Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemokines and Their Receptors in the Central Nervous System

Chemokines are a family of proteins associated with the trafficking of leukocytes in physiological immune surveillance and inflammatory cell recruitment in host defence. They are classified into four classes based on the positions of key cystiene residues: C, CC, CXC, and CX3C. Chemokines act through both specific and shared receptors that all belong to the superfamily of G-protein-coupled receptors. Besides their well-established role in the immune system, several recent reports have demonstrated that these proteins also play a role in the central nervous system (CNS). In the CNS, chemokines are constitutively expressed by microglial cells, astrocytes, and neurons, and their expression can be increased after induction with inflammatory mediators. Constitutive expression of chemokines and chemokine receptors has been observed in both developing and adult brains, and the role played by these proteins in the normal brain is the object of intense study by many research groups. Chemokines are involved in brain development and in the maintenance of normal brain homeostasis; these proteins play a role in the migration, differentiation, and proliferation of glial and neuronal cells. The chemokine stromal cell-derived factor 1 and its receptor, CXCR4, are essential for life during development, and this ligand-receptor pair has been shown to have a fundamental role in neuron migration during cerebellar formation. Chemokine and chemokine receptor expression can be increased by inflammatory mediators, and this has in turn been associated with several acute and chronic inflammatory conditions. In the CNS, chemokines play an essential role in neuroinflammation as mediators of leukocyte infiltration. Their overexpression has been implicated in different neurological disorders, such as multiple sclerosis, trauma, stroke, Alzheimer's disease, tumor progression, and acquired immunodeficiency syndrome-associated dementia. An emerging area of interest for chemokine action is represented by the communication between the neuroendocrine and the immune system. Chemokines have hormone-like actions, specifically regulating the key host physiopathological responses of fever and appetite. It is now evident that chemokines and their receptors represent a plurifunctional family of proteins whose actions on the CNS are not restricted to neuroinflammation. These molecules constitute crucial regulators of cellular communication in physiological and developmental processes.
Ventilated Hearth Structures in the Casma Valley, Peru

Recent investigations in the Casma Valley on the north-central coast of Peru have uncovered a series of circular and rectangular/square structures, each containing a central hearth associated with either four subfloor ventilation shafts or a single open ventilation trough. The structures date to the Late Preceramic period (2500-1800 B. C.) and the Initial period (1800-900 B. C.). All are small and were originally roofed with perishable materials to hold in heat and smoke from the central hearth. It seems likely that these ventilated hearths represent a coastal variant of the Kotosh Religious Tradition that has been well documented in the Peruvian Highlands. The structures probably served as ritual chambers for small groups of people, somewhat analogous to the sweathouses of various Native American groups.
Exogenous IL‐6 Inhibits Acute Inflammatory Responses and Prevents Ischemia/Reperfusion Injury after Intestinal Transplantation

Interleukin‐6 (IL‐6) is a pleiotropic acute reactant cytokine involved in inflammatory responses. To explore the role of IL‐6 in inflammation, this study examined the efficacy of exogenous IL‐6 in preventing intestinal ischemia/reperfusion (I/R) injury associated with small bowel transplantation (SBTx). Syngenic orthotopic SBTx was performed in Lewis rats after 6‐h graft preservation in University of Wisconsin (UW) at 4 °C. IL‐6 mutein (IL‐6m, 500 μg/kg), a recombinant molecular variant of human IL‐6, was subcutaneously given to donors 2 h before harvesting (IL‐6mD) or to excised grafts by luminal infusion (IL‐6mG). Animal survival was 100% and 75% in IL‐6mD (p < 0.05 vs. control) and IL‐6mG groups, respectively, compared with 64.3% in untreated controls. The severity of I/R injury (e.g. epithelial denudation, villous congestion) was reduced with IL‐6m, in addition to a striking increase in re‐epithelization. With IL‐6m, neutrophil extravasation was markedly reduced in intestinal grafts and in remote organs (e.g. lung). IL‐6m mediated anti‐inflammatory effects through the inhibition of I/R‐induced up‐regulation of intragraft and circulating IL‐1‐β, tumor necrosis factor‐α (TNF‐α) and IL‐6. IL‐6m also increased intestinal graft tissue blood flow. These results show that IL‐6 is effective in protecting the intestine from cold I/R injury by maintaining graft blood flow and reducing pro‐inflammatory cytokine up‐regulation and neutrophil infiltration.
Sitagroi, radiocarbon and the prehistory of south-east Europe

