Convergent Synthesis of Two Heterogeneous Fluxes from Glucose and Acetate for High-Yield Citramalate Production.

Biological production of citramalate has garnered attention due to its wide application for food additives and pharmaceuticals, although improvement of yield is known to be challenging. When glucose is used as the sole carbon source, carbon loss through decarboxylation steps for providing acetyl-CoA from pyruvate is inevitable. To avoid this, we engineered a strain to co-utilize glucose and cost-effective acetate while preventing carbon loss for enhancing citramalate production. The production pathway diverged to independently supply the precursors required for the synthesis of citramalate from glucose and acetate, respectively. Moreover, the phosphotransferase system was inactivated and the acetate assimilation pathway and the substrate ratio were optimized to enable the simultaneous and efficient utilization of both carbon sources. This yielded results (5.0 g/L, 0.87 mol/mol) surpassing the yield and titer of the control strain utilizing glucose as the sole carbon source in flask cultures, demonstrating an economically efficient strain redesign strategy for synthesizing various products.

In vivo photoacoustic monitoring of vasoconstriction induced by acute hyperglycemia.

Postprandial hyperglycemia, blood glucose spikes, induces endothelial dysfunction, increasing cardiovascular risks. Endothelial dysfunction leads to vasoconstriction, and observation of this phenomenon is important for understanding acute hyperglycemia. However, high-resolution imaging of microvessels during acute hyperglycemia has not been fully developed. Here, we demonstrate that photoacoustic microscopy can noninvasively monitor morphological changes in blood vessels of live animals' extremities when blood glucose rises rapidly. As blood glucose level rose from 100 to 400 mg/dL following intraperitoneal glucose injection, heart/breath rate, and body temperature remained constant, but arterioles constricted by approximately -5.7 ± 1.1% within 20 min, and gradually recovered for another 40 min. In contrast, venular diameters remained within about 0.6 ± 1.5% during arteriolar constriction. Our results experimentally and statistically demonstrate that acute hyperglycemia produces transitory vasoconstriction in arterioles, with an opposite trend of change in blood glucose. These findings could help understanding vascular glucose homeostasis and the relationship between diabetes and cardiovascular diseases.

Performance estimation of optical skin probe in short wavelength infrared spectroscopy based on Monte-Carlo simulation.

Optical throughput and optical path length are key parameters to obtain high signal to noise ratio and sensor sensitivity for the detection of skin tissue components based on short wavelength infrared (SWIR) spectroscopy. These parameters should be taken into account at the stage of optical system design. We aim to develop a method to estimate the optical efficiency and the effective water path length of a newly designed SWIR spectroscopy skin measurement system using Monte-Carlo photon migration simulation. To estimate the optical efficiency and the effective water path length, we investigated the characteristics of Monte-Carlo photon migration simulation utilizing one layered simple skin model. Simulation of photon transport in skin was conducted for transmission, transflection, and reflection optical configurations in both first overtone (1540 ~ 1820 nm) and combination (2040 ~ 2380 nm) wavelength ranges. Experimental measurement of skin spectrum was done using Fourier transform infrared spectroscopy based system to validate the estimation performance. Overall, the simulated results for optical efficiency and effective water path length are in good agreements with the experimental measurements, which shows the suggested method can be used as a means for the performance estimation and the design optimization of various in-vivo SWIR spectroscopic system.

Long-term follow-up results of cytarabine-containing chemotherapy for acute promyelocytic leukemia.

BACKGROUND/AIMS: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). METHODS: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. RESULTS: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. CONCLUSION: Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Fully integrated photoacoustic microscopy and photoplethysmography of human in vivo.

Photoacoustic microscopy (PAM) is used to visualize blood vessels and to monitor their time-dependent changes. Photoplethysmography (PPG) measures hemodynamic time-series changes such as heart rate. However, PPG's limited visual access to the dynamic changes of blood vessels has prohibited further understanding of hemodynamics. Here, we propose a novel, fully integrated PAM and photoplethysmography (PAM-PPG) system to understand hemodynamic features in detail. Using the PAM-PPG system, we simultaneously acquire vascular images (by PAM) and changes in the blood volume (by PPG) from human fingers. Next, we determine the heart rate from changes in the PA signals, which match well with the PPG signals. These changes can be measured if the blood flow is not blocked. From the results, we believe that PAM-PPG could be a useful clinical tool in various clinical fields such as cardiology and endocrinology.

