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1.
Opt Express ; 31(23): 38049-38063, 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-38017922

ABSTRACT

Statistical probability distributions characterizing received optical power fluctuations, or scintillation, enable performance predictions of space-to-ground optical communication systems. In this paper, we present measurements of stellar scintillation over a wide range of elevation angles and turbulence conditions collected simultaneously with a 5 cm and 40 cm telescope aperture, which allows a comparison between minimal and significant aperture averaging conditions. The measured data is compared to a reasonable set of candidate probability distribution functions (PDFs), including lognormal, which is most often cited in the literature for weak to moderate scintillation. For scintillation indices (SIs) less than about 0.2, the Nakagami-m distribution provides the best representation of the collected data for both apertures and imposes a greater lasercom link penalty than a lognormal distribution, which has been inaccurately implemented as the default probability distribution in the literature. For larger values of the SI, the scintillation is best characterized by a Gamma-Gamma distribution. Additionally, the measured temporal covariance for weak to moderate scintillation conditions is found to be in reasonably good agreement with theoretical predictions.

3.
Opt Express ; 26(21): 26787-26809, 2018 Oct 15.
Article in English | MEDLINE | ID: mdl-30469759

ABSTRACT

In this work, we consider optical downlink from space-based laser sources and develop a consistent quantitative analysis of the collected power fluctuations by finite receiving apertures, and both the corresponding temporal covariance and power spectral density (PSD). Here we assume weak to moderate scintillation conditions where lognormal statistics are valid. We derive both exact solutions and highly accurate engineering easy to implement approximations for the downlink aperture-averaging factor, and both the corresponding aperture-averaged signal temporal covariance and PSD. Additionally, highly accurate elementary analytic scaling relations are derived for the corresponding aperture-averaged characteristic correlation time and scintillation bandwidth, which are in good agreement with available experimental observations. Finally closed form expressions for the so-called quasi-frequency that is central to the determination of level crossing rates and duration of fades and surges in a propagation channel are derived. Wherever possible, we endeavor to derive "user friendly" accurate engineering approximations for the various statistical quantities of interest.

4.
Opt Express ; 23(17): 22867-82, 2015 Aug 24.
Article in English | MEDLINE | ID: mdl-26368254

ABSTRACT

Based on the Rytov approximation we have developed for weak scintillation conditions a general expression for the temporal averaged variance of irradiance. The present analysis provides, for what we believe is the first time, a firm theoretical basis for the often-observed reduction of irradiance fluctuations of an optical beam due to atmospheric turbulence. Accurate elementary analytic approximations are presented here for plane, spherical and beam waves for predicting the averaging times required to obtain an arbitrary value of the ratio of the standard deviation to the mean of an optical beam propagating through an arbitrary path in the atmosphere. In particular, a novel application of differential absorption measurement for the purpose of measuring column-integrated concentrations of various so-called greenhouse gas (GHG) atmospheric components is considered where the results of our analysis indicates that relatively short averaging times, on the order of a few seconds, are required to reduce the irradiance fluctuations to a value precise enough for GHG measurements of value to climate related studies.

5.
Opt Express ; 20(18): 20680-3; discussion 20684-7, 2012 Aug 27.
Article in English | MEDLINE | ID: mdl-23037115

ABSTRACT

Recently, an exponentiated Weibull distribution model was presented for describing the effects of aperture averaging on scintillation of Gaussian beams propagating through atmospheric turbulence. The model uses three parameters that are derived from physical quantities so that in principle the model could be used to predict optical link performance. After reviewing this model, however, we find several inconsistencies that render it unusable for this purpose under any scintillation conditions.

6.
Appl Opt ; 51(9): 1396-406, 2012 Mar 20.
Article in English | MEDLINE | ID: mdl-22441488

ABSTRACT

This paper analyzes the dynamics of objective laser speckles as the distance between the object and the observation plane continuously changes. With the purpose of applying optical spatial filtering velocimetry to the speckle dynamics, in order to measure out-of-plane motion in real time, a rotational symmetric spatial filter is designed. The spatial filter converts the speckle dynamics into a photocurrent with a quasi-sinusoidal response to the out-of-plane motion. The spatial filter is here emulated with a CCD camera, and is tested on speckles arising from a real application. The analysis discusses the selectivity of the spatial filter, the nonlinear response between speckle motion and observation distance, and the influence of the distance-dependent speckle size. Experiments with the emulated filters illustrate performance and potential applications of the technology.

