Miracle-dz/UniFAR-FTUs huggingface dataset:
Object/Context Specific Memory Deficits following Medial Frontal Cortex Damage in Mice

Recent evidence suggests that the medial prefrontal cortex (MFC) is important for processing contextual information. Here we evaluate the performance of mice with MFC damage in a discrimination task that requires an association between an object and the context in which it was experienced (the object/context mismatch task), as well as a version of the novel object preference task that does not require knowledge of contextual information to resolve. Adult C57/BL6 mice received aspiration lesions of the MFC or control surgery. Upon recovery, mice were tested in the object/context mismatch and novel object preference tasks. The object/context mismatch task involved exposing mice to two different contexts, each of which housed a unique pair of identical objects. After a brief delay, mice were re-exposed to one of the contexts, this time with one object that was congruent with that context and one that was not. Novel object preference was performed within a single context, housing an identical pair of objects. After the initial exposure and following a brief delay, mice were re-exposed to the context, this time housing a familiar and a novel object. Control mice were able to successfully resolve the object/context mismatch and novel object preference discriminations, investigating the incongruent/novel object within each task significantly greater than chance. Mice with MFC damage experienced deficits in the object/context mismatch task but not the novel object preference task. These findings add to a growing body of evidence that demonstrate a critical role for the MFC in contextual information processing.
Augmenting the virtual domain with physical and social elements: towards a paradigm shift in computer entertainment technology

In this paper, means of enriching computer entertainment experiences by emphasizing physical and social game elements are discussed. A conceptual framework in which the relations between the virtual, the physical, and the social domains are modelled is presented. Interfaces that mediate between the domains are discussed along with a complementary software architecture that helps developing hybrid computer games. Finally, sample games that follow the approach of physical and social augmentation are presented.
Mechanical Properties and Tensile Failure Analysis of Novel Bio-absorbable Mg-Zn-Cu and Mg-Zn-Se Alloys for Endovascular Applications.

In this paper, the mechanical properties and tensile failure mechanism of two novel bio-absorbable as-cast Mg-Zn-Se and Mg-Zn-Cu alloys for endovascular medical applications are characterized. Alloys were manufactured using an ARC melting process and tested as-cast with compositions of Mg-Zn-Se and Mg-Zn-Cu, being 98/1/1 wt. % respectively. Nanoindentation testing conducted at room temperature was used to characterize the elastic modulus (E) and surface hardness (H) for both the bare alloys and the air formed oxide layer. As compared to currently available shape memory alloys and degradable as-cast alloys, these experimental alloys possess superior as-cast mechanical properties that can increase their biocompatibility, degradation kinetics, and the potential for medical device creation.
Anti-α-enolase antibody limits the invasion of myeloid-derived suppressor cells and attenuates their restraining effector T cell response

ABSTRACT Pancreatic Ductal Adenocarcinoma (PDA) is a very aggressive tumor for which effective therapeutical strategies are still lacking. Globally, the 5 y survival rate is 5–7% and surgery is the only potentially curative treatment. Immunotherapy represents a novel possibility for treating PDA, and myeloid-derived suppressor cells (MDSC), which are increased in cancer patients and correlate with metastatic burden and cancer stage, offer a new target in cancer therapy. We have previously shown that antibodies against the PDA-associated antigen α-enolase (ENO1) are detected in more than 60% of PDA patients and correlate with a better prognosis. Furthermore, ENO1-DNA vaccination in mice induced anti-ENO1 antibodies that mediated antitumor activity. In this study, the effects of anti-ENO1 binding on MDSC functions and on the T cell response were evaluated. Here, we show that MDSC express ENO1 on their surface, which increased after LPS stimulation. Moreover, anti-ENO1 mAb inhibited adhesion to endothelial cells, as well as in vitro and in vivo migration. Similarly, after ENO1 mAb treatment of MDSC, arginase activity decreased, while the secretion of pro-inflammatory cytokines (particularly IL-6) increased, and co-stimulatory molecule expression and suppression functions were only partially affected. Finally, we found that activated T cells in the presence of anti-ENO1 mAb-treated MDSC increased IFNγ and IL-17 secretion and decreased IL-10 and TGFβ secretion compared to control MDSC. In conclusion, anti-ENO1 antibodies may inhibit in vivo the infiltration into the tumor microenvironment of MDSC, and attenuate their restraining of effector T cell response, opening a new perspective to render PDA immunotherapy more effective.
Handle Region Peptide Counteracts the Beneficial Effects of the Renin Inhibitor Aliskiren in Spontaneously Hypertensive Rats

