Benefits, challenges, and usability evaluation of DeloreanJS: a back-in-time debugger for JavaScript.

JavaScript Web applications are a common product in industry. As with most applications, Web applications can acquire software flaws (known as bugs), whose symptoms are seen during the development stage and, even worse, in production. The use of debuggers is beneficial for detecting bugs. Unfortunately, most JavaScript debuggers (1) only support the "step into/through" feature in an execution program to detect a bug, and (2) do not allow developers to go back-in-time at the application execution to take actions to detect the bug accurately. For example, the second limitation does not allow developers to modify the value of a variable to fix a bug while the application is running or test if the same bug is triggered with other values of that variable. Using concepts such as continuations and static analysis, this article presents a usable debugger for JavaScript, named DeloreanJS, which enables developers to go back-in-time in different execution points and resume the execution of a Web application to improve the understanding of a bug, or even experiment with hypothetical scenarios around the bug. Using an online and available version, we illustrate the benefits of DeloreanJS through five examples of bugs in JavaScript. Although DeloreanJS is developed for JavaScript, a dynamic prototype-based object model with side effects (mutable variables), we discuss our proposal with the state-of-art/practice of debuggers in terms of features. For example, modern browsers like Mozilla Firefox include a debugger in their distribution that only support for the breakpoint feature. However DeloreanJS uses a graphical user interface that considers back-in-time features. The aim of this study is to evaluate and compare the usability of DeloreanJS and Mozilla Firefox's debugger using the system usability scale approach. We requested 30 undergraduate students from two computer science programs to solve five tasks. Among the findings, we highlight two results. First, we found that 100% (15) of participants recommended DeloreanJS, and only 53% (eight) recommended Firefox's debugger to complete the tasks. Second, whereas the average score for DeloreanJS is 71.6 ("Good"), the average score for Firefox's debugger is 55.8 ("Acceptable").

Amenamevir, a Helicase-Primase Inhibitor, for the Optimal Treatment of Herpes Zoster.

Acyclovir, valacyclovir, and famciclovir are used for the treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Helicase-primase inhibitors (HPIs) inhibit replication fork progression that separates double DNA strands into two single strands during DNA synthesis. The HPIs amenamevir and pritelivir have novel mechanisms of anti-herpetic action, and their once-daily administration has clinical efficacy for genital herpes. Among HPIs, amenamevir has anti-VZV activity. The concentrations of HSV-1 and VZV required for the 50% plaque reduction of amenamevir were 0.036 and 0.047 µM, respectively. We characterized the features of amenamevir regarding its mechanism, resistance, and synergism with acyclovir. Its antiviral activity was not influenced by the viral replication cycle, in contrast to acyclovir. A clinical trial of amenamevir for herpes zoster demonstrated its non-inferiority to valacyclovir. To date, amenamevir has been successfully used in over 1,240,000 patients with herpes zoster in Japan. Post-marketing surveillance of amenamevir in Japan reported side effects with significant potential risk identified by the Japanese Risk Management Plan, including thrombocytopenia, gingival bleeding, and palpitations, although none of these were serious. The clinical efficacy and safety profiles of amenamevir were established in patients with herpes zoster. Therefore, amenamevir as an HPI opens a new era of anti-herpes therapy.

DSSM: Distributed Streaming Data Sharing Manager.

Developing robot control software systems is difficult because of a wide variety of requirements, including hardware systems and sensors, even though robots are demanding nowadays. Middleware systems, such as Robot Operating System (ROS), are being developed and widely used to tackle this difficulty. Streaming data Sharing Manager (SSM) is one of such middleware systems that allow developers to write and read sensor data with timestamps using a Personal Computer (PC). The timestamp feature is essential for the robot control system because it usually uses multiple sensors with their own measurement cycles, meaning that measured sensor values with different timestamps become useless for the robot control. Using SSM allows developers to use measured sensor values with the same timestamps; however, SSM assumes that only one PC is used. Thereby, if one process consumes CPU resources intensively, other processes cannot finish their assumed deadlines, leading to the unexpected behavior of a robot. This paper proposes an SSM middleware, named Distributed Streaming data Sharing Manager (DSSM), that enables distributing processes on SSM to different PCs. We have developed a prototype of DSSM and confirmed its behavior so far. In addition, we apply DSSM to an existing real SSM based robot control system that autonomously controls an unmanned vehicle robot. We then reveal its advantages and disadvantages via several experiments by measuring resource usages.

