Gboxin is an oxidative phosphorylation inhibitor that targets glioblastoma.

Cancer-specific inhibitors that reflect the unique metabolic needs of cancer cells are rare. Here we describe Gboxin, a small molecule that specifically inhibits the growth of primary mouse and human glioblastoma cells but not that of mouse embryonic fibroblasts or neonatal astrocytes. Gboxin rapidly and irreversibly compromises oxygen consumption in glioblastoma cells. Gboxin relies on its positive charge to associate with mitochondrial oxidative phosphorylation complexes in a manner that is dependent on the proton gradient of the inner mitochondrial membrane, and it inhibits the activity of F0F1 ATP synthase. Gboxin-resistant cells require a functional mitochondrial permeability transition pore that regulates pH and thus impedes the accumulation of Gboxin in the mitochondrial matrix. Administration of a metabolically stable Gboxin analogue inhibits glioblastoma allografts and patient-derived xenografts. Gboxin toxicity extends to established human cancer cell lines of diverse organ origin, and shows that the increased proton gradient and pH in cancer cell mitochondria is a mode of action that can be targeted in the development of antitumour reagents.

X-ray processing of a realistic ice mantle can explain the gas abundances in protoplanetary disks.

The Atacama Large Millimeter Array has allowed a detailed observation of molecules in protoplanetary disks, which can evolve toward solar systems like our own. While CO, [Formula: see text], HCO, and [Formula: see text] are often abundant species in the cold zones of the disk, [Formula: see text] or [Formula: see text] are only found in a few regions, and more-complex organic molecules are not observed. We simulate, experimentally, ice processing in disks under realistic conditions, that is, layered ices irradiated by soft X-rays. X-ray emission from young solar-type stars is thousands of times brighter than that of today's sun. The ice mantle is composed of a [Formula: see text]:[Formula: see text]:[Formula: see text] mixture, covered by a layer made of [Formula: see text] and CO. The photoproducts found desorbing from both ice layers to the gas phase during the irradiation converge with those detected in higher abundances in the gas phase of protoplanetary disks, providing important insights on the nonthermal processes that drive the chemistry in these objects.

Does positive feeling lead to more impulsiveness? - Implication of previous rewarded experience on location-dependent motoric impulsivity.

Positive feeling or rewarding experience is crucial for individuals to operative their cognitive activities via an outcome evaluation of incentive reinforcement. For a long time, rewarding process or outcome evaluation is assumed greatly influenced by neuronal construct that holds individuals' impulsiveness, a capacity to inhibit unwanted behaviors provoked in a given situation. In the present study, we proposed that the outcome evaluation or rewarding experience can influence the occurrence of impulsiveness too. We hypothesized that animals would be more likely to deliver impulsive action in the place where it was previously associated with reinforcing process, in which central dopamine may play an important role. By employing five-choice serial reaction time task (5-CSRTT), we examined whether one of the five holes where rats made a correct response to get the reward would gain a higher probability to deliver premature or perseverative activities than other holes in the next trial of 5-CSRTT under baseline or longer waiting period condition. The effects of D1 receptor antagonist SCH23390 were also evaluated in the above paradigm. We demonstrated that (i) the influence on motoric impulsive response from previous rewarded experience can be described in a behavioral paradigm such as the 5-CSRTT, (ii) both prematures and perseverations at the hole associated with previous rewarding were about one-fifth of probability, however were statistically not correlated unless the interventions of inter-trial interval = 7 plus SCH23390, and (iii) the hole associated with the positive reinforcement of the 5-CSRTT appears more likely for rats to carry out an intuitive impetus under SCH23390 in a longer waiting condition. Our results may shed some insight toward the role of rewarding process in impulsive behavior.

Utilization of Inertial Measurement Units for Determining the Sequential Chain of Baseball Strike Posture.

