Miracle-dz/UniFAR-FTUs huggingface dataset:
Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration

The analysis of the interaction of strontium (Sr) with bone mineral is of interest because a new agent containing Sr (S 12911) has shown positive effects on bone mass in various animal models of osteoporosis and is currently being developed for preventive and curative treatment of postmenopausal osteoporosis. Iliac bone samples were obtained from 20 male monkeys: 4 untreated control animals, 12 animals sacrificed at the end of a 13‐week treatment with high dose levels of S 12911 (750, 275, or 100 mg/kg/day orally), and 4 animals sacrificed 6 weeks after the end of a 13‐week treatment with S 12911 (750 or 100 mg/kg/day orally). The distribution of Sr was determined and quantified by X‐ray microanalysis. Changes at the crystal level were evaluated by X‐ray diffraction and Raman microspectrometry. In the control animals, traces of Sr were found to be homogeneously distributed throughout the bone tissue. In the treated monkeys, Sr could only be detected in calcified matrix. In monkeys sacrificed at the end of the treatment, Sr was found to be dose‐dependently incorporated into the mineral substance of the compact and cancellous bone. Sr was heterogeneously distributed with three to four times more Sr in new than in old compact bone, and approximately two and a half times more Sr in new than in old cancellous bone. The bone Sr content dramatically decreased in the animals sacrificed 6 weeks after the end of the treatment. Diffraction showed no significant changes in the characteristics of the crystal lattice. Sr appeared to be easily exchangeable from bone mineral and was slightly linked to mature crystals through ionic substitutions. Even at the highest dose level tested, less than 1 calcium ion out of 10 was substituted by 1 Sr ion in each crystal. In conclusion, taken up by bone, Sr was heterogeneously distributed with a higher concentration in new than in old bone but induced no major modifications of the bone mineral (crystallinity, crystal structure) at the crystal level. As a result, a treatment with S 12911 Sr salt should not induce any alteration of bone mineral.
Specific Inner Retinal Layer Cell Damage in an Autoimmune Glaucoma Model Is Induced by GDNF With or Without HSP27.

PURPOSE Previously, immunization of rats with ocular antigens induced retinal ganglion cell (RGC) degeneration. We investigated the effect of immunization with glial cell line-derived neurotrophic factor (GDNF) or GDNF in combination with heat shock protein 27 (GDNF+HSP) on RGCs and other retinal cells. METHODS Rats were immunized with GDNF or GDNF+HSP. After 4 weeks, retinas were stained with Brn-3a and NeuN to quantify RGCs. GFAP and vimentin staining were used to investigate macroglia. Microglia were marked with Iba1 and ED1. Amacrine cells were labeled with parvalbumin and ChAT. Photoreceptors were evaluated with rhodopsin and opsin staining and bipolar cells with PKCα and recoverin. For these cell types, Western blotting was also performed. RESULTS Retinas of immunized animals showed a significant loss of Brn-3a+ and NeuN+ RGCs. No significant changes could be observed in regard to macroglia. An increase in Iba1+ microglia was detected in both groups, but little change in regard to activated microglia. A loss of cholinergic amacrine cells was seen in the GDNF+HSP group by immunohistochemistry and in both groups via Western blot analysis. AII amacrine cells, bipolar cells, and photoreceptors were not affected. CONCLUSIONS Immunizations led to loss of RGCs and cholinergic amacrine cells and a strong increase in microglial cells. Our data suggest that RGC loss is the consequence of immunization with GDNF. Astrocyte activity and its neuroprotective effects seem to be inhibited by GDNF immunization. We presume more complex interactions between GDNF and HSP27 because no additive effects could be observed.
Differential Protein Expression in Phenotypic Variants of Streptococcus pneumoniae

