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In computer systems, user authentication technology is required to identify users who use computers. In modern times, various user authentication technologies, including strong security features based on ownership, such as certificates and security cards, have been introduced. Nevertheless, password-based authentication technology is currently mainly used due to its convenience of use and ease of implementation. However, according to Verizon's "2022 Data Breach Investigations Report", among all security incidents, security incidents caused by password exposures accounted for 82%. Hence, the security of password authentication technology is important. Consequently, this article analyzes prior research on keyboard data attacks and defense techniques to draw the fundamental reasons for keyboard data attacks and derive countermeasures. The first prior research is about stealing keyboard data, an attack that uses machine learning to steal keyboard data to overcome the limitations of a C/D bit attack. The second prior research is an attack technique that steals keyboard data more efficiently by expanding the features of machine learning used in the first prior research. In this article, based on previous research findings, we proposed a keyboard data protection technique using GAN, a Generative Adversarial Network, and verified its feasibility. To summarize the results of performance evaluation with previous research, the machine learning-based keyboard data attack based on the prior research exhibited a 96.7% attack success rate, while the study's proposed method significantly decreased the attack success rate by approximately 13%. Notably, in all experiments, the average decrease in the keyboard data classification performance ranged from a minimum of -29% to a maximum of 52%. When evaluating performance based on maximum performance, all performance indicators were found to decrease by more than 50%.

Background: Hearing rehabilitation with auditory training (AT) is necessary to improve speech perception ability in patients with hearing loss. However, face-to-face AT has not been widely implemented due to its high cost and personnel requirements. Therefore, there is a need for the development of a patient-friendly, mobile-based AT program., Objective: In this study, we evaluated the effectiveness of hearing rehabilitation with our chat-based mobile AT (CMAT) program for speech perception performance among experienced hearing aid (HA) users., Methods: A total of 42 adult patients with hearing loss who had worn bilateral HAs for more than 3 months were enrolled and randomly allocated to the AT or control group. In the AT group, CMAT was performed for 30 minutes a day for 2 months, while no intervention was provided in the control group. During the study, 2 patients from the AT group and 1 patient from the control group dropped out. At 0-, 1- and 2-month visits, results of hearing tests and speech perception tests, compliance, and questionnaires were prospectively collected and compared in the 2 groups., Results: The AT group (n=19) showed better improvement in word and sentence perception tests compared to the control group (n=20; P=.04 and P=.03, respectively), while no significant difference was observed in phoneme and consonant perception tests (both P>.05). All participants were able to use CMAT without any difficulties, and 85% (17/20) of the AT group completed required training sessions. There were no changes in time or completion rate between the first and the second month of AT. No significant difference was observed between the 2 groups in questionnaire surveys., Conclusions: After using the CMAT program, word and sentence perception performance was significantly improved in experienced HA users. In addition, CMAT showed high compliance and adherence over the 2-month study period. Further investigations are needed to validate long-term efficacy in a larger population., Trial Registration: Clinical Research Information Service (CRiS) KCT0006509; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22110&search_page=L., (© Jae Sang Han, Ji Hyung Lim, Yeonji Kim, Aynur Aliyeva, Jae-Hyun Seo, Jaehyuk Lee, Shi Nae Park. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

Background and Objective: This study investigated the spatial and temporal features of muscle synergy during two types of curved walking (CW), according to whether the analyzed legs were located on the outside (OCW) or inside (ICW) on the basis of the curve direction during CW, in patients with stroke., Methods: Thirteen patients with stroke and seven age-matched healthy controls participated in this study. Using the autoencoder technique, four muscle synergies were extracted from eight muscles of the paretic legs in patients with stroke and the dominant legs in healthy controls. Walking speed, variance accounted for (VAF) of the four synergies, and each synergy with the same number were compared. Pearson's correlation and activation peak timing calculation were used to identify spatial and temporal features, respectively., Results: Regarding walking speed in patients with stroke, ICW was significantly faster than OCW (P = 0.027). Regarding spatial features, muscle weighting values of patients with stroke in synergy 3 that were mainly involved in the early swing phase had the lowest similarity [r = 0.30] during OCW, and synergy 4 that was mainly involved in the late swing phase had the lowest similarity [r = 0.39] during ICW compared to the healthy group. Meanwhile, in terms of temporal features, activation peak timings of patients with stroke in synergy 1, which was mainly involved in the early stance phase, and synergy 2, which was mainly involved in the mid-late stance phase, were significantly delayed during OCW (P < .001, P = 0.003), while peak timings of synergy 1 and synergy 3 were delayed during ICW (P = .004, P = .002)., Significance: Based on distinctive features of spatial synergy during the swing phase of CW and temporal synergy during the swing-stance transition phase of CW in patients with stroke in gait rehabilitation, specific approaches need to be considered depending on the curve direction and each gait phase., Competing Interests: Declaration of Competing Interest The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The risk factor for cholelithiasis include low physical activity. With an aging society, the number of bedridden patients who undergo percutaneous endoscopic gastrostomy (PEG) has increased, and cholelithiasis has often been found in these patients. This study aimed to evaluate the risk factors correlated with cholelithiasis in adults who underwent PEG. This retrospective single-center design study reviewed patients who underwent PEG and were confirmed to have cholelithiasis through imaging from March 1996 to December 2021. The investigated variables were age, sex, body mass index (BMI, kg/m 2 ), cause of PEG insertion, initial physical activity status, laboratory findings on PEG insertion day, and incidence of acute cholecystitis. The differences between categorical and continuous variables were analyzed using Student's t test and chi-square test. We enrolled 576 eligible patients who underwent PEG insertion. A total of 161 patients were detected with cholelithiasis (28.0%). The overall independent risk factors for cholelithiasis in patients who underwent PEG insertion were increased C-reactive protein (CRP) levels and decreased physical activity status (bedridden state). The incidence of cholelithiasis was increased by up to 30.7%, especially in patients with bedridden status. However, the incidence of acute cholecystitis among cholelithiasis group was only 5.6%. BMI and total cholesterol were positively correlated with the size of gallbladder (GB) stones. One of the major risk factors for cholelithiasis is decreased physical activity, especially in patients who underwent PEG insertion. Abdominal imaging is recommended to confirm the presence of cholelithiasis and to consider prophylaxis for cholelithiasis, especially in bedridden patients with elevated initial CRP levels at the time of PEG insertion., (© 2023. The Author(s).)

