Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipidomic Analysis Links Mycobactin Synthase K to Iron Uptake and Virulence in M. tuberculosis

The prolonged survival of Mycobacterium tuberculosis (M. tb) in the host fundamentally depends on scavenging essential nutrients from host sources. M. tb scavenges non-heme iron using mycobactin and carboxymycobactin siderophores, synthesized by mycobactin synthases (Mbt). Although a general mechanism for mycobactin biosynthesis has been proposed, the biological functions of individual mbt genes remain largely untested. Through targeted gene deletion and global lipidomic profiling of intact bacteria, we identify the essential biochemical functions of two mycobactin synthases, MbtK and MbtN, in siderophore biosynthesis and their effects on bacterial growth in vitro and in vivo. The deletion mutant, ΔmbtN, produces only saturated mycobactin and carboxymycobactin, demonstrating an essential function of MbtN as the mycobactin dehydrogenase, which affects antigenicity but not iron uptake or M. tb growth. In contrast, deletion of mbtK ablated all known forms of mycobactin and its deoxy precursors, defining MbtK as the essential acyl transferase. The mbtK mutant showed markedly reduced iron scavenging and growth in vitro. Further, ΔmbtK was attenuated for growth in mice, demonstrating a non-redundant role of hydroxamate siderophores in virulence, even when other M. tb iron scavenging mechanisms are operative. The unbiased lipidomic approach also revealed unexpected consequences of perturbing mycobactin biosynthesis, including extreme depletion of mycobacterial phospholipids. Thus, lipidomic profiling highlights connections among iron acquisition, phospholipid homeostasis, and virulence, and identifies MbtK as a lynchpin at the crossroads of these phenotypes.
Propagation of granulocytic Ehrlichia spp. from human and equine sources in HL-60 cells induced to differentiate into functional granulocytes

Ehrlichia spp. from human and equine sources in the northeastern Unites States were detected by PCR, isolated, and propagated in the HL-60 promyelocytic leukemia cell line. Growth of Ehrlichia from both equine and human sources was enhanced by addition of retinoic acid, which causes granulocytic differentiation of the HL-60 cells. DNA sequencing of a portion of the 16S rDNA gene supported the hypothesis that the same pathogen was responsible for both equine and human granulocytic ehrlichiosis.
Construction, Analysis, and β-Glucanase Screening of a Bacterial Artificial Chromosome Library from the Large-Bowel Microbiota of Mice

ABSTRACT A metagenomic (community genomic) library consisting of 5,760 bacterial artificial chromosome clones was prepared in Escherichia coli DH10B from DNA extracted from the large-bowel microbiota of BALB/c mice. DNA inserts detected in 61 randomly chosen clones averaged 55 kbp (range, 8 to 150 kbp) in size. A functional screen of the library forβ -glucanase activity was conducted using lichenin agar plates and Congo red solution. Three clones with β-glucanase activity were detected. The inserts of these three clones were sequenced and annotated. Open reading frames (ORF) that encoded putative proteins with identity to glucanolytic enzymes (lichenases and laminarinases) were detected by reference to databases. Other putative genes were detected, some of which might have a role in environmental sensing, nutrient acquisition, or coaggregation. The insert DNA from two clones probably originated from uncultivated bacteria because the ORF had low sequence identity with database entries, but the genes associated with the remaining clone resembled sequences reported in Bacteroides species.
Massive compensatory hyperinflation

A 14-year-old girl presented with a 1-year history of insidious onset dyspnoea. Three years previously, she had been treated for 6 months with directly observed antituberculous treatment for sputum smear positive pulmonary tuberculosis (TB) and the treatment was successful. Chest radiograph demonstrated gross mediastinal shift to the right side with hyperinflated left hemithorax (figure 1). A CT scan demonstrated massive hyperinflation and anterior herniation of left lung across the midline to the right side with complete …
A monoclonal antibody against human complement component C3: the production of C3 by human cells in vitro