ABSTRACT Streptococcus pneumoniae undergoes spontaneous phase variation resulting in opaque and transparent colony forms. Differences in colony opacity correlate with differences in virulence: the transparent variants are more capable of colonizing the nasopharynx, whereas the opaque variants show increased virulence during systemic infections. To gain insight into the pathogenesis of pneumococcal disease at the molecular level, protein expression patterns of the phenotypic variants of two pneumococcal strains were compared by high-resolution two-dimensional protein electrophoresis. In comparison with transparent variants, the opaque variants reduced the expression of two proteins and overexpressed one protein. The proteins were identified by mass spectrometric analysis. The protein overexpressed in the opaque phenotype revealed significant homology to elongation factor Ts of Helicobacter pylori. One of the two proteins that were underexpressed in the opaque variants revealed significant homology to the proteinase maturation protein PrtM ofLactocobacillus paracasei, a member of the family of peptidyl-prolyl cis/trans isomerases. A consensus lipoprotein signal sequence suggests that the putative proteinase maturation protein A, designated PpmA, is located at the surface of the pneumococcus and may play a role in the maturation of surface or secreted proteins. The second underexpressed protein was identified as pyruvate oxidase, SpxB. The lower SpxB expression in opaque variants most probably explains the reduced production of hydrogen peroxide, a reaction product of SpxB, in this variant. Since aspxB-defective pneumococcal mutant has decreased ability to colonize the nasopharynx (B. Spellerberg, D. R. Cundell, J. Sandros, B. J. Pearce, I. Idanpaan-Heikkila, C. Rosenow, and H. R. Masure, 1996. Mol. Microbiol. 19:803–813, 1996), our data suggest that SpxB plays an important role in enhancing the ability of transparent variants to efficiently colonize the nasopharynx.
Examining Play Counts and Measurements of Injury Incidence in Youth Football.

CONTEXT Whereas researchers have provided estimates for the number of head impacts sustained within a youth football season, less is known about the number of plays across which such impact exposure occurs. OBJECTIVE To estimate the number of plays in which youth football players participated during the 2013 season and to estimate injury incidence through play-based injury rates. DESIGN Descriptive epidemiology study. SETTING Youth football. PATIENTS OR OTHER PARTICIPANTS Youth football players (N = 2098; age range, 5-15 years) from 105 teams in 12 recreational leagues across 6 states. MAIN OUTCOME MEASURE(S) We calculated the average number of athlete-plays per season and per game using independent-samples t tests to compare age groups (5-10 years old versus 11-15 years old) and squad sizes (<20 versus ≥20 players); game injury rates per 1000 athlete-exposures (AEs) and per 10 000 athlete-plays; and injury rate ratios (IRRs) with 95% confidence intervals (CIs) to compare age groups. RESULTS On average, youth football players participated in 333.9 ± 178.5 plays per season and 43.9 ± 24.0 plays per game. Age groups (5- to 10-year-olds versus 11- to 15-year-olds) did not differ in the average number of plays per season (335.8 versus 332.3, respectively; t2086.4 = 0.45, P = .65) or per game (44.1 versus 43.7, respectively; t2092.3 = 0.38, P = .71). However, players from smaller teams participated in more plays per season (373.7 versus 308.0; t1611.4 = 8.15, P < .001) and per game (47.7 versus 41.4; t1523.5 = 5.67, P < .001). Older players had a greater game injury rate than younger players when injury rates were calculated per 1000 AEs (23.03 versus 17.86/1000 AEs; IRR = 1.29; 95% CI = 1.04, 1.60) or per 10 000 athlete-plays (5.30 versus 4.18/10 000 athlete-plays; IRR = 1.27; 95% CI = 1.02, 1.57). CONCLUSIONS A larger squad size was associated with a lower average number of plays per season and per game. Increasing youth football squad sizes may help reduce head-impact exposure for individual players. The AE-based injury rates yielded effect estimates similar to those of play-based injury rates.
Psychiatric comorbidity among adolescents with substance use disorders: findings from the MECA Study.

