cssi/SciSciGPT-SciSciNet huggingface dataset:
Melanomas, from the cell cycle point of view (Review).

Transformation of melanocytes to metastatic melanoma cells is characterized by unrestricted proliferation under growth-factor-deprived conditions, genetic loss of cyclin dependent kinase (CDK) inhibitors (CKI, e.g. p16INK4A), and aberrant production of autocrine growth factors (e.g. basic fibroblast growth factor). The latter induces increased expression of positive CDK regulators (e.g. cyclin D1) and reduced expression of additional CKIs (e.g. p27KIP1). Combined, these events lead to sustained CDK activity and hyperphosphorylation/inactivation of the retinoblastoma tumor suppressor protein (Rb). The persistent Rb phosphorylation causes the accumulation of E2F and the transcription of its target genes whose products promote cell cycle progression.
A Modular Synthesis of Annonaceous Acetogenins

A synthesis of four Annonaceous acetogenins, asiminocin, asimicin, asimin, and bullanin, by a modular approach from seven fundamental subunits, A−G, is described. The approach employs a central core aldehyde segment, C, to which are appended an aliphatic terminus, A or B, a spacer subunit, D or E, and a butenolide terminus, F or G. Coupling of the A, B, D, and E segments to the core aldehyde unit is effected by highly diastereoselective additions of enantiopure allylic indium or tin reagents. The butenolide termini are attached to the ACD, BCE, or BCD intermediates by means of a Sonogashira coupling. The design of the core, spacer, and termini subunits is such that any of the C30, C10, or C4 natural acetogenins or stereoisomers thereof could be prepared. IC50 values for the four aforementioned acetogenins against H-116 human colon cancer cells were found to be in the 10-3 to 10-4 μM range. The IC90 activities were ca. 10-3 μM for asimicin and asimin but only 0.1−1 μM for bullanin and asiminocin.
Transformation by the v‐fms oncogene product: An analog of the CSF‐1 receptor

The product of the c-fms proto-oncogene is related to, and possibly identical with, the receptor for the macrophage colony-stimulating factor, M-CSF (CSF-1). Unlike the product of the v-erbB oncogene, which is a truncated version of the EGF receptor, the glycoprotein encoded by the v-fms oncogene retains an intact extracellular ligand-binding domain so that cells transformed by v-fms express CSF-1 receptors at their surface. Although fibroblasts susceptible to transformation by v-fms generally produce CSF-1, v-fms-mediated transformation does not depend on an exogenous source of the growth factor, and neutralizing antibodies to CSF-1 do not affect the transformed phenotype. An alteration of the v-fms gene product at its extreme carboxyl-terminus represents the major structural difference between it and the c-fms-coded glycoprotein and may affect the tyrosine kinase activity of the v-fms-coded receptor. Consistent with this interpretation, tyrosine phosphorylation of the v-fms products in membranes was observed in the absence of CSF-1 and was not enhanced by addition of the murine growth factor. Cells transformed by v-fms have a constitutively elevated specific activity of a guanine nucleotide-dependent, phosphatidylinositol-4,5-diphosphate-specific phospholipase C. We speculate that the tyrosine kinase activity of the v-fms/c-fms gene products may be coupled to this phospholipase C, possibly through a G regulatory protein, thereby increasing phosphatidylinositol turnover and generating the intracellular second messengers diacylglycerol and inositol triphosphate.
Ventilatory patterns during steady state and progressive exercise.

