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The perfect-fluid cosmology in the (1 + d + D)-dimensional Kaluza-Klein space-times for an arbitrary barotropic equation of state p = (gamma - 1)rho is quantized by using the Schutz's variational formalism. We make efforts in the ...
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The perfect-fluid cosmology in the (1 + d + D)-dimensional Kaluza-Klein space-times for an arbitrary barotropic equation of state p = (gamma - 1)rho is quantized by using the Schutz's variational formalism. We make efforts in the mathematics to solve the problems in two cases. In the first case of the stiff fluid gamma = 2 we exactly solve the Wheeler-DeWitt equation when the d space is flat. After the superposition of the solutions the wave-packet function is obtained exactly. We analyze the Bohmian trajectories of the final-stage wave-packet functions and show that the scale functions of the flat d spaces and the compact D spaces will eventually evolve into the nonzero finite values. In the second case of gamma approximate to 2, we use the approximated wave function in the Wheeler-DeWitt equation to find the analytic forms of the final-stage wave-packet functions. After analyzing the Bohmian trajectories we show that the flat d spaces will be expanding forever while the scale function of the contracting D spaces would not become zero within finite time. Our investigations indicate that the quantum effect in the quantum perfect-fluid cosmology could prevent the extra compact D spaces in the Kaluza-Klein theory from collapsing into a singularity or that the "crack-of-doom" singularity of the extra compact dimensions is made to occur at t = infinity.
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Conditional deletion of the mouse Forkhead Box (Fox) m1b targeted allele in adult hepatocytes (Foxm1, previously called HFH-11B, Trident, Win, or MPP2) demonstrated that the Foxm1b transcription factor is essential for hepatocyte ...
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Conditional deletion of the mouse Forkhead Box (Fox) m1b targeted allele in adult hepatocytes (Foxm1, previously called HFH-11B, Trident, Win, or MPP2) demonstrated that the Foxm1b transcription factor is essential for hepatocyte mitosis during liver regeneration. To determine the role of Foxm1b in liver development, we have generated Foxm1b -/- mice that deleted the Foxm1b exons encoding the winged helix DNA binding and transcriptional activation domains. Here, we show that all of the Foxm1b -/- embryos died in utero by 18.5 days postcoitum (dpc). Embryonic Foxm1b -/- livers displayed a 75% reduction in the number of hepatoblasts, resulting from diminished DNA replication and a failure to enter mitosis causing a polyploid phenotype. Reduced hepatoblast mitosis was associated with decreased protein levels of the Polo-like kinase 1 and Aurora B kinase, which phosphorylate regulatory proteins essential for orchestrating mitosis and cytokinesis. Diminished proliferation of Foxm1b -/- hepatoblasts contributed to abnormal liver development with significant reduction in the number of large hepatic veins compared to embryonic wild-type (WT) liver. Furthermore, embryonic Foxm1b -/- livers did not develop intrahepatic bile ducts, and these presumptive biliary hepatoblasts failed to express either biliary cytokeratins or nuclear levels of hepatocyte nuclear factor 1beta. These results suggest that Foxm1b is critical for hepatoblast precursor cells to differentiate toward biliary epithelial cell lineage. Finally, we used a hepatoblast-specific Cre recombinase transgene to mediate deletion of the Foxm1b fl/fl allele in the developing liver, and these embryos died in utero and exhibited diminished hepatoblast proliferation with similar abnormalities in liver morphogenesis, suggesting that the defect in liver development contributed to embryonic lethality.
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Foxm1 is a member of the Forkhead Box (Fox) family of transcription factors. Foxm1 (previously called Foxm1b, HFH-11B, Trident, Win, or MPP2) is expressed in multiple cell types and plays important roles in cellular proliferation,...
