Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of the Kynurenine-NAD+ Pathway Leads to Energy Failure and Exacerbates Apoptosis in Pneumococcal Meningitis

Pneumococcal meningitis causes neurological sequelae, including learning and memory deficits in up to half of the survivors. In both humans and in animal models of the disease, there is apoptotic cell death in the hippocampus, a brain region involved in learning and memory function. We previously demonstrated that in an infant rat model of pneumococcal meningitis, there is activation of the kynurenine(KYN) pathway in the hippocampus, and that there was a positive correlation between the concentration of 3-hydroxykynurenine and the extent of hippocampal apoptosis. To clarify the role of the KYN pathwayin the pathogenesis of hippocampal apoptosis in pneumococcal meningitis, we specifically inhibited 2 key enzymes of the KYN pathwayand assessed hippocampal apoptosis, KYN pathway metabolites, and nicotinamide adenine dinucleotide (NAD) concentrations by high-performance liquid chromatography. Pharmacological inhibition of kynurenine 3-hydroxylase and kynureninase led to decreased cellular NAD+ levels and increased apoptosis in the hippocampus. The cerebrospinalfluid levels of tumor necrosis factor and interleukin-1&agr; and -&bgr; werenotaffected. Our data suggest that activation of the KYN pathwayin pneumococcal meningitis is neuroprotective by compensating foran increased NAD+ demand caused by infection and inflammation;this mechanism may prevent energy failure and apoptosis in the hippocampus.
Erythropoietin-induced changes in brain gene expression reveal induction of synaptic plasticity genes in experimental stroke

Erythropoietin (EPO) is a neuroprotective cytokine in models of ischemic and nervous system injury, where it reduces neuronal apoptosis and inflammatory cytokines and increases neurogenesis and angiogenesis. EPO also improves cognition in healthy volunteers and schizophrenic patients. We studied the effect of EPO administration on the gene-expression profile in the ischemic cortex of rats after cerebral ischemia at early time points (2 and 6 h). EPO treatment up-regulated genes already increased by ischemia. Hierarchical clustering and analysis of overrepresented functional categories identified genes implicated in synaptic plasticity—Arc, BDNF, Egr1, and Egr2, of which Egr2 was the most significantly regulated. Up-regulation of Arc, BDNF, Dusp5, Egr1, Egr2, Egr4, and Nr4a3 was confirmed by quantitative PCR. We investigated the up-regulation of Egr2/Krox20 further because of its role in neuronal plasticity. Its elevation by EPO was confirmed in an independent in vivo experiment of cerebral ischemia in rats. Using the rat neuroblastoma B104, we found that wild-type cells that do not express EPO receptor (EPOR) do not respond to EPO by inducing Egr2. However, EPOR-expressing B104 cells induce Egr2 early upon incubation with EPO, indicating that Egr2 induction is a direct effect of EPO and that EPOR mediates this effect. Because these changes occur in vivo before decreased inflammatory cytokines or neuronal apoptosis is evident, these findings provide a molecular mechanism for the neuroreparative effects of cytokines and suggest a mechanism of neuroprotection by which promotion of a plastic phenotype results in decreased inflammation and neuronal death.
Codes on the Klein quartic, ideals, and decoding

A sequence of codes with particular symmetries and with large rates compared to their minimal distances is constructed over the field GF (2^{3}) . In the sequence there is, for instance, a code of length 21 and dimension 10 with minimal distance 9 , and a code of length 21 and dimension 16 with minimal distance 3 . The codes are constructed from algebraic geometry using the dictionary between coding theory and algebraic curves over finite fields established by Goppa. The curve used in the present work is the Klein quartic. This curve has the maximal number of rational points over GF (2^{3}) allowed by Serre's improvement of the Hasse-Weil bound, which, together with the low genus, accounts for the good code parameters. The Klein quartic has the Frobenius group G of order 21 acting as a group of automorphisms which accounts for the particular symmetries of the codes. In fact, the codes are given alternative descriptions as left ideals in the group-algebra GF (2^{3})[G] . This description allows for easy decoding. For instance, in the case of the single error correcting code of length 21 and dimension 16 with minimal distance 3 . decoding is obtained by multiplication with an idempotent in the group algebra.
Pathogenicity of Entomopathogenic Fungi Metarhizium anisopliae and Beauveria bassiana (Hypocreales: Clavicipitaceae) Isolates to the Adult Pea Leafminer (Diptera: Agromyzidae) and Prospects of an Autoinoculation Device for Infection in the Field

