Miracle-dz/UniFAR-FTUs huggingface dataset:
Suppression of murine allergic contact dermatitis by CTLA4Ig. Tolerance induction of Th2 responses requires additional blockade of CD40-ligand.

Blockade of costimulation through the B7-CD28 pathway by CTLA4Ig can lead to Ag-specific T cell tolerance. Most models studied to date involve a Th1-dependent response. To investigate whether the tolerizing effects of CTLA4Ig might vary depending upon the cytokine nature of the immune response, we studied its effects on contact hypersensitivity (CHS) in response to two allergens. In BALB/c mice, both 2,4-dinitrofluorobenzene (DNFB) and FITC induce CHS. However, the DNFB response is Th1-predominant, while the FITC response is Th2 predominant. CTLA4Ig treatment during primary sensitization induced long-lasting unresponsiveness to DNFB, with 88% and 76% inhibition of primary (first challenge) and secondary (re-sensitization and re-challenge) CHS, respectively. In contrast, CTLA4Ig inhibited primary CHS to FITC by over 82% but had little effect on secondary CHS. Consistent with its effects on CHS, the suppressive effect of CTLA4Ig on Th2 cells was short-lived in FITC-sensitized mice, while Th1-like cytokine-secreting cells remained reduced in DNFB-sensitized mice, even when the animals were rechallenged with DNFB. The addition of anti-CD40L Ab to CTLA4Ig was able to induce long-lasting unresponsiveness to FITC, indicating the ability of cells mounting this Th2 response to receive costimulatory signals through either pathway. In conclusion, CHS can be mediated by both Th1 and Th2 cells, and the ability of CTLA4Ig to lead to long-standing nonresponsiveness in this model depends on the nature (i.e., cytokine profile) of the immune response.
Reactions of 5-methylcytosine cation radicals in DNA and model systems: Thermal deprotonation from the 5-methyl group vs. excited state deprotonation from sugar

Abstract Purpose: To study the formation and subsequent reactions of the 5-methyl-2′-deoxycytidine cation radical (5-Me-2′-dC•+) in nucleosides and DNA-oligomers and compare to one-electron oxidized thymidine. Materials and methods: Employing electron spin resonance (ESR), cation radical formation and its reactions were investigated in 5-Me-2′-dC, thymidine (Thd) and their derivatives, in fully double-stranded (ds) d[GC*GC*GC*GC*]2 and in the 5-Me-C/A mismatched, d[GGAC*AAGC:CCTAATCG], where C* = 5-Me-C. Results: We report 5-Me-2′-dC•+ production by one-electron oxidation of 5-Me-2′-dC by Cl2•− via annealing in the dark at 155 K. Progressive annealing of 5-Me-2′-dC•+ at 155 K produces the allylic radical (C-CH2•). However, photoexcitation of 5-Me-2′-dC•+ by 405 nm laser or by photoflood lamp leads to only C3′• formation. Photoexcitation of N3-deprotonated thyminyl radical in Thd and its 5′-nucleotides leads to C3′• formation but not in 3′-TMP which resulted in the allylic radical (U-CH2•) and C5′• production. For excited 5-Me-2′,3′-ddC•+, absence of the 3′-OH group does not prevent C3′• formation. For d[GC*GC*GC*GC*]2 and d[GGAC*AAGC:CCTAATCG], intra-base paired proton transferred form of G cation radical (G(N1-H)•: C(+ H+)) is found with no observable 5-Me-2′-dC•+ formation. Photoexcitation of (G(N1-H)•:C(+ H+)) in d[GC*GC*GC*GC*]2 produced only C1′• and not the expected photoproducts from 5-Me-2′-dC•+. However, photoexcitation of (G(N1-H)•:C(+ H+)) in d[GGAC*AAGC:CCTAATCG] led to C5′• and C1′• formation. Conclusions: C-CH2• formation from 5-Me-2′-dC•+ occurs via ground state deprotonation from C5-methyl group on the base. In the excited 5-Me-2′-dC•+ and 5-Me-2′,3′-ddC•+, spin and charge localization at C3′ followed by deprotonation leads to C3′• formation. Thus, deprotonation from C3′ in the excited cation radical is kinetically controlled and sugar C-H bond energies are not the only controlling factors in these deprotonations.
Temperature and myogenesis in embryos of the Atlantic herring Clupea harengus

