cssi/SciSciGPT-SciSciNet huggingface dataset:
Randomizing regression tests using game theory

As software evolves, the number of test-cases in the regression test suites continues to increase, requiring testers to prioritize their execution. Usually only a subset of the test cases is executed due to limited testing resources. This subset is often known to the developers who may try to "game" the system by committing insufficiently tested code for parts of the software that will not be tested. In this new ideas paper, we propose a novel approach for randomizing regression test scheduling, based on Stackelberg games for deployment of scarce resources. We apply this approach to randomizing test cases in such a way as to maximize the testers' expected payoff when executing the test cases. Our approach accounts for resource limitations (e.g., number of testers) and provides a probabilistic distribution for scheduling test cases. We provide an example application of our approach showcasing the idea of using Stackelberg games for randomized regression test scheduling.
Molecular characterization of V59E NIS, a Na+/I- symporter mutant that causes congenital I- transport defect.

I− is actively transported into thyrocytes via the Na+/I− symporter (NIS), a key glycoprotein located on the basolateral plasma membrane. The cDNA encoding rat NIS was identified in our laboratory, where an extensive structure/function characterization of NIS is being conducted. Several NIS mutants have been identified as causes of congenital I− transport defect (ITD), including V59E NIS. ITD is characterized by low thyroid I− uptake, low saliva/plasma I− ratio, hypothyroidism, and goiter and may cause mental retardation if untreated. Studies of other ITD-causing NIS mutants have revealed valuable information regarding NIS structure/function. V59E NIS was reported to exhibit as much as 30% of the activity of wild-type NIS. However, this observation was at variance with the patients’ phenotype of total lack of activity. We have thoroughly characterized V59E NIS and studied several amino acid substitutions at position 59. We demonstrated that, in contrast to the previous report, V59E NIS is inactive, althou...
Characterization of Interleukin-1 Receptor-associated Kinase in Normal and Endotoxin-tolerant Cells

Interleukin-1 receptor-associated kinase (IRAK), a signal transducer for interleukin-1, has also been suggested to participate in the Toll-like receptor-mediated innate immune response to bacterial endotoxin lipopolysaccharide (LPS). Using the human promonocytic THP-1 cell line, we demonstrated that the endogenous IRAK is quickly activated in response to bacterial LPS stimulation, as measured by its in vitro kinase activity toward myelin basic protein. LPS also triggers the association of IRAK with MyD88, the adaptor protein linking IRAK to the Toll-like receptor/interleukin-1β receptor intracellular domain. Macrophage cells with prolonged LPS treatment become tolerant to additional dose of LPS and no longer express inflammatory cytokines. Endotoxin tolerance is a common phenomenon observed in blood from sepsis patients. We observed for the first time that the quantity of IRAK is greatly reduced in LPS-tolerant THP-1 cells, and its activity no longer responds to further LPS challenge. In addition, IRAK does not associate with MyD88 in the tolerant cells. Furthermore, application of AG126, a putative tyrosine kinase inhibitor, can substantially alleviate the LPS-induced cytokine gene expression and can also decrease IRAK level and activity. Our study indicates that IRAK is essential for LPS-mediated signaling and that cells may develop endotoxin tolerance by down-regulating IRAK.
Molecular anatomy of a transcription activation patch: FIS–RNA polymerase interactions at the Escherichia coli rrnB P1 promoter

FIS, a site-specific DNA binding and bending protein, is a global regulator of gene expression in Escherichia coli. The ribosomal RNA promoter rrnB P1 is activated 3- to 7-fold in vivo by a FIS dimer that binds a DNA site immediately upstream of the DNA binding site for the C-terminal domain (CTD) of the alpha subunit of RNA polymerase (RNAP). In this report, we identify several FIS side chains important specifically for activation of transcription at rrnB P1. These side chains map to positions 68, 71 and 74, in and flanking a surface-exposed loop adjacent to the helix-turn-helix DNA binding motif of the protein. We also present evidence suggesting that FIS activates transcription at rrnB P1 by interacting with the RNAP alphaCTD. Our results suggest a model for FIS-mediated activation of transcription at rrnB P1 that involves interactions between FIS and the RNAP alphaCTD near the DNA surface. Although FIS and the transcription activator protein CAP have little structural similarity, they both bend DNA, use a similarly disposed activation loop and target the same region of the RNAP alphaCTD, suggesting that this is a common architecture at bacterial promoters.
The relation between glucose utilization, lactic acid production and utilization and the growth cycle of L strain fibroblasts.