The purpose of this study was to employ inertial measurement units (IMU) with an eye-tracking device to investigate different swing strategies between two levels of batters. The participants were 20 healthy males aged 20 to 30 years old, with ten professional and ten amateur batters. Eye gaze position, head, shoulder, trunk, and pelvis angular velocity, and ground reaction forces were recorded. The results showed that professional batters rotated segments more rhythmically and efficiently than the amateur group. Firstly, the professional group spent less time in the preparation stages. Secondly, the maximum angular velocity timing of each segment of the professional group was centralized in the swing cycle. Thirdly, the amateur group had significantly earlier gaze timing of the maximum angular velocity than the professional group. Moreover, the maximum angular velocity timing of the gaze was the earliest parameter among the five segments, and significantly earlier (at least 16.32% of cycle time) than the maximum angular velocity of the head, shoulder, trunk, and pelvis within the amateur group. The visual-motor coordination strategies were different between the two groups, which could successfully be determined by wearable instruments of IMU.

Computing the relevant colors that describe the color palette of paintings.

In this paper, we introduce an innovative parameter that allows us to evaluate the so-called "relevant colors" in a painting; in other words, the number of colors that would stand out for an observer when just glancing at a painting. These relevant colors allow us to characterize the color palette of a scene and, on this basis, those discernible colors that are colorimetrically different within the scene. We tried to carry out this characterization of the chromatic range of paints according to authors and styles. We used a collection of 4,266 paintings by 91 painters, from which we extracted various parameters that are exclusively colorimetric to characterize the range of colors. After this refinement of the set of selected colors, our algorithm obtained an average number of 18 relevant colors, which partially agreed with the total 11-15 basic color names usually found in other categorical color studies.

Galectin-3 Enhances Avian H5N1 Influenza A Virus-Induced Pulmonary Inflammation by Promoting NLRP3 Inflammasome Activation.

Highly pathogenic avian influenza A H5N1 virus causes pneumonia and acute respiratory distress syndrome in humans. Virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. Galectin-3, a ß-galactoside-binding protein widely distributed in immune and epithelial cells, regulates various immune functions and modulates microbial infections. Here, we describe galectin-3 up-regulation in mouse lung tissue after challenges with the H5N1 influenza virus. We investigated the effects of endogenous galectin-3 on H5N1 infection and found that survival of galectin-3 knockout (Gal-3KO) mice was comparable with wild-type (WT) mice after infections. Compared with infected WT mice, infected Gal-3KO mice exhibited less inflammation in the lungs and reduced IL-1ß levels in bronchoalveolar lavage fluid. In addition, the bone marrow-derived macrophages (BMMs) from Gal-3KO mice exhibited reduced oligomerization of apoptosis-associated speck-like proteins containing caspase-associated recruitment domains and secreted less IL-1ß compared with BMMs from WT mice. However, similar levels of the inflammasome component of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) were observed in two genotypes of BMMs. Co-immunoprecipitation data indicated galectin-3 and NLRP3 interaction in BMMs infected with H5N1. An association was also observed between galectin-3 and NLRP3/apoptosis-associated speck-like proteins containing caspase-associated recruitment domain complex. Combined, our results suggest that endogenous galectin-3 enhances the effects of H5N1 infection by promoting host inflammatory responses and regulating IL-1ß production by macrophages via interaction with NLRP3.

A digital assessment system for evaluating kinetic tremor in essential tremor and Parkinson's disease.

