Application of polyimide films as a nuclear track detector (2): A latent track structure study with Fourier transform infrared spectroscopy.

This paper reports the relation between latent track structure and the detection threshold of etch pits formation in UPILEX-S® and Kapton. At the similar stopping power value, effective track core radii and G values for heavier ions are lower than those of lighter ions. These results would be due to the difference of the radial dose distribution for low- and high-velocity ions. The G value starts more rapidly rising above 600 and 1000 keV/µm for Kapton and UPILEX-S®, respectively. The detection threshold of UPILEX-S is 4000 keV/µm for Ar ions, at which effective track core radii of all functional groups are larger than 2 nm. Since the length of a molecule unit of UPILEX-S® is about 1.4 nm, at least more than two molecule units have to be damaged for the etch pit formation. A similar discussion is applicable to Kapton, whose detection threshold is significantly lower than UPILEX-S®.

Application of polyimide films as a nuclear track detector (1): A systematic study of track registration sensitivity.

This paper reports the variation of track registration sensitivity as a function of the stopping power of heavy ions in UPILEX-S® films, which is known as the most radiation tolerant polyimide (PI). The detection thresholds in the stopping power for etch pit formation are determined as 4,000, 4,100, 4,800, and 5600 keV/µm for 40Ar, 84Kr, 132Xe and 238U ions, respectively. Furthermore, we investigate the latent track structure in two kinds of PI films (UPILEX-S® and Kapton) by means of FT-IR spectroscopy. At the similar stopping power value, the radiation chemical yields (G value) for heavier ions are lower than those of lighter ions. This is due to the difference of the radial dose distribution for low and high velocity ions.

Long-term effects of low-intensity training with slow movement on motor function of elderly patients: a prospective observational study.

BACKGROUND: Slow-motion training, which comprises exercising using extremely slow-movements, yields a training effect like that of high-intensity training, even when the applied load is small. We developed a slow-training exercise program that allows elderly people to safely use their own body weight without a machine. Previously, it was confirmed that functional gait and lower limb muscle strength were improved by low-intensity training using bodyweight training for 3 months. This study evaluated the long-term effects of low-intensity training using body weight with slow-movements on the motor function of frail, elderly patients. METHODS: Ninety-six elderly men and women aged 65 years or older whose level of nursing care was classified as either support required (1 and 2) or long-term care required (care levels 1 and 2) volunteered to participate. Two facilities were used. Participants at the first facility used low-intensity training using body weight with slow-movements (low-stress training [LST] group, n = 65), and participants at another facility used machine training (MT group, n = 31). Exercise interventions were conducted for 12 months, once or twice per week, depending on the required level of nursing care. Changes in motor function were examined. RESULTS: Post-intervention measurements based on the results of the chair-stand test after 12 months showed significant improvements from pre-intervention levels (P < 0.0001) in the LST group and MT group. Although the ability of performing the Timed Up & Go test and the ability to stand on one leg with eyes open improved in both groups, no significant change was observed. When changes after 12 months were compared between the two groups, no significant difference was observed for any variables. CONCLUSIONS: Slow body weight training for 12 months without a machine improved the lower limb muscle strength. Therefore, it could have the same effects as training using a machine. TRIAL REGISTRATION: UMIN000030853 . Registered 17 January 2018 (retrospectively registered).

Pharmacokinetic and Pharmacodynamic Profiles of Glyco-Modified Atrial Natriuretic Peptide Derivatives Synthesized Using Chemo-enzymatic Synthesis Approaches.

Atrial natriuretic peptide (ANP) exerts beneficial pharmacological effects in the treatment of various cardiovascular disorders, such as acute congestive heart failure (ADHF). However, the clinical use of ANP is limited to the continuous intravenous infusion owing to its short half-life (2.4 ± 0.7 min). In the present study, we conjugated the glyco-modified ANP with a monoclonal antibody (mAb) or an Fc via chemo-enzymatic glyco-engineering using EndoS D233Q/Q303L. The most potent derivative SG-ANP-Fc conjugate extended the half-life to 14.9 d and the duration of blood pressure lowering effect to over 28 d. This new biologic modality provides an opportunity to develop outpatient therapy after ADHF.