Abstract 1. 1. Glucose and lactate metabolism of L strain fibroblasts growing in an agitated suspension was correlated with the growth phase of the culture and with changes in the average cell volume and pH changes in the medium. 2. 2. In agreement with previous work, it was found that the rate of glucose uptake and lactate production was most rapid during the first part of the logarithmic growth period. It was found, however, that lactate was taken up by the cells when glucose was still present in relatively high concentrations. During the last half of the logarithmic growth period, lactate was rapidly taken up and the rate of glucose uptake was low. Lactate was found to accumulate in the medium for the second time as the cultures entered the plateau phase of growth. Later in the plateau phase, lactate was reduced to very low values and glucose was exhausted from the medium after 192 hrs. 3. 3. From the observation that the pH decreased while lactate decreased in concentration it was concluded that other factors causing pH depression must have been functioning at that time. 4. 4. A calculation of the rate of cell carbohydrate metabolism indicated that there was no constant relation between the rate of carbohydrate uptake per cell and the rate of mitosis during progressive intervals of the growth cycle. It is hypothesized that the rate of cell carbohydrate metabolism is directly related to average cell volume.
Role of antidiuretic activity in the inhibition of renin secretion by vasopressin in anesthetized dogs.

Abstract The nature of the activity of vasopressin which is responsible for the inhibition of renin secretion was studied by comparing the effects of vasopressin (AVP) and analogs of AVP in anesthetized water-loaded dogs. Infusion of AVP (1.0 ng/kg/min) increased mean arterial pressure (MAP) and decreased heart rate (HR) and free water clearance (CH2O). Plasma renin activity (PRA) decreased from 11.9±4.7 to 3.8±1.7 ng/ml /3 hr ( p ). A selective antidiuretic agonist, 1-deamino-8-D-arginine vasopressin (1.0 ng/kg/min), which had no effect on MAP or HR but was effective as AVP in decreasing CH2O, decreased PRA from 13.5±4.6 to 7.0±2.9 ng/ml /3 hr ( p ). Infusion of a selective vasoconstrictor agonist, 2-phenylalanine-8-ornithine oxytocin (1.0 ng/kg/min), increased MAP and decreased HR but did not decrease CH2O or PRA. A vasoconstrictor antagonist, d(CH2)5Tyr(Me)AVP (10 μg/kg), completely blocked the MAP and HR responses to AVP but did not block the decrease in CH2O or PRA ( 5.9±1.8 to 2.9±1.6 ng/ml /3 hr ) ( p ). Infusion of the 0.45% saline vehicle had no significant effect on MAP, HR, CH2O or PRA. These results indicate that the inhibition of renin secretion by vasopressin in anesthetized water-loaded dogs is due to its antidiuretic activity.
Fourier series windows on and off resonance using multiple coils and longitudinal modulation and longitudinal modulation

Abstract Descriptions of Fourier series windows (FSWs) using multiple coils for in vivo NMR spectroscopy are presented. Spatially dependent phase shifts in experiments implemented with separate transmitter and receiver coils are shown to exist and are theoretically analyzed on and off resonance. With computer simulations, we illustrate the occurrence of unwanted dispersive signals in such experiments. A new approach to the FSW experiment is introduced in which the magnetization is longitudinally modulated and dispersive signals are not produced in experiments executed with multiple transmitter coils. In addition, the longitudinally modulated FSWs avoid localization artifacts due to off resonance excitation within a reasonable chemical-shift range for in vivo 31P spectroscopy.
On the Negative-Order Norm Accuracy of a Local-Structure-Preserving LDG Method

The accuracy in negative-order norms is examined for a local-structure-preserving local discontinuous Galerkin method for the Laplace equation (Li and Shu, in Methods Appl. Anal. 13:215---233, 2006). With its distinctive feature in using harmonic polynomials as local approximating functions, this method has lower computational complexity than the standard local discontinuous Galerkin method while keeping the same order of accuracy in both the energy and the L 2 norms. In this note, numerical experiments are presented to demonstrate some accuracy loss of the method in negative-order norms.
Comparison of radioimmunoassay and liquid chromatography tandem mass spectrometry for determination of juvenile hormone titers.

Abstract This paper compares the results of juvenile hormone (JH) titer determinations in two insect species, Melanoplus sanguinipes, a migratory grasshopper, and Acyrthosiphon pisum, the pea aphid, using a chiral-specific JH radioimmunoassay (RIA) and liquid chromatography tandem mass spectrometry (LC-MS/MS), after extraction of JH with either hexane or isooctane–methanol. We compared results of JH titer determinations done on extracts of M. sanguinipes hemolymph taken from animals flown to exhaustion in tethered flight tests or unflown controls and from whole body extracts of A. pisum raised at two different temperatures. In each case the two different treatments experienced by the experimental animals were expected to result in widely differing JH titers. Methoprene and precocene II were used as internal standards. Samples were split and titers determined simultaneously with both the LC-MS/MS and RIA procedures. Unambiguous detection of JH III by LC-MS/MS was done by identification of its specific parent ion and its mass fingerprint (m/z 289, 267, 249, 235, 217, and 189). We conclude that isooctane–methanol-extracted JH samples can be accurately analyzed by LC-MS/MS, but not by RIA without further separation of JH from contaminating lipids. Hexane extracted JH samples from hemolymph can be analyzed accurately by both RIA and LC-MS/MS. However, the RIA results from whole body extracts of aphids reared at two different temperatures were initially obscured with excess lipids even when hexane was the extraction solvent. Thus samples were further purified by Waters Sep-Pak C18 column, but contaminating phospholipids continued to cause problems with the RIA assay. The detection limit of JH III standard for RIA was 13.75±2.39 pg whereas that for LC-M/MS was 8.25±1.44 pg in our experimental conditions.
Absorption intensities of the multipole-field-induced double transitions involving a homonuclear-heteronuclear pair of hydrogen molecules in condensed phase

