cssi/SciSciGPT-SciSciNet huggingface dataset:
Managing inadequate responses to frontline treatment of chronic myeloid leukemia: A case-based review

The tyrosine kinase inhibitors (TKIs) imatinib, nilotinib, and dasatinib are the standard of care for treating patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML). Compared with interferon-based treatment, the previous standard of care, imatinib is associated with significantly higher cytogenetic response rates and prolonged overall survival. Nilotinib and dasatinib, both newer and more potent TKIs, significantly improve cytogenetic and molecular response rates compared with imatinib. Despite significant advances in CML treatment enabled by the TKIs, a fraction of patients who receive frontline treatment with a TKI demonstrate inadequate response. The reasons for this vary, but in many cases, inadequate response can be attributed to non-adherence to the treatment regimen, intolerance to the drug, intrinsic or acquired resistance to the drug, or a combination of reasons. More often than not, strategies to improve response necessitate a change in treatment plan, either a dose adjustment or a switch to an alternate drug, particularly in the case of drug intolerance or drug resistance. Improved physician-patient communication and patient education are effective strategies to address issues relating to adherence and intolerance. Because inadequate response to TKI treatment correlates with poor long-term outcomes, it is imperative that patients who experience intolerance or who fail to achieve appropriate responses are carefully evaluated so that appropriate treatment modifications can be made to maximize the likelihood of positive long-term outcome.
A homogenization model of the annulus fibrosus.

Abstract The objective of this study was to use a homogenization model of the anisotropic mechanical behavior of annulus fibrosus (AF) to address some of the issues raised in structural finite element and fiber-reinforced strain energy models. Homogenization theory describes the effect of microstructure on macroscopic material properties by assuming the material is composed of repeating representative volume elements. We first developed the general homogenization model and then specifically prescribed the model to in-plane single lamella and multi-lamellae AF properties. We compared model predictions to experimentally measured AF properties and performed parametric studies. The predicted tensile moduli ( E θ and Ez) and their dependence on fiber volume fraction and fiber angle were consistent with measured values. However, the model prediction for shear modulus ( G θ z ) was two orders of magnitude larger than directly measured values. The values of E θ and Ez were strongly dependent on the model input for matrix modulus, much more so than the fiber modulus. These parametric analyses demonstrated the contribution of the matrix in AF load support, which may play a role when protoeglycans are decreased in disc degeneration, and will also be an important design factor in tissue engineering. We next compared the homogenization model to a 3-D structural finite element model and fiber-reinforced energy models. Similarities between the three model types provided confidence in the ability of these models to predict AF tissue mechanics. This study provides a direct comparison between the several types of AF models and will be useful for interpreting previous studies and elucidating AF structure–function relationships in disc degeneration and for functional tissue engineering.
A generic probabilistic risk assessment for low-level waste burial grounds

Abstract A generic probabilistic risk assessment is developed for buried low-level radioactive waste from nuclear power production. Transfer probabilities from the ground to human ingestion are estimated from geochemical analogues, with justifications based on requirements of the regulations of U.S. Nuclear Regulatory Commission and comparisons of dietary intakes of various elements with their measured concentration ratios from soil to vegetation. These are combined with dose conversion factors from ICRP-30, risk estimates from BEIR-III, and recent elaborate estimates of waste quantities expected from the nuclear industry to give an estimate of 4 × 10 −4 deaths/GWe-yr among the public from buried low level waste integrated over all future time. This result is more probably an over-estimate than an under-estimate of the actual health effects.
Effect of pore distribution and flow segregation on dispersion in porous media ag

In order to study the effect of the pore size distribution and flow segregation on dispersion in a porous media, the dispersion of solute in an array of parallel pores is considered. Equations are obtained for the dispersion coefficient in laminar and turbulent flow, as a function of the particle Peclet number. The theory fits quite well cumulative experimental data from various researchers in the Peclet number range from 10/sup -3/ to 10/sup 6/. The model also predicts some trends, backed by experimental data, regarding the effect of particle size, particle size distribution and fluid velocity on dispersion.
Cytological effects of juice or puree from irradiated strawberries.

SUMMARY Vicia faba roots were treated 4 hr with undiluted juice or puree from strawberries irradiated with 200 or 400 Krad of gamma radiation from Co60 and from control berries. 200 Krad would be the highest feasible dose for strawberries as a fungicidal treatment to extend shelf life without causing unfavorable changes in fruit quality. The differences between percentages of abnormal anaphases after treatments with juice or puree from irradiated and control berries were not significant at the 1% level (“t” test) in all the 7 experiments with 200 Krad as the radiation dose, and in 6 of 7 experiments when the dose was 400 Krad. In 1 experiment with a 400-Krad dose, the difference between percentages of abnormal anaphases was barely significant at the 5% level of confidence.
Hall magnetohydrodynamics on block-adaptive grids

