Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Dendritic Cells Respond to Helicobacter pylori, Promoting NK Cell and Th1-Effector Responses In Vitro1

Helicobacter pylori infection leads to chronic gastric inflammation. The current study determined the response of human APCs, NK cells, and T cells toward the bacteria in vitro. Human monocyte-derived dendritic cells (DC) were incubated with bacteria for 48 h. Intact H. pylori at a multitude of infection 5 stimulated the expression of MHC class II (4- to 7-fold), CD80, and CD86 B7 molecules (10- to 12-fold) and the CD83 costimulatory molecule (>30-fold) as well as IL-12 secretion (>50-fold) in DCs, and thereby, strongly induced their maturation and activation. CD56+/CD4− NK cells, as well as CD4+/CD45RA+ naive T cells, were isolated and incubated with DCs pulsed with intact bacteria or different cellular fractions. Coculture of H. pylori-pulsed DCs with NK cells strongly potentiated the secretion of TNF-α and IFN-γ. Coculture of naive T cells with H. pylori-pulsed DCs significantly enhanced TNF-α, IFN-γ, and IL-2 secretion as well as T-bet mRNA levels, while GATA-3 mRNA was lowered. However, the effect appeared attenuated compared with coculture with Escherichia coli. A greater stimulation was seen with naive T cells and DCs pulsed with H. pylori membrane preparations. Intact H. pylori potently induced the maturation and activation of human monocyte-derived DC and thereby promote NK and Th1 effector responses. The strong activation of NK cells may be important for the innate immune response. Th1-polarized T cells were induced especially by incubation with membrane preparations of H. pylori, suggesting that membrane proteins may account for the specific adaptive immune response.
Potent Activity of Indolequinones against Human Pancreatic Cancer: Identification of Thioredoxin Reductase as a Potential Target

The indolequinone ES936 {5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione} was previously developed in our lab as an antitumor agent against pancreatic cancer. The objective of this study was to identify indolequinones with improved potency against pancreatic cancer and to define their mechanisms of action. Pancreatic cancer cell lines PANC-1, MIA PaCa-2, and BxPC-3 were used in in vitro assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) and clonogenic assays]; indolequinones displayed potent cytotoxicity against all three cell lines, and two specific classes of indolequinone were particularly potent agents. These indolequinones induced caspase-dependent apoptosis but no redox cycling or oxidative stress in MIA PaCa-2 and BxPC-3 cells. Selected indolequinones were also screened against the NCI-60 cell line panel and were found to be particularly effective against colon, renal, and melanoma cancer cells. A potential target of these indolequinones was identified as thioredoxin reductase. Indolequinones were found to be potent inhibitors of thioredoxin reductase activity both in pancreatic cancer cells and in cell-free systems. The mechanism of action of the indolequinones was shown to involve metabolic reduction, loss of a leaving group to generate a reactive electrophile resulting in alkylation of the selenocysteine residue in the active site of thioredoxin reductase. In vivo efficacy of the indolequinones was also tested in the MIA PaCa-2 pancreatic tumor xenograft in nude mice, and lead indolequinones demonstrated high efficacy and low toxicity. Inhibition of thioredoxin reductase represents a potential novel target in pancreatic cancer and may provide a biomarker of effect of lead indolequinones in this type of cancer.
Magnetic resonance imaging in the differential diagnosis and monitoring of the treatment of multiple sclerosis

Treatments with potentially beneficial effects on the course of multiple sclerosis are now emerging and magnetic resonance imaging techniques are needed which have a high specificity for diagnosing multiple sclerosis, and which can characterize the heterogeneous nature of multiple sclerosis lesions and define disease evolution over time. Differential diagnosis may be improved by the use of gadolinium-enhanced magnetic resonance imaging, high-resolution spinal cord and optic nerve magnetic resonance imaging and non-conventional magnetic resonance imaging techniques. In the monitoring of treatment, a number of different approaches have been used to increase magnetic resonance imaging accuracy in describing and predicting disease activity and evolution. These include optimization of the acquisition and post-processing of data obtained with conventional magnetic resonance imaging techniques (T2-weighted and postcontrast T1-weighted sequences) and the use of newer nonconventional magnetic resonance imaging techniques.
Motor Control as the Control of Perception

