Because compact solid-state blue/green lasers can generate high power, and short wavelength radiation, it is applied in micromaching, laser display, underwater ranging, and so forth. It is a very cost-effective approach to develop such lasers, if the laser output characteristics can be estimated precisely using software simulation. The purpose of this study is to use an optics software GLAD (General Laser Analysis and Design) to model our intracavity frequency-doubled blue/green lasers. The GLAD software considers the wave nature of laser, such as dispersion and diffraction. Moreover, it employs a modular design in modeling linear or nonlinear optical components. In order to get more precised estimation of the laser output characteristics of a quasi-three-level laser, the laser model in GLAD was modified to take into account the reabsorption loss in gain medium. In our experiment, blue/green microchip lasers were developed. We used a 3W LD to pump a quasi-three-level laser with the Nd:YAG crystal as gain medium and KNbO3 crystal as the intracavity SHG crystal for the generation of blue laser. The laser generates 17.6 mW of blue power with a cavity length of 4 mm. With almost the same structure except using Nd:YVO4 crystal as gain medium and KTP crystal as the intracavity SHG crystal for generation of green laser, the laser produces 627 mW of green power with a cavity length of 6 mm.

Sacoglossa belongs to the Subclass of Opithsobrabchia (Class: Gastropoda). There are about 300 species in the world. The radula of Sacoglossa is composed of ascending limb, descending limb, and a ascus sac to store used teeth. This ascus sac is a unique character of sacoglossans in mollusus. In this study, I compared the morphology, and the composition of elements in sacoglossan radulae. A total of 16 species in 5 families, including 12 new records, has been observed. Their teeth morphology was triangular or blade-like. The radula sac is surrounded by a layer of epithelium cells and the arrangement of the teeth in the sac was linear, dense or fraction. Positive correlations between body length and the number of ascending radular teeth, descending radular teeth, teeth in ascus sac or the total number of teeth were found except for Volvatella vigourouxi (Family: Volvatellidae). The elemental compositions in various radula parts were examined by energy dispersive spectrometer. I found that sacoglossan teeth were composited by Fe, Na, Mg, Si, P, S and Ca, and no significant difference among parts but significantly different among species. In contrast, elemental compositions of sacoglossans were significantly different from Tambja sp. (Order: Nudibranchia), Aplysia parvula (Order: Anaspidea) and Cellana toreuma (Order: Archaeogastropoda). In the meantime, sacoglossans and Tambja sp. were closer than others. Additionally, hollow or broken teeth were found in some sacogloosan ascus indicates that tooth reabsorption may present. However, further study is necessary to elucidate the reabsorption mechanism.

Nephrotic syndrome (NS) is a set of symptoms defined by heavy proteinuria and associated with a host of kidney diseases that cause injury to the glomerulus, the filtration apparatus of the kidney. Primary podocytopathies (Px), a group of diseases including minimal change disease (MCD), primary focal segmental sclerosis (pFSGS), and lupus podocytopathy (LP), are the principal cause of idiopathic NS in both children and adults. The hallmark feature of Px is the ultrastructural finding of podocyte foot process effacement (FPE), so current differential diagnosis of Px relies on technically exhaustive electron microscopy (EM) analysis. During routine immunofluorescence (IF) microscopy of many Px cases, we have observed punctate IgG (P-IgG) immunoreactivity in the glomerulus. P-IgG may represent a disease-specific reactivity that could not only provide clues for understanding Px etiology but could also serve as a diagnostic tool. However, we have found that P-IgG may be misinterpreted as protein reabsorption granules (PRGs), a morphological feature seen in proteinuric conditions. We sought to definitively characterize the key characteristics of PRGs and P-IgG in order to differentiate these features. To accomplish this, we reviewed prior IF immunostaining of MCD biopsies to evaluate anti-human IgG and anti-human albumin staining. We conducted additional IF staining on archived MCD biopsies using antibodies against IgG and against the markers of PRGs: albumin, megalin, and cubilin. We found that the P-IgG demonstrates a diffuse, global distribution pattern that is specific to glomerular epithelium and is fine and scattered. Conversely, the PRGs are coarse, clustered, and frequently demonstrate a focal, segmental pattern in the glomeruli and tubules. Co-staining with albumin and megalin revealed that the P-IgG and the PRGs do not colocalize in the tissue. While the cubilin antibody positively stained the tubular epithelium, it did not stain glomeruli. Our results showed that punctate IgG and protein reabsorption granules are morphologically and constitutionally distinct and do not colocalize with each other, indicating that P-IgG is highly likely to represent a distinct process from epithelial protein reabsorption.

