cssi/SciSciGPT-SciSciNet huggingface dataset:
Targeting mitochondria metabolism for cancer therapy

Mitochondria have a well-recognized role in the production of ATP and the intermediates needed for macromolecule biosynthesis, such as nucleotides. Mitochondria also participate in the activation of signaling pathways. Overall, accumulating evidence now suggests that mitochondrial bioenergetics, biosynthesis and signaling are required for tumorigenesis. Thus, emerging studies have begun to demonstrate that mitochondrial metabolism is potentially a fruitful arena for cancer therapy. In this Perspective, we highlight recent developments in targeting mitochondrial metabolism for the treatment of cancer.
An experimental and computational study of the burning rates of ultra-lean to moderately-rich H2/O2/N2 laminar flames with pressure variations

By using the counterflow flame technique, laminar flame speeds of H2/O2/N2 mixtures have been experimentally determined in the fuel stoichiometric range of ultra-lean to moderately-rich, oxygen concentration range of 7.4 to 30 molar percent of the oxidizer, and pressure range of 0.2 to 2.25 atm. These results are then compared with the numerically-determined values obtained by using several existing H2/O2 kinetic schemes. Results show that, while these kinetic schemes accurately predict the propagation speeds of high-temperature flames, they substantially underpredict those of low-temperature flames. Furthermore, while the experimental pressure exponents of the mass burning rates exhibit a minimum-point, parabola-like behavior with increasing pressure, indicating the initial, negative influence of the H−O2 termination reaction and the subsequent availability of a positive channel which facilitates radical production, the calculated results fail to show the increasing trend in the pressure range investigated. It is suggested that existing kinetic schemes may require revision in the intermediate-temperature regime strongly influenced by the HO2 and H2O2 chemistry.
The role of ocelli in circadian singing rhythms of crickets

. . There is a direct quantitative relationship between the free-running period (r) of the circadian stridulation rhythm of male Australian field crickets, Teleogryllus commodus (Walker), and the intensity of the constant light conditions. Both T. commodus and the house cricket, Acheta domesticus (L.), show free-running periods of the singing rhythm of c. 24 h when the light intensity is 0.00025 lux. In both species the severance of the three ocellar nerves significantly slows the circadian period which is indicative of a reduced perception of the available light intensity. To test whether this period reduction is a peripheral or a central effect, electro-retinograms (ERGs) were recorded from compound eyes of male T. commodus with the ocelli fully functional, then occluded, and then uncovered. The size of the compound eye ERG is reduced by 20% with ocellar occlusion and can subsequently be fully restored to the intact level, which indicates that the ocellar effect is a peripheral one. Intensified CoCl2 fills reveal one neurone in A. domesticus and two in T. commodus which travel from the lateral ocellar nerve out into the ipsilateral optic lobe of the compound eye. These neurones all terminate in or distal to the lobular neuropile. The data are interpreted to indicate a role for ocelli in modulating the light intensity perception of the compound eye. The final effect of the ocellar afferents is at a peripheral level prior to the input of the visual information to the optic lobe circadian pacemaker. Hence ocelli play an indirect role in circadian rhythmicity, augmenting the sensitivity of the primary photoreceptors to better perceive photic entrainment signals.
Haptic rendering with predictive representation of local geometry

Haptic rendering of large and detailed virtual objects can require a significant computational load. Built out of a vast number of primitives, the object models can strain algorithms such as collision detection and constrained optimization, which are widely used in haptics applications. Nevertheless, to provide the necessary fidelity, haptic servo loops need to operate at 1 kHz or above. Separating the haptic processes from the more time consuming processes has long been a standard technique to protect more sensitive servo loops from the computational burden of collision detection and graphic display. In addition, local approximation techniques have been developed to allow fast update rates on small areas of the overall model around a known contact point. Operations on the complete model are only executed at a much slower rate. However, none of the existing methods fully exploit the model's topological information. We propose the use of the quadedge data structure to store the object model in addition to a hierarchical data structure used in collision detection. The compact, edge-based graph structure provides a topological map and the necessary tools to navigate easily along the model's surface. Also, we propose to use a velocity vector as an indicator of the intended user's motion. Such information leads to the prediction of the user's position within a short time frame. The proposed methods allow us to efficiently build local intermediate models based on predictions of the contact point movement.
Facilitating the Interpretation of GPR Refraction Data for Stratigraphic Analysis

