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US 5268454 A Abstract Conjugates of stable nonimmunogenic polymers and analogs of immunogens that possess the specific B cell binding ability of the immunogen but lack T cell epitopes and which, when introduced into individuals, induce humoral anergy to the immunogen are disclosed. Accordingly, these conjugates are useful for treating antibody-mediated pathologies that are caused by foreign or self immunogens.
Claims(11) 1. A method for making a conjugate useful for inducing specific B cell anergy to an immunogen implicated in an antibody-medicated pathology, the conjugate comprising a nonimmunogenic biologically stable polymer and an analog of the immunogen wherein (i) the analog binds specifically to B cells to which the immunogen binds specifically and (ii) the conjugate lacks a T cell epitope, comprising the steps of:
(a) convalently bonding the analog of the immunogen lacking T cell epitopes to a nonimmunogenic polymer to form a conjugate; and (b) separating the conjugate from the reaction mixture. 2. The method of claim 1 wherein the immunogen is an external immunogen.
3. The method of claim 2 wherein the external immunogen is a biological drug, an allergen, or an idiopathic contrast medium.
4. The method of claim 1 wherein the immunogen is a self-immunogen.
5. The method of claim 4 wherein the self-immunogen is that associated with thyroiditis, diabetes, stroke, male infertility, myasthenia gravis, rheumatic fever, or Rh hemolytic disease.
6. The method of claim 1 wherein the immunogen and analog are of the same chemical class.
7. The method of claim 6 wherein the immunogen and analog are polypeptides.
8. The method of claim 1 wherein the immunogen and analog are of different chemical classes.
9. The method of claim 1 wherein the polymer is a copolymer of d-lysine and D-glutamic acid.
10. The method of claim 1 wherein the polymer is a polyethylene glycol.
11. A method for making a composition useful for inducing specific B cell anergy to an immunogen implicated in an anti-body medicated pathology, the composition comprising a pharmaceutically acceptable vehicle and a conjugate of a nonimmunogenic biologically stable polymer and an analog of the immunogen wherein (i) the analog binds specifically to B cells to which the immunogen binds specifically and (ii) the conjugate lacks a T cell epitope, comprising the steps of:
(a) convalently bonding the analog of the immunogen lacking T cell epitopes to an nonimmunogenic polymer to form a conjugate; (b) separating the conjugate from the reaction mixture; and (c) combining the conjugate with a pharmaceutically acceptable vehicle. Description This invention is in the field of immunology and concerns compositions and methods for inducing humoral energy for the purpose of treating antibody-medicated pathologies. More specifically, the invention relates to conjugates of nonimmunogenic stable polymers and analogs of immunogens that lack T cell epitopes. In order to survive in a world of pathogenic or potentially pathogenic microorganisms, higher organisms have evolved immune systems which can specifically recognize virtually any foreign substance through its characteristic molecules. This recognition frequently results in the production of specific proteins called antibodies which bind only to the foreign substance which induced their synthesis, causing the elimination of the invading microorganism. Occasionally an animal's immune system makes antibodies which recognize some of its own molecules, generating an autoimmune state that may affect the animal's health adversely. The induction of specific antibodies in response to an immunogen involves the interaction of multiple cell types, including thymus-derived lymphocytes (T cells), macrophages, and bone marrow-derived lymphocytes (B cells). B cellspossess surface immunoglobulin by which they are able to bind immunogens, the first step in their activation and clonal expansion The site(s), region(s) or domain(s) of the immunogen to which the immunoglobulin binds is called a "B cell epitope". In the second step of B cell activation and expansion, T cells are activated through interaction with the B cell bound-immunogen at a site, region or domain of the immunogen called a "T cell epitope". Once activated, the T cells provide positive signal(s) to the B cells to which the immunogen is bound and they proceed to differentiate and to produce and secrete antibody Positive signals from the T cell include the secretion of lymphokines, and/or direct contact between the B cells and T cells. T cell epitopes may be different or more restricted in scope than B cell epitopes. As discussed above, in order for an immunogen to elicit T dependent antibodies, it must have epitopes recognized by both B and T cells. Past attempts to treat antibody-mediated pathologies have involved both general and specific suppression of the immune response. General suppression has typically employed broad spectrum, nonspecific immunosuppressants such as cyclophosphamide or steroids. Because these nonspecific drugs suppress many aspects of the immune system, they eliminate its required and beneficial functions as well as the malfunction causing the condition being treated. They are thus used with extreme caution, if at all, and subject the patient to risk from secondary infections or other undesirable side effects. Because of the disadvantages of general immunosuppression, methods for specifically suppressing an immune response to an immunogen without affecting the normal functions of the immune system are highly preferred for treating antibody-mediated pathologies. The present invention concerns compositions and methods for specifically suppressing the humoral response to immunogens. Prior attempts to induce specific immunosuppression have focused on conjugating haptens and immunogens to nonimmunogenic polymeric carriers. Benacerraf, Katz and their colleagues used conjugates of haptens and antigens and copolymers of D-lysine and D-glutamic acid (D-EK). Their initial studies involved conjugates of the synthetic hapten 2,4-dinitrophenyl (DNP) in guinea pigs and mice and showed the conjugates were capable of inducing humoral unresponsiveness. These initial studies were then extended to conjugates of other haptens and conjugates of immunogens. While the results with haptens were repeatable, and although their patents (U.S. Pat. Nos. 4,191,668 and 4,220,565) allege the approach is effective in inducing tolerance to immunogens, subsequent work has shown that conjugates of D-EK and immunogens do not provide a means for inducing humoral unresponsiveness to the immunogen. For instance, Liu et. al., J. Immun. (1979) 123:2456-2464, report that subsequent studies of those conjugates demonstrate that the conjugates "do not induce unresponsiveness at the level of protein specific B cells." Similarly, Butterfield et. al., J. Allergy Clin. Immun. (1981) 67:272-278, reported that conjugates of ragweed immunogen and D-EK actually stimulated both IgE and IgG responses to the immunogen. This subsequent work and other data dealing with conjugates of nonimmunogenic polymers and immunogens (Saski et. al., Scand. J. Immun. (1982) 16:191-200; Sehon, Prog. Allergy (1982) 32:161-202; Wilkinson et. al., J. Immunol. (987) 139:326-331, and Borel et. al., J. Immunol. Methods (1990) 126:159-168) appear to indicate that the anergy, if any, obtained with such conjugates is due to suppression by T cell activity, not B cell unresponsiveness. Several other references deal with conjugates of nonimmunogenic polymers and DNA. See U.S. Pat. Nos. 4,191,668; U.S. Pat. No. 4,650,625; J. Clin. Invest. (1988) 82:1901-1907; and commonly owned U.S. Pat. application Ser. No. 07/494,118. As a whole, these references indicate that these DNA conjugates may suppress the production of antibodies to this lupus autoimmunogen. It should be noted in this regard that DNA, like haptens, does not possess T cell epitopes. In sum, applicants believe the prior art shows that antibody production to conjugates of nonimmunogenic stable polymers and haptens or DNA, neither of which have T cell epitopes, may provide B cell unresponsiveness. Applicants also believe that conjugates of immunogens do not provide B cell unresponsiveness but may activate T cells to directly suppress the immune response. The present invention resides in the discovery that the failure of the prior conjugates of nonimmunogenic stable polymers and immunogens to induce B cell anergy (unresponsiveness) was due to the fact that the immunogens contained both B and T cell epitopes and that if the latter were eliminated, the conjugate would be effective for inducing B cell anergy. Accordingly, one aspect of the invention is a composition for inducing specific B cell anergy to an immunogen comprising a conjugate of a nonimmunogenic biologically stable carrier polymer and an analog of the immunogen that (a) binds specifically to B cells to which the immunogen binds and (b) lacks the T cell epitope(s) of the immunogen. Pharmaceutical compositions of the above-described conjugates and pharmaceutically acceptable carriers or vehicles are another aspect of the invention. A further aspect of the invention is a method of inducing specific B cell anergy to an immunogen in an individual comprising administering to the individual an effective amount of the above-described conjugate. Yet another aspect of the invention is a method of treating an individual for an antibody-mediated pathology in which undesired antibodies are produced in response to an immunogen comprising administering to the individual a therapeutically effective amount of the above-described conjugate. FIG. 1 graphically illustrates the detection of B cell epitopes in immunized CAF1 mice as described in Example 1. The unconjugated 17 per peptide (L-42) and L-42 and L53 conjugates were tested for B cell epitopes with anti-MIR sera. Unconjugated L-42 and L-53 were tested with normal mouse serum (NMS) as a control. FIG. 2, similarly, illustrates the detection of T cell epitopes as described in Example 1. FIG. 3 illustrates the suppression of antibodies to peptide "L-53" as described in Example 1. FIGS. 4 and 5 are graphs of the results described in Example 4. As used herein the term "B cell anergy" intends unresponsiveness of those B cells requiring T cell help to produce and secrete antibody and includes, without limitation, clonal