Miracle-dz/UniFAR-FTUs huggingface dataset:
Without Informed Consent

The requirement of always obtaining participants' informed consent in research with human subjects cannot always be met, for a variety of reasons. This paper describes and categorises research situations where informed consent is unobtainable. Some of these kinds of situations, common in biomedicine and psychology, have been previously discussed, whereas others, for example, those more prevalent in infrastructure research, introduce new perspectives. The advancement of new technology may lead to an increase in research of these kinds. The paper also provides a review of methods intended to compensate for lack of consent, and their applicability and usefulness for the different categories of situations are discussed. The aim of this is to provide insights into one important aspect of the question of permitting research without informed consent, namely, how well that which informed consent is meant to safeguard can be achieved by other means.
Routing Engine Architecture for Next Generation Routers: Evolutional Trends

The routing engine is the essential part of a router. As a software component, the routing engine is used to control the router activities and to build the data forwarding table. Along with the hardware evolution, several software generations for routing engines have been experienced. In this paper, we first review the different routing engine architectures over the time and their main components. In some previous papers, we have investigated new directions for routing engine development for next generation routers, where specific distributed architectures have been proposed for several routing protocols. Taking into account the increasing traffic in the core networks, we next propose a framework integrating all specific distributed routing protocol architectures in order to significantly improve the scalability of the next generation routers. Bottlenecks are reduced, resulting in improving both the overall performance and the resiliency in the presence of faults. The scalability of the proposed distributed framework is estimated with respect to each routing protocol.
Effect of Zinc Supplementation on GH, IGF1, IGFBP3, OCN, and ALP in Non-Zinc-Deficient Children

Objective: Because most publications on growth and development deal with children with zinc deficiency, we decided to study the effects of this micronutrient on the secretion of growth hormone (GH), insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), osteocalcin (OCN), and alkaline phosphatase (ALP) in healthy and eutrophic children. This study is original because the methodology was unique. Methods: Forty schoolchildren participated in the study, 17 females and 23 males, aged 8 and 9 years. The study was carried out during a 3-month period. It was characterized as a triple-blind randomized controlled trial. The children were divided in a control group (20 schoolchildren using 10% sorbitol) and experimental group (20 schoolchildren using zinc). All were submitted to oral zinc supplementation (10 mg Zn/day) and venous zinc administration (0.06537 mg Zn/kg of body weight). Blood samples were collected at 0, 60, 120, 180, and 210 min. All schoolchildren were also submitted to anthropometric, clinical, and dietetic assessments as well as biochemistry analyses. Results: Oral zinc supplementation in the experimental group (1) stimulated an increase in the consumption of protein and fat (p = 0.0007, p < 0.0001, p < 0.0001, respectively), (2) increased basal serum zinc (p < 0.0001), (3) increased plasma ALP (p = 0.0270), and (4) showed a positive correlation for IGF1, IGFBP3, and OCN, comparing before and after oral zinc supplementation (p = 0.0011, p < 0.0001, p < 0.0446, respectively). During zinc administration, plasma IGF1 and IGFBP3 increased significantly in the experimental group (p = 0.0468, p < 0.0001, respectively). Plasma GH increased in the experimental group but without statistical difference comparing before and after oral zinc supplementation. Conclusions: Zinc supplementation stimulated an increase in the consumption of some macronutrients and basal serum zinc and improved plasma alkaline phosphatase levels. Zinc administration increased hormones of the GH-IGF1 system.
Discoidin domain receptor 1 activation suppresses α2β1 integrin‐dependent cell spreading through inhibition of Cdc42 activity

