Miracle-dz/UniFAR-FTUs huggingface dataset:
Decorin-Binding Protein of Borrelia burgdorferi Is Encoded within a Two-Gene Operon and Is Protective in the Murine Model of Lyme Borreliosis

ABSTRACT Isolated outer membranes of Borrelia burgdorferi were used in immunoblotting experiments with sera from immune mice to identify new putative Lyme disease vaccine candidates. One immunoreactive polypeptide migrated on polyacrylamide gels just proximal to outer surface protein C and comigrated with [3H]palmitate-labeled polypeptides. A degenerate oligonucleotide primer based upon internal amino acid sequence information was used to detect the corresponding gene within a B. burgdorferi total genomic library. The relevant open reading frame (ORF) encoded a polypeptide comprised of a 24-amino-acid putative signal peptide terminated by LLISC, a probable consensus sequence for lipoprotein modification, and a mature protein of 163 amino acids. Immunoblots of a recombinant fusion protein corresponding to this ORF supported the idea that the encoded protein was a previously reported decorin-binding protein (DBP) of B. burgdorferi N40 (B. P. Guo, S. J. Norris, L. C. Rosenberg, and M. Höök, Infect. Immun. 63:3467–3472, 1995). However, further DNA sequencing revealed the presence of a second ORF, designated ORF-1, whose termination codon was 119 bp upstream of the dbpgene. ORF-1 also encoded a putative lipoprotein with a mature length of 167 amino acids. Northern blots, Southern blots, and primer extension analyses indicated that ORF-1 and dbp comprised a two-gene operon located on the 49-kb linear plasmid. Both proteins, which were 40% identical and 56% similar, partitioned into Triton X-114 detergent extracts of B. burgdorferi isolated outer membranes. Mice infected with B. burgdorferi produced high titers of antibodies against the ORF-1-encoded protein and DBP during both early and later stages of chronic infection. Both DBP and the ORF-1-encoded protein were sensitive to proteinase K treatment of intact borreliae, suggesting that they were surface exposed. In active immunization experiments, 78% of mice immunized with recombinant DBP were immune to challenge. While it is not clear whether the two lipoproteins encoded by the ORF-1-dbp operon have analogous decorin-binding functions in vivo, the combined studies implicate DBP as a new candidate for a human Lyme disease vaccine.
Efficacy of deep brain stimulation of the subthalamic nucleus in Parkinson’s disease 4 years after surgery: double blind and open label evaluation

Objective: To evaluate the long term (4 years) efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson’s disease. Methods: We performed a double blind crossover evaluation of the efficacy of DBS of the STN in the “off” medication condition in 10 patients with Parkinson’s disease. Assessments included the Unified Parkinson’s Disease Rating Scale (UPDRS) part III (motor) and two timed tests (arm tapping and walking). Open evaluation of the effect of stimulation in the off and on drug states preoperatively and at 1 and 4 years postoperatively was also conducted. The latter assessment included the UPDRS parts II (activities of daily living) and III (dyskinesia scale and global assessment) as judged by the patient and examiner. The mean amount of levodopa daily dose at base line, 1 year, and 4 years after surgery was compared. Results: A significant (p<0.04) effect of stimulation was observed in the overall group regarding both the UPDRS motor and the timed tests. Open evaluation also showed a significant benefit of STN DBS with respect to preoperative assessment in both the motor and activities of daily living scales, dyskinesia scale, and in global assessment. Levodopa daily dose was reduced by 48% and 50% at 1 and 4 years, respectively. There was no difference between the 1 and 4 years evaluations in any of the parameters evaluated. Complications due to stimulation were minor. Conclusions: DBS of the STN provides a significant and persistent anti-parkinsonian effect in advanced Parkinson’s disease 4 years after surgery.
Second to fourth digit ratio: ethnic differences and family size in English, Indian and South African populations