deletion of immature and/or mature B cells and/or the inability of B cells to produce antibody. "Unresponsiveness" means a therapeutically effective reduction in the humoral response to an immunogen. Quantitatively the reduction (as measured by reduction in antibody production) is at least 50%, preferably at least 75%, and most preferably 100%. "Antibody" means those antibodies which are T cell dependent. As used herein the term "immunogen" means a chemical entity that elicits a humoral immune response when injected into an animal. Immunogens have both B cell epitopes and T cell epitopes. As used herein "individual" denotes a member of the mammalian species and includes humans, primates, mice and domestic animals such as cattle and sheep, sports animals such as horses, and pets such as dogs and cats. The term "analog" of an immunogen intends a molecule that (a) binds specifically to an antibody to which the immunogen binds specifically and (b) lacks T cell epitopes. Although the analog will normally be a fragment or derivative of the immunogen and thus be of the same chemical class as the immunogen (e.g., the immunogen is a polypeptide and the analog is a polypeptide), chemical similarity is not essential. Accordingly, the analog may be of a different chemical class than the immunogen (e.g., the immunogen is a carbohydrate and the analog is a polypeptide) as long as it has the functional characteristics (a) and (b) above. The analog may be a protein, carbohydrate, lipid, lipoprotein, glycoprotein, lipopolysaccharide or other biochemical entity. Further, the chemical structure of neither the immunogen nor the analog need be defined for the purposes of this invention. "Nonimmunogenic" is used to describe the carrier polymer means that the carrier polymer elicits substantially no immune response when it is administered by itself to an individual. Immunogens that are involved in antibody mediated pathologies may be external (foreign to the individual) immunogens such as biological drugs, allergens, idiopathic contrast media, and the like or self-immunogens (autoimmunogens) such as those associated with thyroiditis (thyroglobulin), stroke (cardiolipin), male infertility (α-sperm), myasthenia gravis (acetylcholine receptor), rheumatic fever (carbohydrate complex), and Rh hemolytic disease (D immunogen). Analogs to such immunogens may be identified by screening candidate molecules to determine whether they (a) bind specifically to serum antibodies to the immunogen and (b) lack T cell epitopes. Specific binding to serum antibodies may be determined using conventional immunoassays and the presence or absence of T cell epitopes may be determined by conventional T cell activation assays. In this regard an analog which "binds specifically" to serum antibodies to the immunogen exhibits a reasonable affinity thereto. The presence or absence of T cell epitopes may be determined using the tritiated thymidine incorporation assay described in the examples. Analogs that fail to induce statistically significant incorporation of thymidine above background are deemed to lack T cell epitopes. It will be appreciated that the quantitative amount of thymidine incorporation may vary with the immunogen. Typically a stimulation index below about 2-3, more usually about 1-2, is indicative of a lack of T cell epitopes. A normal first step in identifying useful analogs is to prepare a panel or library of candidates to screen. For instance, in the case of protein or peptide analogs, libraries may be made by synthetic or recombinant techniques such as those described by Geysen et. al. in Synthetic Peptides as Antigens; Ciba Symposium (1986) 119:131-149; Devlin et. al., Science (1990) 249:404-406; Scott et. al., Science (1990) 249:386-390; and Cwirla et. al. , PNAS USA (1990) 87:6378-6382. In One synthetic technique, peptides of about 5 to 30 amino acids are synthesized in such a manner that each peptide overlaps the next and all linear epitopes are represented. This is accomplished by overlapping both the carboxyl and amino termini by one less residue than that expected for a B cell epitope. For example, if the assumed minimum requirement for a B cell epitope is six amino acids, then each peptide must overlap the neighboring peptides by five amino acids. In this embodiment, each peptide is then screened against antisera produced against the native immunogen, either by immunization of animals or from patients, to identify the presence of B cell epitopes. Those molecules with antibody binding activity are then screened for the presence of T cell epitopes as described in the examples. The molecules lacking T cell epitopes are useful as analogs in the invention. If the T cell epitope(s) of an immunogen are known or can be identified, T cell random screening of candidate analogs is not necessary. In such instances, the T cell epitope(s) may be altered (e.g., by chemical derivatization, or elimination of one or more components of the epitope) to render them inoperative or be eliminated completely, such as, for instance, in the case of peptides, by synthetic or recombinant procedures. The analogs are coupled to a nonimmunogenic polymeric carrier to prepare the conjugates of the invention. Preferred polymeric carriers are biologically stable, i.e., they exhibit an in vivo excretion half-life of days to months, and are preferably composed of a synthetic single chain of defined composition. They will normally have a molecular weight in the range of about 5,000 to about 200,000, preferably 5,000 to 30,000. Examples of such polymers are polyethylene glycol, poly-D-lysine, polyvinyl alcohol, polyvinyl pyrrolidone, immunoglobulins, and "D-EK", a copolymer of D-glutamic acid and D-lysine. Particularly preferred carrier polymers are D-EKs having a molecular weight of about 5,000 to about 30,000, and an E:K (D-glutamic acid:D-lysine) mole ratio of approximately 60:40, as described in U.S. Patent Application Serial No. 07/494,118, referenced above. Conjugation of the analog to the carrier polymer may be effected in any number of ways, typically involving one or more crosslinking agents and functional groups on the analog and carrier. Polypeptide analogs will contain amino acid sidechain groups such as amino, carbonyl, or sulfhydryl groups that will serve as sites for coupling the analog to the carrier. Residues that have such functional groups may be added to the analog if the analog does not already contain same. Such residues may be incorporated by solid phase synthesis techniques or recombinant techniques, both of which are well known in the peptide synthesis arts. In the case of carbohydrate or lipid analogs, functional amino and sulfhydryl groups may be incorporated therein by conventional chemistry. For instance, primary amino groups may be incorporated by reaction with ethylendiamine in the presence of sodium cyanoborohydride and sulfhydryls may be introduced by reaction of cysteamine dihydrochloride followed by reduction with a standard disulfide reducing agent. In a similar fashion the carrier may also be derivatized to contain functional groups if it does not already possess appropriate functional groups. With specific reference to conjugating peptide analogs and D-EK or other proteinaceous carriers, coupling is preferably carried out using a heterobifunctional crosslinker, such as sulfosuccinimidyl(4-iodoacetyl) aminobenzoate, which links the ε amino group on the D-lysine residues of D-EK to a sulfhydryl side chain from an amino terminal cysteine residue on the peptide to be coupled. This method is preferably carried out such that an average of 3 to 5 analog molecules are coupled to each D-EK molecule and the average molecular weight of the D-EK prior to coupling is 5,000 to 30,000 daltons. The conjugates will normally be formulated for administration by injection (e.g., intraperitoneally, intramuscularly, etc.). Accordingly, they will typically be combined with pharmaceutically acceptable carriers such as saline, Ringer's solution, dextrose solution, and the like. The conjugate will normally constitute about 0.01% to 10% by weight of the formulation. The conjugate is administered to an individual in a "therapeutically effective amount", i.e., an amount sufficient to produce B cell anergy to the involved immunogen and effect prophylaxis, improvement or elimination of the antibody-mediated condition being addressed. The particular dosage regimen, i.e., dose, timing and repetition, will depend on the particular individual and that individual's medical history. Normally, a dose of about 10 μg to 1 mg conjugate/kg body weight will be given, daily for three consecutive days. Other appropriate dosing schedules would be 3 doses per week, or one dose per week. Repetitive administrations, normally timed according to B cell turnover rates, may be required to achieve and/or maintain a state of humoral anergy. Such repetitive administrations will typically involve treatments of up to 1 mg/kg of body weight every 30 to 60 days, or sooner, if an increase in antibody titer is detected. Alternatively, sustained continuous release formulations of the conjugates may be indicated for some pathologies. Various formulations and devices for achieving sustained release are known in the art. Anti-T helper cell treatments may be administered together with the conjugates. Such treatments usually employ agents that suppress T cells such as steroids or cyclosporin. The following examples are intended to further illustrate the invention and its uniqueness. These examples are not intended to limit the scope of the invention in any manner. B Cell Anergy to the Acetylcholine Receptor Preparation of Peptides and D-EK/Peptide Conjugates: The α-subunit of the acetylcholine receptor of Torpedo californicus is described by Stroud, R. M., and Finer-Moore, J., Ann. Rev. Cell Biol. (1985) 1:317:351, and Sumikawa, K., et. al., Nucl. Acids Res. (1982) 10:5809-22. The peptide defined by residues 47-127 of that α-subunit is called the major immunogenic region (MIR). Two peptides, L-42 and L-53, corresponding to residues 61-77 and 112-127 of that α-subunit, were synthesized using conventional solid-phase methods and purified to homogeneity by HPLC. An amino terminal cysteine was added to each sequence for the purpose of attachment of the peptide to D-EK via a thio ether linkage. Each peptide (40 mg) was dissolved in 0.1M sodium borate buffer, pH 9.0. The solution was reacted