Upregulation and overexpression of discoidin domain receptor 1 (DDR1) have been implied in the regulation of kidney development and progression of cancers. Our previous studies with Mardin–Darby canine kidney (MDCK) cells showed that overexpression of DDR1 inhibited cell spreading, whereas dominant negative DDR1 promoted cell spreading on collagen‐coated dish. Cell spreading is an important characteristic for cell differentiation and survival. However, little is known about the molecular mechanisms underlying the role of DDR1 in cell spreading. We have found here a novel signaling pathway of DDR1 consisting of Cdc42 that regulates the assembly and disassembly of cytoskeleton and cell spreading in MDCK cells. Cell spreading involves the organization of cytoskeleton that is mainly regulated by Rho‐family GTPases. We assessed the activity of Rho‐family GTPases and transfected MDCK cells with constitutively active or dominant negative GTPases, and quantified the extent of cell spreading. These results showed that DDR1 decreased the filamentous actin ratio and Rac1/Cdc42 activities, but had no effects on RhoA activity. Neither constitutively active nor dominant negative Rac1 altered DDR1‐inhibited cell spreading. Constitutively active Cdc42 could rescue the DDR1‐inhibited cell spreading, whereas dominant negative Cdc42 inhibited cell spreading, indicating that DDR1‐inhibited cell spreading is Cdc42 dependent. With the use of α2β1 integrin blocking antibody, we showed that collagen‐induced Cdc42 activation was mediated by α2β1 integrin. Moreover, ectopic FAK expression enhanced the Cdc42 activity. Reducing FAK activity by dominant negative FAK (FRNK) markedly abolished the Cdc42 activity. These findings show that DDR1a/b activation inhibits cell spreading through suppressing α2β1 integrin‐mediated Cdc42 activation. J. Cell. Physiol. 218: 146–156, 2009. © 2008 Wiley‐Liss, Inc.
Pattern-Reconfigurable Microstrip Patch Antenna With Multidirectional Beam for WiMAX Application

A parasitic planar patch antenna capable of multi directional pattern reconfiguration is presented. The antenna structure consists of a driven element surrounded by four parasitic elements that act either as reflector(s) or director(s) depending on the switching arrangement. Beam reconfiguration is achieved by using four p-i-n diode switches where the effect of switching technique on the overall element performance is investigated numerically and experimentally. The proposed antenna achieves nine distinguished main beam angular positions. Moreover, the proposed antenna has achieved excellent realized gain levels at all configuration scenarios with a minimum value of 7 dBi. Simulation and measurement results show good agreement and promising applications of such antenna structure in enhanced WiMAX systems.
Predictors of Medication-Refill Adherence in an Indigent Rural Population

Objective. We evaluated the association of medication refill adherence with demographic and prescription characteristics to determine whether such factors could guide intervention strategies in an indigent rural population. Methods. The study was conducted at a University-based internal medicine practice serving an indigent rural population. Refill data for diabetes, hypertension, and hypercholesterolemia drugs from a closed pharmacy system were used to calculate mean adherence (for all drugs taken by each patient) and minimum adherence (that of the least adhered to drug) for 1984 patients during a 9-month period. Results. Mean refill adherence was <80% for 33% of the population and minimum refill adherence was <80% for 55% of the patients. Increasing age, race (white), and prescription length were associated with higher mean and minimum adherence, independent of income, prescription copay, and insurance status. Number of drugs taken had a positive mean but negative minimum adherence association. Gender, number of primary care visits, and dosage schedule were not independently associated with adherence. The model explained 6.8% of the variance in mean adherence. Conclusions. In a rural indigent population, medication refill adherence was associated with race, age, and prescription length, though these factors explained only a small amount of adherence variability. Although ingestion adherence is the goal, refill adherence is a necessary condition for ingestion adherence. To enhance adherence, physicians need better predictors to target their efforts to patients most in need of attention. Prescription claims data could serve this purpose.
Pathogenesis of Autographa californica M nucleopolyhedrovirus in fifth instar Spodoptera frugiperda.

We have characterized infection and pathogenesis of an Autographa californica M nucleopolyhedrovirus recombinant, AcMNPV-hsp70/lacZ, carrying the lacZ reporter gene, in penultimate (fifth) instar Spodoptera frugiperda. Bioassays revealed that while <0.1 p.f. u. of budded virus was required to generate an LD(50) by intrahaemocoelic injection, approximately 6000 occlusions were required orally to achieve the same mortality in newly moulted fifth instar (5(0)) larvae. In pathogenesis experiments, 78 % of the 5(0) larvae inoculated orally with 6000 occlusions of AcMNPV-hsp70/lacZ were LacZ-positive at 8 h post-inoculation (p.i.) and 50 % had LacZ signals in tracheal cells indicating that in these larvae infection had been transmitted from the midgut to secondary target cells. At 24 h p.i. , maximum numbers of midgut and midgut-associated tracheal foci were observed (mean of 35 foci per infected larva), and 88 % of the larvae were LacZ-positive. The extremely low foci-per-occlusion ratio (0.006) indicated that successful infection of midgut cells was the primary barrier to fatal infection. A second barrier involved the loss of infected tracheal cells associated with the midgut. At 24 h p.i. , 88 % of the inoculated larvae had a systemic infection, but in bioassays only 51 % succumbed to polyhedrosis disease. The absence of melanized tracheal cells in the insects throughout the time-course suggested that the larvae that cleared their infections (38 %) did so by a mechanism other than a classical immune response.
Protease Activation and Inflammation in Acute Pancreatitis