7.
Endoscopy ; 39(5): 428-33, 2007 May.
Article in English | MEDLINE | ID: mdl-17516349

ABSTRACT

BACKGROUND AND STUDY AIMS: We studied the ability of a photocrosslinkable chitosan in DMEM/F12 medium to maintain submucosal thickness and to reduce bleeding after mucosal resection. We also investigated the behavior of chitosan hydrogels with regard to wound healing. METHODS: The gastric submucosal layer of heparinized rats was injected with the photocrosslinkable chitosan in medium (which was then irradiated with ultraviolet light to form a hydrogel), or with sodium hyaluronate, or hypertonic saline, and three investigations were done, using three different sets of rats. The first and second were measurement of the thickness of the layer, and of the amount of bleeding induced by mucosal resection, respectively. Thirdly, the effects of the chitosan hydrogel on wound healing were examined histologically. RESULTS: Gastric submucosal layers of chitosan hydrogel-treated animals remained significantly thicker than those of other groups for at least 6 h after injection. The total amount of bleeding 20 min after mechanical mucosal resection was 170.0 +/- 20.0 mg, 678.3 +/- 226.3 mg, and 1020.0 +/- 104.1 mg in the chitosan hydrogel, sodium hyaluronate, and hypertonic saline groups, respectively. Histological study revealed that the focus of bleeding was surrounded by chitosan hydrogel and that almost all the hydrogel was biodegraded within 4 weeks. Furthermore, a discernible, but not statistically significant effect of the chitosan hydrogel on wound healing was observed. CONCLUSIONS: The chitosan hydrogel produced mucosal elevation after submucosal injection with ultraviolet irradiation, and it significantly reduced bleeding after mucosal resection. Our newly developed chitosan hydrogel in medium might be a promising submucosal agent for endoscopic mucosal resection.


Subject(s)
Chitosan/administration & dosage , Endoscopy, Gastrointestinal/methods , Gastric Mucosa/pathology , Injections/methods , Animals , Endoscopy, Gastrointestinal/adverse effects , Gastrointestinal Hemorrhage/etiology , Injections/adverse effects , Male , Rats , Rats, Sprague-Dawley
8.
Appl Opt ; 42(14): 2521-2; discussion 2523-5, 2003 May 10.
Article in English | MEDLINE | ID: mdl-12749564

ABSTRACT

This comment demonstrates several errors in the derivation of speckle contrast and corresponding measurements reported by Cheng et at. (Appl. Opt. 41, 4148 (2002)] for a 4f optical system. In particular, the theoretical derivation is wrong: It is used outside of its domain of validity, and the experimental results do not support the theoretical analysis.

