Miracle-dz/UniFAR-FTUs huggingface dataset:
The Chédiak-Higashi syndrome; the nature of the giant neutrophil granules and their interactions with cytoplasm and foreign particulates. I. Progressive enlargement of the massive inclusions in mature neutrophils. II. Manifestations of cytoplasmic injury and sequestration. III. Interactions between 

Defective bactericidal functioning of polymorphonuclear leukocytes (PMNs) from patients with the Chédiak-Higashi syndrome (CHS) has been related in previous reports to a failure of the giant granules characteristics of the disorder to participate in degranulation after uptake of foreign particulates by neutrophils. However, the reason massive CHS inclusions do not fuse with and discharge their contents into phagocytic vacuoles has not been defined. The problem is particularly puzzling because it has been postulated that the hugh organelles in CHS neutophils originate by fusion of small azurophilic granules in promyelocytes and myelocytes. The present series of investigations into the cytopathology of the CHS has employed electron microscopy and ultrastructural cytochemistry to characterize the progressive enlargement of the hugh bodies in mature PMNs, their interaction with cytoplasmic constituents resulting in various manifestations of cell injury, and their response to foreign particulates. Each study clarifies abnormal features of the giant organelles essential to the understanding of their role in the defective bactericidal function of CHS neutrophils. The first report demonstrates that most of the hugh inclusions in PMNs are not primary lysosomes. The interaction and fusion of giant azurophilic granules with each other, with normal-sized primary and secondary granules, and with cytoplasmic components converts the massive primary granules into huge secondary lysosomes. Transformation to secondary hysosomes represents a critical alteration in the state of the giant granules that underlies their damaging influence on the cytoplasm and loss of reactivity wtih phagocytic vacuoles.
The reducing sugars liberated during the bacterial synthesis of polysaccharides from sucrose.

SUMMARY: Paper chromatography was used for studying qualitatively and quantitatively the reducing sugars liberated from sucrose during the synthesis of polysaccharides by certain bacteria. Glucose and fructose were the only sugars detected, varying in amount with the bacteria and with the type of polysaccharide synthesized. The results suggest that both polymerizing and hydrolytic enzymes were present.
Cyclooxygenase 2 inhibition protects motor neurons and prolongs survival in a transgenic mouse model of ALS

The pathogenesis of cell death in amyotrophic lateral sclerosis (ALS) may involve glutamate‐mediated excitotoxicity, oxidative damage, and apoptosis. We used a transgenic mouse model of ALS to determine the effect of inhibition of cyclooxygenase‐2 in treating the disease. Cyclooxygenase‐2, present in spinal neurons and astrocytes, catalyzes the synthesis of prostaglandin E2. Prostaglandin E2 stimulates glutamate release from astrocytes, whereas cyclooxygenase‐2 also plays a key role in the production of proinflammatory cytokines, reactive oxygen species, and free radicals. Treatment with a selective cyclooxygenase‐2 inhibitor, celecoxib, markedly inhibited production of prostaglandin E2 in the spinal cords of ALS mice. Celecoxib treatment significantly delayed the onset of weakness and weight loss and prolonged survival by 25%. Spinal cords of treated ALS mice showed significant preservation of spinal neurons and diminished astrogliosis and microglial activation. Our results suggest that cyclooxygenase‐2 inhibition may benefit ALS patients. Ann Neurol 2002
Establishment of liver specific glucokinase gene knockout mice: a new animal model for screening anti-diabetic drugs.

