cssi/SciSciGPT-SciSciNet huggingface dataset:
Simultaneously Inhibiting BCL2 and MCL1 Is a Therapeutic Option for Patients with Advanced Melanoma

There is an urgent need to develop treatments for patients with melanoma who are refractory to or ineligible for immune checkpoint blockade, including patients who lack BRAF-V600E/K mutations. This is often the case in patients diagnosed with rare melanoma subtypes such as mucosal and acral melanoma. Here, we analyzed data from the cutaneous melanoma The Cancer Genome Atlas Network (TCGA) transcriptomic and proteomic databases for differential expression of apoptosis molecules between melanomas with or without BRAF hotspot mutations. Our data indicated higher B-cell CLL/lymphoma 2 (BCL2) expression in melanoma without BRAF hotspot mutations, suggesting that BH3 mimetics, such as ABT-199 (venetoclax, a small molecule against BCL2), may be a potential therapeutic option for these patients. We explored the efficacy of combining two BH3 mimetics, ABT-199 and a myeloid cell leukemia sequence 1 (MCL1) inhibitor (S63845 or S64315/MIK665) in cutaneous, mucosal and acral melanomas, in vitro and in vivo. Our data indicate this combination induced cell death in a broad range of melanoma cell lines, including melanoma initiating cell populations, and was more potent in melanoma cells without BRAF-V600E/K mutations. Our knockdown/knockout experiments suggest that several pro-apoptotic BCL2 family members, BCL2-like 11 (apoptosis facilitator) (BIM), phorbol-12-myristate-13-acetate-induced protein 1 (NOXA) or BID, play a role in the combination-induced effects. Overall, our study supports the rationale for combining an MCL1 inhibitor with a BCL2 inhibitor as a therapeutic option in patients with advanced melanoma.
Decays of 39 Ca and 41 Sc

The decays of $^{39}\mathrm{Ca}$ and $^{41}\mathrm{Sc}$ have been studied because of the related interest in the magnitude of the axial coupling constant in nuclear matter. $^{39}\mathrm{Ca}$ was produced in the $^{39}\mathrm{K}(p,n)^{39}\mathrm{Ca}$ reaction at ${E}_{p}=10$ MeV and its half-life was measured as 860.4 \ifmmode\pm\else\textpm\fi{} 3.0 msec resulting in an $\mathrm{ft}$ value of 4283 \ifmmode\pm\else\textpm\fi{} 25 sec. The half-life of $^{41}\mathrm{Sc}$, formed in the $^{40}\mathrm{Ca}(p,\ensuremath{\gamma})^{41}\mathrm{Sc}$ reaction with 3-MeV protons on thick Ca, is 596.3 \ifmmode\pm\else\textpm\fi{} 1.7 msec. From the $\ensuremath{\gamma}$-ray energies of 2882.6 \ifmmode\pm\else\textpm\fi{} 0.3 keV and 3696.9 \ifmmode\pm\else\textpm\fi{} 0.5 keV measured at the 1.84- and 2.68-MeV resonances the $Q$ value of the $^{40}\mathrm{Ca}(p,\ensuremath{\gamma})^{41}\mathrm{Sc}$ reaction is found to be 1085.7 \ifmmode\pm\else\textpm\fi{} 1.4 keV. This leads to a $^{41}\mathrm{Sc}$ mass excess of -28 642.2 \ifmmode\pm\else\textpm\fi{} 1.7 keV, to a $^{41}\mathrm{Sc}$ decay energy of 6494.9 \ifmmode\pm\else\textpm\fi{} 2.0 keV, and to an $\mathrm{ft}$ value of 2849 \ifmmode\pm\else\textpm\fi{} 9 sec. An upper limit of 2\ifmmode\times\else\texttimes\fi{}${10}^{\ensuremath{-}3}$ is placed on the $\ensuremath{\beta}$ branching of $^{41}\mathrm{Sc}$ to excited states of $^{41}\mathrm{Ca}$. If the free-space value of ${g}_{A}$ is used to extract the Gamow-Teller matrix element ${〈\ensuremath{\sigma}〉}_{\mathrm{exp}}$ from these data we find $\frac{{〈\ensuremath{\sigma}〉}_{\mathrm{exp}}}{{〈\ensuremath{\sigma}〉}_{\mathrm{s}.\mathrm{p}.}}$ values of 0.685 \ifmmode\pm\else\textpm\fi{} 0.009 and 0.761 \ifmmode\pm\else\textpm\fi{} 0.006 for $^{39}\mathrm{Ca}$ and $^{41}\mathrm{Sc}$, respectively, where the ${〈\ensuremath{\sigma}〉}_{\mathrm{s}.\mathrm{p}.}$ are the relevant single-particle matrix elements.
A grateful eye towards the future? Dispositional gratitude relates to consideration of future consequences

Abstract Although individual differences in dispositional gratitude have been shown to relate with both personal well-being and intergenerational beneficence, no work has yet examined whether trait gratitude is correlated with consideration of future consequences for one's self. Across six studies (total N = 2758) we find robust evidence for a significant and positive correlation between dispositional gratitude and consideration of future consequences (CFC): r = 0.33, SE = 0.02, Z = 16.82, p
Field cross-fostering and in vitro rearing demonstrate negative effects of both larval and adult exposure to a widely used fungicide in honey bees (Apis mellifera).

