Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of Sirt1/FXR Signaling Pathway Attenuates Triptolide-Induced Hepatotoxicity in Rats

Triptolide (TP), a diterpenoid isolated from Tripterygium wilfordii Hook F, has an excellent pharmacological profile of immunosuppression and anti-tumor activities, but its clinical applications are severely restricted due to its severe and cumulative toxicities. The farnesoid X receptor (FXR) is the master bile acid nuclear receptor and plays an important role in maintaining hepatic metabolism homeostasis. Hepatic Sirtuin (Sirt1) is a key regulator of the FXR signaling pathway and hepatic metabolism homeostasis. The aims of this study were to determine whether Sirt1/FXR signaling pathway plays a critical role in TP-induced hepatotoxicity. Our study revealed that the intragastric administration of TP (400 μg/kg body weight) for 28 consecutive days increased bile acid accumulation, suppressed hepatic gluconeogenesis in rats. The expression of bile acid transporter BSEP was significantly reduced and cholesterol 7α-hydroxylase (CYP7A1) was markedly increased in the TP-treated group, whereas the genes responsible for hepatic gluconeogenesis were suppressed in the TP-treated group. TP also modulated the FXR and Sirt1 by decreasing its expression both in vitro and in vivo. The Sirt1 agonist SRT1720 and the FXR agonist obeticholic acid (OCA) were used both in vivo and in vitro. The remarkable liver damage induced by TP was attenuated by treatment with either SRT1720 or OCA, as reflected by decreased levels of serum total bile acids and alkaline phosphatase and increased glucose levels. Meanwhile, SRT1720 significantly alleviated TP-induced FXR suppression and FXR-targets involved in hepatic lipid and glucose metabolism. Based on these results, we conclude that Sirt1/FXR inactivation plays a critical role in TP-induced hepatotoxicity. Moreover, Sirt1/FXR axis represents a novel therapeutic target that could potentially ameliorate TP-induced hepatotoxicity.
Fusion of perpendicular anisotropic MRI sequences

The quality of magnetic resonance images (MRI) is often limited by anisotropic voxels necessitated by acquisition considerations. Examination of the 3D anatomy and post-processing of such images is challenged by the partial volume effects due to such anisotropic voxels. We propose a method based on the separable wavelet transform to fuse anisotropic clinical images, which are often acquired in perpendicular directions, for example axial, sagittal and coronal, into a single fine-resolution image. We investigate several possible wavelet filters, fusion rules and the number of decomposition levels. Our method shows promising results of restoring features apparently lost due to the partial volume effect.
Follow-Up Two Years After Diagnosis of Diabetes in Patients With Psychosocial Problems Receiving an Intervention by a Medical Social Worker

We followed up the psychosocial situation two years after diabetes diagnosis in patients (n = 82) aged 18–65 years, with psychosocial problems (PSP; n = 27) or not (NPSP; n = 55). We used a social questionnaire, the Hospital Anxiety and Depression scale (HAD), the Sense of Coherence scale (SOC), and the General Coping Questionnaire (GCQ). The PSP group had a more difficult situation with more strained economy, lower social support, more anxiety and depression, and lower SOC on both occasions. Being in the PSP group predicted experiencing a strong negative influence of the disease at follow-up. Regarding coping strategies, “problem focusing” decreased in both PSP and NPSP over time. “Social trust” and “intrusion” decreased only in NPSP. Otherwise the coping pattern was unchanged, with PSP showing lower scores on “self-trust” and “minimization” and higher scores on “protest,” “isolation,” and “intrusion. ” The most influenced areas at follow-up in the PSP group were work, relationship to partner and economy, and in the NPSP leisure-time activities, sexual life and work. Our findings underline the need to identify patients with psychosocial problems early.
ResearchAssessment of insulin resistance by a 13 C glucose breath test : a new tool for early diagnosis and follow-up of high-risk patients