Theoretical expressions are derived for the integrated absorption coefficients of various zero-phonon double transitions involving a homonuclear-heteronuclear pair of hydrogen molecules in condensed phase. The formulas given in this paper can be applied to transitions in the absorption spectra of solid parahydrogen (or orthodeuterium, or solid HD, HT, etc.) matrices that contain a low concentration of impurity molecules which do not possess a permanent dipole moment (e.g., ${\mathrm{N}}_{2}).$
A Numerical Study of Wavenumber Selection in Finite-Amplitude Rayleigh Convection

Abstract Numerical integrations are performed for the equations governing two-dimensional convection flows in a fluid layer confined between two horizontal parallel plates and heated uniformly from below with free surface boundary conditions at the bottom and top of the fluid. In comparison with several previous works using a similar approach, a special feature in this work is that a large horizontal domain (10 times the critical wavelength or 28.28 times the height) is covered by the grid net so that the preferred mode of finite-amplitude convection flows is investigated. The Rayleigh number covered here is less than four times the critical Rayleigh number. Either random or sinusoidal perturbations with various wavelengths and with various amplitudes are introduced to initiate the motion. In all cases considered, the system achieves an approximate steady state. It is found that: 1) steady-state solutions are not determined uniquely by only the Rayleigh and Prandtl numbers, but also by the initial conditi...
Structural and functional lability induced by diethyl ether on the sarcoplasmic reticulum membrane.

Abstract Structural and functional changes occuring in sarcoplasmic reticulum vesicles following exposure to low concentrations (5–7%, v/v) of diethyl ether in aqueous media, were studied by electron microscopy and by kinetic measurements of Ca 2+ transport and ATPase activity. Electron microscopy of thin sectioned and freeze-fractured sarcoplasmic reticulum vesicles provided detailed resolution of Ca-ATPase amphiphilic molecules displaying ‘lollipop’ portions on the outer surface of the vesicle, and non-polar moieties penetrating the membrane's hydrophobic interior. This asymmetric disposition of ATPase molecules was disrupted in vesicles exposed to ether and then centrifuged and/or resuspended in aqueous media. Such vesicles had a tendency to undergo fragmentation, and the distribution of ATPase molecules was markedly altered. The continuous fuzzy layer of lollipops became discontinuous, and the intramembranous particles became randomly distributed over both the concave and the convex freeze-fracture membrane faces. Functionally, the vesicles lost their ability to accumulate calcium in the presence of ATP, although high rates of ATPase activity were maintained. Vesicles which were simply exposed to ether, without being subjected to centrifugation and/or homogenization, did not appear altered ultrastructurally, and retained their ability to accumulate calcium. In fact, the enzyme turnover and the maximal levels of calcium uptake were increased. It is concluded that diethyl ether interferes with lipid-lipid and protein-lipid interactions in the sarcoplasmic reticulum vesicle membrane, thereby facilitating molecular motions which may be a limiting factor in the transport mechanism. On the other hand, these weakened interactions permit structural denaturation and loss of the ability to maintain a transmembrane Ca 2+ gradient when the vesicles are subjected to mechanical perturbations which are harmless in the absence of ether.
Self-calibration of a noisy multiple-sensor system with genetic algorithms

This paper explores an image processing application of optimization techniques which entails interpreting noisy sensor data. The application is a generalization of image correlation; we attempt to find the optimal gruence which matches two overlapping gray-scale images corrupted with noise. Both taboo search and genetic algorithms are used to find the parameters which match the two images. A genetic algorithm approach using an elitist reproduction scheme is found to provide significantly superior results. The presentation includes a graphic presentation of the paths taken by tabu search and genetic algorithms when trying to find the best possible match between two corrupted images.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
A study of paramyosin aggregation using transient electric birefringence techniques.

The aggregation of several forms of the molluscan muscle protein paramyosin at low concentration and at low ionic strength was studied in the pH range 6–10 using transient electric birefringence techniques. In the lower part of this pH range, the aggregates exhibit negative birefringence, but this changes to positive birefringence when the pH increases. Analysis of the field-free birefringence decay transients of the paramyosin solutions showed that all aggregates coexisted with paramyosin monomer and allowed a determination of the rotational diffusion constant of the aggregates present at each pH. The size and shape of these aggregates were estimated from their rotational diffusion constants and were compared with the known characteristics of larger aggregates such as paracrystals. The positively birefringent aggregates appear to be staggered dimers at certain values of pH; at other pH values, these aggregates appear to be higher aggregates, probably formed by lateral aggregation of monomer or dimer onto one of these staggered dimers. The staggered dimers are formed by overlap of 200–600 A along each cylindrical paramyosin molecule, in agreement with the 530-A overlap distance found in paramyosin paracrystals by Cohen et al. (1971) J. Mol. Biol.56, 223–237. Some speculations are presented about the nature of the negatively birefringent species.
Experimental and theoretical studies of H2O oxidation by neutral Ti2O4,5 clusters under visible light irradiation