We present a conservative second order accurate finite volume discretization of the magnetohydrodynamics equations including the Hall term. The scheme is generalized to three-dimensional block-adaptive grids with Cartesian or generalized coordinates. The second order accurate discretization of the Hall term at grid resolution changes is described in detail. Both explicit and implicit time integration schemes are developed. The stability of the explicit time integration is ensured by including the whistler wave speed for the shortest discrete wave length into the numerical dissipation, but then second order accuracy requires the use of symmetric limiters in the total variation diminishing scheme. The implicit scheme employs a Newton-Krylov-Schwarz type approach, and can achieve significantly better efficiency than the explicit scheme with an appropriate preconditioner. The second order accuracy of the scheme is verified by numerical tests. The parallel scaling and robustness are demonstrated by three-dimensional simulations of planetary magnetospheres.
Control of the development of the ipsilateral retinothalamic projection in Xenopus laevis by thyroxine: Results and speculation

The ipsilateral retinothalamic projection of the frog Xenopus laevis is formed by the axons of a subset of retinal ganglion cells which are found throughout peripheral and non-nasodorsal retina. Unlike the crossed retinotectal and retinothalamic projections, which begin to form during early embryonic stages, the ipsilateral projection does not begin to develop until late in tadpole life, at stages when thyroxine first becomes detectable in the circulation. Blocking the production of thyroid hormone in tadpoles prevents the development of the ipsilateral projection, in a reversible manner. Intraocular injection of thyroxine can "rescue" the development of the projection in tadpoles which otherwise remain premetamorphic. In addition, the projection from one eye of a metamorphically-blocked tadpole can be induced to form by an intraocular injection of thyroxine at a dose which has no detectable effect on retinal development in the other, untreated eye. These results indicate that the development of the ipsilateral retinothalamic projection is dependent upon thyroxine, and strongly suggest that the hormone acts at the level of the eye, rather than at the optic chiasm or thalamic target, to bring about the development of a new pathway. A number of ways in which thyroxine might act in the system are discussed.
Acute and long-term effects of captopril on left and right ventricular volumes and function in chronic heart failure

Abstract To more fully delineate the effects of captopril (CPT) on cardiac size and function in patients with chronic congestive heart failure (CHF), we performed blood pool scintigraphy in conjunction with hemodynamic measurements during the initiation of vasodilator therapy and repeat scintigraphy after 2 and 12 weeks. Measurements of both right and left ventricular volumes and ejection fraction were made before and 90 minutes after the first 25 mg dose of CPT in 14 patients. Overall, heart rate fell modestly, from 82 ± 10 to 77 ± 11 bpm ( p p p p p p 2 , respectively, were not significant, although both indices rose significantly at the time of each individual's peak effect. Six patients were discharged on CPT and underwent follow-up nuclear studies: the acute decrease in ventricular volumes was sustained, as was the slight improvement in ejection fractions. These findings indicate that the major acute effect of CPT in CHF is a reduction in the preload of both ventricles. This reduction in diastolic volumes and pressures persists during chronic therapy.
Towards a predictive model of electroporation-based therapies using pre-pulse electrical measurements

Electroporation-based therapies have been gaining momentum as minimally invasive techniques to facilitate transport of exogenous agents, or directly kill tumors and other undesirable tissue in a non-thermal manner. Typical procedures involve placing electrodes into or around the treatment area and delivering a series of short and intense electric pulses to the tissue/tumor. These pulses create defects in the cell membranes, inducing non-linear changes in the electric conductivity of the tissue. These dynamic conductivity changes redistribute the electric field, and thus the treatment volume. In this study, we develop a statistical model that can be used to determine the baseline conductivity of tissues prior to electroporation and is capable of predicting the non-linear current response with implications for treatment planning and outcome confirmation.
Some nutrient interrelations during total intravenous alimentation in adult man--a review.

Selected aspects of total parenteral nutrition in man are reviewed with emphasis on carbohydrate, lipid, and hormonal interactions. In an experiment to test for the essentiality of a specific amino acid, a normal adult man received all major and minor nutrients, except lipids, by intravenous alimentation for 48 days. A chemical deficiency of essential fatty acids without clinical symptoms was promptly observed in four plasma lipid fractions and the phospholipid fraction of erythrocytes. With the glucose providing 2,600 kcal/day, blood glucose remained normal, but a hypertrigly ceridemia was observed. Plasma insulin rose and cortisol fell. To meet the essential fatty acid and energy requirements of man, critical experiments are needed to define the safe utilization of lipid emulsions during prolonged intravenous nutrition.
TRANSPORTATION AND COLOR MAINTENANCE OF HANGING BEEF

Environmental conditions (temperature, humidity and air velocity) were monitored inside refrigerated trailers loaded with beef carcasses during stationary and in-transit trials. The effects on meat color maintenance were followed on meat samples located throughout the trucks. The effect of initial carcass heat load on color maintenance during transport was studied utilizing a simulated trailer environment. Results show that an excellent environment is maintained in refrigerated trailers for beef color maintenance in-transit despite fluctuations in outside temperature and over-the-road conditions. Results from tests in which carcasses with elevated internal round temperature (15°C) were held in a simulated trailer environment suggests that shipping of such carcasses in refrigerated trailers could lead to bacterial growth and discoloration in-transit.
Going public: historical perspectives on working women.