[Dissolution and maintenance of portal vein thrombosis with antithrombin III and edoxaban in liver cirrhosis:a case report].

A male patient in his 70s was referred to our department. He was found to have alcoholic liver cirrhosis, esophageal varices, and portal vein thrombosis. Antithrombin III (ATIII) formulation was administered. The thrombus was almost completely lysed 2 days after administration. Because portal vein thrombosis could recur, edoxaban, a direct oral anticoagulant (DOAC), was introduced to prevent recurrence. After 4 months, he showed no recurrence of portal vein thrombosis. In the present case, the combination of an ATIII formulation as initial treatment and edoxaban as maintenance therapy was safe and effective. The combination of ATIII and edoxaban may be a treatment option for patients with portal vein thrombosis.

Recovery of Silver Using Adsorption Gels Prepared from Microalgal Residue Immobilized with Functional Groups Containing Sulfur or Nitrogen.

Although biodiesel oil extracted from microalgae attracts much attention as one of the most promising green energies, its high production cost is a big problem, impeding its extensive use. In order to lower the production cost, the effective use of microalgal residue after extracting biofuel was investigated as a feed material of functional materials. In the present work, a new adsorbent for silver(I) was prepared by immobilizing functional groups of polyethylene-polyamine or dithiooxamide, which exhibita high affinity for soft Lewis acids such as silver(I) ions. Their adsorption behaviors for silver(I) were investigated from aqueous nitrate and acidothiourea media. The effects of the concentrations of nitrate and thiourea, as well as of sulfuric acid, were qualitatively interpreted. From the study of adsorption isotherms on these gels, they were found to exhibita higher adsorption capacity than the majority of those reported to date.

Surgical treatment of confirmed intratendinous rotator cuff tears: retrospective analysis after an average of eight years of follow-up.

HYPOTHESIS: This study evaluated clinical features, diagnostic techniques, and summarized the results of open repair in a series of surgically confirmed cases of intratendinous rotator cuff tears. MATERIALS AND METHODS: Between 1986 and 1999, 19 patients (17 men and 2 women) with intratendinous rotator cuff tears underwent surgery. Clinical findings, diagnostic results, and surgical findings were evaluated. The shoulder scores of the Japanese Orthopaedic Association (JOA) and the American Shoulder and Elbow Surgeons (ASES) were used to assess recovery at an average of 92 months (range, 31-231 months). RESULTS: All patients had symptoms consistent with rotator cuff tendonitis. History of overt trauma was noted in 16 (84.2%). Neither ultrasound nor magnetic resonance imaging proved reliable for preoperative diagnosis. Surgery was performed if at least 6 months of conservative treatment, such as rest, heat, and physical therapies, failed. The definitive diagnosis was established intraoperatively with a longitudinal split along the fibers of the supraspinatus tendon. None of the intratendinous lesions had communication to the subacromial bursa or the glenohumeral joint. Excision of the intratendinous tear and repair resulted in improvement in pain and total scores of both JOA (66.8 vs 94.1) and ASES (37.1 vs 91.0). CONCLUSIONS: Intratendinous rotator cuff tears were difficult to diagnose preoperatively. Our data suggest that conservative treatment failed, anterior acromioplasty and excision of the diseased portion of the tendon, followed by tenorrhaphy, proved effective. Satisfactory outcomes were achieved in 18 patients (94.7%) in this series.

Charles Neer: on the giant of the shoulder.

