Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Antioxidant Role of Alcohol Dehydrogenase E from Escherichia coli*

Alcohol dehydrogenase E (AdhE) is an Fe-enzyme that, under anaerobic conditions, is involved in dissimilation of glucose. The enzyme is also present under aerobic conditions, its amount is about one-third and its activity is only one-tenth of the values observed under anaerobic conditions. Nevertheless, its function in the presence of oxygen remained ignored. The data presented in this paper led us to propose that the enzyme has a protective role against oxidative stress. Our results indicated that cells deleted in adhE gene could not grow aerobically in minimal media, were extremely sensitive to oxidative stress and showed division defects. In addition, compared with wild type, mutant cells displayed increased levels of internal peroxides (even higher than those found in a ΔkatG strain) and increased protein carbonyl content. This pleiotropic phenotype disappeared when the adhE gene was reintroduced into the defective strain. The purified enzyme was highly reactive with hydrogen peroxide (with a Ki of 5 μm), causing inactivation due to a metal-catalyzed oxidation reaction. It is possible to prevent this reactivity to hydrogen peroxide by zinc, which can replace the iron atom at the catalytic site of AdhE. This can also be achieved by addition of ZnSO4 to cell cultures. In such conditions, addition of hydrogen peroxide resulted in reduced cell viability compared with that obtained without the Zn treatment. We therefore propose that AdhE acts as a H2O2 scavenger in Escherichia coli cells grown under aerobic conditions.
Pharmacokinetics, antifungal activity and clinical efficacy of anidulafungin in the treatment of fungal infections

Importance of the field: Anidulafungin is one of three available intravenous echinocandins that plays an important role in the treatment of serious fungal infections. Currently, anidulafungin is approved for the treatment of esophageal candidiasis, candidemia and other invasive Candida infections including intra-abdominal abscesses and peritonitis. Areas covered in this review: This paper covers a comprehensive review of anidulafungin. What the reader will gain: The reader will be provided the most recent data available regarding the pharmacology, pharmacokinetics, in vitro activity and clinical utility of anidulafungin for the treatment of serious fungal infections. Take home message: Echinocandin antifungals, such as anidulafungin, are now considered first line for the treatment of candidemia and invasive candidiasis, particularly in critically ill patients or those who have previously received azole therapy. Anidulafungin has potent in vitro activity against Candida and Aspergillus species, predictable pharmacokinetics that does not require dosage adjustment, few drug interactions and is well tolerated. Because of these favorable characteristics, anidulafungin is an important addition to our antifungal armamentarium.
The study of moderator between the Psychological contract and job burnout

Based on the environment-person matching model, salesmen are surveyed through a formal questionnaire, and then descriptive analysis, correlation analysis, regression analysis and variance analysis are conducted to test the moderation effect of working contexts between the psychological contract and the job burnout. The main conclusions of this study are as follows: (1) Working situations moderate the relationship between the psychological contract and job burnout of salesmen; (2) Workload, interaction justice, and person-organization-fit moderate the relationship between the psychological contract and job burnout.
Harmonic control strategy for universal operation of wind turbine systems

Universal wind power generation systems (WPGS) should be able to operate both grid-connected and in island mode without compromising the power quality. The control system of a universal WPGS has to manage the different connections and provide harmonic disturbances compensation. This paper proposes the use of resonant filters for harmonics rejection both in grid-connected and island operation mode but within a different control structure. The proposed control has been tested in simulation.
Ciencia y mito: el caso del dinosaurio

Este trabajo, encuadrado en un cuento hiperbreve, plantea que los mitos nacen y transitan por una singular cornisa entre un proceder cientifico epistemologico y otro que no es tal, pudiendo disparar busquedas cientificas o bien empantanarlas e intenta demostrar, asimismo, que los dinosaurios no han escapado a estas consideraciones. Se efectua un breve recorrido por los registros fosiles disponibles sobre la evolucion de los dinosaurios hasta el letal destino de este superorden y su actual conocimiento. A su vez, se citan algunos mitos universales vinculados con los dinosaurios y su comparacion con la evidencia cientifica, mencionandose igualmente otros mas puntuales y regionales como los grifos, M’Koo, Mokele-Mbembe, Ogopogo, Chac o Chan, Teyu-Jagua, Mboi-Tui, Lizzie, Nessie, el “monstruo” del lago Lacar y Nahuelito, ligados con dinosaurios, en forma estricta o no. Se concluye que el debate cientifico sobre los dinosaurios se halla abierto y proseguira, desde que sus connotaciones miticas, que lo precedieron y forman parte de nuestra herencia cultural como fusion de pensamiento magico, creencias religiosas y narraciones trasvasadas, se retroalimenta con cada hallazgo hecho a este respecto. Esta conviccion se sustenta en que tales ficciones, atemporales y permanentes, enlazan simultaneamente lo externo y perceptible con nuestros anhelos, esperanzas y temores, por lo que el dinosaurio continua batallando entre una presencia mitica, irracional e imprecisa y otra que avanza y retrocede configurando trabajosamente lo que denominamos “ciencia”
Gray Matter Reduction in Currently Depressed Patients of Major Depressive Disorder: A Meta-Analysis

