Beta-Alpha-… the corner is well-reinforced. Perhaps not as strong, but strong enough. Quantity is key and you have that by the bucket.
I've no idea what this technique is called. Answers on a postcard.
Build yourself a cut list for both versions, turn a load of sheets into ¾" stock and take it to the mitre saw. You're going to save yourself a ton of OSB this way but more than anything you're going to save time. You're going to be able to set a stop block and cut up to copies one after another.
You're going to save so much wood, you might be able to upgrade to a nice ply.
Glue up becomes interesting. Build yourself a template, or a negative and that can help you align things. Don't be afraid to do this in multiple steps. Normally I would say you could assemble each stacked part first and then assemble the shape but the quantity and the material would make this too tedious to try and bring together.


text:
S&P Global Ratings revised its outlook for BCS Financial Group and its operating subsidiaries (BCS) from ‘stable’ to ‘positive.’
S&Р Global Ratings expects BCS to benefit from the operating environment, extending its market share and diversifying its revenue base. The ‘positive’ outlook for the ratings of its subsidiaries reflects S&P’s expectations that stronger regulatory oversight in Russia and favourable growth prospects in the retail equity markets particularly will enable BCS to achieve sustainable and controlled business growth in the next 12 months, without increasing its risk profile.
S&P also highlighted its positive view of the operating environment, which will help support 2021-2022 growth for equity market participants. According to S&P, the positive operating environment means BCS can offer its customers high-quality services in key areas such markets access and market-making, structured and other specialised products.
S&P also believes that BCS’s continued diversification of its clientele base and revenue sources, mitigating income volatility and curtailing dependence on trading revenue will generate a more stable commission revenue stream for the business going forward.
The ‘positive’ outlook reflects S&Р’s judgement that strengthening BCS’s business and financial risk profiles may have a positive influence on the performance of the non-operational holding company.
‘The positive outlook by S&P is good news for BCS, signalling that the company is developing in a sustainable way. We will continue our efforts to keep BCS growing and are optimistic for what 2021 holds. ” said MD, co-CEO BCS Global Markets Maxim Safonov.
It has recently come to our attention that some individuals in Estonia with whom we have no business relationship have received phone calls from an individual purporting to be a BCS GM employee and soliciting BCS GM investment services and investments. Please note that BCS GM does not maintain an office in Estonia. We also take no action to promote our services in Estonia through phone calls or otherwise. If you ever have any questions of whether a person contacting you is actually an employee of BCS GM, please do not hesitate to contact us at +44 20 7065 2161 or email at firstname.lastname@example.org
We also strongly recommend that you report any such cases to the national police.

domain: economics


text:
While China will suffer from a trade war with the United States, some experts say the Asian giant has more resilience than the U.S.
The "Chinese government has plenty of financial resources to step in," said Arthur Kroeber, founding partner of Hong Kong-based financial services and research firm Gavekal Dragonomics.
"I think the Chinese government has looked at this and is prepared to act," Kroeber said, speaking by phone from Beijing.
In the last few decades, the communist government in Beijing has built China into the world's second-largest economy with a state-backed form of capitalism and has expanded the nation's global reach. A large portion of that growth came from heavy-handed policies that favored domestic industries, displaced more than a million people for infrastructure projects and generated questionably high levels of debt.
But key to China's rise has been access to the global market, particularly the U.S. consumer. And in the very near term, that makes the Asian giant vulnerable to increased tensions with the U.S.
China was the largest source of goods imported to the U.S.in 2015, according to an estimate from the Office of the U.S. Trade Representative. The U.S. goods trade deficit with China was $366 billion in 2015, meaning the U.S. bought far more from China than the other way around.
"If there is a full-fledged trade war, China is going to get hurt disproportionately to the U.S.," said Jacob Shapiro, director of analysis at Geopolitical Futures, an online publication that analyzes and forecasts the course of global events.
"It's not really about what China wants. China needs access to the U.S. consumer market," Shapiro said. He doesn't expect tensions to escalate into a trade war.
U.S. President Donald Trump has promised a policy of "America First" and bringing back jobs, ostensibly lost to China. He has also threatened tariffs on goods imported from the Asian giant and chosen a group of outspoken China critics for top positions on trade policy.
However, Beijing has an array of tools to strike back with, and the message from the state is it will use them. China's state-backed Global Times said in an English editorial after the U.S. presidential election that:
"A batch of Boeing orders will be replaced by Airbus. U.S. auto and iPhone sales in China will suffer a setback, and U.S. soybean and maize imports will be halted. China can also limit the number of Chinese students studying in the U.S."
"There's an array of things China could do that are not trade related that would enable them to persuade in a personal way," Kroeber said, adding that Beijing could also make China a tougher business environment for U.S. companies operating there.
In the last few weeks, China's president, Xi Jinping, and other top Chinese leaders have also stepped up efforts to promote China as a globalization-friendly alternative to Trump's protectionist stance. The power play is especially important this year. Xi is set to consolidate his authority at a Communist Party congress this fall.
The political support for free trade rhetoric is more divided in the U.S.
"Trump also needs to show he's making things better for the American worker," Shapiro said. "He's also limited" in power due to the U.S. democratic system of checks and balances.
The challenge is if trade tensions escalate, Shapiro said, "the U.S. is going to be hurt anyways" from disruption to the supply chain. Many products sold in the U.S. are partly or wholly manufactured in China.
To be sure, it's still unclear whether U.S-China tensions will heat up into a trade war that decimates one party over the other. China's economy is by no means as advanced as that of the United States, but can increasingly hold its own while U.S. presidents come and go. Meanwhile, deep business relations between the two countries will be complicated to unravel.
"I don't see trade as a zero-sum game where, if one country benefits the other loses," said Ira Kalish, chief global economist at Deloitte. "Certainly both countries depend on one another substantially."