The organic anion transporting polypeptide 4c1 (Oatp4c1) was previously identified as a novel uptake transporter predominantly expressed at the basolateral membrane in the rat kidney proximal tubules. Its functional role was suggested to be a vectorial transport partner of an apically-expressed efflux transporter for the efficient translocation of physiological substrates into urine, some of which were suggested to be uremic toxins. In vitro studies in polarized cell lines showed that upon transfection rat Oatp4c1 localizes at the apical membrane. The objectives of this project were to further validate the subcellular localization of Oatp4c1/OATP4C1 in rat and human tissues as well as their localization and function in polarized cells. Using several complementary biochemical, molecular and proteomic methods as well as antibodies amenable to immunohistochemistry, immunofluorescence, and immunoblotting, we investigated the expression pattern of Oatp4c1 in epithelial cell lines and in the rat kidney and mammary gland (MG). Collectively, these data demonstrated that rat Oatp4c1 localized at the apical cell surface of polarized epithelium and primarily in the proximal straight tubules, the S3 segment of proximal tubule, in the juxtamedullary cortex. Drug uptake studies in Oatp4c1-expressing cells demonstrated that Oatp4c1- mediated estrone-3-sulfate (E3S) uptake was ATP-independent and pH-dependent. The increased E3S transport activity at acidic extracellular pH was ascribed to the increased maximum transport rate (Vmax). In addition, E3S transport inhibition by various substrates suggests that Oatp4c1 possesses multiple substrate binding sites. The apical localization of Oatp4c1 in the rat kidney and MG is a novel finding and implies that this transporter protein plays a role in the reabsorption, not vectorial secretion, of its substrates. In addition, the upregulation of Oatp4c1 expression during lactation indicates that it is involved in reuptake of xenobiotic from the milk, resulting in their reduced exposure to the suckling infants, or that it functions as a scavenger system. Further, studies to identify physiological substrates are needed to better understand the significance of Oatp4c1 function in renal and mammary epithelium.

Os bisfosfonatos são drogas capazes de inibir a reabsorção óssea por meio de seu efeito direto sobre as células ósseas, interferindo na dinâmica dos tecidos mineralizados. O alendronato (ALN), um tipo de bisfosfonato nitrogenado, foi utilizado com o objetivo de investigar os seus efeitos sobre os tecidos dentários e periodontais após luxação lateral de molares com as raízes em desenvolvimento. Ratos Wistar com 21 dias de idade tiveram os segundos molares superiores luxados lateralmente. Doses diárias de 2,5 mg / kg de ALN começaram no dia seguinte à luxação; os controles receberam solução salina estéril. As maxilas foram fixadas, descalcificadas e incluídas em parafina ou em resina Spurr 7, 14 e 21 dias pós-luxação. Os cortes foram corados com H & E, incubados por histoquímica TRAP e imuno marcados para osteopontina (OPN), bem como para análise ultraestrutural. Após 21 dias, o ápice dos molares luxados sem ALN estava aberto e desorganizado, coberto por uma camada irregular de cemento celular. Os molares luxados dos animais tratados com ALN apresentaram alguns locais de anquilose, bem como lacunas de reabsorção na superfície do cemento. Os osteoclastos TRAP positivos foram mais numerosos no grupo ALN, apesar de sua aparência latente e sua localização, afastados das trabéculas ósseas, em relação aos controles, achado que foi confirmado com a análise ultraestrutural. A imunomarcação de OPN revelou uma linha grossa imunopositiva na dentina, que deve ter surgido a partir do momento da luxação, enquanto que as amostras tratadas com ALN não apresentaram alterações na dentina. Os resultados indicam que o alendronato inibe algumas alterações na dentina e na formação do cemento, induzidas pelo trauma dental de luxação. / Bisphosphonates are drugs that inhibit bone resorption through its direct effect on bone cells, interfering with the dynamics of mineralized tissues. Alendronate (ALN), a nitrogenated bisphosphonate, was used in order to investigate their effects on dental and periodontal tissues after lateral dislocation of molars with developing roots. Twenty one days old Wistar rats had their second molars laterally l. Daily doses of 2.5 mg / kg ALN started the day following the dislocation, while controls received saline solution. The maxillae were fixed, decalcified and embedded in paraffin or in Spurr resin after 7, 14 and 21 days post-dislocation. The sections were stained with H & E, incubated for TRAP, immunolabeled for osteopontin (OPN), and ultrastructurally analyzed by transmission electron microscopy. After 21 days, the apex of the luxated molar without ALN was open and disorganized, covered by an irregular layer of cellular cementum. The luxated molar from ALN-treated animals showed some areas of ankylosis and resorption lacunae on the cementum surface. TRAP-positive osteoclasts were more numerous in the ALN group, despite their latent appearance compared to controls, a finding that was ultrastructurally confirmed. OPN immunostaining revealed a thick immunopositive line in dentin, which must be resultant from the moment of dislocation, while the samples treated with ALN showed no changes in dentin. The results indicate that alendronate inhibits some changes in dentin and cementum formation induced by dental trauma of lateral luxation.

