Ultra-lightweight living structural material for enhanced stiffness and environmental sensing.

Natural materials such as bone, wood, and bamboo can inspire the fabrication of stiff, lightweight structural materials. Biofilms are one of the most dominant forms of life in nature. However, little is known about their physical properties as a structural material. Here we report an Escherichia coli biofilm having a Young's modulus close to 10 â€‹GPa with ultra-low density, indicating a high-performance structural material. The mechanical and structural characterization of the biofilm and its components illuminates its adaptable bottom-up design, consisting of lightweight microscale cells covered by a dense network of amyloid nanofibrils on the surface. We engineered E. coli such that 1) carbon nanotubes assembled on the biofilm, enhancing its stiffness to over 30 â€‹GPa, or that 2) the biofilm sensitively detected heavy metal as an example of an environmental toxin. These demonstrations offer new opportunities for developing responsive living structural materials to serve many real-world applications.

High Procalcitonin, C-Reactive Protein, and α-1 Acid Glycoprotein Levels in Whole Blood Samples Could Help Rapid Discrimination of Active Tuberculosis from Latent Tuberculosis Infection and Healthy Individuals.

Tuberculosis (TB) management is important for prompt discrimination of latent TB infection (LTBI) from active TB and proper treatment. Whole blood Interferon-gamma (IFN-γ) release assay (IGRA) is used to diagnose LTBI based on the secretion of IFN-γ by T-cells in the whole blood by using a specific antigen of Mycobacterium tuberculosis. However, the ability of IGRA to distinguish active TB from LTBI is considerably limited. Distinguishing active TB from LTBI is necessary to identify indicators that can be used to effectively manage TB and develop diagnostic methods. In the present study, we used a Luminex multiplex bead array (a bead-based antibody−antigen sandwich method). The whole blood level of acute phase proteins (APPs), such as endoglin (ENG), procalcitonin (PCT), C-reactive protein (CRP), and α1-acid glycoprotein (AGP), in active TB, LTBI, and healthy individuals were analyzed and quantified. The APP test results for the serum and whole blood samples showed that the levels of PCT, CRP, and AGP were significantly increased (p < 0.0500; area under curve = 0.955) in active TB. The level of these markers in the whole blood of active TB, LTBI, and healthy individuals could provide data for effective diagnosis and treatment of TB.

Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis.

Early diagnosis increases the treatment success rate for active tuberculosis (ATB) and decreases mortality. MicroRNAs (miRNAs) have been studied as blood-based markers of several infectious diseases. We performed miRNA profiling to identify differentially expressed (DE) miRNAs using whole blood samples from 10 healthy controls (HCs), 15 subjects with latent tuberculosis infection (LTBI), and 12 patients with ATB, and investigated the expression of the top six miRNAs at diagnosis and over the treatment period in addition to performing miRNA-target gene network and gene ontology analyses. miRNA profiling identified 84 DE miRNAs in patients with ATB, including 80 upregulated and four downregulated miRNAs. Receiver operating characteristic curves of the top six miRNAs exhibited excellent distinguishing efficiency with an area under curve (AUC) value > 0.85. Among them, miR-199a-3p and miR-6886-3p can differentiate between ATB and LTBI. Anti-TB treatment restored the levels of miR-199b-3p, miR-199a-3p, miR-16-5p, and miR-374c-5p to HC levels. Furthermore, 108 predicted target genes were related to the regulation of cellular amide metabolism, intrinsic apoptotic signaling, translation, transforming growth factor beta receptor signaling, and cysteine-type endopeptidase activity. The DE miRNAs identified herein are potential biomarkers for diagnosis and therapeutic monitoring in ATB.

Predictors for False-Negative Interferon-Gamma Release Assay Results in Hemodialysis Patients with Latent Tuberculosis Infection.

