Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Immunodeﬁciency Virus Type 1 Nef Selectively Associates with a Catalytically Active Subpopulation of p21-Activated Kinase 2 (PAK2) Independently of PAK2 Binding to Nck or b -PIX

We have recently identiﬁed the Nef-associated serine-threonine kinase (NAK) as the p21-activated kinase 2 (PAK2). Here we have taken advantage of the possibility to manipulate the functional properties of NAK by transfecting PAK2 cDNA or its mutant derivatives in order to further characterize the Nef-NAK complex. To exclude the possibility that some Nef variants might interact with PAK1 instead of PAK2, we also examined the identity of NAK complexed with divergent human immunodeﬁciency virus type 1 HIV-1 Nef proteins. All tested Nef proteins, including SF2, NL4-3, BH10, and HAN-2, associated with PAK2 but not with PAK1. By exchang-ing different regions between these two PAK proteins, the selective ability of PAK2 to associate with Nef could be mapped to the carboxy-terminal part of its regulatory domain. Binding of PAK2 with the adapter protein Nck or b -PIX was found to be dispensable for the assembly of the Nef-PAK2 complex, whereas an intact Cdc42-Rac1 interactive binding motif was required. Most importantly, we found that NAK represented a distinct subpopulation of the total cellular PAK2 characterized by a high speciﬁc kinase activity. Thus, although only a small fraction of cellular PAK2 could be found in complex with Nef, NAK represented a major part of cellular PAK2
Modulation of responses of feline ventral spinocerebellar tract neurons by monoamines

Ventral spinocerebellar tract neurons located in laminae V–VII of cat lumbar spinal cord were tested for the effects of ionophoretically applied monoamines and receptor selective agonists. Extracellularly recorded responses, monosynaptically evoked by group I afferents in a muscle nerve, were compared before, during, and after ionophoresis. They were analyzed with respect to changes in the number of evoked spikes and in the latency. Both serotonin (5‐HT) and noradrenaline (NA) were found to facilitate responses of all neurons tested. Ionophoresis of three serotonin subtype receptor agonists (5‐carboxamidotryptamine maleate, 5 methoxytryptamine HCl, and alpha‐methyl 5‐hydroxytryptamine) and of two NA receptor agonists (phenylephrine and isoproterenol) likewise had a facilitatory effect. However, three other 5‐HT receptor agonists (8‐hydroxy‐dipropylaminotetraline hydrobromide), 2‐methyl 5‐hydroxytryptamine, and 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane HCl and two NA receptor agonists (tizanidine and clonidine) had the opposite effect because they depressed responses of the tested neurons. These results show that information forwarded by means of the ventral spinocerebellar tract may be modulated by monoamines and that several receptor subtypes, located pre‐ or postsynaptically, may be involved. The results also demonstrate that transmission by means of group I muscle afferents may not only be facilitated by monoamines but also depressed by selective receptor subtype activation. J. Comp. Neurol. 443:298–309, 2002. © 2002 Wiley‐Liss, Inc.
The Neural Correlates of Verbal and Nonverbal Semantic Processing Deficits in Neurodegenerative Disease

ObjectiveTo investigate the neural correlates of verbal and nonverbal semantic processing in neurodegenerative disease. BackgroundSemantic memory is often impaired in neurodegenerative disease. Neuropsychologic and functional neuroimaging studies suggest that the semantic processing of verbal and nonverbal stimuli may depend on partially distinct brain networks. MethodsWe examined this possibility using voxel-based morphometry to correlate performance on verbal and nonverbal versions of a semantic association task with regional gray matter atrophy in 144 individuals with a variety of neurodegenerative diseases. ResultsResults showed that, regardless of stimulus type, semantic processing correlated with atrophy in both temporal lobes. In addition, material-specific correlations were found in left temporal regions for verbal stimuli and the right fusiform gyrus for nonverbal stimuli. ConclusionsThese results provide evidence for a differential role of the left and right hemispheres in the extraction of semantic information from verbal and pictorial representations. Areas in right inferior temporal lobe may be necessary to access structural descriptions of visually presented objects.
PORTLESS low power mux architecture with line hard duplication

