Miracle-dz/UniFAR-FTUs huggingface dataset:
Reactive Oxygen Species–Mediated Synergism of Fenretinide and Romidepsin in Preclinical Models of T-cell Lymphoid Malignancies

T-cell lymphoid malignancies (TCLM) are in need of novel and more effective therapies. The histone deacetylase (HDAC) inhibitor romidepsin and the synthetic cytotoxic retinoid fenretinide both have achieved durable clinical responses in T-cell lymphomas as single agents. We investigated the potential for using these two agents in combination in TCLMs. We demonstrated cytotoxic synergy between romidepsin and fenretinide in 15 TCLM cell lines at clinically achievable concentrations that lacked cytotoxicity for nonmalignant cells (fibroblasts and blood mononuclear cells). In vivo, romidepsin + fenretinide + ketoconazole (enhances fenretinide exposures by inhibiting fenretinide metabolism) showed greater activity in subcutaneous and disseminated TCLM xenograft models than single-agent romidepsin or fenretinide + ketoconazole. Fenretinide + romidepsin caused a reactive oxygen species (ROS)–dependent increase in proapoptotic proteins (Bim, tBid, Bax, and Bak), apoptosis, and inhibition of HDAC enzymatic activity, which achieved a synergistic increase in histone acetylation. The synergistic cytotoxicity, apoptosis, and histone acetylation of fenretinide + romidepsin were abrogated by antioxidants (vitamins C or E). Romidepsin + fenretinide activated p38 and JNK via ROS, and knockdown of p38 and JNK1 significantly decreased the synergistic cytotoxicity. Romidepsin + fenretinide also showed synergistic cytotoxicity for B-lymphoid malignancy cell lines, but did not increase ROS, acetylation of histones, activation of p38 + JNK, or cytotoxicity in nonmalignant cells. Romidepsin + fenretinide achieved synergistic activity in preclinical models of TCLMs, but not in nonmalignant cells, via a novel molecular mechanism. These data support conducting clinical trials of romidepsin + fenretinide in relapsed and refractory TCLMs. Mol Cancer Ther; 16(4); 649–61. ©2017 AACR.
Molecular Architecture and Function of the SEA Complex, a Modulator of the TORC1 Pathway*

The TORC1 signaling pathway plays a major role in the control of cell growth and response to stress. Here we demonstrate that the SEA complex physically interacts with TORC1 and is an important regulator of its activity. During nitrogen starvation, deletions of SEA complex components lead to Tor1 kinase delocalization, defects in autophagy, and vacuolar fragmentation. TORC1 inactivation, via nitrogen deprivation or rapamycin treatment, changes cellular levels of SEA complex members. We used affinity purification and chemical cross-linking to generate the data for an integrative structure modeling approach, which produced a well-defined molecular architecture of the SEA complex and showed that the SEA complex comprises two regions that are structurally and functionally distinct. The SEA complex emerges as a platform that can coordinate both structural and enzymatic activities necessary for the effective functioning of the TORC1 pathway.
Is the asset growth anomaly driven by macroeconomic states?

ABSTRACT This study examines the asset growth anomaly in the presence of different macroeconomic states. The results show that the asset growth effect is strongly associated with macroeconomic conditions. When the economy is quiet, the spread between low and high investment firms is small and insignificant. In times of economic stress, the spread is economically large and statistically significant. The results support risk-based explanations for the asset growth effect in line with q-theory.
Trade and investment policy preferences and public opinion in Mexico

Individual policy preferences are crucial long-run determinants of economic policy in democratic states. We analyze the preferences of ordinary Mexican citizens toward economic globalization using a new and unprecedented national-level public opinion survey: México y el Mundo/Global Views 2004. We examine preferences regarding two distinct dimensions of economic policy: international trade and foreign investment. We find weak support for the dominant economic models of policy preference formation, which posit that preferences are a straightforward function of relative economic advantage. We find strong support for the effect of non-economic values on trade and investment policy preferences. We also find some support for retrospective and sociotropic theories of attitude formation.
BLENDER: Enabling Local Search with a Hybrid Differential Privacy Model