This study was conducted to differentiate the ventilatory and metabolic response to supine exercise at low levels (VO2 less than 1000 ml/min) from the well-documented response to high level upright exercise. Further, the respiratory cycle during exercise is analysed in terms of inspiratory time, flow and expiratory time as well as tidal volume and frequency. Using a canopy system for non-invasive measurement of breathing patterns and gas exchange, nine male subjects were studied while performing steady state (SSE) and progressive exercise (PRE). Work loads were: SSE 1-5 Kgm/sec for 17 min; PRE 1.5, 2.5, 3.75 and 5.0 Kgm/sec with 2 min increments. Total work was the same (1548 Kg . m) in both types of exercise. With SSE tidal volume (Vt) and respiratory rate (integral of) rose 70% and 30%, respectively. Minute ventilation (Ve) rose 113%. With PRE, integral of rose during the first work level, then remained stable, while Vt and Ve rose with each incremental exercise level. In both cases a decrease in expiratory time accounted for the major component of the decrease in total cycle time. With the onset of exercise, the rate of increase of inspiratory time and respiratory frequency exceeded that of tidal volume and inspiratory flow. This would suggest that these two groups of parameters are controlled by separate mechanisms, possibly, timing being under neurogenic control and flow determined by humoral factors. The respiratory quotient decreased with both forms of exercise and remained low throughout the exercise period.
Case Report: Storm and Acid, Together… !

The authors discuss the case of a 32-year-old woman, with history of Graves' disease, who was noncompliant with her medications. She presented with thyroid storm and concomitant diabetic ketoacidosis. She had no history of diabetes, and this was the first presentation of diabetes. Type 1 diabetes mellitus and Graves' disease are both autoimmune diseases and can occur in concurrence, but such presentation wherein extremes of both disorders, namely thyroid storm and diabetic ketoacidosis occur together, is very rare and requires early diagnosis and management.
Direct Charge Number and Molecular Weight Determination of Large Individual Ions by Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

The coupling of electrospray ionization (ESI) techniques with Fourier transform ion cyclotron resonance (FTICR) mass spectrometry allows the analysis of individual (i.e., single) multiply charged ions. In this paper, we demonstrate that individual large ions can be directly characterized through their excitation and ejection behavior in the FTICR cell. We also report the direct measurement of the charge carried by an individual poly(ethylene glycol) ion (5 [times] 10[sup 6] nominal molecular weight) and thus obtain the molecular weight of an individual ion ([approximately] 4.1 [times] 10[sup 6]) directly from the m/z measurement. These results confirm that the observed ions are indeed large individual molecular ions produced by ESI, as opposed to small fragments, and that an approximate molecular weight can be directly measured on the basis of charge determination and measured m/z. This capability augments the ability for more precise mass determination based upon the observation of a known reaction process (e.g., proton transfer) for individual ions. 39 refs., 5 figs., 1 tab.
Social comparison, negative body image, and disordered eating behavior: The moderating role of coping style

Comparing one's body to those of individuals perceived as more attractive is common among college women, and has been associated with increases in body dissatisfaction and disordered eating. Not all college women are vulnerable to the negative influence of these upward body comparisons; however, little is known about characteristics that may distinguish more vulnerable women. Coping styles, which represent individuals' responses to negative events, are a key area of opportunity for better understanding the relationship between body comparison and weight-related experiences in this population. College women (n =628) completed an electronic assessment of demographics, upward body comparison, body dissatisfaction, disordered eating behavior, and coping styles. Controlling for reported BMI, positive reframing coping style moderated the relationship between upward body-focused comparison and body dissatisfaction (p =0.02), such that women who engaged in more (vs. less) positive reframing showed a weakened relationship between upward body-focused comparison and body dissatisfaction. Controlling for BMI and body dissatisfaction, both self-blaming (p =0.02) and self-distracting (p =0.009) styles also moderated the relationship between upward body-focused comparison and disordered eating behaviors, such that women who more (vs. less) strongly endorsed self-blaming and self-distracting styles appeared more susceptible to the negative influence of upward body comparison. These findings underscore the importance of upward body comparison for body dissatisfaction and disordered eating among college women, and highlight coping style as a key factor in these relationships. Increased attention to upward body comparison and coping style may improve quality of life and contribute to the prevention of disordered eating in this vulnerable population.
Data-Preservation in Scientific Workflow Middleware

This paper investigates Data-Preservation, a feature of Scientific Workflow Middleware (SWM) useful for supporting data provenance and "smart recomputation." We observe that in order for an SWM supporting Data Preservation to achieve decent performance, it should execute on top of copy-on-write file systems. Unfortunately, most file systems in-use at scientific computing facilities were designed without copy-on-write semantics. In response, we design, implement and evaluate a middleware-level solution that is based on user-provided hints and parallelization. The solution can be deployed on top of current file systems and is able to scale almost arbitrarily. Our validation is based on real use-cases from astrophysics and experiments on a cluster with 4 file systems.
Restraint-stress-induced changes in exploratory behavior appear to be mediated by norepinephrine-stimulated release of CRF