A cell filtration platform that affords accurate size separation and minimizes fouling was developed. The platform features an ultra-thin porous membrane (UTM) filter, a pumping head filtration with backflush (PHF), and cell size measurement (CSM) software. The UTM chip is an ultrathin free-standing membrane with a large window area of 0.68 mm 2 , a pore diameter of 5 to 9 μm, and a thickness of less than 0.9 μm. The PHF prevents filter fouling. The CSM software analyzes the size distributions of the supernatants and subnatants of isolated cells and presents the data visually. The D 99 particle size of cells of the chronic myeloid leukemia (CML) line K562 decreased from 22.2 to 17.5 μm after passage through a 5-μm filter. K562 cells could be separated by careful selection of the pore size; the recovery rate attained 91.3%. The method was compared to conventional blocking models by evaluating the mean square errors (MSEs) between the measured and calculated filtering volumes. The filtering rate was fitted by a linear regression model with a significance that exceeded 0.99 based on the R 2 value. The platform can be used to separate various soft biomaterials and afford excellent stability during filtration.

High electrochemical polarization during a redox reaction in the electrode of aqueous zinc-bromine flow batteries largely limits its practical implementation as an effective energy storage system. This study demonstrates a rationally-designed composite electrode that exhibits a lower electrochemical polarization by providing a higher number of catalytically-active sites for faster bromine reaction, compared to a conventional graphite felt cathode. The composite electrode is composed of electrically-conductive graphite felt (GF) and highly active mesoporous tungsten oxynitride nanofibers (mWONNFs) that are prepared by electrospinning and simple heat treatments. Addition of the 1D mWONNFs to porous GF produces a web-like structure that significantly facilitates the reaction kinetics and ion diffusion. The cell performance achieves in this study demonstrated high energy efficiencies of 89% and 80% at current densities of 20 and 80 mA cm -2 , respectively. Furthermore, the cell can also be operated at a very high current density of 160 mA cm -2 , demonstrating an energy efficiency of 62%. These results demonstrate the effectiveness of the mWONNF/GF composite as the electrode material in zinc-bromine flow batteries., (© 2023 Wiley-VCH GmbH.)

Tangent flow-driven ultrafiltration (TF-UF) is an efficient isolation process of milk exosomes without morphological deformation. However, the TF-UF approach with micro-ultrafiltration SiN x membrane filters suffers from the clogging and fouling of micro-ultrafiltration membrane filter pores with large bioparticles. Thus, it is limited in the long term, continuous isolation of large quantities of exosomes. In this work, we introduced electrophoretic oscillation (EPO) in the TF-UF approach to remove pore clogging and fouling of with micro-ultrafiltration SiN x membrane filters by large bioparticles. As a result, the combined EPO-assisted TF (EPOTF) filtration can isolate large quantities of bovine milk exosomes without deformation. Furthermore, several morphological and biological analyses confirmed that the EPOTF filtration approach could isolate the milk exosomes in high concentrations with high purity and intact morphology. In addition, the uptake test of fluorescent-labeled exosomes by the keratinocyte cells visualized the biological function of purified exosomes. Hence, compared to the TF-UF process, the EPOTF filtration produced a higher yield of bovine milk exosomes without stopping the filtering process for over 200 h. Therefore, this isolation process enables scalable and continuous production of morphologically intact exosomes from bovine milk, suggesting that high-quality exosome purification is possible for future applications such as drug nanocarriers, diagnosis, and treatments.

Ransomware is one type of malware that involves restricting access to files by encrypting files stored on the victim's system and demanding money in return for file recovery. Although various ransomware detection technologies have been introduced, existing ransomware detection technologies have certain limitations and problems that affect their detection ability. Therefore, there is a need for new detection technologies that can overcome the problems of existing detection methods and minimize the damage from ransomware. A technology that can be used to detect files infected by ransomware and by measuring the entropy of files has been proposed. However, from an attacker's point of view, neutralization technology can bypass detection through neutralization using entropy. A representative neutralization method is one that involves decreasing the entropy of encrypted files by using an encoding technology such as base64. This technology also makes it possible to detect files that are infected by ransomware by measuring entropy after decoding the encoded files, which, in turn, means the failure of the ransomware detection-neutralization technology. Therefore, this paper derives three requirements for a more sophisticated ransomware detection-neutralization method from the perspective of an attacker for it to have novelty. These requirements are (1) it must not be decoded; (2) it must support encryption using secret information; and (3) the entropy of the generated ciphertext must be similar to that of plaintext. The proposed neutralization method satisfies these requirements, supports encryption without decoding, and applies format-preserving encryption that can adjust the input and output lengths. To overcome the limitations of neutralization technology using the encoding algorithm, we utilized format-preserving encryption, which could allow the attacker to manipulate the entropy of the ciphertext as desired by changing the expression range of numbers and controlling the input and output lengths in a very free manner. To apply format-preserving encryption, Byte Split, BinaryToASCII, and Radix Conversion methods were evaluated, and an optimal neutralization method was derived based on the experimental results of these three methods. As a result of the comparative analysis of the neutralization performance with existing studies, when the entropy threshold value was 0.5 in the Radix Conversion method, which was the optimal neutralization method derived from the proposed study, the neutralization accuracy was improved by 96% based on the PPTX file format. The results of this study provide clues for future studies to derive a plan to counter the technology that can neutralize ransomware detection technology.

Background and Objectives : Clinically, it is beneficial to determine the knee osteoarthritis (OA) subtype that responds well to conservative treatments. Therefore, this study aimed to determine the differences between varus and valgus arthritic knees in the response to conservative treatment. We hypothesized that valgus arthritic knees would respond better to conservative treatment than varus arthritic knees. Materials and Methods : Medical records of 834 patients who received knee OA treatment were retrospectively reviewed. Patients with Kellgren-Lawrence grades III and IV were divided into two groups according to knee alignment (varus arthritic knee, hip-knee-ankle angle [HKA] > 0° or valgus arthritic knee, HKA < 0°). The Kaplan-Meier curve with total knee arthroplasty (TKA) as an endpoint was used to compare the survival probability between varus and valgus arthritic knees at one, two, three, four, and five years after the first visit. A receiver operating characteristic (ROC) curve was used to compare the HKA thresholds for TKA between varus and valgus arthritic knees. Results : Valgus arthritic knees responded better to conservative treatment than varus arthritic knees. With TKA as an endpoint, the survival probabilities for varus and valgus arthritic knees were 24.2% and 61.4%, respectively, at the 5-year follow-up ( p < 0.001). The thresholds of HKA for varus and valgus arthritic knees for TKA were 4.9° and -8.1°, respectively (varus: area under the ROC curve [AUC] = 0.704, 95% confidence interval [CI] 0.666-0.741, p < 0.001, sensitivity = 0.870, specificity = 0.524; valgus: AUC = 0.753, 95% CI 0.693-0.807, p < 0.001, sensitivity = 0.753, specificity = 0.786). Conclusions : Conservative treatment is more effective for valgus than for varus arthritic knees. This should be considered when explaining the prognosis of conservative treatment for knees with varus and valgus arthritis.