The present study aimed to clinically evaluate the effect of T-cell dysfunction in hemodialysis (HD) patients with latent tuberculosis (TB) infection (LTBI) who were false-negatives in the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. Whole blood samples from a total of 20 active TB patients, 83 HD patients, and 52 healthy individuals were collected, and the QFT-GIT test was used for measuring Mycobacterium tuberculosis (MTB)-specific interferon gamma (IFN-γ) level. The positive rate of the IFN-γ release assays (IGRAs) in HD patients was lower than the negative rate. The mean value of MTB-specific IFN-γ level, which determines the positive rate of the IGRA test, was highest in active TB, followed by HD patients and healthy individuals. Among HD patients, phytohemagglutinin A (PHA)-stimulated IFN-γ levels of approximately 40% were 10.00 IU/mL or less. However, there was no low level of PHA-stimulated IFN-γ in the healthy individuals. This reveals that T-cell function in HD patients was reduced compared to healthy individuals, which leads to the possibility that QFT-GIT results in HD patients are false-negative. The clinical manifestations of TB in patients on HD are quite non-specific, making timely diagnosis difficult and delaying the initiation of curative treatment, delay being a major determinant of outcome.

Combined analysis of whole blood interferon gamma release assay and complete blood count analysis for rapid discrimination of active tuberculosis and latent tuberculosis infection.

Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (MTB), is a serious infectious disease with high infection and mortality rates and is a public health problem around the world. According to the World Health Organization (WHO) report, one-third of the world's population is latently infected with MTB, and 5 to 10% of those with latent TB infection (LTBI) have the potential to develop active TB once in their lifetime. Therefore, TB management for promptly distinguishing LTBI from active TB and for proper treatment is important. LTBI is currently diagnosed using the tuberculin skin test (TST) and interferon gamma (IFN-γ) release assay (IGRA). However, this test is substantially limited by its inability to distinguish active TB from LTBI. It is necessary to discover indicators that can be used for effective TB management and to develop diagnostic methods. In the present study, we used IGRA and complete blood count (CBC) analysis for discrimination of active TB, LTBI, and healthy control groups. The results showed that the number of WBC was significantly increased in the group with active TB (p < 0.0100) and level of hemoglobin (Hb) was significantly decreased (p < 0.0010) in the CBC than those of the healthy control and LTBI groups. In the WBC differential count, the number of neutrophils and monocytes were increased (p < 0.0010) in active TB group, where as those of lymphocytes were significantly decreased (p < 0.0100) in active TB group compared healthy control group. Results verified that the levels of total WBC, Hb, neutrophils, lymphocytes and monocytes were statistically significant (p < 0.0500) and the AUC was approximately 0.8613. In addition, receiver operating characteristic (ROC) curve analysis was performed to confirm the clinical usefulness between active TB and healthy control groups. In conclusion, based on these data demonstrated that the usefulness of these potential indicators for differential diagnosis, according to the result can be provided for effective diagnosis and treatment by comparing the expression patterns of the markers in the whole blood of the active TB, LTBI, and healthy control groups. Furthermore, this study needs to investigate a larger number of clinical specimens later to develop biomarkers according to the state of infection with MTB such as LTBI and active TB, as well as after treatment.

Cytokine and Chemokine mRNA Expressions after Mycobacterium tuberculosis-Specific Antigen Stimulation in Whole Blood from Hemodialysis Patients with Latent Tuberculosis Infection.

There have been few reports on the kinetics of hemodialyzed (HD) patients' immune responses in latent tuberculosis infection (LTBI). Therefore, in the present study, messenger ribonucleic acid (mRNA) expression levels of nine immune markers were analyzed to discriminate between HD patients with LTBI and healthy individuals. Nine cytokines and chemokines were screened through relative mRNA expression levels in whole blood samples after stimulation with Mycobacterium tuberculosis (MTB)-specific antigens from HD patients with LTBI (HD/LTBI), HD patients without LTBI, and healthy individuals, and results were compared with the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. We confirmed that the C-C motif chemokine 11 (CCL11) mRNA expression level of the HD/LTBI group was significantly higher than the other two groups. Especially, the CCL11 mRNA expression level of the >0.7 IU/mL group in the QFT-GIT test was significantly higher than the <0.2 IU/mL group in the QFT-GIT test and the 0.2-0.7 IU/mL group in the QFT-GIT test (p = 0.0043). The present study reveals that the relative mRNA expression of CCL11 was statistically different in LTBI based on the current cut-off value (i.e., ≥0.35 IU/mL) and in the >0.7 IU/mL group. These results suggest that CCL11 mRNA expression might be an alternative biomarker for LTBI diagnosis in HD patients.