domain: finance


text:
Extreme Makeover: The iPhone Edition
Elan’s free g!Mobile app works with the iPhone, iPod touch and iPad.
A Minnesota-based homebuilder is hoping to sell houses based on tech extras.
A powder room, finished basement, good school system, heart-shaped swimming pool; there are certain perks that make a home a must-have. However, if one homebuilder has his way, iPhone control will soon be added to the standard list of extras.
Twin Cities-based builder Rocky DiGiacomo has started putting iPhone functionality into his a few of his home offerings. According to the Star Tribune, these features will allow some lucky homeowners to tap into the garage door, the HVAC system, security cameras, and even the A/V setup, all via that extra-special handheld. The equipment can vary, but DiGiacomo has been using Elan’s free g!Mobile app to deliver the iPhone goods.
“We’re trying to piggyback on the hoopla over iPhones,” DiGiacomo told the paper.
It certainly sounds like good business sense, given the current iPhone frenzy (see your local Verizon store for some of that). That said, DiGiacomo says that the equipment alone can cost $20,000. It seems like a bit of a stretch, especially in this economy. Even DiGiacomo admits that it can be a tough sell.
However, I’m all for standing out, and it looks like DiGiacomo has his hook. It sounds like an interesting business model, as well as a good add-on for an iPhone user. There are plenty of apps out there; do you think this is something people will want to see in a real estate listing?
After all, if there is one guy that wants a toilet-shaped house, there have to be millions that wants this sort of functionality as a standard, right? Would you buy a house based on iPhone compatibility? Sound off in the comments section below.
Return to full story:

domain: news


text:
How Many Energy Are Burned Enjoying Video Games?
The Nintendo Change , reaching two spectacular sales milestones previously 10 days, has notched a 3rd. I consider the Change as a a lot better realization of the design philosophy/technique behind the Wii U: the Wii U was designed to allow for an ‘untethered' gaming experience, but this was restricted by two main components - comparatively poor battery life (of the controller) and brief vary.
The Nintendo DS is region free within the sense that any console will run a Nintendo DS recreation purchased wherever in the world; nevertheless, the Chinese language version of iQue DS video games can solely be played on the Chinese language iQue DS, whose bigger firmware chip incorporates the required Chinese language character glyph photos, this restriction is removed on Nintendo DSi
and 3DS techniques.
Not only to coach your AI for each game (DeepMind's results depend on playing each sport many hundreds of occasions to train on it) but to tune your whole system to work higher on the games you know you will prepare on. Most of the people who defend the Nintendo Wii should you look nearer they'll appear to emphasize the Virtual Console part more.
Im utilizing a Via rhine ii crossover ethernet cable connect from my xbox to my harddrive and im utilizing ICS. Nintendo is also using pal codes for the Change, which we had been actually hoping they'd finally eradicate. The following time you might be within the video store, take a good take a look at what is on the shelf. If you cherished this short article and you would like to receive more facts regarding theconsoleclub.gr/el retro video games
kindly visit the webpage. In addition to the portability, the Deluxe Switch version also packs in a smattering of recent characters, karts and gameplay tweaks that weren't in the authentic. When you'll be able to copy Wii video games on your pc it gives you the proper strategy to backup any game you need. Hello coffeegginmyrice, thanks for dropping by. Pixlr is nice for the vintage and retro look.
At E3 2017, a smattering of thrilling games was revealed, together with Metroid Prime 4 , Anthem , The Crew 2 , Skull & Bones , and the upcoming Pokémon title for Nintendo Change. There are many games obtainable that kids and adults can get pleasure from, from army games to games where you exercise. Este concorrente é especializado no mesmo segmento da Eletrônica Borguinny: comércio de videogames, como Ps2 e 3 e Nintendo (Wii, PSP, Xbox 360), além de jogos e acessórios dos mesmos. Video games might be exhausting to choose up and learn , especially for these not accustomed.
In actual fact, some main retro gaming tournaments happen using basic video games from the GameCube, such because the preventing game Super Smash Bros Melee. In truth, in relation to third social gathering, Nintendo does finest in this by licensing makers like UNCOMMON, Retro Studios, and Sega. You may understand the most effective Wii Fit Plus video games for dropping pounds by looking at every one's METs, or metabolic equivalents, which relate to how a lot power you employ to perform an exercise. You export the model right into a format that online game design software understands.
Laughter - board games that are the most fun are inclined to have an element of humor and will get individuals laughing. Dan's collection consists of 20 completely different Nintendo 64 techniques from all over the world - all an identical on the inside, however wanted resulting from variations in how they look. Actually online game craze for young boys is pretty regular and is basically nothing new.
Copying or downloading games that you simply did not legally purchase is a violation of not solely your local laws, but in addition worldwide copyright law. This simplicity is a lovely idea, which is almost definitely a part of the explanation that retro games like Shovel Knight and Axiom Verge are so in style in the present day. There's at the moment no equal for Xbox One, though Microsoft's blended actuality headsets are expected to finally work with the Xbox One household. Love this style, I'm thinking of trying to get Animal Crossing it simply keeps arising after I search for games to play. For one, the AC power port is barely altered to account for the Wii U's new, bigger adapter.
Of the third-occasion video games accessible at launch, most were quick conversions of familiar PlayStation and Xbox titles: Call of Duty, Batman, Fifa... few of these exploited the GamePad feature-set in actually revolutionary methods. Merely connect a small, hidden channel on a system so that the console will get hold of that libdi file. The Xbox 360 CPU had high latencies for all the things, with memory latencies being particularly unhealthy. A Kanji studying DS software that has a bit for hiragana and katakana observe, although the main target is on Kanji. That means you can play Xbox One games wherever in the house, not just in the lounge. To the left of the lower touchscreen is an analog nub that Nintendo dubs the circle pad.

