cssi/SciSciGPT-SciSciNet huggingface dataset:
Mitochondrial benzodiazepine receptors as potential modulators of intermediary metabolism

Abstract The notion that benzodiazepine receptors modulate the GABA regulated anion channel in the CNS is widely appreciated. However, binding sites for benzodiazepines are also abundant in peripheral tissues. These ‘peripheral-type' benzodiazepine receptors are distinct from their ‘central-type' counterparts in pharmacological properties, phylogenetic and ontogenetic appearance, tissue distribution and subcellular localization. Robert Anholt reviews recent evidence which shows that these peripheral benzodiazepine binding sites are associated with the mitochondrial outer membrane. This, together with a variety of effects of peripheral-type benzodiazepines on cell growth and differentiation, suggests that these receptors may represent important control sites for the modulation of intermediary metabolism.
Skeletal myogenesis in the mouse esophagus does not occur through transdifferentiation.

Summary: To determine the developmental history of murine esophageal skeletal muscle, smooth muscle cells were fate mapped by lineage-specific recombination and phenotypically marked by eGFP. Examination of embryonic and postnatal tissues revealed that esophageal skeletal muscle does not arise from transdifferentiation of committed smooth muscle cells. genesis 36:81–82, 2003. © 2003 Wiley-Liss, Inc.
Nanoporous Au: An Unsupported Pure Gold Catalyst?

The unique properties of gold especially in low temperature CO oxidation have been ascribed to a combination of various effects. In particular, particle sizes below a few nanometers and specific particle−support interactions have been shown to play important roles. In contrast, recent reports revealed that monolithic nanoporous gold (npAu) prepared by leaching a less noble metal, such as Ag, out of the corresponding alloy can also exhibit a remarkably high catalytic activity for CO oxidation, even though no support is present. Therefore, it was claimed to be a pure and unsupported gold catalyst. We investigated npAu with respect to its morphology, surface composition, and catalytic properties. In particular, we studied the reaction kinetics for low temperature CO oxidation in detail, taking the mass transport limitation due to the porous structure of the material into account. Our results reveal that Ag, even if removed almost completely from the bulk, segregates to the surface, resulting in surface conce...
Anlage tumors about the mouth.

Abstract Neoplasms of anlage or cell rest origin occurring about the mouth are derived from ectoderm. The cell rests from which the growths eventually develop apparently were separated at various stages of the development of the individual, hence their varied patterns. Genetically oldest are the growths imitating a part of the body, the teratomas; next are the mixed tumors mimicking an organ; youngest are the growths mimicking a tissue. All these neoplasms are benign, that is, they are expanding rather than infiltrating growths. They are usually encapsulated and may be removed in toto and when so treated usually do not recur. Therefore, following early recognition complete surgical removal is the treatment of choice.
Observably split multiplets—data analysis and interpretation in terms of large-scale aspherical structure

SUMMARY We study aspherical structure of the deep Earth using normal mode splitting. Analysing 10 previously unresolved high-Q multiplets in the frequency band 5-10 mHz allows us to double the number of modal constraints on the aspherical structure of the core. We find that all the multiplets are anomalously split and exhibit predominantly parabolic splitting though some of the low-m singlets are not well-resolved. The parabolic splitting suggests that coupling to nearby modes is unimportant and that the structure sensed by these multiplets is dominantly axisymmetric and of harmonic degree 2. Four of the newly observed modes have less than 3 per cent of their potential energy in the inner core. Taken together with published observations of anomalously split multiplets, the following statements can be made. Anomalously split modes have typically 45 per cent of their potential energy below the core-mantle boundary (CMB) whereas modes with little energy in the core (less than 30 per cent) are not anomalously split. Some of the anomalously split modes have less than 3 per cent potential energy below the inner core boundary (ICB). These observations make it extremely difficult to invoke inner core structure of any kind as the source of anomalous splitting and have led to a search for alternative causes. Several studies have shown that the magnetic field is too small to cause anomalous splitting and a steady fluid flow in the outer core would cause splitting that is symmetrical in frequency and can therefore be ruled out. Anomalous structure of harmonic degree s= 2 in the outer core, with the density constrained to be in hydrostatic equilibrium, can explain a large amount of the signal but leads to an extremely unusual Vp/ρ relation. We therefore conclude that the cause of anomalous splitting is currently unknown.
Physical examination of sexually abused children and adolescents.

