Miracle-dz/UniFAR-FTUs huggingface dataset:
GEOMETRY OF INTERCALATION OF PSORALENS IN DNA APPROACHED BY MOLECULAR MECHANICS*

The results of molecular mechanical calculations on intercalation complexes of 3‐car‐bethoxypsoralen, 5‐methoxypsoralen, 8‐methoxypsoralen, 7‐methylpyrido[3,4‐c]psoralen (MepyPs) and 7‐methylpyrido[4,3‐c]psoralen (2N‐MePyPs) with the double stranded duodecanucleotide d(CGCGATATCGCG)2 are presented. In the energy‐minimized structures, the psoralens are intercalated with their plane orthogonal to the helix axis. Stacking interactions between the furan ring of the psoralen and the adjacent bases are maximized in most derivatives studied, whereas the effect of the various substituents of the psoralen ring is to specifically push part of the molecule towards either the minor or the major groove, preventing a symmetrical intercalation (with respect to the two strands of the DNA). The relative position of the psoralen ring and of the adjacent thymine foreshadows the formation of furan‐side monoadducts in 3‐CPs, MePyPs and 2N‐MePyPs, whereas the formation of a pyrone‐side monoadduct appears as geometrically more favourable in 5‐MOP and both furan‐ and pyrone‐side monoadducts can be geometrically envisaged in 8‐MOP. A good correlation therefore exists between the more or less favourable equilibrium geometries and the experimentally observed photoreactions. The present study is the first attempt to characterize the geometrical parameters as part of a complex set of geometrical, dynamical and excited state parameters governing the overall DNA‐psoralen photoreaction.
Na+‐H+ exchange in resident alveolar macrophages: activation by osmotic cell shrinkage

Intracellular pH (pH;) homeostasis in resident alveolar macrophages (mφ) under nominally CO2‐free conditions is mediated primarily by the activity of plasmalemmal H+‐ATPase, The mφ also possess an Na+‐H+ exchanger (NHE) but this mechanism has no de tectable role in pHi regulation in the physiologic range. To further explore the physiological significance of the NHE in this cell type, resident alveolar mφ from rabbits were subjected to a hyperosmotic challenge (620 mOsm/kg) in the nominal absence of C02‐HCO3 ‐. Os motic cell shrinkage was accompanied by an amiloridesensitive increase in baseline pHi The NHE‐mediated rate of pH; recovery from intracellular acid loads also in creased under hyperosmotic conditions. Cell shrinkage caused an alkaline shift in the pHi set point of the NHE without altering the exchanger's affinity for extracellular Na+. The results indicate that Na+‐H+ exchange in resi dent alveolar mφ is activated by osmotic cell shrinkage and imply that the NHE may be involved in volume regulatory responses of the cell. J. Leukoc. Biol. 57: 609–616; 1995.
A comparative study of the life-histories of mammalian schistosomes

SUMMARY Available data in the literature pertaining to the life-history characteristics of all known species of mammalian schistosomes have been gathered, and correlations between such variables as length of pre-patent period, adult worm size, rate of progeny production and progeny size have been explored. Accommodation of the schistosome life-cycle to the constraints imposed by certain host characteristics such as life-expectancy and size is discussed. Of the 23 known species of mammalian schistosomes, 20 species apparently rely to a major extent on relatively large-bodied and long-lived mammals such as primates, ungulates and proboscideans for their transmission. Only 1 species, Schistosomatium douthitti, is exclusively dependent on rodents for its transmission. S. douthitti attains maturity within its definitive host faster than any other mammalian schistosome, and is the only species known to be capable of producing viable eggs by facultative parthenogenesis. For all species of mammalian schistosomes, adult worm size, as estimated by female length, is positively correlated with the number of uterine eggs contained within the female (r = 0·682). For the 7 species for which data exist, rate of egg production/worm pair/day is positively correlated with uterine egg counts (r = 0·873) and inversely correlated with egg length (r = −0·787) and miracidium length (r = −0·953). Length of the pre-patent period is positively correlated with egg length (r = 0·503). With respect to the molluscan host, the number of cercariae produced by snails is positively correlated with the shell size of the snail (r = 0·657). For the 5 species for which data exist, the rate of egg production is inversely correlated with shell size of the intermediate host (r = −0·955) and the common logarithm of the number of cercariae produced (r = −0·893). Comparisons between species suggest that exceptionally low rates of cercariae production in the intermediate host may be compensated for by rapid rates of egg production in the definitive host, implying a degree of integration in the schistosome life-cycle not previously appreciated. Most species of mammalian schistosomes have long-lived definitive hosts, and snail hosts capable of producing many cercariae; compensatory relationships are therefore less obvious in such species. Additional quantitative data on all aspects of schistosome life-histories, particularly rate and duration of egg production, are needed to confirm or refute the relationships discussed above.
B‐cell chronic lymphocytic leukaemia cells express and release transforming growth factor‐β