Exploratory behavior, measured by the time an animal spends investigating objects in a novel environment, has been shown to be sensitive to prior exposure of the animal to stressors. Using this paradigm, it was demonstrated previously that both corticotropin- releasing factor (CRF) and the alpha 2-adrenoreceptor antagonist, idazoxan, elicited stress-like decreases in exploratory behavior. Because an activation of cerebral noradrenergic systems is observed during stress, following intracerebroventricular (i.c.v.) administration of CRF, or following peripheral administration of idazoxan, the involvement of noradrenergic systems in the behavioral effect of restraint and CRF was examined. Inhibition of norepinephrine (NE) release using the alpha 2-agonist clonidine (25 micrograms/kg, i.p.) or the noradrenergic-selective neurotoxin DSP-4 antagonized the restraint-induced decrease in exploratory behavior. The combination of these 2 treatments completely prevented this effect of restraint. The alpha 1-receptor antagonist prazosin (200 micrograms/kg) also prevented the behavioral effect of restraint, whereas the alpha 1-agonist phenylephrine (50 or 100 ng, i.c.v.) decreased exploratory behavior. None of these treatments consistently altered locomotor activity as measured by the number of entries into the different compartments or the number of rears. These results implicate noradrenergic systems in the stress-related changes in this behavior, consistent with our parallel measures on the production of NE catabolites. Thus, both CRF and noradrenergic systems appear to be involved in the effect of restraint on exploratory behavior in this task. Neither DSP-4 nor prazosin had any effect on the CRF-induced decrease in exploratory behavior. However, the CRF antagonist alpha-helical CRF (20 micrograms, i.c.v.) reversed the decrease in exploratory behavior induced by phenylephrine. The most likely explanation is that the 2 systems act in tandem such that noradrenergic systems regulate the release of brain CRF via an alpha 1-adrenoreceptor. This arrangement parallels that involved in the release of hypothalamic CRF to activate the pituitary- adrenal axis. The implications of these results for research on stress- related behaviors and for the etiology of depression are discussed.
Aging and Declining Testosterone: Past, Present, and Hopes for the Future

As men age, serum testosterone (T) levels decline, whereas serum luteinizing hormone (LH) levels increase somewhat or remain unchanged. Age-related reductions in T levels may be associated with alterations in body composition; energy level; muscle strength; physical, sexual, and cognitive functions; and mood. The predominant contributor to the decline in serum T levels is the decreased ability of the aging testes to make T. As in humans, the Brown Norway rat demonstrates age-related reductions in serum T levels in the setting of unchanged or modestly increased serum LH levels. In this rat model, the ability of aged Leydig cells, the terminally differentiated T-producing cells of the testis, to produce T in response to LH stimulation is significantly diminished. This review begins with a discussion of what is known of the molecular mechanisms by which T synthesis declines with Leydig cell aging. It concludes with a brief history of T replacement therapy, current guidelines, controversies related to T replacement therapy in older men, and proposed future clinical directions.
Tale in the Multi-Core Era: Is Java Still Competitive to Host SIP Applications?

Multi-core platforms are becoming prevailing in telecom infrastructures, and many SIP(Session Initiation Protocol) enabled applications are using Java as the development language and runtime environment. It is important to understand the workload characteristics and performance issues of Java based SIP stack over multi-core platforms. In this paper, two RFC 3261 compliant Java based SIP stacks, the JAIN-SIP and a proprietary SIP stack are studied in depth. Especially we focused on the typical performance issues caused by either Java language features or the workload of SIP protocol, including scalability of SIP stack, resource contention issue and GC impact with SIP memory usage pattern. Some optimization techniques and their drawbacks are also discussed along with the performance evaluation. It turns out that due to the complex combination of SIP protocol semantics and Java language features, the performance of Java based SIP stack tends to be far from competitive on multicore platforms. Extensive optimization and certain improvements of program structure and object management policy may help, however, may, on the other hand, sacrifice some key values of the java language, e.g. easy development.
Surface-functionalized nanoparticles for targeted gene delivery across nasal respiratory epithelium