domain: hobby


text:
Full Name: Allison Nelson Jefferson Davis Lauderdale
Date of birth: March 9, 1862
Date of death: December 12, 1938
Terms of Service top
||Dates of Service
||Counties in District
Jan 11, 1921 - Jan 9, 1923
Somerville / Burleson
Biographical Notes and Resources top
- Allison N. Lauderdale, birth date 3/9/1862 in Washington County, death date 12/12/1938 in Beaumont, Jefferson County, retired farmer.
FamilySearch Texas Deaths, 1890-1976.
- Allison N. Lauderdale, birth date 3/9/1862, death date 12/12/1938, burial in Oaklawn Cemetery, Somerville, Burleson County.
Find a Grave.
- Death notice, Allison Nelson Jefferson Davis Lauderdale, "Father of Beaumont Man is Buried Today," 12/13/1938, p. 7, "one time member of the Texas legislator [sic]," death date 12/12/1938, buried at Somerville.
Port Arthur News.
- Obituary, Allison Nelson Jefferson Davis Lauderdale, "Lauderdale Rites Held at Somerville Tuesday Morning," The Caldwell News and The Burleson County Ledger, 12/15/1938, p. 1, crediting Harrie P. Woodson Memorial Library.
Portal to Texas History (University of North Texas Libraries).
- 37th Legislature (1921) - A.N. Lauderdale, postoffice Somerville, nativity Texas, age 58 (born circa 1863), 58 years in Texas, farmer, Democrat.
Texas Legislative Manual.
Composite Photographs on Display in the Capitol
Committee Information top
This website is a work in progress. Information on this website is provided as a public service by the Legislative Reference Library. The Legislative Reference Library makes no representation as to its completeness or accuracy and makes no warranty in regard to its use. Users assume all risk of reliance on the information included on this site.
Have a question, comment or contribution? Email the Library or call 512-463-1252.
Many photos in Texas Legislators: Past and Present are used with permission of the Texas State Preservation Board. For permission to reproduce these photos, please contact the Texas State Preservation Board graphics coordinator at 512-475-3060.

domain: library


Blogs by Megan Townsend, GLAAD's Entertainment and Operations Coordinator
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GLAAD Media Award recipients were announced in 16 of this year's 33 media categories at the 24th Annual GLAAD Media Awards, presented nationally by Ketel One Vodka and Wells Fargo and locally by Delta Air Lines at the New York Marriott Marquis and Suites in New York on Saturday night.
Recording artist Carly Rae Jepsen, who withdrew as headliner of the 2013 National Scout Jamboree following a campaign launched by GLAAD and Eagle Scout Derek Nance, today spoke with MTV News about her decision to drop out of the concert. Bill Gates recounts his time as a Boy Scout but urges the organization to end it's anti-gay ban "because it's 2013."
MTV stars Nicole "Snooki" Polizzi and Jenni "JWoww" Farley will appear and recording artist Jake Shears will perform at the 24th Annual GLAAD Media Awards in New York on March 16, presented nationally by Ketel One Vodka and Wells Fargo, GLAAD announced today.


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Will Nicole and Yvonne go home with a statue? Join us for all the action from the 2019 Golden Globe Awards.
- by Melissa Singer & Karl Quinn
The annual awards season kicks off in earnest with the Golden Globes on Monday, and this year it is all about diversity.
- by Karl Quinn
The Golden Globes provide the highest-profile pit stop on the way to the Academy Awards.
- by Kyle Buchanan
Time's Up founders announce expansion on the eve of its one-year anniversary at the Golden Globes.
- by Nicole Economos
The nominated song is a collaboration between Sivan and Jónsi of Sigur Ros, and was written for a specific scene in the film starring Nicole Kidman.
- by Daile Cross
The Hollywood Foreign Press Association has nominated a superhero movie as best picture for the first time. Can the Academy do anything but follow suit?
- by Karl Quinn
Handmaid's Tale costume designer Ane Crabtree reflects of the legacy of her dystopic designs.
- by Mary Ward
Gary Ablett speaks of 'roller-coaster' week as he gets to Geelong ahead of funeral of sister Natasha
Gary Ablett has paid tribute to his late sister Natasha and thanked Geelong, Gold Coast and the "wider community" for their support after he rejoined the Cats on Thursday.
- by Daniel Cherny
There were thank-yous to producers, agents and co-stars. Then his speech careered into a story about what humanitarians call "dirty beer".
- by Ebony Bowden
As the debate continues raging among journalists about how aggressively to call out Donald Trump's lies, a new episode reminds us why it's so important not to flinch from reckoning with the possibility that conventional journalistic techniques just aren't going to cut it during the Trump era.
- by Greg Sargent
Donald Trump dismisses 'over-rated' Meryl Streep as a 'flunky' for Hillary Clinton after Golden Globes criticism
Mr Trump repeatedly fired back at Streep, calling her an "over-rated actress" and a "flunky" for his former political opponent, Hillary Clinton.

domain: entertainment


text:
In a shallow dish whisk together cornstarch (or flour), chili powder, salt, and pepper.
In a second shallow dish, whisk together the eggs.
In a third shallow dish, add the pork rind crumbs (or panko crumbs).
Cut avocados in half, longwise - cutting in the center of the avocado from top to bottom. Remove the pit and peel.
Then, cut the halves into 1/2-inch thick slices, yielding about 8 to 10 slices per avocado.
Dredge each avocado slice into cornstarch to coat both sides entirely, shake off any excess.
Transfer to the beaten egg, turn to coat well; lift it up and let excess egg slide off.
Transfer to crumbs; turn and coat, while pressing crumbs to adhere on both sides.
Spray the air fryer basket with nonstick cooking spray.
To the air fryer basket, arrange as many avocado fries as it fits without touching each other. You’ll probably have to cook these in batches.
Lightly spray the avocado slices with cooking oil.
Set the air fryer to 400˚F and cook the avocado fries for 3 minutes.
Flip them over on their sides, lightly spray with cooking oil, and continue to cook for 3 to 4 more minutes, or until crispy and golden brown.
Repeat with remaining batches.
In the meantime, combine ranch and buffalo sauce in a dipping bowl; mix and stir until well combined.
Garnish avocado fries with chopped cilantro and serve with lime wedges and the dipping sauce.