with citraconic anhydride (400 μL) at room temperature; the pH was maintained above 7.0 by addition of IM NaOH. The solution was then made 20 mM in dithiothreitol and was warmed at 37� C. for 20 minutes to reduce the peptide. The mixture was quickly desalted over G-10 Sephadex columns which were equilibrated with 0.1M sodium borate, pH 7.0. D-EK (200 mg, weight average mw≃10,000-30,000) was dissolved in 2.0 mL of 0.1M sodium borate. Sulfosuccinimidyl (4-iodoacetyl) aminobenzene (SSIAB, 10 mg, Pierce Chemical) was added to the mixture and the mixture was reacted for 90 minutes at room temperature in the dark. The mixture was then desalted over a 10 mL G-25 column, equilibrated with 0.1M sodium borate, pH 7.0. The desalted SSIAB-D-EK was mixed with the reduced and desalted peptide and reacted overnight. The resulting conjugate was placed in dialysis tubing with a 14 Kd cutoff and was dialyzed against 5% acetic acid to remove citraconyl groups. The dialysis buffer was changed to phosphate-buffered saline and the dialysis continued. Detection of B cell epitopes: CAFl mice were immunized (day 0) intraperitoneally (i.p.) with 50 μg of recombinant torpedo MIR absorbed onto alum plus B. pertussis vaccine (Iverson, G. M., (1986) Handbook of Experimental Immunology, Vol. 2, p. 67, D. M. Weir ed., Blackwell Scientific Publications, Palo Alto, CA). The mice received a booster injection of the same protein in saline, IP, on day 21 and were bled from the tail vein on day 28. Sera from these mice (anti-MIR sera) were used to screen peptides L-42 and L-53 for the presence of B cell epitopes, as follows. The sera were added to microtiter wells coated with 10 μg/ml of the indicated peptide conjugates. The plates were incubated at 37� C. for one hour, washed 3 times, 100 μl of alkaline phosphatase-conjugated goat antimouse antibody was added, incubated at 37� C. for one hour, washed 3 times, and 100 μl of developer (substrate) was added to each well. The plates were incubated at room temperature for 30 minutes and the amount of color in each well was determined in a Titertek� Multiskan. Results are illustrated graphically in FIG. 1. The notation "17 mer" corresponds to the unconjugated L-42 peptide. The L-53 peptide is a 16 mer. The curve labelled "L-42 or L-53 NMS contains the values obtained using normal mouse serum (NMS) instead of the anti-MIR sera on plates coated with either L-42 or L-53. As shown in FIG. 1, both peptides reacted specifically with antibodies from the immunized mice indicating the presence of B cell epitopes on both peptides. Detection of T cell epitopes: T cell activation was assayed by the general procedure of Bradley, M. L., (1980) in Mishell and Shigii, eds., Selected Methods in Cellular Immunology (W. H. Freeman and Co., San Francisco, CA), p. 164. CAF1 mice were immunized on the footpad with 50 μg MIR in Complete Freund's Adjuvant (CFA) on day 0. On day 7 the popliteal lymph nodes were removed and placed in culture in microtiter plates using 5�105 cells per well. L-42, L-53 D-EK conjugates thereof were added to the cultures, and on day 4, 1 μCi of tritiated thymidine was added to each well to measure proliferation of T cells. The cultures were harvested on a day 5 with a Skatron� cell harvester. The amount of incorporated 3 H-thymidine was determined in a Beckman 6800� liquid scintillation counter. The stimulation index was calculated by dividing the CPM incorporated with peptide by the CPM incorporated from cultures without any peptide. A stimulation index >2-3 was indicative of the presence of a T cell epitope on the peptide added to the well. As shown in FIG. 2, L-42 but not L-53 possessed T cell epitopes in this assay. Induction of B Cell Anergy to L-53 by L-53/D-EK Conjugate: CAF1 mice were immunized with 50 μg of MIR, i.p., absorbed onto alum plus B. pertussis vaccine on day 0. On days 21, 22 and 23 the mice (6 mice per group) received 10 or 100 μg of either L-42/D-EK conjugate or L-53-D-EK conjugate. One group received only saline. On day 28 all mice received a booster injection of MIR in saline and on day 35 all mice were bled and assayed for the presence of antibodies to L-42 and L-53 in their sera, using an ELISA assay as described above with respect to FIG. 1. The results for antibodies to L-42 are shown in FIG. 3A and for antibodies to L-53 are shown in FIG. 3B. The L-53 conjugate suppressed antibody formation to L-53 but not to L-42. The L-42 conjugate did not suppress the antibody response to either L-42 or L-53 but rather may have increased antibody production to L-42. The antibody titers are expressed as a percent of a standard sera. The p values were determined by a Student t test comparing each dose to the saline control. This example is further evidence that conjugates of immunogens and D-EK do not induce B cell anergy. Synthesis of Ovalbumin-D-EK Conjugate: Chicken egg ovalbumin (50 mg) was dissolved in 5 mL of 0.1M sodium borate buffer, pH 9.0, containing 10 mM EDTA. After the addition of 3.0 mg of 2-iminothiolane (Traut's reagent), the mixture was reacted for 2.5 hours at room temperature. D-EK (54 mg), dissolved in 0.5M sodium borate, pH 9.0, at a concentration of 100 mg/mL, was reacted with SSIAB (18 mg; Pierce Chemical) for 2.5 hours in the dark, at room temperature. The two reaction mixtures described above were desalted separately on G- 25 columns (Pharmacia; 10 mL column volume, equilibrated with 0.1M sodium borate, pH 9.0) and the excluded fractions were combined and reacted for 16 hours at 4� C., in the dark. The reaction product was fractionated by gel filtration over Sephacryl S-200 (490 mL, Pharmacia) columns, equilibrated with 0.2M ammonium bicarbonate. Fractions containing conjugate, as assessed by polyacrylamide gel electrophoresis, in the presence of sodium dodecyl sulfate (SDS-PAGE), were pooled and dried under vacuum. The dried material was reacted with 0.8 mL of citraconic anhydride, maintaining the pH between 7 and 9 by the addition of IM NaOH, in order to efficiently separate conjugated ovalbumin from unreacted protein. The citraconylated conjugate was rechromatographed over S-200, and fractions containing high molecular weight material (>80,000 daltons), as assessed SDS-PAGE, were used for biological studies. Chicken ovalbumin, when conjugated to D-EK, does not induce B cell anergy in mice immunized to chicken ovalbumin: Female CAF1 mice were primed with chicken ovalbumin (ova; 100 μg/mouse, i.p.) precipitated on alum, with B. pertussis vaccine added as an adjuvant. Sixteen weeks later, the mice were divided into two groups of six mice each. One group (control) was treated with saline, and the second group was injected with a conjugate of ova and D-EK (ova-D-EK; 200 μg/mouse/day, i.p.). The mice were dosed on three successive days. One week after the first dose, the mice in both groups were boosted, i.p., with ova in saline (100 μg/mouse). One week later, the mice were bled from a tail vein. The plasma was harvested and assayed for the amount of antiova antibodies by an ELISA assay. As shown in Table 1, the ova-D-EK conjugate did not suppress the anti-ova response. TABLE 1______________________________________ μL Equivalents1 of Anti-Ova � S.D. (Percent of Anti-OvaGroup Treatment Standard1 Serum � S.D.)______________________________________1 saline 70.7 � 362 ova- -- D-EK 160.2 � 167______________________________________ 1 The amount of antiova antibody was determined in an ELISA, measure against a standard pool of sera obtained from CAF1 mice immunized an boosted with ova. The values shown are the mean and standard deviation fo the six mice in each group. This example is still further evidence that conjugates of immunogens and D-EK do not induce B cell anergy. Synthesis of MIR-D-EK Conjugate: MIR was modified on its carboxyl-terminus to include a sequence of 8-amino acids (Arg-Ser-Lys-Ser-Lys-Ser-Lys-Cys (SEQ. ID NO.: 1)). The amino-terminus was extended by one amino acid, proline. Purified modified MIR (250 mg) was reduced with 100 mM dithiothreitol and was desalted over Sephadex G-25 (Pharmacia), equilibrated with 0.1 M sodium borate buffer, pH 9.0, containing 10 mM EDTA. D-EK (400 mg) was reacted with SSIAB (29 mg) as in the previous examples. The product was desalted over G-25. The excluded volumes from the modified MIR and D-EK G-25 column runs were Excess SSIAB groups were quenched with 2-mercaptoethanol, d the reaction mixture was concentrated to 20 mL over a PM-10 membrane (Amicon Corporation). The mixture was treated with 1.0 mL of citraconic anhydride and chromatographed over S-300 (Pharmacia; 1.8 L), equilibrated with 5% ammonium hydroxide. Fractions containing two or more modified MIR groups per D-EK, as assessed by SDS-PAGE, were pooled and used for biological studies. MIR-D-EK conjugate contains T cell epitopes in rats immunized with MIR from the same species: T cell activation was assayed by the general procedure of Bradley, suora. Female Lewis rats were immunized in the footpad with MIR (50 μg) in complete Freund's adjuvant (CFA) on day 0. On day 7, the popliteal lymph nodes were removed and placed in culture in microtiter plates using 5.105 cells per well. MIR-D-EK was added, and, after four days of culture, the wells were pulsed with tritiated thymidine (1-μCi) to measure proliferation of T cells. The cultures were collected after 5 days of culture with a Skatron� cell harvester. The amount of incorporated 3 H-thymidine was determined by scintillation spectrometry. The stimulation index was calculated by dividing the counts incorporated in the absence of the conjugate. A stimulation index of greater than 2-3 was considered indicative of the presence of a T cell epitope on the added conjugate. The stimulation index was 4 or greater at all concentrations of MIR-D-EK tested (10 μg/mL to 400 mg/mL). This proves that T cells from MIR-immunized rats recognize T cell epitopes on the MIR-D-EK conjugate in this assay. MIR-D-EK does not induce B cell anergy in rats immunized with MIR: Female Lewis rats were primed with MIR (100 μg/rat) in CFA. Six months later, the rats were divided into three groups of three rats each. One group was treated with saline (control) and the other two groups were treated with MIR-D-EK (100 μg/rat, i.p.) on three successive days. After one week, the rats in the control group and one group that had been treated with MIR-D-EK ere boosted with recombinant MIR (1000 μg/rat, i.p.) in saline. One week later, all