A monoclonal antibody (WM1) against the third component of human complement (C3) was produced by fusing P3‐X63‐Ag8 mouse myeloma cells with spleen cells from BALB/c mice immunized with purified C3. The specificity of WM1 antibody against C3 was established by its capacity to inhibit a standard C3 hemolytic assay and to immunoprecipitate C3 from human serum in the presence of S. aureus bacteria. Indirect binding assays indicate that the antibody is directed against the C3c portion of C3. The immunoprecipitation technique was used to screen for the presence of C3 in the culture supernatants of various cell lines. By this means, C3 was identified as a secreted product of human primary fibroblasts, transformed fibroblasts and D98/AH‐2, a HeLa derivative, but not of other human cell lines. WM1 was unable to immunoprecipitate C3 from rabbit or mouse fibroblast culture supernatants.
HIV/AIDS among Inmates of and Releasees from US Correctional Facilities, 2006: Declining Share of Epidemic but Persistent Public Health Opportunity

Because certain groups at high risk for HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) come together in correctional facilities, seroprevalence was high early in the epidemic. The share of the HIV/AIDS epidemic borne by inmates of and persons released from jails and prisons in the United States (US) in 1997 was estimated in a previous paper. While the number of inmates and releasees has risen, their HIV seroprevalence rates have fallen. We sought to determine if the share of HIV/AIDS borne by inmates and releasees in the US decreased between 1997 and 2006. We created a new model of population flow in and out of correctional facilities to estimate the number of persons released in 1997 and 2006. In 1997, approximately one in five of all HIV-infected Americans was among the 7.3 million who left a correctional facility that year. Nine years later, only one in seven (14%) of infected Americans was among the 9.1 million leaving, a 29.3% decline in the share. For black and Hispanic males, two demographic groups with heightened incarceration rates, recently released inmates comprise roughly one in five of those groups' total HIV-infected persons, a figure similar to the proportion borne by the correctional population as a whole in 1997. Decreasing HIV seroprevalence among those admitted to jails and prisons, prolonged survival and aging of the US population with HIV/AIDS beyond the crime-prone years, and success with discharge planning programs targeting HIV-infected prisoners could explain the declining concentration of the epidemic among correctional populations. Meanwhile, the number of persons with HIV/AIDS leaving correctional facilities remains virtually identical. Jails and prisons continue to be potent targets for public health interventions. The fluid nature of incarcerated populations ensures that effective interventions will be felt not only in correctional facilities but also in communities to which releasees return.
Understanding the Educational Values of Video Games from the Perspective of Situated Learning Theory and Game Theory

The educational values of video games have been widely acknowledged and discussed, and a deep understanding of the learning process provides crucial theory basis for understanding video game. This paper tries to answer the question how video games can enhance learning based upon the situated learning theory and game theory. Legitimate peripheral participation is the core concept for situated learning theory, which illustrates that learning is unintentional and situated within authentic activity, context, and culture, and it is a process of participation in communities of practice in real context. Based upon the core idea of situated learning, the ideal learning environment should make students get engaged in the learning activities, provide the delicately designed learning contexts, and encourage students' active participation in the dynamic learning process. Correspondingly, James Paul Gee [1], in his book What Video Games Have to Teach Us about Learning and Literacy, proposed that the theory of learning in good video games is close to the best theories of learning in cognitive science and good theories of learning are embedded in the video games, which also fit with the modernity, high-technology development and globalization. People get deeply immersed when they play games. There are so many strengths in games that should be studied and utilized for learning purposes. What's more, educational games also help students to gain the knowledge and skills that are needed in the 21st century. This paper will make a comprehensive discussion upon the connection between situated learning theory and video games.
Empirically-based Control of Natural Language Generation

In this paper we present a new approach to controlling the behaviour of a natural language generation system by correlating internal decisions taken during free generation of a wide range of texts with the surface stylistic characteristics of the resulting outputs, and using the correlation to control the generator. This contrasts with the generate-and-test architecture adopted by most previous empirically-based generation approaches, offering a more efficient, generic and holistic method of generator control. We illustrate the approach by describing a system in which stylistic variation (in the sense of Biber (1988)) can be effectively controlled during the generation of short medical information texts.
Styrene Maleic Acid-Pirarubicin Disrupts Tumor Microcirculation and Enhances the Permeability of Colorectal Liver Metastases