The development of axial muscles has been investigated in spring-spawning Atlantic herring (Clupea harengus L.) reared at 5, 8, 12 and 15 °C. In 1994, around 90 % of embryos hatched after 28 days at 5 °C, 16 days at 8 °C, 9 days at 12 °C and 8 days at 15 °C. The somites were formed from cells of the paraxial mesoderm in a rostral to caudal direction, starting at the neural plate stage. Somites were added at rates ranging from one every 3 h at 5 °C to one every 52 min at 15 °C. A small number of myoblasts, located adjacent and lateral to the notochord, elongated to span the somite to form mononuclear myotubes. The majority of muscle fibres were formed by the fusion of 2­5 myoblasts to produce multinucleated myotubes that subsequently differentiated into either superficial or inner fibre types. The timing of myogenesis with respect to somite stage and the initial appearance of the gut, pectoral fin buds and pronephric tubules was found to vary with development temperature. For rostral myotomes, the synthesis of contractile filaments and myofibril assembly were first observed at the 42-, 38- and 27-somite stages at 5, 8 and 12 °C, respectively. The differentiation of myotubes into morphologically recognisable muscle fibre types first occurred at the 62-somite stage at 5 °C, at the 48-somite stage at 8 °C and as early as the 40-somite stage at 12 °C. Cell proliferation experiments with 5-bromo-2'-deoxyuridine showed that another population of myoblasts was activated on the surface of muscle fibres just prior to hatching. Development temperature also affected muscle cellularity; there were 43 % more inner muscle fibres in the myotomes of 1-day-old larvae reared at 12 °C than at 5 °C (P<0.02).
Brain injuries in early foetal life: consequences for brain development

Learning disability and cerebral palsy are often related to factors present before birth. We report three patients (two with schizencephaly, one with unilateral cerebellar agenesis) in whom the timing of an insult to the foetus was known. In the first case, the mother had a trauma at 16 weeks of pregnancy and schizencephaly was discovered in the male infant associated with a left hemiplegia. In the second child, amniocentesis performed at 16 weeks into pregnancy may have been responsible for the same cortical anomaly. In the third case, sequential foetal echographies clearly demonstrated that an apparent unilateral cerebellar agenesis was related to an haemorrhagic event secondary to cerebellar trauma that occurred at 19 weeks of pregnancy. It is suggested that these brain malformations are related to an ischemic mechanism or a traumatic event in foetal life.
Differential transcription of Eomes and T‐bet during maturation of mouse uterine natural killer cells

During human and rodent uterine decidualization, transient but abundant numbers of uterine natural killer (uNK) cells appear, proliferate, and differentiate. uNK cells share features with peripheral NK cells but are specialized to promote interferon‐γ (IFN‐γ)‐mediated, pregnancy‐associated, structural changes in maternal placental arteries. In CD8+ T cells and NK cells, the transcription factors T‐bet and eomesodermin (Eomes) regulate maturation and effector functions, including IFN‐γ production. No studies are reported for uNK cells. Implantation sites in T‐bet null mice, which have a defect in NK cell maturation, had uNK cells normal in morphology and number and normally modified spiral arteries. As Eomes null mice are not viable, real‐time polymerase chain reaction comparisons between C57Bl/6J (B6) and alymphoid (Rag20/0γc0/0) mice were used to assess uNK cell expression of T‐bet, Eomes, and the target genes IFN‐γ, granzyme A, and perforin. Gestation dated (gd) uterine tissues (mixed cell composition) and 200 morphologically homogeneous, laser‐capture, microdissected uNK cells of different maturation stages were used. In uterus, Eomes transcripts greatly outnumbered those of T‐bet, whether donors were nonpregnant or pregnant, and increased to gd10. In uNK cells, transcripts for T‐bet, Eomes, and IFN‐γ were most abundant in mature stage cells, and transcripts for granzyme A and perforin were lower at this stage than in immature or senescent cells. Thus, Eomes dominance to T‐bet discriminates regulation of the uNK cell subset from that observed for peripheral NK cells.
Modified finite-difference beam propagation method based on the generalized Douglas scheme for variable coefficients