A new photo excitation fast flow reactor system is constructed and used to investigate reactions of neutral TimOn clusters with H2O under visible (532 nm) light irradiation. Single photon ionization at 118 nm (10.5 eV) is used to detect neutral cluster distributions through time of flight mass spectrometry. TimOn clusters are generated through laser ablation of a titanium target in the presence of 4% O2/He carrier gas. Association products Ti2O4(H2O) and Ti2O5(H2O) are observed for reactions of H2O and TimOn clusters without irradiation. Under 532 nm visible light irradiation of the fast flow reactor, only the Ti2O5(H2O) feature disappears. This light activated reaction suggests that visible radiation can induce chemistry for Ti2O5(H2O), but not for Ti2O4(H2O). Density functional theory (DFT) and time-dependent (TD) DFT calculations are performed to explore the ground and first excited state potential energy surfaces (PES) for the reaction Ti2O5 + H2O → Ti2O4 + H2O2. A high barrier (1.33 eV) and a thermodynamically unfavorable (1.14 eV) pathway are obtained on the ground state PES for the Ti2O5 + H2O reaction; the reaction is also thermodynamically unfavorable (1.54 eV) on the first singlet excited state PES. The reaction is proposed to occur on the ground state PES through a conical intersection ((S1/S0)CI), and to generate products Ti2O4 and H2O2 on the ground state PES. This mechanism is substantiated by a multi-reference ab initio calculation at the complete active space self-consistent field (CASSCF) level. The S0-S1 vertical excitation energy of Ti2O4 (3.66 eV) is much higher than the 532 nm photon energy (2.33 eV), suggesting this visible light driven reaction is unfavorable for the Ti2O4 cluster. The TDDFT calculated optical absorption spectra of Ti2O4 and Ti2O5 further indicate that Ti2O5 like structures on a titanium oxide surface are the active catalytic sites for visible light photo-catalytic oxidation of water.
Hybrid Ablation Therapy: Current Status and Future Development

Ventricular tachycardia (VT) contributes to significant morbidity and mortality for patients with structural heart disease. The implantable cardioverter-defibrillator (ICD) has been demonstrated to help in reducing mortality in this patient population. The ICD, however, cannot prevent future shocks and also contributes to significant anxiety for patients. Anti-arrhythmic drugs also have limited efficacy and are frequently not tolerated owing to various side effects. Catheter ablation of VT has now been shown to reduce recurrent VT episodes in numerous randomized trials. In addition, recent publications have suggested that an early ablation procedure prior to VT development may improve patient outcomes. Although percutaneous epicardial access has been well described and is relatively safe, patients with prior surgery frequently have pericardial adhesions which make a percutaneous approach difficult and/or not feasible. In these patients, a hybrid surgical approach may be warranted for successful ablation of VT. However, the surgical approach requires detailed planning, coordination with cardiac surgeons and an integrated multidisciplinary approach. Recent studies have also been initiated to determine the value of hybrid approaches to atrial fibrillation. Further Reading: Bourke T, Mathuria N, Michowitz Y, Shivkumar K. Hybrid techniques and neuraxial modulation for treatment of ventricular tachycardia. Future Cardiol. 2011; 7(3): 273–276. Shivkumar K. Percutaneous epicardial ablation of atrial fibrillation. Heart Rhythm. 2008; 5(1): 152–154.
Science in the service of citizens and consumers.

A new approach to public knowledge of science focuses on what the public want to know rather than what scientists think they should know. Chris Toumey reports.
Blood pressure control for acute ischemic and hemorrhagic stroke.

Purpose of review Acute stroke, including the subtypes of ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH), typically involves significant fluctuations in blood pressure (BP). Treatment of BP after all stroke types is controversial. In each case, there are theoretical dangers to leaving BP alone as well as altering it artificially. In this article, we review the role of BP in each stroke subtype and the existing evidence for BP optimization. Recent findings Except in patients receiving thrombolytic therapy, there is insufficient evidence to recommend active BP management in ischemic stroke. In ICH, the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) trial and Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT) have demonstrated that systolic BP reduction to 140 mmHg is well tolerated and associated with attenuation of hematoma expansion. The impact of BP reduction on outcomes is being evaluated in the ongoing phase III ATACH II and INTERACT 2 trials. No evidence exists to recommend definitive BP management strategies in acute SAH, although hypertension should likely be avoided before an aneurysm is secured, and hypotension should be avoided altogether. Summary Evidence for BP management in acute stroke is limited, although large randomized trials are currently in progress for both ischemic stroke and ICH. BP management in SAH remains woefully understudied.
A qualitative study of the adoption of buprenorphine for opioid addiction treatment

Qualified physicians may prescribe buprenorphine to treat opioid dependence, but medication use remains controversial. We examined adoption of buprenorphine in two not-for-profit integrated health plans, over time, completing 101 semi-structured interviews with clinicians and clinician-administrators from primary and specialty care. Transcripts were reviewed, coded, and analyzed. A strong leader championing the new treatment was critical for adoption in both health plans. Once clinicians began using buprenorphine, patients' and other clinicians' experiences affected decisions more than did the champion. With experience, protocols developed to manage unsuccessful patients and changed to support maintenance rather than detoxification. Diffusion outside addiction and mental health settings was nonexistent; primary care clinicians cited scope-of-practice issues and referred patients to specialty care. With greater diffusion came questions about long-term use and safety. Recognizing how implementation processes develop may suggest where, when, and how to best expend resources to increase adoption of such treatments.
A history of teaching machines.

