Miracle-dz/UniFAR-FTUs huggingface dataset:
Tryptophan Metabolism Contributes to Radiation-Induced Immune Checkpoint Reactivation in Glioblastoma

Purpose: Immune checkpoint inhibitors designed to revert tumor-induced immunosuppression have emerged as potent anticancer therapies. Tryptophan metabolism represents an immune checkpoint, and targeting this pathway's rate-limiting enzyme IDO1 is actively being investigated clinically. Here, we studied the intermediary metabolism of tryptophan metabolism in glioblastoma and evaluated the activity of the IDO1 inhibitor GDC-0919, both alone and in combination with radiation (RT). Experimental Design: LC/GC-MS and expression profiling was performed for metabolomic and genomic analyses of patient-derived glioma. Immunocompetent mice were injected orthotopically with genetically engineered murine glioma cells and treated with GDC-0919 alone or combined with RT. Flow cytometry was performed on isolated tumors to determine immune consequences of individual treatments. Results: Integrated cross-platform analyses coupling global metabolomic and gene expression profiling identified aberrant tryptophan metabolism as a metabolic node specific to the mesenchymal and classical subtypes of glioblastoma. GDC-0919 demonstrated potent inhibition of this node and effectively crossed the blood–brain barrier. Although GDC-0919 as a single agent did not demonstrate antitumor activity, it had a strong potential for enhancing RT response in glioblastoma, which was further augmented with a hypofractionated regimen. RT response in glioblastoma involves immune stimulation, reflected by increases in activated and cytotoxic T cells, which was balanced by immune checkpoint reactivation, reflected by an increase in IDO1 expression and regulatory T cells (Treg). GDC-0919 mitigated RT-induced Tregs and enhanced T-cell activation. Conclusions: Tryptophan metabolism represents a metabolic node in glioblastoma, and combining RT with IDO1 inhibition enhances therapeutic response by mitigating RT-induced immunosuppression. Clin Cancer Res; 24(15); 3632–43. ©2018 AACR.
Beyond Tax Avoidance: Offshore Firms’ Institutional Environment and Financial Reporting Quality

We explore how firms’ operations in Offshore Financial Centers (OFCs) through subsidiaries or affiliates affect the quality of financial reporting. Using a unique and large sample of firms that have headquarters in the 15 countries with the strictest legal regimes and have subsidiaries or affiliates in OFCs, we find that such firms exhibit lower financial reporting quality than comparable firms without OFC operations. We also find that as OFC characteristics become more prevalent, firms are more likely to engage in both accrual-based and real earnings management. More importantly, after disentangling OFC characteristics into the opportunity for tax avoidance, regulation arbitrage and secrecy policies, we find that beyond tax avoidance, regulation arbitrage and the secrecy policies of OFCs significantly affect financial reporting quality. The causal effect of OFC operations is supported by the analysis of financial reporting quality when firms set up OFC operations. Our findings are robust to various additional tests addressing potential endogeneity issues. We conclude that the assessment of a firm’s institutional environment must encompass the registration status of its subsidiaries or affiliates as well as its own.
Oxidation of Methyl tert-Butyl Ether by Alkane Hydroxylase in Dicyclopropylketone-Induced and n-Octane-Grown Pseudomonas putida GPo1

ABSTRACT The alkane hydroxylase enzyme system in Pseudomonas putida GPo1 has previously been reported to be unreactive toward the gasoline oxygenate methyl tert-butyl ether (MTBE). We have reexamined this finding by using cells of strain GPo1 grown in rich medium containing dicyclopropylketone (DCPK), a potent gratuitous inducer of alkane hydroxylase activity. Cells grown with DCPK oxidized MTBE and generated stoichiometric quantities of tert-butyl alcohol (TBA). Cells grown in the presence of DCPK also oxidized tert-amyl methyl ether but did not appear to oxidize either TBA, ethyl tert-butyl ether, or tert-amyl alcohol. Evidence linking MTBE oxidation to alkane hydroxylase activity was obtained through several approaches. First, no TBA production from MTBE was observed with cells of strain GPo1 grown on rich medium without DCPK. Second, no TBA production from MTBE was observed in DCPK-treated cells of P. putida GPo12, a strain that lacks the alkane-hydroxylase-encoding OCT plasmid. Third, all n-alkanes that support the growth of strain GPo1 inhibited MTBE oxidation by DCPK-treated cells. Fourth, two non-growth-supporting n-alkanes (propane and n-butane) inhibited MTBE oxidation in a saturable, concentration-dependent process. Fifth, 1,7-octadiyne, a putative mechanism-based inactivator of alkane hydroxylase, fully inhibited TBA production from MTBE. Sixth, MTBE-oxidizing activity was also observed in n-octane-grown cells. Kinetic studies with strain GPo1 grown on n-octane or rich medium with DCPK suggest that MTBE-oxidizing activity may have previously gone undetected in n-octane-grown cells because of the unusually high Ks value (20 to 40 mM) for MTBE.
In Long-Term Bedridden Elderly Patients with Dietary Copper Deficiency, Biochemical Markers of Bone Resorption Are Increased with Copper Supplementation during 12 Weeks