domain: food


Blunkett in compulsory company pensions plan
Last updated at 10:34 20 June 2005
Official reports say more than 12 million people are not saving enough for their old age and Mr Blunkett acknowledged the current system was unsustainable because people were now living longer.
Prime Minister Tony Blair has warned there would be "real difficulties" with compulsory savings. But Mr Blunkett said just giving people information "is not enough".
Mr Blair has asked the Pensions Commission to look at ways of reforming the pensions system. It is due to release its findings in November.
Options under consideration are higher taxes, a higher retirement age, or compulsory savings.
Mr Blunkett insisted he did not have a plan yet. But he hinted he could look at compulsion.
"We have a responsibility to make sure there is sufficient for people to live on," he said.
"I think it is a very interesting question as to whether Government has a responsibility for actually making people go beyond that. But we certainly have a responsibility to ensure they know the consequences of not doing that."
'Good occupational pensions'
He told BBC1's The Politics Show: "Whilst the evidence is that good information, education, awareness is vital... the truth is if four million people who have good occupational pensions to which the employer is contributing are not taking up the option of adding their resources in at this stage, we have a problem. In other words information is not enough."
Mr Blunkett said he had an open mind on the way forward. He said he had not ruled anything in or out. Opponents have accused the Government of wanting to kick the issue into the long grass, putting off a decision until after the next election. But Mr Blunkett said the Government would make a decision within the next two years.
"Over the next two years we will make the decision because as everybody, I think with good will, wants a consensus we have got to spend the time trying to build as far as we can a coalition of those who know there is a challenge - not a crisis - but a challenge for the future.
"We don't want to end up as we have for instance with so many women where the contributions they have paid have not entitled them to a full basic pension, never mind the added personal pensions that we are talking about here."
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text:
- It's just a game, but catching Pokémon figurines with your smartphone starts here and become a pest. This is clear from messages on Twitter, among other police forces.
The police have their hands full with reports of suspicious and sometimes dangerous situations around the game. Since the app was launched a few days ago, Pokemon Go hype worldwide. The intention is that the user captures the familiar characters from the TV series Pokemon with his smartphone. For non-users, there is nothing to see, it is a virtual world that can only be seen through the camera of the phone is.
The result of the hype is that players take to the streets individually or with a group to catch the creatures. This happens day and night. The players have eyes only for the smartphone screen and, according to the police make dangerous situations. Reports about were among the police Eindhoven and Haarlemmermeer.
'Fancy' ladies by ribbon on Mac
Love: boy consolation French fan
Oops! Cameron blunder with microphone
The Eindhoven police tweeted:,, Just targeted group who ran towards the center. All a cellphone in hand with eyes only for the display. When addressing one appeared to be looking for Pokémon. So you still learn every day what. '
The Academic Medical Center Amsterdam (AMC) also had to deal with Pokemon Go. There are people walking around in areas prohibited for visitors. In a tweet reported the hospital:,, There is a sick Pokémon in the AMC- we'll take care of him. We would appreciate it if you'm not visiting '
Moreover, the app, created by Nintendo, not yet officially available in the Netherlands. is it still possible to download here via digital shortcuts.
If blind people look at their phone screen to play Pokemon Go, without looking around,,, it is inevitable that the number of fatalities will increase. ' Before that warns Traffic Safety Netherlands Tuesday. Each year, an estimated ten to one hundred people died in traffic because they or others are busy with their mobile phone.
The organization calls on people to be responsible.,, People are so immersed in the game that they do not perceive their environment. There's insecurity, for yourself and for other road users, 'says a spokesman.


text:
Nottingham Trent University, Former Registry Office
Experienced in the engineering requirements of both new build and historic buildings (and particularly, timber structures), Rolton Group were appointed by long-standing client Nottingham Trent University to provide geotechnical, civil and structural engineering services, to assist with the restoration and development of a site that formerly housed the Grade II registry office on Shakespeare Street, Nottingham.
he aim of the project was to refurbish the existing building to create a new space, including meeting rooms, boardrooms, event facilities, the Deputy Dean’s office and other office spaces. A new two storey extension was also created on the site, to house a new kitchen and lobby area with a link to another building.
Ahead of and throughout the project, Rolton Group’s structural engineers regularly visited the site to conduct a number of surveys, including a visual survey of the roof trusses to assess the condition of the joints in order to advise the university how best to proceed. The investigations revealed the existing building had previously been altered, repaired and refurbished (in part, because of damage sustained during World War II and through changes over time). However, not all of the alterations were structurally viable and many areas needed addressing. Rolton Group liaised closely with the university’s architect, MEP team and small works department to ensure the necessary remedial works were identified and completed in a timely fashion, keeping the project to its original programme.
In a previous modification, a suspended ceiling was created, covering and damaging the ornate ceiling of the building’s main hall. This left holes punched through the lath and plaster ceiling, damaging it. In addition, the connections of the cut timber roof trusses had opened up, presenting a structural concern.
Rolton Group provided two different roof truss remediation methods, with the selected ‘clamping’ option ensuring the remainder of the ornate ceiling was preserved, reducing the cost and time required.
The team was also tasked with installing a new disabled access lift – a challenge given the Grade II listed status of the building. They successfully designed a new steel frame lift shaft with a reinforced concrete lift pit positioned between the existing brickwork walls, giving great consideration to ensuring this was achieved without compromising the heritage of the existing Grade II listed building.
The building lies on a former row of old terrace houses that were demolished many years ago, meaning that the ground locally was disturbed to a depth of approx. 3.5m. Rolton Group’s geotechnical team assessed the site ahead of the creation of the new two storey extension. Following thorough investigations, the team provided valuable advice to resolve issues with the ground conditions. Old material from the ground was removed and the site went through a process of backing filling with granular sub-base. A reinforced raft foundation was subsequently designed as the best solution for this new development.
In addition, Rolton Group’s civil and structural team was involved in designing and supporting the construction of the new extension which would house a kitchen and lobby area. They provided design layout and levels of private storm and foul drainage connections to the existing drainage on-site, providing diversions where necessary, as well as delivering the design, specification and detailing of individual steel members, precast concrete upper floor, masonry design and roof trusses for the structural element of the build.
Image credit: Nottingham Trent University