Uroguanilina (UGN) é um peptídeo normalmente sintetizado no intestino que modula o balanço de sódio através de ações renais. Investigamos os efeitos e os mecanismos de sinalização envolvidos na ação da UGN sobre a secreção de H+, em túbulos renais de ratos e em células LLC-PK1 (proximais) e MDCK-C11 (distais). Nos estudos in vivo foi utilizada a técnica de microperfusão estacionária, na qual medimos a secreção de H+ em túbulos proximais e distais de rins de rato, utilizando um microeletrodo sensível a H+. Nos estudos in vitro, para medir a atividade de NHE3 e H+-ATPase, utilizamos microscopia de fluorescência, usando BCECF como sonda sensível a pH. Nossos dados indicam que UGN inibe a secreção de hidrogênio em túbulos proximais e em células LLC-PK1 por um mecanismo dependente da inibição do permutador NHE3, envolvendo a ativação de PKG e PKA. Nosso estudo também sugere que UGN inibe a secreção de hidrogênio em túbulos distais de rato e em células MDCK-C11, envolvendo a inibição da atividade da H+-ATPase por um mecanismo dependente de PKG / Uroguanylin (UGN) is a peptide usually synthesized in the intestine that modulates sodium balance through actions on the kidney. We investigate the effects and signaling mechanisms involved in the UGN action on hydrogen secretion in rat renal tubules and in LLC-PK1 and MDCK-C11 cells. In the in vivo studies we used the stationary microperfusion method, measuring hydrogen secretion in proximal and distal tubules by a H+ sensitive microelectrode. In the in vitro studies, we used fluorescence microscopy to measure the activity of NHE3 and H+-ATPase, using BCECF as pH sensitive dye. Our data indicate that UGN inhibits the hydrogen secretion in proximal tubules and in LLC-PK1 cells by a mechanism dependent on the inhibition of NHE3, involving the activation of PKG and PKA. Our study also suggests that UGN inhibits hydrogen secretion in distal tubules and MDCK-C11 cells., and the inhibition of H+-ATPase by a mechanism dependent on PKG is involved in this distal effect of UGN.

<p>Several studies have reported beneficial effects of C-peptide supplementation in diabetic patients and animal models of insulinopenic diabetes. However, it is also established that good glycemic control is essential to minimize the risk of diabetes-induced complications. This thesis investigates potential mechanisms for the beneficial effect of C-peptide on glomerular hyperfiltration, and a novel, painless route of insulin administration.</p><p>The results demonstrate that both C-peptide and its C-terminal penta-peptide sequence reduce the diabetes-induced glomerular hyperfiltration within an hour. The results also indicate that C-peptide possibly reduces diabetes-induced hyperfiltration via three different mechanisms: 1. Constriction of the afferent arteriole was demonstrated on isolated vessels from diabetic mice. 2. A net dilation of the efferent arteriole was evident <i>in vivo</i>. 3. Inhibition of the Na⁺/K⁺-ATPase was demonstrated <i>in vivo</i> in diabetic rats as well as <i>in vitro</i> on isolated proximal tubular cells from diabetic rats. All these mechanisms are known regulators of the net glomerular filtration pressure.</p><p>The last part of this thesis demonstrates that intradermal administration with a newly developed patch-like microneedle device results in similar insulin concentration compared to standard subcutaneous delivery. </p><p>These findings provide an insight for the beneficial effects of C-peptide on diabetic kidney function, and shows that this effect can be achieved by infusion of the C-terminal penta-peptide sequence alone. This thesis also presents a novel, painless alternative to insulin injections that is controllable, requires minimal training, and therefore presents several advantages compared to current standard therapy.</p>