The accuracy of the implicit finite-difference beam propagation method (FD-BPM), in which the phase term is not split, is improved using the generalized Douglas scheme. The propagation error of the fundamental mode in two- and three-dimensional waveguides is evaluated by the mode-mismatch loss calculation. It Is demonstrated that the truncation error is reduced to O(/spl Delta/x)/sup 4/ in the transverse direction, even when the parabolic wave equation contains variable coefficients, The computational time is almost identical to the conventional FD-BPM based on the Crank-Nicholson scheme. <<ETX>>
Iterated Ontology Revision by Reinterpretation

Iterated applications of belief change operators are essential for different scenarios such as that of ontology evolution where new information is not presented at once but only in piecemeal fashion within a sequence. I discuss iterated applications of so called reinterpretation operators that trace conflicts between ontologies back to the ambiguous of symbols and that provide conflict resolution strategies with bridging axioms. The discussion centers on adaptations of the classical iteration postulates according to Darwiche and Pearl. The main result of the paper is that reinterpretation operators fulfill the postulates for sequences containing only atomic triggers. For complex triggers, a fulfillment is not guaranteed and indeed there are different reasons for the different postulates why they should not be fulfilled in the particular scenario of ontology revision with well developed ontologies.
Equilibrium simulation of the Nordic electricity spot price

We develop a bottom-up, midterm model for the Nord Pool system price. Models for consumption, generation and exchange are combined using a market equilibrium approach. Scenarios for the most influential stochastic factors are created using statistical models. Forecasted price scenarios yield an indication on the expected future system price, and the uncertainty in future prices. Compared to stochastic dynamic programming based models, we use an empirical function to approximate the water value, with a possible benefit in terms of computational effort. In addition to providing a picture of the price distribution, the model can be applied to learn about the impact of fundamental variables. In particular, we study the relative influence of each of the stochastic factors. The performance of the model is evaluated in numerical examples over a two-year forecast period. Overall, we conclude the model provides realistic forecasts of the system price and its distribution. The performance under normal market conditions may deviate from our results, due to the extraordinary drop in fuel prices caused by the financial crisis.
The Davey-MacKay Coding Scheme for Channels With Dependent Insertion, Deletion, and Substitution Errors

In this paper, we propose a new channel model which introduces dependent insertion, deletion, and substitution (DIDS) errors. This channel model mimics the write channel found in bit-patterned media recording (BPMR) systems. It consists of a ternary Markov state channel and a two-state binary symmetric channel (BSC). The ternary Markov state channel produces data-dependent and paired insertion-deletion errors while the two-state BSC produces random substitution errors, as well as burst-like substitution errors in the vicinity of insertions and deletions. In addition, we modify the inner decoder of the Davey-MacKay (DM) coding scheme for the proposed channel model. For the case where there are no burst-like substitution errors, computer simulations show that our modified inner decoder (which takes into account the dependencies between synchronization errors) yields superior frame error rate (FER) performance compared to that when the symbol-level inner decoder by Briffa (which ignores the dependencies between synchronization errors) is used. As the (computational) complexity of our inner decoder increases with the length of the burst-like substitution errors, we further propose a reduced-complexity variant of our inner decoder to handle these errors. Computer simulations show that under iterative decoding, FERs below 10-5 can be achieved with the reduced-complexity variant and a code of rate 0.71, when the insertion/deletion rates are low (≤10-3) and the burst-like error lengths before and after a synchronization error are short (≤5).
Regulation of Vascular Endothelial Growth Factor Production by Leydig Cells In Vitro: The Role of Protein Kinase A and Mitogen-Activated Protein Kinase Cascade1