domain: design


text:
Children from Crawley Ridge Junior School saved up their 2p’s to give the elderly folk a delicious afternoon tea which would match that of a five star hotel. The children first met the folks at their weekly coffee morning at St Paul’s in July when they sang to them and served up refreshments. The group obviously made an impression on the youngsters as the children decided to collect their pennies and in total raised £50. Fun and laughter was shared by all with a hearty sing-along of favourite songs, topped off with a delicious spread of dainty sandwiches, cream scones and scrumptious cakes.
The coffee morning is for seniors and runs every Thursday at St Paul’s from 10.30am until 12pm. It is a lovely opportunity to meet friends old and new and share a cuppa. Everyone is welcome and there is always a plentiful supply of home made cakes and of course pots of coffee and tea.
You can just turn up on the day, but if you would like to know more call Claire Isherwood on 07854 549154.


text:
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Captain C.H. Davis founded Wimauma in 1902. The town site was located on a 55-mile railroad route from Durant to Manatee County and into Sarasota. Wimauma, a farm based community, has 6,500 year-round residents, and increases with the farming seasons to 11,000+. Wimauma is truly special because of the vast diversity of its residents and businesses. There are ‘bodegas and cantinas’ along with bakeries, small businesses and several schools. There are three farmworker missions that support and meet the needs of the migrant community. Wimauma is also home to the Wimauma Church of God Camp Meeting and Convention Center, drawing hundreds of visitors to Wimauma.

domain: geography


text:
On Thursday, many Americans watched and waited as the House Republicans passed an appeal for Obamacare, called the American Health Care Act (AHCA).
One Washington, D.C., college student, Zoey Salsbury decided she would set out to make the GOP face the consequences of their decision.
Salsbury launched a new website called mailmetothegop.com. The website allows you to donate your ashes to be mailed to the member of Congress which you specify.
“Millions of Americans rely on protections and coverage from the Affordable Care Act, or Obamacare. The Republicans new bill will gut these protections and many will die,” the website reads. “They deserve to know it. Fill out our form and we’ll help you get papers in order to send your ashes to a GOP member of Congress if you pass,” it continues.
The website also has a section for you to explain why the decision of the GOP will kill you, and so far, many people have already explained their reason why.
The new AHCA could potentially kill people by discontinuing their coverage or denying them access to medications, surgeries and other treatments.
“Yes, it is real,” Salsbury, a junior at American University, said on Thursday, not long after the website was crashed from the influx of traffic.
Salsbury still has health insurance under her parents today, thanks to a provision in the Affordable Care Act allowing children to stay under their parents’ health care plan until they reach the age of 26.
While the GOP bill has no chance of passing the senate, if it did it would still keep the popular provision that allows children to remain under their parents’ policies until age 26. However, other regulations would cast millions off of insurance.
The new bill would undermine Obamacare protections for the sick, poor and those with pre-existing medical conditions.
“Many of my friends will die” if this becomes law, she said. “People will literally die, and they don’t see that that’s going to happen.”
The National Funeral Directors Association said it is only legal to ship cremated remains via the U.S. Postal Service, which give you an idea of what the packaging for your remains might look like.
Salsbury said she launched the website on a whim, after discussing the new bill with a few of her friends who could potentially be effected by it.
“It’s really morbid and not fun to talk about,” she added. “But that’s the reality of passing a health care bill like this.”

domain: law


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A little about yourself and what you have to offer this wedding community?
Shannon Goode has worked in the beauty industry since 1997 and owns GoodeHair.
While working in salons, owning a salon in Indiana, and kick-starting her wedding hair business in Ohio, she has become an industry leader in styling techniques and "how to."
Her experience also includes being a part of the education team for Alterna and TIGI. These have all given her experience in the creative art of fine event styling and updo creation. Working behind the camera at beautifully styled shoots, productions & commercial creations, and for major broadcasts has given Shannon the passion to style in an innovative, forward focused fashion.
Outside of creating hair masterpieces, Shannon loves to spend time in her hammock on a quiet nature trail, running for miles, and climbing trees whenever possible.
Do you have a wedding website, blog, or registry link?
How is everything with you, I picked interest on you after going through your short profile and deemed it necessary to write you immediately. I have something very vital to disclose to you, but I found it difficult to express myself here, since it's a public site.Could you please get back to me on ( firstname.lastname@example.org ) for the full details. Have a nice day Thanks God bless.

domain: artistic


Samsung Galaxy J7 Plus is in pre-order in Thailand at the price of THB 12,900, equivalent to about 328 euros.
OnePlus 5 could have a monochrome sensor as per Huawei tradition
The news that will arrive with Android O will be many and, as it could not be otherwise, the performance will be one of the areas impreved
With the HTC One X10, a previously unknown Android smartphone is dipped, which wants to score with special features.
Google and Apple apparently assume that the security vulnerabilities published under the name "Vault 7" have already been largely closed.
You can set up your Android Wear 2.0 smartwatch to do likewise by taking after these bearings.