In the course of attending conferences over the past several years, I have noticed that over lunch or drinks in the evening, women participants will often break off into small groups; inevitably one will turn to the other and ask, "How do you manage?" The conversation that follows, women's locker room talk, if you will, is devoted to comparing arrangements for child care or the logistics involved in working weekends-a candid sharing of strategies for coping. The intensity of the discussion sometimes suggests that ours is the first generation to face this situation in quite this way. Those of us who came to age in the 1950s and 1960s may suffer from a historical amnesia: our collective memory goes back through our parents' generation only to the 1920s, to the time when women defined themselves primarily as wifecompanions to their husbands. And given this shortened view, we see our predicaments as unique. One benefit of the recent scholarship in women's history is to cure this amnesia. The writings have revealed that through most of the nineteenth and into the twentieth century, large numbers of middle-class women "went publ ic"-albeit in a very special way. They were able to leave their homes in the name of bringing maternal and domestic virtue to the larger society. One of the best ways to explore how this dynamic operated, and at the same time to appreciate a driving force in the new feminist scholarship, is to examine the fourth and most recent volume of The Dictionary of Notable American Women. The volume covers women who died between 1950 and 1970, and the editors frankly wanted the entries to aid in a search for "roots and role models" and to direct "strategies for the future." Accord~ ingly, contributors were instructed to "indicate the reasons why a woman chose a particular way of life, the major stages in the evolution of her career, and the relationship between her public and personal life." The
Adolescents as victims of familial violence: a hospital based surveillance.

Adolescent abuse is an important and understudied issue in society. The objective of this study was to examine the epidemiology of physical injuries due to maltreatment among adolescents aged 10 – 19 years. Subjects came from seven hospitals/trauma centres in Washington DC that were involved in the Washington DC Initiative to Reduce Infant Mortality and Prevention of Childhood Injuries Study. From 1996 – 1998, information was gathered about all injuries to adolescents aged 10 – 19 years that resulted in a visit to a participating emergency department. This paper focuses on the subset 178 adolescents aged 10 – 19 years who presented with physical injuries due to maltreatment. It was found that 55% of victims of abuse were female. Abuse victims were more likely to be female than those with unintentional injury. The most common injuries were contusions to the extremities (29%). Mothers were the most common perpetrators (48%). A total of 64% of victims were assaulted with an object/weapon and the most common ...
Limitations of Current EVAR Endografts and Potential Solutions for Their Deficiencies

All current endovascular aneurysm repair (EVAR) devices have defined limitations that prevent the endovascular therapist from using them to treat all forms of aortoiliac aneurysm disease. Short, angulated infrarenal aortic neck pathology, occlusive disease in iliac access arteries, need for preservation of important branch vessel arterial flow, endograft migration, and endoleak all represent major impediments for successful EVAR. Need for secondary intervention after EVAR in a significant number of patients has detracted from universal acceptance for this therapy. New devices in manufacturers' pipelines may provide solutions for many of the current EVAR device deficiencies. As these new devices become more complex, meticulous patient follow-up to verify anticipated outcomes and new training paradigms for the future endovascular therapist will be required.
Talking to histone: methylated RelA serves as a messenger.

The mammalian NF-κB family of transcription factors functions as a major regulator of innate and adaptive immunity and inflammatory responses, plays critical roles in controlling cell proliferation, differentiation and apoptosis by regulating a wide range of genes that govern these various processes 1. The prototypical NF-κB (p50 and RelA heterodimer) is sequestered and inactivated in the cytoplasm by a family of inhibitors, called IκBs, in unstimulated cells. NF-κB is activated in response to a variety of stimuli, including inflammatory cytokines and viral and bacterial infections, which lead to the activation of the IκB kinase complex (IKK), phosphorylation and degradation of IκBs, and the nuclear translocation of the NF-κB heterodimer.
Quantifying overwash flux in barrier systems : an example from Martha's Vineyard, Massachusetts, USA

Abstract Coastal barriers are particularly susceptible to the effects of accelerated sea-level rise and intense storms. Over centennial scales, barriers are maintained via overtopping during storms, which causes deposition of washover fans on their landward sides. Understanding barrier evolution under modern conditions can help evaluate the likelihood of future barrier stability. This study examines three washover fans on the undeveloped south shore of Martha's Vineyard using a suite of vibracores, ground penetrating radar, high resolution dGPS, and LiDAR data. From these data, the volumes of the deposits were determined and range from 2.1 to 2.4 × 104 m3. Two of these overwash events occurred during Hurricane Bob in 1991. The water levels produced by this storm have a calculated return interval of ~ 28 years, implying an onshore sediment flux of 2.4–3.4 m3/m/yr. The third washover was deposited by a nor'easter in January 1997, which has a water level return interval of ~ 6 years, suggesting a flux of 8.5 m3/m/yr. These onshore fluxes are smaller than the erosional flux of sediment resulting from shoreline retreat, suggesting that the barrier is not in long-term equilibrium, a result supported by the thinning of the barrier in recent years.
A comparison of the relative risk of vessel injury with conical versus pyramidal laparoscopic trocars in a rabbit model