Effects of low-intensity bodyweight training with slow movement on motor function in frail elderly patients: a prospective observational study.

BACKGROUND: Slow-motion training, an exercise marked by extremely slow movements, yields a training effect like that of a highly intense training, even when the applied load is small. This study evaluated the effects of low-intensity bodyweight training with slow movement on motor function in frail, elderly patients. METHODS: Ninety-seven elderly men and women aged 65 years or older, whose level of nursing care was classified as either support required (1 and 2) or long-term care required (care level 1 and 2), volunteered to participate. Two facilities were used. Participants in the first facility used low-intensity bodyweight training with slow movement (the LST group, n = 65), and participants in another facility used machine training (the control group, n = 31). Exercises were conducted for 3 months, once or twice a week, depending on the required level of nursing care. Changes in motor function were examined. RESULTS: Post-exercise measurements showed significant improvements from the pre-exercise levels after 3 months, based on the results of the Timed Up and Go test (p = 0.0263) and chair-stand test (p = 0.0016) in the low-intensity exercise with slow movement and tonic force generation (LST) group. Although the ability to stand on one leg with eyes open tended to improve, no significant change was found (p = 0.0964). CONCLUSIONS: We confirmed that carrying out LST bodyweight training for 3 months led to improvements in ambulatory function and lower-limb muscle strength. In this way, it is possible that LST training performed by holding a bar or by staying seated on a chair contributes to improved motor function in elderly patients within a short time. TRIAL REGISTRATION: UMIN000030853 . Registered 17 January 2018. (retrospectively registered).

Fast computer hologram generation by flexible-ratio adaptive point-spread spherical wave synthesis.

We propose a flexible-ratio adaptive point-spread spherical wave synthesis method for fast computer-generated hologram calculation. The conventional adaptive point-spread algorithm uses a fixed ratio between the major and minor axes of the point source, whereas the proposed method uses flexible-ratio sources, i.e., ellipses, for more effective calculation. Numerical simulation was conducted to validate the proposed method. The results show that the proposed method has the potential to achieve faster calculation, compared to the calculation in conventional methods, without significant image degradation.

α-Glucosidase inhibitor miglitol attenuates glucose fluctuation, heart rate variability and sympathetic activity in patients with type 2 diabetes and acute coronary syndrome: a multicenter randomized controlled (MACS) study.

BACKGROUND: Little is known about clinical associations between glucose fluctuations including hypoglycemia, heart rate variability (HRV), and the activity of the sympathetic nervous system (SNS) in patients with acute phase of acute coronary syndrome (ACS). This pilot study aimed to evaluate the short-term effects of glucose fluctuations on HRV and SNS activity in type 2 diabetes mellitus (T2DM) patients with recent ACS. We also examined the effect of suppressing glucose fluctuations with miglitol on these variables. METHODS: This prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group comparative study included 39 T2DM patients with recent ACS, who were randomly assigned to either a miglitol group (n = 19) or a control group (n = 20). After initial 24-h Holter electrocardiogram (ECG) (Day 1), miglitol was commenced and another 24-h Holter ECG (Day 2) was recorded. In addition, continuous glucose monitoring (CGM) was performed throughout the Holter ECG. RESULTS: Although frequent episodes of subclinical hypoglycemia (≤4.44 mmo/L) during CGM were observed on Day 1 in the both groups (35% of patients in the control group and 31% in the miglitol group), glucose fluctuations were decreased and the minimum glucose level was increased with substantial reduction in the episodes of subclinical hypoglycemia to 7.7% in the miglitol group on Day 2. Holter ECG showed that the mean and maximum heart rate and mean LF/HF were increased on Day 2 in the control group, and these increases were attenuated by miglitol. When divided 24-h time periods into day-time (0700-1800 h), night-time (1800-0000 h), and bed-time (0000-0700 h), we found increased SNS activity during day-time, increased maximum heart rate during night-time, and glucose fluctuations during bed-time, which were attenuated by miglitol treatment. CONCLUSIONS: In T2DM patients with recent ACS, glucose fluctuations with subclinical hypoglycemia were associated with alterations of HRV and SNS activity, which were mitigated by miglitol, suggesting that these pathological relationships may be a residual therapeutic target in such patients. Trial registration Unique Trial Number, UMIN000005874 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006929 ).