In the world of orthopedics, certain giants have become known as associated with a single subspecialty or for work on a single joint. Among these are John Charnley, for his work on total hip arthroplasty, and Amory Codman, for his work on the shoulder. But in the second half of the 20th century, the true giant of shoulder surgery was Charles Neer. His contributions to our subspecialty may not have been surpassed by any orthopedic surgeon for any subspecialty. This article explores his life and his contributions to shoulder surgery from those who knew him best.

Neer modified inferior capsular shift procedure for recurrent anterior instability of the shoulder in judokas.

BACKGROUND: Little has been written about the operative repair of recurrent anterior instability of the shoulder in a single sport: in this case, Judo. PURPOSE: The clinical efficacy of the Neer modified inferior capsular shift as an open procedure for injured judokas was investigated. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Fifty athletes (42 male and 8 female, 52 shoulders) took part in this study. The average age at surgery was 20 years (range, 14-38 years), and the mean follow-up period was 61 months (range, 24-172 months). The operation was performed on 29 tsurité (a lapel grip) shoulders and on 23 hikité (a sleeve grip) shoulders. The 2 grips are functionally and technically different from each other. RESULTS: Three cases of shoulder instability (5.8%) recurred after surgery. The average loss of external rotation was 9.6 degrees with the arm at the side and 11.6 degrees with the arm in 90 degrees of abduction. The average Rowe and UCLA scores were 37.3 and 20.8 points preoperatively and 86.7 and 32.4 points at the final follow-up, respectively (P < .05). The return rate to the near-preinjury sports activity levels (>90% recovery: grades 1 and 2) was significantly lower in the tsurité shoulders (48.1%) than in the hikité shoulders (85.7%). CONCLUSION: The overall recovery of more than 90% of preinjury activity levels in judo was 65% after modified inferior capsular shift for traumatic anterior instability of the shoulder. The tsurité shoulder should be treated with minimal restriction limitation in external rotation so that it is not limited postoperatively.

Galactolipid synthesis in chloroplast inner envelope is essential for proper thylakoid biogenesis, photosynthesis, and embryogenesis.

The biogenesis of thylakoid membranes, an indispensable event for the photoautotrophic growth of plants, requires a significant increase in the level of the unique thylakoid membrane lipid monogalactosyldiacylglycerol (MGDG), which constitutes the bulk of membrane lipids in chloroplasts. The final step in MGDG biosynthesis occurs in the plastid envelope and is catalyzed by MGDG synthase. Here we report the identification and characterization of an Arabidopsis mutant showing a complete defect in MGDG synthase 1. The mutant seeds germinated as small albinos only in the presence of sucrose. The seedlings lacked galactolipids and had disrupted photosynthetic membranes, leading to the complete impairment of photosynthetic ability and photoautotrophic growth. Moreover, invagination of the inner envelope, which is not seen in mature WT chloroplasts, was observed in the mutant, supporting an old hypothesis that envelope invagination is a major event in early chloroplast biogenesis. In addition to the defective seedling phenotype, embryo development was arrested in the mutant, although seeds with impaired embryos could germinate heterotrophically. These results demonstrate the importance of galactolipids not only in photosynthetic growth but also in embryogenesis.

Progesterone-dependent and -independent expression of the multidrug resistance type I gene in porcine granulosa cells.

A primary role of plasma membrane P-glycoprotein (P-gp), encoded by multidrug resistance type I (MDR1), is to protect against naturally occurring xenotoxics. Progesterone (P(4)) profoundly influences MDR1 expression in granulosa cells and luteal cells. Here, P(4) regulation of MDR1 expression was investigated in porcine granulosa cells using the P(4)-mediated promoter activity assay and a P4 receptor (PR) antagonist (RU-486). The promoter activity was measured chronologically for 48 h in cells transfected with the PR response element-containing pGL3. LH could stimulate the promoter activity through endogenous P4, with a maximum activity at 5 h. MDR1 mRNA level was highly maintained at 24-36 h. Conversely, exogenous P4 prolonged the promoter activity to further 10 h, and the high level of MDR1 mRNA was maintained even at 48 h. RU-486 completely inhibited the promoter activity, but the level of MDR1 mRNA rapidly increased in the presence of RU-486. The granulosa cells may become susceptible to RU-486 as a xenotoxic to rapidly express MDR1 for protection against it. These results indicate that MDR1 is expressed in porcine granulosa cells through P4-dependent and -independent regulations.

