Enhancing quantum teleportation efficacy with noiseless linear amplification.

Quantum teleportation constitutes a fundamental tool for various applications in quantum communication and computation. However, state-of-the-art continuous-variable quantum teleportation is restricted to moderate fidelities and short-distance configurations. This is due to unavoidable experimental imperfections resulting in thermal decoherence during the teleportation process. Here we present a heralded quantum teleporter able to overcome these limitations through noiseless linear amplification. As a result, we report a high fidelity of 92% for teleporting coherent states using a modest level of quantum entanglement. Our teleporter in principle allows nearly complete removal of loss induced onto the input states being transmitted through imperfect quantum channels. We further demonstrate the purification of a displaced thermal state, impossible via conventional deterministic amplification or teleportation approaches. The combination of high-fidelity coherent state teleportation alongside the purification of thermalized input states permits the transmission of quantum states over significantly long distances. These results are of both practical and fundamental significance; overcoming long-standing hurdles en route to highly-efficient continuous-variable quantum teleportation, while also shining new light on applying teleportation to purify quantum systems from thermal noise.

Novel transplant of combined platelet-rich fibrin Releasate and bone marrow stem cells prevent bone loss in Ovariectomized osteoporotic mice.

BACKGROUND: Osteoporosis is a metabolic bone disorder characterized by deterioration in the quantity and quality of bone tissue, with a consequent increase susceptibility to fracture. METHODS: In this study, we sought to determine the efficacy of platelet-rich fibrin releasates (PRFr) in augmenting the therapeutic effects of stem cell-based therapy in treating osteoporotic bone disorder. An osteoporosis mouse model was established through bilateral ovariectomy on 12-week-old female ICR (Institute of Cancer Research) mice. Eight weeks postoperatively, the ovariectomized (OVX) mice were left untreated (control) or injected with PRFr, bone marrow stem cells (BMSCs), or the combination of BMSCs and PRFr. Two different injection (single versus quadruple) dosages were tested to investigate the accumulative effects of BMSCS and PRFr on bone quality. Eight weeks after injection, the changes in tibial microstructural profiles included the percentage of bone volume versus total tissue volume (BV/TV, %), bone mineral density (BMD, g/cm3), trabecular number (Tb.N, number/mm), and trabecular separation (Tb.Sp, mm) and bony histology were analyzed. RESULTS: Postmenopausal osteoporosis model was successfully established in OVX mice, evidenced by reduced BMD, decreased BV/TV, lower Tb.N but increased Tb.Sp. Eight weeks after injection, there was no significant change to BMD and bone trabeculae could be detected in mice that received single-injection regimen. In contrast, in mice which received 4 doses of combined PRFr and BMSCs, the BMD, BV/TV, and TB.N increased, and the TB.Sp decreased significantly compared to untreated OVX mice. Moreover, the histological analysis showed the trabecular spacing become narrower in OVX-mice treated with quadruple injection of BMSCs and combined PRFr and BMSCs than untreated control. CONCLUSION: The systemic administration of combined BMSCs and PRFr protected against OVX-induced bone mass loss in mice. Moreover, the improvement of bony profile scores in quadruple-injection group is better than the single-injection group, probably through the increase in effect size of cells and growth factors. Our data also revealed the combination therapy of BMSCs and PRFr has better effect in enhancing osteogenesis, which may provide insight for the development of a novel therapeutic strategy in osteoporosis treatment.

Enhanced Bone Formation in Osteoporotic Mice by a Novel Transplant Combined with Adipose-derived Stem Cells and Platelet-rich Fibrin Releasates.