BACKGROUND: Spiral drawing on papers is a common tremor evaluation tool for diagnosing patients with essential tremor (ET) or Parkinson's disease (PD). No standard drawing methods and parameters that use graphic tablets are yet available for objective evaluation. METHODS: This study established a tremor assessment system for tremor severity by using graphic tablets. Twelve patients with ET and twelve patients with PD were tested to establish system algorithms, and six additional patients were tested with the developed system to evaluate its performance. The patients also performed spiral drawing with three guiding paradigms on a graphic tablet: traced along a given spiral (S1), performed freehand drawing (S2), and traced along a guiding point (S3). Three parameters were calculated to quantify tremor severity: the means of radial difference per radian (|dr/dθ|), the means of radial difference per second (|dr/dt|), and the area under curve (AUC) of the frequency spectrum of the velocity. Each patient's drawing was also evaluated using a visual rating scale (VRS) by experienced physicians. The interrater reliability was examined to identify the most consistent test paradigm. RESULTS: The parameter |dr/dθ| and AUC correlated well with the VRS (R > 0.8) in S1, S2 and S3 tests. The S1 test presented the best interrater reliability (Weighted Kappa coefficient, k = 0.80) among three tests. The Weighted Kappa coefficients are 0.67 and 0.71 in S2 and S3 tests, respectively. CONCLUSIONS: We developed three different guiding paradigms for spiral drawing on a digital graphic tablet for clinical tests. Three parameters were calculated to represent the tremor severity in spiral drawing and used to quantify temporal and spatial characteristics of tremor, and provided good correlation with current clinical assessments. The test "traced along a given spiral" is recommended due to its good interrater reliability.

The difference in visuomotor feedback velocity control during spiral drawing between Parkinson's disease and essential tremor.

In a spiral task, the accuracy of the spiral trajectory, which is affected by tracing or tracking ability, differs between patients with Parkinson's disease (PD) and essential tremor (ET). However, not many studies have analyzed velocity differences between the groups during this task. This study aimed to examine differences between the groups related to this characteristic using a tablet. Fourteen PD, 12 ET, and 12 control group participants performed two tasks: tracing a given spiral (T1) and following a guiding point (T2). A digitized tablet was used to record movements and trajectory. Effects of direct visual feedback on intergroup and intragroup velocity were measured. Although PD patients had a significantly lower T1 velocity than the control group (p < 0.05), they could match the velocity of the guiding point (3.0 cm/s) in T2. There was no significant difference in the average T1 velocity between ET and the control groups (p = 0.26); however, the T2 velocity of ET patients was significantly higher than the control group (p < 0.05). They were also unable to adjust the velocity to match the guiding point, indicating that ET patients have a poorer ability to follow dynamic guidance. When both groups of patients have similar action tremor severity, their ability to follow dynamic guidance was still significantly different. Our study combined visual feedback with spiral drawing and demonstrated differences in the following-velocity distribution in PD and ET. This method may be used to distinguish the tremor presentation of both diseases, and thus, provide accurate diagnosis.

Toll-like receptor 4 is essential to preserving cardiac function and survival in low-grade polymicrobial sepsis.

BACKGROUND: Toll-like receptor 4 (TLR4), the receptor for endotoxin, mediates hyperinflammatory response and contributes to high mortality during both endotoxin shock and severe sepsis. However, little is known about the role of TLR4 in the pathogenesis of low-grade polymicrobial sepsis, which is often associated with immunosuppression. METHODS: Low-grade polymicrobial sepsis was generated by cecum ligation and puncture. Mortality was monitored in wild- type (C57BL/10ScSn) and TLR4def (C57BL/10ScCr) mice. Ex vivo heart and individual cardiomyocyte function were assessed in Langendorff (Hugo Sachs Elektronik; Harvard Apparatus, Holliston, MA) and IonOptix systems (IonOptix, Milton, MA), respectively. Serum chemistry was tested for liver and kidney injury. Cytokines were examined using a multiplex immunoassay. Neutrophil migratory and phagocytic functions were assessed using flow cytometry. Reactive oxygen species were measured using redox-sensitive dichlorodihydrofluorescein dye. RESULTS: Following cecum ligation and puncture, wild-type mice developed bacterial peritonitis with mild cardiac dysfunction (n=3 in sham and n=8 in cecum ligation and puncture) and a mortality of 23% within 14 days (n=22). In comparison, septic TLR4def mice had deleterious cardiac dysfunction (n=6 in sham and n=10 in cecum ligation and puncture), kidney and liver injury (n=7), and much higher mortality at 81% (n=21). The deleterious effects observed in septic TLR4def mice were associated with increased local and systemic cytokine response, reduced neutrophil migratory and phagocytic function, increased reactive oxygen species generation in leukocytes, and impaired bacterial clearance. CONCLUSION: TLR4 plays an essential role in host defense against low-grade polymicrobial sepsis by mediating neutrophil migratory/phagocytic functions, attenuating inflammation, reducing reactive oxygen species generation, and enhanced bacterial clearance.

