Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumor necrosis factor α gene expression and the response to interferon in chronic hepatitis C

Tumor necrosis factor α (TNF‐α) is a cytokine with pleiotropic properties that is induced in a variety of pathological situations including viral infections. In this work, we analyzed the expression of TNF‐α gene in patients with chronic hepatitis C. Serum TNF‐α levels were found to be elevated in all chronic hepatitis C patients including those cases presenting sustained biochemical remission of the disease after interferon therapy. Untreated patients with chronic hepatitis C showed increased TNF‐α messenger RNA (mRNA) levels in the liver and mononuclear cells as compared with healthy controls. After completion of treatment with interferon, patients experiencing sustained complete response showed values of TNF‐α mRNA, both in the liver and in peripheral mononuclear cells, within the normal range, significantly lower than patients who did not respond to interferon and than those with complete response who relapsed after interferon withdrawal. Pretreatment values of TNF‐α mRNA were lower in long‐term responders to interferon than in cases who failed to respond to the treatment. Values of TNF‐α mRNA in the liver or in mononuclear cells were higher in specimens with positive hepatitis C virus (HCV) RNA than in those samples where the virus was undetectable. Neither the intensity of the liver damage nor the amount of HCV RNA in serum or in cells showed correlation with the levels of TNF‐α transcripts in peripheral mononuclear cells but it was found that high TNF‐α values were associated with genotype 1b. In conclusion, there is an enhanced expression of TNF‐α in HCV infection. High levels of this cytokine may play a role in the resistance to interferon therapy.
Rates of pediatric and adolescent injuries by year of age.

OBJECTIVE The purpose of this study was to analyze causes of injury hospitalization/death by individual year of age and by specific causes of injury and to examine how well aggregate age groups represented individual year-of-age rates. METHODS Hospital discharge data and death certificate data for California residents age 0 to 19 years with a principal external cause of injury code (E-code) of E800 to E869, E880 to E929, or E950 to E999, calendar year 1997, were analyzed. Annual rates of injury hospitalization/death by year of age were calculated using combined hospital discharges and deaths as the numerator for major causes and important subcategories. For comparison, rates of injury hospitalization/death were calculated for conventional vital statistics age groups: <1 year, 1 to 4 years; 5 to 9 years, 10 to 14 years, and 15 to 19 years. RESULTS In 1997 in California, 35 277 children and adolescents 0 to 19 years were hospitalized and 1934 died as a result of injury, a ratio of 17 hospitalizations to 1 death. The distribution was bimodal with rates highest among 18-year-olds (732/100 000) and 1-year-olds (495/100 000). Except for children who were 5 to 9 years of age, the group rates for all injuries were not reflective of the individual year-of-age rates. In specific categories of injuries, variation in rates by year of age were masked by age group rates for unintentional poisoning among 1- to 4-year-olds, self-inflicted poisoning for 10- to 19-year-olds, falls from playground equipment among 5- to 9-year-olds, falls from furniture among 1- to 4-year-olds, and motor vehicle occupant injury rates among 10- to 19-year-olds. The peak rate of falls from playground equipment among 6-year-olds (34/100 000) was more than twice the rate for 9-year-olds (15/1000,000). Motor vehicle occupant injury rates doubled between 10 and 14 years of age and quadrupled between 14 and 18 years of age. CONCLUSIONS Analyses using conventional age groups did not identify the age of highest risk for many causes of childhood injury. Changes in the rates often transected the traditional age groups and were not apparent with conventional age group analysis. These data can inform on the age at which to begin a specific injury intervention and on how to allocate resources. These data allow pediatricians and other health professionals to be anticipatory in providing injury prevention counseling. The greatest impact can be achieved by making the counseling topic most age appropriate in anticipation of the high-risk period.
Thinned fiber Bragg gratings as refractive index sensors