Abstract OBJECTIVE: Our purpose was to compare the relative risk of vessel injury after use of a 5 mm conical-tipped trocar, a 5 mm pyramidal-tipped trocar, and a 10 mm pyramidal-tipped trocar in a rabbit vessel model. STUDY DESIGN: Plastic templates were placed in front of and behind 108 mesenteric vessels in 11 anesthetized New Zealand White rabbits. Laparoscopic trocars were inserted through the templates and mesentery. The incidence of vessel injury was determined at distances from the vessels ranging from 0 to 5 mm. RESULTS: The 5 mm conical trocar resulted in a vessel injury rate of 88% at 0 mm from the vessel but 0% at 1 or 2 mm. The 5 mm pyramidal trocar resulted in 100%, 88%, and 62% injury rates of 0, 1, and 2 mm from the vessels, respectively. The 10 mm pyramidal trocar resulted in a 100% injury rate at 0, 1, 2, or 3 mm from the vessels and 80% and 40% at 4 mm and 5mm, respectively. CONCLUSION: The relative risk of vessel injury is significantly increased by the use of pyramidal-tipped trocars when compared with conical-tipped trocars, especially if larger diameter trocars are used.
CT of acute abdominal aortic disorders.

Aortic aneurysm rupture, aortic dissection, penetrating atherosclerotic ulcer, acute aortic occlusion, traumatic aortic injury, and aortic fistula represent acute abdominal aortic conditions. Because of its speed and proximity to the emergency department, helical CT is the imaging test of choice for these conditions. MR imaging also plays an important role in the imaging of aortic dissection and penetrating atherosclerotic ulcer. Ultrasound is helpful when CT is not readily available and the patient is unable or too unstable to undergo MR imaging. Because CT is the dominant imaging method for diagnosing acute abdominal aortic conditions, this article focuses on CT techniques and manifestations of this group of acute abdominal disorders.
The development of the segmental pattern of skin sensory innervation in embryonic chick hind limb

1. The development of dermatomes in the chick hind limb was investigated with both electrophysiological recording from and horseradish peroxidase (HRP) labelling of neurones in lumbosacral dorsal root ganglia (d.r.g.s). The embryonic stages studied spanned the period before and after cell death. 2. In mature embryos, after the bulk of cell death, physiological mapping showed that the location of the dermatome of each d.r.g. is consistent from embryo to embryo. HRP studies showed that axons from each d.r.g. project through the limb to the skin via a characteristic set of nerve trunks. Both the dermatomes and axonal projection pathways of adjacent d.r.g.s partially overlap one another, producing an orderly progression in the location of dermatomes and projection pathways along and within the limb, respectively. 3. In younger embryos, before cell death, the location and amount of overlap of dermatomes, as well as the axonal projection pathways, are similar to the mature pattern. D.r.g.s that innervate distal skin on the shank and foot in mature embryos do not project out cutaneous nerve trunks in the thigh or contact nearby skin on the thigh at earlier stages. 4. Axons from a single d.r.g. initially contact the skin at one or more characteristic spots; the dermatomes then enlarge, adding fine axonal branches. 5. Carbon-marking experiments showed that there are no large distal migrations of skin on the limb during the stages studied. 6. Together these findings show that dermatomes on the chick hind limb do not develop by skin sensory axons simply growing to the nearest available skin, nor are axons towed to their final location by skin movements. Moreover, dermatomes are not shaped by cell death and the elimination of random or excessive axonal projections in the limb or the skin. It appears that skin sensory axons from each d.r.g. grow directly to their target skin along a defined set of pathways and establish their dermatome precisely at its characteristic location.
Interface between zinc phosphate-deposited steel fibres and cement paste

In an attempt to protect steel fibre reinforcements from corrosion and improve their adherence to cement pastes, we deposited a zinc phosphate (ZnPh) conversion coating on the surface of the fibres. At the interfacial contact zones between the cement paste and ZnPh, alkali-induced dissolution caused the dissociation of abundant PO 4 3− ions from the ZnPh. The interaction of PO 4 3− ions with Ca2+ ions from the pastes led to the formation of hydroxyapatite and brushite in the vicinity of the dissolved ZnPh surface. Such intermediate calcium phosphate compounds played important roles in (1) improving the cement-fibre interfacial bonds, and (2) repairing the damage of the ZnPh surfaces dissolved by alkali. These processes protected the steel fibre from corrosion.
Hydrologic Regimes Revealed Bundles and Tradeoffs Among Six Wetland Services