Sexual abuse of children has come to the forefront of our national consciousness through continued exposure in newspapers, in magazines, and on television. Despite this media attention, many pediatricians have not been trained to evaluate cases of suspected sexual abuse. Because estimates of the prevalence of sexual abuse in the general population range into the millions, 1 it is likely that the office-based pediatrician will encounter more and more cases. Although guidelines for evaluation of child abuse exist, 2 professional journals are now beginning to address sexual abuse. A recent article by Krugman 3 reviewed the role of the office-based pediatrician in sexual abuse cases. Some points that he discussed included maintaining a high index of suspicion for both direct and masked presentations of sexual abuse; interviewing skills needed for both the child and family; legal ramifications; and the need for a coordinated effort among the many groups of professionals involved in each case, in an effort to minimize separate, repetitive, and traumatic evaluations. This article is intended to supplement Krugman9s by providing a detailed description of the vaginal examination of the prepubertal child and adolescent. PHYSICAL EXAMINATION The prerequisite of a thorough, sensitive examination is time. This is the one element most lacking in a busy office or emergency room. Preparing the child for the examination will take more time the examination itself; this preparation is the most important part of the examination process. PHYSICAL EXAMINATION The prerequisite of a thorough, sensitive examination is time. This is the one element most lacking in a busy office or emergency room. Preparing the child for the examination will take more time than the examination itself; this preparation is the most important part of the examination process.
Effects of design on stress distribution of intracoronal gold restorations

Eight intracoronal and extracoronal designs for gold restorations with different tapers to the lateral walls were evaluated to determine the most efficient design in distributing occlusal stresses. Eight intracoronal and extracoronal designs for gold restorations with different tapers to the lateral walls were investigated to determine the most efficient design in distributing occlusal stresses. It was found that the occlusal wall of an inlay cavity with a 7° taper and no bevel resulted in a better stress distribution than a cavity preparation with a greater taper or a long bevel. It was shown further that a wide inlay preparation resulted in less stress if the cusps were protected by gold.
Phenocopies induced by thymine in Escherichia coli.

A uracilless strain ofE. coli upon starvation for uracil adapts to synthesize this compound. These adaptations are of two sorts, heritable and non-heritable. The latter are induced by the presence of thymine although little or none of the uracil is synthesized by the demethylation of thymine. The non-heritable adaptations arise in a discontinuous fashion at a rate 10 times as high as the genetic reversions. The non-heritable uracil-independent cells are considered to be phenocopies because they mimic the phenotype of the genetic revertants.
Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients

Conventional risk factors of cardiovascular disease and mortality in the general population such as body mass, serum cholesterol, and blood pressure are also found to relate to outcome in maintenance dialysis patients, but often in an opposite direction. Obesity, hypercholesterolemia, and hypertension appear to be protective features that are associated with a greater survival among dialysis patients. A similar protective role has been described for high serum creatinine and possibly homocysteine levels in end-stage renal disease (ESRD) patients. These findings are in contrast to the well-known association between over-nutrition and poor outcome in the general population. The association between under-nutrition and adverse cardiovascular outcome in dialysis patients, which stands in contrast to that seen in non-ESRD individuals, has been referred to as "reverse epidemiology." Publication bias may have handicapped or delayed additional reports with such paradoxical findings in ESRD patients. The etiology of this inverse association between conventional risk factors and clinical outcome in dialysis patients is not clear. Several possible causes are hypothesized. First, survival bias may play a role since only a small number of patients with chronic kidney disease (CKD) survive long enough to reach ESRD. Hence, the dialysis patients are probably a distinctively selected population out of CKD patients and may not represent the risk factor constellations of their CKD predecessors. Second, the time discrepancy between competitive risk factors may play a role. For example, the survival disadvantages of under-nutrition, which is frequently present in dialysis patients, may have a major impact on mortality in a shorter period of time, and this overwhelms the long-term negative effects of over-nutrition on survival. Third, the presence of the "malnutrition-inflammation complex syndrome" (MICS) in dialysis patients may also explain the existence of reverse epidemiology in dialysis patients. Both protein-energy malnutrition and inflammation or the combination of the two are much more common in dialysis patients than in the general population and many elements of MICS, such as low weight-for-height, hypocholesterolemia, or hypocreatininemia, are known risk factors of poor outcome in dialysis patients. The existence of reverse epidemiology may have a bearing on the management of dialysis patients. It is possible that new standards or goals for such traditional risk factors as body mass, serum cholesterol, and blood pressure should be considered for these individuals.
The use of conducting polymers and colloids in the through hole plating of printed circuit boards

Abstract There has been a considerable amount of activity in the last few years aimed at the development of alternative methods for the plating of printed circuit boards through holdes. Processes involving colloids or conducting polymers have been particularly important front runners. In this paper the scientific and technical aspects of plating through holes are described and discussed. Methods which have been recently used to examine these processes (in particular scanning probe microscopies) are also discussed.
Four case studies of prospective science teachers' beliefs concerning constructivist teaching practices

To gain a better understanding of the emerging constructivist beliefs and classroom practices, case studies were constructed for four prospective teachers who were purposely selected as a result of their scores on the Classroom Learning Environment Survey (CLES) (Taylor, Fraser, & White, A classroom environment questionnaire for science educators interested in the constructivist reform of school science. Paper presented at the annual meeting of the National Association for Research in Science Teaching, Anaheim, CA, 1994). The case studies provided insight into two primary questions (1) what are the beliefs of the prospective science teacher regarding constructivist teaching practices and (2) are these beliefs consistent with subsequent classroom practice? The components of constructivist teaching by Taylor, Fraser, and White (1994) were used as a theoretical framework in conjunction with Ajzen and Fishbein's components of the Theory of Planned Behavior (Ajzen, 1985). Data collection consisted of document analysis, classroom observation, and interviews. Data were analyzed using the constant comparative method. Findings from the case studies suggest that at least two kinds of beliefs were in operation: central beliefs and peripheral beliefs. The central beliefs were defined as those dictating subsequent teaching behaviors; whereas the peripheral beliefs were those that were stated but not operationalized. © 2002 Wiley Periodicals, Inc. Sci Ed86:783–802, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10038
The effect of foreign ions on the stability of activated alumina

