Miracle-dz/UniFAR-FTUs huggingface dataset:
N-Substituted Pyrrole Derivatives as Novel Human Immunodeficiency Virus Type 1 Entry Inhibitors That Interfere with the gp41 Six-Helix Bundle Formation and Block Virus Fusion

ABSTRACT A recently approved peptidic human immunodeficiency virus type 1 (HIV-1) fusion inhibitor, T-20 (Fuzeon; Trimeris Inc.), has shown significant promise in clinical application for treating HIV-1-infected individuals who have failed to respond to the currently available antiretroviral drugs. However, T-20 must be injected twice daily and is too expensive. Therefore, it is essential to develop orally available small molecule HIV-1 fusion inhibitors. By screening a chemical library consisting of “drug-like” compounds, we identified two N-substituted pyrroles, designated NB-2 and NB-64, that inhibited HIV-1 replication at a low micromolar range. The absence of the COOH group in NB-2 and NB-64 resulted in a loss of anti-HIV-1 activity, suggesting that this acid group plays an important role in mediating the antiviral activity. NB-2 and NB-64 inhibited HIV-1 fusion and entry by interfering with the gp41 six-helix bundle formation and disrupting the α-helical conformation. They blocked a d-peptide binding to the hydrophobic pocket on surface of the gp41 internal trimeric coiled-coil domain. Computer-aided molecular docking analysis has shown that they fit inside the hydrophobic pocket and that their COOH group interacts with a positively charged residue (K574) around the pocket to form a salt bridge. These results suggest that NB-2 and NB-64 may bind to the gp41 hydrophobic pocket through hydrophobic and ionic interactions and block the formation of the fusion-active gp41 core, thereby inhibiting HIV-1-mediated membrane fusion and virus entry. Therefore, NB-2 and NB-64 can be used as lead compounds toward designing and developing more potent small molecule HIV-1 fusion inhibitors targeting gp41.
Remittances Inflows, Gain of Foreign Exchange or Trade Loss? New Evidence from Low, Lower-Middle and Middle-Income Groups

This study examines the relationship between remittances, exchange rate and export competitiveness for 58 countries from low, lower-middle and middle-income groups. In order to investigate this relationship, and building on our previous work found in Khurshid (2016), we applied the System Generalized Method of Moment Regression (SGMM) and bootstrapped panel Ganger causality approach using newly constructed remittances series for a period lasting from 1988 to 2014. The results unravel evidence that remittances appreciate the exchange rate and adversely affect competitiveness in lower-middle and middle-income countries whereas, the exchange rates negatively affect exports in the middle-income group. The consumption and spending effects remain dominating in causing the Dutch Disease in all groups. On the topic of remittances-exchange rate and remittances- export causal nexus, we find mixed results for the three income groups. There is not a clear consensus about the direction of the causal link, which means the findings are country- specific. The outcomes have significant policy implications for the groups in our analysis.
Neural Stem Cell Targeting of Glioma Is Dependent on Phosphoinositide 3‐Kinase Signaling

The utility of neural stem cells (NSCs) has extended beyond regenerative medicine to targeted gene delivery, as NSCs possess an inherent tropism to solid tumors, including invasive gliomas. However, for optimal clinical implementation, an understanding of the molecular events that regulate NSC tumor tropism is needed to ensure their safety and to maximize therapeutic efficacy. We show that human NSC lines responded to multiple tumor‐derived growth factors and that hepatocyte growth factor (HGF) induced the strongest chemotactic response. Gliomatropism was critically dependent on c‐Met signaling, as short hairpin RNA‐mediated ablation of c‐Met significantly attenuated the response. Furthermore, inhibition of Ras‐phosphoinositide 3‐kinase (PI3K) signaling impaired the migration of human neural stem cells (hNSCs) toward HGF and other growth factors. Migration toward tumor cells is a highly regulated process, in which multiple growth factor signals converge on Ras‐PI3K, causing direct modification of the cytoskeleton. The signaling pathways that regulate hNSC migration are similar to those that promote unregulated glioma invasion, suggesting shared cellular mechanisms and responses.
Naloxone Does Not Increase the Minimum Alveolar Anesthetic Concentration of Sevoflurane in Mice