In this work, highly sensitive refractive index measurements have been experimentally demonstrated by using thinned fiber Bragg grating (FBG) sensors. When the cladding diameter is reduced, significant changes in the effective refractive index occur due to surrounding medium refractive index modifications, leading to Bragg wavelength shifts. Uniformly thinned FBGs have been obtained by using wet chemical etching in hydrofluoric acid solutions. In order to prove sensor sensitivity, experimental tests have been carried out by using glycerine solutions with well-known refractive indices. Obtained results agree well with the numerical analysis carried out by using the three-layer fiber model. If the cladding layer is completely removed, resolutions of /spl ap/10/sup -5/ and /spl ap/10/sup -4/ for the outer refractive index around 1.450 and 1.333, respectively, are possible. Finally, a novel approach based on the selective etching along the grating region has been analyzed, leading to high-sensitivity refractive index sensors based on intensity measurements.
A Serious Game: Performance Management in Italian Ministries

ABSTRACT In 2009, extensive performance management measures were introduced in Italian ministries, following a significant legislative initiative. The objectives that were initially set, however, have not yet been reached. In the paper, the authors discuss this issue, starting with the consideration of the main limits on the introduction of performance measurement systems in public organizations. The discussion leads to the conclusion that the shortcomings of performance management depend not only on the persistence of an administrative paradigm, but also on the underestimated impact of control over organizational behavior; where the latter is linked not to mechanical logic processes, but to more sophisticated forms of reactivity or even counter-intuitive sense-making processes.
Identification of Binary Interactions between Human Cytomegalovirus Virion Proteins

ABSTRACT Human cytomegalovirus (HCMV) virions are composed of a DNA-containing nucleocapsid surrounded by a tegument layer and host-derived lipid envelope studded with virally encoded glycoproteins. These complex virions are estimated to be composed of more than 50 viral proteins. Assembly of HCMV virions is poorly understood, especially with respect to acquisition of the tegument; however, it is thought to involve the stepwise addition of virion components through protein-protein interactions. We sought to identify interactions among HCMV virion proteins using yeast two-hybrid analysis. Using 33 known capsid and tegument proteins, we tested 1,089 pairwise combinations for binary interaction in the two-hybrid assay. We identified 24 interactions among HCMV virion proteins, including 13 novel interactions among tegument proteins and one novel interaction between capsid proteins. Several of these novel interactions were confirmed by coimmunoprecipitation of protein complexes from transfected cells. In addition, we demonstrate three of these interactions in the context of HCMV infection. This study reveals several new protein-protein interactions among HCMV tegument proteins, some of which are likely important for HCMV replication and pathogenesis.
Integration of New Neurons into Functional Neural Networks

Although it is established that new granule cells can be born and can survive in the adult mammalian hippocampus, there remains some question concerning the functional integration of these neurons into behaviorally relevant neural networks. By using high-resolution confocal microscopy, we have applied a new strategy to address the question of functional integration of newborn neurons into networks that mediate spatial information processing and memory formation. Exploration-induced expression of the immediate-early gene Arc in hippocampal cells has been linked to cellular activity observed in electrophysiological recordings under the same behavioral conditions. We investigated whether mature (5-month-old), newborn granule cells express Arc in response to a discrete spatial experience by detecting the expression of Arc in combination with NeuN (neuron-specific nuclear protein)-positive and bromodeoxyuridine-positive cells. We found that mature new granule cells do indeed express Arc in response to an exploration experience, supporting the idea that these cells are well integrated into hippocampal circuits. The proportion of mature newborn neurons that expressed Arc in response to exploration, however, was significantly higher (∼2.8%) than the proportion of cells that expressed Arc in the already existing population of granule cells (∼1.6%; p < 0.01). This finding extends previous data suggesting that the cellular physiology of newborn granule neurons differs from that of the existing population by indicating that these properties are retained in mature adult-generated neurons. Thus, these data have interesting implications for network models of spatial information processing and the role of hippocampal circuits in memory, indicating that mature new neurons are selectively recruited into hippocampal cell assemblies in higher proportions than older cells.
Manipulation of dendritic cell functions by human cytomegalovirus