Abstract The thermal stability and physical properties of a spinel-structure, activated alumina are studied as a function of the precursor material, a low-temperature, highly amorphous alumina impregnated with varying concentrations of Li + , K + , or Mg 2+ . Measurements of physical properties such as surface area, density, and pore volume, and spectroscopic data from X-ray diffraction and the Mossbauer effect are allied in the characterization of the bulk and surface occupation of the foreign ions and the effects of these on thermal stability. Foreign-ion contents leading to maximum stability are determined.
The processed provisional splint in periodontal prostheses.

Summary A technique has been described whereby a heat-processed provisional splint was fabricated with the factors of esthetics and long-term serviceability being of prime importance. Additional advantages of the use of a well-adapted provisional restoration in a periodontal prosthesis are as follows: (1) They facilitate periodontal treatment by allowing total visibility and access to surgical sites when the splint is removed. (2) The splinting effect may enhance healing and periodontal-ligament reat-tachment by stabilizing mobile abutments. (3) The patient's ability to render adequate home care for a fixed prosthetic restoration may be evaluated and reinforced before making cast restorations. (4) The patient's cooperation is assured during an extended period of restorative care when an esthetic, comfortable, provisional splint is provided.
DISTRIBUTION OF FOUR POTENTIAL TRANSMITTER AMINO ACIDS IN MONKEY RETINA

— Discrete layers from frozen dried sections of Rhesus monkey retina were analyzed for each of four amino acids. Peak levels of glycine were found near the border of the inner nuclear and inner reticular layers, and were high throughout these two layers. The levels were less than 50% of the peak in the adjacent ganglion cells and outer reticular layers and fell to very low levels elsewhere. GABA was much more sharply restricted to the inner reticular layer and fell off on both sides to levels of 10% or less of the peak in the fiber and photoreceptor cell layers. Glutamate and aspartate were highest in the ganglion cell layer. On a lipid-free dry weight basis the peak aspartate level was about twice that of brain. Moderately high levels of both aspartate and glutamate were found in the inner reticular and fiber layers. Elsewhere the levels ranged from 20 to 50% of the peak, and both amino acids were relatively low in optic nerve. The amino acid distributions are compatible with a transmitter function for GABA in amacrine cells and for glycine in horizontal and amacrine cells. Glutamate and aspartate may be especially high in Muller fibers, ganglion cells or both.
Management middleware for enterprise grids

Management continues to be a problem for grids. A diversity of systems is in use. Their integration into more comprehensive management solutions that would simplify management, address the scale of grids and enable a higher degree of automation is difficult. This paper presents a management middleware that normalizes management for enterprise grids. Management tasks are rendered as autonomous services following a model-based approach. The paper first introduces the problem domain of managing enterprise grids and then describes the approach to a solution. The concept of a service delivery controller (SDC) is introduced that allows describing management tasks in terms of desired and observed state models, based on which a controller function autonomously performs tasks. The implementation of SDC inform of the SDC toolkit is discussed next. The SDC toolkit is based on the Globus Toolkit GT4. It extends GT4 by the standard for Web services distributed management (WSDM) and SDC-specific capabilities. Finally, a scenario is described where the developed approach and implementation have been applied to management of the Oracle 10g (grid) database system.
The Neuroecology of Dimethyl Sulfide: A Global-Climate Regulator Turned Marine Infochemical

Information transfer influences food-web dynamics in the marine environment, but infochemicals involved in these processes are only beginning to be understood. Dimethylsulfoniopropionate (DMSP) is produced by phytoplankton and other marine algae, and has been studied primarily in the context of sulfur cycling and regulation of global climate. My laboratory has been investigating DMSP and its breakdown product, dimethyl sulfide as infochemicals associated with trophic interactions in marine habitats, including sub-Antarctic and coral reef ecosystems. Using a neuroecological approach, our work has established that these biogenic sulfur compounds serve as critical signal molecules in marine systems and provides us with a more mechanistic understanding of how climate change may impact information transfer within marine food webs.
Lifetime Health Services Use by Male Drug-Abusing Offenders:

A modified version of the Andersen and Newman model of health services use was used to examine how male drug-abusing offenders use health services during their lifetimes. Hierarchical regression models were employed to determine the extent to which (a) sociodemographic information, (b) drug use and criminal history, and (c) illness-level factors were predictive of the use of these services. In general, these models explained a moderate level of the variance in services use, with illness-level factors accounting for the majority of variance. Implications for health services in criminal justice settings are discussed.
Use of outpatient commitment or related civil court treatment orders in five U.S. communities.