Background: The second to fourth digit ratio (2D:4D) is lower in men than in women. 2D:4D may be established in utero and is negatively correlated with sperm counts and testosterone in men and positively correlated with oestrogen in men and women. Negative associations between male 2D:4D and family size and positive associations between female 2D:4D and family size have been found in some European populations. Aim: The study seeks to investigate the relationship between 2D:4D and family size in samples from Europe, Asia and Africa. Subjects and methods: Measurements of right hand 2D:4D were made in English (Merseyside, n = 403), Indian (Sugali and Yanadi, n = 160) and South African (Zulu, n = 258) populations. Results: 2D:4D was weakly sexually dimorphic and showed strong ethnic differences. There were significant associations between 2D:4D and family size. For males these included negative associations in English and South African samples, and in the total sample. In females there was a positive association in the English sample, a negative association in the South African sample, and the total female sample showed a positive relationship between 2D:4D and family size. Conclusions: 2D:4D showed weak sex and strong ethnic differences. Low values of 2D:4D were associated with large family size in men. The situation was less clear in women but on balance there was evidence to support a relationship between high values of 2D:4D and large family size.
Polyamines in Type 5 Adenovirus-Infected Cells and Virions

The incorporation of l-[14C]ornithine and [14C]putrescine into putrescine, spermidine, and spermine in type 5 adenovirus-infected KB cells was identical to that in uninfected control cells early in infection, but incorporation into putrescine stopped after 8 to 12 h and the rate of incorporation into spermidine was reduced between 12 and 20 h after infection. The amount of polyamines found associated with purified virus could neutralize a maximum of 3 to 4% of the virus DNA, but the small quantities of polyamines detected could not be distinguished from nonspecific binding of polyamines to virions. These data suggest that polyamines are probably not integral components of adenovirus particles.
Sirolimus inhibits growth of human hepatoma cells alone or combined with tacrolimus, while tacrolimus promotes cell growth.

AIM Standard immunosuppression after organ transplantation stimulates tumor growth. Sirolimus has a strong antiproliferative and a tumor inhibiting effect. The purpose is to assess the effect on tumor growth of the immuno-suppressive compounds sirolimus and tacrolimus alone and in combination on cells of human hepatocellular carcinoma. METHODS We used the human cell lines SK-Hep 1 and Hep 3B derived from hepatocellular carcinoma. Proliferation analyses after treatment with sirolimus, tacrolimus, or the combination of both were performed. FACS analyses were done to reveal cell cycle changes and apoptotic cell death. The expression of apoptosis-related proteins was estimated by Western blots. RESULTS Sirolimus alone or combined with tacrolimus inhibited the growth of both cell lines after 5 d by up to 35% in SK-Hep 1 cells, and by up to 68% in Hep 3B cells at 25 ng/mL. Tacrolimus alone stimulated the growth by 12% after 5 ng/mL and by 25% after 25 ng/mL in Hep 3B cells. We found an increase of apoptotic Hep 3B cells from 6 to 16%, and a G1-arrest in SK-Hep 1 cells with an increase of cells from 61 to 82%, when sirolimus and tacrolimus were combined. Bcl-2 was down-regulated in Hep 3B, but not in SK-Hep 1 cells after combined treatment. CONCLUSION Sirolimus appears to inhibit the growth of hepatocellular carcinoma cells alone and in combination with tacrolimus. Sirolimus seems to inhibit the growth stimulation of tacrolimus.
The astronaut ergonomics assessment methodology in microgravity environment

This paper introduces a modified methodology on basis of the RULA (Rapid Upper Limb Assessment) to assess the astronaut ergonomics for space flight in microgravity environment. The proposed methodology under the combination of the neutral configuration in microgravity with the joint movement ranges to establish the assessment criterion for the modified RULA methodology to assess the ergonomics in the microgravity environment.
Relevance of Viral Phenotype in the Early AIDS Outcome of Pediatric HIV-1 Primary Infection