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Foxm1 is a member of the Forkhead Box (Fox) family of transcription factors. Foxm1 (previously called Foxm1b, HFH-11B, Trident, Win, or MPP2) is expressed in multiple cell types and plays important roles in cellular proliferation, differentiation and tumorigenesis. Genetic deletion of Foxm1 from mouse respiratory epithelium during initial stages of lung development inhibits lung maturation and causes respiratory failure after birth. However, the role of Foxm1 during postnatal lung morphogenesis remains unknown. In the present study, Foxm1 expression was detected in epithelial cells of conducting and peripheral airways and changing dynamically with lung maturation. To discern the biological role of Foxm1 in the prenatal and postnatal lung, a novel transgenic mouse line that expresses a constitutively active form of FoxM1 (FoxM1 N-terminal deletion mutant or FoxM1-DeltaN) under the control of lung epithelial-specific SPC promoter was produced. Expression of the FoxM1-DeltaN transgene during embryogenesis caused epithelial hyperplasia, inhibited lung sacculation and expression of the type II epithelial marker, pro-SPC. Expression of FoxM1-DeltaN mutant during the postnatal period did not influence alveologenesis but caused focal airway hyperplasia and increased proliferation of Clara cells. Likewise, expression of FoxM1-DeltaN mutant in conducting airways with Scgb1a1 promoter was sufficient to induce Clara cell hyperplasia. Furthermore, FoxM1-DeltaN cooperated with activated K-Ras to induce lung tumor growth in vivo. Increased activity of Foxm1 altered lung sacculation, induced proliferation in the respiratory epithelium and accelerated lung tumor growth, indicating that precise regulation of Foxm1 is critical for normal lung morphogenesis and development of lung cancer.
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The forkhead box m1 (Foxm1 or Foxm1b) transcription factor (previously called HFH-11B, Trident, Win, or MPP2) is expressed in a variety of tissues during embryogenesis, including vascular, airway, and intestinal smooth muscle cell...
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The forkhead box m1 (Foxm1 or Foxm1b) transcription factor (previously called HFH-11B, Trident, Win, or MPP2) is expressed in a variety of tissues during embryogenesis, including vascular, airway, and intestinal smooth muscle cells (SMCs). Although global deletion of Foxm1 in Foxm1(-/-) mice is lethal in the embryonic period due to multiple abnormalities in the liver, heart, and lung, the specific role of Foxm1 in SMC remains unknown. In the present study, Foxm1 was deleted conditionally in the developing SMC (smFoxm1(-/-) mice). The majority of smFoxm1(-/-) mice died immediately after birth due to severe pulmonary hemorrhage and structural defects in arterial wall and esophagus. Although Foxm1 deletion did not influence SMC differentiation, decreased proliferation of SMC was found in smFoxm1(-/-) blood vessels and esophagus. Depletion of Foxm1 in cultured SMC caused G(2) arrest and decreased numbers of cells undergoing mitosis. Foxm1-deficiency in vitro and in vivo was associated with reduced expression of cell cycle regulatory genes, including cyclin B1, Cdk1-activator Cdc25b phosphatase, Polo-like 1 and JNK1 kinases, and cMyc transcription factor. Foxm1 is critical for proliferation of smooth muscle cells and is required for proper embryonic development of blood vessels and esophagus.
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The Forkhead Box m1 (Foxm1) transcription factor is expressed in cardiomyocytes and cardiac endothelial cells during heart development. In this study, we used a novel Foxm1 -/- mouse line to demonstrate that Foxm1-deletion causes ...
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The Forkhead Box m1 (Foxm1) transcription factor is expressed in cardiomyocytes and cardiac endothelial cells during heart development. In this study, we used a novel Foxm1 -/- mouse line to demonstrate that Foxm1-deletion causes ventricular hypoplasia and diminished DNA replication and mitosis in developing cardiomyocytes. Proliferation defects in Foxm1 -/- hearts were associated with a reduced expression of Cdk1-activator Cdc25B phosphatase and NFATc3 transcription factor, and with abnormal nuclear accumulation of the Cdk-inhibitor p21(Cip1) protein. Depletion of Foxm1 levels by siRNA caused altered expression of these genes in cultured HL-1 cardiomyocytes. Endothelial-specific deletion of the Foxm1 fl/fl allele in Tie2-Cre Foxm1 fl/fl embryos did not influence heart development and cardiomyocyte proliferation. Foxm1 protein binds to the -9,259/-9,288-bp region of the endogenous mouse NFATc3 promoter, indicating that Foxm1 is a transcriptional activator of the NFATc3 gene. Foxm1 regulates expression of genes essential for the proliferation of cardiomyocytes during heart development.
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We investigated whether exercise provides beneficial effects to attenuate intermittent hypoxia (IH)-induced myocardial apoptosis. Male Sprague-Dawley rats were randomly assigned to four groups: control (CON), IH, exercise (EXE) or...