9.
Br J Cancer ; 86(11): 1803-12, 2002 Jun 05.
Article in English | MEDLINE | ID: mdl-12087470

ABSTRACT

Periodate-treated, non-anticoagulant heparin-carrying polystyrene consists of about ten periodate-oxidized, alkaline-degraded low molecular weight-heparin chains linked to a polystyrene core and has a markedly lower anti-coagulant activity than heparin. In this study, we evaluated the effect of non-anticoagulant heparin-carrying polystyrene on tumour growth and metastasis. Non-anticoagulant heparin-carrying polystyrene has a higher activity to inhibit vascular endothelial growth factor-165-, fibroblast growth factor-2- or hepatocyte growth factor-induced human microvascular endothelial cell growth than heparin, ten periodate-oxidized-heparin and ten periodate-oxidized-low molecular weight-heparin, which is probably due to the heparin-clustering effect of non-anticoagulant heparin-carrying polystyrene. Non-anticoagulant heparin-carrying polystyrene inhibited human microvascular endothelial cell, B16 melanoma and Lewis lung cancer cell adhesion to Matrigel-coated plates. Non-anticoagulant heparin-carrying polystyrene also showed strong inhibitory activities in the tubular formation of endothelial cells on Matrigel and B16-melanoma and Lewis lung cancer cell invasion in a Matrigel-coated chamber assay. In vivo studies showed that growth of subcutaneous induced tumours and lung metastasis of B16-melanoma and Lewis lung cancer cells were more effectively inhibited by non-anticoagulant heparin-carrying polystyrene than ten periodate-oxidized-heparin and ten periodate-oxidized-low molecular weight-heparin. Furthermore, non-anticoagulant heparin-carrying polystyrene markedly reduced the number of CD34-positive vessels in subcutaneous Lewis lung cancer tumours, indicating a strong inhibition of angiogenesis. These results suggest that non-anticoagulant heparin-carrying polystyrene has an inhibitory activity on angiogenesis and tumour invasion and may be very useful in cancer therapy.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Endothelium, Vascular/cytology , Heparin/pharmacology , Lung Neoplasms/blood supply , Lung Neoplasms/secondary , Polystyrenes/pharmacology , Animals , Cell Division/drug effects , Endothelium, Vascular/drug effects , Fibroblasts/cytology , Fibroblasts/drug effects , Heparin/analogs & derivatives , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Male , Mice , Mice, Inbred C57BL , Microcirculation , Neoplasm Invasiveness , Neoplasm Metastasis/prevention & control , Rabbits , Swine
10.
Surgery ; 130(5): 844-50, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11685194

ABSTRACT

BACKGROUND: In various surgical cases, effective tissue adhesives are required for both hemostasis (eg, intraoperative bleeding) and air sealing (eg, thoracic surgery). We have designed a chitosan molecule (Az-CH-LA) that can be photocrosslinked by ultraviolet (UV) light irradiation, thereby forming a hydrogel. The purpose of this work was to evaluate the effectiveness and safety of the photocrosslinkable chitosan hydrogel as an adhesive with surgical applications. METHODS: The sealing ability of the chitosan hydrogel, determined as a bursting pressure, was assessed with removed thoracic aorta, trachea, and lung of farm pigs and in a rabbit model. The carotid artery and lung of rabbits were punctured with a needle, and the chitosan hydrogel was applied to, respectively, stop the bleeding and the air leakage. In vivo chitosan degradability and biologic responses were histologically assessed in animal models. RESULTS: The bursting pressure of chitosan hydrogel (30 mg/mL) and fibrin glue, respectively, was 225 +/- 25 mm Hg (mean +/- SD) and 80 +/- 20 mm Hg in the thoracic aorta; 77 +/- 29 mm Hg and 48 +/- 21 mm Hg in the trachea; and in the lung, 51 +/- 11 mm Hg (chitosan hydrogel), 62 +/- 4 mm Hg (fibrin glue, rubbing method), and 12 +/- 2 mm Hg (fibrin glue, layer method). The sealing ability of the chitosan hydrogel was stronger than that of fibrin glue. All rabbits with a carotid artery (n = 8) or lung (n = 8) that was punctured with a needle and then sealed with chitosan hydrogel survived the 1-month observation period without any bleeding or air leakage from the puncture sites. Histologic examinations demonstrated that 30 days after application, a fraction of the chitosan hydrogel was phagocytosed by macrophages, had partially degraded, and had induced the formation of fibrous tissues around the hydrogel. CONCLUSIONS: A newly developed photocrosslinkable chitosan has demonstrated strong sealing ability and a great potential for use as an adhesive in surgical operations.


Subject(s)
Biological Dressings , Chitin , Animals , Chitin/analogs & derivatives , Chitosan , Hydrogel, Polyethylene Glycol Dimethacrylate , Lung/pathology , Lung/surgery , Male , Pressure , Rabbits , Swine
11.
J Biomed Mater Res ; 56(4): 536-44, 2001 Sep 15.
Article in English | MEDLINE | ID: mdl-11400131