Osteoporotic fracture is the main complication of osteoporosis (OP) and accounts for millions of injuries annually. Local intervention by intra-marrow injection has been a good option for preventing osteoporotic bone loss when the osteoporotic femoral fracture has been treated. In this study, tail vein transplantations were examined to evaluate the cell-based therapeutic approach for treating OP with adipose-derived stem cells (ADSCs) and platelet-rich fibrin releasates (PRFr) in an ovariectomized (OVX) mice model. Thirty-six 12-wk-old female ICR mice were randomly divided into six groups: untreated control; sham-operated; OVX-control; OVX-ADSCs; OVX-PRFr; and OVX-ADSCs+PRFr. Starting 8 wk after ovariectomy, the OVX mice received tail vein injections once each week for four consecutive weeks, then were evaluated radiographically and histopathologically 8 wk after the first injection. We also assessed changes to bone trabeculae in the proximal tibial growth plate. In OVX mice treated with ADSCs or PRFr alone, or with a combination of ADSCs and PRFr, the trabecular bone mineral density (BMD), bone volume ratios (BV/TV), and numbers (Tb.N) in the proximal tibia areas were significantly higher than that in the OVX-control group. Significant differences between OVX-treated mice and OVX controls were found for trabecular separation, but not for trabecular thickness. These results indicate that ADSCs or PRFr treatment enhances bone microarchitecture in OP. The treatment of bone loss of OVX mice with ADSCs+PRFr induced greater bone consolidation with bone tissue production (P < 0.01) when compared to the others. Thus, we conclude that the transplantation of ADSCs combined with PRFr might provide an alternative strategy for the treatment of various bone disorders in OP with an unlimited source of cells and releasates.

The pig as an experimental model for mid-dermal burns research.

This was a novel, prospective and interventional animal study designed to develop and evaluate a new infliction device for the experimental burn model. Four paired sets of contact burns measuring 36mm diameter were inflicted on the dorsum of an anesthetized pig using a stainless steel round bar heated up to 80-110°C. The bar was applied using a push-pull force gauge designed to control 1kgf mechanical force applied to the skin for a period of 20s. The left dorsum was used for macroscopic observation and the right dorsum was used for histopathological evaluation. A total of eight burns were covered with moist saline dressings and given daily treatments of xylocaine (lidocaine HCl) gel. This procedure was followed for a period of 24 days. Full-thickness biopsies were obtained for histologic analysis to determine the extent of injury. Statistical analysis showed a high correlation between the exposure temperature and histopathological assessment. The results found the depth of injury to the collagen (Seg1) correlated with the temperature (Ti) at which the burns was inflicted, Seg1=0.038Ti-2.57 (r=0.973, P<0.05). Also, the histological studies show a high correlation between the depth of collagen denaturation in wounds and the exposure temperature, Seg1=0.0268Ti-0.165 (r=0.991, P<0.05). This model is useful to assess more closely the therapeutic agents used for wound healing in experimental burn wounds.

Wild-type H- and N-Ras promote mutant K-Ras-driven tumorigenesis by modulating the DNA damage response.

Mutations in KRAS are prevalent in human cancers and universally predictive of resistance to anticancer therapeutics. Although it is widely accepted that acquisition of an activating mutation endows RAS genes with functional autonomy, recent studies suggest that the wild-type forms of Ras may contribute to mutant Ras-driven tumorigenesis. Here, we show that downregulation of wild-type H-Ras or N-Ras in mutant K-Ras cancer cells leads to hyperactivation of the Erk/p90RSK and PI3K/Akt pathways and, consequently, the phosphorylation of Chk1 at an inhibitory site, Ser 280. The resulting inhibition of ATR/Chk1 signaling abrogates the activation of the G2 DNA damage checkpoint and confers specific sensitization of mutant K-Ras cancer cells to DNA damage chemotherapeutic agents in vitro and in vivo.

A postmarketing surveillance study on erbitux (cetuximab) in patients with metastatic colorectal cancer refractory to irinotecan-containing treatment.