Embedded cache memories consumes a large percentage of the dynamic and static energy in System-On-Chip (SOC). Energy consumption expects to increase in advanced technologies. Write and read operations operate charging and discharging of large bitline capacitances. Multiplexors are introduced in 6T-SRAM to reduce column size. Unfortunately read current is not reduced and even increases. Considering the 5T Portless SRAM, an original multiplexor structure is presented that offers a significant gain in active energy consumption. The multiplexor benefits from a hard line duplication technique that copies an addressed line into an other line in one clock cycle. The advantages of the latter duplication technique are presented in details. Moreover Portless bitcell is more stable, suffers less leakage than 6T SRAM bitcell. The paper confirms that Portless SRAM is a candidate alternative structure to 6T SRAM in advanced technologies.
Mixed‐method research for child outcomes in intersex conditions

Intersex encompasses a range of inborn errors of metabolism and dysmorphisms, having in common anomalous genitalia. The neonatal diagnosis may be unclear but genital atypia is not. Reconstructive surgery has been the standard of care for more than four decades. Although the conditions are ageless, selfdescriptions of long-term effects are rare, as are the anomalies themselves. For the purposes of this discussion, neonatal genital appearance is meant to reflect inadequate androgen effects in genetic males or inappropriate androgen effects in genetic females. This discussion briefly describes what is known about children’s experiences of and with intersex and intersex treatments, and how such experiences are knowable.
The retro-GCN 4 leucine zipper sequence forms a stable three-dimensional structure

The question of whether a protein whose natural sequence is inverted adopts a stable fold is still under debate. We have determined the 2.1-Å crystal structure of the retro-GCN4 leucine zipper. In contrast to the two-stranded helical coiled-coil GCN4 leucine zipper, the retro-leucine zipper formed a very stable, parallel four-helix bundle, which now lends itself to further structural and functional studies.
Cross-Slot-Coupled Wide Dual-Band Circularly Polarized Rectangular Dielectric Resonator Antenna

A cross-slot-coupled wide dual-band circularly polarized (CP) rectangular dielectric resonator antenna (DRA) is investigated. The DRA has a large aspect ratio of 3.2:1. By using a cross-slot of unequal slot arms, three sets of degenerate orthogonal modes of TE111, TE121, and TE131 can be excited simultaneously to generate dual-band CP fields. It is found that the lower band is composed of the TE111 and TE121 modes, while the upper band is formed by the TE131 mode. The 3-dB axial-ratio (AR) bandwidths are 19.8% and 6.2% for the lower and upper bands, respectively. To verify the simulation, measurement was carried out and reasonable agreement was obtained.
Oxidative stress and TGFbeta in kidney-transplanted patients with cyclosporin-induced hypertension. Effect of carvedilol and nifedipine.

Cyclosporin is a powerful stimulator of oxidative stress signaling, leading to TGFbeta production, NO degradation, endothelial dysfunction, hypertension and post-transplant nephropathy. Carvedilol, alpha1-beta-blocker with strong antioxidant activity, may interfere with this chain of events. Therefore, we measured monocyte ecNOS, TGFbeta and heme oxygenase-1 (HO-1) mRNA level and plasma nitrite/nitrate, 3-nitrotyrosine, an estimate of peroxynitrite, and total plasma antioxidant power in kidney-transplanted patients with post-transplant hypertension, before and after treatment with carvedilol, 25 - 50 mg o.d. orally for 4 months (n = 15). The dihydropyridine calcium channel blocker nifedipine (n = 10) was used as comparator antihypertensive drug. Blood pressure fell to a similar extent with both drugs. Carvedilol increased plasma antioxidant power and HO-1 mRNA and reduced 3-nitrotyrosine and TGFbeta mRNA levels, while the same was not observed with nifedipine. Monocyte ec NOS mRNA levels and plasma nitrite/nitrate were higher in the patients than in a normotensive healthy control group and were unaffected by either treatment. In conclusion, carvedilol reduces the oxidative stress and corrects the altered cellular signaling mediated by oxidative stress in CsA-induced post-transplant hypertension. Therefore, it may prevent long-term complications, such as endothelial dysfunction, fibrogenesis and post-transplant nephropathy by decreasing NO degradation and production of TGFbeta, a key fibrogenic cytokine, and by activating HO-1 production.
Emotion regulation behavior during a separation procedure in 18-month-old children of mothers using cocaine and other drugs