Single-pixel digital holography with phase-encoded illumination.

We demonstrate imaging of complex amplitude objects through digital holography with phase-structured illumination and bucket detection. The object is sampled with a set of micro-structured phase patterns implemented onto a liquid-crystal spatial light modulator while a bucket detector sequentially records the irradiance fluctuations corresponding to the interference between object and reference beams. Our reconstruction algorithm retrieves the unknown phase information from the full set of photocurrent measurements. Interestingly, the sampling functions can be codified onto the reference beam, so they can be nonlocal with respect to the object. Finally, we show that the system is well-fitted for transmission of the object information through scattering media.

Evaluation of Enzymatic Deinking of Non-impact Ink Laser-Printed Paper Using Crude Enzyme from Penicillium rolfsii c3-2(1) IBRL.

Application of microbial enzymes for paper deinking is getting tremendous attention due to the rapidly increasing of waste paper every year. This study reports the deinking efficiency of laser-printed paper by the lignocellulolytic enzyme from Penicillium rolfsii c3-2(1) IBRL strain compared to other enzyme sources as well as commercial available enzymes. High enzymatic deinking efficiency of approximately 82 % on laser-printed paper was obtained by pulp treatment with crude enzyme from P. rolfsii c3-2(1) IBRL. However, this crude enzyme was found to reduce the paper strength properties of the pulp based on the results of tensile, tear and burst indices, most probably due to the cellulose degradation. This was further proven by the low viscosity of paper pulp obtained after enzymatic treatment and increasing of sugar production during the treatment. Balancing to this detrimental effect on paper pulp, high deinking efficiency was achieved within a short period of time, in which the enzymatic treatment was conducted for 30 min that enabled contribution to higher brightness index obtained, thus promoting savings of time and energy consumption, therefore environmental sustainability. Extensive research should be conducted to understand the nature and mechanism of enzymatic deinking process by the crude enzyme from P. rolfsii c3-2(1) IBRL in order to improve paper strength properties.

Characterization of oil-palm trunk residue degradation enzymes derived from the isolated fungus, Penicillium rolfsii c3-2(1) IBRL.

This study characterizes crude enzymes derived from Penicillium rolfsii c3-2(1) IBRL, a mesophilic fungus isolated from the local soil of Malaysia. Prior to enzyme activity evaluation, P. rolfsii c3-2(1) IBRL was inoculated into a broth medium containing oil-palm trunk residues for the preparation of crude enzymes. Oil-palm trunk residues were optimally hydrolysed at pH5.0 and 50°C. P. rolfsii c3-2(1) IBRL-derived crude enzymes displayed higher thermal stability compared with the commercial enzymes, Celluclast 1.5 L and Acellerase 1500. Moreover, the hydrolysing activities of the P. rolfsii c3-2(1) IBRL-derived crude enzymes (xylan, arabinan, and laminarin) were superior compared to that of Celluclast 1.5 L and Acellerase 1500, and exhibit 2- to 3-fold and 3- to 4-fold higher oil-palm trunk residues-hydrolysing specific activity, respectively. This higher hydrolysis efficiency may be attributed to the weak 'lignin-binding' ability of the P. rolfsii c3-2(1) IBRL-derived enzymes compared to the commercial enzymes.

Cellulose hydrolysis ability of a Clostridium thermocellum cellulosome containing small-size scaffolding protein CipA.