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We investigated whether exercise provides beneficial effects to attenuate intermittent hypoxia (IH)-induced myocardial apoptosis. Male Sprague-Dawley rats were randomly assigned to four groups: control (CON), IH, exercise (EXE) or IH interspersed with EXE (IHEXE). IH rats were exposed to repetitive hypoxia-reoxygenation cycles (30 s of 5% O(2); 45 s of 21% O(2), 6 h day(-1)) during the light phase (1000-1600 h) for 12 consecutive days. EXE rats were habituated to treadmill running for 5 days, permitted 2 days of rest, followed by 5 exercise bouts (30 m min(-1) for 60 min on a 2% grade) on consecutive days during the dark phase (2000-2200 h). IHEXE rats were exposed to IH during the light phase interspersed with exercise programs during the dark phase on the same day. Apoptosis levels, cytochrome c (Cyt-c), cleaved caspase-3, oxidative stress and antioxidant capacity were determined in the left ventricular (LV) myocardium. IH rats showed higher myocardial levels of the apoptotic index, mitochondria-released Cyt-c, cleaved caspase-3 and oxidative stress and lower catalase activity levels than CON rats (p < 0.05, for all). These changes were not observed in EXE rats (p > 0.05, for all) except that catalase activity increased (p < 0.05). IHEXE rats showed lower myocardial levels of apoptotic index, mitochondria-released Cyt-c, cleaved caspase-3 and oxidative stress and higher catalase activity levels (p < 0.05, for all) than IH rats. We conclude that short-term exercise provides potent cardioprotective effects by attenuating IH-induced myocardial apoptosis.
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PURPOSE: The fixation and incorporation of ruptured rotator cuff tendon to bone is a major concern in rotator cuff repair surgery. Rotator cuff repair usually fails at the tendon-bone interface, especially in case of large or mass...
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PURPOSE: The fixation and incorporation of ruptured rotator cuff tendon to bone is a major concern in rotator cuff repair surgery. Rotator cuff repair usually fails at the tendon-bone interface, especially in case of large or massive tears. To enhance tendon-bone healing, an injectable hydrogel made with periosteal progenitor cells(PPCs) and poly (ethylene glycol) diacrylate (PEGDA) tethered with bone morphogenic protein-2(BMP-2) was developed to encourage extracellular matrix synthesis for tendon-to-bone healing in rotator cuff repair. METHODS: The infraspinatus tendon was cut from the greater tuberosity and repaired through a transosseous tunnel with the injectable progenitor cell-BMP-2 hydrogel applied between the tendon-bone interface. The injectable hydrogel was prepared from 10% poly (ethylene glycol) diacrylate (PEGDA) containing 0.05% of the photoinitiator. BMP-2 tethered with poly(ethylene glycol) (PEG) was blended to the hydrogel. Rabbit periosteal progenitor cells (PPCs) isolated from periosteum were mixed with hydrogel and injected on the tendon-bone interface. Ultraviolet radiation (365 nm) was applied for 60 s to photopolymerize the injection and solidify the hydrogel. The rabbits were killed at 4 and 8 weeks. The morphological characteristics of the healing tendon-to-bone interface were evaluated by histological and immunohistochemical methods. The biomechanical test was done to determine healing attachment strength. RESULTS: At both the 4- and 8-week killing, histological analysis of the tendon-bone interface showed an increasing fibrocartilage and bone layer formed in the tendon-bone interface in PEGDA group. At 4 weeks, fibrocartilage-like tissue was observed in a focal area. At 8 weeks, further matrix deposition occurred with fibrocartilage formation in the tendon-bone junction, and bone formation appeared near host bone. Immunohistochemistry revealed the presence of aggrecan and type II collagen. Biomechanical testing revealed a higher maximum pull-out load at all time points with a statistically significant difference at 4 and 8 weeks postoperatively. CONCLUSION: PEGDA hydrogel was approved as an adequate matrix for the encapsulation of cells and signal factor, and as an effective local delivery method to the tendon-bone interface through injection and photopolymerization. The PPCs-BMP2-hydrogel provides a powerful inductive ability between the tendon and the bone and enhances tendon-bone healing through the neoformation of fibrocartilage.
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PURPOSE: In this case-series outcome study, we present our surgical technique for single-bundle anterior cruciate ligament (ACL) reconstruction with periosteum-enveloping hamstring tendon graft at a minimum of 2 years' follow-up. ...