Background: Doxorubicin is a commonly used chemotherapy limited by cardiotoxicity. Pirarubicin, derived from doxorubicin, selectively targets tumors when encapsulated in styrene maleic acid (SMA), forming the macromolecular SMA pirarubicin. Selective targeting is achieved because of the enhanced permeability and retention (EPR) effect. SMA-pirarubicin inhibits the growth of colorectal liver metastases, but tumor destruction is incomplete. The role played by the tumor microcirculation is uncertain. This study investigates the pattern of microcirculatory changes following SMA-pirarubicin treatment. Methods: Liver metastases were induced in CBA mice using a murine-derived colon cancer line. SMA-pirarubicin (100 mg/kg total dose) was administered intravenously in 3 separate doses. Twenty-four hours after chemotherapy, the tumor microvasculature was examined using CD34 immunohistochemistry and scanning electron microscopy. Tumor perfusion and permeability were assessed using confocal in vivo microscopy and the Evans blue method. Results: SMA-pirarubicin reduced the microvascular index by 40%. Vascular occlusion and necrosis were extensive following treatment. Viable cells were arranged around tumor vessels. Tumor permeability was also increased. Conclusion: SMA-pirarubicin damages tumor cells and the tumor microvasculature and enhances tumor vessel permeability. However, tumor necrosis is incomplete, and the growth of residual cells is sustained by a microvascular network. Combined therapy with a vascular targeting agent may affect residual cells, allowing more extensive destruction of tumors.
The combination of stabilized plasmid lipid particles and lipid nanoparticle encapsulated CpG containing oligodeoxynucleotides as a systemic genetic vaccine

DNA vaccines offer unique potential for generating protective and therapeutic immunity against infectious and malignant diseases. Unfortunately, rapid degradation and poor cellular uptake has significantly limited the efficacy of ‘naked’ plasmid DNA vaccines. We have previously described stabilized plasmid lipid particles (SPLP) as effective nonviral gene delivery vehicles for the transfection of tumours at distal sites following intravenous administration. Based on their low toxicity and favourable transfection profile following systemic administration, we investigate SPLP as gene delivery vehicles for the generation of a systemically administered genetic vaccine.
On the Role of Attention in Binocular Rivalry: Electrophysiological Evidence

During binocular rivalry visual consciousness fluctuates between two dissimilar monocular images. We investigated the role of attention in this phenomenon by comparing event-related potentials (ERPs) when binocular-rivalry stimuli were attended with when they were unattended. Stimuli were dichoptic, orthogonal gratings that yielded binocular rivalry and dioptic, identically oriented gratings that yielded binocular fusion. Events were all possible orthogonal changes in orientation of one or both gratings. We had two attention conditions: In the attend-to-grating condition, participants had to report changes in perceived orientation, focussing their attention on the gratings. In the attend-to-fixation condition participants had to report changes in a central fixation target, taking attention away from the gratings. We found, surprisingly, that attending to rival gratings yielded a smaller ERP component (the N1, from 160–210 ms) than attending to the fixation target. To explain this paradoxical effect of attention, we propose that rivalry occurs in the attend-to-fixation condition (we found an ERP signature of rivalry in the form of a sustained negativity from 210–300 ms) but that the mechanism processing the stimulus changes is more adapted in the attend-to-grating condition than in the attend-to-fixation condition. This is consistent with the theory that adaptation gives rise to changes of visual consciousness during binocular rivalry.
MLF: raising ML to the power of system F

We propose a type system MLF that generalizes ML with first-class polymorphism as in System F. Expressions may contain second-order type annotations. Every typable expression admits a principal type, which however depends on type annotations. Principal types capture all other types that can be obtained by implicit type instantiation and they can be inferred.All expressions of ML are well-typed without any annotations. All expressions of System F can be mechanically encoded into MLF by dropping all type abstractions and type applications, and injecting types of lambda-abstractions into MLF types. Moreover, only parameters of lambda-abstractions that are used polymorphically need to remain annotated.
The neural basis of intuitive and counterintuitive moral judgment