We propose a hybrid model of differential privacy that considers a combination of regular and opt-in users who desire the differential privacy guarantees of the local privacy model and the trusted curator model, respectively. We demonstrate that within this model, it is possible to design a new type of blended algorithm that improves the utility of obtained data, while providing users with their desired privacy guarantees. We apply this algorithm to the task of privately computing the head of the search log and show that the blended approach provides significant improvements in the utility of the data compared to related work. Specifically, on two large search click data sets, comprising 1.75 and 16 GB, respectively, our approach attains NDCG values exceeding 95% across a range of privacy budget values.
Development of a time-cycled volume-controlled pressure-limited respirator and lung mechanics system for total liquid ventilation

Total liquid ventilation can support gas exchange in animal models of lung injury. Clinical application awaits further technical improvements and performance verification. Our aim was to develop a liquid ventilator, able to deliver accurate tidal volumes, and a computerized system for measuring lung mechanics. The computer-assisted, piston-driven respirator controlled ventilatory parameters that were displayed and modified on a real-time basis. Pressure and temperature transducers along with a lineal displacement controller provided the necessary signals to calculate lung mechanics. Ten newborn lambs (<6 days old) with respiratory failure induced by lung lavage, were monitored using the system. Electromechanical, hydraulic, and data acquisition/analysis components of the ventilator were developed and tested in animals with respiratory failure. All pulmonary signals were collected synchronized in time, displayed in real-time, and archived on digital media. The total mean error (due to transducers, analog-to-digital conversion, amplifiers, etc.) was less than 5% compared with calibrated signals. Components (tubing, pistons, etc.) in contact with exchange fluids were developed so that they could be readily switched, a feature that will be important in clinical settings. Improvements in gas exchange and lung mechanics were observed during liquid ventilation, without impairment of cardiovascular profiles. The total liquid ventilator maintained accurate control of tidal volumes and the sequencing of inspiration/expiration. The computerized system demonstrated its ability to monitor in vivo lung mechanics, providing valuable data for early decision making.
Competition, Product Proliferation and Welfare: A Study of the U.S. Smartphone Market

This paper studies (1) whether, from a welfare point of view, oligopolistic competition leads to too few or too many products in a market, and (2) how a change in competition affects the number and the composition of product offerings. We address these two questions in the context of the U.S. smartphone market. Our findings show the market contains too few products and that a reduction in competition decreases both product number and product variety. These results suggest that merger policies should be stricter when we take into account the effects of a merger on product choice in addition to those on pricing.
Prevalence of neonatal septicaemia in the University of Port Harcourt Teaching Hospital, Nigeria

Background : Septicaemia is a major cause of morbidity and mortality in the neonatal period. Early detection of neonatal septicaemia is often hampered by its subtle and nonspecific symptoms and signs thus a high index of suspicion is needed. Objectives: To determine the prevalence of neonatal sept ic a emia , ident i fy the predisposing factors, clinical features and causative organisms in the University of Port Harcourt Teaching Hospital. Methods: Four hundred and six neonates with clinical suspicion of sepsis were recruited into the study over a six months period. Blood culture was used as gold standard for the diagnosis of neonatal septicaemia. Results: One hundred and sixtynine (41.6%) neonates had positive blood culture giving a prevalence rate of neonatal septicaemia as 33.1%. The predominant predisposing factors were out-born delivery (68.0%), birth asphyxia (30.2%) and prematurity (21.4%) while the major clinical features of septicaemia were respiratory distress (30.2%), fever (26.6%) and poor suck (22.5%). Klebsiella pneumoniae ( 6 5 . 4 % ), Staphylococcus aureus (15.4%) and Escherichia coli (7.7%) were the commonest organisms isolated in neonates with septicaemia. Conclusion : Prevalence of blood culture-proven septicemia is high, being 33.1%. Klebsiella pneumoniae is the predominant cause of neonatal septicaemia in Port Harcourt. Key Words : Neonatal septicaemia; Prevalence; Port Harcourt.
The Content and Process of Counseling Leadership: Implications for Research and Practice

