Miracle-dz/UniFAR-FTUs huggingface dataset:
RENAL-SELECTIVE DELIVERY AND ANGIOTENSIN-CONVERTING ENZYME INHIBITION BY SUBCUTANEOUSLY ADMINISTERED CAPTOPRIL-LYSOZYME

In previous studies, we have demonstrated that the low molecular weight protein lysozyme can be used as a renal-selective drug carrier for delivery of the angiotensin-converting enzyme (ACE) inhibitor captopril. Typically, such macromolecular drug-targeting preparations are administered intravenously. In the present study, we investigated the fate of captopril-lysozyme following subcutaneous administration, a convenient route for long-term treatment. The absorption from the subcutaneous injection site and renal uptake of lysozyme were determined by gamma scintigraphy in rats. Bioavailability, renal accumulation, and stability of the captopril-lysozyme conjugate were evaluated by high performance liquid chromatography analysis and by ACE activity measurements. Lysozyme was absorbed gradually and completely from the subcutaneous injection site within 24 h and accumulated specifically in kidneys. After subcutaneous injection of the captopril-lysozyme conjugate, higher renal captopril levels and lower captopril-lysozyme levels in urine indicated the improved renal accumulation in comparison with intravenous administration of the conjugate, as well as its stability at the injection site. After both treatments, captopril-lysozyme conjugate effectuated renal ACE inhibition, whereas plasma ACE was not inhibited. In conclusion, our results demonstrate that we can use the subcutaneous route to administer drug delivery preparations like the captopril-lysozyme conjugate.
Summary Review of the Health Effects Associated With Phenol

Phenol, a monohydroxy derivative of benzene, occurs naturally in animal waste and by decomposition of organic wastes. It is also produced by man, originally by fractional distillation of coal tar, but more recently by cumene hydroperoxidation and toluene oxi dation. As a result of large production volume and natural sources, occupational and environmental exposure to phenol is likely. Phenol poisoning can occur by skin absorption, vapor inhalation, or ingestion, and, regardless of route of exposure, can result in det rimental health effects. Acute toxicity has been observed in man and experimental animals, resulting in muscle weakness, convul sions, and coma. In addition, studies have shown that although teratogenic effects have not been associated with exposure to phenol by either inhalation or oral route, high doses of phenol are fetotoxic. This paper addresses these studies and others in an attempt to determine if human health is at risk to those levels of phenol present in the environment and workplace. However, because data are limited, further research is necessary to analyze the mutagenic and carcinogenic potential of this chemical.
Energy optimal trajectory planning of an underwater robot using a genetic algorithm

This paper presents optimal trajectory planning for an autonomous underwater robot. The optimization parameter is taken as the energy consumed by the robot to traverse its arm tip from a predefined initial point to a final point. The bond graph technique is used for modeling the robot and a genetic algorithm is used as an optimization tool. A polynomial trajectory is considered so that the tip movement is smooth. SYMBOLS Shakti¯ is used as bond graph modeling software and its special feature of generation of CPP code containing the robot model’s expressions is used. The genetic algorithm is implemented on the generated CPP code. Simulation and results for an energy efficient trajectory are presented.
Targeted Gene Disruption in the Xenopus tropicalis Genome using Designed TALE Nucleases

Transcription activator-like effector nucleases (TALENs) are attractive and powerful molecular tools for targeted gene disruption because of their simple design and quick assembly. To evaluate the utility of TALENs in genome editing in Xenopus tropicalis, we prepared nine pairs of TALENs for the tyrosinase, noggin and MMP-9TH genes. All of the TALENs had some activity in a single-strand annealing assay using a cultured frog cell line, suggesting double-stranded DNA cleavage activity by the TALENs at their target site. The injection of mRNAs encoding TALENs into fertilized X. tropicalis embryos resulted in Cel-1 cleavage of the PCR fragment containing the target site amplified from embryo genomic DNA, indicating that a mutation in the target gene had occurred during embryogenesis. These mutations were confirmed by the sequencing of clones derived from the PCR fragments of genomic DNA. Patches of vitiligo were observed in tadpoles raised from fertilized eggs that had been injected with mRNAs of TALENs for the tyrosinase gene. TALENs containing the repeat variable di-residue (RVD) NN appeared to show more activity than TALENs containing RVD NK, although both RVD NN and NK preferentially associate with a G nucleotide.
Circadian Patterns of Locomotor Activity and Body Temperature in Blind Mole-Rats, Spalax ehrenbergi

