Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of anxiety circuits by serotonergic systems

Anxiety is a complex emotional state associated with sustained heightened autonomic and behavioral arousal and an increase in avoidance behavior. Anxiety-related behavior is a form of risk assessment behavior that is associated with a level of uncertainty or unpredictability regarding the outcome of emotionally salient events, often when both rewarding and aversive outcomes are possible. In this review, we highlight recent advances in our understanding of the neural circuits regulating anxiety states and anxiety-related behavior with an emphasis on the role of brainstem serotonergic systems in modulating anxiety-related circuits. In particular, we explore the possibility that the regulation of anxiety states and anxiety-related behavior by serotonergic systems is dependent on a specific, topographically organized mesolimbocortical serotonergic system that originates in the mid-rostrocaudal and caudal parts of the dorsal raphe nucleus.
Intrahepatic and peripheral blood virus‐specific cytotoxic T lymphocyte activity is associated with a response to combination IFN‐α and ribavirin treatment among patients with chronic hepatitis C virus infection *

Summary. This report describes an association between intrahepatic and peripheral blood cytotoxic T lymphocytes (CTL) activity present prior to receiving treatment, and a response to combination interferon‐α (IFN‐α) and ribavirin therapy for chronic hepatitis C virus (HCV) infection. Recombinant vaccinia virus constructs were used to expand and detect cytotoxic effectors against the entire genotype 1a HCV polyprotein. Six patients with a sustained response to therapy were significantly more likely to display intrahepatic and peripheral blood HCV‐specific CTL activity than patients who relapsed or had no treatment response. Limited longitudinal data suggested that rather than combination therapy acting to enhance the CTL response to achieve viral clearance, detectable CTL prior to treatment increases the likehood of the host responding to the direct antiviral activity of IFN‐α and ribavirin.
Antigenic, structural, and functional relationships between fimbriae and the hemagglutinating adhesin HA-Ag2 of Porphyromonas gingivalis

While the adhesive properties of Porphyromonas gingivalis are known to allow colonization of the subgingival tissues, the roles of fimbriae and adhesin molecules in hemagglutination remain unclear. The purpose of this study was to analyze the antigenic, structural, and functional relationships of these two components. Five populations of monoclonal antibodies were produced against (i) the hemagglutinating adhesin HA-Ag2 resolved by crossed immunoelectrophoresis (CIE), (ii) native fimbriae, and (iii) each of the three immunoprecipitates, Ag8a, Ag8b, and Ag8c, that define fimbriae by CIE. The tests used for characterization of the monoclonal antibodies included immunoblot reactivity, inhibition of hemagglutination, capacity to dissociate immunoprecipitates by CIE, localization of recognized epitopes by immunoelectron microscopy, and epitope mapping by competition enzyme-linked immunosorbent assay. The results from the different immunochemical tests clearly showed a close antigenic relationship between fimbriae and the hemagglutinating adhesin HA-Ag2. We were able to establish that the epitopic domain H1 of HA-Ag2 is hemagglutinin specific and that domain F2 is fimbria specific. Our data indicate that the polymeric structural unit of fimbriae must be complexed to HA-Ag2, the adhesin, to confer hemagglutination activity to the bacterial cells.
Haemophilus influenzae localized in epithelial cell layers is shielded from antibiotics and antibody-mediated bactericidal activity.