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Solicitor from child abuse inquiry voices doubts over evidence
PUBLISHED November 9, 2012
It comes as new evidence suggests that Lord McAlpine, whose name has circulated on the internet as the man accused, is a victim of mistaken identity.
Chris Saltrese, a lawyer at the Waterhouse inquiry, suggested that the allegations of some of those said to have been abused lacked substance making it difficult for those faced with the claims to respond to.
He told BBC Radio 4's Today programme: "There is no evidence, apart from somebody's story, and sometimes the complainant in these cases can't even say what year it was, what house it was in, what town it was in even.
"As a consequence, it is very very difficult for a defendant and his lawyers to grapple with that kind of thing."
Yvette Cooper, the shadow home secretary, was pressed on Today to spell out what fresh allegations merited reopening the North Wales case, but declined to do so, saying that this was a matter for police to judge.
"I don't think it is for me to comment on the veracity of different allegations," she said. "I think it is right that the police should decide on the scale of the evidence and not for me to comment on live radio."
She added: "If they decide there is no evidence or the Crown Prosecution Service decide there is no evidence, then that is the way the criminal justice system works.
"We have a criminal justice system which operates within the bounds of the law. It is right that we let them pursue this and do that job for these very serious crimes, rather than us trying to pre-empt those judgments in one direction or the other."
Lord McAlpine, the Thatcher-era Tory treasurer, was smeared online following allegations of abuse made on the BBC's Newsnight programme last week, which did not name him.
Steve Messham, a former resident of the Wrexham care home at the centre of the allegations, claimed he had been taken to a Wrexham hotel and abused by a prominent Tory more than a dozen times.
But a local councillor who was also a victim of abuse at the Bryn Estyn home told the Guardian he did not believe Lord (Alistair) McAlpine was involved.
Keith Gregory said he thought a different member of the McAlpine family who lived locally may have been mistaken for Lord McAlpine.
A man who children at the care home believed to be a McAlpine would arrive there in an expensive car, he said.
Jimmie McAlpine, who chaired the north of England builders Alfred McAlpine Ltd, was said in his Times obituary to have an interest in vintage cars, and to have amassed "what was at one time the biggest private collection in Britain."
The Waterhouse inquiry into the abuse allegations recorded that, according to Mr Messham's statement to the police, "X (the letter used to hide the identity of the McAlpine family member) had several different motor cars and would wait for him at the bottom of Bryn Estyn Lane."
Reporters covering the inquiry at the time concluded that Lord McAlpine could not be the person referred to as the abuser because Mr Messham said his abuser was dead, whereas Lord McAlpine is alive. And when a Times reporter put Lord McAlpine's name to Messham in 1996, he said his abuser was in fact called Tom.
Another boy who originally appeared to corroborate the accusation later confirmed that he had only been shown a photograph of Lord McAlpine by a journalist subsequently, and said this was his sole knowledge of him. Lord McAlpine has strongly denied the allegations.
It came as David Cameron warned that homosexual men were at risk of a "witch-hunt" yesterday after he was confronted with a list of suspected paedophiles live on television.
ITV was heavily criticised after the presenter Phillip Schofield inadvertently exposed the list of alleged
child abusers to viewers during an interview on the This Morning programme.
A Conservative MP asked regulators to investigate whether ITV had broken the broadcasting code and Jonathan Dimbleby described Mr Schofield's behaviour as "cretinous". Downing Street warned that innocent men were at risk of "trial by Twitter", amid inquiries into alleged abuse by Jimmy Savile and other celebrities, and claims that a senior Tory figure raped a boy of 13 in north Wales in the 1970s.
Sources said Mr Cameron was unhappy about ITV's "silly stunt" and his aides felt the issue was "badly handled". During the interview, the Prime Minister did not look at the list, which Mr Schofield had compiled from the internet.
Þ Jimmy Savile's former chauffeur and flatmate has been arrested over abuse allegations. Ray Teret, 71, was detained at his home in Altrincham, Cheshire, on suspicion of rape. A 61-year-old arrested at the same time was also being questioned on suspicion of rape. Police said the allegations were not linked to the inquiry into abuse by the late DJ.

domain: sociology


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Weve all heard the advice that to lose weight you need to simply count calories and eat less. The idea is that if you go into starvation mode your basal metabolic rate drops so youre burning less calories and thats what everybody calls starvation mode.
Dr Jason Fung explains how your basal metabolic rate increases with long fasting and how mere calorie restriction just brings your bodys metabolism down.
Dr jason fung fasting and metabolism. Jason Fung MD is a nephrologist and expert in the use of intermittent fasting and low-carbohydrate diets for the treatment of Type 2 diabetes. Four consecutive days of fasting increases basal metabolism by 13. Note that fasting may not be right for you especially if you have diabetes or a metabolic disorder.
Fung also suggests homemade salted bone broth in place of lunch on fasting days to maintain sodium levels. James DiNicolantonio of the upcoming The Longevity Solution. Studies of alternate daily fasting ADF shows the same thing.
If a specific diet can lower the BMR then a different diet must be able to raise it. He trained in Los Angeles and Toronto as a kidney specialist. Fung is a nephrologist and expert on the use of fasting as a clinical tool to promote patient health.
Jockers to reveal the secret to life as old as 2000 years in the past. Lets talk about the basal metabolic rate changes during fasting. Fungs views have attracted criticism from several experts.
The idea is that if you go into starvation mode your. One of the big reasons for its failure is the decrease in metabolic rate or the number of calories that the body burns each day for energy. 872018 Myths of Intermittent Fasting.
Yes the basal metabolic rate BMR is not fixed. By Jason Fung MD Co-founder of The Fasting Method. Most of the group fasts his team were leading on FB was a mix of 1 and 2 meal days with most being 1 meal to keep the body looking for the higher calories.
Jason Fung joins Dr. For both protocols snacking is prohibited and its important to stay well hydrated with water green tea and coffee. James Fung and author Jimmy Moore reveal the numerous benefits of fasting.
Early in his medical career it became obvious to him that conventional treatments were failing patients. Dr Jason Fung explains how your basal metabolic rate increases with long fasting and how mere calorie restriction just brings your bodys metabolism down. Hes a Canadian nephrologist a researcher a world expert on intermittent fasting and an author.
I generally suggest fasting and LCHF diets. Plus theyll also address one of the main reasons most people have never attempted to fast. And even helps clear out toxins and damaged cells which lowers risk for cancer and enhances brain function.
Studies of fasting show that basal metabolism doesnt shut down during fasting it revvs itself up. A process that can help people lose weight improve brain function promote longevity speed up the metabolism strengthen the immune system and contribute to self-enlightenment. 1252016 Studies of fasting show that basal metabolism doesnt shut down during fasting it revvs itself up.
Four consecutive days of fasting increases basal metabolism by 13. Lessens inflammation which improves a range of health issues from arthritic pain to asthma. Studies of alternate daily fasting ADF shows the same thing.
Jason Fung MD is a Toronto-based nephrologist obesity expert co-host of the Low Carb MD Podcast author of The Obesity Code The Diabetes Code and The Complete Guide to Fasting and co-author with Dr. He is the author of The Obesity Code The Complete Guide to Fasting and The Diabetes Code and he founded a clinically applicable health program that provides fasting strategies to promote weight loss enhance cellular rejuvenation and manage blood sugars. So during fasting what you see in this study was over four days of fasting you can see the weight is steadily dropping which is what we expect and then the REE which is the Resting Energy Expenditure actually goes up over four days of fasting.
Silver PhD director of the Vanderbilt University Medical Centers Diet Body Composition and Human Metabolism Core in Tennessee noted that intermittent fasting may not be sustainable in the long-term when it comes to getting rid of weight. 2962018 The researchers combed through dozens of animal and human studies to explain how simple fasting improves metabolism lowering blood sugar. 2742016 From Dr Fung hes said its unrealistic to get enough calories to keep the metabolism where you need it with only one meal that is why its not recommended.
A severe calorie-restricted diet such as 800 calories per day is almost guaranteed to lower your BMR. We also know that this advice rarely if ever works. Starvation Mode with Dr Jason Fung – YouTube.
If youre looking for an effective way to lose weight and work on your metabolism then this episode is for you. The Truth about Metabolism.