In infants the clinical course of HIV-1 infection is bimodal, differing considerably from that of adults. The effect of HIV-1 phenotypic features and plasma viral load on the clinical course of infection has been well established in adults, whereas in children it remains controversial. The aim of this study was to prospectively evaluate the effect of HIV-1 replication phenotypes during the first year of primary infection in the development of premature immunosuppression and early pediatric AIDS. In 62 vertically infected children replication rates of HIV-1 isolates from primary cultures and syncytium-inducing capability in MT-2 cell line were evaluated, together with plasma viral load. It was observed that rapid replication rate and syncytium-inducing phenotype accelerate the early onset of pediatric AIDS (p = 0.02 and p = 0.04, respectively). Rapid replication kinetics was the only significantly independent variable for early clinical outcome (risk ratio, 2.48;p = 0.02). Both viral properties contributed to rapid CD4+ T-cell depletion (p = 0.05 for rapid replication rate, p = 0.01 for syncytium-inducing viral phenotype). Plasma viral burden higher than 5.5 log10 copies/mL after 6 mo of age tended to be associated with disease progression. In conclusion, initial HIV-1 biologic features in pediatric primary infection by vertical transmission may influence the progression to early immunosuppression and development of AIDS.
TOPS: Trial Of Prevention Strategies for low back pain in patients recently recovered from low back pain—study rationale and protocol

Introduction Low back pain (LBP) is the health condition that carries the greatest disability burden worldwide; however, there is only modest support for interventions to prevent LBP. The aim of this trial is to establish the effectiveness and cost-effectiveness of group-based exercise and educational classes compared with a minimal intervention control in preventing recurrence of LBP in people who have recently recovered from an episode of LBP. Methods and analysis TOPS will be a pragmatic comparative effectiveness randomised clinical trial with a parallel economic evaluation combining three separate cohorts (TOPS Workers, TOPS Primary Care, TOPS Defence) with the same methodology. 1482 participants who have recently recovered from LBP will be randomised to either a comprehensive exercise and education programme or a minimal intervention control. Participants will be followed up for a minimum of 1 year. The primary outcome will be days till recurrence of LBP. Effectiveness will be assessed using survival analysis. Cost-effectiveness will be assessed from the societal perspective. Ethics and dissemination This trial has been approved by the University of Sydney Human Research Ethics Committee (HREC) (ref: 2015/728) and prospectively registered with the Australian and New Zealand Clinical Trials Registry (ref: 12615000939594). We will also obtain ethics approval from the Australian Defence Force HREC. The results of this study will be submitted for publication in a prominent journal and widely publicised in the general media. Trial registration number Australian and New Zealand Clinical Trial Registry (ANZCTR) 12615000939594.
A Spatio-temporal Distance Based Two-Phase Heuristic Algorithms for Vehicle Routing Problem

Vehicle Routing Problem with Time Windows (VRPTW) is a well-known NP-hard problem. An effective method to solve this problem is to partition the customers first and then create and improve the routes. Conventionally, customers are partitioned by spatial distance only. In this paper, we propose to use a spatiotemporal distance to group customers. A new tabu search algorithm with a self-adaptive objective function is employed to improve the route. With 56 Solomon benchmark problems, different strategies have been tested and compared. Computational results show that proposed spatiotemporal distance is more efficient than spatial distance when solving narrow time window VRPTW problems, which can provide many known best solutions.
Detecting chaos in a duopoly model via symbolic dynamics

This paper considers a Cournot duopoly model assuming isoelastic demand and smooth cost functions with built-in capacity limits. When the firms cannot obtain positive profits they are assumed to choose small "stand-by" outputs rather than closing down, in order to avoid substantial fitting up costs when market conditions turn out more favorable. It is shown that the model provides chaotic behavior. In particular, the system has positive topological entropy and hence the map is chaotic in the Li-Yorke sense. Moreover, chaos is not only topological but also physically observable.
Inhibition of invasion, gelatinase activity, tumor take and metastasis of malignant cells by N‐acetylcysteine