ABSTRACT

Heparin-carrying polystyrene (HCPS), consisting of low molecular weight heparin chains linked to a synthetic polystyrene core, is able to attach to polymeric surfaces. In this study, HCPS has efficiently bound to collagen-coated micro-plates and collagen membranes thereby retaining the binding of heparin-binding growth factors, such as vascular endothelial growth factor (VEGF)(165) or fibroblast growth factor (FGF)-2. Both human skin fibroblast cells and human umbilical vein endothelial cells have shown a good adherence to both collagen- and HCPS-bound collagen substrata. The growth rate of the fibroblast cells on the HCPS-bound collagen substratum in the presence of low concentrations of FGF-2 is higher than on a collagen surface. The fibroblast cells grow at a significantly higher rate on the HCPS-bound collagen substratum retained with FGF-2. Similarly, the growth rate of the endothelial cells on the HCPS-bound collagen substrata in the presence of low concentrations of either FGF-2 or VEGF(165) is higher than on collagen. The endothelial cells also grow at a significantly higher rate on the HCPS-bound collagen substratum retained with either FGF-2 or VEGF(165). These results indicate that HCPS-bound collagen substrata with various bioactive heparin-binding molecules may provide novel biomaterials controlling cellular activities such as growth and differentiation.


Subject(s)
Biocompatible Materials , Collagen , Endothelium, Vascular , Polystyrenes , Cell Adhesion , Cell Division/drug effects , Cells, Cultured , Cells, Immobilized , Endothelial Growth Factors/pharmacology , Endothelium, Vascular/growth & development , Fibroblast Growth Factor 2/pharmacology , Heparin , Humans , Lymphokines/pharmacology , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
12.
Wound Repair Regen ; 9(6): 513-21, 2001.
Article in English | MEDLINE | ID: mdl-11896994

ABSTRACT

Application of ultraviolet light irradiation to a photocrosslinkable chitosan aqueous solution resulted in an insoluble, flexible hydrogel like soft rubber within 60 seconds. In order to evaluate its accelerating effect on wound healing, full-thickness skin incisions were made on the backs of mice and subsequently a photocrosslinkable chitosan aqueous solution was added into the wound and irradiated with UV light for 90 seconds. Application of the chitosan hydrogel significantly induced wound contraction and accelerated wound closure and healing compared with the untreated controls. Histological examination also showed an advanced contraction rate on the first 2 days and tissue fill rate on days 2 to 4 in the chitosan hydrogel-treated wounds. Furthermore, in cell culture studies, chitosan hydrogel culture medium supplemented with 5% fetal-bovine serum was found to be chemoattractant for human dermal fibroblasts in an invasion chamber assay using filters coated with Matrigel and in a cell migration assay. Due to its ability to accelerate wound contraction and healing, chitosan hydrogel may become accepted as an occlusive dressing for wound management.


Subject(s)
Biocompatible Materials/administration & dosage , Biopolymers/administration & dosage , Chitin/administration & dosage , Wound Healing/drug effects , Animals , Cell Movement , Cells, Cultured , Chitin/analogs & derivatives , Chitosan , Cross-Linking Reagents , Female , Fibroblasts/drug effects , Fibroblasts/physiology , Hydrogels , Mice , Mice, Inbred C57BL , Skin/cytology , Wound Healing/physiology
13.
J Biochem ; 127(5): 797-803, 2000 May.
Article in English | MEDLINE | ID: mdl-10788788

ABSTRACT

Heparin-carrying polystyrene (HCPS) consists of low-molecular-weight heparin chains enriched in trisulfated disaccharide structures linked to a polystyrene core. In this study, the interactions between HCPSs of various molecular weights and heparin-binding growth factors, VEGF(165), FGF-2, and HGF, were compared to the interactions of the same factors with native heparin, periodate-oxidized heparin (IO(4)-heparin) and periodate-oxidized alkaline-degraded heparin (IO(4)-LMW-heparin). The binding of each growth factor to heparin-agarose beads (heparin-beads) was more strongly inhibited by HCPSs in a molecular weight-dependent manner than by native heparin or the modified heparins, indicating a stronger interaction between HCPS and these growth factors. HCPSs also inhibit heparin-binding growth factor-induced endothelial cell growth in a molecular weight-dependent manner much more strongly than the native or modified heparins. However, HCPSs did not inhibit the mitogenic activity of VEGF(121), which has a non-heparin-binding nature. Thus, HCPSs exhibit enhanced abilities to interact with each of the heparin-binding growth factors studied and to inhibit heparin-binding growth factor-induced endothelial cell proliferation in a molecular weight-dependent manner. These effects might be ascribed to the heparin-clustering effect of HCPSs.