three groups of rats were bled from the tail vein. The plasma was harvested and assayed for the amount of anti-MIR antibodies by an ELISA assay. Table 2 below reports the data from those assays. TABLE 2______________________________________ μg/ml anti-MIR2 P vs.Group Treatment MIR Boost (mean � S.D.) Group 1______________________________________1 Saline Yes 130.5 � 74.72 MIR- -- D-EK Yes 85.5 � 31.1 0.1953 MIR- -- D-EK No 230.6 � 31 0.049______________________________________ 2 The concentration of antiMIR antibodies was determined in an ELISA measured against a standard pool of rat antiMIR sera. The values shown ar the mean and standard deviation of the three rats in each group. P values were determined by a student t test. Group 2 is not significantly different from Group 1. Group 3 (the nonboosted group) is significantly higher than Group 1. As shown in Table 2, the data on Group 1 animals (saline control) indicate that MIR itself is an immunogen. The data for the Group 2 and 3 animals indicate that the MIR-D-EK conjugate did not affect the anti-MIR response. In fact, MIR-D-EK boosted the anti-MIR response in Group 3. These tests, taken together with the results of Example 1 show that the moiety conjugated to D-EK will cause anergy in B cells recognizing that moiety if the moiety either does not contain a T cell epitope or is not recognized by T cells. Synthesis of 17-mer (L-42) peptide-KLH conjugate: Reduced L-42 (see Example 1) was conjugated to keyhole limpet hemocyanin (KLH) using thioether chemistry similar to that described above with respect to D-EK. L-42 lacks a T cell epitope(s) in mice immunized with L-42-KLH: Activation of T cells by peptides was measured by the general procedure of Bradley, supra. Female CAF1 mice were immunized in the footpad with L-42 peptide conjugated KLH (L-42-KLH; 50 μg) in CFA on day 0. On day 7, the popliteal lymph nodes were removed and placed in culture in microtiter plates, at a cell density of 5.105 cells/well. Peptides were added, and, after four days of culture, the wells were pulsed with 1 μCi of tritiated thymidine to measure proliferation of T cells. The cultures were collected after 5 days of culture with a cell harvester. The amount of incorporated 3 H-thymidine was determined by scintillation spectrometry. The stimulation index was calculated by dividing the counts incorporated in the absence of peptide. An index of greater than 2-3 is indicative of the presence of a T cell epitope on the added peptide. The data in FIG. 4 demonstrate that the L-42 did not stimulate the growth of T cells taken from L-42-KLH-immunized mice, and therefore did not contain an epitope(s) recognized by T cells induced by immunization with L-42-KLH. L-42-D-EK conjugate induces a B cell anergy in mice immunized to L-42-KLH: CAF1 mice were primed with 100 μg/mouse of L- 42-KLH on alum plus B. pertussis vaccine as an adjuvant. Three weeks later, the mice were divided into groups of six mice each. One group was treated by i.p. injections on three successive days with saline (control); the other groups were similarly treated with L-42-KLH (50 μg/mouse, i.p.), and, after a wait of one week, they were bled from the tail vein. The plasma was harvested and assayed for the amount of anti-L-42 antibodies by an ELISA assays. Data are expressed as a percent of a standard serum. An asterisk indicates that a data point was significantly different from the control as determined by a Student t test. The data in FIG. 5 demonstrate that the L-42 response, but not the anti-KLH response, was suppressed in this assay by the L-42-D-EK conjugate. Thus, the studies summarized in Example 1 and these data demonstrate the L-42-D-EK induces B cell anergy when the mice are immunized in a manner that does not induce the proliferation of T cell clones that recognize the L-42 peptide On the other hand, L-42-D-EK did not induce B cell anergy in animals that were immunized with an immunogen (MIR) which induced T cells that recognized the L-42 peptide. Modifications of the above-described modes for carrying out the invention that are obvious to those of ordinary skill in the fields of immunology, chemistry, medicine and related arts are untended to be within the scope of the following claims. Patent Citations
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February 16, 2010 A Hollywood Purim spoof on 'Wolfman'http://www.jewishjournal.com/blog/item/a_hollywood_purim_spoof_on_wolfman_20100216/ |
Last week I blogged about a Purim sketch show in New York created by a bunch of Hollywood comedy writers known as The Shushan Channel. Every year, this group of self-deprecating and comedic Jews uses the holiday as an excuse to poke fun at Jewish neuroses and gentile behaviors. The main event, of course, is a big bash thrown at the 92nd Street Y, so if you don't live in New York, you can't join in the fun. But for those of us who live on the West Coast, like one of its creators and former "Tonight Show" writer Rob Kutner, or even elsewhere in America, you can enjoy their annual video spoof, which circulates widely via youtube. "Wolfman DDS" is about a Jewish dentist who is part werewolf and disturbs his family by eating uncooked meat and not paying taxes on time. It's not quite as funny as last year's "Meshugene Men"—a Jewish version of "Mad Men"—which could have won a youtube Oscar had such a thing existed. "Wolfman" is a valiant effort, but it doesn't quite tap into the zeitgeist the way "Meshugene Men" did. Watch it nonetheless and judge for yourself: |
JewishJournal.com is produced by TRIBE Media Corp., a non-profit media company whose mission is to inform, connect and enlighten community © Copyright 2015 Tribe Media Corp. |

subset: commoncrawl


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Granite Surface Plate $10 Off
Super flat surface perfect for leveling plane blades. Buy Now $26.99
Excalibur Scroll Saw Package
Geta great scroll saw with free stand and foot switch. Right Now $899.99
JET Benchtop Spindle Saner $389.99
Take some of the chore out of sanding difficult pieces. Save $100
Look up product instructions, videos and articles about your favorite tools using our Learning Center.
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Looks OK; not used yet.
By HalM
from Mississippi
About Me Avid Do-It-Yourselfer
Comments about Norton 10" Sanding Disc, 120 Grit :
Used on my table saw to sand edges of boards.
Wrong GRIT sent
By Dave
from Brandon, SD
This is a good product and performs as it should. However, I ordered 120 grit and received 80 grit sanding disks
Will buy more when they wear out
By Russ
from REVIEW_NUMBER_FIELD_PREFIX12569
veary good
Works well.
By DavyC
from Smyrna, DE
It would be helpful if you had a backing plate available for use with this.


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Find commute times to your work, school, gym and more.
LUXURY Townhome for RENT!
- This property is no longer listed on Rent.com. For this reason please note that any pricing or description information may not be up-to-date.
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Alarm, Clubhouse, Fitness Center, Swimming Pool
Property Details
Beautiful,Entirely Upgraded, Corner Unit. 3-Bedroom, 2 Bath, One Car Garage Condo/townhome in the gated community of Hampton Hills
3 miles to Sawgrass Mills, 2006 Beautiful, Entirely Upgraded, Corner Unit. 3-Bedroom, 2 Bath, One Car Garage. Plantation Shutters Installed On Every Window. Stainless Steel Appliance, wood cabinets In The Kitchen and Bathrooms, Granite Countertops, Custom Designed Closets in all bedrooms. Upgraded, Tiled All The Way To Ceiling Shower and Bathtubs In Both Bathrooms, roman tub in master bath. 10ft Ceilings, Upgraded Floors throughout. Surround sound wired! Open floor plan! Excellent A Schools!
Leasing Terms
At least 12 month lease-available for long-term lease
$1675 a month includes water, sewer, trash, basic cable and security system.
$1500 security deposit required
$1000 condo association deposit required (refundable upon lease term end) Note: this is required by the Hampton Hills Association and is not associated with the property deposit.
Pet ok depending on size and type-please call for details
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Pets Accepted. Call for service animal policy.
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Northside Digital Library - Access to downloadable eBooks, audiobooks, and music 24/7 for all students and NISD staff (requires login)
Think Through Math - provided by state of Texas for all students in grades 3-8; click here for Parent Letter (English & Spanish).
Pearson Realize- online curriculum program for instruction and student assignments; click here for Parents' Guide
iStation (Home Use) - use this link to download iStation at home.
River Deep Math - contains lessons assigned by classroom teacher; click here for Parents' Guide.
Skills Practice - language arts and math
Math - activities by grade level
Math Playground - fun educational math games
Money - practice counting money
Multiplication.com - games to help you learn how to multiply
Tumblebooks - ebooks for ekids (chapter books have been added)
Thanksgiving Scavenger (Fact) Hunt (get paper copy of questions from your teacher) - click the speaker icons to have it read to you
Online Web Quest - View the slideshow (click the speaker icon to hear it read); click the back button; play the Web Quest.
QR Codes:
Create Your QR Code on Vocaroo (voice)
Create Your QR Code (text)
Big 6 Research Links:
Texas Indians (4th grade)
Decades of the 20th Century (5th grade)


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Lots of pockets and sturdy construction make this backpack ideal for toting anything from school books to your current crochet project. A must-have for girls on the go!
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US 5443469 A Abstract An intramedullary reaming tissue protection guard consisting of a cylindrical tube and having means of applying suction is disclosed.
Claims(3) 1. An intramedullary reaming, tissue protection guard comprising a cylindrical tube, said tube having a tapered leading end, at least a portion of said tube being double walled and having opening means therein for applying suction at or adjacent to said leading end and said tube having a slot incorporated within it at its other end and in a portion of said tube to accommodate the insertion and withdrawal of the reaming apparatus.