This study examined the association between maternal cocaine use and children's emotional regulation. Using a brief separation procedure, we observed 78 18-month-old at-risk children and their mothers from three defined maternal groups: no drug use; no cocaine use but a positive history for alcohol, tobacco, and/or marijuana; and cocaine use with or without alcohol, tobacco, and/or marijuana. Coded videotaped behavior identified three maternal constructs (separation style, physical engagement, and emotional engagement) and three child constructs (negative reactivity to separation, initial regulatory activity, and follow-up positive emotional engagement). Cocaine-using mothers displayed less emotional engagement than other mothers. Children with cocaine-using mothers displayed less negative reactivity and follow-up positive emotional engagement than their counterparts. Child reactivity was connected to maternal drug use, whereas emotional engagement during reunion was linked to birthweight and maternal behavior. Results suggest a possible impairment or restriction of emotional expression and regulation in the face of stress and/or maternal disengagement that is more common among cocaine-exposed children with their mothers.
Genetic Variation in Oocyte Phenotype Revealed Through Parthenogenesis and Cloning: Correlation with Differences in Pronuclear Epigenetic Modification1

Abstract Previous studies revealed that oocytes of different genetic strains (e.g, C57BL/6 and DBA/2) modify maternal and paternal pronuclei differently, affecting early preimplantation development. To determine whether these strain-dependent effects would also apply to oocyte modifications of somatic cell nuclei introduced during cloning procedures, we compared the efficiency of development of parthenogenetic and cloned embryos made with DBA/2, C57BL/6, and (B6D2)F1 oocytes. Our results reveal significant differences in the ability of oocytes of different genetic backgrounds to support parthenogenetic development in different culture media. Additionally, our results reveal oocyte strain-dependent differences in the ability to support cloned embryo development beyond what can be accounted for on the basis of differences in parthenogenesis. Thus, the previously documented differences in oocyte-directed parental genome modification are accompanied in the same strains by differences in the ability of oocytes to modify somatic cell nuclei and support clonal development, raising the possibility that these oocyte functions may be mediated by related mechanisms. These results provide a genetic basis for further studies seeking to identify specific genes that determine oocyte phenotype, as well as genes that determine the success of nuclear reprogramming and clonal development.
Restoration of erectile function with intracavernous injections of endothelial progenitor cells after bilateral cavernous nerve injury in rats

Endothelial progenitor cells (EPCs) are bone marrow‐derived endothelial cells capable of circulating, proliferating, and differentiating into mature endothelial cells. Circulating EPCs can be directly recruited to some extent at sites of injury, and their administration could accelerate repair or endothelialization of the damaged tissue. We investigated the effects of intracavernous injections of EPCs into the corpora cavernosa of rats with erectile dysfunction (ED) caused by bilateral cavernous nerve (CN) injury. Overall, 24 male Sprague–Dawley rats were randomized into three groups: sham surgery, vehicle‐only, or EPC treatment. Rats in the EPC treatment and vehicle‐only groups were subjected to bilateral CN injury before injection of EPCs or vehicle, respectively, into the corpora cavernosa. Four weeks after surgery, erectile function was assessed by measuring maximum intracavernosal pressure (ICP), change in ICP, area under the ICP curve, and ratio of change in ICP and mean arterial pressure (MAP; ΔICP/MAP). Penile tissue was histomorphometrically analyzed for the expression of neural nitric oxide synthase (nNOS), neurofilament‐1 (NF‐1), von Willebrand factor (vWF), endothelial NOS (eNOS), and smooth muscle cell content. Maximum ICP and all other functional parameters of erectile function were significantly reduced in the vehicle‐only group vs. the sham and EPC treatment groups (all p < 0.001). Smooth muscle cell content was decreased in the vehicle‐only vs. the sham and EPC treatment groups (both p < 0.01). Expressions of vWF and eNOS in the dorsal artery were significantly higher in the EPC treatment than the vehicle‐only group (p < 0.05). In conclusion, EPC treatment restored erectile function in a rat model of bilateral CN injury through recruitment of EPCs toward the dorsal artery and preservation of smooth muscle cells in the corpus cavernosum. These findings elucidate the therapeutic potential of EPCs for treating ED in humans.
Executive Dysfunction in School-Age Children With ADHD