Abstract Pollinators and other insects are experiencing an ongoing worldwide decline. While various environmental stressors have been implicated, including pesticide exposure, the causes of these declines are complex and highly debated. Fungicides may constitute a particularly prevalent threat to pollinator health due to their application on many crops during bloom, and because pollinators such as bees may consume fungicide-tainted pollen or nectar. In a previous study, consumption of pollen containing the fungicide Pristine® at field-relevant concentrations by honey bee colonies increased pollen foraging, caused earlier foraging, lowered worker survival, and reduced colony population size. Because most pollen is consumed by young adults, we hypothesized that Pristine® (25.2% boscalid, 12.8% pyraclostrobin) in pollen exerts its negative effects on honey bee colonies primarily on the adult stage. To rigorously test this hypothesis, we used a cross-fostering experimental design, with bees reared in colonies provided Pristine® incorporated into pollen patties at a supra-field concentration (230 mg/kg), only in the larvae, only in the adult, or both stages. In contrast to our predictions, exposure to Pristine® in either the larval or adult stage reduced survival relative to control bees not exposed to Pristine®, and exposure to the fungicide at both larval and adult stages further reduced survival. Adult exposure caused precocious foraging, while larval exposure increased the tendency to forage for pollen. These results demonstrate that pollen containing Pristine® can induce significant negative effects on both larvae and adults in a hive, though the magnitude of such effects may be smaller at field-realistic doses. To further test the potential negative effects of direct consumption of Pristine® on larvae, we reared them in vitro on food containing Pristine® at a range of concentrations. Consumption of Pristine® reduced survival rates of larvae at all concentrations tested. Larval and adult weights were only reduced at a supra-field concentration. We conclude that consumption of pollen containing Pristine® by field honey bee colonies likely exerts impacts on colony population size and foraging behavior by affecting both larvae and adults.
Understanding others through observed touch: neural correlates, developmental aspects and psychopathology

Touch is an essential and powerful part of social interactions in humans. It is used to convey feelings and thoughts and aids in forming and maintaining social bonds throughout life. When we view others giving or receiving social touch, we automatically convert the sight of touch between others into an internal representation of touch and thus recognize, to some extent, what the other person is feeling. Nevertheless, the mechanisms through which this process occurs are just beginning to be elucidated. Here, we review the neural correlates that underpin observed touch perception, we discuss deficits in this ability in several psychopathologies and we review developmental studies that tackle this ability in the very early stages of infancy.
Treatment and outcomes among patients ≥85 years hospitalized with community-acquired pneumonia

Our objective was to describe community-acquired pneumonia (CAP) among patients ≥85 years and compare them to patients aged 65–74. This was a retrospective cohort study. The study setting included 638 hospitals in the USA participating in the Premier database from 2010 to 2015. The study participants were 488,382 adults aged ≥65 years hospitalized with CAP. Patients ≥85 years were more likely to be white (79.8% vs 76.2%), female (58.1% vs 48.3%), and admitted with aspiration pneumonia (17.1% vs 7.0%) as compared with those aged 65–75 years. They had higher rates of dementia (30.4% vs 7.8%), but lower rates of diabetes (11.2% vs 17.6%) and chronic obstructive pulmonary disease (25.5% vs 54.7%). While Staphylococcus aureus (33.4%) was the most common pathogen across all age groups, patients aged ≥85 were more likely to have Escherichia coli pneumonia (16.1% vs 10.7%) compared with those aged 65–74. In adjusted models, patients aged ≥85 had greater in-hospital mortality (OR 1.14, 95% CI 1.11 to 1.18), but were less likely to be admitted to the intensive care unit (OR 0.54, 95% CI 0.53 to 0.55) and receive mechanical ventilation (OR 0.47, 95% CI 0.46 to 0.48). They also had lower rates of acute kidney injury (OR 0.95, 95% CI 0.91 to 1.00) and Clostridium difficile infection (OR 0.91, 95% CI 0.85 to 0.99), shorter lengths of stay (mean multiplier 0.93, 95% CI 0.92 to 0.93) and lower cost (mean multiplier 0.81, 95% CI 0.80 to 0.81), and were more likely to be discharged to a skilled nursing facility (OR 2.19, 95% CI 2.15 to 2.24) or hospice (OR 2.19, 95% CI 2.11 to 2.27). In conclusion, patients aged ≥85 have different comorbidities and etiologies of CAP, receive less intense treatment, and have greater mortality than patients between 65 and 75 years.
Accuracy of linear drilling in temporal bone using drill press system for minimally invasive cochlear implantation