" The development of teaching machines is traced from the patented educational devices of the 19th century through the initial teaching machines of Sidney Pressey in the 1920s to the machines invented by B. F. Skinner in the 1950s. The obscurity of Pressey's pioneering work in this field contrasted with the fame achieved by Skinner is discussed in a historical context. The final sections discuss the short-lived success and eventual failure of classroom teaching machines in the 1950s and 1960s. The latest report from the Dean Concerning the teaching machine Is that Oedipus Rex Could have learned about sex By machine and not bothered the Queen. --(cited in Skinner, 1983, p. 200) The December 1957 issue of Contemporary Psychology (CP) marked the completion of the journal 's second year of publication under the editorship of America's premier historian of psychology, Harvard University's Edwin G. Boring. In his monthly column, entitled "CP Speaks," Boring praised the recent publication of a laboratory manual of operant conditioning methods authored by Lloyd Homme and David Klaus. As an aside, he commented that Homme was visiting at Harvard where he was "working on another idea that originated with [B. F.] Skinner, the technique for teaching by machine" (Boring, 1957, p. 313). Boring, who in his historical writings had cautioned that origins are rarely unequivocal, should have known better than to make such an assertion of priority. What historians call an origin myth might have been in the making except for the action of Ohio State University psychologist Horace English who wrote to Boring on January 30, 1958: When the public press gave Skinner credit for originating "teaching by machine," it did not seem worth while to protest. But when the scholarly editor of CP falls into this trap; dear, oh dear. Be it known that Sidney Pressey published descriptions of machines which gave reinforcement by immediate knowledge of results and of one machine which gave reinforcement in the form of a piece of candy--when the child pressed the right lever, if you please. There have been at least six doctoral dissertations devoted to finding the effectiveness of such machines . . . . Most of this was before our friend Skinner even finished grade school. Originate, indeed! . . . . This note is not for publication but it should lead to some sort of correction. Sidney hasn't said beans in my hearing; maybe he does not know of Skinner's new proposal. Does Skinner have any idea of the wealth of research that has preceded him? In fact, B. E Skinner did know about Pressey's work, and Pressey was familiar with what Skinner was doing. Of the foursome, only Boring was unaware of Pressey's early work, and the letter from English elicited the following prompt response from the embarrassed 71-year-old
Vibrio vulnificus: Did Hippocrates Describe a Fatal Case?

In the fifth century B.C., Hippocrates described a fatal illness in a man who lived on an island in the Aegean Sea. This acute infection was characterized by black bullous skin lesions, rapidly progressive septicemia, and death on the second day. It is hypothesized that this disease was caused by Vibrio vulnificus.
Postmenopausal estrogens and progestogens and the incidence of gynecologic cancer

We reviewed the published medical literature to assess the impact of the use of estrogens, with and without progestogens, on the incidence of gynecologic cancer in postmenopausal women. Long-term use of an estrogen preparation that is not accompanied by a progestogen is associated with a large increase in the risk of endometrial cancer, an association that almost certainly is a causal one. The incidence of endometrial cancer in women who receive combined estrogen-progestogen therapy is not elevated to nearly the same degree. There are suggestions that, depending on the particular combined regimen, the incidence need not be elevated at all beyond that of a women who has never taken hormones. The occurrence of other forms of gynecologic cancer appear not to be associated with the use of unopposed estrogens, though relevant data on cervical cancer are sparse. The relation of ovarian, cervical and vulvar cancer to the prior use of combined estrogen-progestogen therapy has only begun to be evaluated.
Buckling of stiffened plates under axial compression and lateral pressure

Abstract The subject of this paper is the buckling behavior of a rectangular plate, with parallel thin-walled stiffeners attached to one side, subjected to a combination of axial compression and lateral pressure. The plate is modeled by the Von Karman plate equations and the stiffeners by a nonlinear beam theory recently derived. An analytical solution is obtained for the buckling load corresponding to a torsional tripping mode of the stiffeners. This solution is compared with the experiments and theories of other researchers.
Keeping Track of the Time: Emending the Counterfactual Analysis of Causation

I will focus on the most well developed analysis, David Lewis's (1973, 1986a) version, although the emendation that I suggest can be modified and applied to other counterfactual analyses.' The analysis for deterministic causation states that for any two actual, distinct events c and e, e depends counterfactually on c iff, had c not occurred, e would not have occurred.2 Causation is the ancestral of counterfactual dependence: c causes e iff there is a chain of counterfactual dependencies running from c to e. The probabilistic version of the analysis (1986a: 175-84) states that e depends probabilistically on c iff, given c, there is a chance x of e's occurring, and if c were not to occur, there would be a chance y of e's occurring, where x is much greater than y. Causation is again taken as the ancestral, this time of probabilistic dependence, so c causes e iff there is a chain of probabilistic dependencies running from c to e. The chance of the effect's occurring is assessed immediately after the cause occurs, and the truth value of the counterfactual at each step is evaluated based upon that chance.
Two Tragic Forms of Child Sexual Abuse: Are They Often Overlooked?