Summary Transforming growth factor‐β (TGF‐β) has been described as a potent inhibitor of various cell types, among others of primitive haematopoietic progenitors in vitro, and as a negative autocrine regulator of normal B lymphocyte growth and differentiation. In the present study we investigated TGF‐β gene expression in peripheral blood mononuclear cells (PBMC) and in B cells from patients with B‐cell chronic lymphocytic leukaemia (B‐CLL) and from normal controls. Monocyte depleted B‐CLL cells expressed constitutively mRNA for TGF‐β1 and secreted low amounts of TGF‐β activity into the culture medium. Stimulation of cells by phorbol ester noticeably enhanced mRNA levels as well as protein secretion in most cases. TGF‐β activity was of the same magnitude as in normal controls. We next analysed TGF‐β in highly enriched B lymphocytes from B‐CLL (95100% CD19+), and found that TGF‐β secretion was up to 3 times higher than in the original PBMC population. It is discussed that B‐CLL cells might escape from negative regulation by TGF‐β and, on the other hand, inhibit normal haematopoietic cell proliferation and thereby achieve a growth advantage in the haematopoietic tissues.
Identification of a circular intermediate in the transfer and transposition of Tn4555, a mobilizable transposon from Bacteroides spp

Transmissible cefoxitin (FX) resistance in Bacteroides vulgatus CLA341 was associated with the 12.5-kb, mobilizable transposon, Tn4555, which encoded the beta-lactamase gene cfxA. Transfer occurred by a conjugation-like mechanism, was stimulated by growth of donor cells with tetracycline (TC), and required the presence of a Bacteroides chromosomal Tcr element. Transconjugants resistant to either FX, TC, or both drugs were obtained, but only Fxr Tcr isolates could act as donors of Fxr in subsequent matings. Transfer of Fxr could be restored in Fxr Tcs strains by the introduction of a conjugal Tcr element from Bacteroides fragilis V479-1. A covalently closed circular DNA form of Tn4555 was observed in donor cells by Southern hybridization, and the levels of this circular transposon increased significantly in cells grown with TC. Both the cfxA gene and the Tn4555 mobilization region hybridized to the circular DNA, suggesting that this was a structurally intact transposon unit. Circular transposon DNA purified by CsCl-ethidium bromide density gradient centrifugation was used to transform Tcs B. fragilis 638, and Fxr transformants were obtained. Both the circular form and the integrated Tn4555 were observed in transformants, but the circular form was present at less than one copy per chromosomal equivalent. Examination of genomic DNA from Fxr transformants and transconjugants revealed that Tn4555 could insert at a wide variety of chromosomal sites. Multiple transposon insertions were present in many of the transconjugants, indicating that there was no specific barrier to the introduction of a second transposon copy.
In vivo damage and recA-dependent repair of plasmid and chromosomal DNA in the radiation-resistant bacterium Deinococcus radiodurans