Parasites and blood-meal hosts of the tsetse fly in Tanzania: a metagenomics study.

BACKGROUND: Tsetse flies can transmit various Trypanosoma spp. that cause trypanosomiasis in humans, wild animals, and domestic animals. Amplicon deep sequencing of the 12S ribosomal RNA (rRNA) gene can be used to detect mammalian tsetse hosts, and the 18S rRNA gene can be used to detect all associated eukaryotic pathogens, including Trypanosoma spp. METHODS: Tsetse flies were collected from the Serengeti National Park (n = 48), Maswa Game Reserve (n = 42), and Tarangire National Park (n = 49) in Tanzania in 2012-13. Amplicon deep sequencing targeting mammal-specific 12S rRNA and 18S rRNA genes was performed to screen the blood-feeding sources of tsetse flies and eukaryotic parasites in tsetse flies, respectively. RESULTS: 12S rRNA gene deep sequencing revealed that various mammals were blood-feeding sources of the tsetse flies, including humans, common warthogs, African buffalos, mice, giraffes, African elephants, waterbucks, and lions. Genes of humans were less frequently detected in Serengeti (P = 0.0024), whereas African buffaloes were detected more frequently as a blood-feeding source (P = 0.0010). 18S rRNA gene deep sequencing showed that six tsetse samples harbored the Trypanosoma gene, which was identified as Trypanosoma godfreyi and Trypanosoma simiae in subsequent ITS1 gene sequencing. CONCLUSIONS: Through amplicon deep sequencing targeting the 12S rRNA and 18S rRNA genes, various mammalian animals were identified as blood-meal sources, and two Trypanosoma species were detected in tsetse flies collected from the Maswa Game Reserve, Serengeti National Park, and Tarangire National Park in Tanzania. This study illustrates the patterns of parasitism of tsetse fly, wild animals targeted by the fly, and Trypanosoma spp. carried by the fly in Tanzania. It may provide essential data for formulating better strategies to control African trypanosomes.

Temperature Correction to Enhance Blood Glucose Monitoring Accuracy Using Electrical Impedance Spectroscopy.

Electrical methods are among the primarily studied non-invasive glucose measurement techniques; however, various factors affect the accuracy of the sensors used. Of these, the temperature is a critical factor; hence, the effects of temperature on the electrical properties of blood components are investigated in this study. Furthermore, the changes in the electrical properties of blood according to the glucose level are corrected by considering the effects of temperature on the electrical properties. An impedance sensor is developed and used to measure whole blood impedance in 10 healthy participants at various temperatures and glucose levels. Subsequently, the conductivities of the plasma and cytoplasm were extracted. Changes in the electrical properties of the blood components are then analyzed using linear regression and repeated measures ANOVA. The electrical conductivities of plasma and cytoplasm increased with increasing temperatures (plasma: 0.0397 (slope), 0.7814 (R2), cytoplasm: 0.014 (slope), 0.694 (R2)). At three values of increasing glucose levels (85.4, 158.1, and 271.8 mg/dL), the electrical conductivities of the plasma and cytoplasm decreased. These tendencies are more significant upon temperature corrections (p-values; plasma: 0.001, 0.001, cytoplasm: 0.003, 0.002). The relationships between temperature and electrical conductivity changes can thus be used for temperature corrections in blood glucose measurement.

Direct observation of glucose fingerprint using in vivo Raman spectroscopy.