ABSTRACT Seventeen isolates of Metarhizium anisopliae (Metschnikoff) Sorokin and three isolates of Beauveria bassiana (Balsamo) Vuillemin (Hypocreales: Clavicipitaceae) were evaluated for their pathogenicity to the adult pea leafminer, Liriomyza huidobrensis (Blanchard) (Diptera: Agromyzidae), in the laboratory. Flies were contaminated with dry conidia through a velvet material wrapped around the inner side of a cylindrical plastic tube. All the isolates were pathogenic to the pea leafminer, causing mortality between 40 and 100% at 5 d after exposure. The lethal time for 50% mortality (LT50) ranged from 2.6 to 5.4 d, whereas the LT90 values varied between 3.2 and 9.1 d depending on the isolate. An autoinoculation device was evaluated in cage field experiments using only one of the virulent isolates, M. anisopliae ICIPE 20. The device was loaded with 2–3 g of dry conidia. Mortality of up to 100% was observed in flies captured from fungus-treated cages held under laboratory conditions. The average number of spores picked up by a single fly visiting the device increased with days after inoculation. One day after the inoculation, adults picked up an average of 4.1 ± 0.7 × 105 conidia and 39.6 ± 4.0 × 105 conidia 5 d after inoculation. Depending on the sampling date, the LT50 varied between 1.8 and 3.4 d. Results indicate that some isolates of B. bassiana and M. anisopliae are highly pathogenic to L. huidobrensis, suggesting a potential for their use in the control of this pest. They also suggest the possibility of L. huidobrensis suppression with fungi using an autoinoculation device.
Living with the 2-digit year-Year 2000 maintenance using a procedural solution

The paper is based on experience at the (US) Defense Logistics Agency Systems Design Center (DSDC) in developing and implementing a tool set and processes for remediation of the Year 2000 problem using a procedural approach. The problem and four general solution strategies are briefly described. DSDC's reasons for early focus on a “windowing” approach are discussed. The tools are discussed in terms of the problems they address and the degree of automation they can (and cannot) supply. A step by step process for mainframe batch COBOL, based on the tools, is summarized
Resumptive pronouns as last resort: Implications for language acquisition

In this paper I will be concerned with the acquisition of resumptive pronouns (RPs) appearing in restrictive relative clauses in Brazilian Portuguese and English. The distribution of RPs across languages is not uniform. While some languages make productive use of these elements (like Hebrew), other languages have a more restricted distribution of RPs (like English). Sells (1984), referring to these two types of languages, calls the first type ‘true resumptive languages’ and the second, ‘intrusive pronoun languages’. It is important to note that there is variation in the distribution of RPs even among the ‘true resumptive languages’. That is, it is not the case that true resumptive languages allow RPs to appear everywhere indistinctively. Language-specific constraints may require RPs in some positions or disallow them from others. Observe in the chart below the distribution of RPs in Northern Palestinian Arabic (PA), Hebrew, Brazilian Portuguese (BP), and English:
Burden and cost of inpatient care for HIV-positive paediatric patients--status in the Cape Town metropole during the second week of March 1999. Paediatric HIV Census Group.

OBJECTIVE To determine the burden of the HIV epidemic on paediatric inpatient facilities in the teaching hospitals of the Cape metropole and tributaries to these hospitals. SETTING Second- and third-level hospitals. METHOD During the second week of March 1999 a multicentre collaborative census was performed of all paediatric beds in the teaching hospitals of Cape Town and all facilities draining to and from them. RESULTS One hundred and six HIV-infected patients were identified from a total of 1,264 beds. Thirty-nine children were in second-level beds or in a long-term residential facility. Fifty-six children were in second-level beds designated for acute care, and occupied 12% of all such beds. Ten children were in beds designated for the care of tuberculosis. Thirty-two (56%) of the acute admissions were for gastro-enteritis, and 13 (23%) were for pneumonia. In 10 children (18% of all admissions) recognised complications of HIV infection were direct causes of admission. For 29 children (35% of all admissions) the current admission was the first; the remainder had had a mean of 2.4 previous admissions. Fourteen children (25%) had received oxygen, and 26 (46%) had received intravenous therapy. Mean lifetime hospitalisation cost per infected child was calculated to be R19,712. The projected cost of a local initiative to reduce mother-to-child transmission is between R8,326 and R10,806 per vertical infection prevented. CONCLUSION The inpatient burden of HIV-infected children in Cape Town reflects an early stage of the epidemic. Compared with projected lifetime hospitalisation cost for infected children, an intervention to reduce vertical transmission cost would be cost effective.
Association of Increasing GFR with Change in Albuminuria in the General Population.