The thiol N‐acetylcysteine (NAC) is currently considered one of the most promising cancer chemopreventive agents by virtue of its multiple and coordinated mechanisms affecting the process of chemical carcinogenesis. Recent studies have shown that an unpaired cysteine residue in the propeptide plays a key role in inactivation of latent metastasis‐associated metalloproteinases: the present study was designed to assess whether NAC could also affect tumor take, invasion and metastasis of malignant cells. As assessed by zymographic analysis, NAC completely inhibited the gelatinolytic activity of type‐IV collagenases in the cells tested (gelatinases A and B). Moreover, NAC was efficient in inhibiting the chemotactic and invasive activities of tumor cells of human (A2058 melanoma) and murine origin (K1735 and B16‐F10 melanoma cells as well as C87 Lewis lung carcinoma cells) in Boyden‐chamber assays, which are predictive of the invasive and metastatic properties. Reduced glutathione (GSH) had a similar, although less effective activity. The number of lung metastases decreased sharply when B16‐F10 murine melanoma cells, injected i.v. into nude mice, were pre‐treated with NAC and resuspended in medium supplemented with 10 mM NAC. In other experiments NAC was given in drinking water, starting 48‐72 hr before subcutaneous inoculation of either B16‐F10 cells or of their highly metastatic variant B16‐BL6, or intramuscular injection of LLC cells. In all experiments NAC treatment decreased the weight of the locally formed primary tumor and produced a dose‐related delay in tumor formation. Spontaneous metastasis formation by B16‐F10 and B16‐BL6 tumors was slightly yet significantly reduced by oral administration of NAC. However, this was not observed for Lewis lung tumors. These data indicate that NAC affects the process of tumor‐cell invasion and metastasis, probably due to inhibition of gelatinases by its sulfhydryl group, with the possible contribution of other mechanisms, including the potent antioxidant activity of this thiol. © 1995 Wiley‐Liss, Inc.
Significant increase of colonic mutated crypts correlates with age in sporadic cancer and diverticulosis cases, with higher frequency in the left‐ than right‐side colorectum

Mild periodic acid–Schiff (mPAS) staining can discriminate non‐O‐acetylated (mPAS‐positive) from O‐acetylated (mPAS‐negative) epithelial sialoglycoproteins in human colonic mucosa, allowing the three haplotypes expressed from a single polymorphic autosomal gene (oat) to be distinguished. In heterozygotes, we previously demonstrated wholly mPAS‐positive (stem cell mutated) crypts and clusters of two or more mPAS‐positive crypts to be significantly increased with duration of ulcerative colitis. To establish whether such an increase in the number of mutated crypts with age also occurs in normal individuals or in cases with diverticulosis, the O‐acetylation phenotype in the non‐cancerous colonic mucosa of 47 sporadic colorectal cancer patients who were heterozygotes for oat was tested with mild‐PAS staining. PAS‐positive crypts were assessed histologically in relation to age and compared between the left (sigmoid colon and rectum) and right (cecum and ascending colon) sides of the colorectum. Wholly mPAS‐positive (stem cell mutated) crypts and foci in heterozygotes were found to be increased significantly (P < 0.0001) in the left side with aging (r = 0.598 and 0.643, respectively). Such a positive correlation with aging was also confirmed in 19 diverticulosis cases without cancer (r = 0.797 and 0.793, respectively). The frequency of mutated crypts and foci on the right side was significantly lower than on the left side in both spontaneous colorectal cancer and diverticulosis cases. The results provide support for an intimate relationship between accumulation of mutated crypts with aging, possibly with significance for colorectal cancer development. Furthermore, the environment in the right side of the colon may be different from that in the left side in this regard. (Cancer Sci 2006; 97)
Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis.

OBJECTIVE To evaluate the contribution of metabolites (methotrexate [MTX] and folate polyglutamate [PG] levels) and pharmacogenetic biomarkers in the folate pathway to the effects of MTX in patients with rheumatoid arthritis not previously treated with this antifolate. METHODS Forty-eight MTX-naive adult patients were enrolled in a prospective longitudinal study. MTX therapy was initiated at 7.5 mg/week and was increased every 4-6 weeks until a therapeutic response was achieved. Response was assessed using the Disease Activity Score in 28 joints (DAS28). Red blood cell (RBC) MTX and folate PG levels were measured with 9 common polymorphisms in the folate pathway. Statistical analyses consisted of generalized linear models and multivariate regressions. RESULTS After 6 months of therapy, the median weekly MTX dosage was 17.5 mg and the median decrease in the DAS28 was 2.0. There was a large interpatient variability in RBC MTXPG levels (median 35 nmoles/liter [interquartile range 28-51] at month 6). Patients with a lesser decrease in the DAS28 (fewer improvements) had lower RBC MTXPG levels (P < 0.05) despite the higher MTX dose administered (P < 0.05). RBC folate PG levels decreased significantly during treatment, and a lesser decrease in RBC folate PGs was associated with a lesser decrease in the DAS28 (P < 0.05). Primary side effects were gastrointestinal and neurologic in nature. Risk genotypes associated with toxicity were in gamma-glutamyl hydrolase (-401CC), 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (347GG), methylenetetrahydrofolate reductase (1298AC/CC), methionine synthase (2756AA), and methionine synthase reductase (66GG). CONCLUSION RBC MTXPG levels are a useful means by which to monitor therapy. The genetic associations presented generate hypotheses, and confirmation in independent cohorts is warranted.
Theory-based Learning Analytics: Using Formal Concept Analysis for Intelligent Student Modelling