OBJECTIVE: Outpatient commitment and a number of related civil court mechanisms are used to attempt to improve adherence to mental health treatment in the community. This study examined lifetime us...
Challenges to the State-of-the-practice of Solution Convergence Verification

The main goal of solution verification is to assess the convergence of numerical predictions as a function of discretization variables such as element size Δx or time step Δt. The challenge is to verify that the approximate solutions of the discretized laws-of-conservation or equations-of-motion converge to the solution of the continuous equations. In the case of code verification where the continuous solution of a test problem is known, common practice is to obtain several discrete solutions from successively refined meshes or grids; calculate norms of the solution error; and verify the rate with which discrete solutions converge to the continuous solution. With solution verification, where the continuous solution is unknown, common practice is to obtain several discrete solutions from successively refined meshes or grids; estimate an extrapolation of the continuous solution; verify the rate-of-convergence; and estimate numerical uncertainty bounds. The formalism proposed to verify the convergence of discrete solutions derives from postulating how truncation error behaves in the asymptotic regime of convergence. The contribution of this work is to challenge the commonly accepted view of verification and illustrate a number of difficulties encountered during the analysis of general-purpose codes. Examples are given from the disciplines of computational hydro-dynamics that involve the calculation of smooth or shocked solutions of non-linear, hyperbolic equations such as the 1D Burger equation or 2D Euler equations; and engineering mechanics that involve the calculation of smooth solutions of linear or non-linear, elliptic equations. A non-exhaustive list of topics that warrant further research includes: extending the state-of-the-practice to non-scalar quantities (curves, multiple-dimensional fields); studying the coupling between space and time discretizations; defining a reference mesh for the estimation of solution error; and developing technology to verify adaptive mesh refinement calculations in computational engineering and physics. (Approved for unlimited, public release, LA-UR-06-8078, Unclassified.)
Site-specific excision repair of 1-nitrosopyrene-induced DNA adducts at the nucleotide level in the HPRT gene of human fibroblasts: effect of adduct conformation on the pattern of site-specific repair.

Studies showing that different types of DNA adducts are repaired in human cells at different rates suggest that DNA adduct conformation is the major determinant of the rate of nucleotide excision repair. However, recent studies of repair of cyclobutane pyrimidine dimers or benzo[a]pyrene diol epoxide (BPDE)-induced adductsatthenucleotidelevelinDNAofnormalhumanfibroblastsindicatethattherateofrepairofthesame adduct at different nucleotide positions can vary up to 10-fold, suggesting an important role for local DNA conformation. To see if site-specific DNA repair is a common phenomenon for bulky DNA adducts, we determined the rate of repair of 1-nitrosopyrene (1-NOP)-induced adducts in exon 3 of the hypoxanthine phosphoribosyltransferase gene at the nucleotide level using ligation-mediated PCR. To distinguish between the contributions of adduct conformation and local DNA conformation to the rate of repair, we compared the resultsobtainedwith1-NOPwiththoseweobtainedpreviouslyusingBPDE.TheprincipalDNAadductformed by either agent involves guanine. We found that rates of repair of 1-NOP-induced adducts also varied significantly at the nucleotide level, but the pattern of site-specific repair differed from that of BPDE-induced adductsatthesameguaninepositionsinthesameregionofDNA.Theaveragerateofexcisionrepairof1-NOP adducts in exon 3 was two to three times faster than that of BPDE adducts, but at particular nucleotides the rate was slower or faster than that of BPDE adducts or, in some cases, equal to that of BPDE adducts. These results indicate that the contribution of the local DNA conformation to the rate of repair at a particular nucleotide position depends upon the specific DNA adduct involved. However, the data also indicate that the conformation of the DNA adduct is not the only factor contributing to the rate of repair at different nucleotide positions. Instead, the rate of repair at a particular nucleotide position depends on the interaction between the specific adduct conformation and the local DNA conformation at that nucleotide.
A single atrial extrastimulus can distinguish sinus tachycardia from 1:1 paroxysmal tachycardia.

We have developed a tachycardia detection scheme for use in an antitachycardia pacemaker in which the use of a properly timed atrial extrastimulus provides a means of discriminating sinus tachycardia from pace-terminable 1:1 tachycardias. An atrial extrastimulus is delivered in late diastole (80 ms premature), and the ventricular response is monitored. In sinus tachycardia, the ventricular response is expected to appear early as well, but in pace-terminable tachycardias, such as AV reentrant and ventricular with VA conduction, the ventricular rhythm will be unperturbed. Testing of the algorithm was performed in 34 patients. In 29 patients, atrial extrastimuli were delivered during sinus tachycardia, and in 22 patients during various types of 1:1 paroxysmal tachycardia. In one patient the procedure was completely automated, i.e., delivery of the atrial extrastimuli and diagnosis were microcomputer controlled. In 28/29 cases, the delivery of an atrial extrastimulus 80 to 120 ms early during sinus tachycardia elicited a ventricular response at least 28 ms early. In 22/22 patients with 1:1 paroxysmal tachycardia, atrial extrastimuli 80 to 120 ms early failed to produce a significant change in ventricular cycle length. This technique appears to be promising for prevention of inadvertent pacing of sinus tachycardia in an antitachycardia pacemaker.
THE MEASUREMENT OF SHEAR FORCE BY CORE LOCATION IN LONGISSIMUS DORSI BEEF STEAKS FROM FOUR TENDERNESS GROUPS1