OBJECTIVE To investigate the extent to which adolescents in the community with current substance use disorders (SUD) experience co-occurring psychiatric disorders. METHOD Diagnostic data were obtained from probability samples of 401 children and adolescents, aged 14 to 17 years, and their mothers/caretakers, who participated in the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. RESULTS The rates of mood and disruptive behavior disorders are much higher among adolescents with current SUD than among adolescents without SUD. Comparison with adult samples suggests that the rates of current comorbidity of SUD with psychiatric disorders are the same among adolescents as adults, and lower for lifetime disruptive disorders/antisocial personality disorder among adolescents than adults. CONCLUSIONS The high rate of coexisting psychiatric disorders among adolescents with SUD in the community needs to be taken into account in prevention and treatment programs.
Management of feline distal tibial fractures using a hybrid external skeletal fixator.

OBJECTIVE To document the results of management of feline distal tibial fractures with circular-linear hybrid external skeletal fixators. METHODS Retrospective examination of case records and radiographs of cats with distal tibial fractures managed with hybrid external skeletal fixators. Signalment, pre-operative fracture conformation, post-operative fracture reduction, implant complications, time to tibial and fibular fracture healing and time to hybrid external skeletal fixators removal were analysed. RESULTS Case records of eight cats were reviewed and included three closed fractures and five type 1 open fractures. Post-operative fracture reduction was considered appropriate in all cases. Healing of five tibial fractures was complete and hybrid external skeletal fixators were removed within a mean of 13 weeks. Healing of the fibular fracture was complete within a mean of 12 · 1 weeks. Three tibial fractures demonstrated non-union and were revised after a mean duration of 24 weeks. All three non-union fractures were open on presentation. CLINICAL SIGNIFICANCE Feline distal tibial fractures may be managed with hybrid external skeletal fixators, however, non-union still occurs. In this study type I open feline distal tibial fractures appeared more likely to develop non-union.
A Novel IRC Botnet Detection Method Based on Packet Size Sequence

Botnets&#12288;have become a serious threat to Internet and are often deployed to control a large pool of zombies and perform notorious activities such as DDoS, information theft and spam sending. In this paper, a new method is developed for detecting IRC botnets by analyzing the characteristic of packet size sequence of the TCP conversation between IRC zombies and their command and control (C&C) servers. In comparison with IRC chat, the TCP conversations within IRC botnets show a nature of approximate periodicity defined as quasi-periodicity in this paper. A simple yet effective detection method is presented to detect IRC botnets by measuring the quasi-periodicity degree and packet average size of IRC conversations based on ukkonen algorithm. We evaluated our method using real-world IRC botnet traces captured from honeynet. The results show that our method can detect real-world IRC botnets from IRC traffic with high accuracy and has a low false positive rate.
Phosphatidate Kinase, a Novel Enzyme in Phospholipid Metabolism (Purification, Subcellular Localization, and Occurrence in the Plant Kingdom)

Microsomal membranes from suspension-cultured Catharanthus roseus cells possess an enzymic activity that catalyzes the ATP-dependent phosphorylation of phosphatidic acid (PA) to form diacylglycerol pyrophosphate (H. Behrbohm, J.B. Wissing [1993] FEBS Lett 315: 95–99). This enzyme activity, PA kinase, was purified and characterized. Plasma membranes, obtained from C. roseus microsomes by aqueous two-phase partitioning, were extracted, and PA kinase was purified 3200-fold by applying different chromatographic steps that resulted in a specific activity of about 10 [mu]mol min-1 mg-1. Sodium dodecyl sulfate-gel electrophoresis of the fractions obtained from the final chromatographic step revealed a 39-kD protein that correlated with the enzyme activity; PA kinase activity could be eluted from this protein band. Subcellular localization, investigated with C. roseus cells, showed that the activity was confined to membrane fractions, and at least 80% was associated with plasma membranes. The data revealed the same distribution within the cellular membranes of PA kinase as reported for diacylglycerol kinase, which is a typical plasma membrane-located enzyme. Furthermore, PA kinase activity was detected in the calli of 16 different plant species and in the different organs of C. roseus plants and obviously occurs ubiquitously in the plant kingdom.
Stoichiometry of G protein subunits affects the Saccharomyces cerevisiae mating pheromone signal transduction pathway