A minimally invasive approach for cochlear implantation involves drilling a narrow linear path through the temporal bone from the skull surface directly to the cochlea for insertion of the electrode array without the need for an invasive mastoidectomy. Potential drill positioning errors must be accounted for to predict the effectiveness and safety of the procedure. The drilling accuracy of a system used for this procedure was evaluated in bone surrogate material under a range of clinically relevant parameters. Additional experiments were performed to isolate the error at various points along the path to better understand why deflections occur. An experimental setup to precisely position the drill press over a target was used. Custom bone surrogate test blocks were manufactured to resemble the mastoid region of the temporal bone. The drilling error was measured by creating divots in plastic sheets before and after drilling and using a microscope to localize the divots. The drilling error was within the tolerance needed to avoid vital structures and ensure accurate placement of the electrode; however, some parameter sets yielded errors that may impact the effectiveness of the procedure when combined with other error sources. The error increases when the lateral stage of the path terminates in an air cell and when the guide bushings are positioned further from the skull surface. At contact points due to air cells along the trajectory, higher errors were found for impact angles of $$45^{\circ }$$ and higher as well as longer cantilevered drill lengths. The results of these experiments can be used to define more accurate and safe drill trajectories for this minimally invasive surgical procedure.
Evaluation of IT portfolio options by linking to business services

The management of IT portfolios in most enterprises is a complex and challenging ongoing process. IT portfolios typically contain large numbers of inter-related elements. In this paper, we present a model and a method for determining and evaluating IT portfolio options for use as a decision aid in the ongoing management of the portfolio. Business benefits of the portfolio options are articulated by linking IT portfolio elements to componentized business services. Characteristics of the IT portfolio elements are abstracted to a level of granularity suited for portfolio analysis. Our model allows various forms of uncertainty that are utilized in the evaluation. Our evaluation method determines a set of portfolio options with the associated cost/benefits tradeoffs. Business constraints and pruning methods are used to present only the relevant and available options and their tradeoffs to the IT portfolio manager.
Utilizing the BiTE (bispecific T-cell engager) platform for immunotherapy of cancer

Various approaches of T-cell-based cancer immunotherapy are currently under investigation, among these are BiTE® (bispecific T-cell engager) antibody constructs, which have a unique design and mechanism of action. They are constructed by genetically linking onto a single polypeptide chain the minimal binding domains of monoclonal antibodies for tumor-associated surface antigens and for the T-cell receptor-associated molecule CD3. Concurrent engagement of the target cell antigen and CD3 leads to activation of polyclonal cytotoxic T-cells, resulting in target cell lysis. Blinatumomab, a BiTE targeting CD19, is being investigated in a broad range of B-cell malignancies and has recently been approved in the USA by the US FDA for Philadelphia chromosome-negative relapsed/refractory B-acute lymphoblastic leukemia under the trade name BLINCYTO™. The BiTE platform is one of the clinically most advanced T-cell immunotherapy options.
A cosmic conundrum

A new incarnation of Einstein's cosmological constant may point the way beyond general relativity
Interaction Control of a Non-Backdriveable MR-Compatible Actuator Through Series Elasticity

This research aims at developing a magnetic resonance (MR)-compatible equivalent of an exoskeleton used for wrist movement rehabilitation therapy of neurological patients. As a crucial step towards the accomplishment of this goal, this paper investigates the development of a novel actuation architecture suitable for interaction control in MR environments, the MR-SEA (SEA stands for Series Elastic Actuator). MR-SEA consists of the combination of a non-backdriveable MR-compatible actuator and of a compliant force-sensing element. The preliminary design of a 1 DOF actuator is presented, in addition to non-linear dynamical model of the system featuring the most relevant actuator non linearities. A switching controller is proposed, and the asymptotic stability of the resulting discontinuous dynamical system is demonstrated for force control in blocked output conditions. Simulation results show that the proposed system is adequate for the implementation of force control for wrist movement protocols in fMRI, demonstrating a bandwidth higher than 8 Hz for force control. For stiffness control, simulation results demonstrate that the system is passive for all values of desired virtual stiffness lower than the stiffness of the physical spring, and isolated stability is obtained for the entire range of stiffness values considered.Copyright © 2013 by ASME
Typing on flat glass: examining ten-finger expert typing patterns on touch surfaces

Touch screen surfaces large enough for ten-finger input have become increasingly popular, yet typing on touch screens pales in comparison to physical keyboards. We examine typing patterns that emerge when expert users of physical keyboards touch-type on a flat surface. Our aim is to inform future designs of touch screen keyboards, with the ultimate goal of supporting touch-typing with limited tactile feedback. To study the issues inherent to flat-glass typing, we asked 20 expert typists to enter text under three conditions: (1) with no visual keyboard and no feedback on input errors, then (2) with and (3) without a visual keyboard, but with some feedback. We analyzed touch contact points and hand contours, looking at attributes such as natural finger positioning, the spread of hits among individual keys, and the pattern of non-finger touches. We also show that expert typists exhibit spatially consistent key press distributions within an individual, which provides evidence that eyes-free touch-typing may be possible on touch surfaces and points to the role of personalization in such a solution. We conclude with implications for design.
Impact of membrane immobilization on particle formation and trichloroethylene dechlorination for bimetallic Fe/Ni nanoparticles in cellulose acetate membranes.