domain: medical


There was robust coverage of this week’s announcement of a new federal program that will enable incarcerated Americans to receive Pell Grants and pursue postsecondary education while in prison.
Ford Foundation President Darren Walker praised the news:
“The promise of the Second Chance Pell Pilot Program has been demonstrated time and time again with profound results. When incarcerated individuals have access to high quality higher education it reduces recidivism and transforms the lives of individuals and communities. This is a moment of opportunity to reform our criminal justice system into one that values and restores humanity and justice. A system that is worthy of our ideals includes programs that restore dignity to individuals and also make common sense.”
For more perspectives, check out our blog posts on the work that helped lead to the Pell Grants program, the latest strides in sentencing reform, and last year’s TEDx event at Ironwood State Prison. Plus: Our Q&A with Bard Prison Initiative founder Max Kenner.
News and Analysis
“Obama is reinstating Pell Grants for prisoners. But will politics eventually trump cost and data?” The Marshall Project, July 30, 2015
Studies have found a wide variety of benefits to post-secondary education in prison, including fewer disciplinary infractions, higher rates of post-release employment, and improved self-image. In one notable study, a sociologist argued that college’s positive benefits stem from reduced “prisonization” — the classroom makes inmates feel less like inmates and more like everyday people.
“Pell Grants to be restored for prisoners,” The Wall Street Journal, July 27, 2015
While incarcerated at Hudson County Correctional Facility, [Wesley Caines, 49] used a privately funded program to earn an associate degree, then a bachelor’s and a master’s, after studying the work of Nietzsche and W.E.B. Du Bois. He’s now working for a Brooklyn firm helping other ex-offenders re-enter society. “Prison is perhaps one of the most dehumanizing environments that any human being could find themselves in,” he said. “One of the best ways to make transformative gains is to be educated.”
“Philanthropists, lawmakers behind new push for college education in prison,” The Wall Street Journal, July 27, 2015
“There is nothing proven to be less expensive and more effective than college,” said Max Kenner, executive director of the Bard Prison Initiative, which annually enrolls nearly 300 prisoners in degree programs from Bard College in New York.
“College access seen as key to curbing recidivism,” Diverse Issues in Higher Education, July 29, 2015
“Just because someone’s been locked up, just because they may be gang-involved doesn’t mean that we shouldn’t have incredibly high expectations for these individuals or that we shouldn’t put forth every effort into getting them to and through college,” said Mark Culliton, CEO of College Bound Dorchester, an organization that works with high school dropouts and former gang members to get them into community college.
“Bipartisan push builds to relax sentencing laws,” The New York Times, July 29, 2015
“I’ve long believed there needed to be reform of our criminal justice system,” said Mr. Boehner, endorsing a House bill that would change the system. “We’ve got a lot of people in prison, frankly, that don’t really in my view need to be there. It’s expensive to house. Some of these people are in there for what I’ll call flimsy reasons.”
“Why Criminal Justice Reform Has a Chance,” MSNBC, July 29, 2015
It wasn’t long ago that any Democratic talk about criminal-injustice reforms would be met with immediate, knee-jerk talking points about “soft-on-crime” liberals who want to “coddle” criminals. Last month, however, as Rachel noted on the show, even House Speaker John Boehner (R-Ohio) said he “absolutely” supports bipartisan reforms.
“America’s mass incarceration system: Freedom’s next frontier,” Reuters, July 24, 2015
For the victims of this system locked in prison cells, this moment when a substantive national conversation is unfolding and when policy changes are in process is more than welcome. For them, it is a lifeline.