ABSTRACT This article applies the Integrative Process Model of Leadership to the conceptualization, research, and practice of counseling leadership. The model broadens perspective on leadership to consider processes among leaders, individuals (e.g., followers), groups, and contexts, thereby allowing counselors to better understand how to lead and allowing researchers to study leadership from multiple angles. Implications for counseling leadership research and practice are discussed.
Firing properties of hippocampal neurons in a visually symmetrical environment: contributions of multiple sensory cues and mnemonic processes

The location-specific firing of hippocampal place cells can easily be brought under the control of experimenter-defined cues. Nevertheless, there is evidence that these firing fields are not determined just by immediate sensory input, but also by earlier states of the nervous system (O'Keefe and Speakman, 1987). Here, we report further on the roles of multiple visual cues and mnemonic processes in determining the firing of place cells. Rats were trained to chase food pellets in a cylinder with homogeneous gray walls and 1 white cue card. After a cell's field was recorded in this “standard” condition, probe sessions were conducted in which a second card was placed 180 degrees away from the first. This configuration created a diametrically symmetrical environment in which pairs of locations 180 degrees apart were identical with respect to views of the wall and cards. If place cells are strongly controlled by these immediately available views, firing in the 2-card configuration should be diametrically symmetrical. Alternatively, because the rat moves freely in the cylinder, information is available that pairs of visually identical places are not truly the same. If some mnemonic process stores and updates information about the rat's paths during the session, it is possible that the firing pattern will be different in 2 such places, especially because the original training was conducted in the 1-card, asymmetrical environment. Thirteen of 18 cells had a single, asymmetric firing pattern after the second card was introduced; the field was the same size and shape as in the 1-card configuration and in the same spatial relation to 1 of the 2 cards. The field position during 2-card sessions could be rotated 180 degrees by starting the rat by one card or the other. In further probe sessions in which the cue cards, entry location, and background cues were, in various combinations, rotated in relation to each other, these cells always showed a single field, similar in size and shape to that in the standard, and in the same relationship as in the standard to as many cues as possible. The remaining 5 cells showed complex changes over repeated 2-card sessions, and 3 of these showed paired fields, 180 degrees apart for at least some of the sessions. In one case, the second field disappeared with repeated exposures to 2 cards; in another, the second field persisted when only 1 card was used. We conclude that place cells are influenced both by the immediate sensory configuration and by internal neural states related to earlier experience in the environment.
Endonasal laser dacryocystorhinostomy and external dacryocystorhinostomy outcome profile in a general ophthalmic service unit: a comparative retrospective study.

PURPOSE To evaluate the outcome profile of endonasal laser dacryocystorhinostomy (ENL-DCR) in comparison with external dacryocystorhinostomy (ENL-DCR) carried out as part of general ophthalmic service within the same center. METHODS Patients who have undergone external or endonasal laser DCR in the authors institute with a minimum follow-up of 9 months and at least 3 months after removal of the tubes were invited to participate in this research. We used a questionnaire and a systematic clinical examination for detecting lacrimal passage patency and function. Patients were classified into categories: complete anatomical and physiological success; anatomical success with partial relief of symptoms; anatomical success with no relief of symptoms; anatomical failure. The endoscopic view of the ostium vertical location has been classified into four levels. RESULTS One hundred and ten external-DCR and 53 Endonasal-DCR procedures were evaluated. Free communication (anatomical success) was achieved in 82% undergoing Ext-DCR and in 58% undergoing ENL-DCR. A significant number of patients continued to have symptoms in spite of a patent fistula (54% for Ext-DCR and 39% for ENL-DCR). The site of the opening of the internal ostium was significantly related to the persistence of symptoms in spite of free communication (P < 0.001, chi-square test). CONCLUSION In this series of patients undergoing DCR in a general ophthalmic unit, the standard Ext-DCR technique has a higher anatomical success rate than the endoscopic laser DCR but not necessarily with equivalent rate of relief of symptoms. An inferiorly placed ostium is more likely to result in complete relief of symptoms.
Parents' attitudes to children's participation in randomized controlled trials.