A wide variety of organisms exhibit circadian rhythms, regulated by internal clocks that are entrained primarily by the alternating cycle of light and darkness. There have been few studies of circadian rhythms in fossorial species that inhabit a microenvironment where day-night variations in most environ mental parameters are minimized and where exposure to light occurs only infrequently. In this study, daily patterns of locomotor activity and body tem perature (Tb) were examined in adult blind mole-rats (Spalax ehrenbergi). These fossorial rodents lack external eyes but possess rudimentary ocular structures that are embedded in the Harderian glands and covered by skin and fur. Most individual mole-rats exhibited circadian rhythms of locomotor activity, but some animals were arrhythmic. Individuals that did exhibit robust rhythms of loco motor activity also showed rhythms of Tb. In most cases, Tb was highest during the phase of intense locomotor activity. Locomotor activity rhythms could be entrained to light:dark cycles, and several mole-rats exhibited entrainment to non-24-h light cycles (T-cycles) with period lengths ranging from T = 23 h to T = 25 h. Some individuals also showed entrainment to daily cycles of ambient temperature. There was considerable interindividual variation in the daily pat terns of locomotor activity among mole-rats in virtually all the conditions of environmental lighting and temperature employed in this study. Thus, whereas it appears likely that photic cues have a significant role in the entrainment of circadian rhythms in mole-rats, the amount of variability in rhythm patterns among individuals appears to be much greater than for most species that have been studied.
Predicting Corporate Financial Sustainability Using Novel Business Analytics

Measuring and managing the financial sustainability of the borrowers is crucial to financial institutions for their risk management. As a result, building an effective corporate financial distress prediction model has been an important research topic for a long time. Recently, researchers are exerting themselves to improve the accuracy of financial distress prediction models by applying various business analytics approaches including statistical and artificial intelligence methods. Among them, support vector machines (SVMs) are becoming popular. SVMs require only small training samples and have little possibility of overfitting if model parameters are properly tuned. Nonetheless, SVMs generally show high prediction accuracy since it can deal with complex nonlinear patterns. Despite of these advantages, SVMs are often criticized because their architectural factors are determined by heuristics, such as the parameters of a kernel function and the subsets of appropriate features and instances. In this study, we propose globally optimized SVMs, denoted by GOSVM, a novel hybrid SVM model designed to optimize feature selection, instance selection, and kernel parameters altogether. This study introduces genetic algorithm (GA) in order to simultaneously optimize multiple heterogeneous design factors of SVMs. Our study applies the proposed model to the real-world case for predicting financial distress. Experiments show that the proposed model significantly improves the prediction accuracy of conventional SVMs.
Requirement of Nuclear Factor of Activated T-cells in Calcineurin-mediated Cardiomyocyte Hypertrophy*

The calcium-activated phosphatase calcineurin has been implicated as a critical intracellular signal transducer of cardiomyocyte hypertrophy. Although previous data suggested the nuclear factor of activated T-cells (NFAT) as its sole transcriptional effector, the absolute requirement of NFAT as a mediator of calcineurin signaling has not been examined in the heart. We therefore investigated the expression and activation profile of NFAT genes in the heart. Four members (NFATc1–c4) are expressed in cardiomyocytes, elicit nuclear translocation upon calcineurin activation, and are able to drive transactivation of cardiac promoter luciferase constructs. To define the necessary function of NFAT factors as hypertrophic transducers, a dominant negative NFAT construct was created, encompassing part of the N-terminal region of NFATc4 containing a conserved calcineurin-binding motif. Cotransfection of this construct dose-dependently abrogated promoter activation, irrespective of the NFAT isoform used, whereas a control construct with the calcineurin-binding motif mutated displayed no such effects. Adenoviral gene transfer of dominant negative NFAT rendered cardiomyocytes resistant toward all aspects of calcineurin or agonist-induced cardiomyocyte hypertrophy, whereas adenoviral gene transfer of the control construct had no discernable effect on these parameters. These results indicate that multiple NFAT isoforms are expressed in cardiomyocytes where they function as necessary transducers of calcineurin in facilitating cardiomyocyte hypertrophy.
A file-based adaptive prefetch caching design