ABSTRACT Child sexual abuse is a largely invisible enigma. The persistence and pervasiveness of two forms of child sexual abuse in particular, pornography and prostitution, undoubtedly lie in the perpetuation of societal norms that unwittingly support such tragic behaviors. Rooted in the eroticization of power and control in Western culture, as well as in many other countries, it produces a complex set of social problems of unknown scope and magnitude. For the millions of children at risk throughout the world, the overall problem of child sexual abuse must be reconceptualized, and in-depth, long-term investigations of both child pornography and child prostitution must be undertaken.
Computational Study of Proteolysis-Driven Single Cell Migration in a Three-Dimensional Matrix

Cell migration is a fundamental process that is crucial to a variety of physiological events. While traditional approaches have focused on two-dimensional (2D) systems, recent efforts have shifted to studying migration in three-dimensional (3D) matrices. A major distinction that has emerged is the increased importance of cell-matrix interactions in 3D environments. In particular, cell motility in 3D matrices is more dependent on matrix metalloproteinases (MMPs) to degrade steric obstacles than in 2D systems. In this study, we implement the effects of MMP-mediated proteolysis in a force-based computational model of 3D migration, testing two matrix ligand-MMP relationships that have been observed experimentally: linear and log-linear. The model for both scenarios predicts maximal motility at intermediate matrix ligand and MMP levels, with the linear case providing more physiologically compelling results. Recent experimental results suggesting MMP influence on integrin expression are also integrated into the model. While the biphasic behavior is retained, with MMP-integrin feedback peak cell speed is observed in a low ligand, high MMP regime instead of at intermediate ligand and MMP levels for both ligand-MMP relationships. The simulation provides insight into the expanding role of cell-matrix interactions in cell migration in 3D environments and has implications for cancer research.
Stool DNA testing and colon cancer prevention: another step forward.

A noninvasive test that preselects individuals who are likely to have advanced adenomas or cancer for subsequent colonoscopy is a worthy goal. Ahlquist and colleagues' study in this issue provides ...
Aquaporin-4–dependent K+ and water transport modeled in brain extracellular space following neuroexcitation

Potassium (K+) ions released into brain extracellular space (ECS) during neuroexcitation are efficiently taken up by astrocytes. Deletion of astrocyte water channel aquaporin-4 (AQP4) in mice alters neuroexcitation by reducing ECS [K+] accumulation and slowing K+ reuptake. These effects could involve AQP4-dependent: (a) K+ permeability, (b) resting ECS volume, (c) ECS contraction during K+ reuptake, and (d) diffusion-limited water/K+ transport coupling. To investigate the role of these mechanisms, we compared experimental data to predictions of a model of K+ and water uptake into astrocytes after neuronal release of K+ into the ECS. The model computed the kinetics of ECS [K+] and volume, with input parameters including initial ECS volume, astrocyte K+ conductance and water permeability, and diffusion in astrocyte cytoplasm. Numerical methods were developed to compute transport and diffusion for a nonstationary astrocyte–ECS interface. The modeling showed that mechanisms b–d, together, can predict experimentally observed impairment in K+ reuptake from the ECS in AQP4 deficiency, as well as altered K+ accumulation in the ECS after neuroexcitation, provided that astrocyte water permeability is sufficiently reduced in AQP4 deficiency and that solute diffusion in astrocyte cytoplasm is sufficiently low. The modeling thus provides a potential explanation for AQP4-dependent K+/water coupling in the ECS without requiring AQP4-dependent astrocyte K+ permeability. Our model links the physical and ion/water transport properties of brain cells with the dynamics of neuroexcitation, and supports the conclusion that reduced AQP4-dependent water transport is responsible for defective neuroexcitation in AQP4 deficiency.
Stem Cells and Rat Liver Carcinogenesis: Contributions of Confocal and Electron Microscopy