To investigate whether the putative (pro)renin receptor blocker, the handle region peptide (HRP), exerts effects on top of the blood pressure–lowering and cardioprotective effects of the renin inhibitor aliskiren, spontaneously hypertensive rats were implanted with telemetry transmitters to monitor heart rate and mean arterial pressure (MAP). After a 2-week recovery period, vehicle, aliskiren, HRP (100 and 1 mg/kg per day, respectively), and HRP+aliskiren were infused for 3 weeks using osmotic minipumps. Subsequently, the heart was removed to study coronary function according to Langendorff. Baseline MAP and heart rate in vehicle-treated rats were 146±3 mm Hg and 326±4 bpm. HRP did not affect MAP, whereas aliskiren and HRP+aliskiren lowered MAP (by maximally 29±2 and 20±1 mm Hg, respectively) without affecting heart rate. Aliskiren significantly reduced MAP throughout the 3-week infusion period, whereas the blood pressure–lowering effect of HRP+aliskiren returned to baseline within 2 weeks of treatment. In comparison with vehicle, aliskiren increased the endothelium-dependent response to bradykinin and decreased the response to angiotensin II in the coronary circulation, whereas these responses were not altered after treatment with HRP or HRP+aliskiren. HRP did not alter plasma renin activity, plasma angiotensin levels, or the renal angiotensin content, either alone or on top of aliskiren, nor did it alter the aliskiren-induced decrease in renal Ang II type 1 receptor expression. Yet, it did reverse the aliskiren-induced reduction in cardiomyocyte area, without affecting this area when given alone. In conclusion, HRP counteracts the beneficial effects of aliskiren on blood pressure, coronary function, and cardiac hypertrophy in an angiotensin-independent manner.
Feeling better? Trends in general health status.

OBJECTIVES We addressed three questions: Have recent improvements in old-age disability been mirrored in changes in self-reported general health status? Are general health status trends similar for younger and older Americans? Have changes in general health status been uniform across demographic and socioeconomic groups? METHODS Using logistic regression, we analyzed data from the 1982-2003 National Health Interview Surveys (n = 1,445,872 aged 18-69; n = 178,384 aged 70 and older). RESULTS The proportion of people aged 70 and older reporting disability declined at 1.38% per year and the proportion 70 and older reporting poor/fair health declined at 1.85% per year. There was less of a decline in reports of poor/fair health at younger ages. Trends for the 18-69 population showed widening health disparities by income but narrowing of the race/ethnicity and education gaps. In the older population, there was no change for those aged 80-84 and 85 and older, the race/ethnicity gap persisted, and both education and income differentials widened over time. DISCUSSION Declines in proportions reporting poor/fair health among the older population in recent decades mirror declines in disability. Although the younger population has not experienced such progress, its prevalence of poor/fair health is low throughout the 21-year analysis period. Of concern are the growing socioeconomic disparities in health for both younger and older populations.
Difficulties in R&D target-setting addressed through technology forecasting using data envelopment analysis

While multiple studies mention the difficulty of R&D target-setting, few studies exist which bring together reasons for these difficulties; nor do they delve deeply into addressing this issue in detail. Additionally, there are many studies conducted on single or subsets of commercial airplane technology, market, and economic parameters; but few have been conducted from a combined critical technological performance parameter perspective. This paper provides what appears to be one of the first studies outlining reasons for R&D target-setting difficulties through a literature review; then also provides the first set of analyses tied to a larger study applying a quantitative method addressing these difficulties. An emerging operations research method, Technology Forecasting Using Data Envelopment Analysis (TFDEA) was used for this set of initial results; including determining the state-of-art in commercial airplane technology. This is the first time TFDEA has been used as a focus for addressing R&D.
Capless LDO Regulator Achieving −76 dB PSR and 96.3 fs FOM