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Evolutionary biology biology can be traced back to charles darwin there were ideas he rejected aristotle's great chain of being as. Chapter 22 biology problems study play as a young biologist, charles darwin had expected the living plants of temperate south america would time a) all. Choose from 500 different sets of evolution scientists history flashcards on quizlet charles darwin a geologist who had a great influence on darwin he.
Aristotle was the student plato and went on to become the teacher of alexander the great the works of aristotle cover various subjects ranging from: logic, music, theater, metaphysics, physics, poetry, politics, biology, ethics, government, linguistics, and zoology. Darwin and aristotle: not as different as you think the father of 2 biology he himself, he said, had verified aristotle's genius as a naturalist by dipping. Leroi's ambitious aim is to return aristotle to the pantheon of biology's greats, alongside charles darwin and carl linnaeus he has achieved it —nature.
Darwin carried this book with him on his voyage as he witnessed argentina coast earthquakes raising the earth several feet, & marine shells occurring far inland and at great heights in the andes darwin's many observations led him to the idea that species slowly change over time. History shows aristotle and charles darwin as two of the most powerful biologists of all time aristotle's teleological method was supported widely for over 2,000 years one scientist remarks that the aristotelian teleology has been the ghost, the unexplained mystery which has haunted biology through its whole history (ayala, 10. Aristotle the philosopher his name is remembered along with other great philosophers of that time, such as socrates and plato before charles darwin came to. Get this from a library from aristotle's teleology to darwin's genealogy : the stamp of inutility [marco solinas] -- starting with aristotle and moving on to darwin, marco solinas outlines the basic steps from the birth, establishment and later rebirth of the traditional view of living beings, and its overturning. Darwin envisioned the diversity of life as a evolving by a gradual accumulation of minute changes through the actions of _____ operation over vast spans of time natural selection what were two activities in the early part of the 19th century that led scientists to begin thinking that the earth was very old and that life on earth may have had an.
Darwin and scientific racism meet aristotle, shakespeare, and kant the fittest in his book principles of biology like darwin, spencer believed that it. Keltner was kind enough to take some time out work was charles darwin's insights into human goodness because most people equate his name with survival of the fittest, it'll probably. Darwinism: darwinism, theory of the evolutionary mechanism propounded by charles darwin as an explanation of organic change it denotes darwin's specific view that evolution is driven mainly by natural selection. In my opinion aristotle is the greatest biologist of all time 3 recommendations biology i prefer the works of gregor mendel and charles darwin factors such as being in the correct time. Aristotle is known as the father of biologyin the 4th century bc the greek philosopher aristotle traveled to lesvos, an island in the aegean teeming, then as now, with wildlife his fascination with what he found there, and his painstaking study of it, led to the birth of a new science — biology.
Aristotle identified a large charles darwin and wyville thomson made revolutionary contributions to the history of marine biology during this time of exploration. Shifting baselines in honor of darwin day, i'd like to give a little shout out to some of charles darwin's contributions to marine science it's an amazing document, and a great. Cuvier did not live long enough to learn about charles darwin's proof of evolution, but lyell did he came to accept this proof in the early 1860's along with most leading scientists of that time lyell also became a friend of charles darwin. The concluding part, on 'aristotle as theoretical biologist', first explores the basis of charles darwin's great 1882 praise of aristotle, and then, in the first printing of a general lecture long delivered worldwide, provides an overview of aristotle's practice as a philosophically oriented biologist, and 'a proper verdict' on his. The philosophy of biology, like all of western philosophy, began with the ancient greeks although plato ( c 428- c 348 bc ) was little interested in the subject, his student aristotle (384-322), who for a time was a practicing biologist, had much to say about it.
This famous line, from a letter to william ogle, the english translatorof aristotle's parts of animals, has often been quoted as evidence of charles darwin's respect for aristotle's biological writings, and thereby as witness to the quality of aristotle'swork as biologist. It was proposed by charles darwin in on the and to have culminated in darwin's theory of evolution by natural selection view than aristotle's great chain. For example, humans, chimpanzees, gorillas and orangutans are all great apes, so they all belong to the same branch of the tree of life darwin's legacy although darwin's theory of evolution has been modified over time, it remains fundamental to the study of the natural world.
Charles darwin: a centennial tribute aristotle, the father of biology and several other sciences, although he contributed in darwin's time, some physicists. The time however has arrived when biology must, like the other sciences, make a fresh start in a purely speculative direction, free from all entanglement with medical or any other art auguste compte, 1798 to 1857. Darwin and scientific racism meet aristotle, shakespeare, and kant by this time, darwin began to use science to smuggle in irrational ideas into the. Teacher of alexander the great aristotle spent some time traveling within the borders of the greek empire studying the natural world aristotle the biologist was.
In the nineteenth century the great anatomist richard owen introduced a two lecture survey of aristotle's zoological studies by declaring that zoological science sprang from his [aristotle's] labours, we may almost say, like minerva from the head of jove, in a state of noble and splendid maturity (owen 1992, 91. Charles darwin was born in a small town in england in 1809 he was the fifth child of parents robert waring darwin and susannah wedgwood charles' paternal grandfather, erasmus darwin, was one of the well-known intellectuals in england during the 18th century and his maternal grandfather, josiah wedgwood, was a china manufacturer.


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What were your favorite shoes that came out in 2013? We asked all of our Sneak Geeks the same question. Based off each of their rankings, Finish Line has equated an official Best Shoes of 2013 countdown. Stay tuned throughout the month of December as we get closer to the #1 spot.
#19 – Ronnie Fieg x New Balance 1600 “Daytona”
“When Ronnie told me he was going to do a 1600, my first reaction was ‘really? A 1600?’ Once again, he proved me wrong. I mean, just look at the toe. The perforations. Without a doubt, the best NB1600 ever.” – @AndyOliverWPG
“Ronnie has the ‘Midas Touch’ when it comes to his collaborations and true to form he kills it again with the materials, color selection and silhouette choice on the New Balance 1600. In my opinion, this New Balance rivals that of the Concepts 999 Kennedy.” – @krvanch
#20 – Nike Inneva Woven
#21 – atmos x Nike Air Max 1
#24 – Nike Kobe VIII “Area 72”
#25 – Air Jordan 5 “Fear”
Let us know which was your most coveted pair of the year in the comments, and if you agree the picks.