Miracle-dz/UniFAR-FTUs huggingface dataset:
Potent Preclinical Impact of Metronomic Low-Dose Oral Topotecan Combined with the Antiangiogenic Drug Pazopanib for the Treatment of Ovarian Cancer

Low-dose metronomic chemotherapy has shown promising activity in many preclinical and some phase II clinical studies involving various tumor types. To evaluate further the potential therapeutic impact of metronomic chemotherapy for ovarian cancer, we developed a preclinical model of advanced human ovarian cancer and tested various low-dose metronomic chemotherapy regimens alone or in concurrent combination with an antiangiogenic drug, pazopanib. Clones of the SKOV-3 human ovarian carcinoma cell line expressing a secretable β-subunit of human choriogonadotropic (β-hCG) protein and firefly luciferase were generated and evaluated for growth after orthotopic (i.p.) injection into severe combined immunodeficient mice; a highly aggressive clone, SKOV-3-13, was selected for further study. Mice were treated beginning 10 to 14 days after injection of cells when evidence of carcinomatosis-like disease in the peritoneum was established as assessed by imaging analysis. Chemotherapy drugs tested for initial experiments included oral cyclophosphamide, injected irinotecan or paclitaxel alone or in doublet combinations with cyclophosphamide; the results indicated that metronomic cyclophosphamide had no antitumor activity whereas metronomic irinotecan had potent activity. We therefore tested an oral topoisomerase-1 inhibitor, oral topotecan, at optimal biological dose of 1 mg/kg/d. Metronomic oral topotecan showed excellent antitumor activity, the extent of which was significantly enhanced by concurrent pazopanib, which itself had only modest activity, with 100% survival values of the drug combination after six months of continuous therapy. In conclusion, oral topotecan may be an ideal agent to consider for clinical trial assessment of metronomic chemotherapy for ovarian cancer, especially when combined with an antiangiogenic drug targeting the vascular endothelial growth factor pathway, such as pazopanib. Mol Cancer Ther; 9(4); 996–1006. ©2010 AACR.
Eradicating house mice from islands: successes, failures and the way forward

The house mouse (Mus musculus) has been spread throughout the world by the actions of humans. It causes severe impacts to native ecosystems, especially in areas where there are no native mammals. It is possible to eradicate mice from islands but they are harder to eradicate than rats. A review of reported eradication attempts found that 17 attempts on 45 islands worldwide failed; a failure rate of 38%. The effect of operational factors on eradication success was examined, but no significant model was formed. Brodifacoum is the most widely used toxicant and has a 49% success rate. Mouse eradications should be attempted wherever possible and recommendations to help increase the success of a house mouse eradication attempt are given.
Politics of Character Education

Character education’s history in the United States goes back to the beginning of public schools. The emphasis and profile has waxed and waned, frequently with political trends. The current standards-based environment poses particular threats and challenges to character education. In spite of these pressures, character education continues and—by most measures—is growing. This article (a) defines character and examines the history of character education in U.S. public schools; (b) introduces and contrasts the major approaches: traditional character education, caring, and developmental; and (c) outlines and examines current issues including the relationship of character to citizenship education, the family and school roles in character development, the relationship of church and state, federal and state polices and funding of character education programs, and issues of evaluation and research. Although advocating for character education, the approach here to the issues is descriptive and as impartial as possible.
Approach-Avoidance and Affiliation as Functions of the Emotion-Eliciting Quality of an Environment

It was hypothesized that approach toward an environment and the desire to affiliate there are influenced by the emotion-eliciting quality of that environment. In two studies, undergraduates (N = 200, 310) rated these two behaviors in response to settings shown via color photographic slides. As predicted, approach toward the setting was determined by (a) a main effect of its pleasantness, (b) an interaction effect such that approach varied directly with arousing quality of the setting in pleasant settings, but inversely with arousing quality in unpleasant settings (with a significant reversal, however, from moderate to high arousal in unpleasant settings), and (c) a weak inverted-U relationship with arousing quality in neutrally pleasant-unpleasant settings such that approach was greatest in moderately arousing settings.
Sociocultural study of immigrant suicide-attempters: An ecological perspective