Background: Although the effect of copper on bone has been tested in animals and healthy subjects, no studies concerning the effect of copper supplementation on bone metabolism in patients with copper deficiency have been reported because of the rarity of these patients. This study was conducted to investigate the effect of copper supplementation on bone metabolism in copper-deficient patients. Method: This study included 10 patients (83.7 ± 8.3 years) with dietary copper deficiency under long-term bed rest for more than 12 months. They had their diets supplemented with copper sulfate (3 mg/day) over 12 weeks in addition to their diet of only one kind of enteral food with a low concentration of copper. Serum copper and ceruloplasmin, urinary deoxypyridinoline (DPD) and collagen-type 1 N-telopeptide (NTX) (biomarkers of bone resorption), serum osteocalcin (OC) and bone-specific alkaline phosphatase (Bone ALP) (biomarkers of bone formation) were analyzed at baseline, 4 and 12 weeks after copper supplementation. Results: DPD and NTX excretion were significantly increased 4 weeks after copper supplementation (p = 0.009 and p = 0.013, respectively). Serum bone ALP and OC were not significantly changed 12 weeks after copper supplementation (p = 0.051 and p = 0.594). Conclusions: In patients with nutritional copper deficiency, bone resorption markers are increased with copper supplementation.
DETERMINANTS OF INDONESIA’S EXPORTS OF MANUFACTURED PRODUCTS: A PANEL DATA ANALYSIS Faktor Penentu Ekspor Produk Manufaktur Indonesia: Analisis Data Panel

Indonesia’s export has been decreasing since 2012. This problem has raised government’s attention to increase the export performance. One sector that can be improved is manufacturing. This study analyzes the determinants of Indonesia’s manufacturing export from 2005 to 2014. The major factors examined in this study include real exchange rate, foreign direct investment (FDI), gross domestic product (GDP) and trade policies. Those factors are examined by using panel data regression with a random effect model. The results revealed that relative change of exchange rate, real GDP, distance between two countries and average tariffs significantly affected the Indonesia’s manufacturing export. It is recommended that Indonesian government maintains the exports to countries which have high GDP, expand the export market, stabilize Rupiahs exchange rate, encourage local industries to use advanced technologies, and facilitate the simplification of import procedures.
SMEs: aligning IS and the strategic context

Based on multiple-case research, this paper develops a model of strategic information systems (IS) investment in small and medium-sized enterprises (SMEs). IS investment is modelled as a function of an SME's strategic context as defined by its strategic focus, i.e. cost reduction versus value added and its market positioning, i.e. few versus many customers. The paper first investigates the ways in which IS may add value to organizations. It then outlines the use of IS in SMEs. This is followed by an analysis of competitiveness in small businesses. The paper develops an analytical model, which is termed the focus-dominance model, analyses case studies of 27 firms and reports that IS investment is strongly influenced by an SME's strategic context. Four cases are presented in order to illustrate the four different IS profiles identified. Finally, the implications for theory and practice are discussed.
A method for comparing multiple bacterial community structures from 16S rDNA clone library sequences.