Objective: The study examined executive function deficits (EFD) in school-age children (7 to 14 years) with ADHD. Method: A clinical sample of children diagnosed with ADHD (n = 49) was compared to a population sample (n = 196) on eight executive function (EF) measures. Then, the prevalence of EFD in clinical and non-clinical children was examined at the individual level according to three methods previously applied to define EFD, and a fourth method was included to control for the effect of age on performance. Results: Children with ADHD were significantly more impaired on measures of EF than children without ADHD at the group level. However, only about 50% of children with ADHD were found to have EFD at the individual level, and results appeared relatively robust across methods applied to define EFD. Conclusion: As a group, children with ADHD displayed more problems on neuropsychological measures of EF than non-clinical children; at the individual level, there appeared to be heterogeneity in EF impairment.
Induction Therapy for Pediatric and Adult Heart Transplantation: Comparison Between OKT3 and Daclizumab

Background. Induction therapy can reduce morbidity and early mortality in pediatric and adult heart transplant recipients. Monoclonal and polyclonal agents are most widely used; they nonspecifically deplete the T-cell pool and are thus associated with drug-induced side effects. The cytokine release syndrome is one of the most problematic events associated with induction. Daclizumab, a highly humanized, specific interleukin-2 receptor blocker, may be efficacious to the monoclonal agent, OKT3. Due to its specific action and properties, the safety profile of this agent may be superior to OKT3. Methods. Forty subjects received daclizumab and their clinical outcomes were compared against a historical group of 40 subjects who received OKT3. Three- and six-month outcome measures included survival, rejection history, steroid burden, and complications. Results. Mortality was low between the groups with equivalent 6-month survival. No differences in rejection profile or time to the first significant rejection event were detected; no subject had severe acute rejection within the first 180 days. Steroid requirement for maintenance immunosuppression and treatment of rejection was also similar between the groups. Six-month prevalence for complications were significantly different; 55% of OKT3-treated subjects having at least one event compared to 33% of daclizumab-treated subjects (P = 0.04). The likelihood of complications occurred within the first month after transplantation. Conclusions. Daclizumab induction therapy is as efficacious as OKT3 in the prevention of early acute rejection after heart transplantation among pediatric and adult subjects. Complications related to the induction agent are significantly lower in the humanized product.
Aberrant expression of the cell cycle associated proteins TP53, MDM2, p21, p27, cdk4, cyclin D1, RB, and EGFR in cervical carcinomas.

OBJECTIVE The aims of this study were to study aberrant expression and coexpression of the cell cycle associated proteins TP53, p21, p27, cyclin D1, cdk4, RB, EGFR, and MDM2 in cervical carcinomas, to correlate protein alterations with histopathological and clinical parameters, and to evaluate whether these alterations provide prognostic information. METHODS Seventy-four cervical carcinomas and 10 cases of normal cervical epithelium from patients with benign uterine leiomyomas were investigated immunohistochemically for aberrant expression of the cell cycle associated proteins using the biotin-streptavidin-peroxidase method and the OptiMax Plus automated cell staining system. RESULTS In normal cervical epithelium p27 immunostaining was identified in more than 50% of the cells, cdk4 in 5-50% of the cells, and EGFR in less than 5% of the cells, whereas no immunostaining for TP53, p21, MDM2, or cyclin D1 was detected. Positive RB protein staining was identified in all cases of normal cervical epithelium. RB protein staining was also identified in all carcinomas of the cervix uteri. Overexpression of p21 was found in 96% of the tumors, MDM2 in 35%, cdk4 in 69%, cyclin D1 in 3%, and EGFR in 20% of the tumors. A low level of p27 was observed in 65% of the cases. In a previous study, the TP53 protein level has been found to be elevated in 41 of the 74 (55%) cases included in this work. Significant coexpression was seen for TP53 and MDM2 (P = 0. 001); concording results were observed in 67% of the cases. There was no difference in aberrant expression or coexpression of any of the cell cycle regulatory proteins related to histological type, grade of differentiation, FIGO stage, or relapse-free survival. CONCLUSION The high number of cases showing increased levels of p21 and cdk4 and decreased levels of p27 suggests that these proteins may be important in the pathogenesis of cervical carcinoma. Furthermore aberrant expression of MDM2 in a smaller but significant fraction of cases indicates that these proteins could also be involved in the development of these cancers. Finally our results indicate that MDM2 may protect against HPV-induced TP53 protein degradation.
Phenobarbital increases DNA adduct and metabolites formed by ochratoxin A: Role of CYP 2C9 and microsomal glutathione‐S‐transferase