By adapting procedures from refraction seismology, GPR refraction methods appear promising for shallow stratigraphic studies, particularly when the structure consists of bedrock or coarse-grained unconsolidated sediments beneath partially–saturated fine-grained sand, silt or organic rich soil (Bohidar, 2001, Bohidar and Hermance, 2002; Hermance and Bohidar, 2002a). Under appropriate conditions, refracted phases can be readily detected at transmitter-receiver offsets of over 15 m, and from depths of over 2 m. However, if the GPR refraction method is to realize its potential, tools need to be developed that abate some of the time-intensive labor in reducing refraction data for practical surveys. Preconditioning radargram images using non-linear gain controls are particularly effective for detecting the presence of refraction events. Moreover, since the GPR delay time method is especially useful for resolving fine structure of the refracting interface, we have implemented a procedure for “auto-picking” events employing a lagged crosscorrelation analysis between a reference “native wavelet” and each respective GPR trace. Because the refractor velocity can be determined with high precision, refinements in the GPR refraction method make it a useful tool, not only for broadly delineating stratigraphy, but for assessing material properties in-situ, as well.
Differential Effects of cAMP in Neurons and Astrocytes ROLE OF B-RAF

Mitogen-activated protein kinase (MAPK) activation provides cell type-specific signals important for cellular differentiation, proliferation, and survival. Cyclic AMP (cAMP) has divergent effects on MAPK activity depending on whether signaling is through Ras/Raf-1 or Rap1/B-raf. We found that central nervous system-derived neurons, but not astrocytes, express B-raf. In neurons, cAMP activated MAPK in a Rap1/B-raf-dependent manner, while in astrocytes, cAMP decreased MAPK activity. Inhibition of MAPK in neurons decreased neuronal growth factor-mediated survival, and activation of MAPK by cAMP analogues rescued neurons from death. Furthermore, constitutive expression of B-raf in astrocytoma cells increased MAPK activation, as seen in neurons, and enhanced proliferation. These data provide the first experimental evidence that B-raf is the molecular switch which dominantly permits differential cAMP-dependent regulation of MAPK in neurons versus astrocytes, with important implications for both survival and proliferation.
Dependence of tracer diffusion on atomic size in amorphous Ni-Zr

Tracer diffusion coefficients for several impurities and Ni self-atoms were measured in amorphous (a-) ${\mathrm{Ni}}_{50}$${\mathrm{Zr}}_{50}$ at 573 K using secondary-ion-mass spectroscopy, Rutherford backscattering, and radioactive tracer methods. The results showed that atomic mobility in the a-Ni-Zr alloy depends strongly on atomic size, decreasing rapidly with increasing atomic radius. This diffusion behavior is similar to that in \ensuremath{\alpha}-Zr and \ensuremath{\alpha}-Ti and is suggestive of an interstitial-like mechanism of diffusion. The consequences of these results for solid-state amorphization transformations are discussed.
Examination of costs for a lay health educator-delivered translation of the Diabetes Prevention Program in senior centers

Abstract Objective Older adults in the U.S. have high rates of obesity. Despite the demonstrated efficacy of lifestyle interventions among older adults, lifestyle interventions are not widely implemented in community settings. Program delivery by lay health educators (LHEs) might support greater dissemination because of lower delivery cost and greater accessibility. We examined the costs of a LHE-delivered translation of the Diabetes Prevention Program (DPP) evidence-based lifestyle intervention for older adults in Arkansas senior centers. Methods This examination of costs used data from a cluster randomized control trial (conducted 2008–2010) in which 7 senior centers (116 participants) were randomized to implement a LHE-delivered 12-session translation of the DPP lifestyle intervention. We compiled direct lifestyle intervention implementation costs, including training, recruitment, materials, and ongoing intervention implementation support. Weight loss data (at 4-month follow-up) were collected from participants. Results Participant weight loss averaged 3.7 kg at 4-months. The total estimated cost to implement the lifestyle intervention is $2731 per senior center, or $165 per participant. The implementation cost per kilogram lost is $45. Conclusions A LHE-delivered DPP translation in senior centers is effective in achieving weight loss at low cost and offers promise for the dissemination of this evidence-based intervention.
Hyperkalemic Cardiac Arrhythmia Secondary to Spironolactone

Although multiple adverse reactions can occur during the use of spironolactone, the most serious complication is related to its potassium-sparing effect which may induce dangerous and even fatal hyperkalemia. One patient is presented who developed severe hyperkalemia after spironolactone resulting in ventricular standstill and survival following treatment with sodium bicarbonate.
Synthesis of Permutative Quantum Circuits with Toffoli and TISC Gates

We present a new concept of TISC (2-interval symmetric controlled) quantum per mutative gates and how per mutative quantum circuits with no ancilla bits can be built using a combination of Toffoli and TISC gates.
The correlation between wing kinematics and steering muscle activity in the blowfly Calliphora vicina

Determining how the motor patterns of the nervous system are converted into the mechanical and behavioral output of the body is a central goal in the study of locomotion. In the case of dipteran flight, a population of small steering muscles controls many of the subtle changes in wing kinematics that allow flies to maneuver rapidly. We filmed the wing motion of tethered Calliphora vicina at high speed and simultaneously recorded multi-channel electromyographic signals from some of the prominent steering muscles in order to correlate kinematics with muscle activity. Using this analysis, we found that the timing of each spike in the basalare muscles was strongly correlated with changes in the deviation of the stroke plane during the downstroke. The relationship was non-linear such that the magnitude of the kinematic response to each muscle spike decreased with increasing levels of stroke deviation. This result suggests that downstroke deviation is controlled in part via the mechanical summation of basalare activity. We also found that interactions among the basalares and muscles III2–III4 determine the maximum forward amplitude of the wingstroke. In addition, activity in muscle I1 appears to participate in a wingbeat gearing mechanism, as previously proposed. Using these results, we have been able to correlate changes in wing kinematics with alteration in the spike rate, firing phase and combinatorial activity of identified steering muscles.
Second nonocular tumors in survivors of bilateral retinoblastoma: a possible age effect on radiation-related risk.