Culture-independent approaches, based on 16S rDNA sequences, are extensively used in modern microbial ecology. Sequencing of the clone library generated from environmental DNA has advantages over fingerprint-based methods, such as denaturing gradient gel electrophoresis, as it provides precise identification and quantification of the phylotypes present in samples. However, to date, no method exists for comparing multiple bacterial community structures using clone library sequences. In this study, an automated method to achieve this has been developed, by applying pair wise alignment, hierarchical clustering and principle component analysis. The method has been demonstrated to be successful in comparing samples from various environments. The program, named CommCluster, was written in JAVA, and is now freely available, at http://chunlab.snu. ac.kr/commcluster/.
Effect of Feed Length on Settleability, Substrate Uptake and Storage in a Sequencing Batch Reactor Treating an Industrial Wastewater

The paper compares the performance of two Sequencing Batch Reactors (SBRs) treating the same industrial wastewater (composed of formic acid, ethylene glycol and methanol) operated at two different lengths of the feed. The two SBRs were operated in parallel under the same conditions of organic load (0.85 gCOD l−1 d−1) and sludge age (about 10 d), the only difference being the length of the feed: less than 1 min vs. 5 h. In this way the conditions of a plug flow reactor and of a completely mixed reactor were simulated. The two systems were compared on sludge settleability (related to filaments abundance and floc morphology), substrate uptake rates and polyhydroxyalkanoates (PHAs) storage rates. The main difference between the two systems was in the settling properties of the sludge: both SVI and effluent solids were higher in the system with slow feed. With regard to filamentous microorganisms, even though both reactors were inoculated with the same sludge with high concentration of filaments, they were rapidly washed out from both systems. Microscopic observations showed that the reason for the different settling properties of the two sludges was in the floc structure, which was more compact in the system operated with fast feed. These data support the theory of the role of diffusion inside the flocs in determining the settling properties of the sludge. The maximum substrate uptake rates and PHA storage rates were similar in the two systems, showing that also the microorganisms grown at a constant and low substrate concentration were able to quickly increase their activity and to store PHAs when in the presence of a sudden change in substrate concentration.
Prostaglandins A1, A2 and 19‐hydroxy A1; their actions on smooth muscle and their inactivation on passage through the pulmonary and hepatic portal vascular beds

1 . Prostaglandins A1, A2 and 19‐hydroxy A1 have qualitatively similar actions to prostaglandin E1 on smooth muscle. 2 . The prostaglandins A have little activity on gastrointestinal, respiratory and reproductive smooth muscle but are potent depressors of the systemic arterial blood pressure of the dog, cat and rabbit. 3 . Our experiments support the view that the depressor action of the prostaglandins E and A is due to a direct dilator action on many peripheral vascular beds and not due to changes in nervous tone to these beds. 4 . A single passage through the pulmonary circulation of the cat or dog causes substantial loss of the vasodilator activity of prostaglandin E1 but little if any loss of the vasodilator activity of the prostaglandins A. 5 . A single passage through the hepatic portal circulation of the cat causes substantial loss of the vasodilator activity of prostaglandins E1, A1 and A2. 6 . The cat blood pressure and rat fundal strip would be a suitable combination for the parallel biological assay of the prostaglandins A1 and A2.
[Granulocyte macrophage-colony stimulating factor (GM-CSF) in diagnosis and monitoring of non-small cell lung cancer].

Serum tumor markers may be helpful in early diagnosis of cancer, in the initial assessment of the extent of the disease, and in monitoring the tumor growth or tumor volume reduction once cancer has been diagnosed and treatment started. Recent studies have focused on a new family of markers -hematopoietic growth factors, especially on granulocyte-macrophage colony-stimulating factor (GM-CSF). A number of investigations have shown autologous production of GM-CSF in various human cell lines derived from melanoma, gastric or ovarian cancer, and in certain tumors of nonhematopoietic origin. In this study serum level of GM-CSF was measured using a sensitive sandwich ELISA system in 34 patients with non-small cell lung cancer (NSCLC) before and 10, 30, 90, 180 and 270 days after surgical operation. Additionally common accepted tumor markers such as CEA and CYFRA 21.1 were also assayed. Preoperative level of GM-CSF was significantly increased in cancer patients relative to the normal sera (p < 0.02). Concentration of GM-CSF and CYFRA 21.1 were decreased on 10th day, but CEA on 30th day after surgical treatment, although upon comparison of pre- and postoperative tumor markers serum levels significant difference was observed for CYFRA 21.1 (p < 0.05). Levels of GM-CSF were increased in 85%, CEA in 62% and CYFRA 21.1 in 51%. The diagnostic sensitivity and serum levels of GM-CSF were related to the stage of the disease and the combined use of two markers increased the sensitivity compared with the use of only one. These results suggest that GM-CSF, especially in the combination with CYFRA 21.1. , may be useful in the diagnostic and monitoring of patients with NSCLC.
X-search: revisiting private web search using intel SGX