This paper describes a test of Perceptual Control Theory (PCT), which views motor control as part of a process of controlling perceptual inputs rather than motor outputs. Sixteen undergraduate students (M age = 19.9 yr.) were asked to control one of three different perceptual aspects of an animated display—a shape, a motion or a sequence—using the same motor output, a key press. Animation rate was varied while quality of control was measured in terms of the proportion of time that the perception was maintained in the goal state. The results showed that increased animation rate made it hardest to control the more complex perceptions (motion and sequence) even though the same output was used to control all perceptions. This result is consistent with PCT, which predicts that the temporal constraints on control are ultimately a function of the type of perception controlled rather than the type of output used to control it.
Mode Choice Model for Vulnerable Motorcyclists in Malaysia

Objective. In developing countries, motorcycle use has grown in popularity in the past decades. Commensurate with this growth is the increase in death and casualties among motorcyclists in these countries. One of the strategic programs to minimize this problem is to reduce motorcyclists exposure by shifting them into safer modes of transport. This study aims to explore the differences in the characteristics of bus and motorcycle users. It identifies the factors contributing to their choice of transport mode and estimates the probability that motorcyclists might change their travel mode to a safer alternative; namely, bus travel. Methods. In this article, a survey of 535 motorcycle and bus users was conducted in seven districts of Selangor state, Malaysia. A binary logit model was developed for the two alternative modes, bus and motorcycle. Results. It was found that travel time, travel cost, gender, age, and income level are significant in influencing motorcyclists' mode choice behavior. The probability of motorcycle riders shifting to public transport was also examined based on a scenario of a reduction in bus travel time and travel cost. Conclusions. Reduction of total travel time for the bus mode emerges as the most important element in a program aimed at attracting motorcyclists towards public transport and away from the motorcycle mode.
A Toxicology-Based Review of Fentanyl-Related Deaths in New Mexico (1986–2007)

Abstract Since its approval in the United States, fentanyl has become increasingly popular for the medical management of pain and as a substance of abuse. Fentanyl is unique among the opioids in its widespread use with a transdermal delivery system, which contributes to its unique pharmacokinetics and abuse potential. We examined the demographics of deaths with fentanyl identified on toxicologic analysis and reviewed specific challenges in the laboratory detection of postmortem fentanyl levels. The New Mexico Office of the Medical Investigator database was searched for all cases from January 1986 through December 2007 with fentanyl reported as present or quantified. Those deaths with a cause of death identified as drug overdose were then analyzed separately. From 1986 to 2007, 154 cases were identified with fentanyl present in postmortem samples, with 96 of the cases identified as fentanyl-related drug overdoses. The number of fentanyl-related deaths has increased over the past 20 years, corresponding to both statewide increases in the medical use of fentanyl and the abuse of prescription opioids. The demographics of these fentanyl-related overdoses showed that subjects were more likely to be female, white non-Hispanic, and older than those in previously described overdose deaths. Several cases were identified with central and peripheral blood samples and antemortem and postmortem samples available for fentanyl quantification. Given the uncharacteristic demographics of fentanyl-related deaths and the complexity of the laboratory analysis of fentanyl, forensic scientists must use caution in both the detection and interpretation of fentanyl concentrations.
Eradicating Breast Cancer: Longevity Impact on Kuwaiti Women

Objective: To explore salient trends in incidence and mortality from breast cancer among Kuwaiti females and to quantify the number of years that could be saved if breast cancer deaths were eliminated. Methods: Appling life table technique, the paper constructs a bridged, multiple decrement and cancer-elimination life tables for Kuwaiti females. Data sources include Kuwait Cancer Control Center Registry along with vital statistics on mortality by age groups, nationality, and causes of death according to ICD-10 revision. Result: The study finds that, without interventions, nearly 2.5% of Kuwaiti female live births are expected to die from breast cancer. By contrast, if this disease were to be completely eradicated, Kuwaiti females are expected to gain half a year of life expectancy at birth. Likewise, a 10% reduction in deaths attributed to breast cancer would produce a gain of 11 days of life at age 30. The gain would augment to 51 days when death is reduced by 50%. Kuwaiti females aged 50 would add almost 5 months when breast cancer is eradicated, while a 20 percent reduction in breast cancer mortality would raise their life expectancy by 26 days. Conclusion: The results strongly support policy interventions of Kuwait’s government by instituting a well-documented public health policy for chronic diseases and mitigating the increase of cancer prevalence.
TMC125, a Novel Next-Generation Nonnucleoside Reverse Transcriptase Inhibitor Active against Nonnucleoside Reverse Transcriptase Inhibitor-Resistant Human Immunodeficiency Virus Type 1