The objective of this study was to determine whether surface-modified nanoparticles enhance permeability across nasal mucosa, while retaining the effectiveness of the payload. The uptake and permeability of polystyrene nanoparticles (PS-NPs; FluoSpheres) was evaluated across the various regions of the bovine nasal epithelia following conjugation with deslorelin and transferrin. Uptake and transport of PS-NPs, deslorelin-PS-NPs, and transferrin-PS-NPs exhibited regional differences in the order: inferior turbinate posterior (ITP) > medium turbinate posterior (MTP) > medium turbinate anterior (MTA). Uptake and transport also exhibited directionality and temperature dependence in these tissues. Further, uptake as well as transport of functionalized nanoparticles could be inhibited by excess free functionalizing ligand. Confocal microscopy indicated the presence of functionalized nanoparticles in respiratory epithelial cells, as well as other cell types of the nasal tissue. We chose the ITP region for further studies with deslorelin or transferrin-conjugated poly-l-lactide-co-glycolide nanoparticles (PLGA-NPs) encapsulating an anti-VEGF intraceptor (Flt23k) plasmid. Transport of the nanoparticles, as well as the plasmid from the nanoparticles, exhibited the following order: transferrin-PLGA-NPs > deslorelin-PLGA-NPs > PLGA-NPs >> plasmid. The ability of the nanoparticles transported across the nasal tissue to retain the effectiveness of the Flt23k plasmid was evaluated by measuring transfection efficiency (percentage of cells expressing GFP) and VEGF inhibition in LNCaP and PC-3 prostate cancer cells. Transfection efficiencies and VEGF inhibition in LNCaP and PC-3 cells exhibited the following trend: transferrin-PLGA-NPs >or= deslorelin-PLGA-NPs > PLGA-NPs >> plasmid. Further, functionalized nanoparticles exhibited transfection efficiencies and VEGF inhibition significantly superior compared with the routinely used transfecting agent, lipofectamine. Formulating plasmids into nanoparticulate delivery systems enhances the transnasal delivery and gene therapy at remote target cancer cells, which can be further enhanced by nanoparticle functionalization with deslorelin or transferrin.
Spiculated erythrocytes of cholesterol-fed guinea pigs: changes of morphology, composition, and osmotic fragility.

SummaryWe have studied the sequential changes of cholesterol content and morphology in RBC of cholesterol-fed GP and the effects of these changes on their energy metabolism and osmotic fragility. The results suggest that (i) spurring of GP RBC is not accompanied by obvious alterations in their energy metabolism and may be the end result of sequential shape transformations associated with cholesterol-loading, and (ii) neither the morphological abnormalities nor the decreased osmotic fragility of cholesterol-loaded RBC is directly related to the development of the hemolytic anemia.Our thanks go to Dr. T. Hayes, Donner Laboratory, University of California, Berkeley, for the scanning electronmicrograph and for permission to publish it. The replicate experiment (Table I, Expt. 2) was carried out by Jacqueline Fields.
Pyrophosphate-Dependent Fructose-6-Phosphate 1-Phosphotransferase Induction and Attenuation of Hsp Gene Expression during Endosperm Modification in Quality Protein Maize

Quality Protein Maize (QPM) is a hard-endosperm version of the high-lysine opaque2 (o2) maize (Zea mays) mutant, but the genes involved in modification of the soft o2 endosperm are largely unknown. Pyrophosphate-dependent fructose-6-phosphate 1-phosphotransferase (PFP) catalyzes the ATP-independent conversion of fructose-6-phosphate to fructose-1,6-bisphosphate in glycolysis. We found a large increase in transcript and protein levels of the α-regulatory subunit of PFP (PFPα) in QPM endosperm. In vitro enzyme assays showed a significant increase in forward PFP activity in developing endosperm extracts of QPM relative to the wild type and o2. An expressed retrogene version of PFPα of unknown function that was not up-regulated in QPM was also identified. The elevated expression levels of a number of ATP-requiring heat shock proteins (Hsps) in o2 endosperm are ameliorated in QPM. PFPα is also coinduced with Hsps in maize roots in response to heat, cold, and the unfolded protein response stresses. We propose that reduced ATP availability resulting from the generalized Hsp response in addition to the reduction of pyruvate, orthophosphate dikinase activity in o2 endosperm is compensated in part by increased PFP activity in QPM.
Extracting geometric features of aortic valve annulus motion from dynamic MRI for guiding interventions