• Summary: This article discusses the findings of a qualitative study with a sample of suicide attempters in the Chinese immigrant community of New York City from an ecological perspective. • Findings: The narratives of the participants delineate the pathway of their suicide attempts as the culmination of an interactive process of stressors, mental illness, and diminished help-seeking behavior, compounded by immigrant-specific issues, cultural meanings of distress and social barriers to resources. • Application: The transactional dynamics of these risk factors underscore the importance of adopting an integrative and contextualized stance of inquiry in suicide studies and initiating a broad-based community effort in suicide prevention.
Reading for the purpose of responding to literature: EFL students’ perceptions of e-books

As electronic books continue to attract attention as a pedagogical tool in language classrooms, the impact that e-books are expected to have on higher education cannot be ignored. Despite the pervasiveness of e-book reading studies in higher education, most studies show that students’ reactions to e-books are often negative. However, the effects of using e-books are considered beneficial in extensive reading programs in many first- or second-language classrooms. The different results may be due to different reading purposes. In addition, limited studies have investigated whether students’ perceptions of e-books change over time since many of the e-book reading studies used a survey, rather than longitudinal, approach. Thus, this study intended to determine (1) English as a foreign language (EFL) college students’ perceptions of e-books when they read for the purpose of responding to literature rather than for the purpose of intensively studying in an academic context; and (2) whether these perceptions change over time as based on a qualitative perspective. Twenty freshmen enrolled in a literature-based course participated in a semester-long e-book reading. The results showed that the students in this study generally valued the intangible nature of e-books. However, the e-book reading experience was still considered unpleasant to most of the participants in this study. This implies that the reading purpose may not have a great influence on students’ perception of e-books. Despite the overall negative perceptions of e-books, the students also demonstrated some improved attitudes toward reading e-books for an entire semester. The findings indicate that when students are given time and opportunities to read e-books, they are likely to develop e-book reading habits and strategies. It would be a pity if we gave up providing students e-books merely because of their initial negative attitudes.
Corruption and Clientelism in a 'Systemless System': The Europeanization of Maltese Political Culture

This article raises important questions concerning the deployment of stereotypes about traditional and modern political practices by the Maltese people. These stereotypes are often used to make claims against politicians and the state, reflecting various understandings of what the state (or government) is and does. For the Maltese, reform and modernization are often seen as positive developments. However, they are also fraught with risk, as clientelistic practices and systems of patronage are what make Malta's political system functional. Considering these issues through an anthropological lens, the article exposes an inherent tension in Malta - between the traditionalists and modernizers, that is, between those who wish to see Malta 'moving forward' via a process of Europeanization, and those who prefer to cling to Maltese ways of doing things.
Serologic analysis of human rotavirus serotypes P1A and P2 by using monoclonal antibodies

Three human rotavirus (HRV) VP4 serotypes and one subtype have been described on the basis of a fourfold or an eightfold-or-greater difference in neutralization titer when tested with hyperimmune antisera to recombinant VP4 or VP8* (serotypes P1A, P1B, P2, and P3). To start to analyze the antigenic basis underlying serotype specificity, we produced a library of 13 VP4-specific neutralizing monoclonal antibodies (NMAbs) to two HRVs, the serotype P1A strain Wa and the serotype P2 strain ST3, and characterized the reactivity of these NMAbs with a panel of serotypically diverse HRV strains by neutralization assay and enzyme-linked immunosorbent assay (ELISA). We characterized the serotypic specificity of the NMAbs by using a fourfold or an eightfold-or-greater difference in titer against the homologous (i.e., immunogen) and heterologous strains as a criterion for serotype. Some ST3-derived NMAbs reacted specifically with serotype P2 HRVs by ELISA and/or neutralization assay, while some Wa-derived NMAbs reacted specifically by ELISA and/or neutralization assay with some or all serotype P1A HRVs. Other Wa- and ST3-derived NMAbs reacted with some or all serotype P1A and P2 HRV strains by neutralization assay and ELISA. Most NMAbs did not react with serotype P1B or P3 strains. In previous studies, three distinct operationally defined epitopes have been identified on VP4 by examining the reactivity patterns of selected antigenic variants of HRV strain KU. At least one of the NMAbs described here recognizes an epitope unrelated to these previously identified epitopes, since it neutralized both KU and its variants.
A novel hierarchical clustering framework for complex symbolic data exploration