OBJECTIVE: This postmarketing surveillance study evaluated the safety and efficacy of cetuximab therapy in patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC) in Taiwan. METHODS: Patients with EGFR-expressing mCRC who had failed prior irinotecan-based chemotherapy and were receiving cetuximab therapy were monitored for treatment efficacy and safety from the time of first infusion until 28 days after the last infusion regardless of the reasons fordiscontinuation. The study followed 269 patients for approximately 2 years. RESULTS: No unexpected adverse events associated with cetuximab therapy were reported, and most events were grade 1 or 2. The most common drug-related adverse events of any grade were rash (21.6%) and dermatitis acneiform (4.8%). Reported grade 3/4 events were rash (4.5%), dermatitis acneiform (0.4%), and diarrhea (0.4%). Cetuximab treatment for patients receiving second-/third-line (177 patients) or above therapy (92 patients) was associated with a median progression-free survival time of 3.37 and 3.90 months, respectively, and a median overall survival time of 17.6 and 21.1 months, respectively. The response rates for the second-/third-line treatment and fourth-line or above cetuximab treatment groups were similar (21.5% vs 17.4%; P = 0.428). CONCLUSION: Cetuximab showed no unexpected safety findings and was efficacious in treating patients with EGFR-expressing mCRC in community practice in Taiwan.

Efficient division and sampling of cell colonies using microcup arrays.

A microengineered array to sample clonal colonies is described. The cells were cultured on an array of individually releasable elements until the colonies expanded to cover multiple elements. Single elements were released using a laser-based system and collected to sample cells from individual colonies. A greater than an 85% rate in splitting and collecting colonies was achieved using a 3-dimensional cup-like design or "microcup". Surface modification using patterned titanium deposition of the glass substrate improved the stability of microcup adhesion to the glass while enabling minimization of the laser energy for splitting the colonies. Smaller microcup dimensions and slotting the microcup walls reduced the time needed for colonies to expand into multiple microcups. The stem cell colony retained on the array and the collected fraction within released microcups remained undifferentiated and viable. The colony samples were characterized by both reporter gene expression and a destructive assay (PCR) to identify target colonies. The platform is envisioned as a means to rapidly establish cell lines using a destructive assay to identify desired clones.

Sos-mediated cross-activation of wild-type Ras by oncogenic Ras is essential for tumorigenesis.

Mammalian cells contain three closely related ras genes, H-ras, K-ras and N-ras. Although in a given tumour type, oncogenic mutations are selectively observed in only one of the ras genes, the acquisition of the transformed phenotype has been shown to require the contribution of the normal products of the other ras genes. Here we demonstrate that oncogenic K-Ras promotes the activation of wild-type H- and N-Ras. This activation is mediated by oncogenic K-Ras-dependent allosteric stimulation of Sos and confers a growth advantage to oncogenic K-Ras harbouring cancer cells. These findings underscore the complementary functions of oncogenic and wild-type Ras in tumour cells and identify a potential new targeting strategy for Ras-driven tumours.

Selection and separation of viable cells based on a cell-lethal assay.

A method to select and separate viable cells based on the results of a cell-lethal assay was developed. Cells were plated on an array of culture sites with each site composed of closely spaced, releasable micropallets. Clonal colonies spanning multiple micropallets on individual culture sites were established within 72 h of plating. Adjacent sites were widely spaced with 100% of the colonies remaining sequestered on a single culture site during expansion. A laser-based method mechanically released a micropallet underlying a colony to segment the colony into two genetically identical colonies. One portion of the segmented colony was collected with 90% efficiency while viability of both fractions was 100%. The segmented colonies released from the array were fixed and subjected to immunofluorescence staining of intracellular phospho-ERK kinase to identify colonies that were highly resistant or sensitive to phorbol ester-induced activation of ERK. These resistant and sensitive cells were then matched to the corresponding viable colonies on the array. Sensitive and resistant colonies on the array were released and cultured. When these cultured cells were reanalyzed for phorbol ester-induced ERK activity, the cells retained the sensitive or resistant phenotype of the originally screened subcolony. Thus, cells were separated and collected based using the result of a cell-lethal assay as selection criteria. These microarrays enabling clonal colony segmentation permitted sampling and manipulation of the colonies at very early times and at small cell numbers to reduce reagent, time, and manpower requirements.

Micromolded arrays for separation of adherent cells.