The use of membrane immobilization to carry out the batch dechlorination of trichloroethylene (TCE) using bimetallic Fe/Ni (4:1, Fe to Ni) nanoparticles in cellulose acetate membranes is examined using modeling of transport phenomenon based on experimental results. Membranes are synthesized using both gelation and solvent evaporation techniques for phase inversion. The reduction of metal ions within cellulose acetate phase-inversion membranes was accomplished using sodium borohydride reduction to obtain up to 2 wt % total metals. Characterization of the mixed-matrix structure reveals a bimodal particle distribution ranging between 18 and 80 nm within the membrane cross section. The distribution is the result of changes in the morphology of the cellulose acetate support. The diffusivity and linear partitioning coefficient for the chlorinated organic were measured and are 2.0 × 10-8 cm2.s-1 and 3.5 × 10-2 L.g-1, respectively. An unsteady-state model for diffusion through a membrane with reaction was develop...
Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes and urine: pharmacokinetics of broccoli sprout isothiocyanates in humans

Abstract Background : Humans are exposed to substantial quantities of isothiocyanates and glucosinolates from vegetables. Since dietary isothiocyanates are widely regarded as potentially important chemoprotectors against cancer, reliable methods for measuring the plasma and tissue pharmacokinetics of isothiocyanates and their dithiocarbamate metabolites are essential for defining dosing regimens. Methods : Isothiocyanates (ITC) and dithiocarbamates (DTC) react quantitatively with 1,2-benzenedithiol to produce 1,3-benzodithiole-2-thione that can be quantified spectroscopically. Although this cyclocondensation reaction has been highly useful for analyzing plant material and urine samples, the determination of DTC/ITC (the total quantity of DTC and ITC components in a sample that react in the cyclocondensation reaction) in blood and tissues has been hampered by their low levels and the high concentrations of proteins that interfere with the cyclocondensation reaction. The protein content of blood and tissues was reduced by the precipitation with polyethylene glycol (PEG) or ultrafiltration, and the sensitivity of the method was increased substantially by the solid phase extraction of the cyclocondensation product. Results : Pharmacokinetic measurements were made in four human volunteers who received single doses of about 200 μmol of broccoli sprout isothiocyanates (largely sulforaphane, with lesser amounts of iberin and erucin). Isothiocyanates were absorbed rapidly, reached peak concentrations of 0.943–2.27 μmol/l in plasma, serum and erythrocytes at 1 h after feeding and declined with first-order kinetics (half-life of 1.77±0.13 h). The cumulative excretion at 8 h was 58.3±2.8% of the dose. Clearance was 369±53 ml/min, indicating active renal tubular secretion. Conclusion : A sensitive and specific method for quantifying DTC levels in human plasma, serum, and erythrocytes has been devised. Determinations of ITC/DTC levels are important because: (i) dietary isothiocyanates are of potential value in reducing the risk of cancer, and (ii) humans are extensively exposed to DTC as fungicides, insecticides, pesticides and rubber vulcanization accelerators.
A procedure for advection and diffusion in thin cavities

In this paper a finite element formulation is proposed for the calculation of advection and diffusion in a thin cavity. For these kinds of systems, very high aspect ratio elements are necessary for cost-effective simulation. Locally, element dimensions, say in x and y, are comparable, whereas the dimension in the transverse direction z is orders of magnitude smaller than those for x and y. In our formulation, the three-dimensional basis functions for interpolation are constructed as a tensor product of the basis functions that span the lateral (x, y) plane of an element and those that span the transverse direction. Unknowns along the transverse direction are solved implicitly, in a line-by-line fashion, using the tridiagonal matrix algorithm, while the “out-of-line” unknowns are treated either explicitly or semi-implicitly. Several applications to material processing are discussed, as are the computationally-intensive components of three variations of our basic procedure.
Thrombus-Targeted Nanocarrier Attenuates Bleeding Complications Associated with Conventional Thrombolytic Therapy

Purpose To test the hypothesis that thrombus-specific tissue plasminogen activator (tPA)-loaded nanocarriers enhance thrombolytic efficacy and attenuate hemorrhagic complications.
Tobacco Mosaic Virus and Pulmonary Diseases of Humans

By employing a plant infectivity technique, viable tobacco mosaic virus could not be recovered from specimens of squamous cell carcinoma, emphysema, and normal human lung tissue. A direct immunofluorescence procedure was employed to detect viral protein in lung tissue specimens with negative results. Serologic tests on 174 human sera obtained from patients with a variety of pathologic processes, and from healthy individuals, failed to detect antibodies to TMV.
Equilibrium and stability of magnetostatic atmospheres. I. Dungey-type isothermal states

Two families of analytical solutions are presented that describe isothermal magnetostatic atmospheres in uniform gravity and varying in two Cartesian dimensions. The solutions in each family share a common set of magnetic flux surfaces but have different profiles of field intensity, magnetic shear, and plasma distribution across these flux surfaces such that force balance is satisfied. A family of solutions with this mathematical degree of freedom had previously been found by Dungey. The construction and properties of the new solutions are described. The hydromagnetic stability of these solutions is discussed by using the sufficiency criteria of Hu to determine those profiles of magnetic field and plasma that assure stability for the whole system. Among the stable equilibria found are examples of sheared magnetic structures intruding into a uniformly magnetized, isothermal atmosphere. One of the two families of solutions is extended to equilibrium states that vary fully with all three Cartesian coordinates. These extended solutions allow the possibility of constructing complex structures by juxtapositioning discrete three-dimensional magnetic structures built separately. These two-dimensional and three-dimensional magnetostatic states may be useful as initial states for numerical simulation of time-dependent magnetohydrodynamic processes in the solar atmosphere.
Late Eocene Multituberculates and Other Mammals from Wyoming.

