Synthetic Cord Research Articles

Type I IFN Receptor Signaling on B Cells Promotes Antibody Responses to Polysaccharide Antigens.

We previously reported monophosphoryl lipid A (MPL) and synthetic cord factor trehalose-6,6'-dicorynomycolate (TDCM) significantly increase Ab responses to T cell-independent type 2 Ags (TI-2 Ags) in a manner dependent on B cell-intrinsic TLR4 expression, as well as MyD88 and TRIF proteins. Given the capacity of MPL to drive type I IFN production, we aimed to investigate the extent to which type I IFN receptor (IFNAR) signaling was required for TI-2 responses and adjuvant effects. Using Ifnar1-/- mice and IFNAR1 Ab blockade, we found that IFNAR signaling is required for optimal early B cell activation, expansion, and Ab responses to nonadjuvanted TI-2 Ags, including the pneumococcal vaccine. Further study demonstrated that B cell-intrinsic type I IFN signaling on B cells was essential for normal TI-2 Ab responses. In particular, TI-2 Ag-specific B-1b cell activation and expansion were significantly impaired in Ifnar1-/- mice; moreover, IFNAR1 Ab blockade similarly reduced activation, expansion, and differentiation of IFNAR1-sufficient B-1b cells in Ifnar1-/- recipient mice, indicating that B-1b cell-expressed IFNAR supports TI-2 Ab responses. Consistent with these findings, type I IFN significantly increased the survival of TI-2 Ag-activated B-1b cells ex vivo and promoted plasmablast differentiation. Nonetheless, MPL/TDCM adjuvant effects, which were largely carried out through innate B cells (B-1b and splenic CD23- B cells), were independent of type I IFN signaling. In summary, our study highlights an important role for B-1b cell-expressed IFNAR in promoting responses to nonadjuvanted TI-2 Ags, but it nonetheless demonstrates that adjuvants which support innate B cell responses may bypass this requirement.

Pulmonary Administration of the Liposome-Based Adjuvant CAF01: Effect of Surface Charge on Mucosal Adjuvant Function

Mucosal surfaces of the lungs represent a major site of entry for airborne pathogens, and pulmonary administration of vaccines is an attractive strategy to induce protective mucosal immunity in the airways. Recently, we demonstrated the potential of pulmonary vaccination with the tuberculosis subunit antigen H56 adjuvanted with the cationic liposomal adjuvant formulation CAF01, which consists of the cationic lipid dimethyldioctadecylammonium (DDA) bromide and the synthetic cord factor trehalose-6,6'-dibehenate. However, the cationic charge of DDA represents a major safety challenge. Hence, replacing DDA with a safer zwitterionic or anionic phospholipid is an attractive approach to improve vaccine safety, but the effect of liposomal surface charge on the induction of mucosal immunity after airway immunization is poorly understood. Here, we investigated the effect of surface charge by replacing the cationic DDA component of CAF01 with zwitterionic dipalmitoylphosphatidylcholine (DPPC) or anionic dipalmitoylphosphatidylglycerol (DPPG), and we show that charge modification enhances antigen-specific pulmonary T-cell responses against co-formulated H56. We systematically replaced DDA with either DPPC or DPPG and found that these modifications resulted in colloidally stable liposomes that have similar size and morphology to unmodified CAF01. DPPC- or DPPG-modified CAF01 displayed surface charge-dependent protein adsorption and induced slightly higher follicular helper T cells and germinal center B cells in the lung-draining lymph nodes than unmodified CAF01. In addition, modified CAF01 induced significantly higher levels of H56-specific Th17 cells and polyfunctional CD4+ T cells in the lungs, as compared to unmodified CAF01. However, the strong H56-specific humoral responses induced by CAF01 in the lungs and spleen were not influenced by surface charge. Hence, these results provide insights into the importance of surface charge for liposomal adjuvant function and can also guide the design of safe pulmonary subunit vaccines against other mucosal pathogens.

Experimental Investigation of the Tensile Behavior of Selected Tire Cords Using Novel Testing Equipment.