Modulation of Macrophage Polarization by Phospholipids on the Surface of Titanium.

Macrophage polarization has become increasingly important for the improvement of the biocompatibility of biomaterials. In this study, we coated Ti discs with phospholipids (phosphatidylserine/phosphatidylcholine [4:1 mole/mole]) by evaporating the solvent under vacuum, and observed the polarization of RAW 264.7 cells cultured on the discs. The coated discs were hydrated before cell culture was added. The shape of the hydrated phospholipids varied with the concentration of loaded phospholipids: a perforated layer (0.1 mM), tubules and spheres (1 mM), and spheres (10 mM). RAW 264.7 cells exhibited different morphologies, depending on the concentration of phospholipids. On the coated discs, the gene expression and protein release of TGF-ß1, VEGF, Arg-1, and TNF-α were downregulated, especially with 10 mM phospholipids. The stimulation of mRNA expression and the protein release of those genes by IL-4 and LPS were also disturbed on the phospholipid-coated discs. In conclusion, the polarization of RAW 264.7 cells was prevented by hydrated phospholipids on Ti discs.

Enhanced energy transport in genetically engineered excitonic networks.

One of the challenges for achieving efficient exciton transport in solar energy conversion systems is precise structural control of the light-harvesting building blocks. Here, we create a tunable material consisting of a connected chromophore network on an ordered biological virus template. Using genetic engineering, we establish a link between the inter-chromophoric distances and emerging transport properties. The combination of spectroscopy measurements and dynamic modelling enables us to elucidate quantum coherent and classical incoherent energy transport at room temperature. Through genetic modifications, we obtain a significant enhancement of exciton diffusion length of about 68% in an intermediate quantum-classical regime.

A survey of patterns of practice on palliative radiation therapy for bone metastasis in Korea.

PURPOSE: The aim of this study was to understand the practice patterns of palliative radiation therapy for bone metastasis in Korea among Korean radiation oncologists by survey and to determine the decision factors affecting the prescription of radiation therapy fractionation schedules. METHODS: An Internet-based survey was performed from October 5 to October 23, 2009, among 177 active full members of the Korean Society for Radiation and Oncology (KOSRO). The survey questionnaire included general information about the respondent, three types of clinical scenario, depending on the life expectancy of the patients, and the decision factors that affected the prescription of a radiation therapy schedule. RESULTS: The most prescribed schedule was 30 Gy in 10 fractions regardless of the life expectancy of the patient. Also, it was found that a single fraction was seldom prescribed routinely in Korea. An increasing number prescribed fewer than 10 fractions as the life expectancy shortened; however, the prescription rate of a single fraction was still low. The general performance (and/or accompanying diseases) of patients and the life expectancy were the most considered factors in deciding the prescription of radiation therapy. CONCLUSIONS: Despite the abundant evidence supporting the equivalence of single- and multi-fraction radiation therapy, still, most Korean radiation oncologists continue to prescribe multi-fraction schedules depending on the general performance and life expectancy of the patients. Thus, we confirmed that there was a gap between evidence and practice, and treatment prescriptions can be strongly affected by decision factors other than published literature results.

Cumulative dose on fractional delivery of tomotherapy to periodically moving organ: a phantom QA suggestion.