Dr Renfrew, of the University of Shefield, directed excavations at Sitagroi in north Greece in 1968 and 1969 and in an earlier note here (1970, 13r )says that one of the important aspects of the finds there was that ‘for the jirst time Balkan cultures are seen in direct stratigraphic relation to those of the Aegean’. A series of twenty-six radiocarbon dates, deteumined by the British Museum and Berlin laboratories, from the Sitagroi mound oflers the possibility of a new and detailed understanding of the chronological relations between the Aegean and the Balkans.
Simulation: A Tool to Assist Nursing Professional Development Practitioners to Help Nurses to Better Recognize Early Signs of Clinical Deterioration of Patients

The need to enhance the knowledge and skills of nurses caring for patients exhibiting signs of clinical deterioration has been documented. The literature has further supported the registered nurse as the key individual expected to recognize signs of clinical deterioration in the patient. The use of simulation as an effective teaching strategy has been well documented. The purpose of this project was to use simulation as an educational intervention to increase nurse knowledge, self-confidence, and competency when caring for patients exhibiting signs of clinical deterioration. A significant improvement in nurse knowledge and self-confidence was shown after a simulation-based educational intervention. Competency evaluation during the simulation-based intervention provided information to help nurses when caring for deteriorating patients. Nursing professional development practitioners can use the information from this project in planning educational interventions for staff nurses.
Computer methods in child language research: four principles for the use of archived data

ABSTRACT With the increasing use of computers in language research, there is a need for caution concerning several new issues of data accountability. This paper presents four principles for archive-based language research: Maximum Readability and Minimum Bias; Consistent Encoding for exhaustive computer search; Systematic Contrastiveness; and Data Comparability in elicitation, transcription and coding. These and related principles are illustrated by examples from existing computer archives, and strategies are suggested for minimizing detrimental effects of violations. Finally, the paper describes some implications of the principles for properties of a field-wide and international standard of transcription of language data.
Role of Myocardial Nitric Oxide in Diabetic Ischemia-Reperfusion Dysfunction: Studies in Mice with Myocyte-Specific Overexpression of Endothelial Nitric-Oxide Synthase

We investigated the role of nitric oxide (NO) in myocardial ischemia-reperfusion injury of diabetic mice with myocyte-specific overexpression of endothelial NO synthase (NOS). Four weeks after diabetes induction with streptozotocin (blood glucose ∼29 mM), isolated isovolumic heart function and cellular NO metabolites in response to brief normothermic ischemia-reperfusion were determined. Under normoxic conditions transgenic (TG) hearts from nondiabetic and diabetic animals generated less leftventricular developed pressure compared with wild-type (WT) control hearts, and this abnormality was unaffected by NOS inhibition. During ischemia, the rise in end-diastolic pressure was less in the TG than WT group of nondiabetic hearts, whereas the transgene had no effect in the diabetic group. Similarly, the transgene also improved reperfusion systolic and diastolic function in nondiabetic but not in diabetic hearts. NOS inhibition worsened reperfusion function in diabetic hearts. Postischemic nitrite and cGMP formation were higher in nondiabetic TG than WT hearts, but in diabetic hearts cGMP was no longer elevated. The formation of reactive oxygen species (superoxide and peroxynitrite) during early reperfusion, measured by electron spin resonance spectroscopy, was similar in nondiabetic WT and TG hearts, but it was significantly higher in diabetic TG hearts. Stimulating endogenous NO production with 10 μM bradykinin more strongly reduced myocardial O2 consumption in diabetic TG than diabetic WT hearts perfused in normoxia, whereas there was no difference after ischemia-reperfusion. Thus, providing additional endogenous NO is sufficient to protect nondiabetic hearts against ischemia-induced injury, but for a similar protection in diabetic hearts, effective scavenging of reactive oxygen species is also important.
Expression, cross-linking and characterization of recombinant chitin binding resilin