The exploitation of user search queries by search engines is at the heart of their economic model. As consequence, offering private Web search functionalities is essential to the users who care about their privacy. Nowadays, there exists no satisfactory approach to enable users to access search engines in a privacy-preserving way. Existing solutions are either too costly due to the heavy use of cryptographic mechanisms (e.g., private information retrieval protocols), subject to attacks (e.g., Tor, TrackMeNot, GooPIR) or rely on weak adversarial models (e.g., PEAS). This paper introduces X-Search, a novel private Web search mechanism building on the disruptive Software Guard Extensions (SGX) proposed by Intel. We compare X-Search to its closest competitors, Tor and PEAS, using a dataset of real web search queries. Our evaluation shows that: (1) X-Search offers stronger privacy guarantees than its competitors as it operates under a stronger adversarial model; (2) it better resists state-of-the-art re-identification attacks; and (3) from the performance perspective, X-Search outperforms its competitors both in terms of latency and throughput by orders of magnitude.
Verification of POI and Location Pairs via Weakly Labeled Web Data

With the increased popularity of mobile devices and smart phones, location-based services (LBS) have become a common need in our daily life. Therefore, maintaining the correctness of POI (Points of Interest) data has become an important issue for many location-based services such as Google Maps and Garmin navigation systems. The simplest form of POI contains a location (e.g., represented by an address) and an identifier (e.g., an organization name) that describes the location. As time goes by, the POI relationship of a location and organization pair may change due to the opening, moving, or closing of a business. Thus, effectively identifying outdated or emerging POI relations is an important issue for improving the quality of POI data. In this paper, we examine the possibility of using location-related pages on the Web to verify existing POI relations via weakly labeled data, e.g., the co-occurrence of an organization and an address in Web pages, the published date of such pages, and the pairing diversity of an address or an organization, etc. The preliminary result shows a promising direction for discovering emerging POI and mandates more research for outdated POI.
The subapical compartment: a traffic center in membrane polarity development

Spatially separated apical and basolateral plasma membrane domains that have distinct functions and molecular compositions are a characteristic feature of epithelial cell polarity. The subapical compartment (SAC), also known as the common endosome (CE), where endocytic pathways from both surfaces merge, plays a crucial role in the maintenance and probably the biogenesis of these distinct membrane domains. Although differences in morphology are apparent, the same principal features of a SAC can be distinguished in different types of epithelial cells. As polarity develops, the compartment acquires several distinct machineries that, in conjunction with the cytoskeleton, are necessary for polarized trafficking. Disrupting trafficking via the SAC and hence bypassing its sorting machinery, as occurs upon actin depolymerization, leads to mis-sorting of apical and basolateral molecules, thereby compromising the development of polarity. The structural and functional integrity of the compartment in part depends on microtubules. Moreover, the acquisition of a particular set of Rab proteins, including Rab11 and Rab3, appears to be crucial in regulating molecular sorting and vesicular transport relevant both to recycling to either plasma membrane domain and to de novo assembly of the apical domain. Furthermore, subcompartmentalization of the SAC appears to be key to its various functions.
parC Mutation Conferring Ciprofloxacin Resistance in Streptococcus pyogenes BM4513

Streptococcus pyogenes is responsible for high rates of morbidity due to an increase in invasive group A streptococcal infections and bacteremia worldwide during the last decade (2, 3). The goal of this study was to elucidate the mechanism of fluoroquinolone resistance in S. pyogenes BM4513 isolated in 2000 from the pharynx of a patient at the Hospital de Basurto, Bilbao, Spain.
Clinical evaluation of contact Nd‐YAG laser conization for cervical intraepithelial neoplasia of the uterus