Approximately 10—20 % of patients with acute pancreatitis (AP) develop a severe disease with high mortality and morbidity. Activation of pancreatic proteases, the inflammatory response and impaired pancreatic circulation are pathophysiological events that are important in order for the disease to develop. There is no specific treatment for severe AP, and no useful marker for predicting the severity of the disease upon admission to the hospital. In this thesis, markers of early pathophysiological events in AP are investigated, with emphasis on protease activation and inflammation. ProCarboxypeptidase B (proCAP) is a pancreatic proenzyme which, particularly in severe AP, is activated by trypsin thereby forming Carboxypeptidase B (aCAP ) and the activation peptide of proCarboxypeptidase B (CAPAP). An ELISA method for measurement of serum aCAP in patients with AP was developed, and aCAP was shown to inhibit fibrinolysis in vitro. This may contribute to formation of necrosis in AP. The prediction of severity and pathophysiology was studied in patients with mild (n=124) and severe (n=16) AP. Markers of protease activation (aCAP, CAPAP) and inflammation (Monocyte Chemoattractant protein-1 (MCP-1) and CRP) were found to be elevated within 24 hours in patients with severe AP. Protease activation decreased after 48 hours, yet inflammation persisted for a longer period of time. Markers of pancreatic leakage (proCAP) decreased with time without differences in patients with mild and severe AP. MCP-1 exhibited a good capacity at predicting severe AP upon hospital admission. CAPAP and aCAP may also be useful in predicting the degree of severity. (Less)
Seasonal Birth Patterns of Neurological Disorders

Existing seasonal birth studies were reviewed for multiple sclerosis (MS), Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), epilepsy, cerebral palsy, congenital malformations of the central nervous system and mental retardation. Epilepsy appears to have the most consistent pattern, with an excess of births in winter and a deficit in September. MS, ALS and possibly Parkinson’s disease appear to have an excess of spring births. Studies of cerebral palsy are not conclusive, although there are suggestions that there may be an excess of summer births. The findings for Alzheimer’s disease, congenital malformations of the central nervous system, and mental retardation are contradictory and insufficient to draw any conclusions.
The Chain of Being

For centuries, philosophers, theologians, and scientists have used the idea of the Great Chain of Being to rank all beings, from demons to animals, humans, and gods, along a vertical dimension of morality. Although the idea of a chain of being has largely fallen out of academic favor, we propose that people still use an embodied vertical moral hierarchy to understand their moral world. This social cognitive chain of being (SCCB) encapsulates a range of research on moral perception including dehumanization (the perception of people as lower on the SCCB), anthropomorphism (the perception of animals as higher and the perceptions of gods as lower on the SCCB), and sanctification (the perception of people as higher on the SCCB). Moral emotions provide affective evidence that guide the perception of social targets as moral (e.g., elevation) or immoral (e.g., disgust). Perceptions of social targets along the SCCB enable people to fulfill group and self-serving, effectance, and existential motivations. The SCCB serves as a unifying theoretical framework that organizes research on moral perception, highlights unique interconnections, and provides a roadmap for future research.
Novel insights into the architecture and protein interaction network of yeast eIF 3