Dendritic cells are the most potent antigen-presenting cells of the mammalian immune system and are central to the initiation and maintenance of the adaptive immune response. They are crucial for the presentation of antigen to T cells and B cells, as well as the induction of chemokines and proinflammatory cytokines, which orchestrate the balance of the cell-mediated (Th1) and antibody (Th2) response. This ability of dendritic cells to present antigen and release chemokines and cytokines also bridges the innate and adaptive immune responses by driving T cell activation. These cells thus possess key immunological functions that make them the front line of defence for the targeting and clearance of any invading pathogen and, as such, they underpin the host immune response to infection. For efficient infection, invading pathogens often need to overcome these sentinel immune functions. It is therefore not surprising that pathogens have evolved numerous mechanisms to target dendritic cell functions directly or indirectly during infection, and at least one herpesvirus – human cytomegalovirus – has evolved a life cycle that hijacks dendritic cells for its long-term persistence in the infected host.
Brief Self-Report Scales Assessing Life History Dimensions of Mating and Parenting Effort

Life history theory (LHT) is a powerful evolutionary framework for understanding physiological, psychological, and behavioral variation both between and within species. Researchers and theorists are increasingly integrating LHT into evolutionary psychology, as it provides a strong foundation for research across many topical areas. Human life history variation has been represented in psychological and behavioral research in several ways, including indicators of conditions in the developmental environment, indicators of conditions in the current environment, and indicators of maturation and life milestones (e.g., menarche, initial sexual activity, first pregnancy), and in self-report survey scale measures. Survey scale measures have included constructs such as time perspective and future discounting, although the most widely used index is a constellation of indicators assessing the K-factor, thought to index general life history speed (from fast to slow). The current project examined the utility of two brief self-report survey measures assessing the life history dimensions of mating effort and parenting effort with a large undergraduate sample in the United States. Consistent with the theory, items reflected two inversely related dimensions. In regressions including the K-factor, the Mating Effort Scale proved to be a powerful predictor of other constructs and indicators related to life history variation. The Parenting Effort Scale had less predictive power overall, although it explained unique variance across several constructs and was the only unique predictor of the number of long-term (serious and committed) relationships. These scales may be valuable additions to self-report survey research projects examining life history variation.
Type D Retrovirus Capsid Assembly and Release Are Active Events Requiring ATP

ABSTRACT Mason-Pfizer monkey virus (M-PMV), the prototype type D retrovirus, differs from most other retroviruses by assembling its Gag polyproteins into procapsids in the cytoplasm of infected cells. Once assembled, the procapsids migrate to the plasma membrane, where they acquire their envelope during budding. Because the processes of M-PMV protein transport, procapsid assembly, and budding are temporally and spatially unlinked, we have been able to determine whether cellular proteins play an active role during the different stages of procapsid morphogenesis. We report here that at least two stages of morphogenesis require ATP. Both procapsid assembly and procapsid transport to the plasma membrane were reversibly blocked by treating infected cells with sodium azide and 2-deoxy-d-glucose, which we show rapidly and reversibly depletes cellular ATP pools. Assembly of procapsids in vitro in a cell-free translation/assembly system was inhibited by the addition of nonhydrolyzable ATP analogs, suggesting that ATP hydrolysis and not just ATP binding is required. Since retrovirus Gag polyproteins do not bind or hydrolyze ATP, these results demonstrate that cellular components must play an active role during retrovirus morphogenesis.
The Widom–Rowlinson mixture on a sphere: elimination of exponential slowing down at first-order phase transitions

Computer simulations of first-order phase transitions using ‘standard’ toroidal boundary conditions are generally hampered by exponential slowing down. This is partly due to interface formation, and partly due to shape transitions. The latter occur when droplets become large such that they self-interact through the periodic boundaries. On a spherical simulation topology, however, shape transitions are absent. We expect that by using an appropriate bias function, exponential slowing down can be largely eliminated. In this work, these ideas are applied to the two-dimensional Widom–Rowlinson mixture confined to the surface of a sphere. Indeed, on the sphere, we find that the number of Monte Carlo steps needed to sample a first-order phase transition does not increase exponentially with system size, but rather as a power law , with α≈2.5, and V the system area. This is remarkably close to a random walk for which αRW = 2. The benefit of this improved scaling behavior for biased sampling methods, such as the Wang–Landau algorithm, is investigated in detail.
Obesity is associated with sensorineural hearing loss in adolescents