Isolated teeth of multituberculates have been found in association with late Eocene fossil mammals. Previous studies reported that multituberculates were not found in deposits younger than early Eocene age (Graybull provincial substage or equivalents). This newly found occurrence indicates that these animals are more likely to be late Eocene in age than reworked early Eocene materials
A Randomized, Double-Blind, Placebo-Controlled Trial to Assess Safety and Tolerability of Influenza Virus Vaccine, Trivalent, Types A and B, Live, Cold-Adapted (CAIV-T) in Children and Adolescents with Asthma 1953

A Randomized, Double-Blind, Placebo-Controlled Trial to Assess Safety and Tolerability of Influenza Virus Vaccine, Trivalent, Types A and B, Live, Cold-Adapted (CAIV-T) in Children and Adolescents with Asthma 1953
Testing concurrent programs on relaxed memory models

High-performance concurrent libraries, such as lock-free data structures and custom synchronization primitives, are notoriously difficult to write correctly. Such code is often implemented without locks, instead using plain loads and stores and low-level operations like atomic compare-and-swaps and explicit memory fences. Such code must run correctly despite the relaxed memory model of the underlying compiler, virtual machine, and/or hardware. These memory models may reorder the reads and writes issued by a thread, greatly complicating parallel reasoning.We propose Relaxer, a combination of predictive dynamic analysis and software testing, to help programmers write correct, highly-concurrent programs. Our technique works in two phases. First, Relaxer examines a sequentially-consistent run of a program under test and dynamically detects potential data races. These races are used to predict possible violations of sequential consistency under alternate executions on a relaxed memory model. In the second phase, Relaxer re-executes the program with a biased random scheduler and with a conservative simulation of a relaxed memory model in order to create with high probability a predicted sequential consistency violation. These executions can be used to test whether or not a program works as expected when the underlying memory model is not sequentially consistent.We have implemented Relaxer for C and have evaluated it on several synchronization algorithms, concurrent data structures, and parallel applications. Relaxer generates many executions of these benchmarks with violations of sequential consistency, highlighting a number of bugs under relaxed memory models.
Biodegradation of chemicals in the subsurface environment: Influence of microbial adaptation on the fate of organic pollutants in ground water

A plume of contaminated groundwater originating from an abandoned disposal pit for wood-creosoting waste was characterized. The important organic contaminants in the plume include naphthalene, 1-methylnaphthalene, 2-methylnaphthalene, dibenzofuran and fluorene at individual concentrations of 1,000 to 100 μg/L. Core material from the site was studied to determine if organisms in the subsurface could adapt to this waste and if biological activity influenced the disposition of the plume. Biodegradation of these organic pollutants in subsurface material from the margin of the plume was rapid. No biodegradation of the pollutants was detected in pristine subsurface material from the same geological structure. As a result of this adaptation, the disposition of the plume was not controlled by the rate of utilization of the pollutants by the microorganisms but by the extent of utilization allowed by the supply of oxygen.
Healthcare workers who elected not to receive smallpox vaccination.

Background The goal of the National Smallpox Vaccination Program was to vaccinate a cadre of healthcare workers and first responders who could care for smallpox patients in the event of an attack. Methods Using a convenience sample of health departments (n=49) and hospitals (n=60) in five states, we conducted a telephone interview between July 2003 and April 2004 of healthcare workers and first responders who chose not to receive smallpox vaccination. (Data were analyzed in 2004 and 2005.) Results The response rate was 63%. Of 1895 respondents, 723 (38.2%) reported having a contraindication, 280 (14.8%) reported being contraindicated because of a household member’s condition, and 892 (47.0%) reported having no contraindication to smallpox vaccination. Among respondents with no contraindication, the leading reasons for nonvaccination were concerns about side effects (20.6%) and not feeling that the risk of outbreak was high enough (19.5%). More than half (54.8%) were somewhat or very concerned about having an adverse reaction to the vaccine; Hispanics, blacks, and Asians were significantly more likely than whites to be somewhat or very concerned about side effects. Less than one fifth (17.9%) reported that there was a policy to financially compensate employees who developed side effects from vaccination, and 40.7% reported that there was a policy to provide liability coverage to employees who transmitted vaccinia to a patient. Conclusions Many people who chose not to receive smallpox vaccine perceived their personal risk–benefit balance as not favoring vaccination. The success of future smallpox vaccination efforts or vaccination against other bioterrorist health threats depends on addressing potential barriers to participation including compensation and liability issues, in addition to clearly communicating risks and benefits.
High O6-methylguanine methyl transferase activity is frequently found in human oral cancer cells with p53 inactivation.