Translation initiation in eukaryotes is a multistep process requiring the orchestrated interaction of several eukaryotic initiation factors (eIFs). The largest of these factors, eIF3, forms the scaffold for other initiation factors, promoting their binding to the 40S ribosomal subunit. Biochemical and structural studies on eIF3 need highly pure eIF3. However, natively purified eIF3 comprise complexes containing other proteins such as eIF5. Therefore we have established in vitro reconstitution protocols for Saccharomyces cerevisiae eIF3 using its five recombinantly expressed and purified subunits. This reconstituted eIF3 complex (eIF3) exhibits the same size and activity as the natively purified eIF3 (eIF3). The homogeneity and stoichiometry of eIF3 and eIF3 were confirmed by analytical size exclusion chromatography, mass spectrometry, and multi-angle light scattering, demonstrating the presence of one copy of each subunit in the eIF3 complex. The reconstituted and native eIF3 complexes were compared by single-particle electron microscopy showing a high degree of structural conservation. The interaction network between eIF3 proteins was studied by means of limited proteolysis, analytical size exclusion chromatography, in vitro binding assays, and isothermal titration calorimetry, unveiling distinct protein domains and subcomplexes that are critical for the integrity of the protein network in yeast eIF3. Taken together, the data presented here provide a novel procedure to obtain highly pure yeast eIF3, suitable for biochemical and structural analysis, in addition to a detailed picture of the network of protein interactions within this complex.
Effects of very high doses of human growth hormone (hGH) on the male reproductive system in the dog

Summary. The effects of very high doses of human growth hormone (hGH), pituitary derived or recombinant methionyl‐hGH, on the morphology of reproductive organs and on some hormones in the male dog are described. The studies were part of a toxicological documentation of hGH. A total of 18 male dogs aged 7.5–20.5 months, from four studies were treated subcutaneously with hGH for 20–28 days at dose levels of 3, 10 or 25 IU kg−1 day−1 or 1 IU kg−1 three times weekly. Plasma levels of luteinizing hormone (LH), testosterone and prolactin were determined in one study. Organ weighing, macroscopic and histopathologic examinations of male reproductive organs at the end of the treatment period were included in all studies. Treatment with 25 IU kg−1 day−1 resulted in reduction of testis and prostate weights, degeneration of germ cells and epithelial atrophy in the testis, degenerative changes in epididymis and reduced height of the prostatic epithelium. Similar, although less severe morphological changes were observed after treatment with 10 IU kg−1 day−1. Treatment with 25 IU kg−1 day−1 also caused a marked reduction of plasma prolactin, LH and testosterone levels. These results suggest that repeated administration of very high doses of hGH interferes with the hormonal regulation of the testis in the dog. —
Mutational analysis of Hsp90 function: interactions with a steroid receptor and a protein kinase

Hsp90 is a protein chaperone whose functions are focused on a specific set of target proteins. The nature of Hsp90's interactions with these proteins is poorly understood. To provide tools for examining these interactions, we have isolated eight broadly distributed temperature-sensitive (ts) point mutations in the Hsp90 gene (HSP82) of Saccharomyces cerevisiae. The mutants fall into two distinct classes. One has a classic ts phenotype, with nearly wild-type activity at 25 degrees C and a precipitous loss of function at 34 degrees C. The remaining seven mutants, in contrast, cause a general reduction in Hsp90 function and are ts because they do not provide the high level of function required for growth at high temperatures. The effects of these mutants on two target proteins, a transcription factor (glucocorticoid receptor) and a tyrosine kinase (pp60v-src), provided several insights on Hsp90 function. First, Hsp90 is not only required to help the glucocorticoid receptor achieve a hormone-activable state, it is continuously required to maintain that state. Second, Hsp90's function in the maturation of pp60v-src involves separable roles in protein accumulation and kinase activation. Thus, Hsp90 is an integral component of both the steroid receptor and kinase signaling pathways. Finally, all eight point mutants affect the activation of both the glucocorticoid receptor and pp60v-src, indicating that Hsp90 promotes the activity of these very different target proteins through common mechanisms.
Spectrum of disease in U.S. veteran patients with hepatitis C