OBJECTIVE To explore parents' attitudes to children's participation in randomized controlled trials. STUDY DESIGN Qualitative analysis of focus group discussions involving 33 parents from a pediatric teaching hospital and local school in Australia. Parents varied in age, gender, ethnicity, level of education, research experience, and child's health status. The transcribed discussions were analyzed by theme linkage using the constant comparative method. RESULTS Parents balance risks and benefits when deciding about trial participation for their child. Perceived benefits include the offer of hope, better care of their child, the opportunity to access new treatments, healthcare professionals and health information, meeting others in similar circumstances, and helping others. Perceived risks include potential side effects, being randomized to ineffective treatments, and the inconvenience of participation. The decision for trial participation is also influenced by parental factors (parents' knowledge, beliefs, and emotional responses), child factors (the child's health status and preference about participation), trial factors (the use of placebos and uncertainties of participation), and doctor factors (doctor's recommendations and communication of trial information). CONCLUSIONS Educating parents about trials, improving communication between trialists, pediatricians, and parents, increasing incentives while decreasing inconveniences, and providing decision aids for parents may increase parents' willingness to participate in trials.
Short Beam Shear Strength Evaluations of GFRP Composites: Correlations Through Accelerated and Natural Aging

Short Beam Shear Strength Evaluations of GFRP Composites: Correlations Through Accelerated and Natural Aging William Barker Fiber Reinforced Polymers (FRP) composites have been materials of interest in replacing or reinforcing steel, wood, and concrete, but lack of understanding of degradation under physical and chemical aging is a main concern. Through many years of research, the understanding of aging or durability of GFRPs has improved. To be able to evaluate aging related degradation rates, an accelerated aging methodology under varying environments is introduced. Accelerated aging is a concept used to age composites in a lab controlled environment under varying pH conditions (2 to 13) and temperatures (~ -20° to +160°F). Once acceleratedly aged testing is completed, Arrhenius relationships and Time-Temperature Superposition principles can be used to correlate the accelerated data with the naturally aged data to create strength reduction (knock-down) factors for 100-year service life. In this work, accelerated and natural aged data for glass fiber reinforced vinyl-ester composites was collected through in-lab testing and literature data. Knowing that interlaminar shear strength (ILSS) is the most detrimental mechanical property, this work was solely focused on the degradation of ILSS of glass fiber reinforced vinyl-ester under varying pH environments and temperatures. The degradation of ILSS in composites has been found to follow two aging trends. Most of the ILSS degradation occurs within the first 3-10 years of service followed by a more gradual trend. The focus of this report is to understand the reason behind a large amount of strength loss in the initial service life. Accelerated testing was also performed on vinyl ester composites with different thicknesses, as well as pure vinyl ester samples. Examining how degradation occurs with varying thicknesses and the resin system apart from the composite is very crucial in understanding the reasons behind aging. To achieve 100-year service knock-down factors, a correlation between acceleratedly aged and naturally aged data was formulated. In this study, the correlation was possible in a neutral pH environment due to the lack of natural aged data in alkaline and acidic environments. Therefore, alkaline and acidic environment knock-down factors are based solely on the plots shifted with acceleratedly aged data. Through hundreds of samples tested, alkaline environment is found to be the most detrimental compared to other chemical aging conditions, especially under elevated temperatures (~150°F). Under high alkaline (pH ~ 13) conditions, significant strength loss of up to 70% within the first thirty days of aging was observed, especially under high temperature conditions. 100-year service knock-down factors were arrived at using the Arrhenius relationship. This relationship is formed through reaction rates based solely on temperature dependency.
Concomitant fibromyalgia in rheumatoid arthritis is associated with the more frequent use of biological therapy: a cross-sectional study