Several previous studies concluded that opioid receptors do not mediate the capacity of inhaled anesthetics to produce immobility in the face of noxious stimulation because administration of naloxone (a nonspecific opioid receptor antagonist) does not increase the minimum alveolar anesthetic concentration (MAC) of inhaled anesthetic that produces immobility in 50% of subjects given a noxious stimulation. In contrast, a recent study found that 0.1 mg/kg naloxone given intraperitoneally increased sevoflurane MAC in mice by 18% (P < 0.01). We repeated the recent study with sevoflurane in the same strain of mice, administering nothing (control), 0.1 mg/kg, and 1.0 mg/kg of naloxone. Our study differed in that we also tested a parallel group given saline rather than naloxone. We were blinded to drug administration. MAC decreased 4.8% ± 11.0% (mean± sd) and 2.4% ± 12.5% with the first and second administrations of saline. Similarly, MAC decreased 4.7% ± 7.1% and 5.5% ± 10.0% with the administration of 0.1 mg/kg and 1.0 mg/kg of naloxone. We do not find that naloxone increases MAC. Opioid receptors do not underlie a portion of the capacity of inhaled anesthetics to produce immobility.
Predictors of Intention to Travel to Cuba across Three Time Horizons: An Application of the Theory of Planned Behavior

As the relationship between Cuba and the United States evolves, many Americans are entertaining the idea of travel to Cuba. This study used the Theory of Planned Behavior (TPB) to examine predictors of US residents’ intentions to travel to Cuba across three time horizons: 1 year, 5 years, and 10 years. TPB constructs were administered to a cross-sectional panel of US residents. Results varied by time horizon, with US residents’ negative attitudes toward Cuba having a positive and significant influence on their intention to visit Cuba within one year. This finding suggests that some US residents match Plog’s Allocentric profile of tourists and that the current “rough edges” of Cuba are what attract them to travel in the short rather than long term. Findings from this study provide baseline data that is valuable for Cuban and American tourism organizations, should the US market become more accessible.
Chapter 9 Accounting for the Construction of Research Quality in Australia’s Research Assessment Exercise

Abstract This chapter explores the development and the role of accounting for research quality in Australia’s Excellence in Research for Australia (ERA) assessment exercise. It tracks the progress of performance measurement systems from quantitative to qualitative measurement within the Australian higher education sector since 1970, leading up to the implementation of a formal ERA in 2010, and its subsequent iterations in 2012, 2015, and 2018. Although only a part of the ERA submissions, now certain published research outputs provide the primary evidence for research quality to most ERA panels and are a significant driver of the final rating awarded. Before the authors assess the 2018 exercise, they will examine the ever-changing role of journal publications as a vehicle for academic research output.
Vaccines to prevent viral hepatitis.

At least five different viruses cause hepatitis in humans. Two — hepatitis A virus (HAV) and hepatitis E virus (HEV) — are nonenveloped RNA viruses that are spread predominantly by fecal–oral transmission and cause acute self-limited disease.1,2 The others — hepatitis B virus (HBV), hepatitis delta virus (HDV), and hepatitis C virus (HCV) — are enveloped viruses with various tendencies to cause persistent infection, chronic hepatitis, and, in the case of HBV and HCV, hepatocellular carcinoma.3–5 Fecal–oral transmission does not occur with these viruses, because their lipid envelopes preclude the passage of viable virus from the liver through .
Metabolic aspects of dietary sodium restriction as a therapeutic intervention