Nonencapsulated Haemophilus influenzae frequently persists in the lungs of chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) patients for prolonged periods of time. The bacteria are not eradicated by antibiotic treatment of the patients or by specific antibodies that are found in the sputum and sera of these patients. We investigated whether H. influenzae, when localized in lung epithelial cell layers, is shielded from antibiotics and from antibody-mediated bactericidal activity of specific antibodies. An in vitro model system consisting of lung epithelial NCI-H292 cells on permeable supports was developed to allow long term association of H. influenzae with the cells. Microscopic examination showed increasing numbers of H. influenzae bacteria between the epithelial cells up to 24 h of incubation. Coinciding with the microscopic observations the maximum number of cell-associated bacteria surviving gentamicin treatment of the cell layers was obtained after 24 h of incubation. All H. influenzae strains, and one Haemophilus parainfluenzae strain tested penetrated into the cell layer as determined by gentamicin killing. Cell-associated bacteria were shielded from the bactericidal activity of several antibiotics and from antibody-mediated bactericidal activity. After prolonged incubation in the cell system in the presence of a specific bactericidal antibody against major outer membrane protein (MOMP) P2, antigenic variation occurred due to a point mutation in the MOMP P2 gene, similar to point mutations observed in vivo. We conclude that penetration of H. influenzae between lung epithelial cells results in shielding the bacteria from killing by antibody dependent defense mechanisms and by antibiotics. Therefore, penetration of H. influenzae between epithelial cells may contribute to the persistence of this microorganism in COPD and CF patients.
Multilayer bioactive glass/zirconium titanate thin films in bone tissue engineering and regenerative dentistry

Surface modification, particularly coatings deposition, is beneficial to tissue-engineering applications. In this work, bioactive glass/zirconium titanate composite thin films were prepared by a sol-gel spin-coating method. The surface features of the coatings were studied by scanning electron microscopy, atomic force microscopy, and spectroscopic reflection analyses. The results show that uniform and sound multilayer thin films were successfully prepared through the optimization of the process variables and the application of carboxymethyl cellulose as a dispersing agent. Also, it was found that the thickness and roughness of the multilayer coatings increase nonlinearly with increasing the number of the layers. This new class of nanocomposite coatings, comprising the bioactive and inert components, is expected not only to enhance bioactivity and biocompatibility, but also to protect the surface of metallic implants against wear and corrosion.
Addition of Zinc Improves the Physical Stability of Insulin in the Primary Emulsification Step of the Poly(lactide-co-glycolide) Microsphere Preparation Process

In this study, the effect of zinc on insulin stability during the primary emulsification step of poly(lactide-co-glycolide) microspheres preparation by the water-in-oil-in-water (w/o/w) double emulsion solvent evaporation technique was evaluated. Insulin was emulsified at homogenization speeds of 5000 and 10,000 rpm. Insulin was extracted from the primary w/o emulsion by a method previously reported from our laboratory and analyzed by comprehensive analytical techniques. The differential scanning calorimetry thermograms of insulin with zinc showed a single peak around 83 °C with calorimetric enthalpy values similar to native insulin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of extracted insulin showed a single intense band around 6 kDa, demonstrating the preservation of primary structure. High performance liquid chromatography (HPLC) analysis revealed that no degradation products were formed during the homogenization process. Insulin aggregates residing at the w/o interfaces were found to be of non-covalent nature. In addition, observation of a single characteristic peak for insulin at m/z 5808 in the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrum confirmed the absence of insulin degradation products and covalent dimers. Presence of zinc preserved the secondary structure of insulin as indicated by circular dichroism. In conclusion, these results show that with the addition of zinc, insulin stability can be improved during the primary emulsification step.
Temperature‐dependent sex determination in the american alligator: AMH precedes SOX9 expression

Gonadal morphogenesis is very similar among mammals, birds, and reptiles. Despite this similarity, each group utilises quite different genetic triggers for sex determination. In mammals, testis development is initiated by action of the Y‐chromosome gene SRY. Current evidence suggests that SRY may act together with a related gene, SOX9, to activate another gene(s) in the pathway of testicular differentiation. A downstream candidate for regulation by SRY and SOX9 is AMH. In mouse, Sox9 is expressed in the Sertoli cells of the embryonic testis and it precedes the onset of Amh expression. During mouse gonadogenesis, Amh is confined to the embryonic testis, although it later shows postnatal expression in the ovary. Reptiles such as the American alligator, which exhibit temperature‐dependent sex determination (TSD) do not have dimorphic sex chromosomes and apparently no SRY orthologue. SOX9 is expressed during testis differentiation in the alligator; however, it appears to be expressed too late to cause testis determination. Here we describe the cloning and expression of the alligator AMH gene and show that AMH expression precedes SOX9 expression during testis differentiation. This is the opposite to that observed in the mouse where SOX9 precedes AMH expression. The data presented here, as well as findings from recent expression studies in the chick, suggest that AMH expression is not regulated by SOX9 in the non‐mammalian vertebrates. Dev Dyn 1999;216:411–419. ©1999 Wiley‐Liss, Inc.
Percutaneous mitral valve repair with the MitraClip system: acute results from a real world setting