AIM To characterize the liver-specific role of glucokinase in maintaining glucose homeostasis and to create an animal model for diabetes. METHODS We performed hepatocyte-specific gene knockout of glucokinase in mice using Cre-loxP gene targeting strategy. First, two directly repeated loxP sequences were inserted to flank the exon 9 and exon 10 of glucokinase in genomic DNA. To achieve this, linearized targeting vector was electroporated into ES cells. Then G418- and Gancyclovir-double-resistant clones were picked and screened by PCR analysis and the positives identified by PCR were confirmed by Southern blot. A targeted clone was selected for microinjection into C57BL/6J blastocysts and implanted into pseudopregnant FVB recipient. Chimeric mice and their offspring were analyzed by Southern blot. Then by intercrossing the Alb-Cre transgenic mice with mice containing a conditional gk allele, we obtained mice with liver-specific glucokinase gene knockout. RESULTS Among 161 double resistant clones 4 were positive to PCR and Southern blot and only one was used for further experiments. Eventually we generated the liver specific glucokinase knockout mice. These mice showed increased glucose level with age and at the age of 6 weeks fasting blood glucose level was significantly higher than control and they also displayed impaired glucose tolerance. CONCLUSION Our studies indicate that hepatic glucokinase plays an important role in glucose homeostasis and its deficiencies contribute to the development of diabetes. The liver glucokinase knockout mouse is an ideal animal model for MODY2, and it also can be applied for screening anti-diabetic drugs.
Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochlea

Transcriptional regulatory networks are essential during the formation and differentiation of organs. The transcription factor N-myc is required for proper morphogenesis of the cochlea and to control correct patterning of the organ of Corti. We show here that the Otx2 gene, a mammalian ortholog of the Drosophila orthodenticle homeobox gene, is a crucial target of N-myc during inner ear development. Otx2 expression is lost in N-myc mouse mutants, and N-myc misexpression in the chick inner ear leads to ectopic expression of Otx2. Furthermore, Otx2 enhancer activity is increased by N-myc misexpression, indicating that N-myc may directly regulate Otx2. Inactivation of Otx2 in the mouse inner ear leads to ectopic expression of prosensory markers in non-sensory regions of the cochlear duct. Upon further differentiation, these domains give rise to an ectopic organ of Corti, together with the re-specification of non-sensory areas into sensory epithelia, and the loss of Reissner's membrane. Therefore, the Otx2-positive domain of the cochlear duct shows a striking competence to develop into a mirror-image copy of the organ of Corti. Taken together, these data show that Otx2 acts downstream of N-myc and is essential for patterning and spatial restriction of the sensory domain of the mammalian cochlea. Summary: A microarray-based screen identifies Otx2 as a crucial target of N-myc, and further studies show that Otx2 is essential for spatial restriction of the sensory domain in the mammalian cochlea.
Robustness to Strategic Uncertainty

We introduce a criterion for robustness to strategic uncertainty in games with continuum strategy sets. We model a player's uncertainty about another player's strategy as an atomless probability distribution over that player's strategy set. We call a strategy profile robust to strategic uncertainty if it is the limit, as uncertainty vanishes, of some sequence of strategy profiles in which every player's strategy is optimal under his or her uncertainty about the others. When payoff functions are continuous we show that our criterion is a refinement of Nash equilibrium and we also give sufficient conditions for existence of a robust strategy profile. In addition, we apply the criterion to Bertrand games with convex costs, a class of games with discontinuous payoff functions and a continuum of Nash equilibria. We show that it then selects a unique Nash equilibrium, in agreement with some recent experimental findings.
Dendritic cells contribute to the development of atopy by an insufficiency in IL-12 production.