A body mass index (BMI) ≥ 25 kg/m increases the risk for long-term renal damage, possibly by renal hemodynamic factors. As epidemiological studies suggest interaction of BMI and sodium intake, we studied the combined effects of sodium intake and BMI on renal hemodynamics. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured in 95 healthy men (median age 23 years (95% confidence interval: 22–24), BMI: 23.0 ± 2.5 kg/m 2 ) on low (50 mmol Na + /24h, LS) and high (200 mmol Na + /24h, HS) sodium intake. Mean GFR and ERPF significantly increased by the change to HS (both P<0.001). During HS but not LS, GFR and filtration fraction (FF) positively correlated with BMI (R=0.32 and R=0.28, respectively, both P<0.01). Consequently, BMI correlated with the sodium-induced changes in GFR (R=0.30; P<0.01) and FF (R=0,23; P<0.05). The effects of HS on GFR and FF were significantly different for BMI ≥ 25 versus < 25 kg/m, namely 7.8 ± 12.3 versus 16.1 ± 13.1 mL/min (P<0.05) and -0.1 ± 2.2 and 1.1 ± 2.3% (P<0.05). FF was significantly higher in BMI ≥ 25 versus < 25 kg/m, (22.6 ± 2.9 versus 24.6 ± 2.4%, P<0.05) only during HS. ERPF was not related to BMI. Urinary albumin excretion was increased by HS from 6.0 (5.4–6.7) to 7.6 (6.9–8.9) mg/24h. Results were essentially similar after excluding the only two subjects with BMI > 30 kg/m 2 . BMI is a determinant of the renal hemodynamic response to HS in healthy men, and of GFR and FF during HS, but not during LS. Consequently, HS elicited a hyperfiltration pattern in subjects with a BMI > 25 kg/m 2 that was absent during LS. Future studies should elucidate whether LS or diuretics can ameliorate the long-term renal risks of weight excess. P a rt o n e 27 Chapter 1 proefschrift_Opmaak 1 19-4-2010 14:52 Pagina 27
Faces of Internationalism: Public Opinion and American Foreign Policy

In Faces of Internationalism, Eugene R. Wittkopf examines the changing nature of public attitudes toward American foreign policy in the post-Vietnam era and the role that public opinion plays in the American foreign policymaking process. Drawing on new data-four mass and four elite opinion surveys undertaken by the Chicago Council of Foreign Relations from 1974 to 1986-combined with sophisticated analysis techniques, Wittkopf offers a pathbreaking study that addresses the central question of the relationship of a democracy to its foreign policy. The breakdown of the "consensus" approach to American foreign policy after the Cold War years has become the subject of much analysis. This study contributes to revisionist scholarship by describing the beliefs and preferences that have emerged in the wake of this breakdown. Wittkopf counters traditional views by demonstrating the persistence of U.S. public opinion defined by two dominant and distinct attitudes in the post-Vietnam war years-cooperative and militant internationalism. The author explores the nature of these two "faces" of internationalism, focusing on the extent to which elites and masses share similar opinions and the political and sociodemographic correlates of belief systems. Wittkopf also offers an original examination of the relationship between beliefs and preferences.
microRNA-125a-3p reduces cell proliferation and migration by targeting Fyn

Summary Fyn, a member of the Src family kinases (SFKs), has a pivotal role in cell adhesion, proliferation, migration and survival, and its overexpression is associated with several types of cancer. MicroRNAs (miRNAs) play a major role in post-transcriptional repression of protein expression. In light of the significant functions of Fyn, together with studies demonstrating miR-125a as a tumor-suppressing miRNA that is downregulated in several cancer cell types and on our bioinformatics studies presented here, we chose to examine the post-transcription regulation of Fyn by miR-125a-3p in the HEK 293T cell line. We show that Fyn expression can be dramatically reduced by elevated levels of miR-125a-3p. Following this reduction, the activity of proteins downstream of Fyn, such as FAK, paxillin and Akt (proteins known to be overexpressed in various tumors), is also reduced. On a broader level, we show that miR-125a-3p causes an arrest of the cell cycle at the G2/M stage and decreases cell viability and migration, probably in a Fyn-directed manner. The results are reinforced by control experiments conducted using Fyn siRNA and anti-miR-125a-3p, as well as by the fact that numerous cancer cell lines show a significant downregulation of Fyn after mir-125a-3p overexpression. Collectively, we conclude that miR-125a-3p has an important role in the regulation of Fyn expression and of its signaling pathway, which implies that it has a therapeutic potential in overexpressed Fyn-related diseases.
A quantitative study of enterotoxin production by sheep milk staphylococci