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PURPOSE: In this case-series outcome study, we present our surgical technique for single-bundle anterior cruciate ligament (ACL) reconstruction with periosteum-enveloping hamstring tendon graft at a minimum of 2 years' follow-up. METHODS: From 2000 to 2005, ACL reconstruction with a periosteum-enveloping hamstring tendon graft was performed in 368 patients (372 knees). Of those patients, 312 who completed at least 2 years of follow-up were included for analysis. Four-strand periosteum-enveloping hamstring tendon grafts were used for single-bundle reconstruction. Clinical assessments included the Lysholm knee score, International Knee Documentation Committee score, KT-1000 instrumented testing (MEDmetric, San Diego, CA), thigh muscle assessment, and radiographic evaluation. Radiographs were used to assess femoral and tibial tunnel widening. RESULTS: The 312 study patients were followed up for a mean of 4.6 years (range, 2 to 7 years). The median Lysholm knee scores were 56 points (range, 40 to 70 points) and 95 points (range, 60 to 100 points) before and after surgery, respectively. After reconstruction, 85% of patients could return to moderate or strenuous activity, 5.1% exhibited grade 2 or higher ligament laxity with the anterior drawer test, and 6.1% had a positive pivot shift. Complete range of motion was achieved in 88% of patients. On the basis of International Knee Documentation Committee assessment, 93% of patients had a normal or nearly normal rating. CONCLUSIONS: Satisfactory results can be achieved with the periosteum-enveloping hamstring tendon graft in single-bundle ACL reconstruction with minimal tunnel widening. Bone tunnel enlargement of more than 1 mm was identified in 5.4% of femoral tunnels and 6.1% of tibial tunnels, which was less than in other studies using comparable fixation. LEVEL OF EVIDENCE: Level IV, therapeutic case series.
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Inflammation and granuloma formation in human neurocysticercosis has been attributed to Th1-type immune responses of the host. In the present murine model, over 94% of Taenia solium metacestodes were viable and elicited no granulo...
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Inflammation and granuloma formation in human neurocysticercosis has been attributed to Th1-type immune responses of the host. In the present murine model, over 94% of Taenia solium metacestodes were viable and elicited no granulomatous inflammation, whereas parasites killed by praziquantel treatment elicited rapid granuloma formation that calcified within 2weeks. Osteopontin (OPN) is a Th1-related cytokine that is up-stream of IL-12 and which may play an essential role in granuloma formation and calcification. OPN mRNA expression was down-regulated in tissues surrounding viable cysticerci, but was up-regulated in inflammatory tissues surrounding degenerating cysticerci. Moreover, co-culture with a viable cysticercus or ES products from these metacestodes led to a decrease in OPN, IFN-gamma and IL-12 expression, whereas co-culture with somatic proteins enhanced OPN expression by leukocytes. Addition of recombinant mouse OPN (rmOPN) counteracted the down-regulation of IL-12 and IFN-gamma mRNA expression, but not OPN mRNA expression, in leukocyte cultures. Furthermore, injection of rmOPN into the tissues surrounding implanted cysticerci enhanced inflammatory responses while a similar injection of an anti-rmOPN antibody reduced inflammation. These findings suggest that the suppression of host Th1-type granulomatous inflammation by ES products from T. solium metacestodes is related to down-regulation of OPN gene expression.
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A new band-notched ultra-wideband (UWB) bandpass filter (BPF) with an improved upper stopband is designed using a multi-mode resonator (MMR). The MMR, being a, modified version of a common tri-section stepped-impedance resonator (...
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A new band-notched ultra-wideband (UWB) bandpass filter (BPF) with an improved upper stopband is designed using a multi-mode resonator (MMR). The MMR, being a, modified version of a common tri-section stepped-impedance resonator (TSSIR), is split at its two open ends with the input/output feed lines sandwiched in between to form an interdigital parallel-coupled configuration that results in stronger coupling. In addition, an extended coupling length in the second section of the TSSIR is featured to provide further coupling and impedance-matching tuning. With such a design strategy, coupling gaps of no smaller than 0.1 mm was achieved to obtain the required UWB response. In this design, the first five resonant modes of the MMR and the coupling peaks of the input/output parallel-coupled lines are properly located in the UWB passband to achieve a uniform in-band transmission response. Also, the spur lines and open-circuited stubs are implemented in the MMR to create a 5-GHz notched band and to broaden the upper stopband, respectively. The designed UWB BPF, which being verified by measurement, shows a very good UWB performance. The measured in-band minimum insertion loss and maximum group delay variation except those in the notched band are 0.45 dB and 0.05 ns, respectively, and the upper-end -20-dB stopband bandwidth is about 5.35 GHz. The created notched band is centered at 5.69 GHz with a maximum insertion loss of 37.2 dB and a 3-dB notch bandwidth of 18%.
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