OBJECTIVE:Hepatitis C virus (HCV) infection is more prevalent in U.S. veterans attending Veterans Affairs Medical Centers than in the general population. The purpose of this study was to examine the risk factors, psychiatric and substance abuse conditions, and severity of liver disease in veterans with HCV.METHODS:The medical records and liver biopsies of 206 consecutive patients with HCV attending a multidisciplinary medical/psychiatric chronic hepatitis clinic and who met eligibility criteria for interferon α-2b therapy were reviewed.RESULTS:The mean age was 46.5 ± 6.8 yr and 77% were Vietnam-era veterans. Risk factors included i.v. drug use (64%), blood transfusion (15%), and cocaine use (9%), and were unknown in 12%. The average estimated duration of disease was 24 ± 7.6 yr. A history of alcohol abuse or dependence was identified in 80% of patients. Psychiatric illnesses were present in 60%, the most common being depression and posttraumatic stress disorder. Overall, 89% of patients had documented psychiatric and/or substance abuse diagnoses. Severe fibrosis (stages 3–4) was present in 32% and severe inflammation (grades 2–3) was present in 71% of biopsies. Psychiatric and substance abuse diagnoses did not correlate with severity of liver disease. A total of 145 patients (71%) were prescribed interferon-based treatment. The overall virological sustained response rates were 16% after interferon monotherapy and 28% after interferon/ribavirin therapy. Reasons for not receiving interferon therapy included minimal fibrosis on liver biopsy (37 patients [18%]), worsening medical conditions (nine [4%]), and worsening psychiatric and substance abuse problems (14 [7%]). CONCLUSIONS:Advanced fibrosis is common in this cohort of veteran patients with chronic hepatitis C, and the overwhelming majority of these patients have psychiatric and/or substance abuse diagnoses. Despite these comorbidities, the majority received interferon therapies in the context of a multidisciplinary clinic. These data emphasize the importance of hepatitis C care that includes linkage of medical care and psychiatric services.
Cystamine and cysteamine prevent 3‐NP‐induced mitochondrial depolarization of Huntington's disease knock‐in striatal cells

Cystamine significantly improved motor deficits and extended survival in mouse models of Huntington's disease (HD); however, the precise mechanism(s) by which cystamine and the related compound cysteamine are beneficial remain to be elucidated. Using clonal striatal cell lines from wild‐type (STHdhQ7/HdhQ7) and mutant huntingtin knock‐in (STHdhQ111/HdhQ111) mice, we have tested the hypothesis that cystamine and cysteamine could be beneficial by preventing the depolarization of mitochondria in cell cultures. Treatment with 3‐nitroproprionic acid (3‐NP), a mitochondrial complex II inhibitor, induces mitochondrial depolarization and cell death of mutant HD striatal cells but not of wild‐type cells. The 3‐NP‐mediated decrease in the mitochondrial membrane potential was attenuated by 50 µm cystamine and completely inhibited by 250 µm cystamine. Similar results were obtained using cysteamine (50–500 µm). In addition, both cystamine and cysteamine significantly attenuated the 3‐NP‐induced cell death. Treatment of mutant HD striatal cells with 3‐NP resulted in a robust decrease in the cellular and mitochondrial levels of glutathione (GSH) compared with cells exposed to the vehicle alone. Pre‐treatment of the cells with cystamine and cysteamine completely prevented the 3‐NP‐mediated decrease in cellular and mitochondrial GSH levels. Incubation with l‐buthionine (S,R) sulfoximine (BSO) 250 µm in combination with cystamine (250 µm) or cysteamine (250 µm) prior to being treated with 3‐NP completely prevented the beneficial effects of cystamine and cysteamine on the 3‐NP‐mediated mitochondrial depolarization. These results demonstrate that cystamine and cysteamine prevent the 3‐NP‐induced mitochondrial depolarization of HD striatal cell cultures.
Prediction of externalizing behavior problems from early to middle childhood: The role of parental socialization and emotion expression

Parental emotions and behaviors that contribute to continuity and change in preschool children's externalizing problems were examined. Mothers and fathers were observed interacting with their children, and child-rearing styles were reported. Teachers, mothers, and children reported children's antisocial, oppositional behavior. Externalizing problems showed strong continuity 2 and 4 years later. Proactive parenting (i.e., supportive presence, clear instruction, and limit setting) predicted fewer behavior problems over time, after controlling for initial problems; the converse was true for parental anger. In contrast, the hypothesized ameliorative contribution of parents' positive emotion was not found. Parental contributions were most influential for children whose initial problems were in the clinical range. In particular, parental anger predicted continuation of problems over time. Paternal, as well as maternal, influences were identified. Examination of parental emotions and inclusion of fathers is important to research and intervention with young antisocial children.