Abstract Objective This study aimed to investigate the relationship in bilateral retinoblastoma survivors between the incidence of second tumors and the age when external beam radiation (EBR) was used. Design A retrospective analysis of patients diagnosed with retinoblastoma was performed by examining records for background information and treatment information as well as reviewing documentation of patients with second nonocular tumors. Two telephone interviews were conducted for follow-up as well as inquiries directed to tumor registries and state databases. Participants The original study included 1729 patients treated in New York and Boston; the current study includes only the 1506 patients treated in New York. Of those, 816 patients were diagnosed with bilateral retinoblastoma, had sufficient treatment data to be useful, and survived at least 1 year from diagnosis. Main outcome measures The subjects were observed for evidence of the development of second nonocular tumors. Results There was a significant decrease in tumor-free survival among patients treated with EBR before the age of 12 months, but no significant difference between the group treated with EBR after the age of 12 months and the group not treated with EBR. For tumors in the field of radiation, patients treated with early EBR showed a significant decrease in tumor-free survival when compared to patients treated with late EBR, with no significant difference between late radiation and no radiation. There were no significant differences between groups for tumors out of the field of radiation. Significant differences attributable to the use of EBR were found only for tumors of the skull and face bones and for tumors of the soft tissue of the head. Conclusions The long-term effect of radiation treatment on survivors of bilateral retinoblastoma is to increase the incidence and affect the distribution of second tumors. However, no increased risk is observed for tumors out of the field of radiation among patients who underwent radiation, and the risk for tumors in the field of radiation is heavily dependent on the age at which EBR is given and may be acceptably small to the patient after the age of 12 months.
On extending more parallelism to serial simulators

This paper describes an approach to discrete event simulation modeling that appears to be effective for developing portable and efficient parallel execution of models of large distributed systems and communication networks. In this approach, the modeler develops sub-models using an existing sequential simulation modeling tool, using the full expressive power of the tool. A set of modeling language extensions permit automatically synchronized communication between sub-models; however, the automation requires that any such communication must take a non-zero amount of simulation time. Within this modeling paradigm, a variety of conservative synchronization protocols can transparently support conservative execution of sub-models on potentially different processors. A specific implementation of this approach, U.P.S. (Utilitarian Parallel Simulator), is described, along with performance results on the Intel Paragon.
Mold susceptibility of rigid PVC/wood-flour composites

Rigid PVC/wood-flour composite lumber containing either hardwood (maple) or a softwood (southern pine) wood flour at different levels of wood-flour content was evaluated for susceptibility to fungal colonization and discoloration by using standard tests that mimicked exterior (ASTM G21) and interior (ASTM D3273) environments, respectively. In the exterior test protocol, although both types of PVC/wood-flour composite lumber exhibited fungal colonization and discoloration, the composites containing maple exhibited greater discoloration than those containing pine. Irrespective of wood species, fungal colonization and discoloration in the composite lumber were greater at the bottom faces where they were in constant contact with moisture. The wood content range (50-100 phr) used in this study showed no effect on extent of fungal colonization and discoloration. All composites showed no discoloration in the interior test protocol. Both optical microscopy and environmental scanning electron microscopy clearly demonstrated that wood flour particulates are not completely encapsulated by the PVC matrix, so that exposed wood flour in the surface crevices of the composite lumber may serve as points of moisture sorption and staging points for fungal colonization and discoloration.
A Simple Characterization of Strategic Behaviors in Broadcast Channels

In this letter, we consider the problem of resource allocation between two competing users sharing a binary symmetric broadcast channel. We model the interaction between autonomous selfish users in the resource allocation and analyze their strategic behavior in manipulating the allocation outcome. We analytically show that users will improve their performance (i.e., gain higher allocated rates) if they have more information about the strategy of the competing user.
It Takes Two: Ethical Dualism in the Vegetative State