The performance of switching devices such as display driver ICs is degraded by large power supply noise at switching frequencies from a few hundreds of kilohertz to a few megahertz. In order to minimize the power supply noise, a low-dropout (LDO) regulator with higher power supply rejection (PSR) is essential. In this brief, a capless LDO regulator with a negative capacitance circuit and voltage damper is proposed for enhancing PSR and figure of merit (FOM), respectively, in switching devices. The proposed LDO regulator is fabricated in a $0.18~\boldsymbol {\mu }\text{m}$ CMOS. Measurement results show that the proposed LDO regulator achieves −76 dB PSR at 1 MHz and 96.3 fs FOM with a total on-chip capacitance of as small as 12.7 pF.
CYP2A13 in Human Respiratory Tissues and Lung Cancers: An Immunohistochemical Study with A New Peptide-Specific Antibody

Human cytochrome P450 2A13 (CYP2A13) is highly efficient in the metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and another potent carcinogen, aflatoxin B1 (AFB1). Although previous studies demonstrated that CYP2A13 mRNA is predominantly expressed in human respiratory tissues, expression of CYP2A13 protein in these tissues and the involved cell types have not been determined because of the lack of CYP2A13-specific antibodies. To explore the toxicological and physiological function of CYP2A13, it is important to understand the tissue/cellular distribution of CYP2A13 protein. In this study, we generated a peptide-specific antibody against human CYP2A13 and demonstrated by immunoblot analysis that this antibody does not cross-react with heterologously expressed human CYP2A6 and mouse CYP2A5 proteins, both sharing a high degree of amino acid sequence similarity with CYP2A13. Nor does the antibody cross-react with heterologously expressed human CYP3A4, CYP2S1, or any of the cytochrome P450 enzymes present in the human liver microsomes. Using this highly specific antibody for immunohistochemical staining, we detected a high level of CYP2A13 protein expression in the epithelial cells of human bronchus and trachea, but a rare distribution in the alveolar cells. There was little expression of CYP2A13 protein in different types of lung cancers. In consideration of the high efficiency of CYP2A13 in NNK metabolic activation, our result is consistent with the reported observations that most smoking-related human lung cancers are bronchogenic and supports that CYP2A13-catalyzed in situ activation may play a critical role in human lung carcinogenesis related to NNK and AFB1 exposure.
The integral membrane protein ITM2A, a transcriptional target of PKA-CREB, regulates autophagic flux via interaction with the vacuolar ATPase

The PKA-CREB signaling pathway is involved in many cellular processes including autophagy. Recent studies demonstrated that PKA-CREB inhibits autophagy in yeast; however, the role of PKA-CREB signaling in mammalian cell autophagy has not been fully characterized. Here, we report that the integral membrane protein ITM2A expression is positively regulated by PKA-CREB signaling and ITM2A expression interferes with autophagic flux by interacting with vacuolar ATPase (v-ATPase). The ITM2A promoter contains a CRE element, and mutation at the CRE consensus site decreases the promoter activity. Forskolin treatment and PKA expression activate the ITM2A promoter confirming that ITM2A expression is dependent on the PKA-CREB pathway. ITM2A expression results in the accumulation of autophagosomes and interferes with autolysosome formation by blocking autophagic flux. We demonstrated that ITM2A physically interacts with v-ATPase and inhibits lysosomal function. These results support the notion that PKA-CREB signaling pathway regulates ITM2A expression, which negatively regulates autophagic flux by interfering with the function of v-ATPase.
Incidence and factors associated with flare-ups in a post graduate programme in the indian population