Deinococcus radiodurans R1 and other members of this genus share extraordinary resistance to the lethal and mutagenic effects of ionizing radiation. We have recently identified a RecA homolog in strain R1 and have shown that mutation of the corresponding gene causes marked radiosensitivity. We show here that following high-level exposure to gamma irradiation (1.75 megarads, the dose required to yield 37% of CFU for plateau-phase wild-type R1), the wild-type strain repairs > 150 double-strand breaks per chromosome, whereas a recA-defective mutant (rec30) repairs very few or none. A heterologous Escherichia coli-D. radiodurans shuttle plasmid (pMD68) was constructed and found to be retained in surviving D. radiodurans R1 and rec30 following any radiation exposure up to the highest dose tested, 3 megarads. Plasmid repair was monitored in vivo following irradiation with 1.75 megarads in both R1/pMD68 and rec30/pMD68. Immediately after irradiation, plasmids from both strains contained numerous breaks and failed to transform E. coli. While irradiation with 1.75 megarads was lethal to rec30 cultures, a small amount of supercoiled plasmid was regenerated, but it lacked the ability to transform E. coli. In contrast, wild-type cultures showed a cell division arrest of about 10 h, followed by exponential growth. Supercoiled plasmid was regenerated at normal levels, and it readily transformed E. coli. These studies show that D. radiodurans retains a heterologous plasmid following irradiation and repairs it with the same high efficiency as its chromosomal DNA, while the repair defect in rec30 prevents repair of the plasmid. Taken together, the results of this study suggest that plasmid DNA damaged in vivo in D. radiodurans is repaired by recA-dependent mechanisms similar to those employed in the repair of chromosomal DNA.
Prognostic features for response and survival in elderly patients with de novo acute myeloid leukemia treated with mitoxantrone and intermediate dose cytarabine

Forty-three fit elderly patients with de novo acute myeloid leukemia (AML) received chemotherapy with mitoxantrone and intermediate dose cytarabine (MIDAC) in a phase II clinical trial conducted by the Australasian Leukaemia and Lymphoma Group. The main aim of the study was to evaluate the tolerability and efficacy of MIDAC in inducing durable remissions. While the chemotherapy was generally well tolerated, less than half the patients achieved complete remission (CR) after induction and many of those in CR could not receive planned consolidation cycles. The median overall survival for all patients was 6.5 months and the median disease-free survival for those achieving CR was 8.3 months. Only 2 patients survived beyond 4 years. Factors significantly associated with shorter survival were adverse cytogenetics, marrow dysplasia and increasing age. These results suggest that only selected elderly patients with AML are likely to benefit from aggressive chemotherapy and that novel therapies are required to improve the poor prognosis of this group.
Validity of teacher report for assessing the emergent literacy skills of at-risk preschoolers.

PURPOSE The purpose of this study was to determine the predictive validity of teacher report for assessing the emergent literacy skills of preschool-age children. The aims were twofold: (a) to examine predictive relationships between teacher report and direct behavioral assessment, and (b) to examine the extent to which teacher report accurately differentiates children who are exhibiting low levels of emergent literacy skills relative to their peers. METHOD Forty-four preschool teachers completed a rating form reporting the print-related emergent literacy skills of 209 children who were enrolled in their classrooms. Approximately 2 months later, the children completed direct assessments of these skills. RESULTS Correlations between teacher report and children's performance on direct behavioral assessments were positive, moderate to large in size, and statistically significant. In terms of classifying children into groupings based on risk (e.g., at risk, low risk), global teacher ratings demonstrated a sensitivity of 51.9% and a specificity of 87.9%. CLINICAL IMPLICATIONS The present results indicate that teacher report provides a somewhat valid representation of children's skills. However, the diagnostic accuracy of teacher report for identifying children who are at risk is generally low. With this limitation in mind, teacher report can provide an important complement to current assessment approaches that are used in preschool settings.
Monolithic integration of multiple III-V semiconductors on Si for MOSFETs and TFETs

In this paper we report on our work on the monolithic integration of various III-V compounds on Si using template-assisted selective epitaxy (TASE) and its application for electronic devices. Nanowires, crossbar nanostructures, and micron-sized sheets are epitaxially grown on Si via metal-organic chemical vapor deposition and form the basis for III-V MOSFETs and Tunnel FETs. Epitaxy conditions specific to TASE are discussed and material quality assessed. Here, we focus on InAs and GaSb as a potential all-III-V alternative to complementary group IV technology. Scaled n-FETs as well as both n- and p-channel TFETs are fabricated on Si and illustrate the potential of TASE.
Clinical Impact of Regional Citrate Anticoagulation in Continuous Renal Replacement Therapy in Critically Ill Patients