Ecosystem services are often described as occurring together in bundles, or tending not to occur together, representing tradeoffs. We investigated patterns and potential linkages in the provision of six wetland services in three experimental wetlands by measuring: flow attenuation, as peak flow reduction; stormwater retention, as outflow volume reduction; net primary productivity (NPP), as plant biomass; diversity support, as plant species richness; erosion resistance, as stability of surface soils in a flow path; and water quality improvement, as nutrient and sediment removal. Levels of ecosystem services differed in our system because of differences in hydrologic regime brought on by natural variation in clay-rich subsoils. The fastest-draining wetland (with thin clay layer) provided five of six services at their highest level, but had lowest NPP. In contrast, a ponded wetland (with thick clay layer) that was dominated by cattail (Typha spp.) provided the highest level of NPP, but lowest levels of all other services. Hence, in our site, drainage supported several bundled services, whereas ponding supported such high levels of NPP that other services appeared to be limited (suggesting tradeoffs). These outcomes show that high NPP has the potential to be a misleading indicator of overall ecosystem services. Rather than focusing on NPP, we suggest identifying and establishing hydrologic regimes that can support the services targeted for restoration in future projects. Further direct assessments of multiple services are needed to identify bundles and tradeoffs and provide guidance at the scale of local restoration projects.
SERS based immuno-microwell arrays for multiplexed detection of foodborne pathogenic bacteria

A novel surface enhanced Raman scattering (SERS)-based immuno-microwell array has been developed for multiplexed detection of foodborne pathogenic bacteria. The immuno-microwell array was prepared by immobilizing the optical addressable immunomagnetic beads (IMB) into the microwell array on one end of a fiber optic bundle. The IMBs, magnetic beads coated with specific antibody to specific bacteria, were used for immunomagnetic separation (IMS) of corresponding bacteria. The magnetic separation by the homemade magnetic separation system was evaluated in terms of the influences of several important parameters including the beads concentration, the sample volume and the separation time. IMS separation efficiency of the model bacteria E.coli O157:H7 was 63% in 3 minutes. The microwell array was fabricated on hydrofluoric acid etched end of a fiber optic bundle containing 30,000 fiber elements. After being coated with silver, the microwell array was used as a uniform SERS substrate with the relative standard deviation of the SERS enhancement across the microwell array < 2% and the enhancement factor as high as 2.18 x 107. The antibody modified microwell array was prepared for bacteria immobilization into the microwell array, which was characterized by a sandwich immunoassay. To demonstrate the potential of multiplexed SERS detection with the immuno-microwell array, the SERS spectra of different Raman dye labeled magnetic beads as well as mixtures were measured on the mircrowell array. In bead mixture, different beads were identified by the characteristic SERS bands of the corresponding Raman label.
Studying the impact of elevated neutral to earth voltage on distribution systems due to triplen harmonics

Neutral-earth voltages have been a topic of investigation and research for many generations. Non-linear loads, and the harmonics that they generate have also been a topic of research in more recent years. An unexpected side effect of distributed nonlinear loads is an increase in neutral-earth voltages on distribution systems. A case study was presented that shows a correlation between high levels of zero sequence triplen (especially the 3rd) harmonics in distribution systems and an increase in neutral-earth voltages. A method of modeling distribution systems with distributed nonlinear loads was presented. These models were based upon circuit configurations, conductor data, grounding information, transformer data, and any previous measurement data gathered from the field. Additionally, some means for reducing neutral-earth voltages were presented.
The prevalence of the arcuate artery: a cadaveric study of 72 feet.

The purpose of this study was to quantify the occurrence of the arcuate artery. The arcuate artery was defined as that artery branching off the dorsalis pedis artery at or below the level of the tarsometatarsal joint, tending laterally across the bases of metatarsals 2 through 4, and supplying dorsal metatarsal arteries 2 through 4. The arcuate artery was present in 16.7% of 72 cadaver feet that were dissected and examined, suggesting that the arcuate artery is not the primary blood supply to dorsal metatarsal arteries 2 through 4 as is commonly described. It was determined that the lateral tarsal artery supplied dorsal metatarsal arteries 2 through 4 more frequently (47.2%) than the arcuate artery. The proximal perforating arteries as well as various combinations of all three sources were also found to contribute complete blood supply to dorsal metatarsal arteries 2 through 4. Therefore, a consistent dorsal arterial network, which differentiates throughout development, better explains the blood supply of...
Thermodynamics of hydrogen bonding from molecular orbital theory: 1. Water

To reduce the number of adjustable parameters that appear in the thermodynamic modeling of hydrogen-bonding fluids, the use of ab-initio molecular orbital calculations in the form of Hartree–Fock and density functional theories to compute thermodynamic properties are considered. In particular, the enthalpy and entropy changes on hydrogen bonding for water are computed. The theory, the computational methods and the basis sets used, as well as the results for water, are discussed. The results obtained are compared with those of others and with experimental estimates from the literature to determine the validity of the methods that are then used in this extended study. The results obtained here are also used to examine the validity of mixture group contribution results obtained here are also used to examine the validity of mixture group contribution methods for hydrogen-bonding mixtures, to develop simple estimation procedures for model parameters, and to reduce the number of calculations such as those as those described that need to be done.
Computer networks and the formation of public opinion: an ethnographic study

