Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Typing of Borrelia burgdorferiSensu Lato by Randomly Amplified Polymorphic DNA Fingerprinting Analysis

ABSTRACT To study whether pathogenic clusters of Borrelia burgdorferi sensu lato strains occur, we typed 136 isolates, cultured from specimens from patients (n = 49) with various clinical entities and from ticks (n = 83) or dogs (n = 4) from different geographic regions, by randomly amplified polymorphic DNA (RAPD) fingerprinting with four arbitrary primers. The RAPD patterns were reproducible up to the 95% similarity level as shown in duplicate experiments. In these experiments the purified DNAs prepared on different days, from different colonies, and after various passages were used as templates. With an intergroup difference of 55%, the 136 strains could be divided into seven genetic clusters. Six clusters comprised and corresponded to the established species B. burgdorferi sensu stricto (n = 23), Borrelia garinii(n = 39), Borrelia afzelii(n = 59), Borrelia japonica(n = 1), Borrelia valaisiana(n = 12), and genomic group DN127 (n= 1). One strain from a patient with erythema migrans (EM) did not belong to any of the species or genomic groups known up to now. The RAPD types of B. burgdorferi sensu stricto, B. garinii, and B. afzelii isolates, which may give rise to human Lyme borreliosis (LB), were associated with their geographic origins. A high degree of genetic diversity was observed among the 39B. garinii strains, and six subgroups could be recognized. One of these comprised eight isolates from patients with disseminated LB only and no tick isolates. B. afzelii strains from patients with EM or acrodermatitis chronica atrophicans were not clustered in particular branches. Our study showed that RAPD analysis is a powerful tool for discriminating different Borreliaspecies as well as Borrelia isolates within species.
Fibronectin stimulates Escherichia coli phagocytosis by microglial cells

Microglia express Toll‐like receptors (TLRs) that recognize invading pathogens as well as endogenous proteins such as fibronectin under nonphysiological conditions. Here, we demonstrated that fibronectin stimulates murine microglia in culture in a dose‐dependent manner: microglial cells secreted proinflammatory cytokines and chemokines and increased phagocytosis of Escherichia coli DH5α and E. coli K1 strains. Low levels of fibronectin exerted a synergistic effect on the release of proinflammatory compounds by microglia co‐stimulated with agonists for TLR1/2 (Pam3CSK4) or TLR9 (CpG DNA), but not in combination with the TLR4 agonist lipopolysaccharide (LPS). Phagocytosis of bacterial strains was moderately enhanced when microglia was co‐stimulated with high concentrations of fibronectin and one pathogen‐derived TLR agonist. In conclusion, fibronectin increased proinflammatory and phagocytotic functions in microglia and partially synergized with microbial TLR agonists. © 2009 Wiley‐Liss, Inc.
Bayesian Approach to Channel Estimation for AF MIMO Relaying Systems

In this paper, we investigate the problem of channel estimation in amplify-and-forward multiple-input multiple-output relaying systems operating over random wireless channels. Using the Bayesian framework, novel linear minimum mean square error and expectation-maximization based maximum a posteriori channel estimation algorithms are developed, that provide the destination with full knowledge of all channel parameters involved in the transmission. Moreover, new, explicit expressions for the Bayesian Cramer-Rao bound are deduced for predicting and evaluating the channel estimation accuracy. Our simulation results demonstrate that the incorporation of prior knowledge into the channel estimation algorithm offers significantly improved performance, especially in the low signal-to-noise ratio regime.
Phase Relationships between Sleep-Wake Cycle and Underlying Circadian Rhythms in Morningness-Eveningness