Learning Analytics is one of the most important fields for driving (educational) artificial intelligence. In this paper we briefly introduce one of Europe’s key research initiatives to make a step from primarily statistics and data mining driven ways to do Learning Analytics, towards more theory-grounded, psychopedagogically inspired analyses. One approach we suggest is Formal Concept Analysis, which is a strong theoretical backbone in technology-enhanced learning settings For educators, FCA may provide AI-based analyses of ‘big data’ sets and intuitive representations for a number of pedagogical questions concerning the performance of students on the individualas well as the classlevel.
Genetics of Mosquito Vector Competence

SUMMARY Mosquito-borne diseases are responsible for significant human morbidity and mortality throughout the world. Efforts to control mosquito-borne diseases have been impeded, in part, by the development of drug-resistant parasites, insecticide-resistant mosquitoes, and environmental concerns over the application of insecticides. Therefore, there is a need to develop novel disease control strategies that can complement or replace existing control methods. One such strategy is to generate pathogen-resistant mosquitoes from those that are susceptible. To this end, efforts have focused on isolating and characterizing genes that influence mosquito vector competence. It has been known for over 70 years that there is a genetic basis for the susceptibility of mosquitoes to parasites, but until the advent of powerful molecular biological tools and protocols, it was difficult to assess the interactions of pathogens with their host tissues within the mosquito at a molecular level. Moreover, it has been only recently that the molecular mechanisms responsible for pathogen destruction, such as melanotic encapsulation and immune peptide production, have been investigated. The molecular characterization of genes that influence vector competence is becoming routine, and with the development of the Sindbis virus transducing system, potential antipathogen genes now can be introduced into the mosquito and their effect on parasite development can be assessed in vivo. With the recent successes in the field of mosquito germ line transformation, it seems likely that the generation of a pathogen-resistant mosquito population from a susceptible population soon will become a reality.
A randomized trial of a classroom intervention to increase peers' social inclusion of children with attention-deficit/hyperactivity disorder.

OBJECTIVE Interventions for peer problems among children with attention-deficit/hyperactivity disorder (ADHD) typically focus on improving these children's behaviors. This study tested the proposition that an adjunctive component encouraging the peer group to be socially inclusive of children with ADHD would augment the efficacy of traditional interventions. METHOD Two interventions were compared: contingency management training (COMET), a traditional behavioral management treatment to improve socially competent behavior in children with ADHD, and Making Socially Accepting Inclusive Classrooms (MOSAIC), a novel treatment that supplemented behavioral management for children with ADHD with procedures training peers to be socially inclusive. Children ages 6.8-9.8 (24 with ADHD; 113 typically developing [TD]) attended a summer day program grouped into same-age, same-sex classrooms with previously unacquainted peers. Children with ADHD received both COMET and MOSAIC with a repeated measures crossover design. TD children provided sociometric information about the children with ADHD. RESULTS Whereas the level of behavior problems displayed by children with ADHD did not differ across treatment conditions, children with ADHD displayed improved sociometric preference and more reciprocated friendships, and received more positive messages from peers, when they were in MOSAIC relative to COMET. However, the beneficial effects of MOSAIC over COMET predominantly occurred for boys relative to girls. CONCLUSIONS Data support the concept that adjunctive procedures to increase the inclusiveness of the peer group may ameliorate peer problems among children with ADHD, and suggest the potential utility of modifying MOSAIC to be delivered in regular classroom settings.