Comment se forme l'opinion publique ? La communication interpersonnelle et plus precisement la conversation privee, vehicule les informations d'ordre individuel, qui se transforment ensuite en opinions generalisees. A travers l'exemple de PeaceNet, un reseau informatique international, la discussion politique des utilisateurs est exploitee comme illustration de la formation de l'opinion. Cette forme de communication presente a la fois une qualite d'informations et des caracteristiques des utilisateurs et se differencie donc des autres reseaux utilises pour la discussion politique. Cette etude a pour but de confirmer les travaux de G. Tarde (1969) sur le role preponderant de la discussion dans le processus de formation de l'opinion publique
Functional Roles for Granzymes in Murine Epidermal γδ T-Cell–Mediated Killing of Tumor Targets

Granzymes, a family of serine proteases contained in cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells, play a critical role in killing tumor targets by triggering rapid breakdown of DNA and subsequent apoptosis. We have reported previously that dendritic epidermal T cells, which are skin-specific members of the tissue-type γ δ T-cell family in mice, are capable of killing selected tumor cell lines. Here we report that short-term cultured dendritic epidermal T-cell lines contain significant N-alpha-benzyloxycarbonyl-L-Lys-thiobenzyl esterase activity, produce granzyme A protein, and express constitutively mRNA for granzyme A and B. Messenger RNA expression for granzyme B was also confirmed in freshly procured Thy-1 + epidermal cells (i.e., dendritic epidermal T cells). Finally, preincubation of dendritic epidermal T cell lines with a granzyme inhibitor, dichloroisocoumarin, but not with a cysteine protease inhibitor, E-64, abrogated completely their capacity to trigger DNA breakdown in YAC-1 target cells. These results reinforce the concept that dendritic epidermal T cells represent skin-resident killer cells that share several functional properties with conventional killer leukocytes, thereby playing a local immunosurveillance role against tumor development.
Generalized de Gennes-Takahashi-Tachiki proximity effect theory

We generalize the de Gennes-Takahashi-Tachiki theory of coupled dirty superconductors to include the effects of orbital diamagnetism, spin (Pauli) paramagnetism, spin-orbit scattering, and magnetic impurity scattering. Some new expressions for thin film sandwiches and superlattices are obtained.
Noninvasive Diagnosis of Tricuspid Insufficiency Utilizing the External Doppler Flowmeter Probe

Transcutaneous jugular venous blood velocity was measured with a Doppler flow velocity probe in eight patients with sinus rhythm and angiographically demonstrable tricuspid insufficiency. Peak systolic / diastolic jugular blood velocity was less than 1 in all eight patients (&-x ± 1 standard deviation = 0.63 ± 0.20). In 23 of 25 patients without tricuspid incompetence the systolic/diastolic jugular venous blood velocity was greater than 1 (2.74 ± 1.57, P
Depletion of the catalytic subunit of protein phosphatase-2A (PP2Ac) markedly attenuates glucose-stimulated insulin secretion in pancreatic β-cells

Among various phosphatases, the protein phosphatase 2A (PP2A) is relatively well studied in the islet. Previously, we have demonstrated that the catalytic subunit of PP2A (PP2Ac) undergoes okadaic acid (OKA)-sensitive, reversible carboxylmethylation (CML), which appears to be requisite for glucose-stimulated insulin secretion (GSIS). Using the siRNA approach, we examined, herein, the contributory roles of PP2Ac in GSIS from insulin-secreting pancreatic β-(INS-1 832/13) cells. Immunologically, PP2Ac was detectable in all the subcellular fractions studied in rank order of: cytosol > microsomes > secretory granules = nucleus > mitochondria. Transfection of PP2Ac-specific, but not scrambled-siRNA, markedly attenuated PP2A activity and GSIS in these cells. Together, our findings provide a direct evidence for a positive modulatory role for PP2Ac in signaling steps leading to GSIS.
Relative depletion of an arginine-rich deoxyribonucleo-histone component during tumor induction by the Shope papilloma virus.

Abstract The basic proteins associated with DNA in rabbit epidermis were studied in an attempt to define the role of viral-induced arginase in the induction of papillomas by Shope papilloma virus. After isolation of deoxyribonucleoproteins by extraction with 1.0 M NaCl, histones were separated by electrophoresis on polyacrylamide gels. The papilloma was found to have a greatly reduced content of a protamine-like histone fraction. This protein has an amino acid composition unlike any DNA-associated basic protein yet described. It is relatively rich in arginine, histidine, serine, and glutamic acid. The papilloma's content of this protein can be increased by injection of arginine plus an arginase inhibitor, a treatment known to slow the growth of the tumor. The possible role of this arginine-rich fraction in the regulation of papilloma cell growth is discussed.
Visualization of Communication Patterns in Collaborative Innovation Networks - Analysis of Some W3C Working Groups