BACKGROUND AND OBJECTIVES Hyperfiltration at the single-nephron level has been proposed as an early stage of kidney dysfunction of different origins. Evidence supporting this hypothesis in humans is lacking, because there is no method of measuring single-nephron GFR in humans. However, increased whole-kidney GFR in the same individual implies an increased single-nephron GFR, because the number of nephrons does not increase with age. We hypothesized that an increase in GFR would be associated with an increased albumin-to-creatinine ratio in a cohort of the general population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We measured GFR by iohexol clearance at baseline in 2007-2009 and follow-up after 5.6 years in a representative sample of 1246 persons (aged 50-62 years) who were nondiabetic from the general population of Tromso, northern Norway. Participants were without cardiovascular disease, kidney disease, or diabetes at baseline. We investigated the association between change in GFR and change in albumin-to-creatinine ratio. Increased GFR was defined as a positive change in GFR (change in GFR>0 ml/min) from baseline to follow-up. An albumin-to-creatinine ratio >30 mg/g was classified as albuminuria. RESULTS Change in GFR was positively associated with a change in albumin-to-creatinine ratio in the entire cohort in the multiple linear regression. The albumin-to-creatinine ratiofollow-up-to-albumin-to-creatinine ratiobaseline ratio increased by 8.0% (95% confidence interval, 1.4 to 15.0) per SD increase in change in GFR. When participants with increased GFR (n=343) were compared with those with a reduced GFR (n=903), the ratio increased by 16.3% (95% confidence interval, 1.1 to 33.7). The multivariable adjusted odds ratio for incident albuminuria (n=14) was 4.98 (95% confidence interval, 1.49 to 16.13) for those with an increased GFR (yes/no). CONCLUSIONS Increasing GFR is associated with an increase in albumin-to-creatinine ratio and incident albuminuria in the general nondiabetic population. These findings support single-nephron hyperfiltration as a risk factor for albuminuria in the general population.
Polymorphisms 1704G/T, 2184A/G, and 2245G/A in the rage gene are not associated with diabetic retinopathy in NIDDM: pilot study.

Pilot study perfromed on 531 Caucasian subjects proved that intron polymorphisms 1704G/T, 2184A/G and 2245G/A in the gene encoding receptor of advanced glycation end products (RAGE) are not associated with proliferative diabetic retinopathy in NIDDM.
Risananeiza crassaparies n. sp. from the upper Chattian of Porto Badisco (southern Apulia, Italy).

A new species of Rotaliidae, Risananeiza crassaparies n. sp. , is described from the upper Chattian of the Porto Badisco Calcarenites (Salento Peninsula, Southern Italy). The studied specimens are assigned to the foraminiferal genus Risananeiza based on the presence of vertical canals in both the ventral and dorsal side of the test, and an intraseptal canal system that evolves into marginal sutural canals. The new species differs from the type species of the genus, R. pustulosa, in having a lower chamber lumen, and smaller dimension.
A cost effective, community based heart health promotion project in England: prospective comparative study