Ochratoxin A (OTA), a mycotoxin that induces nephrotoxicity and urinary tract tumors, is genotoxic and can be metabolized not only by different cytochromes P450 (CYP) but also by peroxidases involved in the arachidonic cascade, although the exact nature of the metabolites involved in the genotoxic process is still unknown. In order to establish the relation between OTA genotoxicity and the formation of metabolites, we chose three experimental models: kidney microsomes from rabbit, human bronchial epithelial cells, and microsomes from yeast that specifically express the human cytochrome P450 2C9 or 2B6 genes. OTA‐DNA adducts were analyzed by 32P postlabeling and the OTA derivatives formed were isolated by HPLC after incubation of OTA in the presence of: (1) kidney microsomes from rabbit pretreated or not with phenobarbital (PB); (2) human pulmonary epithelial cells simultaneously pretreated (or not) with PB alone or in the presence of ethacrynic acid (EA); (3) microsomes expressing CYP 2B6 and 2C9. PB pretreatment significantly increased DNA adducts formed after OTA treatment, both in the presence of kidney microsomes and bronchial epithelial cells, and induced the formation of new adducts. Ethacrynic acid, which inhibits microsomal glutathione‐S‐transferase, reduced DNA adduct level. DNA adducts were detected when OTA were incubated with microsomes expressing human CYP 2C9 but not with those expressing CYP 2B6. Several metabolites detected by HPLC were increased after PB treatment. Some of them could be related to DNA‐adduct formation. In conclusion, OTA biotransformation, enhanced by PB pretreatment, increased DNA‐adduct formation through pathways involving microsomal glutathion‐S‐transferase and CYP 2C9. Environ. Mol. Mutagen. 35:123–131, 2000 © 2000 Wiley‐Liss, Inc.
Protective role of Hemidesmus indicus R. Br. root extract against Salmonella typhimurium‐induced cytotoxicity in Int 407 cell line

The present investigation deals with the effect of the chloroform fraction composed of sterols and fatty acids isolated from Hemidesmus indicus root extract (CHI) on Salmonella enterica serovar Typhimurium (S. typhimurium)‐induced cytotoxicity in a human intestinal epithelial cell line (Int 407). The optimum dose was fixed as 100 µg/mL for CHI against S. typhimurium, which was quite safe for Int 407 cells as the CD50 concentration (50% cell death) of CHI was determined to be 500 µg/mL in the Int 407 cell line. CHI‐treated S. typhimurium were 10‐fold less cytotoxic and 40% less adherent to host cells than wild‐type. Treatment of CHI significantly abrogated the invasion ability to 10‐ to 15‐fold in S. typhimurium. The cells infected with CHI‐treated S. typhimurium had a comparable viability to uninfected cells in the epithelial cell detachment assay. Immunofluorescence showed the CHI‐treated bacteria were unhealthy and shrunken rods in comparison with the wild‐type bacteria; those were firmly attached and invaded to deceased and hypertrophoid Int 407 cells. Transmission electron micrographs of Int 407 cells infected with wild bacteria showed a coat of adherent and invaded bacteria completely occupying the cytoplasm with characteristic Salmonella‐containing vacuoles (SCV). Both necrotic and apoptotic type of cell death were observed in cells infected with wild‐type bacteria, whereas most of the cells infected with treated bacteria were normal in morphology and a few had invaded bacteria, but the typical proliferated SCV was not observed in cells infected with CHI‐treated S. typhimurium. In summary, the sterols and fatty acids present in CHI may be capable of taming S. typhimurium by suppressing its cytotoxic activity in an intestinal epithelial cell line. Copyright © 2007 John Wiley & Sons, Ltd.
A self-tuning variable frequency control for multi-level contactless Electric Vehicle charger

This paper proposes a self-tuning controller for a multi-level inductive Electric Vehicle (EV) battery charger application. By controlling the energy injection frequency of the Inductive Power Transfer (IPT) system, multiple charging levels (4 in number) are achieved. Maximum performance is leveraged by the proposed IPT system using its capability of self-tuning the switching operations to the natural resonant frequency of the IPT system, thereby benefiting from soft-switching operations (zero-current switching). Either a digital or analog control circuit can be used to implement the proposed controller. The results are shown by simulating the proposed controller with different charging levels using MATLAB/Simulink. These results show that the proposed controller effectively enables IPT-based contactless EV charging at multiple charging levels, with soft-switching operations. This self-tuning capability is specifically useful in IPT systems that have variable resonance frequency.