To aid neuroscientists in determining the ethical limits of their work and its applications, neuroethical problems need to be identified, catalogued, and analyzed from the standpoint of an ethical framework. Many hospitals have already established either autonomy or welfare-centered theories as their adopted ethical framework. Unfortunately, the choice of an ethical framework resists resolution: each of these two moral theories claims priority at the exclusion of the other, but for patients with neurological pathologies, concerns about the patient’s welfare are treated as meaningless without consideration of the patient’s expressed wishes, and vice versa. Ethicists have long fought over whether suffering or autonomy should be our primary concern, but in neuroethics a resolution of this question is essential to determine the treatment of patients in medical and legal limbo. I propose a solution to this problem in the form of ethical dualism. This is a conservative measure in that it retains both sides of the debate: both happiness and autonomy have intrinsic value. However, this move is often met with resistance because of its more complex nature—it is more difficult to make a decision when there are two parallel sets of values that must be considered than when there is just one such set. The monist theories, though, do not provide enough explanatory power: namely, I will present two recently publicized cases where it is clear that neither ethical value on its own (neither welfare nor autonomy) can fully account for how a vegetative patient should be treated. From the neuroethical cases of Terri Schiavo and Lauren Richardson, I will argue that a dualist framework is superior to its monist predecessors, and I will describe the main features of such an account.
Performance Study of a Whole Genome Comparison Tool on a Hyper-Threading Multiprocessor

We developed a multithreaded parallel implementation of a sequence alignment algorithm that is able to align whole genomes with reliable output and reasonable cost. This paper presents a performance evaluation of the whole genome comparison tool called ATGC – Another Tool for Genome Comparison, on a Hyper-Threading multiprocessor. We use our application to determine the system scalability for this particular type of sequence comparison algorithm and the improvement due to Hyper-Threading technology. The experimental results show that despite of placing a great demand on the memory system, the multithreaded code generated by Intel compiler yields to a 3.3 absolute speedup on a quad-processor machine, with parallelization guided by OpenMP pragmas. Additionally, a relatively high 1 st level cache miss rate of 7-8% and a lack of memory bandwidth prevent logical processors with hyper-threading technology enabled from achieving further improvement.
Covert conditioning and the control of pain.

A rationale for the covert conditioning (CC) approach to pain is given. The general procedure for behavioral analysis, selection and evaluation of CC procedures is presented. Application of the various CC procedures to the modification of pain behavior is described. Case studies are presented. Experimental results, thus far, warrant further research.
The Semantics of Belief Ascriptions

Critique de la theorie de la relation selon laquelle les verbes exprimant les attitudes cognitives manifestent des relations mentales entre les personnes et les propositions. L'A. propose une nouvelle theorie de la signification et de la forme logique des attributions cognitives qui rend compte de l'evidence contre la theorie de la relation. Substituant le concept de signification linguistique a celui de proposition, l'A. developpe une approche compositionnelle de la signification des attributions cognitives, d'une part, et montre que l'evidence qu'il determine permet de refuter d'autres approches contextuelles des attributions, d'autre part
Placement for large-scale floating-gate field-programable analog arrays

Modern advances in reconfigurable analog technologies are allowing field-programmable analog arrays (FPAAs) to dramatically grow in size, flexibility, and usefulness. Our goal in this paper is to develop the first placement algorithm for large-scale floating-gate-based FPAAs with a focus on the minimization of the parasitic effects on interconnects under various device-related constraints. Our FPAA clustering algorithm first groups analog components into a set of clusters so that the total number of routing switches used is minimized and all IO paths are balanced in terms of routing switches used. Our FPAA placement algorithm then maps each cluster to a computational analog block (CAB) of the target FPAA while focusing on routing switch usage and balance again. Experimental results demonstrate the effectiveness of our approach
Managing conduct: a comparative policy analysis of safe schools policies in Toronto, Canada and Buffalo, USA

Public school districts in Buffalo, USA and Toronto, Canada reviewed their safe schools policies in 2008. Revised Codes of Conduct are compared to earlier versions and each other, and a conceptual policy web is used to understand how local, state/provincial, national, and international influences affect local safe school policies. The comparison demonstrates that while influenced by international beliefs about unsafe schools and youth violence, affected by local social, economic, and historical contexts, and constrained by state/provincial and federal policies, local school districts are nevertheless able to exercise some agency. The study also highlights the importance of Ontario's Human Rights Commission as a policy actor, and suggests zero tolerance for non‐serious incidents may be practised in Buffalo schools. This finding and the continued practice of excluding students from schools in both districts as a discipline approach casts doubt on the sincerity of governments' commitments to evidence‐based p...
The structure of non-linear cellular solutions to the Boussinesq equations

A model equation is constructed whose analysis reveals the same features, including stable hexagonal cells, as analysis of genuine approximate equations for the thermal convection problem. Taking advantage of the relative simplicity of the calculations an attempt is made to clarify certain procedures customarily used in non-linear stability theory; in particular, the basis for the usual formal expansions and the appropriateness of neglecting terms of fourth and higher order are discussed. It is demonstrated that a whole class of equations leads to hexagonal cells, thereby giving confidence that results on convection cells found elsewhere in idealized situations will remain valid when more realistic situations are studied.
Dynamic cluster tracking technique for traffic monitoring using on-vehicle radar