Abstract Objective: To determine whether a community based coronary heart disease health promotion project, undertaken over four years, was associated with changes in the prevalence in adults of lifestyle risk factors known to affect the development of coronary heart disease, and to estimate whether such an approach was cost effective. Design: Prospective, comparative study of the effects of a health promotion intervention on coronary heart disease lifestyle risk factors, assessed by postal questionnaire sent to a randomly chosen sample, both at baseline and after four years. Subjects: Intervention and control populations of adults aged 18-64 in Rotherham, both from areas with a high incidence of coronary heart disease and similar socioeconomic composition. Main outcome measures: Changes in prevalence of lifestyle risk factors between the control and intervention communities from 1991 to 1995. The effect of the intervention on certain lifestyle behaviours was evaluated using multiple logistic regression to model the proportion with a particular behaviour in the study communities as a function of age (18-40 or 41-64 years), sex, the year of observation (1991 or 1995), and area (intervention or control). Results: 6.9% fewer people smoked and 8.7% more drank low fat milk in the intervention area, but no other statistically significant changes between the areas were detected. The estimated cost per life year gained was £31. Conclusions: It is possible to have a cost effective impact on coronary heart disease lifestyle risk factors in a population of adults over four years using only modest resources. Key messages Little is known about the cost effectiveness of focused, heart disease health promotion projects in reducing cardiovascular risk factors over a short period in small populations of adults Research was undertaken to estimate the impact of a heart disease health promotion project—Action Heart—and relate the cost to estimates of health gain Major differences were observed in changes in prevalence of active smoking and consumption of low fat milk between the intervention and control areas over four years The estimated cost per life year gained was £31 Further research is required to ascertain whether the changes in risk factors will be sustained after the end of Action Heart
The Etiology And Outcome Of Adult Patients Presenting With Sepsis To The University Teaching Hospital, Lusaka, Zambia.

Background Sepsis accounts for a significant burden of morbidity and mortality.In developed world, it is implicated as the second leading cause of non-cardiac death. Mortality from sepsis is on the increase with a mortality rate of 33-61%. In spite of the high burden of sepsis in sub Saharan Africa, data regarding the etiology and outcome of septic patients is limited. We conducted a prospective cohort study to describe the etiology, characteristic and outcome of patients presenting with sepsis to the University Teaching Hospital in Lusaka, Zambia. Methods Patients who met the inclusion criteria were enrolled into the study and after a thorough examination, bloods were drawn for full blood count, urea and electrolytes, liver function tests and for culture. Samples for culture were collected under aseptic techniques and cultured for aerobic organisms. Biochemical and bacteriological methods were used to identify the isolates and antibiotic sensitivity patterns were determined using agar diffusion methods. Patients were then followed up until they either demised or were discharge. Results A total of 161 patients were enrolled of which 110(68%) were HIV positive and 23(14%) had unknown HIV status. Bacteremia was found in 39 (24%) with the most isolated organism being staphylococcus aureus. Mortality in our cohort of septic patients was determinedat 40%. Identified predictors for in patient mortality were low admission Glasgow coma scale[OR 11.2(CI 3.5-36.4)], positive blood culture[OR 2.38(CI 1.14-4.95)] and HIV status, those with unknown HIV status were more likely to die than those who were HIV negative[OR 8.38(CI2.36-29.7)]. Conclusion Most of the septic patients presenting to UTH had advanced immunosuppression (WHO stage 3 and 4) and had a high mortality rate. Staphylococcus aureus and streptococcus pneumoniae were the highest isolates. Identified predictors for in patient mortality could be used to try and improve outcome in septic patients at UTH.
Psychometric Correlates of Episodic Violent Behaviour

Three groups of neuropsychiatric out-patients, homogeneous according to parameters of violent behaviour, were identified in a previous study using a cluster analysis procedure and compared in this study on psychometric variables. These groups were (a) a group manifesting frequent, impulsive violence (n = 35), (b) a non-violent group (n = 57), and (c) a group whose violent behaviour was much less frequent and severe than in the first group, and more provoked (n = 31). Impulsively violent patients showed language and visual-perceptual deficits, but no other neuropsychological or intellectual deficits. The MMPI F, K and Ma and MacAndrews Alcoholism scales and a perceptual organisation factor derived from the Holtzman Inkblot Test significantly discriminated groups. Results of this and the initial study have implications regarding psychological aspects of aggression and underlying biological mechanisms.
Prefiltering-based ESPRIT for estimating sinusoidal parameters in non-Gaussian ARMA noise

Addresses the ESPRIT algorithm for estimating sinusoidal parameters in non-Gaussian ARMA noise. The authors show that after prefiltering the output data via the estimated AR polynomial of the noise model, a new ESPRIT based on some extensions of ESPRIT can be used to estimate sinusoidal parameters. >
Assessment of adipose tissue metabolism by means of subcutaneous microdialysis in patients with sepsis or circulatory failure