Of 124 staphylococcal strains isolated from sheep milk, 78 produced enterotoxin A, B, C, or D when evaluated by an enzyme-linked immunosorbent assay. Enterotoxins A and D, elaborated by 44 and 43 strains, respectively, showed the highest incidence. Enterotoxin production by coagulase-negative strains (one Staphylococcus cohnii, three S. epidermidis, five S. haemolyticus, and four S. xylosus) was detected. Linear and logarithmic-logarithmic regressions of optical density on enterotoxin concentration yielded the best-fitting equations for enterotoxin quantitation. A significantly higher incidence of enterotoxin producers and significantly higher levels of enterotoxins produced were recorded for coagulase-positive, thermostable nuclease-positive, hemolysis-positive, or mannitol-positive strains. Mannitol utilization was the best test for discriminating between enterotoxigenic and nonenterotoxigenic staphylococci.
Effects of alendronate on bone healing after tooth extraction in rats.

OBJECTIVES Tooth extraction has been identified as an important risk factor for bisphosphonate-induced osteonecrosis of the jaw. Therefore, the main goal of this study was to determine the effects of alendronate on healing of the extraction socket and on interdental alveolar bone after tooth extraction in rats. MATERIALS AND METHODS Animals were injected subcutaneously with vehicle or alendronate for 3-4 weeks before the first mandibular molar was extracted and these treatments were continued during post-extraction periods of 10, 21, 35 and 70 days. Mandibles were processed to evaluate healing of the extraction socket and adjacent alveolar bone by assessing bone formation, bone resorption and vascularity by histomorphometric techniques. RESULTS Alendronate decreased new woven bone formation, blood vessel area, perimeter and number in the extraction socket at 10 days postextraction, but not at later time points. Furthermore, alendronate-treated rats had increased interdental alveolar bone volume and height only at 10 days postextraction. In addition, a 2.5-fold increase in the percentage of empty osteocyte lacunae was found in alveolar bone of alendronate-treated rats only at 10 days postextraction. CONCLUSIONS Alendronate transiently decreases bone formation and vascularity in the extraction socket and delays the removal of interdental alveolar bone after tooth extraction in rats.
The Effects Of Fiscal Policy On Income Inequality In A Model With Heterogeneous Agents

The income inequality is one of the main obstacles to economic development. Understanding the dynamics of this social phenomenon is central to understand economic growth also. Thus based on models that relates fiscal policy, inequality and growth we proposed the following problem: Given the initial distribution of capital, what is the effect of a set of flat-rate taxation, on inequality? In order to answer this question we built a model following the tradition of studies in this area. The model we propose is a version of a competitive equilibrium of the basic neoclassical growth model, which incorporate inequality and heterogeneous agents: poor and rich, allow us to understanding this problem in a dynamic way. We use Ramsey problem to determine the optimal sequences for the three types of tax, capital, labor and consumption in a nonstochastic economy. The analytical solution found suggest that in steady state optimal tax on capital should always be zero regardless of the government’s favoritism towards particular agents. Also the government should financed his transfers using different combinations of taxes on consumption and labor.
Monitoring the effects of treatment in colon cancer cells using immunohistochemical and histoenzymatic techniques.

BACKGROUND Monitoring the effects of treatment in malignant diseases is very important in study of the influence on the cell metabolism. Energy production in cancer cells is abnormally dependent on aerobic glycolysis. In addition to the dependency on glycolysis, cancer cells have other atypical metabolic characteristics. The purpose of the present study is to evaluation and analysis of the colon cancer cells under anti-angiogenic treatment, to establish the changes in the cellular energy metabolism and apoptotic potential. Anti-angiogenic drugs block the vascular endothelial growth factors, preventing the formation of new vessels. MATERIALS AND METHODS We use immunohistochemical analysis of cytochrome c release and histoenzymatic analysis of adenosine triphosphatase (ATP-ase), succinate dehydrogenase (SDH), lactate dehydrogenase (LDH) enzymes. Colorectal tumor tissue samples were obtained by biopsy following the surgical procedures at the County Clinical Hospital of Oradea (Romania). RESULTS The obtained results show that the apoptotic potential of malignant cells increases during the anti-angiogenic treatment, in the same time the rate of glycolysis increases, due to installed hypoxia and reduced ATP synthesis. Our results have been confirmed by international studies too. CONCLUSIONS It was been demonstrated that the apoptotic potential of malignant cells increases significantly during anti-angiogenic treatment. There is growing evidence that cancer's "Achilles' heel" is tumor cell metabolism.
Time course of changes in jugular venous oxygen saturation during hypothermic or normothermic cardiopulmonary bypass in patients with diabetes mellitus