Multiple inertial measurement unit combination and location for recognizing general, fatigue, and simulated-fatigue gait.

BACKGROUND: Muscle fatigue of the lower limbs results in dynamic imbalance and gait instability, increasing the risk of falling. However, people might slow walk without physical muscle fatigue due to mental fatigue. Wearable inertial measurement units (IMU) and machine learning approaches have been well employed for recognizing human activities. RESEARCH QUESTION: The study aims to use a machine learning technique to recognize the data collected from IMUs for physically fatigued or slow-walking gaits. Second, the study aims to reveal the location or the number of IMUs can have the best performance. METHODS: Sixteen healthy adults with six IMUs attached to their heels, toes, sacrum, and head participated in the experiment. On the first day, the participants were instructed to walk along a hallway before and after the fatigue protocol as the Pre- and Post-fatigue gait. On the second day, the participants were instructed to walk along a hallway following the beat of their fatigue gait cadence measured on the first day as the simulated cadence (SC) gait. Gait cycles of each condition were segmented as the inputs of the Long Short-Term Memory (LSTM) model for recognization. RESULTS: The result revealed that the LSTM model could recognize the gait of simulated cadence with the highest accuracy among these three gaits. For the signal body part, the highest accuracy was 93.20 % observed at the IMUs of toes. For the best combination, the IMUs of toes and sacrum achieved the highest accuracy of 95.71 %. SIGNIFICANCE: The machine learning technique of LSTM with one or more IMUs can recognize the gait under normal, physical fatigue, or simulated cadence without muscle fatigue. Our model and approach would be expected to provide conditional warning in multiple fields, such as industrial safety for potential applications.

Automatic real-time occupational posture evaluation and select corresponding ergonomic assessments.

The objective is to develop a system to automatically select the corresponding assessment scales and calculate the score of the risk based on the joint angle information obtained from the imaged process (OpenPose) via image-based motion capture technology. Current occupational assessments, for example, REBA, RULA, and OWAS were used to evaluate the risk of musculoskeletal disorders. However, the assessment result would not be reported immediately. Introducing real-time occupational assessments in different working environments will be helpful for occupational injury prevention. In this study, the decision tree was developed to select the most appropriate assessment method according to the joint angles derived by OpenPose image process. Fifteen operation videos were tested and these videos can be classified into six types including maintenance, handling, assembly, cleaning, office work, and driving. The selected ergonomic assessment method by our developed decision tree in each condition are consistent with the recommendation of the Labour Research Institute. Moreover, the high-risk posture could be identified immediately and provide to the inspector for further evaluation on this posture rather than the whole operation period. This approach provides a quick inspection of the operation movements to prevent musculoskeletal injuries and enhances the application of the scale assessment method in different industrial environments.

Treatment of diabetic rats with a peroxynitrite decomposition catalyst prevents induction of renal COX-2.