Sixty-four longissimus muscle steaks obtained from carcasses of Bos indicus or Bos taurus cattle were used to evaluate shear force requirements from the dorsal to lateral portion of the steak. Steaks were assigned to one of four tenderness groups based on preliminary analysis of shear force requirements of adjacent steaks used in the study. Six dorsal to lateral core positions were incorporated into the test procedures. Shear force requirements of cores of steaks in very tender and tender groups tended (P>0.05) to decrease from the dorsal to lateral position. The increase in shear values from dorsal to lateral was dramatic (P<0.01) in the tough and very tough groups. It appears that overall shear value influences the variation in shear values within the muscle. Location effects of tenderness within the longissimus muscle could be useful in future studies of the physical/biochemical effectors of tenderness.
A role for neuronal nicotinic acetylcholine receptors in ethanol-induced stimulation, but not cocaine- or methamphetamine-induced stimulation

Cocaine (COC), ethanol (EtOH), and methamphetamine (MA) are widely abused substances and share the ability to induce behavioral stimulation in mice and humans. Understanding the biological basis of behavioral stimulation to COC, EtOH, and MA may provide a greater understanding of drug and alcohol abuse. In these studies we set out to determine if neuronal nicotinic acetylcholine receptors were involved in the acute locomotor responses to these drugs, our measure of behavioral stimulation. A panel of acetylcholine receptor antagonists was used to determine if nicotinic receptors were involved in EtOH- and psychostimulant-induced stimulation. We tested the effect of these drugs in genotypes of mice (FAST and DBA/2J) that are extremely sensitive to this drug effect. To determine which acetylcholine receptor subunits may be involved in this response, relative expression of the α3, α6, β2, and β4 subunit genes was examined in mice selectively bred for high and low response to EtOH. Mecamylamine, but not hexamethonium, attenuated the acute locomotor response to EtOH. The acetylcholine receptor antagonist dihydro-β-erythroidine and methyllycaconitine had no effect on this response. The α6 and β4, but not α3 or β2, subunits of the acetylcholine receptor were differentially expressed between mice bred for extreme differences in EtOH stimulation. Mecamylamine had no effect on psychostimulant-induced locomotor activity. Neuronal nicotinic receptors are involved in EtOH, but not psychostimulant, stimulation. These studies suggest a lack of involvement of some nicotinic receptor subtypes, but more work is needed to determine the specific receptor subtypes involved in this behavior.
Identifying the membrane proteome of HIV-1 latently-infected cells

Profiling integral plasma membrane proteins is of particular importance for the identification of new biomarkers for diagnosis and for drug development. We report in this study the identification of surface markers by performing comparative proteomics of established human immunodeficiency virus-1 (HIV-1) latent cell models and parental cell lines. To this end we isolated integral membrane proteins using a biotin-directed affinity purification method. Isolated proteins were separated by two-dimensional gel electrophoresis and identified by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) after in gel digestion. Seventeen different proteins were found to vary on the surface of T-cells due to HIV-1 infection. Of these proteins, 47% were integral membrane proteins, and 18% were membrane-associated. Through the use of complementary techniques such as Western blotting and fluorescent staining, we confirmed the differential expression of some of the proteins identified by MALDI-TOF including Bruton's tyrosine kinase and X-linked inhibitor of apoptosis. Finally, using phosphatidylinositol 3-kinase inhibitors and flavopiridol to inhibit Bruton's tyrosine kinase localization at the membrane and X-linked inhibitor of apoptosis protein expression, respectively, we showed that HIV-1 latently infected cells are more sensitive to these drugs than uninfected cells. This suggests that HIV-1 latently infected cells may be targeted with drugs that alter several pathways that are essential for the establishment and maintenance of latency.
Desert pavement development and landscape stability on the Eastern Libyan Plateau, Egypt

Abstract Desert pavement surfaces of the eastern Libyan Plateau in central Egypt represent a stable landscape preserving Middle and Upper Paleolithic artifacts. Detailed measurements of pavement clasts indicate significant variability in clast size, density, lithology and orientation between pavements, but no spatial relationship among any of these pavement variables over the study area. Pavement characteristics are unrelated to local geomorphic features including slope gradient and aspect, suggesting a desert pavement surface that has developed without significant influence from transporting mechanisms such as overland flow and slope failure. Meridional vertical cracks in surface clasts implicate thermal stresses due to diurnal solar variation as a mechanical weathering process, whereas the presence of a clast-free silty layer within all soil profiles indicates that these are accretionary pavement surfaces that have grown upward over time. The desert pavement in this region has likely developed in situ through mechanical breakdown of surface clasts and desert pedogenesis, indicating long-term stability for this region and minimal taphonomic effects on artifacts > 2 cm in diameter deposited on this surface over the last ca. 100 ka.
138 Molecular Pathogenesis of Chronic Wounds: The Role of β-Catenin and C-MYC