Abstract Many studies have indicated that cancer cells expressing mutant (mt) p53 are resistant to genotoxic stress such as chemotherapy and radiation therapy. Inasmuch as most human oral cancer cells either express mt p53 or are infected with human papillomavirus (HPV), we determined the sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a genotoxic chemical carcinogen, the activity of a DNA repair enzyme O6-methylguanine methyl transferase (MGMT) and the status of p53 in 11 human oral cancer cell lines, 2 HPV-immortalized human oral keratinocytes and 3 normal human oral keratinocyte (NHOK) cultures. Ten cancer cell lines demonstrated significantly higher level of MGMT activities compared to normal or immortalized non-tumorigenic cells, while one cancer cell line showed negligible MGMT activity. All immortalized cells and NHOK showed very low MGMT activity. Interestingly, all cancer cells with high MGMT activity expressed either mt p53 or harbored HPV DNA. However, infection of one cancer cell line (that does not demonstrate the MGMT activity) with retrovirus expressing an mt p53 protein did not alter the sensitivity of cells to MNNG and the enzyme activity. These data indicate that most human oral cancer cells contain moderately high DNA repair enzyme activity, and in doing so may be resistant to genotoxic stress, but the association of p53 with MGMT activities should further be investigated.
Global constraint-insensitive fracture in SiC particulate-reinforced AA 2009

Experimental results prove this hypothesis: the effective plastic fracture strain ([var epsilon][sup [minus]p][sub [line integral]]) for a discontinuously reinforced metal matrix composite (MMC) is insensitive to globally imposed triaxial tensile stress, because the elastic reinforcement independently produces high local matrix constraint during plastic deformation. The value [var epsilon][sup [minus]p][sub [line integral]] is measured for SiC particulate-reinforced AA 2009-T6, with cylindrical circumferentially notched (global constraint ratio, [sigma][sub m]/[bar [sigma]], of 1.0) and smooth tensile specimens ([sigma][sub m]/[bar [sigma]] of 0.3), as a function of temperature. The MMC fractures by microvoid-based processes associated with the SiC at all temperatures. The ratio (r) of smooth to notched specimen [var epsilon][sup [minus]p][sub [line integral]] equals unity from 25 C to 200 C and is less than values of 2 or higher typical of monolithic Al alloys at similar global constraint. This result establishes that global constraint does not degrade MMC fracture resistance because of the unique effect of local matrix constraint. The ratio r for the MMC increases from near 1 at 200 C to a maximum of 3.3 at 250 C, indicating a loss of local matrix constraint, possibly due to reduced matrix-particle load transfer or microvoid nucleation at low strains. Uncertainties hindermore » precise definition of [var epsilon][sup [minus]p][sub [line integral]] vs global [sigma][sub m]/[bar [sigma]]. Global constraint-insensitive fracture for the MMC suggests that plane strain fracture toughness differences between the composite and unreinforced matrix are not well defined by smooth specimen ductilities. Further, MMC fracture toughness should be insensitive to global constraint and associated cracked specimen dimensions.« less
Staining of heterochromatin bands and the determination of rye chromosomes in triticale (wheat × rye hybrid)

Fifteen lines of triticale were studied using the C-banding staining method. A typical, complete chromosomal complement was found in 11 lines, while the remaining lines demonstrated some variations. A slight modification in the technique is discussed.
White-Tailed Deer Trails are Associated with the Spread of Exotic Forbs

ABSTRACT: Exotic forbs are spreading throughout the western United States. Although cattle (Bos taurus) and sheep (Ovis aries) have received much attention as potential exotic vectors and rangeland disturbers, native white-tailed deer (Odocoileus virginianus) are a relatively unexplored cause. Particularly in exurban areas, white-tailed deer are rapidly increasing in density. We attempted to determine if there was an association between white-tailed deer and the spread of exotic forbs. We found that patches immediately adjacent to white-tailed deer trails were more diverse, contained more bare patches, and contained more species of exotic forbs than plots located three meters away. Deer may be facilitating an expansion of exotics, deer may prefer to produce trails near exotics, or deer may simply be following the spread of humans.
The role of auditory experience in the development and maintenance of sound localization

Newborn animals are capable of crude sound localization, indicating that they innately associate certain auditory cues with general locations in space. These associations are shaped and refined during early development by a process that is influenced strongly by sensory experience. The result is a sound localization mechanism that is finely tuned and calibrated to the individual. In adults, this mechanism continues to make limited adjustments in response to sensory experience, thus maintaining its accuracy and precision.
Use of a new platelet function analyzer to detect von Willebrand disease in women with menorrhagia

Abstract Objective The purpose of this study was to assess the usefulness of a new platelet function analyzer in the detection of von Willebrand disease and platelet dysfunction in women with menorrhagia. Study design Women with menorrhagia and control subjects were tested with a platelet function analyzer. If the results were abnormal, further testing was performed for possible von Willebrand disease or platelet dysfunction. Results were compared. Results Of the 108 women with menorrhagia, 28 had an abnormal platelet function analysis results: 7 results were suggestive of von Willebrand disease; 17 results were suggestive of platelet dysfunction, and 4 results were inconclusive. Of the 100 control subjects, 18 subjects had an abnormal platelet function analysis result: 2 results were suggestive of von Willebrand disease; 12 results were suggestive of platelet dysfunction, and 4 results were inconclusive. The prevalence of suspected von Willebrand disease was 6% among women with menorrhagia and 2% among control subjects. Among white women, the prevalence was 10% compared with 1% among control subjects. Conclusion We demonstrated that the platelet function analyzer could be used to detect von Willebrand disease in women with menorrhagia.
Urban Slum Growth and Human Health: A Panel Study of Infant and Child Mortality in Less-Developed Countries, 1990–2005