Subject(s)
Drug Carriers/pharmacology , Endothelium, Vascular/drug effects , Growth Substances/metabolism , Heparin/pharmacology , Polystyrenes/pharmacology , Coronary Vessels/cytology , Disaccharides/analysis , Drug Carriers/chemistry , Endothelial Growth Factors/metabolism , Endothelium, Vascular/cytology , Fibroblast Growth Factor 2/metabolism , Glycoconjugates/chemistry , Glycoconjugates/pharmacology , Growth Inhibitors/pharmacology , Heparin/chemistry , Hepatocyte Growth Factor/metabolism , Humans , Lymphokines/metabolism , Polystyrenes/chemistry , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
14.
J Opt Soc Am A Opt Image Sci Vis ; 17(3): 484-90, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10708029

ABSTRACT

We have developed a new theoretical description of the optical coherence tomography (OCT) technique for imaging in highly scattering tissue. The description is based on the extended Huygens-Fresnel principle, valid in both the single- and multiple-scattering regimes. The so-called shower curtain effect, which manifests itself in a standard OCT system, is an inherent property of the present theory. We demonstrate that the shower curtain effect leads to a strong increase in the heterodyne signal in a standard OCT system. This is in contrast to previous OCT models, where the shower curtain effect was not taken into account. The theoretical analysis is verified by measurements on samples consisting of aqueous suspensions of microspheres. Finally, we discuss the use of our new theoretical model for optimization of the OCT system.


Subject(s)
Models, Theoretical , Optics and Photonics , Tomography
15.
J Biomed Mater Res ; 50(2): 144-52, 2000 May.
Article in English | MEDLINE | ID: mdl-10679678

ABSTRACT

Various sugar-carrying polystyrenes (PSs), which consist of synthetic styrene and sugar moieties, are glycoconjugates that are able to attach to polymeric surfaces. Heparin-carrying PS (HCPS) is especially able to retain the binding of heparin-binding growth factors (GFs) such as vascular endothelial GF 165 (VEGF(165)) or fibroblast GF 2 (FGF-2). Human skin fibroblast cells, human coronary smooth muscle cells, and human coronary endothelial cells have good adherence to the HCPS-coated plate. The growth rate of fibroblast cells on HCPS-coated plates is higher than or comparable to fibronectin-coated, gelatin-coated, or tissue culture treated plates, and the HCPS coating inhibits the growth of smooth muscle cells. On the other hand, the growth rate of endothelial cells on HCPS-coated plates in the presence of either VEGF(165) or FGF-2 is comparable to that on fibronectin-coated, gelatin-coated, and tissue culture treated plates. Endothelial cells grow at a higher rate on HCPS-coated plates retained with either VEGF(165) or FGF-2 than on the other coated plates. These results indicate that growth of various cells can be controlled by the HCPS coating, thereby retaining the bioactivity of molecules such as heparin-binding GFs. Thus, HCPS-coated surfaces control selective growth of various cells.


Subject(s)
Biocompatible Materials , Endothelium, Vascular , Fibroblasts , Heparin , Muscle, Smooth, Vascular , Polystyrenes , Cell Adhesion , Cell Division , Cells, Cultured , Endothelium, Vascular/drug effects , Fibroblasts/drug effects , Humans , Muscle, Smooth, Vascular/drug effects
16.
J Opt Soc Am A Opt Image Sci Vis ; 17(12): 2464-74, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11140505

ABSTRACT

Within the paraxial approximation, a closed-form solution for the Wigner phase-space distribution function is derived for diffuse reflection and small-angle scattering in a random medium. This solution is based on the extended Huygens-Fresnel principle for the optical field, which is widely used in studies of wave propagation through random media. The results are general in that they apply to both an arbitrary small-angle volume scattering function, and arbitrary (real) ABCD optical systems. Furthermore, they are valid in both the single- and multiple-scattering regimes. Some general features of the Wigner phase-space distribution function are discussed, and analytic results are obtained for various types of scattering functions in the asymptotic limit s >> 1, where s is the optical depth. In particular, explicit results are presented for optical coherence tomography (OCT) systems. On this basis, a novel way of creating OCT images based on measurements of the momentum width of the Wigner phase-space distribution is suggested, and the advantage over conventional OCT images is discussed. Because all previous published studies regarding the Wigner function are carried out in the transmission geometry, it is important to note that the extended Huygens-Fresnel principle and the ABCD matrix formalism may be used successfully to describe this geometry (within the paraxial approximation). Therefore for completeness we present in an appendix the general closed-form solution for the Wigner phase-space distribution function in ABCD paraxial optical systems for direct propagation through random media, and in a second appendix absorption effects are included.