Prefetching techniques in disk caching are addressed. An adaptive prefetch design based on a run-time caching statistics of files is presented. Cache hit histories produced by prefetching are used as a measure of the file access sequentialities. Detailed cache design analysis is discussed using simulation results of a trace-driven model with traces collected from a personal system. The curves obtained from the adaptive design, although not the best at every point, track very well with the best curve in each operation. This shows the dynamic intelligence and efficiency of the file-based adaptive prefetching. The file-based design is compared with one that uses the same transition diagram on disk access but without file identification. The file-based adaptive design outperforms the non-file-based one consistently under all cache sizes. <<ETX>>
Low-density code-domain NOMA: Better be regular

A closed-form analytical expression is derived for the limiting empirical squared singular value density of a spreading (signature) matrix corresponding to sparse low-density code-domain (LDCD) non-orthogonal multiple-access (NOMA) with regular random user-resource allocation. The derivation relies on associating the spreading matrix with the adjacency matrix of a large semiregular bipartite graph. For a simple repetition-based sparse spreading scheme, the result directly follows from a rigorous analysis of spectral measures of infinite graphs. Turning to random (sparse) binary spreading, we harness the cavity method from statistical physics, and show that the limiting spectral density coincides in both cases. Next, we use this density to compute the normalized input-output mutual information of the underlying vector channel in the large-system limit. The latter may be interpreted as the achievable total throughput per dimension with optimum processing in a corresponding multiple-access channel setting or, alternatively, in a fully-symmetric broadcast channel setting with full decoding capabilities at each receiver. Surprisingly, the total throughput of regular LDCD-NOMA is found to be not only superior to that achieved with irregular user-resource allocation, but also to the total throughput of dense randomly-spread NOMA, for which optimum processing is computationally intractable. In contrast, the superior performance of regular LDCD-NOMA can be potentially achieved with a feasible message-passing algorithm. This observation may advocate employing regular, rather than irregular, LDCD-NOMA in 5G cellular physical layer design.
RETINAL ADHESIVENESS IN SURGICALLY ENUCLEATED HUMAN EYES

Purpose: Retinal adhesion in rabbits and monkeys has been shown to involve the interphotoreceptor matrix and depend on environmental factors, such as temperature, pH, and calcium concentration. This study was designed to see whether these same factors modulate retinal adhesiveness in humans. Methods: Four surgically enucleated human eyes were studied. Strips of eyecup were placed in experimental baths shortly after enucleation to evaluate environmental conditions. Retinal adhesive strength was quantified by the amount of retinal pigment epithelial pigment adherent to retina peeled from strips of eyecup. Cone and rod sheaths of the interphotoreceptor matrix were studied by microscopic examination of samples stained with the lectins peanut and wheat germ agglutinin. Results: Retinal adhesiveness fell to 0 approximately 40 minutes after enucleation. Adhesive strength was maintained by cold temperature and was weakened by low pH or low calcium in the bath. Cone and rod matrix sheaths became stretched (indicating a bond) as outer segments and retinal pigment epithelium were peeled apart. Conclusion: Retinal adhesion in humans appears to involve similar mechanisms as in rabbits and monkeys.
Sleepiness in patients with moderate to severe sleep-disordered breathing.