Cyclooxygenase (COX)-2 expression is increased in the kidney of rats made diabetic with streptozotocin and associated with enhanced release of prostaglandins stimulated by arachidonic acid (AA). Treatment of diabetic rats with nitro-L-arginine methyl ester (L-NAME) to inhibit nitric oxide synthase or with tempol to reduce superoxide prevented these changes, suggesting the possibility that peroxynitrite (ONOO) may be the stimulus for the induction of renal COX-2 in diabetes. Consequently, we tested the effects of an ONOO decomposition catalyst, 5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron(III) (FeTMPyP), which was administered for 3-4 wk after the induction of diabetes. FeTMPyP treatment normalized the twofold increase in the expression of nitrotyrosine, a marker for ONOO formation, in the diabetic rat and prevented the increase in renal COX-2 expression without modifying the two- to threefold increases in renal release of prostaglandins PGE(2) and 6-ketoPGF(1α) in response to AA. FeTMPyP treatment of diabetic rats reduced the elevated creatinine clearance and urinary excretion of TNF-α and transforming growth factor (TGF)-ß, suggesting a renoprotective effect. Double immunostaining of renal sections and immunoprecipitation of COX-2 and nitrotyrosine suggested nitration of COX-2 in diabetic rats. In cultured human umbilical vein endothelial cells (HUVECs) exposed to elevated glucose (450 mg/dl) or ONOO derived from 3-morpholinosydnonimine (SIN-1), expression of COX-2 was increased and was prevented when endothelial cells were treated with FeTMPyP. These results indicate that elevated glucose increases the formation of ONOO, which contributes to the induction of renal COX-2 in the diabetic rat.

Reduction in Accommodative Response of Schoolchildren by a Double-Mirror System.

PURPOSE: This study first proposed the application of a double-mirror system (DMS) to extend viewing distance and investigate the accommodative response of schoolchildren under a DMS. METHOD: Fifty-seven subjects aged between 7 and 12 years old were recruited in this study, and the experiment was divided into two stages. The first stage consisted of a case history inquiry, a refraction state, and a visual function examination. In the second stage, the subjects gazed at an object at distances of 0.4 m, 2.285 m, and through a DMS, respectively, and their accommodative responses were measured using an open-field autorefractor. RESULTS: There was no significant difference in the schoolchildren's accommodative response between subjects gazing at an object at 2.285 m (0.14 ± 0.35 D, p > 0.05) and those gazing at it through a DMS (0.20 ± 0.35 D). However, their accommodative response showed a significant difference between subjects gazing at an object at 0.4 m and 2.285 m and those gazing at it at 0.4 m and through a DMS. CONCLUSION: In this experiment, the results of the children's accommodative response measured at 2.285 m or through a DMS are very similar. The viewing distance can be extended by a DMS, resulting in accommodative relaxation. This result may have potential applications in myopia control.

Stem-like cells drive NF1-associated MPNST functional heterogeneity and tumor progression.

NF1-associated malignant peripheral nerve sheath tumors (MPNSTs) are the major cause of mortality in neurofibromatosis. MPNSTs arise from benign peripheral nerve plexiform neurofibromas that originate in the embryonic neural crest cell lineage. Using reporter transgenes that label early neural crest lineage cells in multiple NF1 MPNST mouse models, we discover and characterize a rare MPNST cell population with stem-cell-like properties, including quiescence, that is essential for tumor initiation and relapse. Following isolation of these cells, we derive a cancer-stem-cell-specific gene expression signature that includes consensus embryonic neural crest genes and identify Nestin as a marker for the MPNST cell of origin. Combined targeting of cancer stem cells along with antimitotic chemotherapy yields effective tumor inhibition and prolongs survival. Enrichment of the cancer stem cell signature in cognate human tumors supports the generality and relevance of cancer stem cells to MPNST therapy development.

Preclinical Studies of OBI-999: A Novel Globo H-Targeting Antibody-Drug Conjugate.