BACKGROUND IL-12 is a crucial factor in the development and course of allergic diseases. By virtue of their IL-12 production, dendritic cells (DCs) are potent inducers of T(H)1 responses. However, distinct subsets of DCs have also been shown to induce T(H)2 differentiation. OBJECTIVE We hypothesized that DCs from atopic and nonatopic individuals might differ in their propensity to skew T-cell responses to either the T(H)1 type or the T(H)2 type. To this end, we investigated the cytokine patterns produced by DCs from atopic and nonatopic individuals, and we attempted to clarify whether this could be due to different DC lineages or, alternatively, to different microenvironmental factors. METHODS DCs were generated from lymphocyte-depleted PBMCs from atopic and nonatopic donors and fully matured with monocyte-conditioned medium. Production of IL-4, IL-5, IL-10, IL-12, and IL-13 in response to CD40 ligation was measured with ELISA. DC subsets were identified in PBMCs from freshly drawn blood by 3-color flow cytometry. RESULTS Compared with DCs from healthy donors, monocyte-derived DCs from atopic patients produced less bioactive IL-12 and IL-10. DC production of IL-4, IL-13, and IL-5 was not detected. Relatively more CD123(+) DCs, corresponding to T(H)2-inducing "DC2s," were found in PBMCs from atopic patients. CONCLUSION The data suggest that in addition to the described abnormalities in the patients' T-cell populations, DCs might also critically contribute to the atopic/allergic T(H)1 outcome in the patient and thus to the disease.
Characterization of the Polycomb-Group Mark H3K27me3 in Unicellular Algae

Polycomb Group (PcG) proteins mediate chromatin repression in plants and animals by catalyzing H3K27 methylation and H2AK118/119 mono-ubiquitination through the activity of the Polycomb repressive complex 2 (PRC2) and PRC1, respectively. PcG proteins were extensively studied in higher plants, but their function and target genes in unicellular branches of the green lineage remain largely unknown. To shed light on PcG function and modus operandi in a broad evolutionary context, we demonstrate phylogenetic relationship of core PRC1 and PRC2 proteins and H3K27me3 biochemical presence in several unicellular algae of different phylogenetic subclades. We focus then on one of the species, the model red alga Cyanidioschizon merolae, and show that H3K27me3 occupies both, genes and repetitive elements, and mediates the strength of repression depending on the differential occupancy over gene bodies. Furthermore, we report that H3K27me3 in C. merolae is enriched in telomeric and subtelomeric regions of the chromosomes and has unique preferential binding toward intein-containing genes involved in protein splicing. Thus, our study gives important insight for Polycomb-mediated repression in lower eukaryotes, uncovering a previously unknown link between H3K27me3 targets and protein splicing.
Calcium, dairy products, and risk of prostate cancer in a prospective cohort of United States men.

Intake of calcium and/or dairy products has been associated with increased risk of prostate cancer in some epidemiological studies. One potential biological mechanism is that high calcium intake down-regulates 1,25 dihydroxy vitamin D(3), which may increase cell proliferation in the prostate. We examined the association between calcium, dairy intake, and prostate cancer incidence in the Cancer Prevention Study II Nutrition Cohort, a prospective cohort of elderly United States adults. Participants in the study completed a detailed questionnaire on diet, medical history, and lifestyle at enrollment in 1992-1993. After excluding men with a history of cancer or incomplete dietary information, 65,321 men remained for analysis. During follow-up through August 31, 1999, we documented 3811 cases of incident prostate cancer. Multivariate-adjusted rate ratios (RRs) were calculated using Cox proportional hazards models. Total calcium intake (from diet and supplements) was associated with modestly increased risk of prostate cancer [RR = 1.2, 95% confidence interval (CI) = 1.0-1.6 for >or=2000 versus <700 mg/day, P trend = 0.02). High dietary calcium intake (>or=2000 versus <700 mg/day) was also associated with increased risk of prostate cancer (RR = 1.6, 95% CI = 1.1-2.3, P trend = 0.10), although moderate levels of dietary calcium were not associated with increased risk. Dairy intake was not associated with prostate cancer risk. The association between prostate cancer and total calcium intake was strongest for men who reported not having prostate-specific antigen testing before 1992 (RR = 1.5, 95% CI = 1.1-2.0, P trend < 0.01 for >or= 2000 mg/day of total calcium; RR = 2.1, 95% CI = 1.3-3.4 >or=2000 mg/day of dietary calcium, P trend = 0.04). Our results support the hypothesis that very high calcium intake, above the recommended intake for men, may modestly increase risk of prostate cancer.
Effects of sevoflurane and desflurane on the blood and plasma viscosity