Resilin is a polymeric rubber-like protein secreted by insects to specialized cuticle regions, in areas where high resilience and low stiffness are required. Resilin binds to the cuticle polysaccharide chitin via a chitin binding domain and is further polymerized through oxidation of the tyrosine residues resulting in the formation of dityrosine bridges and assembly of a high-performance protein-carbohydrate composite material. We describe for the first time a comprehensive study on the mechanical, structural and biochemical function of chitin binding recombinant Drosophila melanogaster resilin. Various resilin constructs were cloned including the full length gene enabling Ni-NTA purification, as well as heat and salt precipitation for rapid and efficient purification. The binding isotherms and constants (Kd, Bmax) of resilin to chitin via its chitin binding domain were determined and displayed high affinity to chitin, implying its important role in the assembly of the resilin-chitin composite. The structural and elastic properties were investigated using Fourier Transform Infrared Spectroscopy (FTIR), Circular Dichroism (CD) and Atomic Force Microscopy (AFM) with peroxidase crosslinked solid resilin materials. Generally, little structural organization was found by these biophysical methods, suggesting structural order was not induced by the dityrosine crosslinks. Further, the elastomeric properties found from the full length protein compared favorably with the shorter resilin generated previously from exon 1. The unusual elastomeric behavior of this protein suggests possible utility in biomaterials applications.
Structural basis of regulation and oligomerization of human cystathionine β-synthase, the central enzyme of transsulfuration

Significance Cystathionine β-synthase (CBS), the pivotal enzyme of the transsulfuration pathway, regulates the flux through the pathway to yield compounds such as cysteine, glutathione, taurine, and H2S that control the cellular redox status and signaling. Our crystal structures of the full-length wild-type and D444N mutant human CBS enzymes show a unique arrangement of the regulatory CBS motifs, thus making it possible to infer how the enzyme is stimulated by its allosteric activator S-adenosyl-L-methionine and how native tetramers are formed. The structure will allow modeling of numerous mutations causing inherited homocystinuria and the design of compounds modulating CBS activity. Cystathionine β-synthase (CBS) controls the flux of sulfur from methionine to cysteine, a precursor of glutathione, taurine, and H2S. CBS condenses serine and homocysteine to cystathionine with the help of three cofactors, heme, pyridoxal-5′-phosphate, and S-adenosyl-l-methionine. Inherited deficiency of CBS activity causes homocystinuria, the most frequent disorder of sulfur metabolism. We present the structure of the human enzyme, discuss the unique arrangement of the CBS domains in the C-terminal region, and propose how they interact with the catalytic core of the complementary subunit to regulate access to the catalytic site. This arrangement clearly contrasts with other proteins containing the CBS domain including the recent Drosophila melanogaster CBS structure. The absence of large conformational changes and the crystal structure of the partially activated pathogenic D444N mutant suggest that the rotation of CBS motifs and relaxation of loops delineating the entrance to the catalytic site represent the most likely molecular mechanism of CBS activation by S-adenosyl-l-methionine. Moreover, our data suggest how tetramers, the native quaternary structure of the mammalian CBS enzymes, are formed. Because of its central role in transsulfuration, redox status, and H2S biogenesis, CBS represents a very attractive therapeutic target. The availability of the structure will help us understand the pathogenicity of the numerous missense mutations causing inherited homocystinuria and will allow the rational design of compounds modulating CBS activity.
Analysis of Discrete Ill-Posed Problems by Means of the L-Curve

When discrete ill-posed problems are analyzed and solved by various numerical regularization techniques, a very convenient way to display information about the regularized solution is to plot the norm or seminorm of the solution versus the norm of the residual vector. In particular, the graph associated with Tikhonov regularization plays a central role. The main purpose of this paper is to advocate the use of this graph in the numerical treatment of discrete ill-posed problems. The graph is characterized quantitatively, and several important relations between regularized solutions and the graph are derived. It is also demonstrated that several methods for choosing the regularization parameter are related to locating a characteristic L-shaped “corner” of the graph.
Qualité, coût et impact de la prise en charge coordonnée des patients diabétiques de type 2 dans un réseau de santé