It has been recognized that the variable values of symbolic data may take the form of either an interval or a set of stochastic measurements of some underlying patterns. However, most existing work in symbolic data exploration are still concentrated on interval values only. Although some work in stochastic pattern-based symbolic data has been explored, it is not adaptable enough for various types of symbolic data yet. As a result, we bring forward a novel hierarchical clustering framework for complex symbolic data exploration. Our framework is able to be applied on either qualitative multi-valued or interval-valued or stochastic pattern-based symbolic data. Extensive experiments on a series of synthetic data sets have validated its efficiency and effectiveness.
All-Digital ON-Chip Process Sensor Using Ratioed Inverter-Based Ring Oscillator

In this paper, an all-digital ON-chip process sensor using a ratioed inverter-based ring oscillator is proposed. Two types of the ratioed inverter-based ring oscillators, nMOS and pMOS types, are proposed to sense process variation. The nMOS (pMOS)-type ring oscillator is designed to improve its sensitivity to the process variation in the nMOS (pMOS) transistors using the ratioed inverter that consists of only nMOS (pMOS) transistors. A compact process sensor can be realized using only these two types of ring oscillators. For a suitable ON-chip implementation, the output of the proposed process sensor is provided with a digital code. The proposed process sensor is fabricated using a 0.13-μm CMOS technology. Measurement results from 30 fabricated chips show that all chips have the same process corner. To verify whether the proposed sensor can properly sense all the process corners, the threshold voltage of the fabricated chips is shifted by body biasing. The verification results show that the measured code error compared with the postlayout simulation is less than 2.92%.
Properties of two types of calcium channels in clonal pituitary cells

The calcium currents of GH3 cells have been studied using the whole cell variant of the patch-clamp technique. Under conditions that eliminate sodium and potassium currents, we observed inward currents that activated within a few milliseconds, and deactivated with two time constants, approximately 150 microseconds and 3 ms at -80 mV, 18-20 degrees C. The components are called FD and SD (fast deactivating and slow deactivating). Both components are calcium currents, and are greatly reduced when magnesium is substituted for most of the calcium in the bath. In addition to (a) their different rates of deactivation, the two components differ in a number of other properties. (b) The SD component inactivates almost completely, with a time constant of 23 ms at 20 mV, 19 degrees C. The FD component, on the other hand, shows little or no sign of inactivation, and is almost the same in amplitude from 10 to 100 ms. The components thus seem quite independent of each other, and must arise from two independent sets of channels. (c) The FD channels activate more rapidly than SD at 20 mV, by a factor of approximately 2 as is shown in several ways. (d) In 10 Ca or 10 Ba, the activation curve for SD channels is approximately 20 mV more negative than for FD or Na channels. (e) FD channels conduct barium ions more effectively than calcium by a ratio of approximately 2. (f) FD channels "wash out" within minutes after the patch electrode breaks into a cell, whereas SD channel current remains relatively stable. It is argued that SD channels, because of their negative activation threshold, are involved in electrical events near threshold, and that FD channels are best suited for calcium injection once a spike has been initiated.
General quality of life in youth with type 1 diabetes: relationship to patient management and diabetes-specific family conflict.