Predictive sensing applications are starting to find wide applications in automotive safety applications. In collision situations the need to alert the driver and to take effective countermeasures to meet the needs of the vehicle occupant safety is becoming increasingly more dependent on sensors. Electronic systems to provide warning and to implement active adaptation of occupant restraints to provide for enhanced safety protection are becoming more dependent on active safety sensors. This paper deals with a system that uses radar sensors that provides the ability to cluster the number of vehicles based on radar return signals and to actively track their movement with a Kalman filter.
Physical modeling of cell geometric order in an epithelial tissue

In multicellular organisms, cells pack together to form tissues of intricate and well defined morphology. How such cell-packing geometries arise is an important open question in biology, because the functionality of many differentiated tissues depends on their reliable formation. We show that combining adhesive forces due to E- and N-cadherin with a quantitative description of cell membrane elasticity in an interfacial energy model explains not only the qualitative neighbor relations, but also the detailed geometry of a tissue. The characteristic cellular geometries in the eyes of both wild-type Drosophila and genetic mutants are accurately reproduced by using a fixed set of few, physically motivated parameters. The model predicts adhesion strengths in the eye epithelium, quantifies their role relative to membrane elasticity, and reveals how simple minimization of interfacial energy can give rise to complex geometric patterns of important biological functionality.
The influence of prostate size on cancer detection

Abstract Objectives To determine if cancer detection rates vary with prostate size using a sextant core biopsy pattern. Methods We reviewed 1021 transrectal ultrasound (TRUS)-guided sextant pattern prostate biopsies to determine if cancer detection varied based on prostate size. Prostate size was determined using a computer generated elliptical estimation method. Sextant core biopsies were taken, and the patients divided into groups based on estimated size of the prostate and biopsy outcome. Large prostates were those that were estimated by TRUS as 50 cc or more. Prostates were considered small if they were less than 50 cc. Groups were compared based on size and biopsy outcome. Results Adenocarcinoma was detected in 33% (334 of 1021) of the patients. Large prostates were noted in 34% (346 of 1021), of which 23% (80 of 346) had cancer detected by sextant biopsy. Small prostates were noted in 66% (675 of 1021), of which 38% (254 of 675) had cancer detected. The difference in cancer detection in large and small glands using a sextant pattern was statistically significant ( P P P Conclusions Currently no evidence exists to support differing cancer rates based on gland size alone. Our cancer detection rate using a sextant pattern was higher in men with prostates less than 50 cc, and patients diagnosed with cancer had significantly smaller prostates than those with a negative sextant biopsy. Our data suggest that significant sampling error may occur in men with large glands, and more biopsies may be needed under these circumstances. The effects of tumor volume, focality, and specimen size in relation to overall gland size may contribute to these findings.
Occlusal caries formation in vitro: comparison of resinmodified glass ionomer with fluoride-releasing sealant

The purpose of this laboratory study was to evaluate caries-like lesion formation in occlusal enamel adjacent to a light-cured resin-modified glass ionomer utilized as a pit and fissure sealant and a conventional light-cured, fluoride-releasing sealant. Fluoride-free prophylaxis was done on occlusal surfaces of 12 caries-free mandibular molar teeth that had not been exposed to the oral cavity. Occlusal surface morphology was examined by SEM on the uncoated specimens. Each tooth was then sectioned into 2 portions buccolingually, producing mesial and distal tooth halve. Occlusal surfaces of mesial tooth halves were prepared for an experimental light-cured resin-modified glass ionomer (RMG) sealant (PH-SE II, ESPE), and for comparison, a light-cured fluoride-releasing pit and fissure (PFS) sealant (Helioseal F, Ivoclar) was placed on occlusal surfaces of the corresponding distal tooth halves. The sealed occlusal surfaces were examined uncoated by SEM to compare RMG and PFS adaptation. After thermocycling in artificial saliva, caries-like lesions were formed in the occlusal surfaces adjacent to RMG and PFS. Longitudinal sections were taken for comparison of lesion formation adjacent to RMG and PFS. Mean lesion depths in occlusal surfaces were 64 +/- 17 mm for RMG, and 116 +/- 27 mm for PFS (p < 0.05, paired t-test). Occlusal lesions terminated at the point where bonding occurred between the occlusal enamel and RMG or PFS. SEM surface topography demonstrated adequate adaptation of the materials with obliteration of the typical pit and fissure surface morphology by both RMG and PFS. While both the resin-modified glass ionomer and fluoride-releasing sealant materials protected the pit and fissure enamel from caries development, the resin-modified glass ionomer reduced the extent of caries involvement in the adjacent unsealed occlusal incline enamel, when compared with the resin sealant.
Johann Peter Frank: un pionero de la medicina social

H. E. Sigerist (1891-1957), a French philologist and historian of medicine, was the first to show the relationship between medical practice and social conditions and to approach it as an aspect of the history of civilization. The following is one of the lectures he gave at the University of London which presents an excellent background of the history of Western public health: J. P. Frank's pioneering work in the field of social medicine, almost two centuries ago, a contribution that remained virtually unnoticed until Sigerist reappraised it.
A three-way VOT contrast in final position: data from Armenian