Objectif: Evaluer la qualite et les couts d'une prise en charge en reseau comparee a une prise en charge habituelle des patients ayant un diabete de type 2 pendant l'annee 2005 dans la region Provence-Alpes-Cote d'Azur. Methodes : Deux groupes de patients ont ete compares. Le groupe experimental etait constitue des patients inclus dans le reseau et le groupe temoin de patients diabetiques vivant sur la zone geographique couverte par le reseau. La qualite de la prise en charge etait definie par la conformite des pratiques professionnelles aux referentiels de la Haute Autorite de sante. Resultats : L'etude a porte sur un echantillon de 828 patients. Les 414 patients du groupe reseau beneficiaient d'un suivi annuel plus complet que les 414 patients du groupe temoin : trois dosages de l'hemoglobine glyquee (56,4 % vs 46,9 % des patients), un bilan lipidique (80,0 % vs 65,0 %), une recherche d'une microalbuminurie (61,7 % vs 27,3 %), un examen ophtalmologique (59,4 % vs 40,8 %), un electrocardiogramme (87,5 % vs 75,1 %), et un examen dentaire (41,9 % vs 32,9 %). Les patients du groupe reseau presentaient un cout moyen ambulatoire superieur a celui du groupe temoin (2 666 vs 2 289 euros ; p = 0,022) et un cout moyen hospitalier inferieur a celui du groupe temoin (1 462 vs 2 134 euros ; p = 0,04). Les couts totaux de prise en charge ne differaient pas significativement entre les deux groupes. Conclusion : Le niveau de conformite des pratiques professionnelles de prise en charge du diabete de type II etait superieur dans le reseau, sans diminution des couts par rapport a une prise en charge habituelle.
The Mitochondrial DNA Affinities of the Prehistoric People of San Clemente Island: An Analysis of Ancient DNA

Native American mitochondrial DNA belongs to one of five haplogroups defined by lineage-specific markers. Haplogroup frequency distribution is non-random among cultures. At historical contact, the Gabrielino occupied the southernmost California Channel Islands and the adjacent Los Angeles Basin. The Chumash thrived on the northern Channel Islands and Santa Barbara mainland. The Gabrielino were linguistically, culturally, and possibly genetically distinct from the Chumash. Haplogroup frequencies were determined for two prehistoric populations from San Clemente Island (Eel Point and the Nursery Site) to investigate Uto-Aztecan migration onto the southern Channel Islands. Analysis included three measures of genetic distance and phylogenetic analysis, as well as Fisher's exact tests. The Eel Point and Nursery Site frequency distributions were compared to one another, and to extant Uto-Aztecan and Great Basin/California populations. Results suggest that the prehistoric occupants of Eel Point and the Nursery Site were not closely related to one another or to the Chumash.
Aspergillus PCR-Based Investigation of Fresh Tissue and Effusion Samples in Patients with Suspected Invasive Aspergillosis Enhances Diagnostic Capabilities

ABSTRACT Although it is a severe complication in immunocompromised patients, diagnosing invasive fungal disease (IFD), especially invasive aspergillosis (IA), remains difficult. In certain clinical scenarios, examining tissue samples for identification of the infectious organism becomes important. As culture-based methods rarely yield results, the performance of an Aspergillus-specific nested PCR in fresh tissue or pleural effusion samples was evaluated. Fresh tissue (n = 59) and effusion (n = 47) specimens from 79 immunocompromised patients were subjected to an Aspergillus-specific PCR assay. Twenty-six patients had proven (n = 20) or probable (n = 6) IFD, according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria, while the remaining patients were classified as having either possible IFD (n = 30) or no IFD (n = 23). IA was identified as the underlying IFD in 21/26 proven/probable cases. PCR positivity was observed for 18/21 proven/probable and 6 possible IA cases; cases classified as no IA did not show positive signals. Patients with proven IFD (n = 5) with cultures positive for non-Aspergillus molds also had negative Aspergillus PCR results. Aspergillus PCR performance analysis yielded sensitivity and specificity values of 86% (95% confidence interval [CI], 65% to 95%) and 100% (95% CI, 86% to 100%), respectively, thus leading to a diagnostic odds ratio of >200. In this analysis, good diagnostic performance of the PCR assay for detection of IA was observed for tissue samples, while effusion samples showed lower sensitivity rates. PCR testing represents a complementary tool; a positive PCR result strengthens the likelihood of IA, whereas IA seems unlikely in cases with negative results but findings could indicate non-Aspergillus IFD. Thus, PCR testing of these specimens enhances the diagnostic capabilities.
Nerve Growth Factor Translates Stress Response and Subsequent Murine Abortion via Adhesion Molecule-Dependent Pathways1