Noninvasive blood glucose monitoring has been a long-standing dream in diabetes management. The use of Raman spectroscopy, with its molecular specificity, has been investigated in this regard over the past decade. Previous studies reported on glucose sensing based on indirect evidence such as statistical correlation to the reference glucose concentration. However, these claims fail to demonstrate glucose Raman peaks, which has raised questions regarding the effectiveness of Raman spectroscopy for glucose sensing. Here, we demonstrate the first direct observation of glucose Raman peaks from in vivo skin. The signal intensities varied proportional to the reference glucose concentrations in three live swine glucose clamping experiments. Tracking spectral intensity based on linearity enabled accurate prospective prediction in within-subject and intersubject models. Our direct demonstration of glucose signal may quiet the long debate about whether glucose Raman spectra can be measured in vivo in transcutaneous glucose sensing.

Non-invasive assessments of the advanced glycation end products in human skin using reflectance NIR spectroscopy.

Advanced glycation end products (AGE) are produced by non-enzymatic reaction between glucose and biomolecules including proteins. AGE accumulation is known to cause alternations of structure and function in proteins and to be related with an increased risk of diabetic complications, cardiovascular diseases, and aging processes. Conventionally, AGE accumulation has been estimated by measuring auto fluorescence level using ultraviolet (UV) light excitation. In this study, we investigated an alternative approach to estimate auto fluorescence level and thus AGE accumulation in in vivo human skin using NIR (Near-Infrared) spectroscopy. To examine spectral features attributed to glycation in proteins, we first analyzed in vitro NIR spectra from native and glycated protein. Then, we further examined NIR spectra of in vivo skin from human subjects, and estimated their auto fluorescence level using several multivariate regression approaches. Our analysis in in vitro spectra from native and glycated albumin revealed that glycation may affect -CH and -NH stretching. Furthermore, we elucidated that those bands for -CH and -NH may be responsible for the variation in auto fluorescence level in human skin NIR spectra. Finally, auto fluorescence level was estimated from those NIR spectra using several multivariate regression methods: principal component regression (PCR), partial least square regression (PLS-R) and support vector regression (SVR). Among the three methods, SVR showed the best performance. We demonstrated in this study that NIR spectroscopy can be used as an alternative non-invasive method to estimate AGE accumulation in in vivo human skin tissue without UV radiation on skin tissue.

Non-invasive method to monitor molecular changes in human stratum corneum during acute barrier disruption using reflectance NIR spectroscopy.

Stratum corneum is the outer most part of skin for barrier function. Disorder in stratum corneum is related with many skin diseases including acne, atopic dermatitis and psoriasis. In developed countries, about 20% of the population has disorder in the barrier function of stratum corneum. Adhesive tape stripping is a method to disrupt skin barrier function in studying disorder in stratum corneum. In this study, we obtained NIR (Near-Infrared) spectrum of human skin after tape stripping. Changes in skin spectra after barrier disruption were investigated through principal component analysis (PCA) of spectrum. PCA analysis revealed that peaks for -NH stretching and -CH vibration mainly contributed to the spectral variation caused by barrier disruption. Furthermore, second derivative of spectrum revealed that acute barrier disruption contributes to spectral changes in the region related with secondary structure of protein, lipid and water associated with lipid in stratum corneum. We demonstrated that acute barrier disruption affected features in NIR spectrum. These spectral changes revealed that acute barrier disruption affected keratin protein and ceramide in human stratum corneum. These results suggest that NIR spectroscopy can be used to monitor changes in filamentous network and lamellar structure in stratum corneum. NIR spectroscopy can provide non-invasive method to investigate skin disease related with barrier disruption by monitoring disturbance in protein and lipid structure in stratum corneum.

Prevalence of Tick-Borne Pathogens from Ticks Collected from Cattle and Wild Animals in Tanzania in 2012.