2. The device of claim 1 wherein the guard is flexible.
3. The device of claim 1 wherein the guard is curved.
Description In general, the present invention relates to a surgical device. In particular, the present invention is an intramedullary reaming tissue protection guard. While there are many, various retractor devices which have been and are employed, most suffer from the fact that they are not specifically designed or adapted to reaming operations. The present invention overcomes the deficiencies of the prior art as described above by means of a special tubular device, which taken as a whole constitutes a new and novel intramedullary reaming tissue protection guard. Accordingly, it is an object of the present invention to provide a new, and highly effective design and method which overcomes the deficiencies of the prior art as described above. It is a further object of the present invention to provide an intramedullary reaming tissue protection guard. Other objects and a fuller understanding of the invention may be had by referring to the following description and claims taken in conjunction with the accompanying drawings. The present invention overcomes the deficiencies of the prior art and achieves its objectives by providing a new, novel design and method of achieving the protection of sensitive tissue during intramedullary reaming operations. The present invention consists of a cylindrical, tubular member which when properly placed acts as a retractor for and a protector of adjacent tissue during intramedullary reaming operations. In order to facilitate the understanding of the present invention, reference will now be made to the appended drawings of a preferred embodiment of the present invention. The drawings should not be construed as limiting the invention, but rather as being exemplary only. FIG. 1 is a side view of the tissue protection, reaming guard. FIG. 2 is a top view of the guard of FIG. 1. FIG. 3 is a side view of the guard of the present invention showing means for the provision of suction. FIGS. 4, 5, 6, and 7 are alternative means of facilitating suction. FIG. 8 shows a curved embodiment of the present invention. The following is a description of a preferred embodiment of the present invention. The general design of the present invention may be appreciated by reference to the drawings. As will be noted in greater detail hereinafter, the details of the geometries employed may be varied widely to meet specific situations and requirements. However, for purposes illustration, cylindrical configurations and other common surfaces of revolution are here employed. As shown in the Figures, the tissue protection reaming guard of the present invention is basically a cylindrical tube which is intended to protect the sensitive soft tissues during the process of reaming the intramedullary canals of long bones. The reaming of long bones is needed and is a preparatory phase for the actual insertion of an intramedullary nail holding the long bone together and in proper alignment. During this process a flexible reamer is placed over a long guide wire running down the intramedullary canal of a long bone, such as the femur. The flexible reamer is progressively inserted and then retracted out of the long bone while running to produce a reaming of the intramedullary canal to a consistent diameter. This procedure requires that the soft tissue be protected and held away from the moving, flexible reaming apparatus. It is the intent of the present invention to provide a reaming guard to protect the soft tissues during this particular part of such procedures. As noted above the device of the present invention may consist of a cylindrical tube 10 which may at its leading end be tapered in a truncated conic section 12 to facilitate it insertion into the incision or wound. As used herein the term leading end refers to the end of the device inserted into the incision or wound and may be considered to be the proximate end to the bone being reamed. The tube 10 may also be tapered in a transitional section 14 which may also be a truncated conic section to a remote end section 16 which is intended to be sufficiently large in diameter to permit easy insertion of the reaming apparatus and its easy movement and adjustment. The respective transitional sections noted above are shown in FIG. 2. A slot 15 is provided in one side of the tube 10 of sufficient with to accommodate the reamer being repeatedly inserted and withdrawn. The device of the present invention may, also, consist of a cylindrical tube 30 which may at its leading end be tapered in a truncated conic section 32 to facilitate it insertion into the incision or wound. The tube 10 may also be tapered in a transitional section 34 which may also be a truncated conic section to a remote end section 36 which is intended to be sufficiently large in diameter to permit easy insertion of the reaming apparatus and its easy movement and adjustment. Within the tube 30 a suction tube 42 may be provided as an integral part of the wall of tube 30 ending in a nipple 40 for attachment of tubing from a conventional suction device(not shown). The suction tube 42 may end in a double walled section 44 in tapered section 32 to facilitate the suctioning and removal of fluids and debris. Again it should be noted that a slot 35 may be provided in the side of tube 30 to accommodate the insertion and withdrawal of the reamer by the surgeon. The provision of the capability of providing suctioning within the incision or wound as well as protection of the adjacent soft tissue is an important contribution and part of the present invention. By means of the double wall section 44 as shown in FIG. 3, or by means of a series of holes 46, 48, and 50 within the wall section 32, suctioning forces may be applied within the wound when the device is inserted into the wound. By attachment to a vacuum hose intra-operatively the reamings of the intramedullary canal can be collected into the holes 46, 48, 50 and/or the double walled section 44 and removed from the wound. This feature of the present invention is an important characteristic and provides an important capability that is most useful in the reaming of long bones by providing a clearance of the intramedullary contents out of the wound. It is notable that bone and bone fragments of the intramedullary canal that remain within the wound at the end of the surgery may lead to extra bone formation later on providing protuberant or painful areas of ossification in muscle tissue. The better collection of the intramedullary contents provides an important, additional, helpful technique in the intramedullary nailing process which assists the surgeon in the removal of the intramedullary content to prevent heterotopic bone formation. FIG. 5 shows a further alternative in which slots 52, 54, and 56 permit the application of suction within the wound. Similar forces may be applied through slots 60, 62, 64, and 66 as shown in FIG. 6. FIG. 7 shows a further alternative embodiment in which suction may be applied not only through holes 70, 72, 74, 76, 78, and 80 of section 32 but also by means of slots 82, 84, and 86 in the side of tube 30. The device of the present invention may come in a variety of lengths with a diameter adequate to accommodate the reaming apparatus. The diameter may typically be on the order of one inch and the length may typically range between 8 and 16 inches. Portal holes to permit the vacuum extraction and removal of debris may be variably placed around and about the tube. The shape of the device may be straight or curved. The device may be made sufficiently flexible so that it may be curved and shaped as needed for the particular anatomy at hand. The necessary flexibility may be obtained by the provision of a ribbed surface which will allow the device to be flexed into different positions and to hold that particular position. A further embodiment is shown in FIG. 8 in which a flexible section 88 is provided between conic sections 96 and 94. Section 88 may be made adjust ably flexible by means of flexible chain links 90 embedded within plastic wall 92 to give the wall structure additional rigidity while at the same time permitting the same type of flexibility as provided in similarly structured flexible "French curves". Other shapes or configurations of the tubular device too allow for flexibility may be incorporated in accordance with the present invention. Also, a slot 85 may be provided in the tube on the side toward the surgeon to accommodate the reamer and its necessary insertion and withdrawal. Thus, the present invention consists of a cylindrical body which protects the soft tissue of an incision or wound from damage in reaming operations. While specific components such as cylindrical tube shaped devices may be employed and have been referred to throughout as a part of the preferred embodiment of the present invention, any other suitable components or elements which perform the same function, such as hexagonally shaped tubes may be used. The parts herein described may be made of any suitable plastic material. The preferred embodiment has been described in terms of standard cylindrical configurations, but other geometric shapes may be employed using the teachings of the present invention. The present invention has been described in terms of its specific, preferred embodiment but it may obviously be employed in other contexts and operations. While the present invention has been described with reference to specific embodiments, this application is intended to cover those various changes and substitutions which may be made by those skilled in the art without departing from the spirit and scope of the appended claims. Patent Citations
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Alone on the shores of Lake Thirlmere, in acres of mature gardens and woodland, stands Dale Head Hall, an historic Elizabethan lovingly restored into one of Lakeland's finest country house hotels. Dale Head Hall provices you with a warm welcome, elegant accommodation and award-winning cuisine.
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Lake Thirlmere Keswick, England CA12 4TN United Kingdom
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During the Hundred Day Session last spring few pieces of legislation requested by President Roosevelt were denied him by a docile Congress. One was a bill authorizing him to name a nonresident as Governor of Hawaii. The measure squeaked through the House but the Senate let it die as the result of cries of outrage from the insular Democracy.
Having left Republican Governor Lawrence McCully Judd on the job ten months longer than he had a right to expect, President Roosevelt last week named Democrat Joseph Boyd Poindexter of Honolulu as his...
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Lower East Side
Boy, 14, Missing From Lower East Side Since Saturday
Police were searching Wednesday for a 14-year-old boy has been missing since the weekend from his Lower East Side home.
Police Seek 2 Men In String Of ATM Burglaries Around Manhattan
Police on Wednesday were seeking two men who have been seen prying open ATMs mounted outside businesses from the Lower East Side to Chelsea and sometimes making off with cash.
Little Lamb Making Quite The Impression On NYC Streets
You see a lot of wild things on the streets of New York City, and on the Lower East Side there's a little lamb that's getting a lot of attention.
Police: Man Attacked, Sexually Abused Woman On Lower East Side
Police late Thursday were asking for help from the public in finding a suspect who attacked and sexually abused a woman in a Lower East Side building.
Reports: Police Say Woman Bashed Bouncer With Bottle At LES Bar
Police on Monday were searching for a woman who allegedly bashed a bouncer in the head with a bottle in a Lower East Side nightclub this past weekend.
Streit's Matzo Factory Prepares For One Last Passover On Lower East Side
As of now, the company plans to keep their staff during the move and increase production.
Door Fixed At Site Of LES Slashing Attack Following CBS2 Investigation
Residents said they are grateful that the door is finally fixed but they said there are plenty of other problems with the building.
CBS2 Exclusive: Security Issue Exposed At Scene Of Brutal LES Attack
There appears to be a security issue at a city-owned building where a woman was slashed in the face.
NYPD: Suspect Sought For Slashing Woman In The Face
It happened back on Jan. 31 inside a building near the intersection of Jefferson Street and Madison Street on the Lower East Side.
Search Continues For Suspect In Violent Lower East Side Robbery
Police are continuing to search for a suspect in connection with a violent Manhattan mugging that was caught on video.
Search On For Suspect In Violent Robbery Of Woman On Lower East Side
Police on Thursday released surveillance video of the violent attack and robbery of a woman on the Lower East Side late last month.
Toni On! New York: Culinary Crawl Down Clinton Street
This week WLNY's Toni Senecal is taking a culinary crawl on Clinton Street in the Lower East Side. Join her!
Burst Water Main Creates Icy Conditions On Lower East Side
The Department of Sanitation was called in to salt down roads in an effort to the stop icing over of streets.
New Photos Out In Shooting That Left Man Critically Wounded On Lower East Side
Police released new photos Thursday in a shooting that left a man in critical condition on the Lower East Side earlier this week.