OBJECTIVE To evaluate self-report and parent proxy report of child/teen general quality of life in youth with type 1 diabetes, compare their responses with those of a general pediatric population, and identify relationships between diabetes management, diabetes-related family behavior, and diabetes-specific family conflict with quality of life in youth with type 1 diabetes. RESEARCH DESIGN AND METHODS Study participants included 100 children, 8-17 years of age (12.1 +/- 2.3), with type 1 diabetes for 0.5-6 years (2.7 +/- 1.6). Each child and a parent completed the Pediatric Quality of Life Inventory (PedsQL), completed the Diabetes Family Conflict Scale, and provided data on parent involvement in diabetes management. An independent measure of adherence to treatment assessed by the patient's clinician and a measure of glycemic control (HbA(1c)) were also collected. RESULTS PedsQL responses from youth with type 1 diabetes were stable over 1 year and similar to norms from a healthy standardization sample for all three scales of the PedsQL: total, physical, and psychosocial quality of life. After controlling for age, duration of diabetes, sex, HbA(1c), and family involvement, child report of diabetes-specific family conflict (P < 0.01) was the only significant predictor of child report of quality of life (model R(2) = 0.21, P < 0.02). CONCLUSIONS Youth with type 1 diabetes report remarkably similar quality of life to a nondiabetic youth population. Greater endorsement of diabetes-specific family conflict predicted diminished quality of life for the child. As treatment programs focus on intensifying glycemic control in youth with type 1 diabetes, interventions should include efforts to reduce diabetes-specific family conflict in order to preserve the child's overall quality of life.
The Application of Next Generation Sequencing to the Understanding of Antibody Repertoires

In the decade since the human genome sequence was declared complete, the development of next generation sequencing (NGS) or “deep” sequencing to deliver cost-effective genomic sequencing has influenced advances beyond its primary application and changed the research landscape in many other areas. This review will survey recent applications of NGS which have broadened the understanding of natural antibody repertoires (the “antibodyome”) and how these evolve in response to viral infection. We will also report examples where deep sequencing of binding populations, derived from both natural and synthetic repertoires, have been used to benefit antibody engineering. This knowledge will ultimately lead to the design of more effective biological drugs and vaccines.
Norms, Standards, Rights

Preparing European unification European legislators are changing fundamentally important parts of the legal systems of the member states. Furthermore, the internal market will cause many additional social interactions among European citizens. These interactions are influenced not only by law but also by social norms in the different countries. This paper discusses the question how different social norms and different legal systems work together, if there is a need for state intervention not acknowledged before, what the advantages of a uniform European law are and what kind of equilibria are to be expected. The answer will be that many social and legal norms can be best understood as standards with network externalities, creating sometimes separating equilibria, or one dominating equilibrium which may or may not be welfare optimal but will nevertheless prevail over competing alternatives driven by self-enforcing network advantages. Like an avalanche, some social norm or a legal regulation can be self-enfo.
Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish

Summary Hedgehog (Hh) signaling is mediated by the Gli transcription factors and, in the zebrafish, plays an important role in patterning both the neural tube and myotome. Using a null allele of the gli2a gene induced by targeted mutagenesis, we show that Gli2a is completely dispensable in the fish but acts redundantly with Gli1 to regulate expression of known Hh targets, such as ptch2, prdm1a and eng2a, in the myotome and neural tube. To identify novel targets of Hh signaling, we performed chromatin immunoprecipitation sequencing (ChIP-seq) of whole embryo extracts. Samples were significantly enriched for 192 genomic regions, some of which are associated with four known Hh target genes, ptch1, ptch2, gli1 and olig2. Sequence analysis of these regions reveals a high level of conservation of Gli-binding sites from fish to mammals in some, but not all, cases. Expression analysis of other transcription units that are closely associated with peaks identified several putative targets not previously implicated as Hh targets, including myl10, hnmt, lrp4, efemp2, fras1, quo, and lamc1. Each of these genes shows loss of, or reduced expression in, embryos homozygous for an antimorphic allele of gli2a, you-too (yot), consistent with their being direct targets of Gli2a.
Vision guided shortest path estimation using floodfill algorithm for mobile robot applications