To evaluate the role of adipose tissue in the metabolic stress response of critically ill patients, the release of glycerol and lactate by subcutaneous adipose tissue was assessed by means of microdialysis in patients with sepsis or circulatory failure and in healthy subjects. Patients with sepsis had lower plasma free fatty acid concentrations and non‐significant elevations of plasma glycerol concentrations, but higher adipose‐systemic glycerol concentrations gradients than healthy subjects or patients with circulatory failure, indicating a stimulation of subcutaneous adipose lipolysis. They also had a higher lipid oxidation. Lipid metabolism (adipose‐systemic glycerol gradients, lipid oxidation) was not altered in patients with circulatory failure. These observations highlight major differences in lipolysis and lipid utilization between patients with sepsis and circulatory failure. Hyperlactataemia was present in both groups of patients, but the adipose‐systemic lactate concentration gradient was not increased, indicating that lactate production by adipose tissue was not involved. This speaks against a role of adipose tissue in the development of hyperlactataemia in critically ill patients.
The Behçet's disease-associated variant of the aminopeptidase ERAP1 shapes a low-affinity HLA-B*51 peptidome by differential subpeptidome processing

A low-activity variant of endoplasmic reticulum aminopeptidase 1 (ERAP1), Hap10, is associated with the autoinflammatory disorder Behçet's disease (BD) in epistasis with HLA-B*51, which is the main risk factor for this disorder. The role of Hap10 in BD pathogenesis is unknown. We sought to define the effects of Hap10 on the HLA-B*51 peptidome and to distinguish these effects from those due to HLA-B*51 polymorphisms unrelated to disease. The peptidome of the BD-associated HLA-B*51:08 subtype expressed in a Hap10-positive cell line was isolated, characterized by mass spectrometry, and compared with the HLA-B*51:01 peptidome from cells expressing more active ERAP1 allotypes. We additionally performed synthetic peptide digestions with recombinant ERAP1 variants and estimated peptide-binding affinity with standard algorithms. In the BD-associated ERAP1 context of B*51:08, longer peptides were generated; of the two major HLA-B*51 subpeptidomes with Pro-2 and Ala-2, the former one was significantly reduced, and the latter was increased and showed more ERAP1-susceptible N-terminal residues. These effects were readily explained by the low activity of Hap10 and the differential susceptibility of X–Pro and X–Ala bonds to ERAP1 trimming and together resulted in a significantly altered peptidome with lower affinity. The differences due to ERAP1 were clearly distinguished from those due to HLA-B*51 subtype polymorphism, which affected residue frequencies at internal positions of the peptide ligands. The alterations in the nature and affinity of HLA-B*51·peptide complexes probably affect T-cell and natural killer cell recognition, providing a sound basis for the joint association of ERAP1 and HLA-B*51 with BD.
A MASSIVE MOLECULAR GAS RESERVOIR IN THE z = 5.3 SUBMILLIMETER GALAXY AzTEC-3

We report the detection of CO J = 2→1, 5→4, and 6→5 emission in the highest-redshift submillimeter galaxy (SMG) AzTEC-3 at z = 5.298, using the Expanded Very Large Array and the Plateau de Bure Interferometer. These observations ultimately confirm the redshift, making AzTEC-3 the most submillimeter-luminous galaxy in a massive z ≃ 5.3 protocluster structure in the COSMOS field. The strength of the CO line emission reveals a large molecular gas reservoir with a mass of 5.3 × 1010(αCO/0.8) M☉, which can maintain the intense 1800 M☉ yr−1 starburst in this system for at least 30 Myr, increasing the stellar mass by up to a factor of six in the process. This gas mass is comparable to “typical” z ∼ 2 SMGs and constitutes ≳80% of the baryonic mass (gas+stars) and 30%–80% of the total (dynamical) mass in this galaxy. The molecular gas reservoir has a radius of <4 kpc and likely consists of a “diffuse”, low-excitation component, containing (at least) 1/3 of the gas mass (depending on the relative conversion factor αCO), and a “dense”, high-excitation component, containing ∼2/3 of the mass. The likely presence of a substantial diffuse component besides highly excited gas suggests different properties between the star-forming environments in z > 4 SMGs and z > 4 quasar host galaxies, which perhaps trace different evolutionary stages. The discovery of a massive, metal-enriched gas reservoir in an SMG at the heart of a large z = 5.3 protocluster considerably enhances our understanding of early massive galaxy formation, pushing back to a cosmic epoch where the universe was less than 1/12 of its present age.