A shorter phase angle between habitual wake time and underlying circadian rhythms has been reported in evening types (E types) compared to morning-types (M types). In this study, phase angles were compared between 12 E types and 12 M types to verify if this difference was observed when the sleep schedule was relatively free from external social constraints. Subjects were selected according to their Morningness-Eveningness Questionnaire score (MEQ score). There were 6 men and 6 women in each group (ages 19-34 years), and all had a habitual sleep duration between 7 and 9 h. Sleep schedule was recorded by actigraphy and averaged over 7 days. Circadian phase was estimated by the hour of temperature minimum (Tmin) in a 26-h recording and by the timing of the onset of melatonin secretion (dim-light melatonin onset [DLMO]) measured in saliva samples. Phase angles were defined as the interval between phase markers and averaged wake time. Results showed that, in the present experimental conditions, phase angles were very similar in the 2 groups of subjects. However, results confirmed the previously reported correlation between phase and phase angle, showing that a later circadian phase was associated with a shorter phase angle. Gender comparisons showed that for a same MEQ score, women had an earlier DLMO and a longer phase angle between DLMO and wake time. Despite a significant difference in the averaged circadian phases between E-type and M-type groups, there was an overlap in the circadian phases of the subjects of the 2 groups. Further comparisons were made between the 2 circadian types, separately for the subgroups with overlapping or nonoverlapping circadian phases. In both subgroups, the significant difference between MEQ scores, bedtimes, and wake times were maintained in the expected direction. In the subgroup with nonoverlapping circadian phases, phase angles were shorter in E-type subjects, in accordance with previous studies. However, in the overlapping subgroup, phase angles were significantly longer in E types compared to M types. Results suggest that the morningness-eveningness preference identified by the MEQ score refers to 2 distinct mechanisms, 1 associated with a difference in circadian period and phase of entrainment and the other associated with chronobiological aspects of sleep regulation.
Preclinical evaluation of the imipridone family, analogs of clinical stage anti-cancer small molecule ONC201, reveals potent anti-cancer effects of ONC212

ABSTRACT Anti-cancer small molecule ONC201 upregulates the integrated stress response (ISR) and acts as a dual inactivator of Akt/ERK, leading to TRAIL gene activation. ONC201 is under investigation in multiple clinical trials to treat patients with cancer. Given the unique imipridone core chemical structure of ONC201, we synthesized a series of analogs to identify additional compounds with distinct therapeutic properties. Several imipridones with a broad range of in vitro potencies were identified in an exploration of chemical derivatives. Based on in vitro potency in human cancer cell lines and lack of toxicity to normal human fibroblasts, imipridones ONC206 and ONC212 were prioritized for further study. Both analogs inhibited colony formation, and induced apoptosis and downstream signaling that involves the integrated stress response and Akt/ERK, similar to ONC201. Compared to ONC201, ONC206 demonstrated improved inhibition of cell migration while ONC212 exhibited rapid kinetics of activity. ONC212 was further tested in >1000 human cancer cell lines in vitro and evaluated for safety and anti-tumor efficacy in vivo. ONC212 exhibited broad-spectrum efficacy at nanomolar concentrations across solid tumors and hematological malignancies. Skin cancer emerged as a tumor type with improved efficacy relative to ONC201. Orally administered ONC212 displayed potent anti-tumor effects in vivo, a broad therapeutic window and a favorable PK profile. ONC212 was efficacious in vivo in BRAF V600E melanoma models that are less sensitive to ONC201. Based on these findings, ONC212 warrants further development as a drug candidate. It is clear that therapeutic utility extends beyond ONC201 to include additional imipridones.
The Effects of Macroeconomic Aggregates on Fertility Decisions: Theory and Evidence from U.S. Annual Data

Using U.S. data for 1980-2010, this paper studies the effects of various macroeconomic variables, particularly the national debt, government budget deficits and taxes, on fertility decisions over the business cycle. A rise in the debt-GDP ratio, government spending-GDP ratio and the deficit-GDP ratio reduces fertility over the business cycle. On the other hand, a fall in the tax revenues-GDP ratio is associated with lower fertility rates. These results hold even after controlling for other potential determinants of fertility such as the female unemployment rate, female participation rate in the labor force, inflation rate, GDP growth rate, urbanization rate, female life expectancy, marriage rate and divorce rate. I then show that these findings can only be explained by a business cycle model that accounts for moral behavior. Households find it immoral to give more births during periods of mounting national debt and deficits, even following expansionary fiscal policies in the form of higher government spending or lower taxation, so that their children will not need to repay them in the future. JEL Classification: D03; E32; H31; H62; H63; J10; J13.
Hemostasis and Malignancy