Contact Nd.YAG laser conization (laser cone) was performed in 500 patients with preoperatively diagnosed cervical intraepithelial neoplasia (CIN) since September 1983. The patients treated were followed for 12 to 96 months (39.2 months on average). Average operation time was 11.4 minutes. A cure with laser cone (single treatment) was achieved in 98.6%, including cases with microinvasive and invasive carcinoma, post‐operatively. There were only 7 (1.4%) true residual cases of 47 cases (9.4% of total cases) with incomplete excision. High spontaneous cure rates (85.1%) in cases with incomplete excision are considered to be a characteristic of laser cone treatment. The contact laser cone method also got good specimens for histologic examinations. They gave a large amount of information for our follow‐up. The results indicate that contact Nd.YAG laser conization for CIN is an excellent conservative therapy from the point of cure rate, safety, indication, operation time and cone specimen, even compared with CO2 laser conization.
Nonintrusive online rotor permanent magnet temperature tracking for permanent magnet synchronous machine based on third harmonic voltage

In this paper, a novel nonintrusive online rotor PM temperature tracking method for permanent magnet synchronous machine (PMSM) based on the third harmonic voltage is proposed. The proposed method is not affected by inverter nonlinearities and requires no information of winding resistance, d- and q-axis inductances. It is also robust to the speed variation and introduces no perturbation signals. The third PM flux-linkage is estimated and used as the indicator of the rotor PM temperature. Analytical model for the third harmonic voltage based on the magnetic permeance modulation is proposed to analyze the influence of armature currents. Corresponding third PM flux-linkage amplitude extractor is designed based on this analytical model. Moreover, 2 dimensional finite element analysis is also carried out to verify the effectiveness of the proposed analytical model. Self-commissioning method of the third harmonic flux-linkage tracker is also proposed. Finally, experiments on the 12/slot-10/pole surface mounted permanent magnet synchronous machine verifies the proposed online rotor PM temperature tracking method.
Sequence of changes in body composition induced by testosterone and reversal of changes after drug is stopped.

OBJECTIVE --To study the changes in body composition produced by large doses of testosterone and reversal of changes when the drug is discontinued. DESIGN --Weekly injections of testosterone enanthate were given to young adult male volunteers for 12 weeks. Repeated assays of lean body mass (LBM) by potassium 40 counting were made during this period and at intervals during the ensuing 5 to 6 months. PARTICIPANTS AND SETTING --Subjects who were living on their own, who were known to be free of significant disease, and who volunteered as controls for a study of patients with neuromuscular disease. Assays were done in the Clinical Research Center. MAIN OUTCOME MEASURES --Changes in body weight, LBM, and (by subtraction) body fat. RESULTS --Testosterone treatment produced a progressive increase in LBM and a progressive decrease in body fat. Body composition reverted slowly toward normal when the injections were stopped; thus, the effects of testosterone lingered for some time. The magnitude of the observed changes in LBM was in keeping with the change in urinary creatinine excretion reported for these same subjects. CONCLUSION --Testosterone is a powerful anabolic agent that also serves to reduce body fat content.
Safe Medication Prescribing: Training and Experience of Medical Students and Housestaff at a Large Teaching Hospital

Purpose To assess medical students’ and housestaff's knowledge, attitudes, and behaviors regarding safe prescribing. Method In 2003, 214 housestaff (interns and residents) and 77 medical students in medicine and surgery at Barnes-Jewish Hospital, St. Louis, Missouri, were asked to complete an anonymous, self-administered questionnaire about safe prescribing. Questions asked about training in and attitudes about safe-prescribing and current prescribing behaviors. Fisher exact test was used to compare attitudes and behaviors among subgroups. Results Of the 175 (60%) respondents, 73 (59%) of 123 housestaff and eight (15%) of 52 students agreed that their safe-prescribing training was adequate (p < .001), and 145 (83%) total respondents agreed that prescribing errors were unacceptable. Respondents reported always doing the following: 156 (89%) checked prescribing information before prescribing new drugs, 131 (75%) checked for drug allergies, 103 (59%) double-checked dosage calculations, 98 (56%) checked for renal impairment, and 53 (30%) checked for potential drug–drug interactions. Conclusion Routine use of safe medication prescribing behaviors among housestaff and medical students was poor. Contributing factors may have included inadequate training and a culture that does not support safe prescribing. Effective strategies to increase safe medication prescribing need to be identified and implemented.