A variety of data-based services such as cloud services and big data-based services have emerged in recent times. These services store data and derive the value of the data. The reliability and integrity of the data must be ensured. Unfortunately, attackers have taken valuable data as hostage for money in attacks called ransomware. It is difficult to recover original data from files in systems infected by ransomware because they are encrypted and cannot be accessed without keys. There are cloud services to backup data; however, encrypted files are synchronized with the cloud service. Therefore, the original file cannot be restored even from the cloud when the victim systems are infected. Therefore, in this paper, we propose a method to effectively detect ransomware for cloud services. The proposed method detects infected files by estimating the entropy to synchronize files based on uniformity, one of the characteristics of encrypted files. For the experiment, files containing sensitive user information and system files for system operation were selected. In this study, we detected 100% of the infected files in all file formats, with no false positives or false negatives. We demonstrate that our proposed ransomware detection method was very effective compared to other existing methods. Based on the results of this paper, we expect that this detection method will not synchronize with a cloud server by detecting infected files even if the victim systems are infected with ransomware. In addition, we expect to restore the original files by backing up the files stored on the cloud server.

Extracellular vesicles (EVs) have emerged as vehicles that mediate diverse cell-cell communication. However, in-depth understanding of these vesicles is hampered by a lack of a reliable isolation method to separate different types of EVs with high levels of integrity and purity. Here, we developed a nanoporous and ultra-thin membrane structure (NUTS) that warrants the size-based isolation of EVs without cake formation, minimizing the sample loss during the filtration process. By utilizing the micro-electro-mechanical systems (MEMS) technique, we could also control the pore size in nanoscale. We validated the performance of this membrane to separate EVs according to their size range., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Ransomware consists of malicious codes that restrict users from accessing their own files while demanding a ransom payment. Since the advent of ransomware, new and variant ransomwares have caused critical damage around the world, thus prompting the study of detection and prevention technologies against ransomware. Ransomware encrypts files, and encrypted files have a characteristic of increasing entropy. Due to this characteristic, a defense technology has emerged for detecting ransomware-infected files by measuring the entropy of clean and encrypted files based on a derived entropy threshold. Accordingly, attackers have applied a method in which entropy does not increase even if the files are encrypted, such that the ransomware-infected files cannot be detected through changes in entropy. Therefore, if the attacker applies a base64 encoding algorithm to the encrypted files, files infected by ransomware will have a low entropy value. This can eventually neutralize the technology for detecting files infected from ransomware based on entropy measurement. Therefore, in this paper, we propose a method to neutralize ransomware detection technologies using a more sophisticated entropy measurement method by applying various encoding algorithms including base64 and various file formats. To this end, we analyze the limitations and problems of the existing entropy measurement-based ransomware detection technologies using the encoding algorithm, and we propose a more effective neutralization method of ransomware detection technologies based on the analysis results.

Parametric arrays have been widely investigated due to their high directivity in the low-frequency region when measuring the acoustic characteristics of materials, such as sound transmission and reflection properties, in the limited space of acoustic water tanks. Because a parametric array utilizes nonlinear interaction across the frequency components, nonlinear phenomena arise in both the acoustic medium and the hydrophone system. The unwanted nonlinear sound generated in the hydrophone and instrumentation is termed pseudo-sound. This study devised an experiment to measure the pseudo-sound without a truncator to assess the effect of the pseudo-sound in the near field. In order to separately measure the pseudo-sound, the hydrophone was placed close to the projector so that the pseudo-sound was dominantly generated. The method is based on the fact that, if we can suppress a parametric signal by minimizing the propagation path length in the medium, the resulting measured signal can be attributed to the pseudo-sound. The resultant signal levels were matched to the levels at corresponding distances based on the primary levels of a (separately conducted) distance-varying experiment. Finally, the suitability of the proposed technique was evaluated by comparing its results with the pseudo-sound levels measured using a truncator.

As a sound transmitting device that relies on the nonlinearity of a medium, a parametric array (PA) can generate high-directivity low-frequency signals using a small aperture transducer and high-frequency signals. Despite their relatively low source level, the PA is frequently used to measure the acoustic properties of materials in low-frequency regions owing to their high directivity in confined acoustic water tanks. Therefore, methods for improving the source level of secondary signals are of interest. Currently, there are two driving methods for PA: the dual-frequency PA and the broadband PA with amplitude modulation. In this study, we share the results of an elaborate and comparative experimental investigation of these two driving methods. Comparisons are made and discussed in terms of the intensity of the generated secondary signal and its characteristics in the frequency domain. Based on these factors, we confirmed that the broadband PA was more suitable as the sound source of the low-frequency characteristic measurement system of acoustic materials.

Background: Type II diabetes mellitus (DM2) is a significant risk factor for cancers, including breast cancer. However, a proper diabetic breast cancer mouse model is not well-established for treatment strategy design. Additionally, the precise diabetic signaling pathways that regulate cancer growth remain unresolved. In the present study, we established a suitable mouse model and demonstrated the pathogenic role of diabetes on breast cancer progression., Methods: We successfully generated a transgenic mouse model of human epidermal growth factor receptor 2 positive (Her2 + or ERBB2) breast cancer with DM2 by crossing leptin receptor mutant (Lepr db/+ ) mice with MMTV-ErbB2/neu) mice. The mouse models were administrated with antidiabetic drugs to assess the impacts of controlling DM2 in affecting tumor growth. Magnetic resonance spectroscopic imaging was employed to analyze the tumor metabolism., Results: Treatment with metformin/rosiglitazone in MMTV-ErbB2/Lepr db/db mouse model reduced serum insulin levels, prolonged overall survival, decreased cumulative tumor incidence, and inhibited tumor progression. Anti-insulin resistance medications also inhibited glycolytic metabolism in tumors in vivo as indicated by the reduced metabolic flux of hyperpolarized 13 C pyruvate-to-lactate reaction. The tumor cells from MMTV-ErbB2/Lepr db/db transgenic mice treated with metformin had reprogrammed metabolism by reducing levels of both oxygen consumption and lactate production. Metformin decreased the expression of Myc and pyruvate kinase isozyme 2 (PKM2), leading to metabolism reprogramming. Moreover, metformin attenuated the mTOR/AKT signaling pathway and altered adipokine profiles., Conclusions: MMTV-ErbB2/Lepr db/db mouse model was able to recapitulate diabetic HER2 + human breast cancer. Additionally, our results defined the signaling pathways deregulated in HER2 + breast cancer under diabetic condition, which can be intervened by anti-insulin resistance therapy., (© 2021 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