Background Regional citrate anticoagulation (RCA) is being used increasingly in continuous renal replacement therapy (CRRT) as a safer alternative to heparin. However, complex metabolic control to avoid side effects have generated discrepancies about its introduction into everyday practice. We aimed to compare both anticoagulation techniques in terms of efficacy, safety and feasibility. Methods Observational retrospective study performed in 3 specialized ICUs in patients receiving CVVHDF with RCA between January 2013 and May 2016. Heparin-treated patients matched by age, sex and disease severity treated in the preceding year were selected as historic controls. Filter lifetime, number of filters used, haemorrhagic complications and metabolic complications were recorded. Results 54 patients (27 treated with RCA and 27 with heparin) were included in the study. Filter lifetimes in the first 72 hours were 55.1 ± 21.8 hours in the RCA group compared to 38.8 ± 24.8 hours in the heparin group, (p = 0.004). In addition, the number of filters used in the first 72 hours was significantly higher in the heparin group (2.4 ± 1.3 vs. 1.5 ± 0.7; p = 0.004). There was a trend toward a lower incidence of bleeding in the RCA group, with a significantly lower red blood cell transfusion rate (p = 0.027) in the citrate group. No clinically significant metabolic disturbances were observed in the RCA group. Regarding outcomes, there were no significant differences between groups. Conclusions These results suggest that the implementation of CVVHDF with RCA using concentrated citrate solutions prolongs filter lifetime, achieves a longer effective hemodiafiltration time and is a safe and feasible method.
G-protein-coupled Receptor Rhodopsin Regulates the Phosphorylation of Retinal Insulin Receptor*

We have shown previously that phosphoinositide 3-kinase in the retina is activated in vivo through light-induced tyrosine phosphorylation of the insulin receptor (IR). The light effect is localized to photoreceptor neurons and is independent of insulin secretion (Rajala, R. V., McClellan, M. E., Ash, J. D., and Anderson, R. E. (2002) J. Biol. Chem. 277, 43319–43326). These results suggest that there exists a cross-talk between phototransduction and other signal transduction pathways. In this study, we examined the stage of phototransduction that is coupled to the activation of the IR. We studied IR phosphorylation in mice lacking the rod-specific α-subunit of transducin to determine if phototransduction events are required for IR activation. To confirm that light-induced tyrosine phosphorylation of the IR is signaled through bleachable rhodopsin, we examined IR activation in retinas from RPE65-/- mice that are deficient in opsin chromophore. We observed that IR phosphorylation requires the photobleaching of rhodopsin but not transducin signaling. To determine whether the light-dependent activation of IR is mediated through the rod or cone transduction pathway, we studied the IR activation in mice lacking opsin, a mouse model of pure cone function. No light-dependent activation of the IR was found in the retinas of these mice. We provide evidence for the existence of a light-mediated IR pathway in the retina that is different from the known insulin-mediated pathway in nonneuronal tissues. These results suggest that IR phosphorylation in rod photoreceptors is signaled through the G-protein-coupled receptor rhodopsin. This is the first study demonstrating that rhodopsin can initiate signaling pathway(s) in addition to its classical phototransduction.
When drivers' training-courses are shared by different trainers

This paper aims to analyze the consequences of a specific organization of work in driving schools: in France, in some driving schools, several trainers may successively train a single trainee. Consequences on training duration and on trainer activity are analyzed based on data collected in the course of three studies. We show that the duration of driver training increases in the case of multiple trainer switches during a training course. Trainer switches during the course also have consequences on the activity of trainers, since they must, as a result, engage in asynchronous cooperation. We analyzed this cooperation from two points of view: one focused the use of a collective tool, the Trainee Record Form (TRF) designed as a tool for communication between trainers of the same trainee, as well as with the trainee; and one focused on the characteristics of trainer diagnosis at the beginning of a lesson, when he trains someone for the first time. We observe various uses of the TRF, ambiguous written comments that may be read by the future trainer or a lack of collective use. Our data also suggests difficulties in elaborating a diagnosis: with a new trainee, trainers systematically delayed their decisions regarding didactical objectives: to carry these out, they needed to watch the trainee drive. The results of these three studies are discussed in terms of their consequences for training organization and training of driving trainers.
Strong vasopressor support may be futile in the intensive care unit patient with multiple organ failure