The purpose of present study was to compare the effects of desflurane and sevoflurane on blood viscosity in three different shear rates and plasma viscosity. Forty male patients, ASAI-II, undergone tympanoplasty were included in this study. Patients were randomly categorized as anaesthetized either with sevoflurane or desflurane. Anaesthesia was maintained with inspiratory concentrations of sevoflurane 1-1.5 MAC or desflurane. The samples were taken for hemorheological and biochemical examinations before induction of anaesthesia (initial time) and at 60 th and 120 th min of the operation. Blood viscosities were measured by rotational viscometer. Plasma viscosity was measured by capillary viscometer. Patients receiving desflurane showed steady decrease at 23 1/sec shear rate at 60 th and 120 th min and in blood viscosity at 115 1/sec shear rate in 120 th min. Statistically significant decrease in the level of plasma viscosity was observed in the patient group anesthetized with desflurane, between initial time vs 60 th min (p<0.01), initial time vs 120 th min. (p<0.01). Desflurane produced stable effects on the blood circulation. The differences in the blood viscosity should not be overlooked. Keywords : Desflurane, Sevoflurane, Blood viscosity, Plasma viscosity
Genotype-Specific Changes in Vitamin B6 Content and the PDX Family in Potato

Vitamin B6 is one of the most versatile cofactors in plants and an essential phytonutrient in the human diet that benefits a variety of human health aspects. Although biosynthesis of the vitamin has been well resolved in recent years, the main research is currently based on Arabidopsis thaliana with very little work done on major crop plants. Here we provide the first report on interactions and expression profiles of PDX genes for vitamin B6 biosynthesis in potato and how vitamin B6 content varies in tubers of different genotypes. The results demonstrate that potato is an excellent resource for this vitamin and that strong natural variation in vitamin B6 content among the tested cultivars indicates high potential to fortify vitamin B6 nutrition in potato-based foods.
Evaluative Adjectives: An AdjunctControl Analysis

Evaluative adjectives like stupid, smart, silly, and rude have been recognized as a coherent syntactic and semantic class for over forty years (Lees 1960, Bolinger 1961, Vendler 1963, 1968, Quirk et al. 1985). The class has gained recent attention, however, from syntacticians looking to extend analyses of argument alignment in the verbal domain to the adjectival domain (Stowell 1991, Bennis 2000, 2004, Landau 2006) and from semanticists examining the interpretation of ‘vague’ predicates (Barker 2002, inter alia). The majority of these analyses make a starting assumption that the embedded infinitival in an evaluative control structure like (1) is an optional thematic argument of the adjective.
Eliminating Useless Messages in Write-Update Protocols on Scalable Multiprocessors

Cache coherence protocols for shared-memory multiprocessors use invalidations or updates to maintain coherence across processors. Although invalidation protocols usually produce higher miss rates, update protocols typically perform worse. Detailed simulations of these two classes of protocol show that the excessive network traffic caused by update protocols significantly degrades performance, even with infinite bandwidth. Motivated by this observation, we categorize the coherence traffic in update-based protocols and show that, for most applications, more than 90\% of all updates generated by the protocol are unnecessary. We identify application characteristics that generate useless update traffic, and compare the isolated and combined effects of several software and hardware techniques for eliminating useless updates. These techniques include dynamic and static hybrid protocols, false sharing elimination strategies, and coalescing write buffers. Our simulations show that software caching (where coherence is managed under programmer or compiler control) and the dynamic hybrid protocol reduce useless updates the most, but coalescing write buffers produce fewer, albeit larger, coherence messages. As a result, coalescing write buffers usually produce the best running time, except when the block size is large or the bandwidth is limited. Finally, based on the observation that the techniques we consider are unable to eliminate a large number of useless updates, we suggest directions for further reducing the useless traffic in update-based protocols.
Which IoT Protocol? Comparing Standardized Approaches over a Common M2M Application