BACKGROUND Population-based studies suggest that complaints of sleepiness are absent in many individuals with sleep-disordered breathing. We investigated the prevalence of sleepiness as well as factors associated with sleepiness in individuals with moderate to severe sleep-disordered breathing (apnea-hypopnea index > or = 15). DESIGN Cross-sectional study. SETTING The Sleep Heart Health Study. PARTICIPANTS Sleep Heart Health Study participants (N = 6440). MEASUREMENTS AND RESULTS Sleepiness was defined as an Epworth Sleepiness Scale score >10 or a report of at least frequently feeling unrested or sleepy. Forty-six percent of participants with moderate to severe sleep-disordered breathing (n = 1149) reported sleepiness. Characteristics associated with sleepiness after adjustment for confounders included presence of respiratory disease, shorter self-reported weekday and weekend sleep, sleep durations, complaints of insufficient sleep, complaints of sleep maintenance insomnia, early morning awakening, habitual snoring, and complaints of awakening with leg cramps or leg jerks. Some respiratory polysomnography measures were associated with sleepiness, but sleep-stage percentages and measures of sleep disruption were not. CONCLUSIONS In this community-based cohort, subjective sleepiness is absent in many individuals with significant sleep-disordered breathing. Comorbid conditions, including respiratory disease, sleep restriction, insomnia, and nocturnal leg complaints, are important risk factors for sleepiness in individuals with moderate to severe sleep-disordered breathing.
Stock Earnings and Bond Yields in the US 1871-2016: The Story of a Changing Relationship

Using historical data that spans almost 150 years, we examine whether there is a long-run equilibrium relationship between the stock's earnings and bond yields. The novelty of our econometric methodology consists in using a vector error correction model where we allow multiple structural breaks in the equilibrium relationship. The results of our analysis suggest the existence of equilibrium relationship over 1871-1929 and 1958-2017. On the two historical segments, our analysis finds that the stock's earnings yield followed the bond yield in both the short- and long-run, but not the other way around. Perhaps the most important and surprising finding of our empirical study is that, after the break in 1929, a completely new equilibrium relationship re-emerged in 1958 that was later termed as the "Fed model. " Our main argument for the emergence of a new equilibrium relationship is that a major ``paradigm shift" in the stock valuation theory occurred in the late 1950s. To support our argument, we highlight the main historical events that potentially could have caused the transition from the old to the new paradigm. Finally, we identify the primary impetus for the paradigm shift.
A Phase II Study of Second-Line Neoadjuvant Chemotherapy With Capecitabine and Radiation Therapy for Anthracycline-Resistant Locally Advanced Breast Cancer

Objective:According to data from Brazil's National Cancer Institute nearly 30% of the new patients who present with breast cancer have locally advanced disease. These patients are inoperable and tumor reduction is usually attempted with chemotherapy. First-line anthracyclin-based neoadjuvant chemotherapy is often effective; however, about 30% of the patients fail and to date there is no established second-line treatment. We have studied the concomitant use of radiation therapy and capecitabine in this setting, to determine the toxicity and efficacy of this regimen as a second-line neoadjuvant treatment. Patients and Methods:Twenty-eight patients with inoperable locally advanced breast cancer refractory to first-line anthracycline based treatment were enrolled between January 2003 and May 2004. Patients received radiation therapy (50 cGy) and concomitant capecitabine (850 mg/m2) twice daily for 14 days every 3 weeks. Results:This treatment rendered 23 of the 28 patients (82%) operable. The 5 remaining patients did not undergo surgery because of disease progression. The median clinical tumor size decreased from 80 cm2 to 49 cm2. Microscopic residual disease was observed in 3 patients (13%) and another patient achieved a complete pathologic response. The median number of involved lymph nodes was 2 and treatment was well tolerated with no grade 3 or 4 events. Conclusion:Our data indicate that second-line neoadjuvant treatment with radiation therapy and capecitabine is feasible, well tolerated, and effective in patients with locally advanced breast cancer refractory to primary anthracycline-based treatment. These results suggest that a randomized study should be done to compare radiotherapy alone to capecitabine combined with radiotherapy.
Is detection of oral and oropharyngeal squamous cancer by a dental health care provider associated with a lower stage at diagnosis?