We present an efficient, yet inexpensive, approach for isolating viable single cells or colonies from a mixed population. This cell microarray platform possesses innovations in both the array manufacture and the manner of target cell release. Arrays of microwells with bases composed of detachable concave elements, termed microrafts, were fabricated by a dip-coating process using a polydimethylsiloxane mold as the template and the array substrate. This manufacturing approach enabled the use of materials other than photoresists to create the array elements. Thus microrafts possessing low autofluorescence could be fabricated for fluorescence-based identification of cells. Cells plated on the microarray settled and attached at the center of the wells due to the microrafts' concavity. Individual microrafts were readily dislodged by the action of a needle inserted through the compliant polymer substrate. The hard polymer material (polystyrene or epoxy resin) of which the microrafts were composed protected the cells from damage by the needle. For cell analysis and isolation, cells of interest were identified using a standard inverted microscope and microrafts carrying target cells were dislodged with the needle. The released cells/microrafts could be efficiently collected, cultured and clonally expanded. During the separation and collection procedures, the cells remained adherent and provided a measure of protection during manipulation, thus providing an extremely high single-cell cloning rate (>95%). Generation of a transfected cell line based on expression of a fluorescent protein demonstrated an important application for performing on-chip cell separations.

Microtable arrays for culture and isolation of cell colonies.

Cell microarrays with culture sites composed of individually removable microstructures or micropallets have proven benefits for isolation of cells from a mixed population. The laser energy required to selectively remove these micropallets with attached cells from the array depends on the microstructure surface area in contact with the substrate. Laser energies sufficient to release micropallets greater than 100 µm resulted in loss of cell viability. A new three-dimensional culture site similar in appearance to a table was designed and fabricated using a simple process that relied on a differential sensitivity of two photoresists to UV-mediated photopolymerization. With this design, the larger culture area rests on four small supports to minimize the surface area in contact with the substrate. Microtables up to 250 × 250 µm were consistently released with single 10-µJ pulses to each of the four support structures. In contrast, microstructures with a 150 × 150-µm surface area in contact with the substrate could not be reliably released at pulse energies up to 212 µJ. Cassie-Baxter wetting is required to provide a barrier of air to localize and sequester cells to the culture sites. A second asset of the design was an increased retention of this air barrier under conditions of decreased surface tension and after prolonged culture of cells. The improved air retention was due to the hydrophobic cavity created beneath the table and above the substrate which entrapped air when an aqueous solution was added to the array. The microtables proved an efficient method for isolating colonies from the array with 100% of selected colonies competent to expand following release from the array.

Perturbation of cytoskeleton dynamics by the opposing effects of Rac1 and Rac1b.

Rac1, a ubiquitously expressed member of the Rho GTPase family, plays a pivotal role in the regulation of multiple cellular processes including cytoskeleton reorganization, cell growth, differentiation and motility. Here we show that the tumor-specific splice variant of Rac1, Rac1b, negatively regulates Rac1 activity. The expression of Rac1b in HeLa cells interferes with Rac1 activation by PDGF, leads to a reduction in membrane-bound Rac1 and promotes an increase in Rho activity. The antagonistic relationship between Rac1 and Rac1b perturbs the regulatory circuitry that controls actin cytoskeleton dynamics thereby leading to tumor-linked alterations in cell morphology and motility.

Micropallet arrays with poly(ethylene glycol) walls.

Arrays of releasable micropallets with surrounding walls of poly(ethylene glycol) (PEG) were fabricated for the patterning and sorting of adherent cells. PEG walls were fabricated between the SU-8 pallets using a simple, mask-free strategy. By utilizing the difference in UV-transmittance of glass and SU-8, PEG monomer was selectively photopolymerized in the space surrounding the pallets. Since the PEG walls are composed of a cross-linked structure, the stability of the walls is independent of the pallet array geometry and the properties of the overlying solution. Even though surrounded with PEG walls, the individual pallets were detached from the array by the mechanical force generated by a focused laser pulse, with a release threshold of 6 microJ. Since the PEG hydrogels are repellent to protein adsorption and cell attachment, the walls localized cell growth to the pallet top surface. Cells grown in the microwells formed by the PEG walls were released by detaching the underlying pallet. The released cells/pallets were collected, cultured and clonally expanded. The micropallet arrays with PEG walls provide a platform for performing single cell analysis and sorting on chip.