This study was aimed to disclose the prevalence rate of tick-borne pathogens from ticks collected from cattle and wild animals in Tanzania in 2012. Ticks were collected from slaughtered cattle and dead wild animals from November 5 to December 23, 2012 and identified. PCR for detecting Anaplasmataceae, Piroplamidae, Rickettsiaceae, Borrelia spp., and Coxiella spp. were done. Among those tested, Rickettsiaceae, Piroplasmidae, and Anaplasmataceae, were detected in ticks from the 2 regions. Rickettsiaceae represented the major tick-borne pathogens of the 2 regions. Ticks from animals in Maswa were associated with a higher pathogen detection rate compared to that in ticks from Iringa. In addition, a higher pathogen detection rate was observed in ticks infesting cattle than in ticks infesting wild animals. All examined ticks of the genus Amblyomma were infected with diverse pathogens. Ticks of the genera Rhipicephalus and Hyalomma were infected with 1 or 2 pathogens. Collectively, this study provides important information regarding differences in pathogen status among various regions, hosts, and tick species in Tanzania. Results in this study will affect the programs to prevent tick-borne diseases (TBD) of humans and livestock in Tanzania.

[A development of Byzantine Christian charities during the 4(th)-7(th) centuries and the birth of the hospital].

This study aims to examine the beginning and the development of Christian Charities during the 4(th)-6(th) centuries which would eventually result in the birth of the hospital in modern sense in the first half of the 7(th) century. For this purpose, I looked carefully into various primary sources concerning the early Christian institutions for the poor and the sick. Above all, it's proper to note that the first xenodocheion where hospitality was combined with a systematic caring, is concerned with the Trinitarian debate of the 4(th) century. In 356, Eustathios, one of the leaders of homoiousios group, established xenodocheion to care for the sick and the lepers in Sebaste of Armenia, whereas his opponent Aetios, doctor and leader of the heteroousios party, was reckoned to have combined the medical treatment with his clerical activities. Then, Basil of Caesarea, disciple of Eustathios of Sebaste, also founded in 372 a magnificent benevolent complex named 'Basileias' after its founder. I scrupulously analysed several contemporary materials mentioning the charitable institution of Caesarea which was called alternatively katagogia, ptochotropheion, xenodocheion. John Chrysostome also founded several nosokomeia in Constantinople at the end of the 4(th) century and the beginning of the 5(th) century. Apparently, the contemporary sources mention that doctors existed for these Charities, but there is no sufficient proof that these 'Christian Hospitals,' Basileias or nosokomeia of Constantinople were hospitals in modern sense. Imperial constitutions began to mention ptochotropheion, xenodocheion and orphanotropheion since the second half of the 5(th) century and then some Justinian laws evoked nosokomium, brephotrophia, gerontocomia. These laws reveal that 'Christian Hospitals' were well clarified and deeply rooted in Byzantine society already in these periods. And then, new benevolent institutions emerged in the 6(th) century: nosokomeia for a specific class and lochokomeia for maternity. In addition, one of the important functions of Sampson Xenon was, according to Novel 59, to hold a funeral service for the people of Constantinople. Nevertheless, there is no sufficient literary material that could demonstrate the existence of a hospital in modern sense. The first hospital where outpatient service, hospitalization and surgery were confirmed was Sampson Xenon in the first half of the 7th century, figured in the tale of Stephanos of the The Miracles of St. Artemios. Why was the early Byzantine literary so reticent as to write the medical activities in the Christian Charities? It's because Christian innovation didn't rest on the medical treatment but caring for the poor and the sick, depending on the word of Mt. 25.35-36. In this meaning, I'd like to say that the Early Byzantine history of Christian Charities or 'Christian Hospitals' consists of only a footnote of the verse.

Ixodid tick infestation in cattle and wild animals in Maswa and Iringa, Tanzania.

Ticks and tick-borne diseases are important in human and livestock health worldwide. In November 2012, ixodid ticks were collected and identified morphologically from cattle and wild animals in the Maswa district and Iringa urban, Tanzania. Amblyomma gemma, A. lepidum, and A. variegatum were identified from Maswa cattle, and A. variegatum was the predominant species. A. marmoreum, Hyalomma impeltatum, and Rhipicephalus pulchellus were identified from Iringa cattle in addition to the above 3 Amblyomma species, and A. gemma was the most abundant species. Total 4 Amblyomma and 6 Rhipicephalus species were identified from wild animals of the 2 areas. A. lepidum was predominant in Maswa buffaloes, whereas A. gemma was predominant in Iringa buffaloes. Overall, A. variegatum in cattle was predominant in the Maswa district and A. gemma was predominant in Iringa, Tanzania.