Globo H (GH), a hexasaccharide, is expressed at low levels in normal tissues but is highly expressed in multiple cancer types, rendering it a promising target for cancer immunotherapy. OBI-999, a novel antibody-drug conjugate, is derived from a conjugation of a GH-specific mAb with a monomethyl auristatin E (MMAE) payload through a site-specific ThioBridge and a cleavable linker. OBI-999 high homogeneity with a drug-to-antibody ratio of 4 (>95%) was achieved using ThioBridge. OBI-999 displayed GH-dependent cellular internalization and trafficked to endosome and lysosome within 1 and 5 hours, respectively. Furthermore, OBI-999 showed low nanomolar cytotoxicity in the assay with high GH expression on tumor cells and exhibited a bystander killing effect on tumor cells with minimal GH expression. Tissue distribution indicated that OBI-999 and free MMAE gradually accumulated in the tumor, reaching maximum level at 168 hours after treatment, whereas OBI-999 and free MMAE decreased quickly at 4 hours after treatment in normal organs. Maximum MMAE level in the tumor was 16-fold higher than in serum, suggesting that OBI-999 is stable during circulation and MMAE is selectively released in the tumor. Excellent tumor growth inhibition of OBI-999 was demonstrated in breast, gastric, and pancreatic cancer xenograft or lung patient-derived xenograft models in a dose-dependent manner. The highest nonseverely toxic dose in cynomolgus monkeys is 10 mg/kg determined by a 3-week repeated-dose toxicology study demonstrating an acceptable safety margin. Taken together, these results support further clinical development of OBI-999, which is currently in a phase I/II clinical study in multiple solid tumors (NCT04084366). OBI-999, the first GH-targeting ADC, displayed excellent tumor inhibition in animal models across multiple cancer types, including breast, gastric, pancreatic, and lung cancers, warranting further investigation in the treatment of solid tumors.

Toll-like receptor 2 plays a critical role in cardiac dysfunction during polymicrobial sepsis.

OBJECTIVE: To determine the role of toll-like receptor 2 in cardiac dysfunction during polymicrobial sepsis. DESIGN: Controlled animal study. SETTING: University hospital research laboratory. SUBJECTS: Male C57BL/6, wild-type, toll-like receptor 2-/-. INTERVENTION: Polymicrobial peritonitis, a clinically relevant model of sepsis, was generated by cecum ligation and puncture. Wild-type and toll-like receptor 2-/- mice were divided into sham and cecum ligation and puncture groups. The sham animals underwent laparotomy but without cecum ligation and puncture. Twenty-four hours after surgeries, the cardiac function was assessed by serial echocardiography in vivo, a pressure transducer catheter was inserted into the left ventricles of isolated hearts (Langendorff model), and in vitro measurement of Ca2+ transients and sarcomere shortening in adult cardiomyocytes were isolated from the sham and septic animals. In addition, myocardial and serum cytokines, blood white blood cell counts, peritoneal neutrophil recruitment, chemokine receptor expression, and survival rates were examined. MEASUREMENTS AND RESULTS: Compared to septic wild-type mice, toll-like receptor 2-/- mice had markedly improved cardiac function during sepsis, as demonstrated by in vivo tissue Doppler imaging, better-preserved left ventricle function in isolated heart, and improved sarcomere shortening measured in single cardiomyocytes. There was also a significant survival benefit in toll-like receptor 2-/- mice compared to wild-type mice. These favorable outcomes in toll-like receptor 2-/- mice were associated with attenuated cardiodepressant cytokine levels in the myocardium and serum and enhanced neutrophil migratory function. CONCLUSIONS: These studies suggest that toll-like receptor 2 signaling plays a critical role in mediating cardiomyopathy, deleterious myocardial and systemic inflammation, and high mortality during polymicrobial sepsis.

Antidepressant effects on insulin sensitivity and proinflammatory cytokines in the depressed males.