ABSTRACT Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are potent inhibitors of human immunodeficiency virus type 1 (HIV-1); however, currently marketed NNRTIs rapidly select resistant virus, and cross-resistance within the class is extensive. A parallel screening strategy was applied to test candidates from a series of diarylpyrimidines against wild-type and resistant HIV strains carrying clinically relevant mutations. Serum protein binding and metabolic stability were addressed early in the selection process. The emerging clinical candidate, TMC125, was highly active against wild-type HIV-1 (50% effective concentration [EC50] = 1.4 to 4.8 nM) and showed some activity against HIV-2 (EC50 = 3.5 μM). TMC125 also inhibited a series of HIV-1 group M subtypes and circulating recombinant forms and a group O virus. Incubation of TMC125 with human liver microsomal fractions suggested good metabolic stability (15% decrease in drug concentration and 7% decrease in antiviral activity after 120 min). Although TMC125 is highly protein bound, its antiviral effect was not reduced by the presence of 45 mg of human serum albumin/ml, 1 mg of α1-acid glycoprotein/ml, or 50% human serum. In an initial screen for activity against a panel of 25 viruses carrying single and double reverse transcriptase amino acid substitutions associated with NNRTI resistance, the EC50 of TMC125 was <5 nM for 19 viruses, including the double mutants K101E+K103N and K103N+Y181C. TMC125 also retained activity (EC50 < 100 nM) against 97% of 1,081 recent clinically derived recombinant viruses resistant to at least one of the currently marketed NNRTIs. TMC125 is a potent next generation NNRTI, with the potential for use in individuals infected with NNRTI-resistant virus.
The Mammalian AP-3 Adaptor-like Complex Mediates the Intracellular Transport of Lysosomal Membrane Glycoproteins*

In mammalian cells, the mannose 6-phosphate receptors (MPRs) and the lysosomal glycoproteins, lysosomal-associated membrane protein (LAMP) I, lysosomal integral membrane protein (LIMP) II, are directly transported from the trans-Golgi network to endosomes and lysosomes. While MPR traffic relies on the AP-1 adaptor complex, we report that proper targeting of LAMP I and LIMP II to lysosomes requires the AP-3 adaptor-like complex. Overexpression of these proteins, which contain either a tyrosine- or a di-leucine-based-sorting motif, promotes AP-3 recruitment on membranes. Inhibition of AP-3 function using antisense oligonucleotides leads to a selective misrouting of both LAMP I and LIMP II to the cell surface without affecting MPR trafficking. These results provide evidence that AP-3 functions in the intracellular targeting of transmembrane glycoproteins to lysosomes.
Assessment of the accuracy of an MCNPX-based Monte Carlo simulation model for predicting three-dimensional absorbed dose distributions

In recent years, the Monte Carlo method has been used in a large number of research studies in radiation therapy. For applications such as treatment planning, it is essential to validate the dosimetric accuracy of the Monte Carlo simulations in heterogeneous media. The AAPM Report no 105 addresses issues concerning clinical implementation of Monte Carlo based treatment planning for photon and electron beams, however for proton-therapy planning, such guidance is not yet available. Here we present the results of our validation of the Monte Carlo model of the double scattering system used at our Proton Therapy Center in Houston. In this study, we compared Monte Carlo simulated depth doses and lateral profiles to measured data for a magnitude of beam parameters. We varied simulated proton energies and widths of the spread-out Bragg peaks, and compared them to measurements obtained during the commissioning phase of the Proton Therapy Center in Houston. Of 191 simulated data sets, 189 agreed with measured data sets to within 3% of the maximum dose difference and within 3 mm of the maximum range or penumbra size difference. The two simulated data sets that did not agree with the measured data sets were in the distal falloff of the measured dose distribution, where large dose gradients potentially produce large differences on the basis of minute changes in the beam steering. Hence, the Monte Carlo models of medium- and large-size double scattering proton-therapy nozzles were valid for proton beams in the 100 MeV–250 MeV interval.
Vection: The Contributions of Absolute and Relative Visual Motion