Molecular effects of sodium hyaluronate on the healing of avian supracoracoid tendon tear: according to in situ hybridization and real-time polymerase chain reaction.

Hyluronic acid (HA) on tissue healing has been controversial. We examined the molecular pharmacology of HA injection at the suture site in an acute model of supracoracoid tendon laceration using chickens, an injury of a nonweight-bearing joint considered similar to the human shoulder. Expression of mRNAs encoding alpha I (I) and alphaI (III) procollagens was localized using in situ hybridization (ISH). Intensities of mRNA expression for alpha I (I) and alpha I (III) procollagens, transforming growth factor-beta1 (TGF- beta1), basic fibroblast growth factor (bFGF), and insulin-like growth factor (IGF) were determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Histologically, chickens with HA injection (HA group) showed early restoration of continuity at the laceration site than saline-injection controls (saline-injection group). By ISH, the expression rate of cells at the lesion site that contained alpha I (I) and alpha I (III) procollagen mRNAs were somewhat higher in the HA group than in the saline-injection group. By RT-PCR, the HA- and saline-injection groups showed no significant difference in expression of alpha I (I) and alpha I (III) procollagen mRNA between weeks 1 and 6. The saline -injection group exhibited significant decrease in TGF-beta1 expression between weeks 1 and 3, and in bFGF expression between weeks 1 and 2; however, the HA group showed no such decrease. As for IGF, no difference was appreciable in both groups between weeks 1 and 6. A single injection of HA could cause earlier restoration of continuity at the lacerated site of the supracoracoid tendon.

Progesterone regulation of the expression and function of multidrug resistance type I in porcine granulosa cells.

P-glycoprotein (P-gp) coded with the multidrug resistance type I (MDR1) is expressed in various normal tissues including ovaries and may function as detoxification and steroid transport. The present study was performed to analyze the expression and function of MDR1 in granulosa cells stimulated with FSH, LH, estradiol-17beta (E) and progesterone (P). The granulosa cells isolated from porcine ovarian follicles were cultured for 24h in a serum-supplemented medium, and then cultured for 48h with the hormones in a serum-free culture medium. MDR1 was highly expressed in large follicles and induced in cultured granulosa cells stimulated with LH as revealed by RT-PCR. Highly expressed MDR1 resulted in the increased P-gp activity. However, FSH had no effect. P significantly increased the MDR1 expression and P-gp activity in the cells stimulated with LH, whereas E had no stimulatory effect. Aminoglutethimide suppressed the MDR1 expression and P-gp activity, but which were completely restored by P. These results indicate that P participates in MDR1 expression and P-gp function of granulosa cells.

Development of multidrug resistance type I P-glycoprotein function during in vitro maturation of porcine oocyte.

The present study was performed to evaluate the expression and function of P-glycoprotein (P-gp) encoded the multidrug resistance type I (MDR1) gene, protecting from xenotoxics, in porcine oocyte during in vitro maturation. Cumulus-oocyte complexes (COCs) were cultured to obtain the germinal vesicle (GV), first metaphase and second metaphase (MII) oocytes. The P-gp function was assessed by means of the rhodamine 6G (R6G) efflux from oocytes with P-gp inhibitors such as verapamil and PSC-833. The MDR1 transcript was detected in the GV and MII oocytes by RT-PCR analysis using primer sets based on the human gene. P-gp inhibitors significantly blocked the R6G efflux from the MII oocytes, whereas the reagents were ineffective in the GV oocytes. The R6G efflux from oocytes was accelerated at the MII stage more than at the GV stage. Thus, the MDR1-type P-gp function is poor at the GV stage, but the function improves during oocyte maturation.

Vascular endothelial growth factor 121 and 165 in the subacromial bursa are involved in shoulder joint contracture in type II diabetics with rotator cuff disease.