Photoresist with low fluorescence for bioanalytical applications.

The negative photoresist SU-8 has found widespread use as a material in the fabrication of microelectrical-mechanical systems (MEMS). Although SU-8 has been utilized as a structural material for biological MEMS, a number of SU-8 properties limit its application in these bioanalytical devices. These attributes include its brittleness, nonspecific adsorption of biomolecules, and high fluorescence in the visible wavelengths. In addition, native SU-8 is a poor substrate for cellular adhesion. Photoresists composed of resins with epoxide side groups and photoacids were screened for their ability to serve as a low-fluorescence photoresist with sufficient resolution to generate microstructures with dimensions of 5-10 microm. The fluorescence of structures formed from 1002F photoresist (1002F resin combined with triarylsulfonium hexafluoroantimonate salts) was as much as 10 times less fluorescent than similar SU-8 microstructures. The absorbance of 1002F in the visible wavelengths was also substantially lower than that of SU-8. Microstructures or pallets with an aspect ratio as high as 4:1 could be formed permitting 1002F to be used as a structural material in the fabrication of arrays of pallets for sorting adherent cells. Several different cell types were able to adhere to native 1002F surfaces, and the viability of these cells was excellent. As with SU-8, 1002F has a weak adhesion to glass, a favorable attribute when the pallet arrays are used to sort adherent cells. A threshold, laser pulse energy of 3.5 microJ was required to release individual 50 microm, 1002F pallets from an array. Relative to SU-8, 1002F photoresist offers substantial improvements as a substrate in bioanalytical devices and is likely to find widespread use in BioMEMS.

Broadening cell selection criteria with micropallet arrays of adherent cells.

A host of technologies exists for the separation of living, nonadherent cells, with separation decisions typically based on fluorescence or immunolabeling of cells. Methods to separate adherent cells as well as to broaden the range of possible sorting criteria would be of high value and complementary to existing strategies. Cells were cultured on arrays of releasable pallets. The arrays were screened and individual cell(s)/pallets were released and collected. Conventional fluorescence and immunolabeling of cells were compatible with the pallet arrays, as were separations based on gene expression. By varying the size of the pallet and the number of cells cultured on the array, single cells or clonal colonies of cells were isolated from a heterogeneous population. Since cells remained adherent throughout the isolation process, separations based on morphologic characteristics, for example cell shape, were feasible. Repeated measurements of each cell in an array were performed permitting the selection of cells based on their temporal behavior, e.g. growth rate. The pallet array system provides the flexibility to select and collect adherent cells based on phenotypic and temporal criteria and other characteristics not accessible by alternative methods.

DNA methyltransferase 1 expression and promoter methylation of E-cadherin in mucoepidermoid carcinoma.

BACKGROUND: Loss of E-cadherin expression is found frequently in many types of human malignancies, including mucoepidermoid carcinoma (MEC). CpG methylation in the promoter region has proven important in the regulation of gene expression implicated in malignant transformation. DNA methyltransferases (DNMTs) are the major enzymes involved in establishing genomic methylation patterns. The current study was designed to test the hypothesis that CpG methylation of the promoter region of the E-cadherin gene may inactivate its expression and to examine DNMT 1 (DNMT1) protein expression in MEC. METHODS: Genomic DNA was obtained from paraffin embedded sections by laser microdissection in 46 MEC specimens. Methylation status of the E-cadherin promoter was examined by utilizing the methylation-specific polymerase chain reaction assay. To examine E-cadherin and DNMT1 proteins expression levels, the MEC specimens and adjacent epithelial tissues were studied immunohistochemically. Chi-square analysis was used to evaluate the correlation of protein expression and E-cadherin methylation status with clinicopathologic parameters. Comparisons of the survival rate between patients with DNMT1-positive and DNMT1-negative patients were made using Kaplan-Meier analysis. RESULTS: The data showed that all normal tissues expressed E-cadherin, and no promoter methylation was detected. Of the MEC samples analyzed, methylation allele was found in 33 of 46 samples (72%), and reduced E-cadherin expression was found in 21 of 46 samples (45%). DNMT1-positive expression was observed in 29 of 46 MEC samples (63%). A significant correlation was found between E-cadherin expression and the methylation status of E-cadherin promoter (P = 0.021). In addition, increased DNMT1 expression was correlated with histologic grade, clinical stage, and a poor prognosis in patients with MEC. CONCLUSIONS: Hypermethylation of CpG sites at the 5' promoter of E-cadherin was a common event associated with E-cadherin expression levels in MEC, suggesting an epigenetically mediated loss of E-cadherin function in these tumors. Increased DNMT1 protein expression may play a critical role in the carcinogenesis and disease progression of MEC.