Man Charged After Allegedly Stabbing Woman, Being Shot By Police On LES
A man was charged Wednesday after being shot by police after allegedly stabbing a woman in a Lower East Side public housing development earlier this week.


text:
Happy New year from Kody
Kenny S. Metro 1/1/2012 9:09:17 AM
Nice close-up and detail of Kody basking in the warm summer sun.Wishing you and Tony a very Happy New Year! #1433681
Lovely sweet portrait! And a very Happy New Year to you & Tony....and of course Kody!.....=^..^= #9896694Tammy Espino 1/1/2012 11:59:46 AM
Happy New year to you and Tony. Kody looks quite content :) #9896725John Connolly 1/1/2012 12:08:36 PM
A nice close up portrait of Kody, Chris!Wm Nosal 1/1/2012 12:55:43 PM
Wonderful Shot Of Kody, Chris!Happy New Year To You And Tony #9896913
Marta J. Baldwin 1/1/2012 3:24:32 PM
I love the steely gaze Kody has going on here. Great to see he's still around!Happy New Year!!! #9897183
Evy Johansen 1/2/2012 6:47:00 PM
Lovely capture, Chris!! Kody is a beautiful cat! #9899173Chris Ebben 1/5/2012 2:34:06 PM
Kody thanks you all for your lovely comments, keep enjoying the New Year. #9904230Denise M. Beverly 1/12/2012 2:42:05 AM
This looks like my Lillie's buddy Jack. love these gray blue cats. #9915806Chris Ebben 1/13/2012 1:28:54 PM
Many thanks Denise. #9918452Mary K. Robison 6/5/2012 2:38:02 AM
Chris, Kody's face here makes me want to go wake up Riley and squeeze him tight. Your love for her comes through loud and clear in this closeup.Chris Ebben 6/5/2012 3:07:04 AM
Thanks Mary, she certainly is loved & a bit spoilt, if that's possible!! At present she is telling me I should be in bed!!! #10168784Laura E. Swan 12/2/2012 10:31:36 AM
I think Kody's spotted some shrimp??? Lol...I love it! :DWhen I see Kody, I see Fangy. So precious. Both of them. :)))
We love them both 500% and it shows! :D What a blessing our babies have all been.
-Laura :) xo #10446666
Chris Ebben 12/3/2012 3:22:41 AM
You do have good timing!! Guess what she just had for her dinner!! She is spoilt & really loved, yes 500%... I often tell Kody about Fangy. Thanks so much for taking the time to comment=^..^= #10448068Lens aperture f/5.5, shutter speed 1/250sec, focal length 42mm, ISO 80. Taken today, to wish everyone Happy New Year.
Exif: F Number: 5.5, Exposure Bias Value: 0.00, ExposureTime: 10/2500 seconds, Flash: did not fire, compulsory flash mode, ISO: 80, White balance: Auto white balance, FocalLength: 42.50 mm, Model: DSC-H70
Uploaded on 1/1/2012 12:07:49 AM
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Perforated Metal Styles
- Diamond Hole Perforated Metal Panels
- Embossed Sheet Metal
- Slotted Hole Perforated Sheet
- Punched Slotted Tubes
- Perforated Acoustic Screen Panels
- Perforated Metal Sunshade Screen
- Perforated Metal Disc Filters
- Perforated Ceiling Panels
- Perforated Diffusers
- Perforated Ducting
- Perforated Louvers
- Checker Plate
- Round Hole Perforated Sheet
- Square Hole Perforated Sheet
- Semi-Circular Hole Metal Sheet
- Triangle Opening Metal Sheet
- Decorative Opening Metal Sheet
Perforated Materials:
- Perforated Metal Plates for Tubes
- Perforated Stainless Steel
- SUS 304 Punched Plate
- Aluminum Perforated Sheet
- Perforated Copper Sheet
- Mild Steel Perforated Metal
Perforated Metal Products
- Perforated Screen Sheet in Stainless Steel
- Perforated Vent Grille
- Perforated Steel Angle Bead
- Perforated Plate Sieves
- Slotted Filter Sheet
- Perforated Metal Coils
- Perforated Sheets
- Perforated Panels
- Perforated Metal Screen
- Perforated Steel Tube
- Perforated Filters
- Perforated Grills
- Perforated Architecture Mesh
- Perforated Metal Security Screen
- Perforated Cable Tray
- Perforated Channel Cable Tray
- Checkered Tread Plate
Technical Terms:
- Perforated Metal Opening Patterns
- Applications of Perforated Sheet
- Materials Applied for Perforated Metal
- Benefits of Perforated Metal
- Calculation of Sheet Metal Weight
- Open Area Calculation
- Perforated Metal Definition
- Perforated Metal Features
- Terminology of Perforated Metal
Other Sheet Metals
Processing Machines
Perforated Panels
We can supply all types of decorative perforated panels from aluminium, brass, steel and special treatments including colour finishing, dull and bright polishing, dry powder coating, wet paint and galvanizing
We has a choice of designs that can add stunning good looks. The panels can be finished in a variety of ways including powder coating and edge trimmed with various sections, including finished in a wide variety of colours. Perforated panels are available in aluminium, mild steel and stainless steel.
Mild Steel Perforated Panel is made of high quality low carbon plain steel after being perforated on the digital control perforated machines. Mild steel perforated panels have good strength-to-weight ratio, wide range of open area percentages and accurate hole sizes.
We perforated panels can be used with advantage in many situations, for instance when requiring sound reduction, weight saving, air control, filtering, a decorative surface, or simply a non-skid effect.
Uses: Perforated panels are well suited for sorting, facades, ceilings, lamps, shelves, shielding, steps and of course many other purposes as well.


text:
When you're the go-to decorations guy for thousands of merry-makers and are inextricably connected with one of the biggest holiday events in the country, you not only have to be…   Read the Blog
The designer who adds magic to world famous Snowflake Lane gives you tips on how to dress up your decorations in the latest, greatest looks.   See the Gallery
Holiday decorating is no longer just about red, green and candy stripes. Turquoise blues combined with magenta in place of red and lime green rather than forest green are really hot combos this year.   See the Image
Whimsical creatures serve as non-denominational decoration elements that everyone can appreciate, and they bring a sense of magic, fun and playfulness to the holidays, no matter the belief…   See the Image
Note how the orchid arrangement in the foreground, a staple in the house year-round, can be dressed up for the holidays with the addition of festive peppermint sticks.   See the Image
Note how the addition of turquoise and the substitution of lime green for forest green really brightens and freshens this Christmas arrangement. Christmas is all about light and laughter, according…   See the Image
Whether his clients are business or residential, City Flowers' John Hilscher says he can always make them smile with pops of non-traditional color and a sense of whimsy and playfulness.   See the Image
Investing in reusable décor is a great way to decorate on a budget and build your holiday supplies over time. Hilscher's favorite holiday accessory is a snowflake light ball with a simple…   See the Image
To add to the sustainability of your Christmas decor, take a clear glass vase, fill it partially with water and float holly, pyracantha and cranberries inside.   See the Image
The annual holiday showhouse features the work of two-dozen interior designers. It's open to the public through Dec. 21.   See the Gallery


text:
Our Rating: |
their neighbor
Jerry for the first time] Jane Brewster: So Jerry is our new neighbor at the Perry place. And he's handy. Amy: No kidding! Jerry: I'm sorry about the mess, Charley. I was just saying to your mom, I'll have the dumpster gone tomorrow. Charley Brewster: Oh, it doesn't bother me. My mom was... Jane Brewster: Hey, Jerry does night construction on the strip. Charley Brewster: Oh. |


text:
all welcome
Sorry - have been slack havent I? Just lots on - but then we all do.
Welcome new peeps.
mcs - was listening to MT trying to work out which was you (guessing mcs are your initials) but then wondered if I was even listening to the right episode. Fun though.
frc - C plays the french horn.
Susan - sorry, have not been ignoring you and your Claybury questions. I have no idea what the course is like - Wabo? - so on the spikes thing - it may be fine, it may be a slippery nightmare. Hard to tell. But I don't have spikes cos my knees don't like them.
As for chatting on the way round - xc races arent really chattable I find. Maybe at the beginning but after that just trying to stay alive is more my priority because xc is so hard. But - before I put you off completely - it's hard for everyone and there's usually brilliant camaraderie. We're all suffering etc. And it IS only 6k...
We perhaps should aim to warm up together/jog round the course etc which will give us a great opportunity to chat. I'm looking forward to it - esp if it's cold and frosty like today.
Will sign up for Jantastic now that I'm a runner again
markstreet running with daughter on a bike.....on rate your run......
Oh I did Claybury last week. Vets it was. Well Its a nice course, I like it. I did 3 laps and the toughest part is a bit where you go uphill through the woods and then down a sharp hill and if the weather stays at it is I shouldnt think spikes. The ground was hard last weekend and I wore off road shoes.
I must go look see what this race is about, I am not aware of it
Ah, mcs, yes, I remember that. She dropped the water bottle?
Wabo - oh I thought you were racing with us on SAturday? Southern Counties Vets League/Champs or something. Don't really now TBH! Course sounds fab. I like laps. The one we did last week was two laps but round an enormous field where you could pretty much see how far you had to go the whole time (and therefore how far ahead everyone else was...)