Objectives: The study had twin objectives: to assess the incidence of flare-ups (a severe problem requiring an unscheduled visit and treatment) among patients who received endodontic treatment in the Department of Conservative Dentistry and Endodontics in Vyas Dental college and hospital, Jodhpur during a period of one year, and also to examine the correlation with pre-operative and operative variables. Material and Methods: Data was collected from 1023 teeth from 916 patients who had received endodontic treatment over a 12- month period. Information was obtained for each patient treated, including pulp and peri-radicular diagnosis for the tooth, presence of pre-operatory pain, type of medication being used, type of instrumentation technique used and number of appointments needed to complete the root canal treatment. Results: The results showed an incidence of 2.35% for flare-ups from 1023 endodontically treated teeth. Statistical analysis was done using the chi-square test. Conclusions: Flare-ups were found to be affected significantly by gender of patient, presence of radiolucent lesions, patients taking pre-operative analgesic or anti-inflammatory drugs and on type of instrumentation technique. In contrast, there was no correlation between flare-ups and age, different arch/tooth groups and single or multiple visit endodontics. Key words:Anti-inflammatory, flare-ups, instrumentation, prospective.
Iron-Sulfur (Fe/S) Protein Biogenesis: Phylogenomic and Genetic Studies of A-Type Carriers

Iron sulfur (Fe/S) proteins are ubiquitous and participate in multiple biological processes, from photosynthesis to DNA repair. Iron and sulfur are highly reactive chemical species, and the mechanisms allowing the multiprotein systems ISC and SUF to assist Fe/S cluster formation in vivo have attracted considerable attention. Here, A-Type components of these systems (ATCs for A-Type Carriers) are studied by phylogenomic and genetic analyses. ATCs that have emerged in the last common ancestor of bacteria were conserved in most bacteria and were acquired by eukaryotes and few archaea via horizontal gene transfers. Many bacteria contain multiple ATCs, as a result of gene duplication and/or horizontal gene transfer events. Based on evolutionary considerations, we could define three subfamilies: ATC-I, -II and -III. Escherichia coli, which has one ATC-I (ErpA) and two ATC-IIs (IscA and SufA), was used as a model to investigate functional redundancy between ATCs in vivo. Genetic analyses revealed that, under aerobiosis, E. coli IscA and SufA are functionally redundant carriers, as both are potentially able to receive an Fe/S cluster from IscU or the SufBCD complex and transfer it to ErpA. In contrast, under anaerobiosis, redundancy occurs between ErpA and IscA, which are both potentially able to receive Fe/S clusters from IscU and transfer them to an apotarget. Our combined phylogenomic and genetic study indicates that ATCs play a crucial role in conveying ready-made Fe/S clusters from components of the biogenesis systems to apotargets. We propose a model wherein the conserved biochemical function of ATCs provides multiple paths for supplying Fe/S clusters to apotargets. This model predicts the occurrence of a dynamic network, the structure and composition of which vary with the growth conditions. As an illustration, we depict three ways for a given protein to be matured, which appears to be dependent on the demand for Fe/S biogenesis.
Indirect IL-4 Pathway in Type 1 Immunity1

Recall Ag-specific IL-4 was detected in the spleen and in the blood, but not in lymph nodes of mice in which polarized type 1 immunity was induced. This IL-4 was not produced by T cells, but soluble factors secreted by the recall Ag-activated T cells, including IL-3, triggered cells of the innate immune system, primarily mast cells, to secrete IL-4. This notion has profound implications for immunodiagnostics: the detection of apparently recall Ag-specific IL-4 does not necessarily reflect the presence of Th2 or Th0 memory T cells with long-term cytokine commitment as is of interest for assessing adoptive immunity. We found that in vivo the indirect IL-4 pathway did not suffice to trigger IgE isotype switching, but promoted IgG1 production and inhibited type 1 T cell differentiation. Therefore, the indirect IL-4 pathway can explain partial type 2 immune response phenotypes in vivo in face of unipolar Th1 T cell immunity. The representation of mast cells in different tissues may explain why immune responses in certain organs are more type 2 biased. Therefore, the indirect pathway of IL-4 production represents a novel type of interaction between the innate and the adoptive immune system that can contribute to the outcome of host defense and immune pathology.
Determination of T-Lymphocyte Subsets in a North African Population (Tunisia): Establishment of Normal Ranges and Results in HIV-Infected Individuals