There is considerable evidence that the hemostatic system is involved in the growth and spread of malignant disease. There is an increased incidence of thromboembolic disease in patients with cancers and hemostatic abnormalities are extremely common in such patients. Antihemostatic agents have been successfully used to treat a variety of experimental tumors, and several clinical trials in humans have been initiated. Although metastasis is undoubtedly multifactorial, intravascular coagulation activation and peritumor fibrin deposition seem to be important. The mechanisms by which hemostatic activation facilitates the malignant process remain to be completely elucidated. Of central importance may be the presence on malignant cells of tissue factor and urokinase receptor. Recent studies have suggested that these proteins, and others, may be involved at several stages of metastasis, including the key event of neovascularization. Tissue factor, the principal initiator of coagulation, may have additional roles, outside of fibrin formation, that are central to the biology of some solid tumors.
Glioma cells deficient in urokinase plaminogen activator receptor expression are susceptible to tumor necrosis factor-alpha-related apoptosis-inducing ligand-induced apoptosis.

PURPOSE The urokinase plasminogen activation system comprises the ligand urokinase plasminogen activator and the receptor urokinase plasminogen activator receptor (uPAR), which play an important role in the activation of matrix-degrading enzymes that enhance the invasion of cancer cells. Earlier studies have indicated that SNB19 glioblastoma cells expressing antisense uPAR constructs lose their invasive properties when injected in vivo. Additional observations indicated that injected antisense uPAR:SNB19 cells were being lost through apoptotic elimination. EXPERIMENTAL DESIGN SNB19, Vector, and SNB19:asuPAR were analyzed to determine cytotoxicity of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL), receptor expression, and underlying signaling pathways using flow cytometry, immunohistochemistry, RNase protection assay, and c-Jun-NH(2)-terminal kinase activity. RESULTS This study elucidated the susceptibility of antisense uPAR:SNB19 cells to TRAIL under certain experimental conditions in vitro. These uPAR-deficient transfected cells had higher levels of the TRAIL receptors DR4 and DR5 than did the control and vector population as detected by flow cytometry. An RNase protection assay confirmed the elevation of DR4 and DR5 mRNA in the antisense uPAR cells. CONCLUSIONS These findings provide preliminary evidence of a link between TRAIL-induced apoptosis and cell cycle progression in antisense uPAR:SNB 19 cells.
Creating and Leading Analytic Teams

The analysis of intelligence information invariably involves both cognitive and social processes. At core, analysis is a cognitive activity. Although intelligence analysts often draw both on technological aids and on input from others, ultimately it is the human brain that organizes and interprets data to generate an assessment or prediction. A great deal of research has been conducted to identify both the cognitive biases that can compromise the validity of analytic conclusions and the heuristics that can help analysts do their work efficiently and well (see, for example, the well-known book by Richards Heuer [1999] on the psychology of intelligence analysis, research by Gerd Gigerenzer and his colleagues [1999] on "fast and frugal" heuristics, and the other chapters in this volume). Yet analytic work also is an inherently social process. The conduct of intelligence analysis always involves relationships with those who assign analytic tasks and receive analytic products. The threats to the validity of analytic conclusions that can develop when those relationships become politicized are well known. Less widely recognized is the fact that analytic work itself is highly social in character. The lone analyst working in isolation to extract the meaning from a set of data is the exception rather than the rule. Instead, analysts typically draw heavily on the expertise, experience, and insights of their colleagues in developing and testing their conclusions. Most of the analysts who participated in a recent study of 64 analytic units in six U.S. intelligence organizations, for example, worked in groups of various kinds (Hackman & O'Connor, 2004). As intelligence data increase in quantity and diversity, teamwork is likely to become increasingly prominent in the production of analytic reports. This chapter-3-explores the different kinds of teamwork that can be used in analyzing intelligence data, identifies the organizational conditions that foster analytic team effectiveness, and suggests strategies for competently structuring, leading, and working within analytic teams. We use the term " collaborative analysis " to refer to work performed by a set of professionals who share responsibility for using data that are incomplete and/or of uncertain reliability to generate conclusions about something that has happened, is happening, or is likely to happen. Such work involves multiple steps about which considerable research has been done-the identification of an issue of concern, the definition of the problem, the creation or selection of the information to be considered, pooling of knowledge, coordinating members' inputs, and decision-making about …
Chemotherapy and signaling