Neuroimaging studies on moral decision-making have thus far largely focused on differences between moral judgments with opposing utilitarian (well-being maximizing) and deontological (duty-based) content. However, these studies have investigated moral dilemmas involving extreme situations, and did not control for two distinct dimensions of moral judgment: whether or not it is intuitive (immediately compelling to most people) and whether it is utilitarian or deontological in content. By contrasting dilemmas where utilitarian judgments are counterintuitive with dilemmas in which they are intuitive, we were able to use functional magnetic resonance imaging to identify the neural correlates of intuitive and counterintuitive judgments across a range of moral situations. Irrespective of content (utilitarian/deontological), counterintuitive moral judgments were associated with greater difficulty and with activation in the rostral anterior cingulate cortex, suggesting that such judgments may involve emotional conflict; intuitive judgments were linked to activation in the visual and premotor cortex. In addition, we obtained evidence that neural differences in moral judgment in such dilemmas are largely due to whether they are intuitive and not, as previously assumed, to differences between utilitarian and deontological judgments. Our findings therefore do not support theories that have generally associated utilitarian and deontological judgments with distinct neural systems.
A New Power-Saving mechanism for WLAN Broadcast/Multicast services

When a WLAN station has low battery-power, a normal power-saving mechanism is not desirable and sparse wake-up should be used. In that case, the station cannot remain awake throughout every delivery-traffic-indication-message (DTIM) interval, which results in the loss of broadcast and multicast packets. In this paper, we propose a double-buffering power-saving mechanism for stations with low battery power. Broadcast and multicast packets can be delivered to stations with low battery power more reliably with the new scheme
Sequence Variation within Three Important Cytomegalovirus Gene Regions in Isolates from Four Different Patient Populations

ABSTRACT We determined the nucleotide (nt) and amino acid (aa) heterogeneities of three distinct regions of the human cytomegalovirus (CMV) genome for 46 low-passage CMV isolates from four different patient populations (congenitally infected infants, children attending day-care centers, renal transplant recipients, and human immunodeficiency virus-infected individuals) and for two laboratory strains (CMV Ad169 and Towne). The gene regions for the major immediate-early (MIE) exon 4 gene (nt positions 1702 to 1982, aa positions 152 to 244), the DNA polymerase gene (nt positions 2797 to 3046, aa positions 713 to 795), and the glycoprotein B (gB) gene (nt positions 1698 to 1884, aa positions 567 to 628) were sequenced. The sequence information was used to design sets of nested PCR primers directed against the most highly conserved regions identified. MIE was the most variable gene region compared to the variability of the DNA polymerase and gB gene regions. Comparison of the sequences of all 46 isolates with that of Ad169 revealed nt and aa sequence homologies of 87.9 and 87.2%, respectively, within the MIE gene compared to 92.8 and 100% homologies, respectively, within the DNA polymerase gene and 93 and 95.2% homologies, respectively, within the gB gene. Within the MIE gene, compared to the Ad169 nt sequence the homology at the nt level among isolates obtained from children attending day-care centers was high (96.4%), while it was lower (90%) among isolates obtained from the other three patient populations. Preliminary results of a nested PCR with oligonucleotide primers selected from the DNA polymerase gene region with a low level of nt sequence variation indicates that primers selected from this region might be more powerful for use in PCR than primers selected from the MIE gene region.
Forty Years of Invasive Clinical Electrophysiology: 1967–2007