This randomized crossover study investigated whether anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefontal cortex (dlPFC) modulates memory-guided finger isometric maintenance during single motor and dual cognitive-motor tasks, based on electroencephalogram (EEG) signals. Twenty-three healthy participants (14 female; M age = 29.130 years, SD  = 10.918) underwent both sham and 2-mA stimulation sessions over the dlPFC for 20 minutes, with a minimum washout period of seven days. We analyzed finger-force isometric maintenance and event-related spectral perturbation (ERSP) of the EEG during early and later phases of both tasks. We observed a significant motor accuracy improvement ( p  = .014) and significant variation of force output ( p  = .027) with significant decrease in ERSP on the dorsomedial prefrontal cortex (dmPFC) (early phase, p  = .027; later phase, p  = .023) only after 2 mA stimulation. Thus, anodal tDCS over the dlPFC may improve memory-guided force control during cognitive-motor dual tasks.

Context: A simulated horseback riding (SHR) exercise is effective for improvement of pain and functional disability, but its comparative effectiveness with the other is unknown., Objective: The authors aimed to demonstrate the effect of a SHR exercise in people with chronic low back pain., Design: A randomized controlled trial., Settings: Community and university campus., Participants: A total of 48 participants with chronic low back pain were divided into 2 groups, and SHR exercises (n = 24) or stabilization (STB) exercises (n = 24) were performed., Interventions: The exercises were performed for 30 minutes, 2 days per week for 8 weeks., Main Outcome Measures: Numeric rating scale, functional disabilities (Oswestry disability index and Roland-Morris disability), and fear-avoidance beliefs questionnaire (FABQ) scores were measured at baseline and at 4 weeks, 8 weeks, and 6 months., Results: A 2-way repeated analysis of variance identified that between-group comparisons showed significant differences in the FABQ related to work scale (F = 21.422; P = .01). There were no significant differences in the numeric rating scale (F = 1.696; P = .21), Oswestry disability index (F = 1.848; P = .20), Roland-Morris disability (F = 0.069; P = .80), and FABQ related to physical scale (F = 1.579; P = .24). In within-group comparisons, both groups presented significant differences in numeric rating scale (both SHR and STB after 4 wk), Oswestry disability index (both SHR and STB after 6 mo), and Roland-Morris disability (SHR after 6 mo and STB after 8 wk) compared with baseline values. In FABQ-related physical (SHR after 4 wk) and work scales (SHR after 6 mo), there were only significant differences in the SHR compared with baseline values., Conclusions: SHR exercise for 8 weeks had a greater effect than STB exercise for reducing work-related FABQ. The SHR exercise performed in a seated position could substantially decrease pain-related fear disability in young adults with chronic low back pain.

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has been demonstrated to modulate the motor performance of both healthy individuals and patients with neuromuscular disorders. However, the effect of tDCS on motor control of multiple muscles, which is a prerequisite to change in motor performance, is currently unknown. Using dimensionality reduction analysis, we investigated whether bilateral tDCS over M1 modulates the coordinated activity of 12 muscles. Fifteen healthy men participated in this randomized, double-blind crossover study. Each participant received a 20-min sham and 2-mA stimulation bilaterally over M1 (anode on the right M1 and cathode on the left M1), with a minimum washout period of 4 days. Muscle activation and end-point kinematics were evaluated during a task where participants reached out to a marked target with non-dominant hand as fast as possible, before and immediately after tDCS application. We found decreased similarity in motor modularity and significant changes in muscle activation in a specific motor module, particularly when reaching out to a target placed within arm's length and improved smoothness index of movement only following 2-mA stimulation. These findings indicate that clinicians and researchers need to consider the simultaneous effect of bilateral tDCS over M1 on multiple muscles when they establish tDCS protocol to change in motor performance of patients with neuromuscular deficits.

Acute myeloid leukemia (AML) is an aggressive hematopoietic disease characterized by glutamine-dependent metabolism. A novel glutaminase (GLS) inhibitor, CB-839, is currently under evaluation for treatment of hematopoietic malignancies and solid tumors. Our purpose was to measure cellular changes in AML associated with CB-839 treatment and to test the ability of hyperpolarized pyruvate for interrogating these changes to OCI-AML3 cells. Our results show that treatment with CB-839 interfered with the citric acid cycle, reduced the NADH/NAD + ratio and ATP levels, reduced cell proliferation and viability, and reduced the basal and maximal respiratory capacities [oxygen consumption rate (OCR)]. We observed a reduction of the conversion of hyperpolarized pyruvate to lactate in cell lines and in a mouse AML model after CB-839 treatment. Our in vitro and in vivo results support the hypothesis that, in AML, glutamine is utilized to generate reducing equivalents (NADH, FADH 2 ) through the citric acid cycle and that reduction in redox state by GLS inhibition decreases the rate of pyruvate to lactate conversion catalyzed by lactate dehydrogenase. We propose hyperpolarized pyruvate/lactate measurement as a method for direct monitoring of metabolic changes occurring in AML patients receiving CB-839. With further optimization, this method may provide a noninvasive imaging tool to assess the early efficacy of therapeutic intervention with GLS inhibitors., (©2019 American Association for Cancer Research.)

Motor learning plays an important role in upper-limb function and the recovery of lost functionality. This study aimed to investigate the relative impact of transcranial direct current stimulation (tDCS) on learning in relation to the left primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC) during bimanual isometric force-control tasks performed with both hands under different task constraints. In a single-blind cross-over design, 20 right-handed participants were randomly assigned to either the M1 group (n = 10; mean age, 22.90 ± 1.66 years, mean ± standard deviation) or the DLPFC group (n = 10; mean age, 23.20 ± 1.54 years). Each participant received 30 min of tDCS (anodal or sham, applied randomly in two experiments) while performing the bimanual force control tasks. Anodal tDCS of the M1 improved the accuracy of maintenance and rhythmic alteration of force tasks, while anodal tDCS of the DLPFC improved only the maintenance of the force control tasks compared with sham tDCS. Hence, tDCS over the left M1 and DLPFC has a beneficial effect on the learning of bimanual force control., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer that progresses without any symptom, and oftentimes, it is detected at an advanced stage. The lack of prior symptoms and effective treatments have created a knowledge gap in the management of this lethal disease. This issue can be addressed by developing novel noninvasive imaging-based biomarkers in PDAC. We explored in vivo hyperpolarized (HP) 13 C MRS of pyruvate to lactate conversion and ex vivo 1 H NMR spectroscopy in a panel of well-annotated patient-derived PDAC xenograft (PDXs) model and investigated the correlation between aberrant glycolytic metabolism and aggressiveness of the tumor. Real-time metabolic imaging data demonstrate the immediate intracellular conversion of HP 13 C pyruvate to lactate after intravenous injection interrogating upregulated lactate dehydrogenase (LDH) activity in aggressive PDXs. Total ex vivo lactate measurement by 1 H NMR spectroscopy showed a direct correlation with in vivo dynamic pyruvate-to-lactate conversion and demonstrated the potential of dynamic metabolic flux as a biomarker of total lactate concentration and aggressiveness of the tumor. Furthermore, the metabolite concentrations were very distinct among all four tumor types analyzed in this study. Overexpression of LDH-A and hypoxia-inducible factor (HIF-1α) plays a significant role in the conversion kinetics of HP pyruvate-to-lactate in tumors. Collectively, these data identified aberrant metabolic characteristics of pancreatic cancer PDXs and could potentially delineate metabolic targets for therapeutic intervention. Metabolic imaging with HP pyruvate and NMR metabolomics may enable identification and classification of aggressive subtypes of patient-derived xenografts. Translation of this real-time metabolic technique to the clinic may have the potential to improve the management of patients at high risk of developing pancreatic diseases.