In recent years, oncologists have begun to conclude that chemotherapy has reached a plateau of efficacy as a primary treatment modality, even if toxicity can be effectively controlled. Emerging specific inhibitors of signaling and metabolic pathways (i.e., targeted agents) contrast with traditional chemotherapy drugs in that the latter primarily interfere with the DNA biosynthesis and the cell replication machinery. In an attempt to improve on the efficacy, combination of targeted drugs with conventional chemotherapeutics has become a routine way of testing multiple new agents in early phase clinical trials. This review discusses the recent advances including integrative systematic biology and RNAi approaches to counteract the chemotherapy resistance and to buttress the selectivity, efficacy and personalization of anti-cancer drug therapy.
BIOTINYLATED AND CHELATED POLY-L-LYSINE AS EFFECTOR FOR PRETARGETING IN CANCER THERAPY AND IMAGING

Objective: The aim of this study was to synthesise and evaluate polylysine-based effectors for pretargeted radioimmunotherapy and imaging. These molecules can readily be size-modified and charge-modified to decrease the renal uptake of radioactivity, which is often a major problem for small radiolabeled molecules. Several chelators and biotin molecules (for antibody-streptavidin-binding in vivo ) are also easily incorporated into one structure because of the polylysine. Methods: The effectors were synthesised using poly-L-lysine, NHS-LC-biotin, CHX-A’’-DTPA or p -SCN-Bn-DOTA and succinic anhydride. They were characterised, labelled with 213 Bi for targeted α therapy, 68 Ga for PET and 111 In for SPECT, and evaluated in vitro . A kidney uptake study was performed as well with two different-sized 213 Bi-labeled effectors, to evaluate how the difference in size affects the renal filtration. Results: Radiochemical purities between 97.4±0.6 % and 99.6±0.1 % and decay-corrected yields of 80.2±2.4 % after purification were achieved with the radiolabeled molecules, as well as a specific activity of 7.6 × 10 3 GBq/µmol. The avidin binding capacity was 94.4±1.9%. The kidney uptake study demonstrated a reduction of renal absorbed dose by 80% when modifying the molecular size and charge. Conclusion: The synthesised polylysine-based effectors show potential for further in vivo evaluation in pretargeted radioimmunotherapy and imaging.
Cyclic Di-GMP Signaling in Bacteria: Recent Advances and New Puzzles

Cyclic di-GMP \[bis-(3′-5′)-cyclic di-GMP\] (Fig. [1][1]) is a novel second messenger in bacteria that was first described as an allosteric activator of cellulose synthase in Gluconacetobacter xylinus ([49][2]). It is now established that this nucleotide is almost ubiquitous in bacteria, where
Promising particle-based vaccines in cancer therapy

Immunotherapy and preventative cancer vaccines offer the hope of controlling cancer in humans with few of the undesirable side effects associated with current chemotherapy-based methods. Particulate vaccines are effectively taken up by dendritic cells, inducing both T-cell and antibody responses. Virus-like particles (VLPs) have shown preventive efficacy against cervical cancer. Herein we review a range of leading particle-based vaccine approaches: VLPs, immunostimulating complexes, liposomes, synthetic nanoparticles and microparticles (both biocompatible and biodegradable, such as polylactide-co-glycolides and poly[D,L-lactic-co-glycolic] acid). Immune efficacy, regulatory and safety issues, as well the application of immunotherapeutics to immunosuppressed patients with high levels of Tregs are also discussed. We argue that developmental issues (cost and intellectual property lifespan) and the lack of reliable preclinical animal models, rather than the lack of innovative vaccine approaches, currently present a major obstacle to rapid and effective vaccine development.
Associated with Molluscan Shellfish Consumption