Vascular endothelial growth factor (VEGF) is a glycoprotein that plays an important role in neovascularization and increases vascular permeability. We reported that VEGF is involved in motion pain of patients with rotator cuff disease by causing synovial proliferation in the subacromial bursa (SAB). The present study investigates whether VEGF is also involved in the development of shoulder contracture in diabetics with rotator cuff disease. We examined 67 patients with rotator cuff disease, including 36 with complete cuff tears, 20 with incomplete tears, and 11 without apparent tears (subacromial bursitis). The patients were into groups according to the presence or absence of diabetes (14 type II diabetics and 53 non-diabetics). Specimens of the synovium of the SAB were obtained from all patients during surgery. Expression of the VEGF gene in the synovium of the subacromial bursa was evaluated by using the reverse transcriptase polymerase chain reaction. The VEGF protein was localized by immunohistochemistry, and the number of vessels was evaluated based on CD34 immunoreactivity. The results showed that VEGF mRNA was expressed in significantly more diabetics (100%, 14/14) than in non-diabetics (70%, 37/53) (P=0.0159, Fisher's test). Investigation of VEGF isoform expression revealed VEGF121 in all 14 diabetics and in 37 of the 53 non-diabetics, VEGF165 in 12 of the 14 diabetics and in 21 of the 53 non-diabetics, and VEGF189 in 1 of the 14 diabetics and in 2 of the 53 non-diabetics. No VEGF206 was expressed in either group. VEGF protein was localized in both vascular endothelial cells and synovial lining cells. The mean number of VEGF-positive vessels and the vessel area were also significantly greater in the diabetics (p<0.015, Mann-Whitney U test). Synovial proliferation and shoulder joint contracture were more common in the diabetics (P=0.0329 and P=0.073, respectively; Fisher's test). The mean preoperative range of shoulder motion significantly differed in terms of elevation between two groups: 103.8 degrees in diabetics and 124.9 degrees in no diabetics (p=0.0039 Mann-Whitney U test). In contrast, external rotation did not significantly differ: 44 degrees in diabetics and 49 degrees in non-diabetics (p=0.4957, Mann-Whitney U test). These results suggest that VEGF121 and VEGF165 expression in the SAB is responsible for the development of shoulder joint contracture, especially in elevation, among type II diabetic patients with rotator cuff disease.

Interleukin-1-induced glenohumeral synovitis and shoulder pain in rotator cuff diseases.

Synovitis of the subacromial bursa has been identified as a main source of shoulder pain in rotator cuff diseases. Little interest, however, has been paid into the synovitis of glenohumeral joint. The mRNA expression levels of interleukin-1beta (IL-1beta) and interleukin-1 receptor antagonists produced in the synovitis reflect the magnitude of inflammation. The present study was undertaken to determine the relationship between mRNA expression levels of IL-1beta and its receptor antagonists (secreted interleukin-1 receptor antagonist (IL-1ra) and intracellular IL-1ra) in the synovium of the glenohumeral joint and shoulder pain in rotator cuff diseases, analyzing the synovial specimens by reverse transcriptase polymerase chain reaction. Thirty-five patients with rotator cuff diseases were candidates. Based on the presence of cuff perforation, they were divided into two categories: 16 with non-perforating tears and 19 with perforating tears. The degree of shoulder pain was evaluated by use of a visual analogue scale. The pain degree of non-perforating tears was significantly greater than that of perforating tears (P < 0.01). In contrast, the expression levels of the cytokine-mRNAs were constitutively greater in perforating tears than in non-perforating tears (P < 0.01, respectively). The expression levels of the cytokine-mRNAs were inversely correlated with the degree of pain (IL-1beta: r = 0.930; secreted IL-1ra: r = 0.861; intracellular IL-1ra: r = 0.932, P < 0.001 respectively). These results suggest that the expression levels of the cytokine-mRNAs in the synovium of the glenohumeral joint contribute less to the generation of shoulder pain in rotator cuff diseases.