Aims This study sought to evaluate the feasibility and early outcomes of a percutaneous edge-to-edge repair approach for mitral valve regurgitation with the MitraClip® system (Evalve, Inc., Menlo Park, CA, USA). Methods and results Patients were selected for the procedure based on the consensus of a multidisciplinary team. The primary efficacy endpoint was acute device success defined as clip placement with reduction of mitral regurgitation to ≤2+. The primary acute safety endpoint was 30-day freedom from major adverse events, defined as the composite of death, myocardial infarction, non-elective cardiac surgery for adverse events, renal failure, transfusion of >2 units of blood, ventilation for >48 h, deep wound infection, septicaemia, and new onset of atrial fibrillation. Thirty-one patients (median age 71, male 81%) were treated between August 2008 and July 2009. Eighteen patients (58%) presented with functional disease and 13 patients (42%) presented with organic degenerative disease. A clip was successfully implanted in 19 patients (61%) and two clips in 12 patients (39%). The median device implantation time was 80 min. At 30 days, there was an intra-procedural cardiac tamponade and a non-cardiac death, resulting in a primary safety endpoint of 93.6% [95% confidence interval (CI) 77.2–98.9]. Acute device success was observed in 96.8% of patients (95% CI 81.5–99.8). Compared with baseline, left ventricular diameters, diastolic left ventricular volume, diastolic annular septal–lateral dimension, and mitral valve area significantly diminished at 30 days. Conclusion Our initial results with the MitraClip device in a very small number of patients indicate that percutaneous edge-to-edge mitral valve repair is feasible and may be accomplished with favourable short-term safety and efficacy results.
Insulin Receptor Substrate 1 Translocation to the Nucleus by the Human JC Virus T-antigen*

Insulin receptor substrate 1 (IRS-1) is the major signaling molecule for the insulin and insulin-like growth factor I receptors, which transduces both metabolic and growth-promoting signals, and has transforming properties when overexpressed in the cells. Here we show that IRS-1 is translocated to the nucleus in the presence of the early viral protein-T-antigen of the human polyomavirus JC. Nuclear IRS-1 was detected in T-antigen-positive cell lines and in T-antigen-positive biopsies from patients diagnosed with medulloblastoma. The IRS-1 domain responsible for a direct JC virus T-antigen binding was localized within the N-terminal portion of IRS-1 molecule, and the binding was independent from IRS-1 tyrosine phosphorylation and was strongly inhibited by IRS-1 serine phosphorylation. In addition, competition for the IRS-1-T-antigen binding by a dominant negative mutant of IRS-1 inhibited growth and survival of JC virus T-antigen-transformed cells in anchorage-independent culture conditions. Based on these findings, we propose a novel role for the IRS-1-T-antigen complex in controlling cellular equilibrium during viral infection. It may involve uncoupling of IRS-1 from its surface receptor and translocation of its function to the nucleus.
Effects of serotonergic activation by 5-hydroxytryptophan on sleep and body temperature of C57BL/6J and interleukin-6-deficient mice are dose and time related.