Hyperpolarized magnetic resonance spectroscopy enables quantitative, non-radioactive, real-time measurement of imaging probe biodistribution and metabolism in vivo. Here, we investigate and report on the development and characterization of hyperpolarized acetylsalicylic acid (aspirin) and its use as a nuclear magnetic resonance (NMR) probe. Aspirin derivatives were synthesized with single- and double- 13 C labels and hyperpolarized by dynamic nuclear polarization with 4.7 % and 3 % polarization, respectively. The longitudinal relaxation constants (T 1 ) for the labeled acetyl and carboxyl carbonyls were approximately 30 seconds, supporting in vivo imaging and spectroscopy applications. In vitro hydrolysis, transacetylation, and albumin binding of hyperpolarized aspirin were readily monitored in real time by 13 C-NMR spectroscopy. Hyperpolarized, double-labeled aspirin was well tolerated in mice and could be observed by both 13 C-MR imaging and 13 C-NMR spectroscopy in vivo., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: Based on the evidence that the dorsolateral prefrontal cortex (DLPFC) is the main region affected by the aging process, and that tDCS modulates cortical excitability, the aim of the study is to prove the feasibility of tDCS for pain perception and executive function of community-dwelling elderly individuals., Methods: We performed a double-blind, single-arm trial, including a sham period. 5 consecutive anodal tDCS was applied over DLPFC of twenty-four elderly for 20 min during each intervention periods (in order of Sham-1 mA-2 mA). First, we classified chronic non-inflammatory pain sites into three domain (Neck and upper extremity, low back, lower extremity). Then, we used visual analogue scale, pain self-efficacy scale, Tampa scale for kinesiophobia, and Global perceived Effect scale to observe the change in pain perception, as well as Trailing Making Test and Timed Up and Go (dual) to observe the change in executive function. The changes in maximal grip strength and 12-item Short Form survey were measured secondarily., Results: In the results, we observed significant improvement in pain perception and quality of life, while executive function and grip strength did not change significantly., Conclusion: Our findings demonstrated the feasibility of tDCS for aging-related pain perception and suggest that further randomized controlled trials with longer duration are necessary to examine the effects on executive function., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Androgen receptor (AR) signaling affects prostate cancer (PCa) growth, metabolism, and progression. Often, PCa progresses from androgen-sensitive to castration-resistant prostate cancer (CRPC) following androgen-deprivation therapy. Clinicopathologic and genomic characterizations of CRPC tumors lead to subdividing CRPC into two subtypes: (1) AR-dependent CRPC containing dysregulation of AR signaling alterations in AR such as amplification, point mutations, and/or generation of splice variants in the AR gene; and (2) an aggressive variant PCa (AVPC) subtype that is phenotypically similar to small cell prostate cancer and is defined by chemotherapy sensitivity, gain of neuroendocrine or pro-neural marker expression, loss of AR expression, and combined alterations of PTEN, TP53, and RB1 tumor suppressors. Previously, we reported patient-derived xenograft (PDX) animal models that contain characteristics of these CRPC subtypes. In this study, we have employed the PDX models to test metabolic alterations in the CRPC subtypes., Procedures: Mass spectrometry and nuclear magnetic resonance analysis along with in vivo hyperpolarized 1-[ 13 C]pyruvate spectroscopy experiments were performed on prostate PDX animal models., Results: Using hyperpolarized 1-[ 13 C]pyruvate conversion to 1-[ 13 C]lactate in vivo as well as lactate measurements ex vivo, we have found increased lactate production in AR-dependent CRPC PDX models even under low-hormone levels (castrated mouse) compared to AR-negative AVPC PDX models., Conclusions: Our analysis underscores the potential of hyperpolarized metabolic imaging in determining the underlying biology and in vivo phenotyping of CRPC.

Well-coordinated bimanual force control is common in daily life. We investigated the effects of anodal transcranial direct current stimulation (tDCS) over the primary motor cortex on bimanual force control. Under a cross-over study, young adults ( n = 19; female = 6, male = 13) completed three bimanual force control tasks at 5%, 25%, and 50% of bimanual maximum voluntary force (BMVF) before and after real or sham tDCS. Real tDCS enhanced accuracy at all BMVF, reduced variability at 5% BMVF, and increased coordination at 5% BMVF. Real tDCS improved force control at 5% and 25% BMVF, and especially increased bimanual coordination at 5% BMVF. These findings might have implications for establishing interventions for patients with hand force control deficits.

Purpose To assess in a mouse model whether early or late components of glucose metabolism, exemplified by fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) and hyperpolarized carbon 13 ( 13 C)-pyruvate magnetic resonance (MR) spectroscopy, can serve as indicators of response in ovarian cancer to multityrosine kinase inhibitor pazopanib. Materials and Methods In this Animal Care and Use Committee approved study, 17 days after the injection of 2 × 10 6 human ovarian SKOV3 tumors cells into 14 female nude mice, treatment with vehicle or pazopanib (2.5 mg per mouse peroral every other day) was initiated. Longitudinal T2-weighted MR imaging, dynamic MR spectroscopy of hyperpolarized pyruvate, and 18 F-FDG PET/computed tomographic (CT) imaging were performed before treatment, 2 days after treatment, and 2 weeks after treatment. Results Pazopanib inhibited ovarian tumor growth compared with control (0.054 g ± 0.041 vs 0.223 g ± 0.112, respectively; six mice were treated with pazopanib and seven were control mice; P < .05). Significantly higher pyruvate-to-lactate conversion (lactate/pyruvate + lactate ratio) was found 2 days after treatment with pazopanib than before treatment (0.46 ± 0.07 vs 0.31 ± 0.14, respectively; P < .05; six tumors after treatment, seven tumors before treatment). This was not observed with the control group or with 18 F-FDG PET/CT imaging. Conclusion The findings suggest that hyperpolarized 13 C-pyruvate MR spectroscopy may serve as an early indicator of response to tyrosine kinase (angiogenesis) inhibitors such as pazopanib in ovarian cancer even when 18 F-FDG PET/CT does not indicate a response. © RSNA, 2017 Online supplemental material is available for this article.