Aim: Existing studies have shown that gray matter changes may be involved in the pathophysiology of major depression disorder (MDD). However, whether the severity of the disease can affect the change of gray matter was still controversial. The aim of the present study is to identify the changes of gray matter on patients with currently depressed MDD (cMDD) using metaanalysis based on the reported studies with VBM. Methods: A systematic retrieval of PubMed, Web of Science, Embase, Medline, and Science Direct was conducted to identify VBM studies that compared the gray matter differences between MDD patients (untreated or not recovered) and healthy controls. A meta-analysis was then carried out to quantitatively evaluate the gray matter changes of patients with cMDD. Results: Seventeen data sets from 14 studies were used in the present meta-analysis. The results showed reduced gray matter in the left superior temporal gyrus, right superior temporal gyrus, right insula, left median network, and left inferior parietal gyrus in patients with cMDD. It was also shown that the percentage of female patients and the mean age did not have a significant relationship with gray matter changes. Conclusion: The meta-analysis in the present study showed that the gray matter reduction not only exists in the frontal lobe and the hippocampus of patients with cMDD as reported in previous studies, but also exists in the temporal lobe, which may also be important in the pathophysiology basis of MDD.
Stylized Adversarial AutoEncoder for Image Generation

In this paper, we propose an autoencoder-based generative adversarial network (GAN) for automatic image generation, which is called "stylized adversarial autoencoder". Different from existing generative autoencoders which typically impose a prior distribution over the latent vector, the proposed approach splits the latent variable into two components: style feature and content feature, both encoded from real images. The split of the latent vector enables us adjusting the content and the style of the generated image arbitrarily by choosing different exemplary images. In addition, a multiclass classifier is adopted in the GAN network as the discriminator, which makes the generated images more realistic. We performed experiments on hand-writing digits, scene text and face datasets, in which the stylized adversarial autoencoder achieves superior results for image generation as well as remarkably improves the corresponding supervised recognition task.
APPLICATION OF H-inf ROBUST CONTROL FOR PARAPLEGIC STANDING

The aim of this work was to design and test robust H∞ feedback control systems for the control of the upright posture of paraplegic persons standing. While the subject stands in a special apparatus, stabilising torque at the ankle joint is generated by electrical stimulation of the paralyzed calf muscle of both legs using surface electrodes. This allows the subject to stand without the need to hold on to external supports for stability: we call this “unsupported standing”. Sensors in the apparatus allow measurement of ankle moments and the inclination angle. A nested loop structure for control of standing is implemented where an inner loop provides control of the total ankle moment while the controller in the outer loop regulates the inclination angle. A difficulty in using electrically-stimulated muscles as actuators in this setup is the very significant degree of nonlinearity in the muscle response. We therefore focus here on robust H∞-control design for the angle control loop. The design approach is verified in experiments with a paraplegic subject.
Quality Care in Transverse Myelitis: A Responsive Protocol

This study was conducted to aid in the development of a multidisciplinary care center for patients with transverse myelitis. We surveyed the parents of 20 children diagnosed with transverse myelitis between the ages of 0.5 and 21 years to understand their experiences in navigating the health care system. We analyzed acute care events and long-term follow-up in relation to patient satisfaction. Results showed satisfactory ratings in the vicinity of 50% in key areas such as the articulation of a treatment plan. A significant disparity was found in the patients' desire for specialty care and their ability to procure such care. In all, 90% of patients expressed a desire to consult with a psychiatrist, but only 25% were successful in making a visit, a 64% deficit; 70% of respondents also desired to see a gastroenterologist, with only 25% actually doing so, leaving a 43% gap. Recommendations and patient opinions regarding the creation of a collaborative care environment are noted. Research with a larger sample will further elucidate the needs in transverse myelitis patient care.
A robust and reliable stress-induced self-assembly mechanism for optical devices

Based on the MUMPs platform, this study has established an improved surface micromachining process (MUMPs-like process) to improve the reliability of the stress-induced beams. A novel rigid supporting mechanism is devised to prevent the mirror from offset. Furthermore, with this mechanism various pop-up mirrors could be accomplished. According to this MUMPs-like process, devices are fabricated to evaluate the performance of this assembly mechanism.
Elements of the Primary Structure of Thrombomodulin Required for Efficient Thrombin-activable Fibrinolysis Inhibitor Activation*