Phosphorylation by glycogen synthase kinase of inhibitor-2 does not change its structure in free state.

Inhibitor-2 (I2) is a thermostable protein that specifically binds to the catalytic subunit of protein phosphatase-1 (PP1), resulting in the formation of the inactive holoenzyme, ATP-Mg-dependent phosphatase. Phosphorylation of I2 at Thr-72 by glycogen synthase kinase-3 (GSK-3) results in activation of the phosphatase, suggesting that kinase action triggers conformational change in the complex. In this paper, we characterize the effect of GSK-3 phosphorylation on the structure of free state I2[1-172] by nuclear magnetic resonance and circular dichroism spectroscopy, and show that phosphorylation has no significant effect on its conformation. We conclude that the conformational changes of ATP-Mg-dependent phosphatase induced by GSK-3 phosphorylation must depend on the interactions between PP1 and I2.

Retrocaval ureter: report of two cases and literature review.

Retrocaval ureter is a rare congenital anomaly in which the ureter passes behind, and is compressed by, the inferior vena cava. Its etiology is assumed to be abnormal embryologic development of the inferior vena cava as a result of atrophy failure of the right subcardinal vein in the lumbar portion. We report two cases of retrocaval ureter and review the relevant literature. One patient was a 7-year-old boy who presented with right flank pain. The other was a 40-year-old male who was found to have right hydronephrosis accidentally on abdominal sonography during a health examination. Both underwent retrograde pyelography which showed the typical S-shape of a retrocaval ureter. Abdominal computerized tomography and magnetic resonance imaging confirmed the diagnosis of retrocaval ureter. Ureteroureterostomies were performed. One patient showed focal squamous metaplasia of the ureter and the other had chronic inflammation and fibrosis. Follow-up studies showed improvement in hydronephrosis and renal function in both patients. We conclude that retrocaval ureter is a rare disorder and surgical correction is usually effective.

Detection of prostate cancer--experience of seven years in KMUH and review of literature.

Prostate cancer has become the 7th most common malignancy in Taiwan in 2000. To our knowledge, many diagnostic tests have been developed, including digital rectal examination (DRE), transrectal ultrasound (TRUS), prostate specific antigen (PSA), PSA density (PSAD), PSA velocity, age-specific PSA, and free-to-total PSA, but none of them has been proven to be definitely effective in deciding which person is to receive prostate biopsy. Viewpoints vary with clinician and area. A total of 300 patients over 7-year time period received DRE, TRUS, PSA, and PSAD tests and then had prostate biopsy in Kaohsiung Medical University Hospital. We collect our results and review the literature to find the cost-effectiveness of the tests to prevent unnecessary biopsy and delay in diagnosis. Fifty-two patients (19%) with PSA > 4 ng/ml had prostate cancer. Only 10.5% of patients with prostate cancer had abnormal TRUS lesions, and 20% with prostate cancer showed abnormal DRE results. Because of DRE is non-invasive and inexpensive, we commend the annual use of DRE combined with PSA check in males of 50 years and above to screen for prostate cancer, despite the poor sensitivity of DRE. Therefore, in cases where there is either PSA > 4 ng/ml or abnormal DRE results, it is suggested that patients receive prostate biopsy. There is still no definite conclusion in other diagnostic tests including TRUS.