Dirac dynamics in one-dimensional graphene-like plasmonic crystals: pseudo-spin, chirality, and diffraction anomaly.

We introduce a new class of plasmonic crystals possessing graphene-like internal symmetries and Dirac-type spectrum in k-space. We study dynamics of surface plasmon polaritons supported in the plasmonic crystals by employing the formalism of Dirac dynamics for relativistic quantum particles. Through an analogy with graphene, we introduce a concept of pseudo-spin and chirality to indicate built-in symmetry of the plasmonic crystals near Dirac point. The surface plasmon polaritons with different pseudo-spin states are shown to split in the crystals into two beams, analogous to spin Hall effect.

General properties of surface modes in binary metal-dielectric metamaterials.

We present general properties of surface modes in binary metal-dielectric metamaterials. We show mechanism for surface mode formation and analyze their existence conditions for semi-infinite metamaterials in the frame of couple mode theory.

Diabolical point and conical-like diffraction in periodic plasmonic nanostructures.

We present the formation of a singular (diabolical) point in k-space from a periodic metal-dielectric waveguide array. The singularity originates from the balance between alternating normal and anomalous coupling. We numerically demonstrate a strong diffraction anomaly (conical-like diffraction) near the singular point. We also show the evolution of the diffraction pattern with band deformation. The resultant peculiar propagation dynamics of surface plasmon polaritons could provide a new toolset for manipulating light on the nano-scale.

Bisphenol A migration from polycarbonate baby bottle with repeated use.

This study was to quantify the migration of bisphenol A (BPA), from new polycarbonate (PC) baby bottle into the water filled in the bottle, with repeated use up to 100 times and extraction by water temperature ranging from 40 degrees C to 100 degrees C. BPA was determined by GC-MS, operated in the selected ion monitoring mode. The concentrations of BPA, migrated from brand-new PC baby bottle, were 0.03ppb and 0.13ppb at 40 degrees C and 95 degrees C, respectively. However, the concentration of BPA from the bottle used for 6months, were 0.18ppb and 18.47ppb at 40 degrees C and 95 degrees C, respectively. The levels of BPA migration were rapidly increased when the water temperature was over 80 degrees C. The variations of BPA level were divided into three regions; lag effect, steady and aging, which showed different increasing rate. PC baby bottle after being utilized 60 times which was correspond to the baby bottle used for 3months started aging. It also showed an increasing rate of 4.9x10(-2)ppbtime(-1). These results are explained by increase in d-spacing of PC baby bottle. The d-spacing of PC baby bottle increases with repeated use from 0.499nm in brand-new bottles to 0.511nm with bottles which had been used for 6months.

Subwavelength hybrid terahertz waveguides.

We introduce and present general properties of hybrid terahertz waveguides. Weakly confined Zenneck waves on a metal-dielectric interface at terahertz frequencies can be transformed to a strongly confined yet low-loss subwavelength mode through coupling with a photonic mode of a nearby high-index dielectric strip. We analyze confinement, attenuation, and dispersion properties of this mode. The proposed design is suitable for planar integration and allows easy fabrication on chip scale. The superior waveguiding properties at terahertz frequencies could enable the hybrid terahertz waveguides as building blocks for terahertz integrated circuits.

Observation of stimulated emission of surface plasmon polaritons.

We report a direct experimental evidence of stimulated emission of surface plasmon polaritons (SPPs) at telecom wavelengths (1532 nm) with erbium doped glass as a gain medium. We observe an increase in the propagation length of signal surface plasmons when erbium ions are excited optically using pump SPP. The design, fabrication, and characterization of SPP waveguides, thin gold metal strips, embedded in erbium (Er) doped phosphate glass is presented. Such systems can be suitable as integrated devices coupling electronic and photonic data transmissions as well as SPP amplifiers and SPP lasers.