Abstract We previously reported the presence of vascular endothelial growth factor (VEGF) in testicular cells, and high concentrations of VEGF have been measured in semen, although its role in male reproduction remains obscure. In the present study we focus on understanding the mechanism of VEGF production by mouse Leydig cells cultured in vitro. Production of VEGF protein in medium by testicular cells was markedly increased by the addition of hCG in a time- and dose-dependent manner. Gonadotropin-stimulated VEGF production was mediated by cAMP-dependent protein kinase A (PKA), as evidenced by the effect of hCG being mimicked by 8Br-cAMP and being abolished in the presence of a PKA-specific inhibitor, H-89. Protein kinase C was not involved, as evidenced by phorbol 12-myristate 13-acetate having no influence on VEGF production by Leydig cells. In addition to hCG, atrial natriuretic peptide was also able to stimulate VEGF production, suggesting that cGMP is able to cross-activate PKA. A specific Src kinase inhibitor, PP2, could completely block the stimulatory effects of both gonadotropin and 8Br-cAMP on VEGF production by Leydig cells, implying an involvement of the Src kinase pathway. Furthermore, addition of U0126, an inhibitor of MEK 1/2, abolished the increase in VEGF production stimulated by both hCG and 8Br-cAMP. A similar inhibitory effect was observed by the addition of SB203580, a p38 mitogen-activated protein kinase inhibitor. Thus, in conclusion, Leydig cells are able to produce VEGF by a process under gonadotropic control, and PKA plays a key role in this process. Downstream of PKA, it appears that both MEK 1/2 and Src kinase-dependent pathways are involved, although further research will be necessary to determine the precise link between PKA and other kinases involved.
Protein Phosphatase 1 Down Regulates ZYG-1 Levels to Limit Centriole Duplication

In humans perturbations of centriole number are associated with tumorigenesis and microcephaly, therefore appropriate regulation of centriole duplication is critical. The C. elegans homolog of Plk4, ZYG-1, is required for centriole duplication, but our understanding of how ZYG-1 levels are regulated remains incomplete. We have identified the two PP1 orthologs, GSP-1 and GSP-2, and their regulators I-2szy-2 and SDS-22 as key regulators of ZYG-1 protein levels. We find that down-regulation of PP1 activity either directly, or by mutation of szy-2 or sds-22 can rescue the loss of centriole duplication associated with a zyg-1 hypomorphic allele. Suppression is achieved through an increase in ZYG-1 levels, and our data indicate that PP1 normally regulates ZYG-1 through a post-translational mechanism. While moderate inhibition of PP1 activity can restore centriole duplication to a zyg-1 mutant, strong inhibition of PP1 in a wild-type background leads to centriole amplification via the production of more than one daughter centriole. Our results thus define a new pathway that limits the number of daughter centrioles produced each cycle. Author Summary The centrosomes are responsible for organizing the mitotic spindle a microtubule-based structure that centers, then segregates, the chromosomes during cell division. When a cell divides it normally possesses two centrosomes, allowing it to build a bipolar spindle and accurately segregate the chromosomes to two daughter cells. Appropriate control of centrosome number is therefore crucial to maintaining genome stability. Centrosome number is largely controlled by their regulated duplication. In particular, the protein Plk4, which is essential for duplication, must be strictly limited as an overabundance leads to excess centrosome duplication. We have identified protein phosphatase 1 as a critical regulator of the C. elegans Plk4 homolog (known as ZYG-1). When protein phosphatase 1 is down-regulated, ZYG-1 levels increase leading to centrosome amplification. Thus our work identifies a novel mechanism that limits centrosome duplication.
Does Problem Behavior Elicit Poor Parenting?