This study was conducted to evaluate the cumulative dosimetric error that occurs in both target and surrounding normal tissues when treating a moving target in multifractional treatment with tomotherapy. An experiment was devised to measure cumulative error in multifractional treatments delivered to a horseshoe-shaped clinical target volume (CTV) surrounding a cylinder shape of organ at risk (OAR). Treatments differed in jaw size (1.05 vs 2.5cm), pitch (0.287 vs 0.660), and modulation factor (1.5 vs 2.5), and tumor motion characteristics differing in amplitude (1 to 3cm), period (3 to 5 second), and regularity (sinusoidal vs irregular) were tested. Treatment plans were delivered to a moving phantom up to 5-times exposure. Dose distribution on central coronal plane from 1 to 5 times exposure was measured with GAFCHROMIC EBT film. Dose differences occurring across 1 to 5 times exposure of treatment and between treatment plans were evaluated by analyzing measurements of gamma index, gamma index histogram, histogram changes, and dose at the center of the OAR. The experiment showed dose distortion due to organ motion increased between multiexposure 1 to 3 times but plateaued and remained constant after 3-times exposure. In addition, although larger motion amplitude and a longer period of motion both increased dosimetric error, the dose at the OAR was more significantly affected by motion amplitude rather than motion period. Irregularity of motion did not contribute significantly to dosimetric error when compared with other motion parameters. Restriction of organ motion to have small amplitude and short motion period together with larger jaw size and small modulation factor (with small pitch) is effective in reducing dosimetric error. Pretreatment measurements for 3-times exposure of treatment to a moving phantom with patient-specific tumor motion would provide a good estimation of the delivered dose distribution.

Virus-templated iridium oxide-gold hybrid nanowires for electrochromic application.

A highly porous electrode comprised of biologically templated iridium oxide-gold (IrO(2)-Au) hybrid nanowires is introduced for electrochromic applications. A filamentous M13 virus is genetically engineered to display IrO(2)-binding peptides on the viral surface and used as a template for the self-assembly of IrO(2) nanoclusters into a nanowire. The open porous morphology of the prepared nanowire film facilitates ion transport. Subsequently, the redox kinetics of the IrO(2) nanowires seems to be limited by the electric resistance of the nanowire film. To increase the electron mobility in the nanowires, gold nanoparticles are chemically linked to the virus prior to the IrO(2) mineralization, forming a gold nanostring structure along the long axis of the virus. The resulting IrO(2)-Au hybrid nanowires exhibit a switching time of 35 ms for coloration and 25 ms for bleaching with a transmission change of about 30.5% at 425 nm. These values represent almost an order of magnitude faster switching responses than those of an IrO(2) nanowire film having the similar optical contrast. This work shows that genetically engineered viruses can serve as versatile templates to co-assemble multiple functional molecules, enabling control of the electrochemical properties of nanomaterials.

Analysis of changes in dose distribution due to respiration during IMRT.

PURPOSE: Intensity modulated radiation therapy (IMRT) is a high precision therapy technique that can achieve a conformal dose distribution on a given target. However, organ motion induced by respiration can result in significant dosimetric error. Therefore, this study explores the dosimetric error that result from various patterns of respiration. MATERIALS AND METHODS: Experiments were designed to deliver a treatment plan made for a real patient to an in-house developed motion phantom. The motion pattern; the amplitude and period as well as inhale-exhale period, could be controlled by in-house developed software. Dose distribution was measured using EDR2 film and analysis was performed by RIT113 software. Three respiratory patterns were generated for the purpose of this study; first the 'even inhale-exhale pattern', second the slightly long exhale pattern (0.35 seconds longer than inhale period) named 'general signal pattern', and third a 'long exhale pattern' (0.7 seconds longer than inhale period). One dimensional dose profile comparisons and gamma index analysis on 2 dimensions were performed RESULTS: In one-dimensional dose profile comparisons, 5% in the target and 30% dose difference at the boundary were observed in the long exhale pattern. The center of high dose region in the profile was shifted 1 mm to inhale (caudal) direction for the 'even inhale-exhale pattern', 2 mm and 5 mm shifts to exhale (cranial) direction were observed for 'slightly long exhale pattern' and 'long exhale pattern', respectively. The areas of gamma index >1 were 11.88%, 15.11%, and 24.33% for 'even inhale-exhale pattern', 'general pattern', and 'long exhale pattern', respectively. The long exhale pattern showed largest errors. CONCLUSION: To reduce the dosimetric error due to respiratory motions, controlling patient's breathing to be closer to even inhaleexhale period is helpful with minimizing the motion amplitude.