Background/Aims: Insulin resistance (IR) plays an important role in the pathogenesis of diabetes and non-alcoholic fatty liver disease (NAFLD). Current methods for insulin resistance detection are cumbersome, or not sensitive enough for early detection and follow-up. The BreathID® system can continuously analyse breath samples in real-time at the point-of-care. Here we determined the efficacy of the BreathID® using the 13C-Glucose breath test (GBT) for evaluation of insulin resistance. Methods: Twenty healthy volunteers were orally administered 75 mg of 13C-glucose 1-13C. An oral glucose tolerance test (OGTT) was performed immediately; followed by serum glucose and insulin level determinations using GBT. GBT and OGTT were repeated following exercise, which alters insulin resistance levels. Results: Within-subject correlations of GBT parameters with serum glucose and serum insulin levels were high. Before and after exercise, between-subjects correlations were high between the relative insulin levels and the % dose recoveries at 90 min (PDR 90), and the cumulative PDRs at 60 min (CPDR 60). Pairwise correlations were identified between pre-exercise Homeostasis Model Assessment (HOMA) IR at 90 min and PDR 90; HOMA B (for beta cell function) 120 and CPDR 30; HOMA IR 60 and peak time post-exercise; and HOMA B 150 with PDR 150. Conclusions: The non-invasive real-time BreathID® GBT reliably assesses changes in liver glucose metabolism, and the degree of insulin resistance. It may serve as a non-invasive tool for early diagnosis and follow up of patients in high-risk
Economic issues concerning the mobility of scientific inventions and implications for firm strategy

It is well recognized that there are imperfections in the market for knowledge transfer due to the nature of ideas and inventions. This is consistent with market failures commonly discussed in the economics of information literature. Some of the impediments to efficiency axe examined here in three essays—one empirical, one theoretical, and one case study—all of which share the theme of scientific knowledge movement. The first essay is empirical and measures the systematic effects of direct interaction and geographic distance between university and firm scientists on the economic performance of imported inventions. This study concludes that, with respect to licensing royalties, scientific interaction has an elasticity of approximately 3 at the mean, which is highly robust, and that distance does not have a significant effect after controlling for interaction. This suggests imperfections in the market for know-how that are sensitive to distance. The second essay is a case study of an invention from the area of robotics and control systems and augments the empirical work presented in the previous essay by illustrating specific reasons why interaction was important for the commercialization of one particular early stage invention. The third essay develops a game theoretic model involving the strategic manipulation of incentives by an incumbent to create an 'intellectual property commons' for the purpose of preventing the commercial development of a disruptive technology that would otherwise threaten existing industry margins. The strategy of spoiling incentives to commercialize public sector scientific inventions by eliminating exclusive intellectual property rights—the strategy of the commons—is motivated by a fear of cannibalization and supported by a credible threat. It is shown that the degree of cannibalization to which the new technology exposes the old market is responsible for this market failure.
Does pectoralis major flap harvesting induce upper extremity dysfunction?

Objective To evaluate the effect of pectoralis major myocutaneous (PMM) flap reconstruction on upper extremity dysfunction. Methods Patients undergoing PMM flap reconstruction following head and neck cancer resection were enrolled. The control group comprised age-, sex- and clinical characteristic-matched patients undergoing non-PMM flap reconstruction. All patients completed the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire preoperatively and >1 year postoperatively. Results There was no significant difference between pre- and postoperative DASH scores in the control group (n = 46; 2.38 ± 3.33 and 2.99 ± 4.21, respectively). In the PMM flap group (n = 46), the postoperative DASH score was significantly higher than the preoperative score (7.00 ± 9.13 and 2.44 ± 3.50, respectively). In the PMM flap group, flap size was significantly associated with postoperative DASH score. Conclusion PMM flap reconstruction has a small but significant negative effect on upper extremity dysfunction.
The G3 Domain of Versican Enhances Cell Proliferation via Epidermial Growth Factor-like Motifs*