Human Immunodeficiency Virus (HIV) infection is characterized by a depletion of the CD4+ T-lymphocytes. Absolute counts of CD3+CD4+ cells have been used in monitoring the progression of this disease and in assessing clinical trials of drugs developed to treat HIV infection and related complications [6,10]. In 1993, the definition of AIDS was revised to include HIV-infected persons whose CD4+ Tlymphocytes were ≤ 200 per μl, even in the absence of opportunistic infections or neoplasm. Both the CDC (Center for Disease Control) and WHO (World Health Organization) have emphasized the need to study lymphocyte subsets in normal populations [3]. It is thus necessary for a testing laboratory to establish normal ranges for these subsets in its local population. A number of studies have been done on lymphocyte subsets in healthy individuals. There is, however, a paucity of published data about Tunisians and North Africans in general. Therefore, our first objective in the present study was the establishment of normal ranges for CD3+CD4+ and CD3+CD8+ cells in a healthy Tunisian population. After that, the second step was the assessment of lymphocyte subsets in HIV infected individuals.
Familial Pulmonary Capillary Hemangiomatosis Early in Life

Background. Pulmonary capillary hemangiomatosis (PCH) is a rare disease, especially in infancy. Four infants have been reported up to the age of 12 months. So far, no familial patients are observed at this age. Patients. We report three siblings, two female newborns and a foetus of 15-week gestation of unrelated, healthy parents suffering from histologically proven PCH. The first girl presented with increased O2 requirements shortly after birth and patent ductus arteriosus (PDA). She subsequently developed progressive respiratory failure and pulmonary hypertension and died at the age of five months. The second girl presented with clinical signs of bronchial obstruction at the age of three months. The work-up showed a PDA—which was surgically closed—pulmonary hypertension, and bronchial wall instability with stenosis of the left main bronchus. Transient oxygen therapy was required with viral infections. The girl is now six years old and clinically stable without additional O2 requirements. Failure to thrive during infancy and a somewhat delayed development may be the consequence of the disease itself but also could be attributed to repeated episodes of respiratory failure and a long-term systemic steroid therapy. The third pregnancy ended as spontaneous abortion. The foetus showed histological signs of PCH. Conclusion. Despite the differences in clinical course, the trias of PCH, PDA, and pulmonary hypertension in the two life born girls suggests a genetic background.
Influenza A(H3N2) Virus in Swine at Agricultural Fairs and Transmission to Humans, Michigan and Ohio, USA, 2016

In 2016, a total of 18 human infections with influenza A(H3N2) virus occurred after exposure to influenza-infected swine at 7 agricultural fairs. Sixteen of these cases were the result of infection by a reassorted virus with increasing prevalence among US swine containing a hemagglutinin gene from 2010–11 human seasonal H3N2 strains.
Architecture and Implementation of a Low-Power LVDS Output Buffer for High-Speed Applications

This paper presents a new detailed analysis of low-voltage differential signaling (LVDS) output buffers that are intended for use in high-speed integrated circuits. Three theoretically possible architectures of a LVDS output driver are discussed in rigorous detail, resulting in the recognition of the most power-conserving circuit configuration. An innovative realization of this identified low-power architecture is presented in this paper along with computer simulation results and test lab measurement data. The novel LVDS driver is designed using a unique hetero-junction bipolar transistor structure. Computer simulation results show total current consumption of 6.3 mA for the bipolar driver at a 1-GHz clock frequency while operating from a positive supply voltage between 1.7 and 3.3 V, as well as demonstrate full stage compliance with all the requirements of the IEEE 1596.3-1996 standard. The presented version of the buffer was utilized in a multiplexer/demultiplexer chip set that was fabricated in a modern 50-GHz-fT SiGe technology. Test results of the LVDS output buffer taken from five different chip samples reveal high-quality output eyes with more than 0.99 UI opening and close matching between the measured parameters and simulation results
And Sensitivity in Unselected Samples of Twins

It is a common observation that individuals differ greatly in their consumption of alcohol and, if they do drink, in their sensitivity to it. Some people appear greatly affected by even small doses, others consume large amounts of alcohol with little apparent effect on their behaviour or performance. The causes of this normal variation both in consumption and sensitivity are of considerable interest, not least because they may provide clues to the etiology of the abnormal condition alcoholism.