Aramid and polyamide cords are used in a wide range of applications, particularly in the automotive industry (tire reinforcement) and textile industry for military and fireguard purposes. The problem of the reliable experimental study of tensile behavior of synthetic cords is considered in this paper. In the available standards for synthetic cord testing, particularly ASTM D 885-03, the tensile test must result with the cord damage in the middle of gauge length, and the cords should be fixed in the machine clamps. The trial test gave damage near the clamps. We propose a novel testing stage mounted in the testing machine clamps to achieve the uniform tensile stress distribution in the gauge length of the measured cords. The results of the deformations were measured in two ways: using testing machine head displacement and a videoextensometer. Stress curves of four distinguished cords were evaluated and compared. The second method allowed to acquire results differing from the manufacturers’ data from 0.7% to 21.5%, which allowed for the conclusion that the designed test stand allows for obtaining reliable results for stretched cords.

Cell wall skeleton of Mycobacterium bovis BCG enhances the vaccine potential of antigen 85B against tuberculosis by inducing Th1 and Th17 responses.

A safe and effective adjuvant is necessary to induce reliable protective efficacy of the protein-based vaccines against tuberculosis (TB). Mycobacterial components, such as synthetic cord factor and arabinogalactan, have been used as one of the adjuvant components. Mycobacterium bovis bacillus Calmette- Guérin cell-wall skeleton (BCG-CWS) has been used as an effective immune-stimulator. However, it is not proven whether BCG-CWS can be an effective adjuvant for the subunit protein vaccine of TB. In this study, we demonstrated that the BCG-CWS effectively coupled with Ag85B and enhanced the conjugated Ag85B activity on the maturation of dendritic cells (DCs). Ag85B-BCG-CWS-matured DCs induced significant Th1 and Th17 responses when compared to BCG-CWS or Ag85B alone. In addition, significant Ag85B-specific Th1 and Th17 responses were induced in Ag85B-BCG-CWS-immunized mice before infection with M. tuberculosis and maintained after infection. Moreover, Ag85B-BCG-CWS showed significant protective effect comparable to live BCG at 6 weeks after infection and maintained its protective efficacy at 32 weeks post-challenge, whereas live BCG did not. These results suggest that the BCG-CWS may be an effective adjuvant candidate for a protein-based vaccine against TB.

Mitral valve repair in dogs using an ePTFE chordal implantation device: a pilot study

ObjectiveMitral valve (MV) regurgitation due to degenerative MV disease is the leading cause of cardiac death in dogs. We carried out preliminary experiments to determine the feasibility and short-term effects of beating-heart MV repair using an expanded polytetrafluorethylene (ePTFE) chordal implantation device (Harpoon TSD-5) in dogs. AnimalsThis study involved six healthy purpose-bred Beagles (weight range 8.9–11.4 kg). Material and methodsFollowing a mini-thoracotomy performed under general anesthesia, the TSD-5 was used to place 1 or 2 artificial ePTFE cords on the anterior MV leaflet or the posterior MV leaflet via a left-ventricular transapical approach. The procedure was guided and monitored by transesophageal echocardiography. Postoperative antithrombotic treatment consisted of clopidogrel or a combination of clopidogrel and apixaban. Dogs were serially evaluated by transthoracic echocardiography at day 1, 7, 14, 21, and 30. The hearts were then examined for evaluation of tissues reactions and to detect signs of endothelialization. ResultsOne or two chords were successfully implanted in five dogs. Four dogs completed the 30 days follow-up. One dog died intra-operatively because of aortic perforation. One dog died early post-operatively from a hemorrhagic pleural effusion attributed to overly aggressive antithrombotic treatment. One dog developed a thrombus surrounding both the knot and the synthetic cord. Postmortem exam confirmed secure placement of ePTFE knots in the mitral leaflets in all dogs and the presence of endothelialization of the knots and chords. ConclusionsThese preliminary results demonstrate the feasibility of artificial chordal placement using an ePTFE cordal implantation device in dogs.