Versican is a member of the large aggregating chondroitin sulfate proteoglycan family. We have expressed in NIH3T3 fibroblasts a recombinant versican mini-gene comprising the G1 and G3 domains and 15% of the CS domain. We observed that expression of the mini-versican gene stimulated cell proliferation as determined by cell counting and cell cycle analysis. Addition of exogenous mini-versican protein to cultured cells produced the same result. The effects of the mini-versican were greatly reduced when the G3 domain was deleted. Expression of the G3 domain alone promotes cell proliferation, and addition of purified G3 gene products to NIH3T3 fibroblasts and cultured chicken fibroblasts enhances cell growth. Further, deletion of the epidermal growth factor (EGF)-like motifs in the versican G3 domain reduced the effects of the mini-versican on cell proliferation. In the presence of the purified mini-versican protein, antisense oligonucleotides to the EGF receptor inhibited proliferation of NIH3T3 fibroblasts, compared with control sense oligonucleotides. Taken together, these results imply that versican enhances cell proliferation, and this effect is mediated, at least in part, by the action of versican EGF-like motifs on endogenous EGF receptor.
A Credit Union Case Study of the Business Value of IS/IT

This paper investigates the business value of IS/IT investments in the Financial Services Sectors (FSS) in Australia using a case study methodology to develop and refine a conceptual model of the relationship between IS/IT investment and organisational performance. The conceptual model has four main components, IS/IT investment, organisational performance, considerations for strategic information systems planning and managerial effectiveness. A case study of a credit union indicates support for components of the conceptual model. Further, the analysis reveals the existence of intermediary factors, operations, product delivery, customer service and staff. It is concluded that directing IS/IT investments to these areas, particularly when it is done in concert, is most likely to have a positive impact on organisational performance. Lastly, debate on the issue of an IS/IT investment threshold and its applicability to organisations is presented.
PEMANFAATAN PROGRAM PENCEGAHAN PENULARAN HIV DARI IBU KE BAYI OLEH IBU HAMIL DI RSUD JAYAPURA

Prevention of Mother to Child HIV Transmission (PMTCT) adalah suatu program pencegahan penularan HIV dari ibu ke bayi yang dilaksanakan dalamupaya untuk menurunkan angka resiko penularan HIV dari ibu ke bayi, dengan melakukan intervensi terhadap ibu hamil. Penelitian ini bertujuan untuk mendapatkan gambaran pemanfaatan program pencegahan penularan HIV dari ibu ke bayi/PMTCT oleh ibu hamil di RSUD Jayapura. Jenis penelitian ini adalah deskriptif analisis dengan data yang besar kualitatif dengan rancangan studi kasus. Informan penelitian berjumlah 11 orang yang dipilih secara purposive yaitu petugas yang terlibat dalam program PMTCT yang terdiri dari dokter, perawat, manajer kasus, konselor, bidan dan tenaga laboratorium. Metode pengumpulan data dilakukan melalui dua cara yaitu observasi dan wawancara mendalam (in-depth interview). Pemberian informasi tentang HIV dan PMTCT tidak diberikan kepada semua ibu hamil pada saat ANC oleh petugas ANC, padahal lewat ANC bisa menjadi awal pintu masuk upaya PMTCT, sehingga pemberian informasi tersebut tidak harus menunggu keberadaan konselor. Pemanfaatan layanan kesehatan dapat dipengaruhi oleh beberapa dimensi seperti ketersediaan dimana istilahnya akses layanan kesehatan sudah secara tepat berada di tempat dan waktu yang tepat, dimensi kemampuan yang merujuk ke masalah akses keuangan yakni tentang biaya layanan kesehatan dan kemampuan individu untuk membayar bagaimana layanan kesehatan dapat di jangkau pengguna layanan dari sisi harga.
Trends in silicon-on-silicon multichip modules

Three example applications of silicon-on-silicon multichip modules are discussed: a module used in a parallel processor, a low-cost silicon module for a high-volume consumer product application, and a high-performance digital telecommunications module. These applications illustrate the changes occurring in this technology and the forces that are driving these changes. <<ETX>>
Lymphocyte Telomere Length Is Long in BRCA1 and BRCA2 Mutation Carriers Regardless of Cancer-Affected Status