Mutant Clostridium thermocellum YM72 that produces small-size scaffolding protein CipA (ssCipA) was isolated from wild-type YM4. Sequencing of ssCipA revealed that two domains, cohesin 6 and cohesin 7, were not present. Cellulosome prepared from YM72 exhibited a significant reduction of hydrolysis ability on crystalline celluloses such as Sigmacell type-20 and cellulose from Halocynthia. To investigate this influence in vitro, artificial cellulosomes were assembled as recombinant CipA (rCipA) and ssCipA (rssCipA) using native free-cellulosomal subunits. The cellulosome assembled using rssCipA showed a 1.8-fold decrease in the hydrolysis of crystalline cellulose compared with that of rCipA. However, no significant differences in the hydrolysis of carboxymethylcellulose and acid-swollen cellulose were observed. One protein band was missing from the complex that was assembled using rssCipA (confirmed by native-PAGE). The missing protein was identified as CelJ, which is a major cellulosomal subunit. This suggests that insufficient cooperation of CelJ into the cellulosome results in the significant reduction of hydrolysis toward crystalline cellulose. These results indicate that cohesin 6 and 7 may be responsible for the cooperation of CelJ through cohesin and dockerin interactions, and adequate cooperation of CelJ into the cellulosome is important for significant hydrolysis of crystalline cellulose.

Single-shot three-dimensional shape measurement by low-coherent optical path difference digital holography.

A single-shot three-dimensional (3D) shape measurement by low-coherent optical path difference digital holography with small energy consumption is proposed. The use of a superluminescent diode makes it possible. Weighting of the single hologram and numerical reconstruction give the 3D shape of an object. Experimental results using a simple object (the surface of a button cell battery) are given. By comparison with experimental results using a vertical scanning method, the proposed method is confirmed. The effects of a shift interval of the hologram and a zero-order component on a measurement result are also discussed.

Additive effects of cilnidipine, an L-/N-type calcium channel blocker, and an angiotensin II receptor blocker on reducing cardiorenal damage in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes mellitus.

Cilnidipine (Cil), which is an L-/N-type calcium channel blocker (CCB), has been known to provide renal protection by decreasing the activity of the sympathetic nervous system (SNS) and the renin-angiotensin system. In this study, we compared the effects of the combination of Cil and amlodipine (Aml), which is an L-type CCB, with an angiotensin (Ang) II receptor blocker on diabetic cardiorenal damage in spontaneously type 2 diabetic rats. Seventeen-week-old Otsuka Long-Evans Tokushima Fatty rats were randomly assigned to receive Cil, Aml, valsartan (Val), Cil + Val, Aml + Val, or a vehicle (eight rats per group) for 22 weeks. Antihypertensive potencies were nearly equal among the CCB monotherapy groups and the combination therapy groups. The lowering of blood pressure by either treatment did not significantly affect the glycemic variables. However, exacerbations of renal and heart failure were significantly suppressed in rats administered Cil or Val, and additional suppression was observed in those administered Cil + Val. Although Val increased the renin-Ang system, Aml + Val treatment resulted in additional increases in these parameters, while Cil + Val did not show such effects. Furthermore, Cil increased the ratio of Ang-(1-7) to Ang-I, despite the fact that Val and Aml + Val decreased the Ang-(1-7) levels. These actions of Cil + Val might be due to their synergistic inhibitory effect on the activity of the SNS, and on aldosterone secretion through N-type calcium channel antagonism and Ang II receptor type 1 antagonism. Thus, Cil may inhibit the progression of cardiorenal disease in type 2 diabetes patients by acting as an N-type CCB and inhibiting the aldosterone secretion and SNS activation when these drugs were administered in combination with an Ang II receptor blocker.

Speckle reduction in holographic projection by random pixel separation with time multiplexing.

A speckle-reduction method with random locations of sparse object points is proposed for image quality improvement based on a time-multiplexing approach in holographic reconstruction. The object points of a reconstructed image are divided into groups of sparse object points. Pixel separation of the periodic location, in general, is used for the sparse object points. However, an unwanted periodic fringe pattern is caused, and it dominantly degrades the reconstructed image quality. The proposed random pixel separation enables the reconstructed image quality to improve more effectively. The numerical simulation and the optical experiment are presented to confirm the performance of the proposed method.