Standard Eastern Armenian has a three-way VOT contrast among its oral stop series. While it is rare for such a 3-way contrast to be preserved in final position, Standard Eastern Armenian is claimed to do just this (Khachaturian 1988; Ladefoged & Maddieson 1996; Vaux 1998). This phenomenon provides an ideal opportunity to explore how prosodic structure influences the realization of a complex and delicate system of contrast maintained by temporal and saliency distinctions. The cues to this contrast, including VOT, closure duration, and burst amplitude, are examined in a variety of segmental and prosodic environments. The experiment evaluates effects of intonation phrase final, intermediate phrase final, word final, and syllable final positions. We find that the 3-way VOT contrast is maintained in those prosodic domains in which the stop consonants are final. Speakers make significant VOT distinctions among the target consonants within the same boundary condition, and across prosodic conditions, larger prosodic domains exhibit longer VOT values.
Early Phase Morphological Lesions and Transcriptional Responses of Bovine Ileum Infected with Mycobacterium avium subsp. paratuberculosis

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of chronic enteritis in ruminants (Johne's disease) and a possible etiopathologic agent in human Crohn's disease. The host-pathogen interaction in this chronic disease has largely depended on the randomly collected static lesions studied in subclinically or clinically infected animals. We have established and utilized the neonatal calf ligated ileal loop model to study the early temporal host changes during MAP infection. After inoculation of ligated ileal loop with MAP, samples were analyzed for bacterial invasion, histologic and ultrastructural morphologic changes, and gene expression at several times (0.5-12 hours) postinfection. Our results indicate that MAP invades the intestinal mucosa as early as 0.5 hour postinoculation. Distribution and migration of neutrophils, monocytes/macrophages, and goblet cells were confirmed by histopathology, scanning and transmission electron microscopy. Coincident with the morphologic analysis, we measured by real-time polymerase chain reaction gene expression of various cytokines/chemokines that are involved in the recruitment of mononuclear and polymorphonuclear leukocytes to the site of infection. We also detected expression of several other genes, including intestinal-trefoil factor, profilin, lactoferrin, and enteric s-defensin, which may play significant roles in the early MAP infection. Thus, the calf ligated intestinal loop model may be used as a human disease model to understand the role of MAP in the pathogenesis of Crohn's disease.
EVALUATION OF REINFORCER PREFERENCES FOR PROFOUNDLY HANDICAPPED STUDENTS

Five students classified as profoundly/multiply handicapped were trained to use microswitches to indicate reinforcer preferences. The students were trained to emit a designated motoric response (raise arm or raise head) which in turn activated a microswitch. The microswitches were connected to battery-operated toys and devices, and served to provide immediate, contingent consequences to the students for their motoric responding. The results of the investigation were evaluated within a multiple baseline (across students) with alternating treatments (potential reinforcers) design. During baseline, the students were provided with the switches and devices, but the switches were not connected to the devices. During the training conditions, the switches activated the devices. Evaluation of the devices was conducted by recording the cumulative frequency and duration of the students' responses. When the microswitches activated the devices during training, a substantial increase in the duration of motoric responding occurred for all students. In addition, some students performed differentially across devices, suggesting that they had reinforcer preferences.
Differentially charged hollow core/shell lipid-polymer-lipid hybrid nanoparticles for small interfering RNA delivery.

Since the discovery of RNA interference (RNAi), by which the activity of specific genes can be efficiently suppressed, synthetic small interfering RNA (siRNA)-mediated RNAi has been of substantial interest for various disease treatments.[1] However, the safe and effective delivery of siRNA to target cells remains a major hurdle for its widespread clinical applications.[2] Due to its polyanionic and macromolecular characteristics, naked siRNA cannot readily cross the cell membrane, and thus requires specific delivery vehicles to facilitate its intracellular uptake and cytosolic delivery for bioactivity. These delivery vehicles are also expected to improve the pharmacological properties of siRNA by reducing its susceptibility to serum nucleases, renal filtration, and uptake by the mononuclear phagocyte system.
Atomistic simulations of interfaces in metals and alloys

We have used embedded atom potentials to simulate the surfaces, thin films and grain boundaries in metals (Ni and Al) and alloys (NiAl and Ni3Al). The calculated surface relaxations and ripplings of free surfaces are in good agreement with experiments. A new interference phenomena of interlayer relaxation in thin films are observed in the simulation. The segregation behavior of B and S and their effects on the mechanical properties of Ni3Al are correctly predicted with potentials fitted to data obtained by electronic band structure calculations.
The use of gene expression profiling and mutation analysis increases the cost of care for patients with carcinoma of unknown primary; does it also improve survival?