Collaborative Innovation Networks (COINs) are groups of self-motivated individuals from various parts of an organization or from multiple organizations, empowered by the Internet, who work together on a new idea, driven by a common vision. In this paper we report first results of a project that examines innovation networks by analyzing the e-mail archives of some W3C (WWW consortium) working groups. These groups exhibit ideal characteristics for our purpose, as they form truly global networks working together over the Internet to develop next generation technologies. We first describe the software tools we developed to visualize the temporal communication flow, which represent communication patterns as directed acyclic graphs, We then show initial results, which revealed significant variations between the communication patterns and network structures of the different groups., We were also able to identify distinctive communication patterns among group leaders, both those who were officially appointed and other who were assuming unofficial coordinating roles.
Influence of Hyphal Inoculum potential on the Competitive Success of Fungi Colonizing Wood

The relative amounts of hyphal inoculum in forest soils may determine the capacity for fungi to compete with and replace early colonizers of wood in ground contact. Our aim in this study was to test the flexibility of priority effects (colonization timing) by varying the timing of inoculum introduction (i.e., precolonization) and amount of inoculum (i.e., inoculum potential). We controlled these variables in soil-block microcosms using fungi with known competitive outcomes in similar conditions, tracking isolate-specific fungal biomass, and residue physiochemistry over time. In the precolonization trial (experiment I), a brown rot fungus Gloeophyllum trabeum was given 1, 3, or 5 weeks to precolonize wood blocks (oak, birch, pine, and spruce) prior the introduction of a white rot fungus, Irpex lacteus, a more aggressive colonizer in this set-up. In the inoculum potential trial (experiment II), the fungi were inoculated simultaneously, but with eightfold higher brown rot inoculum than that of experiment I. As expected, longer precolonization duration increased the chance for the less-competitive brown rot fungus to outcompete its white rot opponent. Higher brown rot fungal inoculum outside of the wood matrix also resulted in competitive success for the brown rot isolate in most cases. These temporal shifts in fungal dominance were detectable in a ‘community snapshot’ as isolate-specific quantitative PCR, but also as functionally-relevant consequences of wood rot type, including carbohydrate depolymerization and pH. These results from a controlled system reinforce fungal-fungal interaction and suggest that relative inoculum availability beyond the wood matrix (i.e., soils) might regulate the duration of priority effects and shift the functional trajectory of wood decomposition.
Evidence for multivalent structure of T-cell antigen receptor complex

The T-cell antigen receptor (alpha beta or gamma delta TCR) is known to associate with four polypeptides (CD3 gamma, delta, epsilon and zeta) to form the TCR-CD3 complex. Although the six chains are well characterized, the molecular mass of the TCR-CD3 complex and stoichiometry of the components are currently uncertain. We analysed the TCR of a T-T hybridoma which expresses two distinct heterodimers. When the hybridoma was incubated with a mAb (MR9.2) specific for the V alpha 10V beta 5.1 heterodimer, both of the heterodimers were lost from the cell surface, as measured with mAb MR9.2 and MR9.7 (V alpha 1V beta 1-specific). The ability to co-modulate V alpha 1V beta 1 and V alpha 10V beta 5.1 suggested that TCR complexes could contain two alpha beta-heterodimers. Density gradient sedimentation analysis provided further evidence for higher order TCR. The sedimentation patterns of the TCR were compared to that of the B-cell antigen receptor and the well-characterized VSV membrane G-protein as well as to soluble marker proteins. Maximal cell surface murine and human TCR sedimentation coefficients were substantially greater than the 9-10S predicted for a 210 kDa monovalent alpha beta gamma delta epsilon 2 zeta 2 structure. The TCR sedimented in mild non-ionic detergents as large 18 +/- 3S complexes co-migrating with a 443 kDa marker protein. In contrast, the IgM B-cell antigen receptor had a maximal sedimentation coefficient of 10 +/- 3S, consistent with a predicted size of approximately 300 kDa. Taken together, the results suggested that T-cell antigen receptors can contain more than one alpha beta-heterodimer which could be incorporated into a minimal divalent 10-chain TCR-CD3 complex (e.g. alpha beta gamma epsilon epsilon delta zeta zeta alpha beta).
Token-based dictionary pattern matching for text analytics

When performing queries for text analytics on unstructured text data, a large amount of the processing time is spent on regular expressions and dictionary matching. In this paper we present a compilable architecture for token-bound pattern matching with support for token pattern sequence detection. The architecture presented is capable of detecting several hundreds of dictionaries, each containing thousands of elements at high throughput. A programmable state machine is used as pattern detection engine to achieve deterministic performance while maintaining low storage requirements. For the detection of token sequences, a dedicated circuitry is compiled based on a non-deterministic automaton. A cascaded result lookup ensures efficient storage while allowing multi-token elements to be detected and multiple dictionary hits to be reported. We implemented on an Altera Stratix IV GX530, and were able to process up to 16 documents in parallel at a peak throughput rate of 9.7 Gb/s.
Trifunctional conjugation reagents. Reagents that contain a biotin and a radiometal chelation moiety for application to extracorporeal affinity adsorption of radiolabeled antibodies.