STUDY OBJECTIVES Extensive data implicate serotonin (5-hydroxytryptamine [5-HT]) in the regulation of sleep. Jouvet has hypothesized that 5-HT promotes wakefulness, yet is necessary for subsequent non-rapid eye movement (NREM) sleep, actions he proposes to be mediated by sleep factors. Studies in rat support this dual role for 5-HT. The objectives of this study were to (1) determine effects of serotonergic activation on sleep of mice and (2) elucidate a potential role for the cytokine interleukin-6 as a sleep factor mediating serotonergic effects on sleep. DESIGN C57BL/6J and B6.129S6-II6(tm1Kopf)(interleukin-6 knockout [IL-6 KO]) mice were purchased from the Jackson Laboratory and instrumented for recording the electroencephalogram and body temperature. After recovery, separate groups of mice were injected intraperitoneally at either light or dark onset with vehicle or with the 5-HT precursor 5-hydroxytryptophan (5-HTP). Sleep-wake behavior was determined and body temperature recorded for 24 hours after injections. RESULTS 5-HTP induced hypothermia in both mouse strains. When injected at dark onset, the highest dose of 5-HTP (200 mg/kg) increased NREM sleep. Light onset administration initially increased wakefulness, with increases in NREM sleep apparent only during the subsequent dark period. For most parameters, there were no differences in responses between strains. However IL-6 KO mice at some doses exhibited a greater increase in NREM sleep. CONCLUSIONS 5-HTP alters sleep-wake behavior and body temperature of mice in a manner similar to that of rats. Increases in NREM sleep after 5-HTP are apparent only during the dark period, which may represent a fundamental property of the serotonergic system. These results suggest that 5-HT should not be considered either wake promoting or NREM sleep promoting. Rather, the role of 5-HT in the regulation of sleep-wake behavior must be considered within the context of the degree to which the system is activated and the time at which the activation occurs.
Quantification of polyhydroxyalkanoates in mixed and pure cultures biomass by Fourier transform infrared spectroscopy: comparison of different approaches

Fourier transform infrared (FTIR) spectroscopy was used in this study for the rapid quantification of polyhydroxyalkanoates (PHA) in mixed and pure culture bacterial biomass. Three different statistical analysis methods (regression, partial least squares (PLS) and nonlinear) were applied to the FTIR data and the results were plotted against the PHA values measured with the reference gas chromatography technique. All methods predicted PHA content in mixed culture biomass with comparable efficiency, indicated by similar residuals values. The PHA in these cultures ranged from low to medium concentration (0–44 wt% of dried biomass content). However, for the analysis of the combined mixed and pure culture biomass with PHA concentration ranging from low to high (0–93% of dried biomass content), the PLS method was most efficient. This paper reports, for the first time, the use of a single calibration model constructed with a combination of mixed and pure cultures covering a wide PHA range, for predicting PHA content in biomass.
Restricted access: spatial sequestration of damaged proteins during stress and aging

The accumulation of damaged and aggregated proteins is a hallmark of aging and increased proteotoxic stress. To limit the toxicity of damaged and aggregated proteins and to ensure that the damage is not inherited by succeeding cell generations, a system of spatial quality control operates to sequester damaged/aggregated proteins into inclusions at specific protective sites. Such spatial sequestration and asymmetric segregation of damaged proteins have emerged as key processes required for cellular rejuvenation. In this review, we summarize findings on the nature of the different quality control sites identified in yeast, on genetic determinants required for spatial quality control, and on how aggregates are recognized depending on the stress generating them. We also briefly compare the yeast system to spatial quality control in other organisms. The data accumulated demonstrate that spatial quality control involves factors beyond the canonical quality control factors, such as chaperones and proteases, and opens up new venues in approaching how proteotoxicity might be mitigated, or delayed, upon aging.
Vascular pattern localization via temporal signature

Accurate vascular pattern localization has many applications in the diverse scientific and application domains. For example, vascular patterns not only have been widely used as a biometric-based human identification method that is inexpensive, secure and easy to use, but also have produced more accurate heart-rate estimation using conventional RGB camera by defining regions of interest along the vascular patterns instead of the entire exposed skin area. In addition, extracting temporal activity along vascular patterns can further enable targeted monitoring of other physiological parameters, such as blood flow and blood pulse transition time. This paper presents a method for robust and accurate vascular pattern localization using conventional RGB imaging systems. Our approach overcomes current limitations of systems that use still RGB images for vascular pathway localization - which produce low contrast between areas of vascular patterns and skin tissues and are sensitive to skin color variations - by capturing the temporal differences between these two areas from RGB videos.
Phylogeny and Ontogeny of the Habenular Structure