The lack of understanding of molecular pathogenesis of impaired healing in chronic ulcers leads to a serious health issue that contributes to excessive limb amputations and mortality. Using biopsies from patients with chronic wounds, skin organ culture and primary keratinocytes in culture we identified that β-catenin and its downstream target, c-myc, play important role in development of chronic wounds. In contrast to normal epidermis, we observed significant nuclearization of β-catenin and elevated c-myc expression at the non-healing wound edge of patients with chronic ulcers. In vitro studies indicated that activation and stabilization of nuclear β-catenin inhibits wound healing and keratinocyte migration by: blocking EGF response and inducing c-myc. Using Affymetrix large scale microarrays we found that β-catenin downstream target, c-myc, is induced in skin by an inhibitor of wound healing (glucocorticoids) and repressed in the initial phase of normal wound healing, 4 to 48 hr, whereas it becomes de-repressed at 96 hr post wounding. Therefore, the activation of β-catenin/c-myc pathway(s) contributes to impaired healing by inhibiting of keratinocyte migration and altering keratinocyte differentiation. The presence of activated β-catenin and c-myc in the epidermis of chronic wounds may serve as molecular markers of impaired healing and future targets for therapeutic intervention. While β-catenin signaling has been implicated in epithelial development and oncogenesis its role in wound healing has never been postulated. This further illustrates the importance of “tissue context” specificity, because β-catenin in the context of malignant tissue promotes invasion whereas in the context of a wound environment does the opposite.
Mycobacteriophage Vector Systems

Successful application of molecular genetic approaches to the study of mycobacteria necessitates the introduction of recombinant DNA molecules into mycobacterial cells. Efficient methods of introducing DNA into Mycobacterium smegmatis protoplasts have been developed, and the construction of mycobacteriophage recombinant DNA vectors has been initiated. Novel Escherichia coli-Mycobacterium shuttle vectors, termed shuttle phasmids, have been constructed. These vectors were constructed by inserting E. coli cosmids into nonessential regions of mycobacteriophage DNAs. Shuttle phasmids are multifunctional vectors that replicate in E. coli as plasmids and replicate in mycobacteria as phage. The presence of the bacteriophage lambda cos sequences permits the use of the lambda in vitro packaging system for efficient cloning of additional genes into these vectors. Temperate shuttle phasmids have been constructed that can infect and lyse mycobacterial cells or lysogenize mycobacterial cells to stably integrate and express cloned DNA into mycobacterial genomes. Shuttle phasmids can be transduced into a wide variety of mycobacterial species and thus should permit the development of molecular genetic systems for the mycobacteria.
Review article: the management of autoimmune hepatitis beyond consensus guidelines.

Summary Background Consensus guidelines aid in the diagnosis and management of autoimmune hepatitis, but they are frequently based on low-quality clinical evidence, conflicting experiences and divergent opinions. Recommendations may be weak, discrepant or non-existent at critical decision points. Aims To identify the decision points where guidelines are weak or non-existent and review the evidence essential in the decision process. Methods Full-text articles published in English using the keyword ‘autoimmune hepatitis’ were identified by PubMed from 1972 to 2013. Personal experience and investigations in autoimmune hepatitis also identified important contributions. Results Seventy per cent of the guidelines developed by the American Association for the Study of Liver Diseases and 48% of those proposed by the British Society of Gastroenterology are based on low-quality evidence, conflicting experiences or divergent opinions. The key uncertainties in diagnosis relate to the timing of liver biopsy, recognising acute severe (fulminant) disease, interpreting coincidental nonclassical histological changes, accommodating atypical or deficient features in non-White patients, differentiating drug-induced from classical disease and identifying overlap syndromes. The key uncertainties in management relate to pre-treatment testing for thiopurine methyltransferase activity, treating asymptomatic mild disease, determining treatment end points, managing suboptimal responses, incorporating nonstandard medications as front-line and salvage agents, using azathioprine in pregnancy and instituting surveillance for hepatocellular carcinoma. Conclusions Consensus guidelines are fraught with uncertainties in the diagnosis and management of autoimmune hepatitis. Each decision point must counterbalance the current available evidence and tailor the application of this evidence to the individual patient.
Free energy based policy gradients

Despite the plethora of reinforcement learning algorithms in machine learning and control, the majority of the work in this area relies on discrete time formulations of stochastic dynamics. In this work we present a new policy gradient algorithm for reinforcement learning in continuous state action spaces and continuous time for free energy-like cost functions. The derivation is based on successive application of Girsanov's theorem and the use of the Radon Nikodym derivative as formulated for Markov diffusion processes. The resulting policy gradient is reward weighted. The use of Radon Nikodym extends analysis and results to more general models of stochasticity in which jump diffusions processes are considered. We apply the resulting algorithm in two simple examples for learning attractor landscapes in rhythmic and discrete movements.
THE HISTOGENESIS OF CHRONIC URANIUM NEPHRITIS WITH ESPECIAL REFERENCE TO EPITHELIAL REGENERATION