HERE IS YOUR CHANCE !!!!Have you been shunned by Asics?Stuck in a training rut?Got a marathon place and can only run round the block??Busy busy busy and no time to train??I have six lovely mentors all lined up and chomping at their Mizunos to get involvedAll you have to do is to tell us why you should be given the prize of the milleniumYOUR PITCH
Should not threaten to harm small animalsShould not send people to sleep or need a screen breakIt will contain your hopes for a marathon timeIt will contain your marathon entry confirmedIt will contain a brief running history of recent times and pb'sWe would love to hear all about YOU, strengths, weaknesses and limitations---------------------------------------This thread will close on Monday 17th December and then Kittenkat and her esteemed Adjudicator(s) will cogitate the pitches and we will then announce the LUCKY SIX on Christmas Eve Asics 6?? As they said on Channel 4 ... thanks for the warm up
Click on the link below to be taken to the pitching page.....
mcs you in the asics thing? could be something for you..
Or someone else here - Ikle? Get that sub 4?
Important point, if memory serves, you score higher if you have pictures of cute dogs, cats or children. So get some pictures ready.
its not the Asics thing FRC! That's the point of it!
I think its too late now frc, I think we are at the voting stage its that right minni?
I know its not the Asics thing !
Thought mcs might've been in the asics thing already, so not interested in the Forum 6. But if he isn't, then a good candidate.
Wabo - yes too late for the Asics but the forum 6 is much better anyway. You're almost guaranteed a pb!
Forum 6 yes interested need a sub four next year.........only problem is I need a marathon, only got a 21 miler booked in March and the Coniston 14 so need to find a flat marathon.....Milton Keynes might be one. White Peak one is a possibility though I think its rather hilly......off to research.......need a kicking,training,cajoling, nerdling, beating, pacing down to that sub four hour mark. Went out and did four easy at lunch all under 8mmiling so getting quicker with three weeks of training under the belt already. Long run Sunday 14 miler planned......
Get one booked mcs. Edinburgh, end of may 26th or 27th? Very flat, even downhill first 3 miles.
But if Ikle went for it, you know we'd vote for you ! (sorry mcs).
msc - definitely get a pitch in if you find a marathon.
Evening all.
Very slack yet again but busy at work (please let me my last christmas in retail).
Hope all are well. All this talk of fast 10K. Just had my confirmation e-mail from Comrades so thats it better start training


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Gerald and Phyllis Harlan celebrated their 65th wedding anniversary on April 13. They wed April 13, 1948, in Walla Walla. They will also celebrate on the Oregon Coast with their daughters and their families.
They met in elementary school in Dayton. Phyllis moved to Elgin, Ill., in 1939 and came west after schooling, where she was reacquainted with Gerald. Phyllis' maiden name is Literal.
Gerald was parts manager at Tumac Machinery for 38 years and retired from there in 1987. He enjoys reading, photography and landscaping.
Phyllis was assistant food service director at Whitman College for 11 years. She then worked for Walla Walla School District until retiring in 1989. Throughout these years she also taught piano lessons to almost 150 students. She enjoys playing bridge, knitting, playing piano and spending time with family.
Both are members of Trinity Lutheran Church in Walla Walla.
They have two daughters, Joan Cummings of Vancouver, Wash., Kris Schilperoort of Sunnyside, Wash.; and three grandchildren, Christopher Cummings and Reid and Claire Schilperoort.
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View Poll Results: Who will end up being Goldenboy's Golden Boy Ortiz or Khan? | |||
Khan will continue to be GBP's Top Man | 2 | 7.41% | |
Ortiz will take over as GBP's top dog after a few fights | 18 | 66.67% | |
Ortiz and Khan will get attention from GBP in the long run | 7 | 25.93% | |
Voters: 27. You may not vote on this poll |
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I think the key is who can move up in weight more successfully. I'd say ortiz because he's American and can potentially be a bigger draw because of the Mexican fanbase. Maybe they can have two GBs: one for Europe and one for N America.
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I think people are forgetting that Ortiz quit like a dog against Maidana, A guy that Khan beat in fight of the year, Granted Ortiz won the fight with Berto but it was sink or swim for Ortiz and if he lost that second chance at a world title then his career was over. Khan beat Ortiz in the amatuers and is already a world champion with several defences, Not only that he is on the verge of unifying the titles.
I think Khan is still the goldenboy the fact that Oscar chose to attend Khans fight over Ortiz fight shows that, Also Oscar gave Khan a new multi year deal to re sign before his McCloskey fight. The McCloskey fight was always meant to be stay busy fight I dont know the big deal. People are forgetting that Ortiz quit against Maidana, Drew with Peterson because he beat Berto, If Khan beats Bradley he will have done a certain one-one-upmanship |
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For his four daughters and 13 grandchildren, to say nothing of his friends and fellow antique fanciers, the late Forsyth Wickes delighted in opening wide the golden trove that he had gathered in his 16-room home in Newport, R.I.
At Starbord House, dinners were served on an early-1800s English table from porcelain that had belonged to Madame du Barry and the Prince de Condé. The sitting room, library and foyer were crammed with rare 17th and 18th century furniture and objets d'art. When Wickes, a retired lawyer, died in 1964 at the age...
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Win Green
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Description: Do you believe in fairies at the bottom of the garden? Win Green does! Make a wish and have hours of fun playing in our pretty pink and lilac Fairy Cottage. Appliquéd and embroidered with delicate fairies, bluebells, foxgloves and butterflies.
- Light metal frame construction
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- Featuring a fairies and flowers motif
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- Small measures 29"W x 43¼"L x 43¼"H
- Large measures 43¼"W x 52.8"L x 65"H
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Material: Metal, Cotton
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August 27 2013, 01:37 PM | #1096 | ||
Location: England
Re: Starship Size Argument thread
August 27 2013, 02:53 PM | #1097 |
Rear Admiral
Location: Andrew Timson
Re: Starship Size Argument thread
Andrew Timson =============== "Niceness is the greatest human flaw, except for all the others." - Brendan Moody "...don't mistake a few fans bitching on the Internet for any kind of trend." - Keith R.A. DeCandido |
August 27 2013, 03:05 PM | #1098 |
Location: The corner of San Antonio and a bottle of Fireball
Re: Starship Size Argument thread
When the fuck did we get ice cream? |
August 27 2013, 03:14 PM | #1099 | |
Location: RIP Leonard Nimoy
Re: Starship Size Argument thread
Apparently not I can't recall any other shot in a Trek movie being dissected as much as this one has.
- SeerSGB - |
August 27 2013, 04:42 PM | #1100 | |
Re: Starship Size Argument thread
Not to mention being able to withstand the most common threats in battle to some extent (which has shown to be true in Star Trek -- ships seem to be able to withstand a certain amount of battle damage), which again, will be far higher than the pressures of an earth-like planet's oceans. |
August 27 2013, 04:45 PM | #1101 | ||
Vice Admiral
Re: Starship Size Argument thread
In the next film, it will have wheels and roll around on empty plains.
A movie aiming low should not be praised for hitting that target. |
August 27 2013, 05:11 PM | #1102 |
Lieutenant Junior Grade
Location: 221 B Baker Street
Re: Starship Size Argument thread
How many people does it take, Admiral, before it becomes wrong? Hmm? A thousand, fifty thousand, a million? How many people does it take, Admiral!" I'm just here to be around like minded people talking about Star Trek, not to make them upset. |
August 27 2013, 07:02 PM | #1103 | ||||
Rear Admiral
Location: I'm in your ___, ___ing your ___
Re: Starship Size Argument thread
We don't know anything about their actual orbital characteristics when they drop to sublight, but they are definitely not stationary.
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August 27 2013, 07:16 PM | #1104 | |
Rear Admiral
Location: I'm in your ___, ___ing your ___
Re: Starship Size Argument thread
And we can, in fact, have flying cars. It's not actually that hard to do. The reason we don't have a lot of STREET LEGAL flying cars is because it turns out they're not actually all that practical from a transportation standpoint. You know what else isn't practical? Hiding a starship on the bottom of an ocean. It's not actually that hard to do. It's just kind of silly, and your chief engineer is probably going to complain a lot about how stupid this is even if you think you have a good reason for doing it.
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August 27 2013, 09:12 PM | #1105 | ||
Location: USA
Re: Starship Size Argument thread
"Life should be revered simply for the fact that we need to be thankful that we are currently able to consciously appreciate what we are going through right now. ... This moment that we're having right now is highly significant." -Maynard James Keenan |
August 27 2013, 11:27 PM | #1106 | ||
Location: RIP Leonard Nimoy
Re: Starship Size Argument thread
I'd say it applies to the whole crew. They all needed a lesson in being adults, and STID was that lesson.
- SeerSGB - |
August 28 2013, 03:58 AM | #1107 | ||
Rear Admiral
Location: San Antonio, TX
Re: Starship Size Argument thread
I don't remember this much BS going on over the Enterprise D going into the sun or through an asteroid. Why not complain that the crew should have been wiped out in Generations when the saucer crashed landed, or Voyager's crew should have been turned into goo when she crashed on the ice planet in Timeless, but holy crap put Enterprise underwater and the fans get all in a wad. -Chris
"It's important to give it all you have while you have the chance."-Shania |
August 28 2013, 04:13 AM | #1108 | ||||||
Re: Starship Size Argument thread
And before I go on, let me be clear: 'm not arguing they *won't* fall to Earth. I'm arguing they wouldn't do so in the time shown in the film (nowhere near it, actually).
August 28 2013, 04:37 AM | #1109 | |||||
Rear Admiral
Location: I'm in your ___, ___ing your ___
Re: Starship Size Argument thread
On the other hand, Enterprise would have been heading for Earth under impulse power at this point, using the usual subspace trickery to reduce its inertial mass and allow a couple of thrusters to push it along. How close was it to Earth when the field collapsed? Going by visuals alone, ALOT closer than 230,000km.