Objectives: To compare the 28-joint Disease Activity Score (DAS28) and its components in patients with rheumatoid arthritis (RA) with and without concomitant fibromyalgia (FM), and to investigate the use of biological treatment in the two groups. Method: Questionnaires developed to diagnose FM were handed out among RA patients during their planned visits. Values for DAS28 were obtained from the DANBIO registry. Demographic data and data on patients’ medical treatment, disease duration, serological and radiological status were retrieved from patients’ files. The χ2 test and an unpaired t-test were applied to investigate group differences in the use of biological therapy, baseline characteristics, patient-reported outcomes, and DAS28 between groups when appropriate. Results: Questionnaires were completed by 162 out of 264 (61%) patients. Twenty-five patients (15.4%) with concomitant FM were identified. No group differences were found regarding disease duration, age, gender, and serological status. Of the RA patients with concomitant FM, 64% were treated with biological therapy vs. 32% of RA patients without concomitant FM (p = 0.002). The mean DAS28 in the FM group was 4.4 compared to 2.9 in the non-FM group (p < 0.001). Elevated DAS28 in the FM group resulted from a high tender joint count (p = 0.003) and a high visual analogue scale (VAS)-global score (p < 0.001). Erosions were more frequent in the non-FM group (p = 0.04). Conclusions: Concomitant FM in patients with RA is associated with a higher DAS28 due to subjective parameters and with the more frequent use of biological treatments. This raises the question of whether the more frequent use of biologics in these patients is justified by inflammation, or is instead due to persistent pain and other centrally mediated symptoms.
Determinants of Young Marrieds' Life Insurance Purchasing Behavior: An Empirical Investigation

The study examines the variables associated with the amount and type of life insurance purchased by a sample of young newly-married couples. Socioeconomic, demographic, psychographic, and other variables are examined by means of Multiple Classification Analysis. The purchase of a larger than average amount of life insurance was found to be much more likely in households where: (1) the husband did not attend college, (2) current and expected household incomes were in the low and high ranges, (3) net worth was greater, (4) the husband had purchased no life insurance before marriage, and (5) the wife had purchased term insurance before marriage. The purchase of term insurance was found to be much more likely in households where: (1) the net worth was greater, (2) the wife purchased term insurance before marriage, and (3) the insurance agent did not influence the decision. The purchase of life insurance is one of the most important consumer purchasing decisions. In the United States, consumers pay out over $24 billion for life insurance premiums or slightly over three percent of their total disposable personal income. These premium receipts, plus the investment income earned on them, has allowed the life insurance industry to become one of the most powerful financial institutions, controlling over $240 billion in assets. One of the most important market segments for the life insurance industry consists of young married couples. Often the first and most important purchases of life insurance are made at this stage of the life cycle. Life insurance decisions made at this time may have a lasting influence on future life insurance purchases. Thus, it is important for the industry to understand the life insurance purchasing behavior of this market segment. This article examines the variables associated with the amount and the type of life insurance purchased by young newly-married couples. Socioeconomic variables, demographic variables, psychographic variables, and other explanatory factors, some of which have not been investigated Dan R. Anderson, Ph.D., CPCU, is Assistant Professor of Business (Risk Management and Insurance) in the Graduate School of Business of the University of Wisconsin, Madison. John R. Nevin, Ph.D., is Assistant Professor of Business (Marketing) in the Graduate School of Business of the University of Wisconsin, Madison. This paper was submitted in April, 1974.