The new oncologic paradigm of precision medicine is focused on identifying metabolic, proteomic, transcriptomic and genomic variabilities in tumors that can be exploited to tailor treatments and improve patient outcomes. Metabolic changes are a hallmark of cancer, and inhibition of metabolic pathways is now a major strategy in medicinal chemistry for targeting cancers. However, non-invasive biomarkers to categorize metabolic subtypes are in short supply. The purpose of this study was to characterize the intracellular and extracellular metabolic profiles of four prostate cancer cell lines with varying degrees of aggressiveness. We observed metabolic differences between the aggressive prostate cancer cell line PC3 and the even more aggressive, metastatic subline PC3M assessed by hyperpolarized in vivo pyruvate studies, nuclear magnetic resonance spectroscopy, and carbon-13 feeding studies. On further examination of the differences between these two cell lines, we found increased glutamine utilization in the metastatic PC3M subline that led directly to sensitivity to glutaminase inhibitor CB-839. Our study supports the theory that metastatic progression increases glutamine utilization and the inhibition of glutaminolysis could have clinical implications.

Objectives: Little is known about the optimal retraining time for regaining functional fitness through multicomponent training following long-term detraining in older adults. This study first investigated the time course of functional fitness changes during 12-month multicomponent training, 12-month detraining, and 9-month retraining in 18 older adults (68.33±3.46) and then determined the optimal retraining time for regaining the post-training functional fitness level after a 12-month detraining period., Methods: Functional fitness, including lower and upper limb strength, lower and upper limb flexibility, aerobic endurance, and dynamic balance, was assessed at baseline, 12 months post-training, 12 months post-detraining, and 3, 6, and 9 months post-retraining., Results: There were significant increases in all of the functional fitness components except upper limb flexibility at post-training and no significant decreases at post-detraining. For lower and upper limb strength and lower limb flexibility, a 3-month period was required to regain the post-training condition. For aerobic endurance and dynamic balance, a retraining period ≥9months was necessary to regain the post-training functional fitness condition., Conclusions: To regain the post-training condition of all functional fitness components, a retraining period ≥9months was required. This information might be useful for health professionals to encourage older adults not to interrupt retraining until they regain their post-training functional fitness condition., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This article reviews existing and emerging techniques of interrogating metabolism in brain cancer from well-established proton magnetic resonance spectroscopy to the promising hyperpolarized metabolic imaging and chemical exchange saturation transfer and emerging techniques of imaging inflammation. Some of these techniques are at an early stage of development and clinical trials are in progress in patients to establish the clinical efficacy. It is likely that in vivo metabolomics and metabolic imaging is the next frontier in brain cancer diagnosis and assessing therapeutic efficacy; with the combined knowledge of genomics and proteomics a complete understanding of tumorigenesis in brain might be achieved., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Solar fuel production, mimicking natural photosynthesis of converting CO2 into useful fuels and storing solar energy as chemical energy, has received great attention in recent years. Practical large-scale fuel production needs a unique device capable of CO2 reduction using only solar energy and water as an electron source. Here we report such a system composed of a gold-decorated triple-layered ZnO@ZnTe@CdTe core-shell nanorod array photocathode and a CH3NH3PbI3 perovskite solar cell in tandem. The assembly allows effective light harvesting of higher energy photons (>2.14 eV) from the front-side photocathode and lower energy photons (>1.5 eV) from the back-side-positioned perovskite solar cell in a single-photon excitation. This system represents an example of a photocathode-photovoltaic tandem device operating under sunlight without external bias for selective CO2 conversion. It exhibited a steady solar-to-CO conversion efficiency over 0.35% and a solar-to-fuel conversion efficiency exceeding 0.43% including H2 as a minor product.

Purpose: To characterize the prevalence of hypoxia in the leukemic bone marrow, its association with metabolic and transcriptional changes in the leukemic blasts and the utility of hypoxia-activated prodrug TH-302 in leukemia models., Experimental Design: Hyperpolarized magnetic resonance spectroscopy was utilized to interrogate the pyruvate metabolism of the bone marrow in the murine acute myeloid leukemia (AML) model. Nanostring technology was used to evaluate a gene set defining a hypoxia signature in leukemic blasts and normal donors. The efficacy of the hypoxia-activated prodrug TH-302 was examined in the in vitro and in vivo leukemia models., Results: Metabolic imaging has demonstrated increased glycolysis in the femur of leukemic mice compared with healthy control mice, suggesting metabolic reprogramming of hypoxic bone marrow niches. Primary leukemic blasts in samples from AML patients overexpressed genes defining a "hypoxia index" compared with samples from normal donors. TH-302 depleted hypoxic cells, prolonged survival of xenograft leukemia models, and reduced the leukemia stem cell pool in vivo In the aggressive FLT3/ITD MOLM-13 model, combination of TH-302 with tyrosine kinase inhibitor sorafenib had greater antileukemia effects than either drug alone. Importantly, residual leukemic bone marrow cells in a syngeneic AML model remain hypoxic after chemotherapy. In turn, administration of TH-302 following chemotherapy treatment to mice with residual disease prolonged survival, suggesting that this approach may be suitable for eliminating chemotherapy-resistant leukemia cells., Conclusions: These findings implicate a pathogenic role of hypoxia in leukemia maintenance and chemoresistance and demonstrate the feasibility of targeting hypoxic cells by hypoxia cytotoxins., (©2015 American Association for Cancer Research.)

A zinc telluride (ZnTe) film modified with MoS2 and carbon has been studied as a new photocathode for solar hydrogen production from photoelectrochemical (PEC) water splitting. The modification enhances PEC activity and stability of the photocathode. Thus, the MoS2/C/ZnTe/ZnO electrode exhibits highly improved activity of -1.48 mA cm(-2) at 0 VRHE with a positively shifted onset potential up to 0.3 VRHE relative to bare ZnO/ZnTe electrode (-0.19 mA cm(-2), 0.18 VRHE) under the simulated 1 sun illumination. This represents the highest value ever reported for ZnTe-based electrodes in PEC water splitting. The carbon densely covers the surface of ZnTe to protect it against photocorrosion in aqueous electrolyte and improves charge separation. In addition, MoS2 further enhances the PEC performance as a hydrogen evolution co-catalyst.