Why are you so sure that they weren't? Especially since Kirk had earlier ordered Sulu to do exactly that? Vengence blows up, Enterprise heads for Earth at one quarter impulse power. Under normal circumstances that would be a five minute flight; under a sudden power failure and loss of vessel control that turns into more like twenty minutes of twisty-tumbling insanity. It's not that hard to explain. And the interesting thing is, it's such a breathtakingly cool scene that most of us don't mind looking for explanations. It would be one thing if it was a pointlessly concocted idiocy that served no purpose whatsoever (e.g. the dune buggy chase in Nemesis), but in this case we're forced to invoke the Rule of Cool.
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August 28 2013, 04:40 AM | #1110 |
Location: Bloom County
Re: Starship Size Argument thread
... anywho...
Now that I've seen it, and have also had time to mellow, to really think about it, I now find it absolutely, unbearably repulsive in every way except for some of the acting. - about The Wrath of Khan. Interstat, Issue 62: 1982 |
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Beat. Nice mellow springtimey vibe...let me know what you think. thanks!! [media]
Just a beat that I'm working on now...all listens and replies are returned. thanks in advance!!! [media]
[media] let me know what you think. all love is returned. get at me to rhyme over this beat!! thanks for listening.
Another sample flip.... [media]
Nice lil sample that i flipped. let me know what you think and get at me if you wanna rhyme over this!!! [media]
Beat...check it out...all comments welcomed!!! thanx in advance for the love and all comments are returned!!! [media]
[media] a beat I produced just looking to get some new ears on my sound...any love given is def returned and appreciated. love.
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Concerto Italiano – Monica Piccinini – Laura Pontecorvo – Rinaldo Alessandrini
27/04/2015 - 27/04/2015 | Auditorium Teatro Manzoni
Appointment within the 28th edition of Musica Insieme Concert Season.
Appointment within the 28th edition of Musica Insieme Concert Season.
The famous Italian pianist, composer and orchestra conductor Giovanni Allevi presents his last project, "Love".
Jazz, funk, soul, gospel, rock... High quality live music and entertainment!
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October 3 2013, 06:41 PM
C.E. Evans
Vice Admiral
Location: Ferguson, Missouri, USA
Re: Starfleeters?
T'Girl wrote:
C.E. Evans wrote:
I could see that being used in the same sense that "police officer" is used for a beat cop even if that person doesn't really have an officer rank.
That my take on it, Roddenberry was a LA cop like his father, everyone being a Starfleet
wouldn't depend on whether or not you held a officers commission.
But other than that Starfleet is of course exactly like the US Navy.
Oh, there's plenty of instances in which Starfleet isn't like the U.S. Navy, namely in regards to its chain of command and some personnel practices.
"Don't sweat the small stuff--it makes you small-minded..."
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Topic closed. 3 replies. Last post 3 years ago by mraasay.
I dreamt that I won 774.00 a few weeks ago, I haven't seen any of the numbers come out as of yet.
last night I dreampt of my brother showing up to do a small clean up job and telling him it wasn't that much
to clean up. loose trash laying around. my age is 77 and his is 80. of course this is around the casinos. Would
you help me with some numbers? Thanks in advance
win= 709-652
garbage= 564-499 Good luck.
clean 709
play also the 774 , 229
your brother , 080, 709,
you, 707, 708
I thank you both, LKYDEB*594 and MANGOSKIN for the numbers, keep up the goo work,
mraasay from new jersey. I work out all the systems but cannot put any of them together
for the numbers. Thanks again


text:
Hi everyone! I have a question on how to fix too narrow sleeves on a dress that is already sewn. The thing is that a few girls from my dance group ordered some (costumes) dresses from India. They were supposed to be made based on their measurements, but the sleeves are too narrow on all of the dresses. The problem is that the guy left no extra seam allowance What is the best way to fix this so that it would still look presentable, since they are going to perform in those dresses? I thought of opening a seam and adding a panel of the same fabric. Are there any other options? Thank you
------Maja "Only creativity brings us close to paradise." (Hundertwasser)
Yours is a good option. Could you remove the entire sleeve, use one as a pattern, and cut a contrasting sheer? Just make sure to add a bit more to the sides of the sleeve "pattern" before cutting
If the sleeve is too narrow all the way down, your best option is to open up the seam an add fabric all the way down. If it's just at the bicep a gusset could work to give more width and movement.
------I finally have a blog. www.detectivehoundstooth.com :)
I hope you got a return on some of your money. That's really aggravating! Is there no time to have them sent back and fixed?
------Please excuse any typos, ipad keyboards are hard for me.
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Class Details
by: lalalauren
Pattern Details
by: megumi


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I watched the remake of Total Recall today. And I have to say I really enjoyed it even though I thought I might not. Now I willl be honest I would prefer less remakes to be made since movies are more interesting when they are original. But I enjoyed this remake of Total Recall now very different but in my opinion different in a good way. I thought the entire cast did a good job in there roles. I really enjoyed the synthetic robot police cause I am a sucker for robots. But in short in my opinion it was a good movie and I would suggest it because while its a remake to me its different enough to kind of be its own film. Just what I think.
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The Spirit of 1976
Commerce, Community, and the Politics of Commemoration
Publication Year: 2013
Published by: University of Massachusetts Press
Series: Public History in Historical Perspective
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p. C-C
Title Page, Copyright Page
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pp. i-vi
Table of Contents
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pp. vii-ix
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pp. x-xiv
This book began as class prep for the graduate seminar Care and Management of Historical Collections. I needed a topic that would allow students to practice their skills in research, acquisition, and collections care, and the 1976 bicentennial seemed to have produced an abundance of material for students to consider. It was also recent enough to allow for some interesting...
Introduction: In the Spirit of the Revolution
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pp. 1-20
In the summer in 1972, the American Revolution Bicentennial Commission (ARBC) found itself in a situation hotter than the sidewalks of Washington, D.C. A federal body created in 1966 and charged with overseeing the commemoration of the 200th anniversary of the American Revolution, the ARBC stood accused of creating an observance that privileged...
1. Finding a Role for the "Private Sector": The American Revolution Bicentennial Commission, 1966–1973
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pp. 21-46
Bicentennial planning at the federal level suffered from a lack of cultural authority from its very beginnings in 1966. As the Vietnam War unfolded, as the economy faltered, as urban unrest showed that America was failing to live up to the promises of the civil rights movement, as leader after leader collapsed from assassination or corruption, the federal ...
2. The Sellabration: Entrepreneurs as the New Revolutionaries
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pp. 47-68
Around the 200th anniversary of the American Revolution, the private sector of the American economy experienced a revolution of its own. Due to severe criticism aimed at business in the '60s and early '70s, members of the business community were cautious about highly visible participation in public life, but by the dawn of 1980, they had not only grown the...
3. Anti-Schlock: Consumerism and History on the Red, White, and Blue Left
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pp. 69-90
Protest was an important feature of the national birthday, and objections to the anniversary's commercialization came loudly and clearly from the left. Activists commented broadly but to varying degrees on the bicentennial and bicentennial commercialism, discussing the relevance of the American Revolution and American history to contemporary issues and...
4. "Resolving the Commercialism Issue": The American Revolution Bicentennial Administration, 1973–1977
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pp. 91-108
By 1974 federal planners had settled on a strategy that mixed grassroots participation with an emphasis on entrepreneurial spirit, a combination that would achieve some success and restore some measure of public faith in the federal government, or at least in its ability to plan a birthday party. The shift in federal strategy reflected a more significant cultural transition...
5. "Just pick something and do it": Bicentennial Consumerism and Community
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pp. 109-130
While federal planners had starting thinking about the bicentennial about a decade before its arrival, public dialogue about appropriate bicentennial celebration began in earnest around 1974. Though much of the press coverage focused on the American Revolution Bicentennial Commission and its more successful progeny, the ARBA, Americans...
Conclusion: The Morning after
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pp. 131-148
On July 4, 1976, the party was, by most accounts, magnificent. Television news anchor Walter Cronkite called it "the greatest, most colossal birthday party in 200 years."1 Communities everywhere held parades, festivals, cookouts, each taking on the features of local history and culture. People in San Francisco celebrated the bicentennial of the nation...
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pp. 149-170
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pp. 171-175
About the Author
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pp. 176-177
Back Cover
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p. BC-BC
Print-ISBN-13: 9781625340429
Print-ISBN-10: 1625340427
Page Count: 184
Illustrations: 8 illus.
Publication Year: 2013
Series Title: Public History in Historical Perspective


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Celebrating the Classes of 1965, 1970, 1975, 1980, 1985, 1990, 1995,
2000, 2005, 2010 & 2015
Arthur J. Kania Dean John Y. Gotanda welcomes ALL ALUMNI to celebrate the milestone reunions for classes ending in a 5 or 0.
When was the last time you made your way back to Villanova Law School? Last year? Last decade? Not since graduation?
Although your law school years may be far behind, and the all-night study sessions and excitement of Marbury v. Madison and Pennoyer v. Neff are now just a faint and distant memory, the friendships and associations that began at VLS still remain.
There has never been a better time to return to VLS than this fall.
We invite you to come meet your Dean, John Y. Gotanda, and learn about his vision for the Law School, enjoy a tour of your new law school building, reconnect with your classmates, colleagues, professors and friends, and revisit memories of years past in the place you once called home.
Experience VLS without pressure to meet deadlines, finish outlines, or cram for exams and join us in celebrating the continued excellence of your alma mater!
Save the date for November 7, 2015 - A commemoration of how far we've come!
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A block of rooms have been reserved at The Villanova University Conference Center and The Radnor Hotel for the weekend of November 6-7, 2015. Please indicate you are attending the 'Villanova Law School Reunion' when making reservations.
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