The Saccharomyces cerevisiae GPA1, STE4, and STE18 genes encode products homologous to mammalian G-protein alpha, beta, and gamma subunits, respectively. All three genes function in the transduction of the signal generated by mating pheromone in haploid cells. To characterize more completely the role of these genes in mating, we have conditionally overexpressed GPA1, STE4, and STE18, using the galactose-inducible GAL1 promoter. Overexpression of STE4 alone, or STE4 together with STE18, generated a response in haploid cells suggestive of pheromone signal transduction: arrest in G1 of the cell cycle, formation of cellular projections, and induction of the pheromone-inducible transcript FUS1 25- to 70-fold. High-level STE18 expression alone had none of these effects, nor did overexpression of STE4 in a MATa/alpha diploid. However, STE18 was essential for the response, since overexpression of STE4 was unable to activate a response in a ste18 null strain. GPA1 hyperexpression suppressed the phenotype of STE4 overexpression. In addition, cells that overexpressed GPA1 were more resistant to pheromone and recovered more quickly from pheromone than did wild-type cells, which suggests that GPA1 may function in an adaptation response to pheromone.
Is stroke unit care portable? A systematic review of the clinical trials.

BACKGROUND It is not known if mobile stroke teams can achieve the good results seen in trials of geographically discrete stroke wards (stroke units). OBJECTIVE To establish the effectiveness of mobile stroke teams. DESIGN Systematic review of controlled clinical trials that compared peripatetic systems of organised stroke care (stroke team care) with alternative hospital services. METHODS Systematic review and meta-analysis (using Cochrane Collaboration methodology and involving the primary trialists). Clinical outcomes included death, dependency, the need for institutional care and measures of the process of care such as the delivery of key investigations and treatments. RESULTS Six clinical trials (1,085 patients) were identified; five (781 patients) compared some form of stroke team care with conventional care in general medical wards and one (304 patients) compared team care with a comprehensive stroke unit. Compared with care in general wards, stroke team care improved some aspects of the process of care, but clinical outcomes were similar. Compared with a comprehensive stroke unit, stroke team patients were significantly less likely to survive (P <0.001), return home (P < 0.001) or regain independence (P < 0.0001). Most aspects of the process of care were also poorer than in the stroke unit. CONCLUSIONS Care from a mobile stroke team had no major impact on death, dependency or the need for institutional care.
Molecular epidemiology of hepatitis C virus in Iran as reflected by phylogenetic analysis of the NS5B region

Hepatitis C virus (HCV) subtypes were determined in 125 Iranian patients by phylogenetic analysis within the NS5B or 5′‐UTR/core regions. Subtypes 1a and 3a were predominant accounting for 47 and 36%, whereas 1b and 4 accounted for 8 and 7%. This subtype distribution differs from that of Turkey and Pakistan, where subtypes 1b and 3a dominate and also from neighbouring Arabic countries where subtype 4 is the prevalent genotype. The Iranian 1a and 3a strains formed subclusters in the dendrogram indicating that these subtypes are indigenous to Iran. In contrast, the 1b strains intermixed with strains derived worldwide. Subtype 1a was frequent in South Iran (70%), while 3a was more prevalent in North‐West Iran (83%), a region with a high proportion of Turkish inhabitants. Patients infected by blood products had more frequently subtype 1a (57%), while younger drug users had more frequently subtype 3a (54%). Genotype 4 was over‐represented among haemodialysis patients in Tehran. One strain, most similar to genotype 5, was highly divergent in the NS5B region and further analysis is needed to assess the systematic status of this strain. In half of the patients with unknown source of infection only the 5′‐UTR could be amplified, most of which were from North‐West Iran and from patients younger than those with unknown source of infection with typable strains, mean age 29 versus 43 years. In conclusion, the NS5B sequence data revealed population based subtype patterns in Iran, the further study of which may help to understand the molecular epidemiology of HCV in a low‐endemic area. J. Med. Virol. 74:246–252, 2004. © 2004 Wiley‐Liss, Inc.
Exploring the mimicry of polysaccharide antigens by anti-idiotypic antibodies. The crystallization, molecular replacement, and refinement to 2.8 A resolution of an idiotope-anti-idiotope Fab complex and of the unliganded anti-idiotope Fab.