Background: Telomere length has been linked to risk of common diseases, including cancer, and has previously been proposed as a biomarker for cancer risk. Germline BRCA1 and BRCA2 mutations predispose to breast, ovarian, and other cancer types. Methods: We investigated telomere length in BRCA mutation carriers and their non-carrier relatives and further examined whether telomere length is a modifier of cancer risk in mutation carriers. We measured mean telomere length in DNA extracted from whole blood using high-throughput quantitative PCR. Participants were from the EMBRACE study in United Kingdom and Eire (n = 4,822) and comprised BRCA1 (n = 1,628) and BRCA2 (n = 1,506) mutation carriers and their non-carrier relatives (n = 1,688). Results: We find no significant evidence that mean telomere length is associated with breast or ovarian cancer risk in BRCA mutation carriers. However, we find mutation carriers to have longer mean telomere length than their non-carrier relatives (all carriers vs. non-carriers, Ptrend = 0.0018), particularly in families with BRCA2 mutations (BRCA2 mutation carriers vs. all non-carriers, Ptrend = 0.0016). Conclusions: Our findings lend little support to the hypothesis that short mean telomere length predisposes to cancer. Conversely, our main and unexpected finding is that BRCA mutation carriers (regardless of cancer status) have longer telomeres than their non-mutation carrier, non–cancer-affected relatives. The longer telomere length in BRCA2 mutation carriers is consistent with its role in DNA damage response. Overall, it seems that increased telomere length may be a consequence of these mutations, but is not itself directly related to the increased cancer risk in carriers. Impact: The finding that mutation carriers have longer mean telomere lengths than their non-carrier relatives is unexpected but biologically plausible and could open up new lines of research into the functions of the BRCA proteins. To our knowledge, this is the largest study of telomere length in BRCA mutation carriers and their relatives. The null cancer-risk association supports recent large prospective studies of breast and ovarian cancer and indicates that mean telomere length would not be a useful biomarker in these cancers. Cancer Epidemiol Biomarkers Prev; 23(6); 1018–24. ©2014 AACR.
Green Agility for Global Software Development Vendors : A Systematic Literature Review Protocol

Global software development (GSD) is now-a-days pervasive in software industry aiming to develop global standard software through geographically distributed skilled teams in minimum time and cost. In order to meet the demand for green software production and frequent changes in requirements of the clients, GSD developers have revamped traditional methods and trying to incorporate green principles with agile methods for rapid and energy efficient software development. This paper presents our contribution to building a systematic literature review (SLR) protocol for green agile maturity (GAM) for GSD vendor organizations. The protocol aims to systematically review the available literature for the identification of success/risk factors that may have a direct or indirect effect on green and sustainable software development using agile methods. The desired outcome of SLR protocol will be a group of success/risk factors and their concerned practices that will be helpful for vendors to produce green and environmentally sustainable software by incorporating agile principles in global software development.
Characterizing O2 Uptake Response Kinetics During Exercise

It has recently been proposed that the half time for the kinetics of VO2 during exercise may be accurately determined from a linear fit to the exponential response on linear coordinates. We demonstrate that although this is the case for two periods of data utilization, it is not true for any others, and that small variations in this period markedly influence the estimate. Furthermore, it is necessary to know the parameters of the response to determine the appropriate period of data collection. We conclude that the proposed linear estimation procedure is likely to yield erroneous values for VO2 kinetics during exercise.
CysLT1 receptor is a target for extracellular nucleotide-induced heterologous desensitization: a possible feedback mechanism in inflammation

Both cysteinyl-leukotrienes and extracellular nucleotides mediate inflammatory responses via specific G-protein-coupled receptors, the CysLT and the P2Y receptors, respectively. Since these mediators accumulate at sites of inflammation, and inflammatory cells express both classes of receptors, their responses are likely to be crossregulated. We investigated the molecular basis of desensitization and trafficking of the CysLT1 receptor constitutively and transiently expressed in the human monocyte/macrophage-like U937 or COS-7 cells in response to LTD4 or nucleotides. Exposure to agonist induced a rapid homologous desensitization of the CysLT1 receptor [as measured by the reduction in the maximal agonist-induced intracellular cytosolic Ca2+ ([Ca2+]i) transient], followed by receptor internalization (as assessed by equilibrium binding and confocal microscopy). Activation of P2Y receptors with ATP or UDP induced heterologous desensitization of the CysLT1 receptor. Conversely, LTD4-induced CysLT1 receptor activation had no effect on P2Y receptor responses, which suggests that the latter have a hierarchy in producing desensitizing signals. Furthermore, ATP/UDP-induced CysLT1 receptor desensitization was unable to cause receptor internalization, induced a faster recovery of CysLT1 functionality and was dependent upon protein kinase C. By contrast, homologous desensitization, which is probably dependent upon G-protein-receptor kinase 2 activation, induced a fast receptor downregulation and, accordingly, a slower recovery of CysLT1 functionality. Hence, CysLT1 receptor desensitization and trafficking are differentially regulated by the CysLT1 cognate ligand or by extracellular nucleotides. This crosstalk may have a profound physiological implication in the regulation of responses at sites of inflammation, and may represent just an example of a feedback mechanism used by cells to fine-tune their responses.
Switching Inertia and Competitive Asymmetry: A Demand Side Perspective