Carcinoma of unknown primary (CUP) signifies metastatic disease in the absence of a detectable primary site after adequate diagnostic evaluation [1]. The diagnosis carries a poor prognosis, with median survival of just 1 year when treated with cytotoxic agents in contemporary studies [2]. Until recently, the standard approach to CUP patients was to use first line treatment with a cytotoxic drug combination selected based upon the cancer’s histopathologic and immunohistochemical similarity to known primary site cancers [3,4]. Yet, in recent years, advances in genetic and personalized medicine have led to two principal areas of investigation, and departures from the historical treatment approach. Specifically, gene expression profiling can now suggest a tissue of origin (TOO) in previously indeterminate cases, and drug-able mutational analysis
Low temperature partial alcoholysis of triglycerides

Egg triglycerides chromatographed on silicic acid are eluted in a skew curve in which fatty acid composition varies. The triglycerides were cleaved by sodium methoxide in chloroform-methanol at 0°C to yield diglycerides (11.3%) and monoglycerides (17.5% of original triglycerides) after 3 min. Complete cleavage to fatty acid methyl esters and glycerol was obtained at 18 min at 0°C or 5 min at room temperature.
Discussion: Impacts of Vertical Integration on Output Price and Industry Structure

We may expect a tendency toward bilateral monopoly as horizontal integration develops. One sector of a vertically integrated industry may have economies of size that reduce that sector to just a few firms. Collusion among these few firms may bring about collusion among many independent firms in another sector.5 Interest centers on the question of whether growers could be exploited by this sort of horizontal area collusion. As long as the collusion is not strong enough to restrict entry of new firms it is difficult to imagine any serious exploitation. If the colluding firms continue to expand total production, there is also little likelihood of grower exploitation. Exploitation would seem most likely if an area should stop expanding. Farmers could be kept in production at returns which just cover variable costs. With the many alternatives that are normally available to farmers, however, it is difficult to imagine they will remain exploited for any long period of time. One answer of farmers to exploitation by horizontal highly integrated dealers is, of course, horizontal integration of themselves. However, this cannot achieve its objective without power to control the entry of firms into the industry and to regulate production. For this reason it is quite unlikely without government support. If other segments of industry become horizontally integrated, survival of the family farm may depend on the willingness of farm operators to integrate horizontally in order to gain strength in market decisions. Many persons are concerned about whether the family farm will become technologically outmoded and its key enterprises owner-integrated. Survival of family farms depends upon the ability and willingness of farmers to adjust to changing economic conditions. In integrated systems of production farmers must become specialists in providing the services wanted by the market. Furthermore, they must be willing to coordinate their decisions with those of other producers in the industry. If farmers find it difficult to adjust or if gross inefficiency prevails in the industry, vertical owner integration will likely develop.
Deconstructing a lethal foodborne epidemic.

Beginning in early May 2011, northern Germany was the principal site of a massive epidemic of bloody diarrhea and the hemolytic–uremic syndrome caused by Shiga-toxin–producing Escherichia coli. By the time the outbreak ended in early July, there were reports of more than 4000 illnesses, 800 cases of the hemolytic–uremic syndrome, and 50 deaths in Germany and in 15 other countries. As a result of remarkable efforts by public health officials, clinicians, and microbiologists who raced to control the outbreak and to treat its victims, much was learned. As reported in this issue of the Journal by Frank et al. . . .
Male density and rapid evolution of genital morphology in the seed beetle Callosobruchus maculatus

Male reproductive structures are known to be extremely diverse, particularly in insect taxa. Male genital structures are thought to be some of the fastest evolving traits, but the processes responsible for this pattern remain unclear. In the present study we manipulated the mating regimes of Callosobruchus maculatus, a seed beetle, to determine if male genital structures would be altered under forced monogamy and polyandry. Males in this species have an intromittent organ that contains spines that are known to puncture the female reproductive tract. We measured both testes size and genital spine length in monogamous and polyandrous treatments over seven generations. We found that testes size was not significantly different between treatments, but that genital spine length was significantly longer in the polyandrous treatment within seven generations. These results highlight the fact that evolution can occur rapidly when under strong sexual selection, a process that has been implicated in leading to morphological differences in male genitalia.
5ALA in pediatric brain tumors is not routinely beneficial.

Purpose Over recent years, 5-aminoluvolinic acid (5ALA) has been increasingly used for resection guidance in adult high-grade gliomas. However, amongst pediatric patients, publication of intraoperative fluorescence has been limited, with inconsistent outcomes. We describe our experience and intraoperative finding amongst children with various brain tumors that were given 5ALA prior to tumor resection.
A combined experimental, modeling, and computational approach to interpret the viscoelastic response of the white matter brain tissue during indentation

Viscoelastic properties of the white matter brain tissue are systematically studied in this paper utilizing indentation experiments, mathematical modeling, and finite element simulation. It is first demonstrated that the internal stiffness of the instrument needs to be thoroughly obtained and incorporated in the analysis as its contribution to the recorded mechanical response is significant for experiments on very compliant materials. The flat-punch monotonic indentation is then performed indirectly on sagittal plane slices with pushing a large rigid coverslip into the sample surface. The recorded load and displacement data are used for calibrating different viscoelastic models and presenting numerical values for the model elements. Consequently, the accuracy of the findings based on the theoretical models is investigated by performing finite element simulations which suggest a considerable substrate effect that causes violation of the semi-infinite half-space assumption in modeling of the material behavior. Accordingly, correction factors for adjusting the viscoelastic constants are obtained and presented. Since the Maxwell model shows a superior capability in rendering the mechanical response of the brain, an extension of this model to Multimode Maxwell viscoelastic solid is proposed for modeling the tissue behavior under a more complex load-hold-unload indentation cycle that shows acceptable agreement with experimental observations.
Macrophage subpopulations and their impact on chronic allograft rejection versus graft acceptance in a mouse heart transplant model.