Growing evidence suggests that mood disorder is associated with insulin resistance and inflammation. Thus the effects of antidepressants on insulin sensitivity and proinflammatory responses will be a crucial issue for depression treatment. In this study, we enrolled 43 non-diabetic young depressed males and adapted standard testing procedures to assess glucose metabolism during 4-week hospitalization. Before and after the 4-week antidepressant treatment, participants underwent oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity (S(I)), glucose effectiveness (S(G)), acute insulin response, and disposition index (DI) were estimated using the minimal model method. The plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and adiponectin were measured. The Hamilton depression rating scale (HAM-D) total scores were reduced significantly during the course of treatment. There were no significant changes in the parameters of S(I), S(G), and DI. Compared to drug naïve status, the level of plasma IL-6 was significantly elevated (0.77 to 1.30 pg/ml; P = .001) after antidepressant therapy. However, the concentrations of CRP, TNF-alpha, and adiponectin showed no differences during the course of treatment. The results suggest that antidepressants may promote stimulatory effect on the IL-6 production in the early stage of antidepressant treatment.

Thymic squamous cell carcinoma with multiple brain metastases.

Thymic carcinomas are rare epithelial malignancies with marked invasive tendency which can metastasize to distant organs, most commonly to the lung, bone, liver, kidney and extra-thoracic lymph nodes. Central nervous system metastasis is extremely rare and only 45 such cases have been reported in the English literature. We reported a 42-year-old male with thymic squamous cell carcinoma and lung and bones metastases. He underwent thymomectomy and pulmonary lobectomy with concurrent chemo-radiotherapy. Based on the clinical symptoms of severe headache and vomiting and the results of brain computed tomography and magnetic resonance imaging scans, 2 metastatic tumors with a cystic component were diagnosed. We resected the metastatic tumors and the signs of increased intracranial pressure subsided immediately after the operation. The patient underwent continuous chemotherapy systemically and whole brain irradiation for disease control. This presentation suggests that surgical resection with concurrent chemo-radiotherapy is the treatment of choice for thymic carcinomas with brain metastases.

Early life social experience and adulthood impulsivity - Implications of central serotonergic system during development.

Developmental psychology highlights that early life experience is important in shaping later on mental manifestations, and it may apply to social development too. Impulsivity is a specific form of mental manifestation to reflect an impairment of individuals' ability to control their response. Increasing evidence reveals that disturbance of social development from early life, such as isolation rearing since weaning, could affect individuals' behavioral impulsivity. Its underlying mechanism remains unsolved, however manipulation of central 5-HT system provide effective therapeutic utility in both human and animal studies. We hypothesize that the pathophysiology of isolation rearing shares with the underlying mechanism of impulsivity in which a time-dependent change of central 5-HT is involved. The hypothesis can be tested by experiments to work out (i) early life social development serves as a factor in determining the function of central 5-HT in adulthood, and (ii) long term manipulation of central 5-HT can reverse the effects of isolation rearing on behavioral impulsivity and 5-HT related neurochemical profiles.

Multiple Inertial Measurement Unit Combination and Location for Center of Pressure Prediction in Gait.

Center of pressure (COP) during a gait cycle indicates crucial information with regard to fall risk such as balance capacity. The drawbacks of conventional research instruments include inconvenient use during activities of daily living and expensive costs. The present study illustrates the promising fall-relevant information predicted by acceleration and angular velocity data from different placement sensors with machine learning techniques. This approach is inspired by the emerging machine learning technique, specifically the long short-term memory (LSTM), which is often used in time series data and aims to decrease the burden of the user while using the novel wearable technology. The Jaccard similarity coefficient, which implies the consistency of profile alignment between prediction and real situation, achieved 94% accuracy in the walking direction. Furthermore, the number of sensors used and the placement influenced the feasibility of an application. The outcome revealed that the accuracy could exceed 90% with only one sensor placed on the foot in the walking direction, and the toe would be the best location for sensor placement. To examine the performance of machine learning, the current study employed two parameters from different perspectives. One is a commonly used parameter, which represented the error, and the other investigated the similarity between the prediction and ground truth. From a similarity perspective, the parameter can be used as a metric to assess the consistency of profile alignment.