Background: Preexisting diabetic mellitus is a risk factor determining postoperative neurological disorders. The present study assesses the effects of normothermic and hypothermic cardiopulmonary bypass (CPB) on jugular venous oxygen saturation (SjvO2)in patients with preexisting diabetic mellitus.
Characterization of VSG gene expression site promoters and promoter-associated DNA rearrangement events

The expressed variant cell surface glycoprotein (VSG) gene of Trypanosoma brucei is located at the 3' end of a large, telomeric, polycistronic transcription unit or expression site. We show that the region 45 kb upstream of the VSG gene, in the expression site on a 1.5-Mb chromosome, contains at least two promoters that are arranged in tandem, directing the transcription of the expression site. DNA rearrangement events occur specifically, at inactivation of the expression site, and these events delete the most upstream transcribed region and replace it with a large array of simple-sequence DNA, leaving the downstream promoter intact. Because of the placement of simple-sequence DNA, the remaining downstream promoter now becomes structurally identical to previously described VSG promoters. The downstream promoter is repetitive in the genome, since it is present at several different expression sites. Restriction fragment length polymorphism mapping allows grouping of the expression sites into two families, those with and those without an upstream transcription unit, and the DNA rearrangement events convert the expression sites from one type to the other. Deletion of the upstream transcription unit also leads to the loss of several steady-state RNAs. The findings may indicate a role for promoter-associated DNA rearrangement events, and/or interactions between tandemly arranged promoters, in expression site transcriptional control.
Impact of FLT3 internal tandem duplication on the outcome of related and unrelated hematopoietic transplantation for adult acute myeloid leukemia in first remission: a retrospective analysis.

PURPOSE Patients with acute myeloid leukemia (AML) and FLT3/internal tandem duplication (FLT3/ITD) have poor prognosis if treated with chemotherapy only. Whether this alteration also affects outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) remains uncertain. PATIENTS AND METHODS We analyzed 206 patients who underwent HLA-identical sibling and matched unrelated HSCTs reported to the European Group for Blood and Marrow Transplantation with a diagnosis of AML with normal cytogenetics and data on FLT3/ITD (present: n = 120, 58%; absent: n = 86, 42%). Transplantations were performed in first complete remission (CR) after myeloablative conditioning. RESULTS Compared with FLT3/ITD-negative patients, FLT3/ITD-positive patients had higher median leukocyte count at diagnosis (59 v 21 × 10(9)/L; P < . 001) and shorter interval from CR to transplantation (87 v 99 days; P = .04). Other characteristics were similar in the two groups. At 2 years, relapse incidence (RI; ± standard deviation) was higher (30% ± 5% v 16% ± 5%; P = .006) and leukemia-free survival (LFS) lower (58% ± 5% v 71% ± 6%; P = .04) in FLT3/ITD-positive compared with FLT3/ITD-negative patients. In multivariate analyses, FLT3/ITD led to increased RI (hazard ratio [HR], 3.4; 95% CI, 1.46 to 7.94; P = .005), as did older age, female sex, shorter interval between CR and transplantation, and higher number of chemotherapy courses before achieving CR. FLT3/ITD positivity was associated with decreased LFS (HR, 0.37; 95% CI, 0.19 to 0.73; P = .002), along with older age and higher number of chemotherapy courses before achieving CR. CONCLUSION FLT3/ITD adversely affected the outcome of HSCT in the same direction it does after chemotherapy; despite this, more than half of the patients harboring this mutation who received transplants were alive and leukemia free at 2 years. To further improve the results, use of FLT3 inhibitors before or after HSCT deserves investigation.