Deletion and point mutants of soluble thrombomodulin were used to compare and contrast elements of primary structure required for the activation of thrombin-activable fibrinolysis inhibitor (TAFI) and protein C. The smallest mutant capable of efficiently promoting TAFI activation contained residues including the c-loop of epidermal growth factor-3 (EGF3) through EGF6. This mutant is 13 residues longer than the smallest mutant that functioned well with protein C; the latter consisted of residues from the interdomain loop connecting EGF3 and EGF4 through EGF6. Alanine point mutants showed no loss of function in protein C activation for mutations within the c-loop of EGF3. In TAFI activation, however, alanine mutations cause a 50% reduction at Tyr-337, 67% reductions at Asp-338 and Leu-339, and 90% or greater reductions at Val-340, Asp-341, and Glu-343. A mutation at Asp-349 in the peptide connecting EGF3 to EGF4 eliminated activity against both TAFI and protein C. Oxidation of Met-388 in the peptide connecting EGF5 to EGF6 reduced the rate of protein C activation by 80% but marginally, if at all, affected the rate of TAFI activation. Mutation at Phe-376 severely reduced protein C activation but only marginally influenced that of TAFI. A Q387P mutation, however, severely reduced both activities. TAFI activation was shown to be Ca2+-dependent. The response, unlike that of protein C, was monotonic and was half-maximal at 0.25 mmCa2+. Like protein C activation, TAFI activation was eliminated by a monoclonal antibody directed at the thrombin-binding domain (EGF5) but was not affected by one directed at EGF2. Thus, elements of structure in the thrombin-binding domain are needed for the activation of both protein C and TAFI, but more of the primary structure is needed for TAFI activation. In addition, some residues are needed for one of the reactions but not the other.
Investigation of ifosfamide nephrotoxicity induced in a liver–kidney co‐culture biochip

In this article, we present a liver–kidney co‐culture model in a micro fluidic biochip. The liver was modeled using HepG2/C3a and HepaRG cell lines and the kidney using MDCK cell lines. To demonstrate the synergic interaction between both organs, we investigated the effect of ifosfamide, an anticancerous drug. Ifosfamide is a prodrug which is metabolized by the liver to isophosforamide mustard, an active metabolite. This metabolism process also leads to the formation of chloroacetaldehyde, a nephrotoxic metabolite and acrolein a urotoxic one. In the biochips of MDCK cultures, we did not detect any nephrotoxic effects after 72 h of 50 µM ifosfamide exposure. However, in the liver–kidney biochips, the same 72 h exposure leads to a nephrotoxicity illustrated by a reduction of the number of MDCK cells (up to 30% in the HepaRG‐MDCK) when compared to untreated co‐cultures or treated MDCK monocultures. The reduction of the MDCK cell number was not related to a modification of the cell cycle repartition in ifosfamide treated cases when compared to controls. The ifosfamide biotransformation into 3‐dechloroethylifosfamide, an equimolar byproduct of the chloroacetaldehyde production, was detected by mass spectrometry at a rate of apparition of 0.3 ± 0.1 and 1.1 ± 0.3 pg/h/biochips in HepaRG monocultures and HepaRG‐MDCK co‐cultures respectively. Any metabolite was detected in HepG2/C3a cultures. Furthermore, the ifosfamide treatment in HepaRG‐MDCK co‐culture system triggered an increase in the intracellular calcium release in MDCK cells on contrary to the treatment on MDCK monocultures. As 3‐dechloroethylifosfamide is not toxic, we have tested the effect of equimolar choloroacetaldehyde concentration onto the MDCK cells. At this concentration, we found a quite similar calcium perturbation and MDCK nephrotoxicity via a reduction of 30% of final cell numbers such as in the ifosfamide HepaRG‐MDCK co‐culture experiments. Our results suggest that ifosfamide nephrotoxicity in a liver–kidney micro fluidic co‐culture model using HepaRG‐MDCK cells is induced by the metabolism of ifosfamide into chloroacetaldehyde whereas this pathway is not functional in HepG2/C3a‐MDCK model. This study demonstrates the interest in the development of systemic organ–organ interactions using micro fluidic biochips. It also illustrated their potential in future predictive toxicity model using in vitro models as alternative methods. Biotechnol. Bioeng. 2013; 110: 597–608. © 2012 Wiley Periodicals, Inc.
Snus (nass) and oral cancer: A case series report

Snus (nass) is a form of snuff used in a similar manner to American dipping tobacco, but it does not typically result in a need for spitting. Possible hazards associated with this material include malignant and premalignant lesions in the oral cavity and gastrointestinal tract. The use of smokeless tobacco has increased in the Middle East in recent decades, particularly among teenagers and young adults. Therefore, practitioners must be able to recognize malignant and premalignant lesions. Although, an estimated 10-25% of the world's population uses smokeless tobacco, this practice is virtually unknown in Iran. The aim of this study is to report a series of cases of squamous cell carcinoma and verrucous carcinoma occurring in the users of snus, who referred to the Department of Oral Medicine in Kerman Dental School.
Sequences within the last intron function in RNA 3'-end formation in cultured cells