Drawing from various bodies of social scientific literature and research, the authors assess the extent to which infant and child mortality rates in less-developed countries are affected by the percent of domestic populations living in urban slum conditions. Results of first-difference panel model estimates of 80 less-developed countries from 1990 to 2005 indicate that growth in the percent of populations living in urban slum conditions positively affects both forms of mortality, and the effects are much more pronounced for African countries than for less-developed countries in Latin America and Asia. These findings hold, net of economic development, fertility rates, world-economic integration, and other factors. Cross-sectional analyses of infant and child mortality rates in 2005 that include additional controls provide further evidence of the mortality/urban slum relationships found in the panel model estimates. The authors conclude by highlighting the theoretical implications of the results and describ...
Effect of triethyltin on autonomic and behavioral thermoregulation of mice.

The organotin compound, triethyltin (TET), produces toxic effects in a variety of physiological systems. Thermoregulatory control appears to be especially susceptible to TET toxicity, since TET administration has been shown to cause a pronounced hypothermia in rats. To further elucidate effects of TET on thermoregulation, we measured metabolic rate, evaporative water loss (EWL), body temperature, and preferred ambient temperature (Ta) of mice treated intraperitoneally with TET (bromide salt). At a Ta of 23 to 24 degrees C, TET (6 and 8 mg/kg) inhibited metabolic rate by 23 and 66%, respectively. TET resulted in hypothermia at Ta's of 20 and 30 degrees C but not 35 degrees C. TET had little effect on EWL. Mice given TET at doses of 4, 6, and 8 mg/kg selected a cooler Ta (ca. 25 degrees C) compared to controls (ca. 29 degrees C). Thus, the mice selected a Ta associated with a hypothermic body temperature. At a relatively cool Ta, mice treated with TET had a reduced rate of heat production and, consequently, were hypothermic. At a relatively warm Ta, TET had no effect on heat production and did not increase active heat dissipation (i.e., EWL), thus the mice remained normothermic. The behavioral data indicate that TET evokes a type of regulated hypothermia in mice.
Continuous display of presentations sharing clips

Databases were introduced to remove redundancy from conventional file systems and encouragesharing, which resulted in update anomalies when information was modified. With presentations (movies) sharing clips (sequence of frames), continuous display becomes challenging as well. Continuous display requires the system to retrieve the information with no disruptions or delays (hiccups) once a display is initiated. To ensure a continuous display using a multi-disk hardware platform, a video object is striped into subobjects. The system enforces a regular schedule on retrieval of each subobject by controlling the placement of the subobjects across the disks. Now if different presentations share subobjects, each presentation will enforce its own restrictions on the placement of the data, resulting in an irregular schedule. We investigate approaches to render a schedule regular for two alternative display paradigms: Demand and Data driven.
HIV infection and associated risk factors in female prostitutes in Kinshasa, Zaire.

In Africa female prostitutes represent a high risk group for HIV infection. In Kinshasa Zaire 101 (27%) of 377 prostitutes were seropositive to HIV by ELISA and Western blot determination. Seropositivity was significantly associated with the number of lifetime partners with a median number of 600 partners 4 seropositives and 338 for seronegative individuals (P=0.02). Seropositivity was also significantly associated with a history of taking oral medications for the prevention of sexually transmitted diseases and/or pregnancy (odds ratio=2.21 confidence interval [CI]=1.2-4.2) and with the introduction of any product into the vagina for hygiene or other purposes (odds ratio=2.3 CI=1.1-4.7). In addition among 85 prostitutes reporting condom use by their sexual partners during the previous year the use of condoms by 50% or more of partners was associated with a reduced risk of HIV seropositivity (P=0.046). An increased risk of HIV seropositivity was not associated with fellatio anal intercourse or with any type of kissing. 29% of prostitutes reported at least 1 symptom suggestive of HIV infection and seropositivity was associated with weight loss either with or without chronic diarrhea or pruritic dermatitis. These data confirm that African prostitutes are at high risk for HIV infection and that the number of lifetime sexual partners and factors which interfere with the integrity of the vaginal or cervical mucosa may be associated with an increased risk of HIV infection acquired through heterosexual contact. Prevention of heterosexually transmitted HIV infection will require extensive educational programs aimed specifically at the risk associated with number and selection of sexual partners and at promoting safer sexual practices. (authors)
Farming the Tax Code: The Impact of High Marginal Tax Rates on Agricultural Tax Shelters

Surprisingly little scholarly work has examined the practice of “farming the tax code,” in which accounting losses on agricultural investments are used to shelter other income from taxation. Economic theory suggests that the amount of investment in agricultural tax shelters is positively related to the marginal tax rate. This hypothesis is empirically investigated using a sample of federal individual income tax returns filed for 1983. Both the probability of reporting a farm tax loss and the amount of farm losses are increased by a rise in the marginal tax rate, especially among upper income taxpayers.
Harnessing the Dynamical Movement of OmpG Loops for Protein Sensing