Habenula is an epithalamic nucleus connecting the forebrain with the ventral midbrain and hindbrain that plays a pivotal role in decision making by regulating dopaminergic and serotonergic activities. Intriguingly, habenula has also attracted interest as a model for brain asymmetry, since many vertebrates show left–right differences in habenula size and neural circuitry. Despite the functional significance of this nucleus, few studies have addressed the molecular mechanisms underlying habenular development. Mammalian habenula consists of the medial and lateral habenulae, which have distinct neural connectivity. The habenula shows phylogenetic conservation from fish to human, and studies using genetically accessible model animals have provided molecular insights into the developmental mechanisms of the habenula. The results suggest that development of the habenular asymmetry is mediated by differential regulation of the neurogenetic period for generating specific neuronal subtypes. Since the orientation and size ratio of the medial and lateral habenulae differ across species, the evolution of those subregions within the habenula may also reflect changes in neurogenesis duration for each habenular subdivision according to the evolutionary process.
Structural Models of Nonequilibrium Strategic Thinking: Theory, Evidence, and Applications

Most applications of game theory assume equilibrium, justified by presuming either that learning will have converged to one, or that equilibrium approximates people’s strategic thinking even when a learning justification is implausible. Yet several recent experimental and empirical studies suggest that people’s initial responses to games often deviate systematically from equilibrium, and that structural nonequilibrium “level-k” or “cognitive hierarchy” models often out-predict equilibrium. Even when learning is possible and converges to equilibrium, such models allow better predictions of history-dependent limiting outcomes. This paper surveys recent theory and evidence on strategic thinking and illustrates the applications of level-k models in economics. (JEL C70, D03, D82, D83)
Validation of anti-aging drugs by treating age-related diseases

Humans die from age-related diseases, which are deadly manifestations of the aging process. In order to extend life span, an anti-aging drug must delay age-related diseases. All together age-related diseases are the best biomarker of aging. Once a drug is used for treatment of any one chronic disease, its effect against other diseases (atherosclerosis, cancer, prostate enlargement, osteoporosis, insulin resistance, Alzheimer's and Parkinson's diseases, age-related macular degeneration) may be evaluated in the same group of patients. If the group is large, then the anti-aging effect could be validated in a couple of years. Startlingly, retrospective analysis of clinical and preclinical data reveals four potential anti-aging modalities.
Towards agile security assurance

Agile development methodologies are gaining acceptance in the software industry. If they are to be used for constructing security-critical solutions, what do we do about assurance? This paper examines how conventional security assurance suits agile methodologies for developing software-intensive systems. It classifies security assurance methods and techniques with regards to their clash with agile development. Suggestions are made for alleviating mismatches between these two methods.
On-line scheduling of a single machine to minimize total weighted completion time

This paper considers the on-line scheduling of a single machine in which jobs arrive over time, and preemption is not allowed. The goal is to minimize the total weighted completion time. We show that a simple modification of the shortest weighted processing time rule has a competitive ratio of 2. This result is established using a new proof technique which does not rely explicitly on a lower bound on the optimal objective function value. Since it is known that no on-line algorithm can have a competitive ratio of less than 2, we have resolved the open issue of determining the minimum competitive ratio for this problem.
Ultra low power 12-Bit SAR ADC for wireless sensing applications

This paper presents a 12-bit SA-ADC for portable low power wireless sensor systems. The proposed SA-ADC operates for rail-to-rail input range and achieves low power consumption. Split capacitor array based DAC and a novel charge-integration based dynamic comparator are used for low power consumption of the ADC. Measured DNL and INL are -0.59/0.67 LSB and -1.2/1.33 LSB respectively. At sampling rate of 100-kS/s with 1.8-V supply, the ADC consumes only 2-μW power and achieves a SNDR of 64.42-dB, SFDR of 71.2-dB resulting in an FoM of 14-fJ/Conversion-step. The ADC core occupies an area of 0.238-mm2 and is fabricated in AMS 0.35-μm CMOS technology.