This study tested the hypothesis that perceived parenting would show reciprocal relations with adolescents’ problem behavior using longitudinal data from 496 adolescent girls. Results provided support for the assertion that female problem behavior has an adverse effect on parenting; elevated externalizing symptoms and substance abuse symptoms predicted future decreases in perceived parental support and control. There was less support for the assertion that parenting deficits foster adolescent problem behaviors; initially, low parental control predicted future increases in substance abuse but not externalizing symptoms, and low parental support did not predict future increases in externalizing or substance abuse symptoms. Results suggest that problem behavior is a more consistent predictor of parenting than parenting is of problem behavior, at least for girls during middle adolescence.
STRUCTURE, PERFORMANCE, AND THE NET RATE OF ENTRY INTO MANUFACTURING INDUSTRIES*

Traditional theory assigns great importance to free entry and exit by firms in order to insure good industry performance. The well-known empirical results of Bain [1] and Mann [7] have confirmed the theoretical importance of the conditions of entry. Recently, McGuckin [9] has presented evidence which shows an inverse relationship between the net rate of entry and increases in the market share controlled by the largest firms. If entry is likely to diminish the market power held by dominant firms and to lead eventually to improved industry performance, it is of interest to examine the determinants of entry itself. ' This paper reports on an examination of the impact of demand growth, diversification, product promotion, and concentration on price-cost margins and subsequent rates of entry into four-digit Census industries.
Mapping attitudes and awareness with regard to national guidelines: an e-mail survey among decision makers.

INTRODUCTION The adoption of evidence-based guidelines within the mental health field has been slow. Changing inadequate practice is therefore a formidable challenge for mental health-care managers. AIM To explore decision-makers' attitudes and awareness regarding the national guidelines for psychosocial interventions targeting people with schizophrenia. METHOD A questionnaire distributed by e-mail to 592 Swedish decision-makers was analysed using descriptive and comparative techniques. RESULTS Significantly more of the top-level mental health-care managers than politicians stated that they knew about the national guidelines (i.e. their release and content) and they considered the guidelines to be a good source of support for planning and allocating resources. CONCLUSION If those responsible for allocating resources (i.e. politicians) are unaware of the dissemination of national guidelines or their content, and they do not perceive the national guidelines to be a good source of support for planning and allocating resources, this is likely to have a negative influence on the remit of nurse managers as well as nursing practice. IMPLICATIONS FOR NURSING MANAGEMENT Top-level mental health-care managers have a vital role to play in the implementation of national guidelines. However, our findings indicate that implementing national guidelines in practice could be virtually impossible without strategic government support.
Back Pain in a Large Canadian Police Force

Study Design. A survey of a random sample of 1002 members of the Royal Canadian Mounted Police to determine their experience with low back pain. Objectives. To determine the prevalence of low back pain among Royal Canadian Mounted Police members and to assess the validity of the perception that the patrol car seat and the duty belt are causing a higher rate of low back pain among members of the Royal Canadian Mounted Police than in the general population. Summary of Background Data. Low back pain is a common problem throughout the industrialized world, with reported 1‐year prevalence rates between 25% and 62%. Prevalence of low back pain among people who drive motor vehicles for a significant part of the day appears higher than in the general population. Among police officers, 1‐year prevalence rates of between 44% and 62% have been reported. Methods. A computerized database of 14,897 serving regular members was used to identify a sample of officers on active duty. A low back pain questionnaire was mailed to each selected member, eliciting information regarding their experience with low back pain, their exposure to known and putative risk factors, and their opinions about the contribution of these potential risk factors. The respondents to the questionnaire remained anonymous. Results. The response rate was 80%. The prevalence of "chronic or recurring low back pain since joining the force" was 54.9%, which is comparable with the lifetime prevalence reported for the general population. Of those who reported having back problems, only 8.5% had such problems before joining the force. Seventy‐six percent who had low back pain reported having a problem within the last year, giving an overall 1‐year prevalence of 41.8%, which is comparable with that for the general population. The a priori assumption that driving or wearing a duty belt contributed to the problem was shared by most police officers surveyed. However, only about half of the members who replied drove for more than half the working day or wore the duty belt. These members had the same prevalence of low back pain as those who did not drive or wear the duty belt. Conclusions. The prevalence of low back pain in this police force is comparable with that in the general population, and driving a patrol car or wearing the duty belt does not appear to influence the prevalence rate in this population.