Direct glucose production from lignocellulose using Clostridium thermocellum cultures supplemented with a thermostable ß-glucosidase.

BACKGROUND: Cellulases continue to be one of the major costs associated with the lignocellulose hydrolysis process. Clostridium thermocellum is an anaerobic, thermophilic, cellulolytic bacterium that produces cellulosomes capable of efficiently degrading plant cell walls. The end-product cellobiose, however, inhibits degradation. To maximize the cellulolytic ability of C. thermocellum, it is important to eliminate this end-product inhibition. RESULTS: This work describes a system for biological saccharification that leads to glucose production following hydrolysis of lignocellulosic biomass. C. thermocellum cultures supplemented with thermostable beta-glucosidases make up this system. This approach does not require any supplementation with cellulases and hemicellulases. When C. thermocellum strain S14 was cultured with a Thermoanaerobacter brockii beta-glucosidase (CglT with activity 30 U/g cellulose) in medium containing 100 g/L cellulose (617 mM initial glucose equivalents), we observed not only high degradation of cellulose, but also accumulation of 426 mM glucose in the culture broth. In contrast, cultures without CglT, or with less thermostable beta-glucosidases, did not efficiently hydrolyze cellulose and accumulated high levels of glucose. Glucose production required a cellulose load of over 10 g/L. When alkali-pretreated rice straw containing 100 g/L glucan was used as the lignocellulosic biomass, approximately 72% of the glucan was saccharified, and glucose accumulated to 446 mM in the culture broth. The hydrolysate slurry containing glucose was directly fermented to 694 mM ethanol by addition of Saccharomyces cerevisiae, giving an 85% theoretical yield without any inhibition. CONCLUSIONS: Our process is the first instance of biological saccharification with exclusive production and accumulation of glucose from lignocellulosic biomass. The key to its success was the use of C. thermocellum supplemented with a thermostable beta-glucosidase and cultured under a high cellulose load. We named this approach biological simultaneous enzyme production and saccharification (BSES). BSES may resolve a significant barrier to economical production by providing a platform for production of fermentable sugars with reduced enzyme amounts.

Effects of low-carbohydrate/high-monounsaturated fatty acid liquid diets on diurnal glucose variability and insulin dose in type 2 diabetes patients on tube feeding who require insulin therapy.

OBJECTIVE: A low-carbohydrate/high-monounsaturated fatty acid liquid diet (LC/HMD) was investigated for its role in long-term glycemic control in tube-fed type 2 diabetes patients who require insulin therapy. PATIENTS AND METHODS: The study included 10 type 2 diabetes patients requiring insulin therapy who were being tube-fed with a high-carbohydrate liquid diet (HCD). With stable glucose control maintained, these patients were monitored for glucose levels for 4 consecutive days by using continuous glucose monitoring (CGM). The patients were continued on HCD during the first 2 days and were switched to an LC/HMD during the final 2 days. The patients were then continued on the LC/HMD, and seven of the 10 patients were monitored for glucose levels for 2 consecutive days by using CGM after 3 months of feeding with the LC/HMD. Insulin regimens used included basal-bolus insulin in five of these seven patients and intermediate-acting insulin in two patients. RESULTS: Based on CGM data, the indices for glucose variability, such as SDs of 288 glucose levels for 24 h, total area for the range of glucose variability, mean amplitude of glycemic excursions, and 24-h mean glucose levels were significantly decreased 3 months after switching from the HCD to the LC/HMD. Additionally, despite the significant decrease in required insulin dose, the hemoglobin A1c (HbA1c) values were significantly decreased 3 months after switching. CONCLUSIONS: Study results demonstrated that the LC/HMD not only narrowed the range of glucose variability, but also decreased the required insulin dose and HbA1c values in diabetes patients on tube feeding who required insulin therapy, suggesting the LC/HMD may be useful in long-term glycemic control in these patients.

Synthesis and optimization of novel (3S,5R)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as orally active renin inhibitors.