Microstructure and mechanical properties of synthetic brow-suspension materials

Levator palpebrae superioris (LPS) is a muscle responsible for lifting the upper eyelid and its malfunction leads to a condition called “ptosis”, resulting in disfigurement and visual impairment. Severe ptosis is generally treated with “brow-suspension” surgery, whereby the eyelid is cross-connected to the mobile tissues above the eyebrow using a cord-like material, either natural (e.g. fascia lata harvested from the patient) or a synthetic cord. Synthetic brow-suspension materials are widely used, due to not requiring the harvesting of fascia lata that can be associated with pain and donor-site complications.The mechanical properties of some commonly-used synthetic brow-suspension materials were investigated — namely, monofilament polypropylene (Prolene®), sheathed braided polyamide (Supramid Extra® II), silicone frontalis suspension rod (Visitec® Seiff frontalis suspension set), woven polyester (Mersilene® mesh), and expanded polytetrafluoroethylene (Ptose-Up). Each material underwent a single tensile loading to the failure of the material, at three different displacement rates (1, 750 and 1500mm/min).All the materials exhibited elastic–plastic tensile stress–strain behaviour with considerable differences in elastic modulus, ultimate tensile strength, elastic limit and work of fracture. The results suggest that, as compared to other materials, the silicone brow-suspension rod (Visitec® SFSS) might be the most suitable, providing relatively long-lasting stability and desirable performance. These findings, together with other factors such as commercial availability, cost and clinical outcomes, will provide clinicians with a more rational basis for selection of brow-suspension materials.

CAF05: cationic liposomes that incorporate synthetic cord factor and poly(I:C) induce CTL immunity and reduce tumor burden in mice.

Considerable effort has been put into targeting tumors through therapeutic vaccination using dendritic cell-, DNA-, protein-, or peptide-based vaccines. Purified peptides and proteins are generally not immunogenic and need to be administered with an adjuvant that will trigger an appropriate immune response. Safe adjuvants that favor induction of tumor reactive CD8(+) T cells with the capacity to directly kill tumor cells are therefore a high priority. We have previously reported on the effect and mechanism of a cationic adjuvant formulation, CAF01, which incorporates synthetic mycobacterial cord factor and primes protective Th1, Th17, and antibody responses in animal models of bacterial, viral, and parasitic infections. The CAF01 adjuvant is currently in clinical trial. Using CAF01 as a backbone, we recently demonstrated that incorporating the TLR3 ligand polyinosinic/polycytidylic acid [poly(I:C)] primes CD8(+) T cells specific to the SIINFEKL epitope of the model antigen ovalbumin. In the present study, we demonstrate that CAF01/poly(I:C), termed cationic adjuvant formulation 05 or CAF05, can induce CD8(+) T cells that efficiently lyse target cells and significantly reduce tumor growth in two different mouse tumor models: lung B16-OVA melanoma expressing ovalbumin and the self-antigen TRP2, and subcutaneous TC-1 tumors expressing the human papillomavirus-16 protein E7.

Increased potential of a cationic liposome-based delivery system: Enhancing stability and sustained immunological activity in pre-clinical development

The combination of dimethyl dioctadecyl ammonium bromide (DDA) and the synthetic cord factor trehalose dibehenate (TDB) with Ag85B-ESAT-6 (H1 fusion protein) has been found to promote strong protective immune responses against Mycobacterium tuberculosis. The development of a vaccine formulation that is able to facilitate the requirements of sterility, stability and generation of a vaccine product with acceptable composition, shelf-life and safety profile may necessitate selected alterations in vaccine formulation. This study describes the implementation of a sterilisation protocol and the use of selected lyoprotective agents in order to fulfil these requirements. Concomitantly, close analysis of any alteration in physico-chemical characteristics and parameters of immunogenicity have been examined for this promising DDA liposome-based tuberculosis vaccine. The study addresses the extensive guidelines on parameters for non-clinical assessment, suitable for liposomal vaccines and other vaccine delivery systems issued by the World Health Organisation (WHO) and the European Medicines Agency (EMEA). Physical and chemical stability was observed following alteration in formulations to include novel cryoprotectants and radiation sterilisation. Immunogenicity was maintained following these alterations and even improved by modification with lysine as the cryoprotective agent for sterilised formulations. Taken together, these results outline the successful alteration to a liposomal vaccine, representing improved formulations by rational modification, whilst maintaining biological activity.

Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRγ–Syk–Card9–dependent innate immune activation

Novel vaccination strategies against Mycobacterium tuberculosis (MTB) are urgently needed. The use of recombinant MTB antigens as subunit vaccines is a promising approach, but requires adjuvants that activate antigen-presenting cells (APCs) for elicitation of protective immunity. The mycobacterial cord factor Trehalose-6,6-dimycolate (TDM) and its synthetic analogue Trehalose-6,6-dibehenate (TDB) are effective adjuvants in combination with MTB subunit vaccine candidates in mice. However, it is unknown which signaling pathways they engage in APCs and how these pathways are coupled to the adaptive immune response. Here, we demonstrate that these glycolipids activate macrophages and dendritic cells (DCs) via Syk–Card9–Bcl10–Malt1 signaling to induce a specific innate activation program distinct from the response to Toll-like receptor (TLR) ligands. APC activation by TDB and TDM was independent of the C-type lectin receptor Dectin-1, but required the immunoreceptor tyrosine-based activation motif–bearing adaptor protein Fc receptor γ chain (FcRγ). In vivo, TDB and TDM adjuvant activity induced robust combined T helper (Th)-1 and Th-17 T cell responses to a MTB subunit vaccine and partial protection against MTB challenge in a Card9-dependent manner. These data provide a molecular basis for the immunostimulatory activity of TDB and TDM and identify the Syk–Card9 pathway as a rational target for vaccine development against tuberculosis.

Investigation into the Effects of Accelerated Aging Conditions on Adhesion of Resorcinol–Formaldehyde–Latex Treated Synthetic Cords

The adhesion between the interface of synthetic fiber and rubber is achieved by coating the surface of synthetic cord with Resorcinol–Formaldehyde–Latex (RFL) adhesive solution. The strength of adhesion between fiber–RFL–rubber, depends on several factors. These include an optimum coating and curing conditions involving the control of timing, tension and temperature. Even if good adhesion is obtained by controlling the optimum conditions, the adhesion could be lost to some extend, if the RFL coated cords are exposed to indifferent and harsh ambient conditions. In this article, the adhesion behaviour of RFL dipped cord, after prolonged exposure to temperature, humidity and daylight was investigated. The adhesion was monitored by the pull out method. The analysis of the un-aged and aged cords were carried out by contact angle measurement, ATR spectroscopy and cord cross-section microscopic analysis.

Antitumor effect of a synthetic cord factor, 6,6'-di-O-decanoyl-alpha,alpha-trehalose (SS554), in mice.

The antitumor effect on Meth-A fibrosarcoma in BALB/c mice of a synthetic cord factor, 6,6'-di-O-decanoyl-alpha,alpha-trehalose (designated as SS554), was examined. Only intratumoral injection had a curative effect; subcutaneous, per oral, or intravenous routes had no such effect. The co-presence of an oily vehicle has been shown to be necessary for antitumor activity of a natural cord factor. When SS554 was examined in suspensions of sesame oil, squalane, squalene or sesame oil and water emulsion, a 60% cure rate was achieved. However, no such effect was obtained with a suspension in Tween-PBS or a solution. It should also be noted that sequential but independent administrations of SS554 and oil were found to be as effective as the simultaneous administration of oil and SS554 in emulsion form. In the case of the emulsion, the amount of sesame oil necessary was over 10%, or 0.01 ml in absolute terms. Cures were obtained in a dose-dependent manner by injection of SS554 in amounts in excess of 1 mg. The effect of the time of administration was also examined; the best result was obtained when intratumoral injection was done on day 3 after tumor implantation. Mice cured by SS554 exhibited growth inhibition and rejection of rechallenged Meth-A cells. However, this immunity was specific; it did not extend to a rechallenge with RLmale-1 leukemia cells.

Characterization of cationic liposomes based on dimethyldioctadecylammonium and synthetic cord factor from M. tuberculosis (trehalose 6,6′-dibehenate)—A novel adjuvant inducing both strong CMI and antibody responses

Incorporation of the glycolipid trehalose 6,6′-dibehenate (TDB) into cationic liposomes composed of the quaternary ammonium compound dimethyldioctadecylammonium (DDA) produce an adjuvant system which induces a powerful cell-mediated immune response and a strong antibody response, desirable for a high number of disease targets. We have used differential scanning calorimetry (DSC) to investigate the effect of TDB on the gel-fluid phase transition of DDA liposomes and to demonstrate that TDB is incorporated into DDA liposome bilayers. Transmission Electron Microscopy (TEM) and cryo-TEM confirmed that liposomes were formed when a lipid film of DDA containing small amounts of TDB was hydrated in an aqueous buffer solution at physiological pH. Furthermore, time development of particle size and zeta potential of DDA liposomes incorporating TDB during storage at 4 °C and 25 °C, indicates that TDB effectively stabilizes the DDA liposomes. Immunization of mice with the mycobacterial fusion protein Ag85B–ESAT-6 in DDA–TDB liposomes induced a strong, specific Th1 type immune response characterized by substantial production of the interferon-γ cytokine and high levels of IgG2b isotype antibodies. The lymphocyte subset releasing the interferon-γ was identified as CD4 T cells.