17.
J Biomed Mater Res ; 49(2): 289-95, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10571917

ABSTRACT

A photocrosslinkable chitosan to which both azide and lactose moieties were introduced (Az-CH-LA) was prepared as a biological adhesive for soft tissues and its effectiveness was compared with that of fibrin glue. Introduction of the lactose moieties resulted in a much more water-soluble chitosan at neutral pH. Application of ultraviolet light (UV) irradiation to photocrosslinkable Az-CH-LA produced an insoluble hydrogel within 60 s. This hydrogel firmly adhered two pieces of sliced ham with each other, depending upon the Az-CH-LA concentration. The binding strength of the chitosan hydrogel prepared from 30-50 mg/mL of Az-CH-LA was similar to that of fibrin glue. Compared to the fibrin glue, the chitosan hydrogel more effectively sealed air leakage from pinholes on isolated small intestine and aorta and from incisions on isolated trachea. Neither Az-CH-LA nor its hydrogel showed any cytotoxicity in cell culture tests of human skin fibroblasts, coronary endothelial cells, and smooth muscle cells. Furthermore, all mice studied survived for at least 1 month after implantation of 200 microL of photocrosslinked chitosan gel and intraperitoneal administration of up to 1 mL of 30 mg/mL of Az-CH-LA solution. These results suggest that the photocrosslinkable chitosan developed here has the potential of serving as a new tissue adhesive in medical use.


Subject(s)
Biocompatible Materials , Biopolymers , Chitin/analogs & derivatives , Animals , Cell Adhesion , Chitosan , Cross-Linking Reagents , Hemostasis , Humans , Mice
18.
J Control Release ; 57(1): 87-99, 1999 Jan 04.
Article in English | MEDLINE | ID: mdl-10084872

ABSTRACT

A novel macromolecular prodrug of Tacrolimus (FK506), FK506-dextran conjugate, was developed and its physico-chemical, biological and pharmacokinetic characteristics were studied. The conjugate was estimated to contain 0.45% of FK506 and the coupling molar ratio was approximately 1:1 (dextran-FK-506). Adsorption experiments using ion exchangers indicated that FK506-dextran conjugate acted as a weakly negatively charged macromolecule. Low molecular weight radioactive compound(s), which was eluted in the same fractions as [(3)H]FK506, was released from [(3)H]FK506-dextran conjugate by chemical hydrolysis with a half-life of 150 h in phosphate buffer. In vitro immunosuppressive activity of the conjugate, as assessed by the rat lymphocyte stimulation test, was almost comparable to that of free FK506, suggesting that biologically active FK506 could be liberated from the conjugate. In vitro biodistribution studies demonstrated that conjugation with the dextran derivative dramatically changed the pharmacokinetic properties of FK506 after intravenous injection in rats. AUC of the FK506-dextran conjugate was almost 2000 times higher than that of free FK506 and organ uptake clearances of the conjugate were significantly smaller than those of the free drug. Thus, the present study has demonstrated that the FK506-dextran conjugate behaves as a prodrug of FK506 with an extended blood circulating time and can be expected to have an improved therapeutic potency.


Subject(s)
Immunosuppressive Agents/chemical synthesis , Immunosuppressive Agents/pharmacokinetics , Tacrolimus/chemical synthesis , Tacrolimus/pharmacokinetics , Animals , Area Under Curve , Carbohydrate Sequence , Delayed-Action Preparations , Dextrans , Electrochemistry , Ethylenediamines , Immunosuppressive Agents/pharmacology , Kidney/metabolism , Liver/metabolism , Lymphocytes/drug effects , Lymphocytes/immunology , Male , Molecular Sequence Data , Rats , Rats, Inbred Lew , Tacrolimus/pharmacology , Tissue Distribution
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