In a number of applications, the problem of determining the optimum path occurs, to be specific we shall look at the case of finding the optimum path for mobile robots. This paper presents a shortest path estimation scheme utilizing the overhead video capturing device, for mobile robot path planning. The presented scheme applies the floodfill technique to evaluate shortest path on the maze of dimension (7×7 junction wise). The overhead camera takes continuous snapshot of the maze and accordingly the path planning and computations are done. All the complex calculations and shortest path evaluations are accomplished using MATLAB®. The simulation results that have been taken shows, the mobile robot travels successfully from starting point and reaching its goal point. All obstacles that are located in its way have been avoided and shortest path estimation is done successfully.
Cathepsin K Antisense Oligodeoxynucleotide Inhibits Osteoclastic Bone Resorption*

Cathepsin K is a recently identified cysteine protease which is abundantly and selectively expressed in osteoclasts. To evaluate the contribution of cathepsin K to bone resorption processes, we investigated the effect of cathepsin K antisense phosphothiorate oligodeoxynucleotide (S-ODN) on the bone-resorbing activity of osteoclasts. Rabbit osteoclasts were cultured on dentine slices for 24 h in the presence or absence of antisense S-ODN in a medium containing 100 nM Tfx™-50, polycationic liposome, as a carrier of the S-ODN. Uptake of the S-ODN by osteoclasts was confirmed microscopically using fluorescein-labeled S-ODN. The treatment with antisense significantly decreased the amount of cathepsin K protein in osteoclasts. The antisense inhibited the osteoclastic pit formation in a concentration-dependent fashion. At 10 μM the antisense reduced the total pit number and area and average pit depth by 46, 52, and 30%, respectively. The sense and mismatch S-ODNs, which were used as negative controls, had no effect on either the cathepsin K protein level or the pit formation. A nonspecific cysteine protease inhibitor, E-64, also reduced pit formation in a concentration-dependent manner with maximum reductions at 1 μM of 46, 48, and 35% in the above pit parameters. The inhibitory effect of the antisense almost equal to that of E-64 demonstrates that cathepsin K is a cysteine protease playing a crucial role in osteoclastic bone resorption.
Elementary School Children's Ability to Distinguish Hypothetical Beliefs From Statements of Preference.

The authors examined students’ understanding of hypotheses as beliefs that can be empirically verified. Thirty second graders and 30 sixth graders considered cases of disagreement about foods and colors that reflected either alternative hypotheses or different preferences. Their task was to decide whether the validity of each expressed belief could be determined and to justify their decision. Younger students considered both hypotheses and preferences as empirically verifiable, whereas older students were better able to recognize in some cases that preferences are legitimately variable. This lack of distinction may reflect limited metaconceptual ability or a deterministic epistemological view, both of which might interfere with the understanding of the hypothesis-testing process.
Anbarnesa: The Past Tradition, the Future Medicine

Context: In the Iranian traditional medicine, anbarnesa smoke derived from burning female donkey’s dung has long been used for treatment of inflammatory ulcers and infections of the middle and external ear with no significant side effects. The aim of this study was to introduce anbarnesa and discuss its therapeutic effects. Evidence Acquisition: We conducted a systematic search in PubMed, Medline, Google, and Google Scholar databases to find studies on anbarnesa. The keywords searched were as follows: “anbarnesa,” “traditional medicine,” “medicinal smoke,” “donkey,” “dung,” “antimicrobial,” “inflammation,” “infection,” and “cytotoxicity. Results: Literature review reveals that ANNAS (anbarnesa smoke) enhances wound healing, decreases scar formation, inhibits growth of cancer cells (Hela and KB) and has antimicrobial properties. Also, ANNAS combined with propylene glycol is nontoxic in 1/64, 1/128, and 1/256 dilutions. Conclusions: The constituents of anbarnesa smoke mainly possess antibacterial, anti-inflammatory, and growth inhibition effects on cancer cells.