PURPOSE Stage at diagnosis is the most important prognostic indictor for oral and oropharyngeal squamous cell cancers (SCCs). Unfortunately, approximately 50% of these cancers are identified late (stage III or IV). We set out to examinationine the detection patterns of oral and oropharyngeal SCCs and to determine whether detection of these cancers by various health care providers was associated with a lower stage. PATIENTS AND METHODS Data were gathered on 51 patients with newly diagnosed oral or oropharyngeal SCC through patient interview and chart audit. In addition to demographic data, specific inquiry was made regarding the circumstances surrounding the identification of the lesion. The main outcome measure was tumor stage grouping based on detection source. RESULTS Health care providers detecting oral and oropharyngeal SCCs during non-symptom-driven (screening) examinations were dentists, hygienists, oral and maxillofacial surgeons, and, in 1 case, a denturist. All lesions detected by physicians occurred during a symptom-driven examination. Lesions detected during a non-symptom-driven examination were of a statistically significant lower average clinical and pathologic stage (1.7 and 1.6, respectively) than lesions detected during a symptom-directed examination (2.6 and 2.5, respectively). Additionally, a dental office is the most likely source of detection of a lesion during a screening examination (Fisher exact test, P =.0006). Overall, patients referred from a dental office were of significantly lower stage than those referred from a medical office. Finally, patients who initially saw a regional specialist (dentist, oral and maxillofacial surgeon, or otolaryngologist) with symptoms related to their lesion were more likely to have appropriate treatment initiated than those who initially sought care from their primary care provider. CONCLUSION Overall, detection of oral and oropharyngeal SCCs during a non-symptom-driven examination is associated with a lower stage at diagnosis, and this is most likely to occur in a dental office. A regional specialist was more likely than a primary care provider to detect an oral or oropharyngeal SCC and initiate the appropriate treatment during the first visit for symptoms related to the lesion.
The (non-)use of ex post legislative evaluations by the European Commission

ABSTRACT The European Commission has repeatedly emphasized that the results of ex post legislative (EPL) evaluations should be used to improve the quality of its legislative proposals. This article aims to explain the variation in such instrumental use of EPL evaluations by the Commission. Three high-quality EPL evaluations with varying levels of use were studied in-depth to assess the influence of political factors on evaluation use. The results show that, contrary to expectations, EPL evaluations may be used instrumentally even if their recommendations are opposed by important political actors in the legislative process. This article also shows that a lack of salience of the policy field to which an EPL evaluation belongs in the eyes of the Commission could, in combination with the institution's ambition to reduce its legislative output, be a sufficient condition for the non-use of that evaluation.
Purification and characterization of a hemolysin produced by a clinical isolate of Kanagawa phenomenon-negative Vibrio parahaemolyticus and related to the thermostable direct hemolysin

A clinical isolate (strain 4037) of Kanagawa phenomenon-negative Vibrio parahaemolyticus was studied. Although the strain was judged to be Kanagawa phenomenon-negative by various conventional tests, it produced a new hemolysin (named Vp-TRH, for thermostable direct hemolysin [Vp-TDH]-related hemolysin) that was related to the Vp-TDH produced by ordinary Kanagawa phenomenon-positive V. parahaemolyticus. Vp-TRH was purified by ammonium sulfate fractionation and successive column chromatographies on DEAE-cellulose, hydroxyapatite, and Mono Q. The molecular weight of Vp-TRH was estimated as 48,000 by Sephadex G-100 gel filtration, and the molecular weight of the subunit was estimated to be 23,000 by sodium dodecyl sulfate-slab gel electrophoresis. Thus, like Vp-TDH, Vp-TRH seems to be composed of two subunits. The isoelectric point of Vp-TRH was determined to be 4.6. Vp-TRH showed lytic activities different from those of Vp-TDH on erythrocytes from various animals, especially those from calves, chickens, and sheep. The hemolytic activity of Vp-TRH was labile on heat treatment at 60 degrees C for 10 min, unlike that of Vp-TDH. The immunological similarities, but not the identities of Vp-TRH and Vp-TDH, were demonstrated by Ouchterlony, neutralization, and latex agglutination tests. Thus, we conclude that this clinical isolate of Kanagawa phenomenon-negative V. parahaemolyticus produces a new type of hemolysin that is similar, but not identical, to Vp-TDH, which is usually produced by Kanagawa phenomenon-positive V. parahaemolyticus.