Inspection of a visual scene rotating about the vertical body axis induces a compelling sense of self rotation, or circular vection. Circular vection is suppressed by stationary objects seen beyond the moving display but not by stationary objects in the foreground. We hypothesised that stationary objects in the foreground facilitate vection because they introduce a relative-motion signal into what would otherwise be an absolute-motion signal. Vection latency and magnitude were measured with a full-field moving display and with stationary objects of various sizes and at various positions in the visual field. The results confirmed the hypothesis. Vection latency was longer when there were no stationary objects in view than when stationary objects were in view. The effect of stationary objects was particularly evident at low stimulus velocities. At low velocities a small stationary point significantly increased vection magnitude in spite of the fact that, at higher stimulus velocities and with other stationary objects in view, fixation on a stationary point, if anything, reduced vection. Changing the position of the stationary objects in the field of view did not affect vection latencies or magnitudes.
Evaluating the epilepsy and oncological outcomes of pediatric brain tumors causing seizures.

We read with great interest a single center retrospective cohort study by Wessling et al. titled “Brain tumors in children with refractory seizures—a long-term followup study after epilepsy surgery”. This is a well-written and concise study of the post-surgical oncological, epileptological, and psychosocial follow-up of children with seizures secondary to brain tumors. This single-center cohort study includes 107 patients (aged 1.6–17.7 years), treated between 1988 and 2012, the majority with lowgrade tumors (76.6% WHO I, 19.6% WHO II). Tumor localization was temporal in more than half of the patients, and histopathology included gangliogliomas in 57% of the cases, gliomas in 29%, and dysembryoplastic neuroepithelial tumors (DNET) in 14%. In comparison with other studies of post-surgical seizure outcomes in literature, this cohort consisted of disproportionally more ganglioglioma cases—traditionally considered benign tumors with low rates of oncological recurrence and favorable post-surgical seizure outcomes. Post-operative complications, including a 5.6% chance of permanent new deficits and a 2.8% chance of surgical complications, were comparable to other studies in literature.
Inhibition of Nucleotide Excision Repair by High Mobility Group Protein HMGA1*

The mammalian non-histone “high mobility group” A (HMGA) proteins are the primary nuclear proteins that bind to the minor groove of AT-rich DNA. They may, therefore, influence the formation and/or repair of DNA lesions that occur in AT-rich DNA, such as cyclobutane pyrimidine dimers (CPDs) induced by UV radiation. Employing both stably transfected lines of human MCF7 cells containing tetracycline-regulated HMGA1 transgenes and primary Hs578T tumor cells, which naturally overexpress HMGA1 proteins, we have shown that cells overexpressing HMGA1a protein exhibit increased UV sensitivity. Moreover, we demonstrated that knockdown of intracellular HMGA1 concentrations via two independent methods abrogated this sensitivity. Most significantly, we observed that HMGA1a overexpression inhibited global genomic nucleotide excision repair of UV-induced CPD lesions in MCF-7 cells. Consistent with these findings in intact cells, DNA repair experiments employing Xenopus oocyte nuclear extracts and lesion-containing DNA substrates demonstrated that binding of HMGA1a markedly inhibits removal of CPDs in vitro. Furthermore, UV “photo-foot-printing” demonstrated that CPD formation within a long run of Ts (T18-tract) in a DNA substrate changes significantly when HMGA1 is bound prior to UV irradiation. Together, these results suggest that HMGA1 directly influences both the formation and repair of UV-induced DNA lesions in intact cells. These findings have important implications for the role that HMGA protein overexpression might play in the accumulation of mutations and genomic instabilities associated with many types of human cancers.
A New Gradient-Based Mode Selection of Intra Prediction for 4×4 block in H.264/AVC