Macrophages infiltrating the allografts are heterogeneous, consisting of proinflammatory (M1 cells) as well as antiinflammatory and fibrogenic phenotypes (M2 cells); they affect transplantation outcomes via diverse mechanisms. Here we found that macrophage polarization into M1 and M2 subsets was critically dependent on tumor necrosis factor receptor-associated factor 6 (TRAF6) and mammalian target of rapamycin (mTOR), respectively. In a heart transplant model we showed that macrophage-specific deletion of TRAF6 (LysMCre Traf6 fl/fl ) or mTOR (LysMCre Mtorfl/fl ) did not affect acute allograft rejection. However, treatment of LysMCre Mtorfl/fl recipients with CTLA4-Ig induced long-term allograft survival (>100 days) without histological signs of chronic rejection, whereas the similarly treated LysMCre Traf6 fl/fl recipients developed severe transplant vasculopathy (chronic rejection). The presentation of chronic rejection in CTLA4-Ig-treated LysMCre Traf6 fl/fl mice was similar to that of CTLA4-Ig-treated wild-type B6 recipients. Mechanistically, we found that the graft-infiltrating macrophages in LysMCre Mtorfl/fl recipients expressed high levels of PD-L1, and that PD-L1 blockade readily induced rejection of otherwise survival grafts in the LysMCre Mtorfl/fl recipients. Our findings demonstrate that targeting mTOR-dependent M2 cells is critical for preventing chronic allograft rejection, and that graft survival under such conditions is dependent on the PD-1/PD-L1 coinhibitory pathway.
Synthesis and performance of nanostructured silicon/graphite composites with a thin carbon shell and engineered voids

Abstract Utilizing silicon as an anode material for Li-ion batteries has been the subject of many studies. However, due to the huge volume change of silicon during lithiation, the electrochemical performance of silicon is poor. Here, we have investigated a novel yet simple approach to synthesize nanostructured silicon/graphite composites with a carbon coating and engineered voids. High-energy ball mill is employed to convert micrometer-sized silicon and graphite to nanostructured silicon/graphite composite building blocks, while a thin carbon coating is applied to encapsulate these composite agglomerates, followed by partial etching of silicon to create engineered voids inside the composite agglomerates. The batteries made with this tailored nanostructure exhibit improved electrochemical performance over the counterparts made with silicon nanoparticles and exhibited a specific capacity of ∼1800 mA h g−1 discharge capacity at the first cycle, 580 mA h g−1 after 40 cycles, and 350 mA h g−1 after 300 cycles. This study has established a novel method scalable at industry environment and capable of producing low cost Si anodes and clearly shown that the cycle stability of the tailored nanostructure improves with increasing engineered voids in the range we have investigated.
The utility of EEG monitoring in neonates with hyperammonemia due to inborn errors of metabolism.

Abstract Background Continuous EEG studies demonstrate that neonates with seizures due to cerebral pathology, such as hypoxia ischemia, exhibit predominantly electrographic seizures (i.e. those only detected with EEG because they lack clinical features). Previous small case series demonstrate EEG changes and seizures during hyperammonemia associated with inborn errors of metabolism (IEM) but there are no reports utilizing continuous EEG in these conditions. Objective To characterize seizures and evaluate the utility of continuous EEG recording during hyperammonemia due to inborn errors of metabolism. Methods We retrospectively reviewed medical records and EEG tracings of neonates who presented with hyperammonemia due to inborn errors of metabolism who had continuous EEG and full medical records available for review, including follow up. Results Eight neonates with hyperammonemia were studied, 7 had urea cycle defects: Argininosuccinate lyase deficiency [3], (ornithine transcarbamylase deficiency [3], carbomyl phosphate synthase deficiency [1] and one had an organic acidemia: Methylmalonic acidemia [1]. Most common presentations were lethargy and poor feeding at 12–72 h of life. The highest blood ammonia level was 874 μmol/L (median); range 823–1647 μmol/L (normal value Conclusions Seizures occur frequently in neonates with hyperammonemia; most can be detected only with continuous EEG. Seizures may occur when ammonia and glutamine levels are normal. Interburst interval duration is associated with ammonia levels or cerebral dysfunction from other brain pathology. Continuous EEG can be a useful tool for managing infants with hyperammonemia and may be essential for seizure management especially for infants in deep metabolic coma.