Long noncoding RNAs (lncRNAs) significantly influence the development and regulation of genome expression in cells. Here, we demonstrate the role of lncRNA ceruloplasmin (NRCP) in cancer metabolism and elucidate functional effects leading to increased tumor progression. NRCP was highly upregulated in ovarian tumors, and knockdown of NRCP resulted in significantly increased apoptosis, decreased cell proliferation, and decreased glycolysis compared with control cancer cells. In an orthotopic mouse model of ovarian cancer, siNRCP delivered via a liposomal carrier significantly reduced tumor growth compared with control treatment. We identified NRCP as an intermediate binding partner between STAT1 and RNA polymerase II, leading to increased expression of downstream target genes such as glucose-6-phosphate isomerase. Collectively, we report a previously unrecognized role of the lncRNA NRCP in modulating cancer metabolism. As demonstrated, DOPC nanoparticle-incorporated siRNA-mediated silencing of this lncRNA in vivo provides therapeutic avenue toward modulating lncRNAs in cancer., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Hyperpolarized [1-(13)C]-pyruvate has shown tremendous promise as an agent for imaging tumor metabolism with unprecedented sensitivity and specificity. Imaging hyperpolarized substrates by magnetic resonance is unlike traditional MRI because signals are highly transient and their spatial distribution varies continuously over their observable lifetime. Therefore, new imaging approaches are needed to ensure optimal measurement under these circumstances. Constrained reconstruction algorithms can integrate prior information, including biophysical models of the substrate/target interaction, to reduce the amount of data that is required for image analysis and reconstruction. In this study, we show that metabolic MRI with hyperpolarized pyruvate is biased by tumor perfusion and present a new pharmacokinetic model for hyperpolarized substrates that accounts for these effects. The suitability of this model is confirmed by statistical comparison with alternates using data from 55 dynamic spectroscopic measurements in normal animals and murine models of anaplastic thyroid cancer, glioblastoma, and triple-negative breast cancer. The kinetic model was then integrated into a constrained reconstruction algorithm and feasibility was tested using significantly undersampled imaging data from tumor-bearing animals. Compared with naïve image reconstruction, this approach requires far fewer signal-depleting excitations and focuses analysis and reconstruction on new information that is uniquely available from hyperpolarized pyruvate and its metabolites, thus improving the reproducibility and accuracy of metabolic imaging measurements., (©2015 American Association for Cancer Research.)

Magnetic resonance imaging and spectroscopy of hyperpolarized (HP) compounds such as [1-(13)C]-pyruvate have shown tremendous potential for offering new insight into disease and response to therapy. New applications of this technology in clinical research and care will require extensive validation in cells and animal models, a process that may be limited by the high cost and modest throughput associated with dynamic nuclear polarization. Relatively wide spectral separation between [1-(13)C]-pyruvate and its chemical endpoints in vivo are conducive to simultaneous multi-sample measurements, even in the presence of a suboptimal global shim. Multi-channel acquisitions could conserve costs and accelerate experiments by allowing acquisition from multiple independent samples following a single dissolution. Unfortunately, many existing preclinical MRI systems are equipped with only a single channel for broadband acquisitions. In this work, we examine the feasibility of this concept using a broadband multi-channel digital receiver extension and detector arrays that allow concurrent measurement of dynamic spectroscopic data from ex vivo enzyme phantoms, in vitro anaplastic thyroid carcinoma cells, and in vivo in tumor-bearing mice. Throughput and the cost of consumables were improved by up to a factor of four. These preliminary results demonstrate the potential for efficient multi-sample studies employing hyperpolarized agents., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The wearable lung-health monitoring system is proposed with an electrical impedance tomography (EIT). The proposed system has light belt-type form factor which is implemented with the EIT integrated circuit (IC) on the planar-fashionable circuit board (P-FCB) technology. The EIT IC provides programmable current stimulation which is optimally controlled by the results of contact impedance monitoring. The measured data is transmitted to the mobile device and the lung EIT images are reconstructed and displayed with up to 20 frames/s real-time. From the lung EIT image, the measured lung air volume ratio can be used as an indicator of the lung-health, and other various parameters can be extracted to monitor lung status. The proposed wearable system achieves the user convenience for lung-health monitoring which can be used personally at home. The proposed system is fully implemented and verified on both in-vitro and in-vivo tests.

Extensive reprogramming of cellular energy metabolism is a hallmark of cancer. Despite its importance, the molecular mechanism controlling this tumour metabolic shift remains not fully understood. Here we show that 14-3-3σ regulates cancer metabolic reprogramming and protects cells from tumorigenic transformation. 14-3-3σ opposes tumour-promoting metabolic programmes by enhancing c-Myc poly-ubiquitination and subsequent degradation. 14-3-3σ demonstrates the suppressive impact on cancer glycolysis, glutaminolysis, mitochondrial biogenesis and other major metabolic processes of tumours. Importantly, 14-3-3σ expression levels predict overall and recurrence-free survival rates, tumour glucose uptake and metabolic gene expression in breast cancer patients. Thus, these results highlight that 14-3-3σ is an important regulator of tumour metabolism, and loss of 14-3-3σ expression is critical for cancer metabolic reprogramming. We anticipate that pharmacologically elevating the function of 14-3-3σ in tumours could be a promising direction for targeted anticancer metabolism therapy development in future.

Purpose: There is great potential for real-time investigation of metabolism with MRS and hyperpolarized (HP) (13) C agents. Unfortunately, HP technology has high associated costs and efficiency limitations that may constrain in vivo studies involving many animals. To improve the throughput of preclinical investigations, we evaluate the feasibility of performing HP MRS on multiple animals simultaneously., Methods: Simulations helped assess the viability of a dual-coil strategy for spatially localized multivolume MRS. A dual-mouse system was assembled and characterized with bench- and scanner-based experiments. Enzyme phantoms mixed with HP [1-(13) C] pyruvate emulated real-time metabolism and offered a controlled mechanism for evaluating system performance. Finally, a normal mouse and a mouse bearing a subcutaneous xenograft of colon cancer were simultaneously scanned in vivo using an agent containing HP [1-(13) C] pyruvate., Results: Geometric separation/rotation, active decoupling, and use of low input impedance preamplifiers permitted an encode-by-channel approach for spatially localized MRS. A precalibrated shim allowed straightforward metabolite differentiation in enzyme phantom and in vivo experiments at 7 Tesla, with performance similar to conventional acquisitions., Conclusion: The initial feasibility of multi-animal HP (13) C MRS was established. Throughput scales with the number of simultaneously scanned animals, demonstrating the potential for significant improvements in study efficiency., (© 2014 Wiley Periodicals, Inc.)