INTRODUCTION . 419 ILLNESS ASSOCIATED WITH DISPOSAL OF FECAL WASTES AND SEWAGE INTO THE AQUATIC ENVIRONMENT . 420 Wastewater Disposal Practices and Shellfish-Vectored Illnesses . 420 Agents of Viral and Bacterial Gastroenteritis . 421 Hepatitis A Infections . 421 Seasonality of Illness Reports . 422 Relative Incidence of Allocthonous Microbial Agents Involved in Disease Outbreaks . 422 AUTOCHTHONOUS MARINE BACTERIA AS AGENTS OF SHELLFISH-VECTORED ILLNESSES.423 V. vulnificus . 423 V. cholerae. 423 OtherVibiios. SPECIES AND SOURCES OF SHELLFISH FROM ILLNESS REPORTS. VYNTCT I T.eTnN . 424 . -----------------. 424 . 424 A7,A REFERENCES
An FMRI study of number processing in children with fetal alcohol syndrome.

BACKGROUND Number processing deficits are frequently seen in children exposed to alcohol in utero. METHODS Functional magnetic resonance imaging was used to examine the neural correlates of number processing in 15 right-handed, 8- to 12-year-old children diagnosed with fetal alcohol syndrome (FAS) or partial FAS (PFAS) and 18 right-handed, age- and gender-matched controls from the Cape Coloured (mixed ancestry) community in Cape Town, South Africa, using Proximity Judgment and Exact Addition tasks. RESULTS Control children activated the expected fronto-parietal network during both tasks, including the anterior horizontal intraparietal sulcus (HIPS), left posterior HIPS, left precentral sulcus, and posterior medial frontal cortex. By contrast, on the Proximity Judgment task, the exposed children recruited additional parietal pathways involving the right and left angular gyrus and posterior cingulate/precuneus, which may entail verbally mediated recitation of numbers and/or subtraction to assess relative numerical distances. During Exact Addition, the exposed children exhibited more diffuse and widespread activations, including the cerebellar vermis and cortex, which have been found to be activated in adults engaged in particularly challenging number processing problems. CONCLUSIONS The data suggest that, whereas control children rely primarily on the fronto-parietal network identified in previous studies to mediate number processing, children with FAS/PFAS recruit a broader range of brain regions to perform these relatively simple number processing tasks. Our results are consistent with structural neuroimaging findings indicating that the parietal lobe is relatively more affected by prenatal alcohol exposure and provide the first evidence for brain activation abnormalities during number processing in children with FAS/PFAS, effects that persist even after controlling statistically for group differences in total intracranial volume and IQ.
Thalidomide in combination with vincristine, epirubicin and dexamethasone (VED) for previously untreated patients with multiple myeloma

Abstract: The present study aimed to evaluate the side‐effects and efficacy of thalidomide in combination with an anthracycline‐containing chemotherapy regimen in previously untreated myeloma patients. Thalidomide (400 mg/d) was combined with bolus injections of vincristine and epirubicin and oral dexamethasone (VED). Chemotherapy cycles were repeated every 3 wk until no further reduction in myeloma protein was observed, whereas the treatment with thalidomide was continued until disease progression. Thirty‐one patients were enrolled, 12 patients were exclusively treated with thalidomide in combination with VED and 19 patients additionally received high‐dose melphalan, for consolidation. Adverse events and response to therapy were assessed prior to treatment with high‐dose chemotherapy. Response to thalidomide combined with VED was complete remission in six patients (19%), partial remission in 19 patients (61%), stable disease in five patients (16%), and progressive disease in one patient (3.2%). Grade 3 and 4 adverse events consisted of leukocytopenia in 10 patients (32%), and thrombocytopenia and anemia in one patient each (3.2%). Neutropenic infections grade 3 and 4 occurred in seven (23%) and three patients (9.7%), respectively, including two patients (6.5%) who died from septic shock. Deep vein thrombosis occurred in eight patients (26%), constipation in 20 patients (65%), and polyneuropathy in 20 patients (65%). The probability of event‐free survival and overall survival in the whole group of patients at 36 months were 26 and 62%, respectively. In conclusion, the combination of thalidomide with VED appears to be highly effective in previously untreated patients with multiple myeloma, but it is associated with a high rate of thrombotic events, polyneuropathy, and neutropenic infections.