Childhood obesity, defined as body mass index (BMI) ≥ 95%, is a significant health problem associated with a variety of disorders, and in adults it has been found to be a risk factor for hearing loss. We investigated the hypothesis that obese children are at increased risk of sensorineural hearing loss (SNHL).
Chronic Reduction of GIP Secretion Alleviates Obesity and Insulin Resistance Under High-Fat Diet Conditions

Gastric inhibitory polypeptide (GIP) exhibits potent insulinotropic effects on β-cells and anabolic effects on bone formation and fat accumulation. We explored the impact of reduced GIP levels in vivo on glucose homeostasis, bone formation, and fat accumulation in a novel GIP-GFP knock-in (KI) mouse. We generated GIP-GFP KI mice with a truncated prepro-GIP gene. The phenotype was assessed in heterozygous and homozygous states in mice on a control fat diet and a high-fat diet (HFD) in vivo and in vitro. Heterozygous GIP-GFP KI mice (GIP-reduced mice [GIPgfp/+]) exhibited reduced GIP secretion; in the homozygous state (GIP-lacking mice [GIPgfp/gfp]), GIP secretion was undetectable. When fed standard chow, GIPgfp/+ and GIPgfp/gfp mice showed mild glucose intolerance with decreased insulin levels; bone volume was decreased in GIPgfp/gfp mice and preserved in GIPgfp/+ mice. Under an HFD, glucose levels during an oral glucose tolerance test were similar in wild-type, GIPgfp/+, and GIPgfp/gfp mice, while insulin secretion remained lower. GIPgfp/+ and GIPgfp/gfp mice showed reduced obesity and reduced insulin resistance, accompanied by higher fat oxidation and energy expenditure. GIP-reduced mice demonstrate that partial reduction of GIP does not extensively alter glucose tolerance, but it alleviates obesity and lessens the degree of insulin resistance under HFD conditions, suggesting a potential therapeutic value.
Kinetic and Mechanistic Requirements for Helping CD8 T Cells1

The requirements for the generation of fully competent long-lived memory CD8 T cells and in particular the role and the mechanisms of help from CD4 T cells remain ill-defined. Memory CD8 T cells generated in the absence of CD4 T cell help often have an impaired recall proliferation and are thus unable to confer protection against certain pathogens. However, the timing and the mechanisms involved in the delivery of help are still unclear and differ between various experimental systems. In this study, we investigated the role of CD4 T help in generating memory CD8 T cells in a defined heterologous prime-boost system, consisting of priming with replication incompetent virus-like particles and challenge with recombinant vaccinia virus, both sharing only a common lymphocytic choriomeningitis virus-derived CD8 T cell epitope. We show in this system that delivery of help is only essential during the challenge phase for recall proliferation of memory CD8 T cells. Furthermore, we show that generation of proliferation-competent memory CD8 T cells is independent of CD40 and CCR5 and that in vivo IL-2 supplementation neither during priming nor during challenge was able to rescue recall proliferation of “unhelped” memory CD8 T cells.
Microsatellite analysis of the Queensland fruit fly Bactrocera tryoni (Diptera: Tephritidae) indicates spatial structuring: implications for population control

The population structure of a tephritid pest species, the Queensland fruit fly Bactrocera tryoni (Froggatt), has been analysed over a five year period (1994–1998), using six microsatellites. Adult fly samples were collected to cover most regions of eastern and central Australia where the flies are regularly found. Tests for heterogeneity indicated that flies within geographically defined regions were homogeneous. The samples were allocated into five regions, including one very large region, Queensland, which encompasses that portion of the fly‘s range where breeding can occur year-round. With one exception, the collections from different regions were homogeneous between years, showing a fairly static distribution of the species. However, differences between regions were highly significant. The one case of a change in frequency between years indicated a gradual replacement of flies in a marginal region by flies from the main part of the range. The finding of stability in the distribution of a highly mobile insect is of interest, potentially also for other species which have expanded beyond their native range. It is argued that a contributing reason for this stability may be adaptation to different climatic regimes, and that strategies for control based on this hypothesis afford a reasonable chance of success.
Measurement of Colonic Transit Time in Children