The monoclonal antibody YsT9.1 is specific for the lipopolysaccharide A antigen of Brucella abortus. A complex formed between the Fab of YsT9.1 (Ab1) and the Fab of its antidiotopic monoclonal antibody T91AJ5 (Ab2) has been crystallized, and data have been collected to 2.8 A resolution. The space group is monoclinic P2(1), with one molecule per asymmetric unit. The structure was solved using a limited Patterson-correlation search over the asymmetric-unit of rotation space, and has been refined to an R-factor of 0.174. The complex is a head-to-head dimer, with the contact between the two Fabs almost completely restricted to their hypervariable loops. The interactions between the two Fabs in the complex are dominated by tyrosine residues, not only in the formation of hydrogen bonds, but in their participation in an aromatic ring network that spans the two Fv domains. The anti-idiotope was found to be unable to carry an internal image of the antigen and induce polysaccharide-specific "anti-anti-idiotopes" (Ab3) because the polysaccharide binding cleft on the Ab1 is too narrow and deep to allow comprehensive contact with the binding site of Ab2. The antibody T91AJ5 therefore is a class gamma anti-idiotope. The contact surfaces of the two Fabs are highly complementary; however, they are distinctly different in character. Each Fab has two separate binding surfaces of approximately equal size, but while the two binding surfaces of Ab1 are partitioned between the light and heavy chains, the two binding surfaces of Ab2 are shared between the chains, with the heavy chain responsible for about 60% of the total binding area. The structure of the unliganded Fab of Ab2 has also been solved by molecular replacement, and refined to an R-factor of 0.152 at 2.8 A resolution. This Fab crystallizes in the orthorhombic space group P2(1)2(1)2(1), with one molecule per asymmetric unit. The second hypervariable loop of the heavy chain of the Ab2 Fab is observed to undergo a significant and necessary conformational rearrangement in going from the unliganded to complexed form, and thus complex formation is an example of "induced fit" of antigen to antibody. The unliganded Ab1 Fab packs in the standard head-to-tail fashion observed for other Fabs. This mode of packing is precluded in the complex, by its head-to-head nature, and it is found to pack in tilted layers with most intermolecular contacts made between adjacent Ab2 Fab molecules. (ABSTRACT TRUNCATED AT 400 WORDS)
Andrographolide Induces Apoptosis of C6 Glioma Cells via the ERK-p53-Caspase 7-PARP Pathway

Background. Glioma is the most malignant tumor of the central nervous system. Efforts on the development of new chemotherapy are mandatory. Andrographolide (AND), a diterpenoid lactone isolated from the Andrographis paniculata, has been shown to have antitumor activities in several types of cancer cells. Whether AND can exert its antitumor activity in glioblastoma cells remains unknown. This study examined the anticancer effects of AND, both in vitro and in vivo. Methods. Cell apoptosis was assayed by flow cytometry and nuclear staining. The signaling pathway for AND was determined by western blotting. The effects of AND on tumor growth was evaluated in a mouse model. Results and Conclusion. In vitro, with application of specific inhibitors and siRNA, AND-induced apoptosis was proven through ROS-ERK-P53-caspase 7-PARP signaling pathway. In vivo, AND significantly retarded tumor growth and caused regression of well-formed tumors in vivo. Furthermore, AND did not induce apoptosis or activate ERK and p53 in primary cultured astrocyte cells, and it may serve as a potential therapeutic candidate for the treatment of glioma.
Visualizing multidimensional (multivariate) data and relations

The paper provides a review of the field of multidimensional data visualisation and discusses some promising methodologies. It considers some crucial problems and directions. The emphasis is more on concepts and foundations rather than ad hoc methods. Visualization is considered as a collection of transformations from problem domains to a perceptual domain, usually visual. The paper discusses the extension of visualisation from the pixel to icons. <<ETX>>