In cultured cells, little if any mRNA accumulates from an intronless version of the human gene for triosephosphate isomerase (TPI), a gene that normally contains six introns. By deleting introns either individually or in combinations, it was demonstrated by Northern (RNA) blot hybridization that while the deletion of a greater number of introns generally results in a lower level of product mRNA, not all introns contribute equally to mRNA formation. For example, intron 1 appeared to be dispensable, at least when the remaining introns are present, but deletion of the last intron, intron 6, reduced the level of product mRNA to 51% of normal. To determine how intron 6 contributes to mRNA formation, partial deletions of intron 6 were constructed and analyzed. Deletion of the lariat and acceptor splice sites or the donor, lariat, and acceptor splice sites, each of which precluded removal of the intron 6 sequences that remained, reduced the level of product mRNA to < 1 or 27% of normal, respectively. As measured by RNase mapping and cDNA sequencing, the decrease in mRNA abundance that was attributable to the complete and partial intron 6 deletions was accompanied by an increase in the abundance of pre-mRNA that lacked a mature 3' end, i.e., that was neither cleaved nor polyadenylated. We infer from these and other data that sequences within the final intron facilitate proper 3'-end formation, possibly through an association with the components of a productive spliceosome.
Adaptive control of a quadrotor aerial vehicle with input constraints and uncertain parameters

ABSTRACT In this paper, we address the problem of adaptive bounded control for the trajectory tracking of a Quadrotor Aerial Vehicle (QAV) while the input saturations and uncertain parameters with the known bounds are simultaneously taken into account. First, to deal with the underactuated property of the QAV model, we decouple and construct the QAV model as a cascaded structure which consists of two fully actuated subsystems. Second, to handle the input constraints and uncertain parameters, we use a combination of the smooth saturation function and smooth projection operator in the control design. Third, to ensure the stability of the overall system of the QAV, we develop the technique for the cascaded system in the presence of both the input constraints and uncertain parameters. Finally, the region of stability of the closed-loop system is constructed explicitly, and our design ensures the asymptotic convergence of the tracking errors to the origin. The simulation results are provided to illustrate the effectiveness of the proposed method.
Response to Dr. Kadayifçi

TO THE EDITOR: I read with great interest the commentary by Drs. Hookman and Barkin in the “World Literature Review” section of the Journal (February, 2003 issue [1]) on an article by Lin et al. about the use of metformin in the treatment of nonalcoholic steatohepatitis (NASH) (2). Drs. Hookman and Barkin nicely summarized the recent developments in the study of the pathogenesis of NASH and the possible role of metformin in its treatment. However, I would like to respond to some of their comments. They pointed out the possible role of increased leptin in nonalcoholic fatty liver disease in humans and referred to several studies that suggest the function of leptin in the inflammatory response of the liver and the development of NASH in obese patients with hyperlipidemia. In a clinical study, we previously showed that serum leptin levels were significantly higher in NASH patients with high-fat diets and hyperlipidemia. On the basis of this finding, we also pointed out that leptin might contribute to the development of NASH by amplifying selected proinflammatory responses and modifying the effects of insulin on hepatic fat metabolism (3). Perhaps the authors did not notice our article, which was the first clinical study in the medical literature to demonstrate elevated serum leptin levels in NASH patients with hyperlipidemia. In their commentary, they summarized a study by Marchesini et al., which was the first study in humans to show that metformin has some beneficial effect on liver in patients with NASH (4). However, I think they mistakenly omitted this article from the reference list. Reference 39, which was cited after the section in question, refers to another article. The authors have emphasized in their commentary that more studies on the safety and efficacy of metformin in patients with NASH are needed. In a recent, multicenter, randomized, controlled study, we demonstrated that metformin treatment for 6 months caused significant improvement in both metabolic and histologic findings of NASH compared with dietary treatment alone (unpublished data). The histologic improvement by metformin was prominent in the reversing of necroinflammatory activity in the liver but insignificant on fibrosis. We did not observe a significant change on serum lactate levels in our study. Given the results of this study, we encourage the authors to consider that there are enough data to support the use of metformin as a safe drug in patients with NASH.
Analysis of Improved Digital Peak Voltage Control Buck Converter with Different DPWM Modulations

Improved digital peak voltage (IDPV) control algorithm of switching dc-dc converters with trailing-edge, leading-edge, leading-triangle and trailing-triangle pulse-width modulations are studied in the paper. The control laws of switching dc-dc converters with these different modulation methods are derived and compared with buck converter as an example. Small-signal analysis and comparison among different modulation methods has been performed to have a better understanding of IDPV control algorithm.