Oligomeric protein nanopores with rigid structures have been engineered for the purpose of sensing a wide range of analytes including small molecules and biological species such as proteins and DNA. We chose a monomeric β-barrel porin, OmpG, as the platform from which to derive the nanopore sensor. OmpG is decorated with several flexible loops that move dynamically to create a distinct gating pattern when ionic current passes through the pore. Biotin was chemically tethered to the most flexible one of these loops. The gating characteristic of the loop's movement in and out of the porin was substantially altered by analyte protein binding. The gating characteristics of the pore with bound targets were remarkably sensitive to molecular identity - even providing the ability to distinguish between homologues within an antibody mixture. A total of five gating parameters were analyzed for each analyte to create a unique fingerprint for each biotin binding protein. Our exploitation of gating noise as a molecular identifier may open new possibilities for more sophisticated sensor design while OmpG's monomeric structure greatly simplifies nanopore production.
Uncertain feedback loops and robustness in general linear systems

Abstract Our main results are a Riccati equation-based robust stability criterion and a robust stabilization scheme in systems with uncertain loop-gain. These issues are considered in the general framework of time—varying and possibly infinite dimensional linear systems. The current analysis is consequential to the recent development of a time-domain/variational approach to H ∞ control. The report includes also remarks on the trade-off between the type of uniform stability required (Lyapunov vs exponential) and the type of perturbations considered (real vs complex), and on the small gain criterion in time-varying systems.
Structures of apo- and ssDNA-bound YdbC from Lactococcus lactis uncover the function of protein domain family DUF2128 and expand the single-stranded DNA-binding domain proteome.

Single-stranded DNA (ssDNA) binding proteins are important in basal metabolic pathways for gene transcription, recombination, DNA repair and replication in all domains of life. Their main cellular role is to stabilize melted duplex DNA and protect genomic DNA from degradation. We have uncovered the molecular function of protein domain family domain of unknown function DUF2128 (PF09901) as a novel ssDNA binding domain. This bacterial domain strongly associates into a dimer and presents a highly positively charged surface that is consistent with its function in non-specific ssDNA binding. Lactococcus lactis YdbC is a representative of DUF2128. The solution NMR structures of the 20 kDa apo-YdbC dimer and YdbC:dT19G1 complex were determined. The ssDNA-binding energetics to YdbC were characterized by isothermal titration calorimetry. YdbC shows comparable nanomolar affinities for pyrimidine and mixed oligonucleotides, and the affinity is sufficiently strong to disrupt duplex DNA. In addition, YdbC binds with lower affinity to ssRNA, making it a versatile nucleic acid-binding domain. The DUF2128 family is related to the eukaryotic nuclear protein positive cofactor 4 (PC4) family and to the PUR family both by fold similarity and molecular function.
Semi-Blind Data Detection for Unitary Space-Time Modulation in MIMO Communications Systems

We propose an iterative algorithm based on expectation maximization (EM) to jointly estimate the system parameters and decode the data in a MIMO system using unitary space-time block codes. It is assumed that the receiver is unaware of the channel coefficients and their distribution, the average energy of the received signal, the prior probability of each signal in the constellation, and the noise power. The algorithm works for arbitrary modulation schemes and any channel model including Rayleigh and Rician fading. The complexity of the proposed receiver is computed and it is shown to be significantly lower than previously published methods, as it does not require any matrix inversion or trellis search. The performance of the proposed receiver is evaluated by simulations in terms of symbol error rate (SER) vs. signal-to-noise ratio (SNR) and it is shown that with only a few iterations of the algorithm it achieves a performance close to that of the receiver which knows all the parameters.
An art-historical view of social disintegration

One hundred and one Fine Arts college students judged seventeen Western Master paintings of small groups spanning six centuries, using a semantic-differential scale. It was hypothesized that the paintings would portray a decreased sense of social cohesiveness, reflecting Riesman's (1950) characterization of social changes from inner-directed to other-directedness. A factor analysis revealed that one of the two factors extracted, group solidarity, significantly related to century of painting, supporting Riesman's thesis.
Addition of polyunsaturated fatty acids to canola oil by fungal conversion.

Abstract Canola materials including processed flake and cake were investigated as both of carbon and nitrogen sources for the production of new oil containing polyunsaturated fatty acids (PUFAs). With conversion of the fungi Mortierella alpina , modified lipids enhanced the oil profile with the addition of three PUFAs, γ-linolenic acid (GLA, γ-C18:3n6), arachidonic acid (ARA, C20:4n6) and eicosapentaenoic acid (EPA, C20:5n3). The ratio of polyunsaturated to saturated fatty acid (P/S) increased 50% compared to the original canola oil. ARA yield of 20.3 mg/g flake was comparable to 20.1 mg/g glucose, and higher than 12.5 mg/g cake. EPA yield of 3.3 mg/g flake was greater than 2.7 mg/g cake, and much greater than 0.3 mg/g glucose. The mixed culture of two strains, M. alpina and Pythium irregulare , resulted in higher production of ARA and EPA than their single cultures. Mixed culture achieved ARA yields of 26 mg/g flake, 23 mg/g cake and 38 mg/g glucose, and had favorable lipid profiles with P/S of 6.5 and 8.7 for growth on flake and cake, respectively. In addition, a method was developed to estimate the bioconversion rate from digested canola oil to fungal oil, which was nearly 50% when canola flake and cake were utilized as substrate.