We report synthesis and optimization of a series of (3S,5R)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as renin inhibitors. Chemical modification of P1', P2' and P3 portions led to a promising 3,5-disubstituted piperidine 32o showing high renin inhibitory activity and favorable oral exposure in both rats and cynomolgus monkeys with acceptable CYP and hERG current inhibition. Compound 32o exhibited a significant blood pressure lowering effect by oral administration in two hypertensive animal models, double transgenic rats and furosemide pretreated cynomolgus monkeys.

Synthesis method from low-coherence digital holograms for improvement of image quality in holographic display.

In holographic displays, it is undesirable to observe the speckle noises with the reconstructed images. A method for improvement of reconstructed image quality by synthesizing low-coherence digital holograms is proposed. It is possible to obtain speckleless reconstruction of holograms due to low-coherence digital holography. An image sensor records low-coherence digital holograms, and the holograms are synthesized by computational calculation. Two approaches, the threshold-processing and the picking-a-peak methods, are proposed in order to reduce random noise of low-coherence digital holograms. The reconstructed image quality by the proposed methods is compared with the case of high-coherence digital holography. Quantitative evaluation is given to confirm the proposed methods. In addition, the visual evaluation by 15 people is also shown.

Effects of add-on treatment with sitagliptin on narrowing the range of glucose fluctuations in Japanese type 2 diabetes patients receiving insulin therapy.

BACKGROUND: In an earlier continuous glucose monitoring (CGM)-based study, we reported that sitagliptin not only reduced 24-h mean glucose levels but also suppressed postprandial glucose increases, thus reducing the range of glycemic fluctuations in type 2 diabetes patients. In this study, we investigated whether sitagliptin might provide similar benefits in type 2 diabetes patients receiving insulin therapy by using CGM. PATIENTS AND METHODS: The study included a total of 13 type 2 diabetes patients in whom stable glycemic control had been achieved after admission for glycemic control. Insulin regimens used included long-acting insulin preparations once daily in four patients and biphasic insulin preparations twice daily in nine, with the daily insulin dose being 19.0±12.7 U. During the CGM-based study, the patients were given insulin therapy alone on Days 1 and 2 and were given sitagliptin 50 mg/day as add-on treatment on Days 3-6, with their daily insulin doses maintained. RESULTS: The add-on treatment with sitagliptin led to significant decreases in 24-h mean glucose levels and SDs of 288 glucose levels measured by CGM for 24 h, as well as in the indices for magnitude of glucose variability and proportion of time in hyperglycemia, compared with insulin therapy alone (P<0.01), whereas there was no significant change seen in regard to the proportion of time in hypoglycemia with or without add-on treatment with sitagliptin. CONCLUSIONS: This CGM-based study clearly demonstrated that insulin therapy alone, whether with long-acting or biphasic insulin preparations, does not provide adequate glycemic control in type 2 diabetes patients. In contrast, add-on sitagliptin was shown to narrow the range of 24-h glucose fluctuations in these patients, suggesting that add-on treatment with sitagliptin is effective for postprandial glucose control in type 2 diabetes patients receiving insulin therapy.

Novel cellulase recycling method using a combination of Clostridium thermocellum cellulosomes and Thermoanaerobacter brockii ß-glucosidase.

This report describes a novel recycling method utilizing a combination of Clostridium thermocellum cellulosomes and Thermoanaerobacter brockii ß-glucosidase (CglT). To recover cellulosomes and CglT through re-binding to additional cellulose, a chimeric CBM3-CglT was created by fusing carbohydrate binding module (CBM3) from the scaffolding protein CipA into the N-terminal region of CglT. When a recycling test using cellulosomes and CBM3-CglT was performed on microcrystalline cellulose, the process was capable of 4 rounds of recycling (1%w/vcellulose/round). Although irreversible absorption of cellulosomes and CBM3-CglT into the residues was observed when ammonia-pretreated rice straw and delignified rice straw was used as substrates, a maximum of 2 and 4 recycling rounds (1%w/vglucan/round) were achieved, respectively, consistent with a 70% saccharification rate. This novel recycling method using cellulosomes and CBM3-CglT has great potential as an effective lignocellulose degradation system.