Biologically templated photocatalytic nanostructures for sustained light-driven water oxidation.

Over several billion years, cyanobacteria and plants have evolved highly organized photosynthetic systems to shuttle both electronic and chemical species for the efficient oxidation of water. In a similar manner to reaction centres in natural photosystems, molecular and metal oxide catalysts have been used to photochemically oxidize water. However, the various approaches involving the molecular design of ligands, surface modification and immobilization still have limitations in terms of catalytic efficiency and sustainability. Here, we demonstrate a biologically templated nanostructure for visible light-driven water oxidation that uses a genetically engineered M13 virus scaffold to mediate the co-assembly of zinc porphyrins (photosensitizer) and iridium oxide hydrosol clusters (catalyst). Porous polymer microgels are used as an immobilization matrix to improve the structural durability of the assembled nanostructures and to allow the materials to be recycled. Our results suggest that the biotemplated nanoscale assembly of functional components is a promising route to significantly improved photocatalytic water-splitting systems.

Virus-templated assembly of porphyrins into light-harvesting nanoantennae.

Biological molecules can be used as versatile templates for assembling nanoscale materials because of their unique structures and chemical diversities. Supramolecular organization of molecular pigments, as is found in the natural light-harvesting antenna, has drawn attention for its potential applications to sensors, photocatalytic systems, and photonic devices. Here we show the arrangement of molecular pigments into a one-dimensional light-harvesting antenna using M13 viruses as scaffolds. Chemical grafting of zinc porphyrins to M13 viruses induces distinctive spectroscopic changes, including fluorescence quenching, the extensive band broadening and small red shift of their absorption spectrum, and the shortened lifetime of the excited states. Based on these optical signatures we suggest a hypothetical model to explain the energy transfer occurring in the supramolecular porphyrin structures templated with the virus. We expect that further genetic engineering of M13 viruses can allow us to coassemble other functional materials (e.g., catalysts and electron transfer mediators) with pigments, implying potential applications to photochemical devices.

Fractionated high-dose-rate brachytherapy in the management of uterine cervical cancer.

It is well known that intracavitary radiotherapy (ICR), either alone or in combination with external-beam radiotherapy (EBRT) is an essential component of the radiation treatment of uterine cervical cancer. Although low-dose-rate (LDR) brachytherapy has been successfully applied to the management of such patients, several radiation oncologists have experience of using high-dose-rate (HDR) brachytherapy with promising clinical results over the past 4 decades. However, there has been a considerable reluctance by radiation oncologists and gynecologists in North America to employ the HDR remote afterloading technique instead of the more firmly established LDR treatment modality. In contrast, the HDR-ICR system is rapidly gaining acceptance in Korea since the introduction of the Ralstron, remotely controlled afterloading system using HDR Co-60 sources, at the Yonsei Cancer Center in 1979. According to brachytherapy statistics reported by the Korean Society of Therapeutic Radiology and Oncology, in 1997, brachytherapy was performed upon 1,758 Korean patients with uterine cervical cancer, of whom approximately 83% received HDR brachytherapy. In this review, we present our experiences of HDR-ICR for the treatment of uterine cervical cancer. In addition, we discuss the controversial points, which are raised by those considering the use of HDR-ICR for uterine cervical cancer; these issues include physical and radiobiological considerations, and the prospect of future technical improvements.