1. Proliferation of connective tissue in chronic uranium nephritis is early and progressive and due to a direct stimulation on the part of the uranium. 2. The hydronephrotic theory fails to explain the phenomena observed in the progress of the chronic nephritis. 3. Carmine is deposited, as shown by Suzuki, in the proximal convoluted tubule only, and in different amounts in different levels of this segment of the tubule, so that subdivisions may be made. 4. Regeneration begins about the fourth day, but varies in proportion to the dose of renal irritant given. 5. The first cells to appear are large vesicular elements, and there is a gradual development of syncytium-like masses and giant-cells. These last are due to the rapidity of cell division. 6. Small, deeply staining nuclei, which are morphologically identical with the newly regenerated cells described by Thorel and others, are present from the first day of the acute nephritis and are persisting renal cells which have been slightly affected by the toxic agent.
Insulin Growth Factor-I and Epidermal Growth Factor Receptors Recruit Distinct Upstream Signaling Molecules to Enhance AKT Activation in Mammary Epithelial Cells

IGF-I and epidermal growth factor (EGF) stimulate both normal mammary epithelial cell (MEC) growth and tumorigenesis. Whereas both growth factors increase DNA synthesis in MECs, how they evoke a greater response in combination when they activate similar signaling pathways remains unknown. In the present study, we investigated the signaling pathways by which these mitogens act in concert to increase DNA synthesis. Only EGF activated the MAPK pathway, and no further increase in MAPK activation was observed when both mitogens were added together. Both growth factors activated the phosphatidylinositol-3 kinase pathway, and simultaneous treatment enhanced phosphorylation of both AKT and its downstream target, p70S6K. The enhanced activation of AKT was observed at multiple time points (5 and 15 min) and growth factor concentrations (2.5-100 ng/ml). IGF-I activated AKT via insulin receptor substrate-1 and p85, the regulatory subunit of phosphatidylinositol-3 kinase. Treatment with EGF had no effect on insulin receptor substrate-1; however, it activated the EGF receptor, SHC, and c-Src. EGF treatment caused the association of SHC with Grb2 and Gab2 with phospho-SHC, phospho-Gab1, Grb2, and p85. Interestingly, inhibition of Src activation blocked the ability of EGF, but not IGF-I, to activate AKT. This corresponded with a decrease in phosphorylation of the EGF receptor and its association with phospho-SHC as well as downstream signaling. Unexpectedly, inhibition of Src increased basal MAPK activation. This is the first study to show that EGF and IGF-I use separate upstream components within a given MEC line to enhance AKT phosphorylation, contributing to increased DNA synthesis.
Alpha-trimmed image estimation for JPEG steganography detection

In information security, steganalysis has been an important topic since evidences first indicated steganography has been used for covert communication. Among all digital files, numerous devices generate JPEG images due to the capability of compression and compatibility. A large number of JPEG steganography methods are also provided online for free usage. This has spawned significant research in the area of JPEG steganalysis. This paper introduces an image estimation technique utilizing the alpha-trimmed mean for distinguishing clean and steganography images. The hidden information is considered additive noise to the image. The alpha-trimmed method estimates steganographic messages within images in the spatial domain and provide flexibility for classifying various steganography methods in the JPEG compression domain. For three JPEG steganography methods along with three embedding message files applied to an image data set, the proposed method results in better separability between clean and steganographic classes. The results are based on comparisons between the presented method and two existing methods in which classification accuracies are increased by as much as 32%.
Directions of drug discovery in osteoporosis

Osteoporosis is a condition of increasing importance and prevalence in all parts of the world and particularly in Asia. Recent advances have led to the introduction of effective drugs that decrease bone resorption and stabilize bone mass. However, these drugs have been identified by serendipity rather than rational drug design and are not ideal because of limited bioavailability, mode of administration, or other unwanted effects. There is still a place for even more suitable and effective resorption inhibitors than those currently available. The more compelling need in this field is an acceptable drug that is anabolic for bone, that safely and acceptably increases bone mass and improves the disturbances in bone microarchitecture that characterize established and advanced osteoporosis. Possible approaches to identifying more effective resorption inhibitors and new anabolic agents are discussed.
The Lexical Semantics of Adjectives: More Than Just Scales

This is a draft of a chapter for a book, Modification, in preparation for the Cambridge University Press series Key Topics in Semantics and Pragmatics. The full manuscript is also available as a single document on my website, as are some additional chapters. The book is something between a textbook for people who already have a basic background in semantics and a survey of work in the area. For a fuller explanation of its purpose and scope, consult chapter 1 in the full manuscript. Broken links, marked with ??, are to other chapters not included in this document. (You can avoid this by looking at the full manuscript.) Comments would be extremely helpful, so please don’t hesitate to contact me if you have any, even very minor ones.
Predictors of Outcomes in Traumatic Brain Injury