Microscopic analysis in combination with cytochemistry and immunocytochemistry has revealed the presence of four cell types not previously described in the portal area and parenchyma of the liver from an experimental rodent hepatocarcinogenic rat model. Within the intrahepatic bile ductules, which proliferate after administration of chemical carcinogens and partial hepatectomy, small, undifferentiated nonpolarized, nonepithelial cells with a blast-like phenotype and polarized epithelial cells different from the polarized epithelial cells that typically line the walls of the bile ductules were found. In the connective tissue stroma surrounding the bile ductules, nonpolarized epithelial cells with hepatocyte phenotype were found. In the parenchyma, subpopulations of bile ductule epithelial cells that established ATPase-positive bile canalicular structures, including the formation of desmosomes and tight junctions, with parenchymal hepatocytes within the hepatic lobule were found. These observations raise the following questions in this model. Are there undifferentiated progenitor cells with stem cell-like properties within bile ductules? What are the interrelations of the newly described cell types with each other, with parenchymal hepatocytes, with preneoplastic nodules, and with hepatomas? Do the heterogeneous cell types within the bile ductules, in the surrounding connective tissue, and within the hepatic cords represent intermediate stages of single or multiple cell lineage pathways leading to hepatocyte differentiation, liver regeneration, and/or preneoplastic nodule formation?
Investigation of Low Rank Coal Gasification in a Two-Stage Downdraft Entrained-Flow Gasifier

Low-rank coal contains more inherent moisture, high alkali metals (Na, K, Ca), high oxygen content, and low sulfur than high-rank coal. Low-rank coal gasification usually has lower efficiency than high-rank coal, since more energy has been used to drive out the moisture and volatile matters and vaporize them. Nevertheless, Low-rank coal comprises about half of both the current utilization and the reserves in the United States and is the largest energy resource in the United States, so it is worthwhile and important to investigate the low-rank coal gasification process. In this study, the two-stage fuel feeding scheme is investigated in a downdraft, entrained-flow, and refractory-lined reactor. Both a high-rank coal (Illinois No.6 bituminous) and a low-rank coal (South Hallsville Texas Lignite) are used for comparison under the following operating conditions: 1) low-rank coal vs. high-rank coal, 2) one-stage injection vs. two-stage injection, 3) low-rank coal with pre-drying vs. without pre-drying, and 4) dry coal feeding without steam injection vs. with steam injection at the second stage. The results show that 1) With predrying to 12% moisture, syngas produced from lignite has 538 K lower exit temperature and 18% greater Higher Heating Value (HHV) than syngas produced from Illinois #6. 2) The two-stage fuel feeding scheme results in a lower wall temperature (around 100 K) in the lower half of the gasifier than the single-stage injection scheme. 3) Without pre-drying, the high inherent moisture content in the lignite causes the syngas HHV to decrease by 27% and the mole fractions of both H2 and CO to decrease by 33%, while the water vapor content increases by 121% (by volume). The low-rank coal, without pre-drying, will take longer to finish the demoisturization and devolatilization processes, resulting in delayed combustion and gasification processes.
An Individual Differences Perspective Implications for Cognitive Research in Gerontology

This article sketches the fundamental characteristics of an individual differences orientation to gerontological research, with particular reference to adult cognitive development. It is shown that cross-sectional differences in variances and covariances often reported in the gerontological literature are consistent with the hypothesis of individual differences in patterns of change. However, different covariance structures at different cross-sectional age levels are also consistent with the hypothesis that the constructs being measured are qualitatively different at different ages. Longitudinal research explicitly measuring individual differences in change is required to differentiate between the two classes of hypotheses. The article outlines the general features of a research strategy that employs longitudinal designs and structural equation models to examine patterns and predictors of individual differences in adult cognitive development.
Phonology and the Problems of Learning to Read and Write

Learning to read and write depends on abilities that are language related but that go beyond the ordinary abilities required for speaking and listening. Research has shown that the success of learners, whether they are children or adults, is related to the degree to which they are aware of the underlying phonological structure of words. Poor readers are often unable to segment words into their phonological constituents and may have other phonological deficiencies as well. Their difficulties in naming objects and in comprehending sentences, for example, may also stem from a basic problem in the phonological domain.
Abridgment of corona ellipses

The purpose of this investigation is to give a mathematical theory of the cyclograms of corona obtained by a cathode ray oscillograph. In the case investigated a long wire of small diameter is connected to one terminal of an a-c. source; the other terminal of the source is connected to a concentric cylinder of considerable diameter, or to a metal plate at some distance from the wire. A cathode ray oscillograph with two pairs of deflecting plates, at right angles to each other, is so connected that one pair of plates causes deflections of the cathode beam proportional to the values of instantaneous voltage of the source, and the other pair of plates causes deflections proportional to the instantaneous values of the charging and loss current flowing into the wire. So long as the sinusoidal amplitude of the applied voltage is below the visual corona point, the charging current is also sinusoidal, in time quadrature with the voltage. The oscillograph record is therefore an ellipse, with the amplitudes of the voltage and the current as the principal semi-axes. When, however, the minimum ionization voltage is exceeded during a part of each alternation, the cyclogram ceases to be an ellipse, but consists of four portions per cycle, two of which correspond to the intervals of time during which the corona is extinct, and the other two when corona is present, with quite short transients in between. F. W. Peek, (A. I. E. E. TRANS., Vol. XLVI, 1927, p. 1009) published a number of such oscillograph records, with voltage amplitudes both below and above the visual critical point. In order to explain the mechanism of corona formation and the influence of the space charge upon the instantaneous critical voltage, he also produced “artificial corona,” by using two condensers in series, one of which was shunted by a sphere-gap. The purpose of the present investigation is to give a mathematical theory of the observed cyclograms, on the basis of two condensers in series, with the space charge as a fictitious dividing line. To account for the actual motion of ions and the power loss, the condenser nearest the wire is assumed to be shunted by a conductance, and to have a resistance in series. Approximate equations are derived for the current and the voltage as functions of time. For the artificial corona it is shown that the composite curve consists of arcs of two ellipses, with their principal axes along those of the cyclograms. Assuming the visual critical voltage to be known, an expression is derived for the instant of the cycle at which the corona is re-established. For the actual corona, it is shown that the cyclogram also consists of portions of two ellipses, only their principal axes are at some angles with the principal axes of the cyclogram. The theory is applied to one of Mr. Peek's records, and it is shown that both the shape of the experimental curves and the instants at which the corona is re-established check fairly well with the theory.
Ideology and criminal justice: Suggestions for a pedagogical model