Posterior cruciate ligament (PCL) reconstruction--an in vitro study of isometry. Part II. Tests using an experimental PCL graft model.

Isometric positioning of the posterior cruciate ligament (PCL) graft is important for successful reconstruction of the PCL-deficient knee. This study documents the relationship between graft placement and changes in intra-articular graft length during a passive range of motion of the knee. In eight cadaveric knees the PCL was identified and cut. The specimens were mounted in a stabilising rig. PCL reconstruction was performed using a 9-mm-thick synthetic cord passed through tunnels 10 mm in diameter. Three different femoral graft placement sites were evaluated: (1) in four specimens the tunnel was located around the femoral isometric point, (2) in two specimens the tunnel was positioned over the guide wire 5 mm anterior to the femoral isometric point, (3) in two specimens the tunnel was positioned over the guide wire 5 mm posterior to the isometric femoral point. In all knees only one tibial tunnel was created around the isometric tibial point. The location of the isometric points is described in part I of this study. The proximal end of the cord was fixed to the lateral aspect of the femur. Distally, the cord was attached to a measuring unit. The knees were flexed from 0 degrees to 110 degrees, and the changes in the graft distance between the femoral attachment sites were measured in 10 degrees steps. Over the entire range of motion measured, the femoral tunnels positioned around the isometric point produced femorotibial distance changes of within 2 mm. The anteriorly and posteriorly placed tunnels produced considerable changes in femorotibial distance with knee flexion, e.g. about 8 mm at 110 degrees of flexion.

Elastic-quasi-dynamic Solution of the Mallory Tube Test

Abstract A novel numerical approach to model the bending of a straight Mallory tube into a desired configuration is described. The effect of the bimodular behavior of synthetic reinforcement cord on the bending process is reported. The reinforcement used encompasses the most widely used fibers such as polyester, nylon, and rayon. The principal strain magnitudes at the reinforcement layer are computed under pure bending. The internal inflation pressure and the angular velocity at which the tube is rotated do not have a noticeable effect on the strain magnitudes. However, the axial length of the tube, the location of the reinforcing layers inside the thickness of the tube, and the orientation of this layer have shown remarkable influence on the strain distribution. Finally, the strain magnitudes from the numerical solution are compared with the strain magnitude measured from actual photographs of the tube during testing. The calculated strain magnitudes and the measured ones were found to be in good agreement.

3′,6′-anhydro-6- O-corynomycoloyl trehalose: Synthesis and identification as the impurity in synthetic cord factor preparations

Acylation of 2,3,4,2′,3′,4′-hexa- O-benzyl-6,6′-di- O-methanesulphonyl-α-α-trehalose (1) with a reduced amount of potassium corynomycolate yielded a mixture which consisted mainly of 2,3,4,2′,3′,4′-hexa- O-benzyl-6- O-corynomycoloyl-6′- O-methanesulphonyl-α,α-trehalose (2). Catalytic hydrogenolysis of 2 gave the mono-mesylate 4 which was converted into 3′,6′-anhydro-6- O-corynomycoloyl-α,α-trehalose (5) but treatment with sodium hydride. The structure of 5 was studied by mass-spectroscopy. Compound 5 was found to be identical with the byproduct obtained in the acylation of 6,6′-di- O- p-toluenesulphonyl-α,α-trehalose with potassium corynomycolate.

Immunotherapy with an intralesionally administered synthetic cord factor analogue.

Injection of emulsified 6,6'-di-O-2-tetradecyl-3-hydroxyoctadecanoyl-a, a trehalose designated C76, a synthetic analogue of the mycobacterial glycolipid trehalose-6,6'-dimycolate (TDM), into transplants of an established, syngeneic murine fibrosarcoma induced complete regression of tumor in a number of animals. The number of animals in which tumor regressed completely dependent on the amount of oil in the emulsion. On a weight basis, C76 was at least as active as TDM. Intralesional injection of an emulsified mixture of C76 and endotoxin (ET) or of TDM and ET caused regression of an established transplant of a guinea-pig hepatoma in syngeneic animals. In mice, intravenously administered emulsions of C76 were less toxic and less granulomagenic than those made with TDM.