Objective: The aim of the study was to determine the prognosis in patients who needed norepinephrine treatment in our institution in relation to the degree of organ failure and the evolution of the disease process. Design: Retrospective case note analysis of outcome of those patients who needed norepinephrine according to our institutional regimen. Patients: A total of 100 consecutive patients admitted to our 31‐bed medical‐surgical intensive care unit (ICU) who were treated with norepinephrine for severe hypotension and evidence of end‐organ hypoperfusion unresponsive to both fluid resuscitation and dopamine treatment at 20 μg/kg/min. Measurements: The degree of organ dysfunction at the time of starting norepinephrine treatment was assessed by the sequential organ failure assessment (SOFA) score. The time before starting norepinephrine treatment was defined as the time elapsed between ICU admission and that of starting norepinephrine administration. The patients were defined as survivors or nonsurvivors according to their ICU outcome. Results: There were relationships between mortality and the degree of organ dysfunction and mortality and the duration of ICU stay before starting norepinephrine treatment. The mortality rate was 100% in the 30 patients with a total SOFA score of >12 and a delay before starting norepinephrine treatment of >1 day. The mortality rate of the other patients was 63%. The lowest mortality was seen in patients with lower SOFA scores and early norepinephrine administration after admission. Conclusions: Both the time of starting norepinephrine treatment after admission to the ICU and the degree of organ dysfunction have an important bearing on subsequent outcome. Although norepinephrine may be a lifesaving catecholamine in some cases, its administration to patients who have already developed multiple organ failure during their stay in the ICU is associated with a poor outcome.
Ingestion of acapsular Cryptococcus neoformans occurs via mannose and beta-glucan receptors, resulting in cytokine production and increased phagocytosis of the encapsulated form

Cryptococcus neoformans is a pathogenic yeast and a major cause of opportunistic infection in AIDS patients. It is commonly found in an acapsular form in the environment, and infection is likely to occur by inhalation. The lung provides a suitable environment for capsule synthesis, and once encapsulated, C. neoformans becomes resistant to phagocytosis. A stable acapsular mutant of the organism is readily ingested by murine macrophages in vitro, indicating entry via constitutively competent receptors. We demonstrate in this report that this process is inhibitable by particles derived from Saccharomyces cerevisiae that are rich in mannan and beta-glucan, as well as more purified forms of these glycans. Furthermore, ingestion of the acapsular form of C. neoformans induces a range of proinflammatory cytokines, including tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor, which, as we have previously shown, enhance ingestion of serum-opsonized encapsulated C. neoformans in vitro. We demonstrate that ingestion of the acapsular form of the organism also enhances ingestion of the pathogenic encapsulated form. This is dependent on the production of tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor by the macrophages, since addition of neutralizing antibodies to both cytokines inhibited the observed increase in ingestion. Together, these data demonstrate that ingestion of acapsular C. neoformans is mediated via mannose and beta-glucan receptors on the macrophage surface and that this process activates macrophages for enhanced phagocytosis of the encapsulated form via production of macrophage-derived cytokines.
[Profile of immune and allergic dermatoses among children at the outpatient dermatology clinic in Cotonou (Benin)].

OBJECTIVE The aim of this work was to study the profile of immune and allergic dermatoses (IAD) in children consulting at the outpatient dermatology clinic at the National University Hospital in Cotonou (Benin). METHOD This retrospective descriptive study examined records of children consulting with this diagnosis over a 10-year period. RESULTS IAD (902 cases, 37%) were the most common pediatric dermatosis, followed by infectious dermatosis (24%). The sex ratio of children was 0.78. The age groups most strongly affected were those aged 1-30 months (25.39%) and 150-180 months (19.73%). The main IAD were: eczema (47.9%) and prurigo simplex (40.7%). Other IADs included lichen planus (5.1%), toxicoderma (3.8%), urticaria (1.5%), and erythrodermic eczema (1%). The incidence of eczema increased from 13.5% in 2000 to 21.5% in 2009, an increase of 62.2% over 10 years. CONCLUSION IADs are common at the Cotonou hospital clinic and are dominated by eczema, the incidence of which has increased significantly over time.