In this paper, we propose a new gradient-based mode selection of intra prediction for 4times4 block in H.264/AVC video coding standard. In order to achieve rate distortion optimization, H.264/AVC encoder has to code the video by exhaustively trying all the mode combinations, including different intra prediction modes. As a result, the computational complexity of H.264/AVC encoder increases drastically. Based on local edge direction, the proposed method considerably reduces the overall complexity and encoding time by using a few candidate modes instead of all nine modes for intra mode selection of H.264/AVC. The proposed method, which was implemented into JM9.4 provided by Joint Video Team (JVT), can reduce about 58.4% in regard to computation complexity and 51.9% as to encoding time over full search method while maintaining similar PSNR and bite rate
FilGAP, a Rho–ROCK-regulated GAP for Rac, controls adherens junctions in MDCK cells

ABSTRACT Rho family small GTPases are essential for the formation of adherens junctions in epithelial cells. Here, we found that FilGAP (also known as ARHGAP24), a Rac-specific Rho GTPase-activating protein, promoted the formation of adherens junctions in Madin–Darby canine kidney (MDCK) cells. Knockdown of FilGAP by siRNA stimulated the disassembly and migration of MDCK cells induced by hepatocyte growth factor (HGF). By contrast, forced expression of FilGAP induced accumulation of E-cadherin at adherens junctions. Endogenous FilGAP colocalized with E-cadherin at adherens junctions, and depletion of FilGAP reduced the amount of E-cadherin expressed at the surface. The Rac GAP domain of FilGAP was necessary for the suppression of cell scattering induced by HGF. In agreement with this, siRNA-mediated knockdown of both Rac1 and FilGAP suppressed cell scattering induced by HGF. Forced expression of Rho kinase (ROCK, of which there are two isoforms ROCK1 and ROCK2) induced the accumulation of E-cadherin at the adherens junction, and depletion of FilGAP prevented the accumulation of E-cadherin. Moreover, wild-type FilGAP but not a non-phosphorylatable FilGAP mutant rescued the accumulation of E-cadherin at adherens junctions. These results suggest that FilGAP might regulate cell–cell adhesion through inactivation of Rac downstream of Rho–ROCK-signaling in MDCK cells.
Preceding standard therapy is the likely cause of MDS after autotransplants for multiple myeloma

Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) have been reported after autologous transplantation (AT) for lymphoma. It is not clear whether myeloablative therapy used in conjunction with autologous transplantation contributes to the development of MDS/AML or whether the conventional chemotherapy preceding the transplant, and administered over a prolonged period, causes these secondary malignancies. To address this issue, we examined 188 patients with multiple myeloma (MM) who had received AT. 71 patients with no more than one cycle of standard chemotherapy were enrolled in our Total Therapy program, designed to avoid exposure to alkylating agents prior to peripheral blood stem cell mobilization (group 1). The median duration of pre‐transplant therapy in group 1 was 7.6 months and significantly shorter than the 24 months of 117 patients (group 2) with more prolonged conventional therapy (P = 0.0001). All seven patients developing MDS post‐transplantation belonged to group 2 (P = 0.02); the median durations from initial therapy and first transplant were 66 months (range 38–86) and 24 months (range 9–39), respectively. Our findings provide evidence that prolonged standard‐dose alkylating agent therapy prior to transplantation, rather than autotransplant‐supported myeloablative treatment, is associated with development of MDS/AML. Stem cell damaging alkylator treatment should be avoided, not to compromise PBSC collection, but also to reduce the risk of treatment‐related MDS/AML.
Common Law Exceptions to Employment at Will

Employment relationships in the United States were historically governed by the common law doctrine of employment at will. Under this rule, parties to an employment relationship could, in the absence of an explicit contract, unilaterally terminate the match at any time, for any reason, and without penalty. In recent decades, numerous state courts have recognized "exceptions" to employment at will that limit the circumstances of worker dismissal. Using a panel of state labor market aggregates from 1965 to 1994, this article examines the effect of these exceptions on U.S. labor markets. These exceptions are seen to have no effect on aggregate employment nor unemployment. However, temporary employment is observed to increase by a statistically significant 15% following the adoption of an exception. The implied contract exception, in particular, appears to be responsible for this increase.