Purpose: The transient and nonrenewable signal from hyperpolarized metabolites necessitates extensive sequence optimization for encoding spatial, spectral, and dynamic information. In this work, we evaluate the utility of radial single-timepoint and cumulative spectroscopic MRI of hyperpolarized [1-(13) C] pyruvate and its metabolic products at 7 Tesla (T)., Methods: Simulations of radial echo planar spectroscopic imaging (EPSI) and multiband frequency encoding (MBFE) acquisitions were performed to confirm feasibility and evaluate performance for HP (13) C imaging. Corresponding sequences were implemented on a 7T small-animal MRI system, tested in phantom, and demonstrated in a murine model of anaplastic thyroid cancer., Results: MBFE provides excellent spectral separation but is susceptible to blurring and T2 * signal loss inherent to using low readout gradients. The higher readout gradients and more flexible spectral encoding for EPSI result in good spatial resolution and spectral separation. Radial acquisition throughout HP signal evolution offers the flexibility for reconstructing spatial maps of mean metabolite distribution and global dynamic time courses of multiple metabolites., Conclusion: Radial EPSI and MBFE acquisitions are well-suited for hyperpolarized (13) C MRI over short and long durations. Advantages to this approach include robustness to nonstationary magnetization, insensitivity to precise acquisition timing, and versatility for reconstructing dynamically acquired spectroscopic data., (Copyright © 2013 Wiley Periodicals, Inc.)

A one-step and mass-production synthetic route for a flexible reduced tungsten oxide-carbon composite nanofiber (WO(x)-C-NF) film is demonstrated via an electrospinning technique. The WO(x)-C-NF film exhibits unprecedented high content of metal-oxides (∼ 80 wt%) and good flexibility (the tensile strength of the specimen was 6.13 MPa) without the use of flexible support materials like CNTs or graphene. The WO(x)-C-NF film is directly used as an anode in a lithium ion battery (LIB). Compared with previously reported tungsten oxide electrodes, the WO(x)-C-NF film exhibits high reversible capacity (481 mA h g(-1)total electrode), stable cycle, and improved rate performance, without the use of additive carbon, a polymeric binder and a current collector. Moreover, control electrodes fabricated by conventional processes support the positive effects of both the freestanding electrode and metal-oxide embedded carbon 1-D nanofiber structure.

Ionizing radiation (IR) cytotoxicity is primarily mediated through reactive oxygen species (ROS). Since tumor cells neutralize ROS by utilizing reducing equivalents, we hypothesized that measurements of reducing potential using real-time hyperpolarized (HP) magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) can serve as a surrogate marker of IR induced ROS. This hypothesis was tested in a pre-clinical model of anaplastic thyroid carcinoma (ATC), an aggressive head and neck malignancy. Human ATC cell lines were utilized to test IR effects on ROS and reducing potential in vitro and [1-¹³C] pyruvate HP-MRS/MRSI imaging of ATC orthotopic xenografts was used to study in vivo effects of IR. IR increased ATC intra-cellular ROS levels resulting in a corresponding decrease in reducing equivalent levels. Exogenous manipulation of cellular ROS and reducing equivalent levels altered ATC radiosensitivity in a predictable manner. Irradiation of ATC xenografts resulted in an acute drop in reducing potential measured using HP-MRS, reflecting the shunting of reducing equivalents towards ROS neutralization. Residual tumor tissue post irradiation demonstrated heterogeneous viability. We have adapted HP-MRS/MRSI to non-invasively measure IR mediated changes in tumor reducing potential in real time. Continued development of this technology could facilitate the development of an adaptive clinical algorithm based on real-time adjustments in IR dose and dose mapping.

In vivo real time spectroscopic imaging of hyperpolarized ¹³C labeled metabolites shows substantial promise for the assessment of physiological processes that were previously inaccessible. However, reliable and reproducible methods of measurement are necessary to maximize the effectiveness of imaging biomarkers that may one day guide personalized care for diseases such as cancer. Animal models of human disease serve as poor reference standards due to the complexity, heterogeneity, and transient nature of advancing disease. In this study, we describe the reproducible conversion of hyperpolarized [1-¹³C]-pyruvate to [1-¹³C]-lactate using a novel synthetic enzyme phantom system. The rate of reaction can be controlled and tuned to mimic normal or pathologic conditions of varying degree. Variations observed in the use of this phantom compare favorably against within-group variations observed in recent animal studies. This novel phantom system provides crucial capabilities as a reference standard for the optimization, comparison, and certification of quantitative imaging strategies for hyperpolarized tracers.

This study describes the one-pot synthesis and single-cell characterization of ordered, large-pore (>30 nm) mesoporous carbon/silica (OMCS) composites with well-dispersed intermetallic PtPb nanoparticles on pore wall surfaces as anode catalysts for direct formic acid fuel cells (DFAFCs). Lab-synthesized amphiphilic diblock copolymers coassemble hydrophobic metal precursors as well as hydrophilic carbon and silica precursors. The final materials have a two-dimensional hexagonal-type structure. Uniform and large pores, in which intermetallic PtPb nanocrystals are significantly smaller than the pore size and highly dispersed, enable pore backfilling with ionomers and formation of the desired triple-phase boundary in single cells. The materials show more than 10 times higher mass activity and significantly lower onset potential for formic acid oxidation as compared with commercial Pt/C, as well as high stability due to better resistivity toward CO poisoning. In single cells, the maximum power density was higher than that of commercial Pt/C, and the stability highly improved, compared with commercial Pd/C. The results suggest that PtPb-based catalysts on large-pore OMCSs may be practically applied as real fuel cell catalysts for DFAFC.

The kinetics of CO(2) adsorption and desorption over amine-functionalized mesoporous silica were investigated using silicon microcantilever arrays. Three types of mesoporous silica with different pore sizes were synthesized and functionalized with a variety of amine molecules. After depositing the silica sorbents onto the free end of each cantilever in an array, mass changes due to the adsorption and desorption of CO(2) were determined in situ with picogram sensitivity by measuring variations in the cantilever frequencies. The adsorption and desorption kinetics were found to be diffusion-controlled, and the kinetics were accelerated by increasing the temperature and pore size. The activation energies for adsorption and desorption of CO(2) were determined from Arrhenius plots.