A method of removing radiolabeled monoclonal antibodies (mAbs) from blood using a device external to the body, termed extracorporeal affinity-adsorption (EAA), is being evaluated as a means of decreasing irradiation of noncancerous tissues in therapy protocols. The EAA device uses an avidin column to capture biotinylated-radiolabeled mAbs from circulated blood. In this investigation, three trifunctional reagents have been developed to minimize the potential deleterious effect on antigen binding brought about by the combination of radiolabeling and biotinylation of mAbs required in the EAA approach. The studies focused on radiolabeling with (111)In and (90)Y, so the chelates CHX-A' '-DTPA and DOTA, which form stable attachments to these radionuclides, were incorporated in the trifunctional reagents. The first trifunctional reagent prepared did not incorporate a group to block the biotin cleaving enzyme biotinidase, but the two subsequent reagents coupled aspartic acid to the biotin carboxylate for that purpose. All three reagents used 4,7,10-trioxa-1,13-tridecanediamine as water-soluble spacers between an aminoisophthalate core and the biotin or chelation group. The mAb conjugates were radioiodinated to evaluate cell binding as a function of substitution. Radioiodination was used so that a direct comparison with unmodified mAb could be made. Evaluation of the number of conjugates per antibody versus cell binding immunoreactivities indicated that minimizing the number of conjugates was best. Interestingly, a decrease of radioiodination yield as a function of the number of isothiocyanate containing conjugates per mAb was noted. The decreased yields were presumably due to the presence of thiourea functionality formed in the conjugation reaction. Radiolabeling with (111)In and (90)Y was facile at room temperature for conjugates containing the CHX-A' ', but elevated temperature (e.g., 45 degrees C) was required to obtain good yields with the DOTA chelate. Stability of (90)Y labeled mAb in serum, and when challenged with 10 mM EDTA, was high. However, challenging the (90)Y labeled mAb with 10 mM DTPA demonstrated high stability for the DOTA containing conjugate, but low stability for the CHX-A' ' containing conjugate. Thus, the choice between these two chelating moieties might be made on requirements for facile and gentle labeling versus very high in vivo stability. Application of the trifunctional biotinylation reagents to the blood clearance of labeled antibodies in EAA is under investigation. The new reagents may also be useful for other applications.
Transswitching as a means of studying within-subjects conditioning effects

A within-subjects experiment is described in which the transswitching paradigm was used to evaluate the effect of CS-US pairing on conditioned and unconditioned responding. Three different tonic auditory stimuli served as contexts within which the CS was administered alone, the US was administered alone, or the CS and US were paired. The magnitudes of the CR and UR were both influenced by pairing (CR higher and UR lower in paired context). Tonic response differences were not significant. The results demonstrated the utility of the transswitching method for within-subjects conditioning experiments.
Decomposed versus holistic estimates of effort required for software writing tasks

We examine decision analysis' central "decomposition principle" in the context of work-time estimates of software writers. Two experiments examined the abilities of advanced programming students to estimate how long they would take to complete specific software projects. They estimated their own work times both for entire projects and for their constituent subtasks. Estimates showed varying degrees of overoptimism and overpessimism but all were much too tight, with almost half of actual outcomes falling in the 1% tails of estimated distributions. This overtightness was unaffected by task decomposition, question wording, question order, or training in estimation. It was, however, significantly reduced by a procedure aimed at inducing generous upper and lower plausible limits. An underlying model of incomplete search is used to connect these findings to existing themes in cognition and judgment research, as well as to practical application. The findings suggest that the best level of decomposition at which to elicit work-time estimates may depend on task, judge, and elicitation method.
Perceptual framing and cortical alpha rhythm.

Abstract Apparent motion was used as a probe to test the hypothesis that perceptual framing is correlated to the phase of the alpha rhythm. Stimuli were presented phasically with respect to the occipital and parietal alpha cycle, and subjects were asked to judge whether the stimuli appeared simultaneous or sequential. The probability of perceived simultaneity was maximal for the positive phase of the occipital alpha cycle. Visual evoked potentials recorded during stimulus presentation were significantly different, in the late components, for the cases of perceived simultaneity or sequential motion. A brief review of previous experimental and theoretical studies of the relationship of perceptual framing to alpha rhythm is presented.
Solitary Galois Extensions of Algebraic Number Fields

A finite extension K of an algebraic number field k is called k-solitary if for any finite extension L of k the equality of norm groups N K/k K* = N L/k L* implies that K and L are conjugate over k (i.e., K and L are k-isomorphic). In the present work we investigate finite Galois extensions of k which are k-solitary. We prove that if a finite Galois extension K of k is k-solitary, then K/k is a 2-extension. k and every quadratic extension of k is k-solitary. We establish a necessary condition for a finite Galois 2-extension K/k with (K : k) ≥ 4 to be k-solitary. We then investigate covering subgroups, and show that the necessary condition is also a sufficient condition for extensions of degree 4 or 8. We conclude our discussion by constructing a Galois extension E of the field of rational numbers Q with the Galois group isomorphic to the dihedral group of order 8 so that E is Q-solitary.