In 2007, we marked the 40th anniversary of the birth of invasive clinical electrophysiology. Of course, before 1967, cardiac arrhythmias were documented electrocardiographically, and their possible mechanisms were analyzed ingeniously and explained beautifully by giants such as Katz and Pick,1 Scherf and Schott,2 and Bellet.3 In the 1940s and 1950s, Hecht,4 Latour and Puech,5 and Giraud et al6 used catheters to measure intracardiac electric activity and to record the sequence of cardiac activation. In 1958, Furman and Robinson7 showed that in patients with atrioventricular block, the heart could be stimulated by connecting an intraventricular catheter to a stimulator. In 1967, the analysis of the site of origin and mechanism of cardiac arrhythmias became possible in the intact human heart through the use of programmed electric stimulation combined with intracardiac activation mapping. Independently, Durrer et al7 in Amsterdam (in patients with the Wolff-Parkinson-White syndrome) and Coumel and coworkers8 in Paris (in a patient with an atrioventricular junctional tachycardia) showed that by connecting intracardiac catheters to a versatile stimulator, it was possible to reproducibly initiate and terminate clinically occurring tachycardias and to identify the site of origin of the tachycardia and, in the case of a reentrant mechanism, the pathway of the arrhythmia by placing catheters at different sites in the heart.8,9 Soon after, on both sides of the Atlantic, this technique was used to unravel the place of origin of different types of supraventricular tachycardias.10–14 The first book on the use of programmed stimulation of the heart in the analysis of supraventricular tachycardias was published in 1971.15 In the late 1960s, Scherlag et al16 made another important breakthrough in the analysis of cardiac arrhythmias with the reproducible registration of the His bundle electrogram. Not only did this advance …
Computational Intelligence for Evolving Trading Rules

This paper describes an adaptive computational intelligence system for learning trading rules. The trading rules are represented using a fuzzy logic rule base, and using an artificial evolutionary process the system learns to form rules that can perform well in dynamic market conditions. A comprehensive analysis of the results of applying the system for portfolio construction using portfolio evaluation tools widely accepted by both the financial industry and academia is provided.
Driver modeling and alignment for worst-case delay noise

In this paper, we present a new approach to model the impact of cross-coupling noise on interconnect delay. We introduce a new linear driver model that accurately models the noise pulse induced on a switching signal net due to cross coupling capacitance. The proposed model effectively captures the nonlinear behavior of the victim driver gate during the transition and has an average error below 8% whereas the traditional approach using a Thevenin model incurs an average error of 48%. We also discuss the worst case alignment of the aggressor net transitions with respect to the victim net transition, emphasizing the need to maximize not merely the delay of the interconnect alone but the combined delay of the interconnect and receiver gate. We show that the worst case alignment of an aggressor net transition is a function of the receiver gate output loading, victim transition edge rate, and the noise pulse width and height and hence propose a pre-characterization approach to efficiently predict the worst-case alignment. The proposed methods were implemented in an industrial noise analysis tool called ClariNet. Results on industrial designs are presented to demonstrate the effectiveness of our approach.
Querying and clustering Web pages about persons and organizations

One of the most frequent Web surfing tasks is to search for names of persons and organizations. Such names are often not distinctive, commonly occurring, and nonunique. Thus, a single name may be mapped to several entities. We describe a methodology to cluster the Web pages returned by the search engine so that pages belonging to different entities are clustered into different groups. The algorithm uses a combination of named entities, link-based and structure-based information as features to partition the document set into direct and indirect pages using a decision model. It then uses the distinct direct pages as seeds to cluster the document set into different clusters. The algorithm has been found to be effective for Web-based applications.
Using MS‐MLPA as an efficient screening tool for detecting 9p21 abnormalities in pediatric acute lymphoblastic leukemia

Characterization of recurrent genetic lesions in childhood acute lymphoblastic leukemia (ALL) has enabled therapeutic stratification with improved outcomes. The tumor suppressor genes, CDKN2A and CDKN2B, encoding p16INK4a, p14ARF, and p15INK4b have been localized to 9p21. Abnormalities of 9p21 have been reported in 10–30% of childhood ALL using conventional cytogenetics and fluorescence in situ hybridization (FISH). The incidence of 9p21 using more sensitive techniques, such as methylation specific multiplex ligation‐dependent probe amplification (MS‐MLPA), remains uncertain, and thus also the prognostic significance.