Transit times through the whole colon and its segments were measured in 10 healthy children and 14 children suffering constipation secondary to myelomeningocele. The subjects ingested radio-opaque markers on three successive days, and on the fourth a plain abdominal roentgenogram was taken using fast film. In the healthy children, total colonic transit time (mean ± SD) was 37.8 ± 6.2 h, with segmental times of 10.8 ± 3.5 h for the right colon, 12.2 ± 2.7 h for the left, and 14.7 ± 2.1 h for the rectosigmoid; upper normal limits of 17.8 h for the right colon, 17.6 h for the left, 19.1 h for the rectosigmoid, and 50.2 h for the total colonic transit time were established. In the constipated children, the total transit time was 59.9 ± 5.4 h, with segmental times of 15.9 ± 2.3 h for the right colon, 18.9 ± 2.3 h for the left, and 25.0 ± 2.6 h for the rectosigmoid. The technique described is simple, is easy to use in clinical practice, and involves a lower radiation dose than other methods. It may prove useful for measurement of colonic transit time in suitable patients.
Germline recombination in a novel Cre transgenic line, Prl3b1‐Cre mouse

Spermatogenesis is a complex and highly regulated process by which spermatogonial stem cells differentiate into spermatozoa. To better understand the molecular mechanisms of the process, the Cre/loxP system has been widely utilized for conditional gene knockout in mice. In this study, we generated a transgenic mouse line that expresses Cre recombinase under the control of the 2.5 kbp of the Prolactin family 3, subfamily b, member 1 (Prl3b1) gene promoter (Prl3b1‐cre). Prl3b1 was initially reported to code for placental lactogen 2 (PL‐2) protein in placenta along with increased expression toward the end of pregnancy. PL‐2 was found to be expressed in germ cells in the testis, especially in spermatocytes. To analyze the specificity and efficiency of Cre recombinase activity in Prl3b1‐cre mice, the mice were mated with reporter R26GRR mice, which express GFP ubiquitously before and tdsRed exclusively after Cre recombination. The systemic examination of Prl3b1‐cre;R26GRR mice revealed that tdsRed‐positive cells were detected only in the testis and epididymis. Fluorescence imaging of Prl3b1‐cre;R26GRR testes suggested that Cre‐mediated recombination took place in the germ cells with approximately 74% efficiency determined by in vitro fertilization. In conclusion, our results suggest that the Prl3b1‐cre mice line provides a unique resource to understand testicular germ‐cell development. genesis 54:389–397, 2016. © 2016 Wiley Periodicals, Inc.
Pyk2 regulates multiple signaling events crucial for macrophage morphology and migration

The biological role of the protein tyrosine kinase, Pyk2, was explored by targeting the Pyk2 gene by homologous recombination. Pyk2–/– mice are viable and fertile, without overt impairment in development or behavior. However, the morphology and behavior of Pyk2–/– macrophages were impaired. Macrophages isolated from mutant mice failed to become polarized, to undergo membrane ruffling, and to migrate in response to chemokine stimulation. Moreover, the contractile activity in the lamellipodia of Pyk2–/– macrophages was impaired, as revealed by measuring the rearward movement toward the nucleus of fibronectin-coated beads on the lamellipodia in opposition to an immobilizing force generated by optical tweezers. Consistently, the infiltration of macrophages into a carageenan-induced inflammatory region was strongly inhibited in Pyk2–/– mice. In addition, chemokine stimulation of inositol (1, 4, 5) triphosphate production and Ca2+ release, as well as integrin-induced activation of Rho and phosphatidyl inositol 3 kinase, were compromised in Pyk2–/– macrophages. These experiments reveal a role for Pyk2 in cell signaling in macrophages essential for cell migration and function.