Computing devices already permeate working and living environments, while researchers and engineers aim to exploit the potential of pervasive systems in order to introduce new types of services and address inveterate and emerging problems. This process will lead us eventually to the era of urban computing and the Internet of Things (IoT). However, the long-promised improvements require overcoming some significant obstacles introduced by these technological advancements. One such obstacle is the lack of interoperable solutions, to facilitate the use, monitoring and management of the plethora of devices and their services. While seamless machine-to-machine (M2M) and human-to-machine (H2M) interactions are a necessity for secure and truly ubiquitous computing, the current status quo is that of a segregated and incompatible assortment of devices. The resource-constraints of the platforms integrated into smart environments, and their heterogeneity in hardware, network and overlaying technologies, only exacerbate these interoperability issues. Motivated by the above, this paper identifies three promising, standardized protocols, each following a different approach in addressing the above concerns. We evaluate the selected protocols in the context of designing and implementing an application requiring various M2M interactions, namely a policy-based access control framework for IoT devices. Thus, three variants of the application are developed, considering each protocol's intrinsic characteristics and features. Finally, the developed applications are evaluated on a common testbed of embedded devices, allowing us to extract useful conclusions concerning the protocols' performance, their intricacies and their applicability in similar applications.
Decomposing the age-related deficit in free recall

The temporal relations among list items exert a powerful influence on episodic memory retrieval. For example, in free recall, participants exhibit marked recency and contiguity effects: temporal proximity of an item to the time of test and temporal proximity of an item to the justrecalled item both serve to promote retrieval. Previous research has focused on the serial position curve as a means of assessing the role of recency-sensitive processes in memory retrieval. We employ a decomposition method to the serial position curve, partitioning performance into recency-sensitive and contiguity-sensitive processes (e.g., M. W. Howard and M. J. Kahana, 1999). Two experiments examined the age-related deficit in free recall. Although recencysensitive processes, reflecting self-initiated recall, were indistinguishable for young and older adults, contiguity-sensitive processes, reflecting temporal association, were markedly impaired in older adults. This finding of a clear associative deficit in normal aging constitutes direct evidence for M. Naveh-Benjamin’s (2000) associative deficit hypothesis, and suggests that this associative deficit may be responsible for older adults’ well-known impairment in free recall. Although older adults also made many more intrusions than the young, this cannot provide an explanation for the associative deficit. In contrast, an associative deficit could cause more intrusions by means of a lowered recall criterion.
[Disturbed maturation of oligodendrocyte progenitors in lipopolysaccharide-induced hypomyelination in cultured forebrain slices of neonatal rats].

INTRODUCTION This study was performed to determine whether the disturbed maturation of oligodendrocyte (OL) progenitors might be related to lipopolysaccharide (LPS)-induced hypomyelination. MATERIAL AND METHODS We created organotypic cultures of forebrain slices from neonatal rats and explored the morphological changes of glial cells expressing tumour necrosis factor  (TNF-) following LPS exposure. RESULTS We observed marked activation of glial fibrillary acidic protein-positive astrocytes and OX42-positive microglia co-labelled with TNF- four days following LPS exposure. Our results further demonstrated a reduced expression of O4-positive and O1-positive OL progenitors; moreover, we found that their morphologies were suggestive of degeneration (e.g., scanty, rounded bodies with short, fragmented processes and/or cytoplasmic condensation). At seven days following LPS exposure, astrocytes and microglia were still co-labelled for TNF-; however, the expression of O4-positive and O1-positive cells somewhat increased compared to the number observed at 4 days; despite remaining undifferentiated and exhibiting immature morphologies, the cells were likely indicative of regeneration. In contrast, O4-positive and O1-positive cells in controls were well-differentiated, displaying round, thick cell bodies and long, branching processes. CONCLUSIONS In conclusion, maturation arrest and/or under-differentiation of OL progenitors commonly occur during regeneration: they may underlie the degeneration and consequent hypomyelination occurring late after injury, or apoptosis during the acute stage post-injury. Microglia and astrocytes expressing TNF- may also contribute to later myelination failure.