This paper explores challenger strategy from a demand-side perspective. Departing from the traditional supply-side perspective, we highlight the significance of buyer switching inertia as an isolating mechanism affecting competitive heterogeneity and asymmetry across rivals and discuss its implications for designing and deploying challenger strategy. We suggest that by mapping buyers' needs and competitors' capabilities onto a value matrix, the challenger can make more informed decisions on how to compete with and outmaneuver an incumbent rival. With the assistance of discrete choice modeling, we empirically examine the competition between incumbents and challengers in the industrial automation industry. Our results support the existence of switching inertia and imply that challengers are better off by establishing unique strategic positions than by pursuing operational effectiveness.
Expression of matrix metalloproteinases (MMP-2, MMP-9) and their inhibitors (TIMP-1, TIMP-2) in canine testis, epididymis and semen.

This study aims to investigate the role of matrix metalloproteinases (MMPs) in determining semen quality and to evaluate the expression and cellular localization of MMP-2, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in the testes, epididymis and ejaculated spermatozoa. Gelatinase activities between normal (n = 21) and abnormal (n = 25) semen samples showed a significant, sixfold increase in proMMP-2 and MMP-2 activity in high than low sperm concentration samples (p < 0.001). ProMMP-9 and MMP-9 levels were significantly elevated in samples with low sperm counts compared to those with high sperm density (p < 0.001). High levels of proMMP-2 and MMP-2 were associated with high sperm motility (≥70%, p < 0.001). Sperm-rich fraction showed significantly (eight-fold) higher proMMP-9 enzymatic activity compared with prostatic fraction. The mRNA expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 were confirmed in testicular and epididymal tissues. Immunohistochemical staining illustrated the MMP-2-specific strong immunoreactivity in the head of mature spermatids during spermatogenesis, whereas MMP-9, TIMP-1 and TIMP-2 were absent in these cells. Matrix metalloproteinase-9 immunoreactivity was observed in the spermatocyte and round spermatid, whereas TIMP-1 was only exhibited in the residual bodies. Immunolabeling of epididymal and ejaculated sperm demonstrated MMP-2 localization along acrosomal region of sperm, while MMP-9, TIMP-1 and TIMP-2 localization was merely limited to the flagella. In conclusion, spermatozoa initially acquire MMP-2 during their formation at testicular level, and the presence of this protein persists through the epididymal transit and up to ejaculate. The enzymatic activity of MMP-2 and MMP-9 may serve as an alternative biomarker in determining semen quality.
Modeling, Simulation, and Control of Pedestrian Avoidance Maneuver for an Urban Electric Vehicle

In this paper, the mathematical model of an electric vehicle, as well as the control system for avoiding pedestrians in urban traffic is described. The vehicle is modeled as a continuous system consisting of several subsystems. The discrete model of several sensors and actuators, a decision system, and low-level controllers for acceleration/braking and steering systems are added. Based on this model, a pedestrian avoidance maneuver for typical speeds in city traffic is simullated. When the sensory system detects a pedestrian in the vehicle's path, the decision system calculates its trajectory. Using this information, the speed and/or direction that the vehicle must take in order to avoid the accident are estimated. These values are sent to the low-level controllers of the accelerator/brake and steering, which generate the signals to be applied to such systems to achieve the desired trajectory and speed.