Abstract Spontaneous abortion is a frequent threat affecting 10%–25% of human pregnancies. Psychosocial stress has been suggested to be attributable for pregnancy losses by challenging the equilibrium of systems mandatory for pregnancy maintenance, including the nervous, endocrine, and immune system. Strong evidence indicates that stress-triggered abortion is mediated by adhesion molecules, i.e., intercellular adhesion molecule 1 (ICAM1) and leukocyte function associated molecule 1, now being referred to as integrin alpha L (ITGAL), which facilitate recruitment of inflammatory cells to the feto-maternal interface. The neurotrophin beta-nerve growth factor (NGFB), which has been shown to be upregulated in response to stress in multiple experimental settings including in the uterine lining (decidua) during pregnancy, increases ICAM1 expression on endothelial cells. Here, we investigated whether and how NGFB neutralization has a preventive effect on stress-triggered abortion in the murine CBA/J × DBA/2J model. We provide experimental evidence that stress exposure upregulates the frequency of abortion and the expression of uterine NGFB. Further, adhesion molecules ICAM1 and selectin platelet (SELP, formerly P-Selectin) and their ligands ITGAL and SELP ligand (SELPL, formerly P selectin glycoprotein ligand 1) respectively increase in murine deciduas in response to stress. Subsequently, decidual cytokines are biased toward a proinflammatory and abortogenic cytokine profile. Additionally, a decrease of pregnancy protective CD8α+ decidual cells is present. Strikingly, all such uterine stress responses are abrogated by NGFB neutralization. Hence, NGFB acts as a proximal mediator in the hierarchical network of immune rejection by mediating an abortogenic environment comprised of classical signs of neurogenic inflammation.
Interferon monotherapy in chronic hepatitis B

Interferon‐alpha (IFN‐α) has been the only approved agent for the treatment of chronic hepatitis B in most countries, but this is rapidly changing. It is expensive, associated with frequent and unpleasant side effects, has limited efficacy and is ineffective in subjects with no/mild liver necro‐inflammation. Loss of HBsAg and viral replication markers occur 6% and 20%, more often in IFN‐treated subjects than controls. The most important factors that will predict favourable response to IFN‐α therapy are elevated ALT and low serum HBV DNA levels. Chinese patients and children with active liver have similar response rates as Caucasian adults with equivalent ALT levels. Patients with HBeAg negative disease fare less well. Long‐term follow up has shown that most IFN responders maintained their response although very few people have complete eradication of HBV.
Diagnostic Reproducibility of Cervical Intraepithelial Neoplasia 3 and Atrophy in Menopausal Women on Hematoxylin and Eosin, Ki-67, and p16 Stained Slides

Objective. To establish diagnostic accuracy and reproducibility of a diagnosis of cervical intraepithelial neoplasia 3 (CIN 3) in menopausal women on routinely stained hematoxylin and eosin (H&E) slides and compare it to slides processed for p16 and Ki-67. Materials and Methods. Confirmed cases of CIN 3 and benign atrophic changes were reviewed independently by 4 pathologists. The samples were studied on separate occasions using H&E staining, p16, and Ki-67. Differences in sensitivity and specificity between reviewers or methods were tested for significance using the McNemar test, whereas differences in positive and negative predictive values were tested for significance using a marginal probability generalized linear model for agreement. Results. Sensitivity was high for H&E (93.3%-100%) and Ki-67 (93.3%-100%) and lower for p16 (70.0%-90.0%). Intraobserver variability was also lower for p16 (76.7% vs 90.0%, although this difference was not statistically significant, p = .219). p16 agreement, however, for CIN 3 is significantly lower than that for atrophy (76.7% vs 97.4%, p = .018). Conclusions. Routine histopathologic diagnosis of CIN 3 in menopausal women is highly accurate and reproducible. Both H&E and Ki-67 are useful immunohistochemical stains in helping differentiate atrophy from high-grade cervical intraepithelial lesions in postmenopausal cervical biopsies. There may be more disagreement among readers using p16.