INTRODUCTION: The purpose of this study was to retrospectively evaluate patients treated for traumatic brain injuries (TBI) to determine how multiple organ trauma (MOT) and lung injuries sustained at the time of initial injury affect outcome. METHOD: A single institution retrospective review of all patients diagnosed with TBI at a level I trauma center from 2000-2014 was conducted. Clinical outcome was based on Glasgow Outcome Scale (GOS) at hospital discharge. Lung injury was defined as the presence of pulmonary contusions, pneumothorax, hemothorax, rib fractures, or diaphragmatic rupture proven by X-ray or CT scan. MOT was defined as trauma to one body region with an AIS score ≥ 3 plus trauma to two additional body regions with AIS scores ≥ 1.Regression analysis was conducted using SPSS 21. RESULTS: There were 409 patients reviewed. Majority of patients were male (73%), average age was 46y (16-94), average GCS was 7, and 71% had a severe TBI (GCS≤8). Thirty percent of patients had poor outcome (GOS=1-2) Regression analysis indicated age (OR=1.03, pCONCLUSIONS: Age, GCS, ISS, and critical head injuries (AIS≥5) were significant tools in predicting outcome in this patient cohort. Multiple organ trauma and traumatic lung injury may cause significant damage to a patient suffering from a severe TBI, but these injuries do not predict mortality in this patient population. Language: en
For the People, But Not Always by the People - The Extractive Industry Transparency Initiative (EITI), NGOs and Signaling

The EITI is a multisectoral partnership designed to help resource rich countries avoid corruption in the management of extractive industry revenues. It is widely perceived as successful, yet Although EITI is a process designed for the people, it is not always by the people. Not all participating governments have let civil society fully participate in the process or provided civil society consistently with the information they need. Moreover, although some 24 countries (50% of all resource-rich developing countries) have committed to the EITI and taken many of these steps, as of December 2008 only one country - Azerbaijan - has taken all of these steps. As a result, EITI is a work-in-progress. Herein I examine the context in which countries adopt EITI.
Analysis of key operation performance data in manufacturing systems

In modern manufacturing systems, the key performance indicators (KPIs) are defined as a set of metrics to reflect operation performance. The KPIs are not independent and may have intrinsic mutual relationships. In this paper, by categorizing such data into basic and comprehensive KPIs and supporting metrics, we introduce a hierarchical structure for identification and analysis of KPIs in manufacturing operation management, and use it to investigate pairwise relationship and dependencies between KPIs and supporting metrics.
Exploring the Venture Creation Process: Evidences from Tech and Non-Tech Nascent Entrepreneurs

The process of creating new organizations has increasingly become the focus of entrepreneurship research (Gartner, 1990). However, despite the growing literature on this area, there were few studies exploring the venture creation process. Even fewer studies examine venture creation process empirically, with the exceptions of Bhave (1994), Reynolds and Miller (1992), Carter, Gartner and Reynolds (1996) and Delmar and Shane (2002). This study aims to examine various venture creation process attributes across technology-based entrepreneurs (TBEs) and non-technology-based nascent entrepreneurs (N-TBEs). In particular, we address this research question: Do TBEs and N-TBEs differ in their venture creation process in terms of the number of startup activities engaged, gestation duration, association and sequencing patterns of startup activities? The question is examined using the dataset of Panel Study of Entrepreneurial Dynamics (PSED). Overall, we find that TBEs engage more startup activities in planning, legitimacy establishment and resource acquisitions, but not marketing than N-TBEs. TBEs also take longer time to complete gestation process. Additionally, TBEs and N-TBEs share a common set of core activities and with a high degree of similarity in the sequencing patterns of those core activities. What differentiates TBEs from N-TBEs is non-core, peripheral activities. Implications for future research are provided.
Effect of intranasal fluticasone furoate and intraocular olopatadine on nasal and ocular allergen-induced symptoms

BackgroundNasal allergen challenge (NAC) leads to a nasal ocular reflex, which is augmented by allergic inflammation. This study was designed to confirm our previous observation that an intranasal ...
Mechanism of the inhibition of rat brain cholinesterase by diisopropylfluorophosphate, tetraethylpyrophosphate, and eserine.

SummaryThe mechanism of inhibition of rat brain cholinesterase by the 3 most potent anti-cholinesterases, diisopropylfluorophosphate, tetraethylpyrophosphate, and eserine was studied by a method which involves variation in enzyme concentration as well as inhibitor concentration. It was shown that the kinetics of eserine-inhibition may be analyzed by classical methods which ignore enzyme concentration but the cases of the other two inhibitors may not be so treated. Cholinesterase inhibition by the fluoro- and pyrophosphates was shown to be irreversible and to depend upon enzyme concentration and time of incubation of the enzyme with the inhibitor before the addition of substrate. The upper limit of cholinesterase concentration in rat brain was estimated to be 1 × 10-6 molar if structural restrictions are not assumed.