Without the explanatory power of general theoretical principles, criminal justice educators are limited to subjectively describing the structure and function of our systems of criminal justice rather than explaining why these systems behave the way they do. Because of this, criminal justice lacks integrity as a legitimate academic discipline that seeks to meet the objectives of a liberal arts education. This paper explores the establishment of ideology as a first principle of criminal justice, derived from political philosophy and sociological theory. We examine ways to build upon this principle as a means of teaching criminal justice within the guise of the liberal arts tradition by guiding students toward a deeper understanding of the nature of our criminal justice systems and their place in larger society.
Morphologic and molecular genetic aspects of oligodendroglial neoplasms

Morphologic criteria for diagnosing oligodendrogliomas and for classifying them as well-differentiated (World Health Organization grade II) and anaplastic (World Health Organization grade III) are well recognized. Nevertheless, applying these guidelines to specific cases often reveals discrepancies among different observers. In addition, whether a given tumor also contains an astrocytic component may be debatable. Loss of heterozygosity studies have demonstrated that oligodendroglial neoplasms have a high incidence of loss of the 1p and 19q chromosomal arms. Although loss of heterozygosity for portions of 19q are sometimes seen in astrocytic neoplasms, these tumors seldom show complete loss of 19q accompanied by loss of 1p. Loss of 9p or homozygous deletion of the CDKN2 gene or both are associated with anaplastic oligodendrogliomas, whereas loss of 17p or TP53 gene mutations or both are frequent in astrocytomas, but rare in oligodendrogliomas. These observations suggest that molecular genetic parameters could provide an objective, reproducible framework for classifying oligodendroglial neoplasms.
Human platelets pathogen reduced with riboflavin and ultraviolet light do not cause acute lung injury in a two‐event SCID mouse model

Background Pathogen reduction technologies (PRTs) can induce platelet (PLT) lesions that reduce PLT survival and recovery from circulation and may be associated with acute lung injury (ALI). Study Design and Methods Human PLTs (hPLTs) in plasma with or without single or multiple Mirasol PRT treatments were assessed in vitro by aggregation and percentage of P-selectin expression. In vivo studies included PLT recovery in SCID mice and assessment of ALI in a two-event mouse model in which the sensitizing event was lipopolysaccharide injection and the second event was infusion of Mirasol-treated hPLTs. Results A single-dose Mirasol treatment (5 J/cm2) did not induce any change in aggregation in response to adenosine 5′-diphosphate (ADP) while a five-times-repeat Mirasol treatment (5×) increased aggregation response to low concentration of ADP. Mirasol PLTs (1×-5×) had increased percentage of P-selectin–positive PLTs after treatment and decreased aggregation with TRAP as the agonist. In vivo recovery in SCID mice was reduced extensively with Mirasol treatments (1× and 5×). In the two-event model of ALI, only the 5× Mirasol PLTs accumulated in the lung and this was not accompanied by changes in lung histology or increases in MIP-2 levels in bronchoalveolar lavage fluid. Conclusions Mirasol PRT treatment induced PLT activation and reduced in vivo recovery in a SCID mouse model of transfusion. In our two-event mouse model of ALI, the 5× Mirasol hPLTs accumulated in the lung, but did not cause signs of ALI. The 1× Mirasol treatment did not lead to PLT lung accumulation or ALI in this model.
Shape-responsive liquid crystal elastomer bilayers

Monodomain liquid crystal elastomers (LCEs) are shape-responsive materials, but shape changes are typically limited to simple uniaxial extensions or contractions. Here, we demonstrate that complex surface patterns and shape changes, including patterned wrinkles, helical twisting, and reversible folding, can be achieved in LCE–polystyrene (PS) bilayers. LCE–PS bilayer shape changes are achieved in response to simple temperature changes and can be controlled through various material parameters including overall aspect ratio and LCE and polystyrene film thicknesses. Deposition of a patterned PS film on top of an LCE enables the preparation of an elastomer that reversibly twists and a folding leaf-like elastomer, which opens and closes in response to temperature changes. The phenomena are captured through finite element simulations, in quantitative agreement with experiments.