The purpose of this study is to develop a solid-state blue laser which has advantages of high power, short wavelength, and compact. It can be applied in micromaching, LIDAR, underwater ranging, biochemical techniques, and so forth. We increased the peak power of the laser effectively by a low-cost, small, and easy-use passive Q-switching technique. In addition, intracavity frequency-doubling is an economic way to achieve non-linear frequency conversion for blue generation. By integrating of these two techniques, we develop a compact all solid-state high-power blue laser with 83 W peak power at 473 nm. Restricted to reabsorption loss, the optical to optical conversion efficiency of 4F3/2 ¡÷ 4I9/2 quasi-three-level laser is lower than 4F3/2 ¡÷ 4I11/2 four-level laser for Nd:YAG crystal. The reabsorption loss will change with the temperature variation of the gain medium, it enormously affects to the performance and stability of quasi-three-level lasers. Therefore, in addition to make systematic studies of the conversion efficiency of KNbO3, BBO, LBO as the intracavity SHG crystals for generation of high-power blue laser, we use the numerical analysis to investigate the influence of reabsorption loss to quasi-three-level passive Q-switching laser. At present, blue laser with peak power of 83 W and pulse width of 10.6 ns was generated as a result. To our knowledge, the compact all solid-state high-power pulsed blue laser is demonstrated for the first time by integrating of passive Q-switching and intracavity frequency-doubling simultaneously.

Several studies have reported beneficial effects of C-peptide supplementation in diabetic patients and animal models of insulinopenic diabetes. However, it is also established that good glycemic control is essential to minimize the risk of diabetes-induced complications. This thesis investigates potential mechanisms for the beneficial effect of C-peptide on glomerular hyperfiltration, and a novel, painless route of insulin administration. The results demonstrate that both C-peptide and its C-terminal penta-peptide sequence reduce the diabetes-induced glomerular hyperfiltration within an hour. The results also indicate that C-peptide possibly reduces diabetes-induced hyperfiltration via three different mechanisms: 1. Constriction of the afferent arteriole was demonstrated on isolated vessels from diabetic mice. 2. A net dilation of the efferent arteriole was evident in vivo. 3. Inhibition of the Na+/K+-ATPase was demonstrated in vivo in diabetic rats as well as in vitro on isolated proximal tubular cells from diabetic rats. All these mechanisms are known regulators of the net glomerular filtration pressure. The last part of this thesis demonstrates that intradermal administration with a newly developed patch-like microneedle device results in similar insulin concentration compared to standard subcutaneous delivery. These findings provide an insight for the beneficial effects of C-peptide on diabetic kidney function, and shows that this effect can be achieved by infusion of the C-terminal penta-peptide sequence alone. This thesis also presents a novel, painless alternative to insulin injections that is controllable, requires minimal training, and therefore presents several advantages compared to current standard therapy.

Uroguanilina (UGN) é um peptídeo normalmente sintetizado no intestino que modula o balanço de sódio através de ações renais. Investigamos os efeitos e os mecanismos de sinalização envolvidos na ação da UGN sobre a secreção de H+, em túbulos renais de ratos e em células LLC-PK1 (proximais) e MDCK-C11 (distais). Nos estudos in vivo foi utilizada a técnica de microperfusão estacionária, na qual medimos a secreção de H+ em túbulos proximais e distais de rins de rato, utilizando um microeletrodo sensível a H+. Nos estudos in vitro, para medir a atividade de NHE3 e H+-ATPase, utilizamos microscopia de fluorescência, usando BCECF como sonda sensível a pH. Nossos dados indicam que UGN inibe a secreção de hidrogênio em túbulos proximais e em células LLC-PK1 por um mecanismo dependente da inibição do permutador NHE3, envolvendo a ativação de PKG e PKA. Nosso estudo também sugere que UGN inibe a secreção de hidrogênio em túbulos distais de rato e em células MDCK-C11, envolvendo a inibição da atividade da H+-ATPase por um mecanismo dependente de PKG / Uroguanylin (UGN) is a peptide usually synthesized in the intestine that modulates sodium balance through actions on the kidney. We investigate the effects and signaling mechanisms involved in the UGN action on hydrogen secretion in rat renal tubules and in LLC-PK1 and MDCK-C11 cells. In the in vivo studies we used the stationary microperfusion method, measuring hydrogen secretion in proximal and distal tubules by a H+ sensitive microelectrode. In the in vitro studies, we used fluorescence microscopy to measure the activity of NHE3 and H+-ATPase, using BCECF as pH sensitive dye. Our data indicate that UGN inhibits the hydrogen secretion in proximal tubules and in LLC-PK1 cells by a mechanism dependent on the inhibition of NHE3, involving the activation of PKG and PKA. Our study also suggests that UGN inhibits hydrogen secretion in distal tubules and MDCK-C11 cells., and the inhibition of H+-ATPase by a mechanism dependent on PKG is involved in this distal effect of UGN.