Textile structure of high-tenacity high-modulus synthetic cord

Textile structure of high-tenacity high-modulus synthetic cord

Site II-specific inhibition of mitochondrial oxidative phosphorylation by trehalose-6,6′-dimycolate (cord factor) of Mycobacterium tuberculosis

Trehalose-6,6′-dimycolate (cord factor), a toxic glycolipid of Mycobacterium tuberculosis, inhibited the phosphorylation coupled to the oxidation of either succinate or NADH-linked substrates and caused a loss of respiratory control in mouse liver mitochondria. Preincubation of the mitochondrial suspension with cord factor was necessary for this inhibitory action. Liver mitochondria from a variety of animal species were susceptible to the action of cord factor. Phosphorylation coupled to the oxidation of succinate by ferricyanide (site II phosphorylation) was completely damaged, while that associated with the oxidation of ascorbate-TMPD (site III phosphorylation) was not affected by cord factor. Mycolic acid, either alone or with trehalose, acetylated cord factor, and a nontoxic synthetic cord factor analog, 6, x-di-(3′-acetoxy, x-methoxymycolanoyl)- N-acetyl- d-glucosamine, were without effect, while two toxic cord factor analogs, methyl 6-(3′, x-sulphitomycolanoyl)-α- d-glucoside and 6-(3′-acetoxy, x-methoxymycolanoyl)- N-acetyl- d-glucosamine, affected the mitochondrial oxidative phosphorylation as did cord factor. Cord factor stimulated slightly the mitochondrial ATPase. The effect of cord factor and DNP to induce the mitochondrial ATPase was additive. The 14C-labeled cord factor was not firmly bound to mitochondria.

海水中に浸漬された網糸の強さの変化について-II

In the previous paper reporting changes the strength of cords immersed in the sea, the description was mainly concerned with non-treated synthetic cords. Whereas, the present work deals with tarred synthetic cords subjected to the sea immersion to see relationship between the tensile strength and the testing temperature as well as change in the strength that likely occurs during the immersion. The tarred synthetic cords used include Amilan, Cremona, Kanevyan and Saran. Each of them was categorized, as before, into B1 and B2: the former group being immersed continuously, while the latter intermittently. 1) Among the results obtained Figs. 1 and 2 show relationships between the experimental period and either the tensile strength or elongation along with mean testing temperatures which varied depending on a testing day. 2) In laboratory experiments of the same materials as used for the sea immersion it has been confirmed that tensile strength of the cords may be indicated with function of quadric or a higher degree in relation to the testing temperature. Relationship between tensile strength with temperature S0θ or between elongation with temperature E0θ may be expreseed by an experimental formula, respectively: S0θ=a+bθ+cθ2 3 ?? θ ?? 30 E0θ=a'+b'θ+c'θ2 3 ?? θ ?? 30 From the experiments the constant, such as a, b, c, a', b' and c', were obtained as shown in Table 1. 3) When Siθ represents the tensile strength at θ°C of a tarred cord which has been submerged in the sea continuously or intermittently during i days, change of the tensile strength Ki is measured as Ki=Siθ/S0θ In the same way, change in the elongation K'i is K'i=Eiθ/E0θ 4) Let Kjl represent the mean ratio of changes from the tensile strength as of the i-th day to that on the j-th day after inception of the immersion, then kjl={(Ki-Kj)/(j-i)}×100(%) The mean ratio as to the elongation, k'ji is in the same way k'ji={(K'i-K'j)/(j-i)}×l00 (%) The ratios K and K' are obtained theoretically by dK/di=f(i) & dK'/di= ?? (i) K=K0+∫i0f(i)di & K'=K'0+∫i0 ?? (i)di where f (i) is a general form of k and ?? (i) of k'. 5) So far the experiments have revealed that tensile strength of tarred synthetic cords in general tends to be more affected in summer, than any othor season while the strength of a particular synthetic cord, Cremona, is decreased during summer to fall: however, the change in the elongation of these cords seems uniform throughout the submerging perind.