Transcatheter aortic valve implant (TAVI) has emerged as a prominent approach for treating aortic stenosis. Success of such implants depends upon the accurate assessment of the geometric features such as the diameter, center and orientation of the aortic valve annulus (AVA). In this paper, we present a method for extracting these geometric features from magnetic resonance images (MRI). The method is based on finding an optimal fit for a circular ring mimicking AVA in the aortic root. Moreover, the presented approach provides dynamic tracking of the AVA in CINE MR images. This approach can be used for preoperative planning of prosthetic valve implantation, as well as for the emerging MRI guided manual, or with robot-assisted, annuloplasty.
Reproduction in the Mediterranean Fruit Fly: Depletion of Stored Sperm in Females

Recent work has shown that several supposedly polygamous insects are in effect monogamous for much of their lives. Riemann etal. (1967), working with castrated males, demonstrated that female monogamy in the house fly, Musca domestica L., is caused by material from the male ejaculatory duct. In further work Riemann and Thorson (1969) concluded “the effects of the accessory material are essentially quantitative and that increasing amounts of the material produce increased effects ” Tauber (1968) observed that females of Fannia femoralis (Stein) would not remate once inseminated. Barton Browne (1957) found that mated female Dacus (Strumeta) tryoni (Froggatt), the so-called Queensland fruit fly, repel any subsequent attempts at coitus by males. Tzanakakis et al. (1968) working with the tephritid Dacus oleae (Gmelin), the olive fruit fly, found that most females mated about twice in their lives with about 28 days between matings. They speculated that a substance transferred in the semen inhibited subsequent mating; other evidence led them to believe that those females which mated 3 times did so because insufficient inhibiting substance had been transferred at the 1st mating.
UV-CAST: an urban vehicular broadcast protocol

Several vehicular communication applications will involve multicast/broadcast communications where all vehicles in a certain region of interest are the intended recipients of particular messages. While there are several existing broadcast routing protocols for highway VANETs, very few solutions exist for urban VANETs in cities like New York City or Chicago. This article attempts to fill this gap by proposing a new broadcast routing protocol, Urban Vehicular BroadCAST (UV-CAST), which addresses both the broadcast storm and disconnected network problems in urban VANETs. Key challenges imposed by urban VANETs as well as new mechanisms needed for meeting these challenges are identified and presented. Performance of the proposed UV-CAST protocol is evaluated in terms of network reachability, received distance, and network overhead in ideal Manhattan Street scenarios as well as in real cities, such as Pittsburgh. The overall performance of UV-CAST is excellent.
Development of a Semiprescriptive Selection Procedure for Reliability-Based Fatigue Design of High-Mast Lighting Structural Supports

High mast lighting structures are being used to provide illumination for large intersections, particularly for highways located in rural areas. These structures, ranging from approximately 15–40 m (50–130 ft) in height, are exposed to high wind forces that in turn produce a tremendous number of loading cycles each year. A recent high mast lighting structural support failure in the high plains of Colorado near Denver International Airport provided the impetus for this study. These high-mast structures are less than one meter (3.28 ft) in diameter and are quite flexible relative to many civil engineering structures. This flexibility results in large deformations when compared to their diameter, i.e., when combined with the height of these structures. Furthermore, large forces and moments at the base are produced that result in large stresses and stress reversals during multimode excitation. This paper presents the process and results for the development of a reliability-based design procedure for high-mast ...
Management of acute brain injury and associated respiratory issues

Acute brain injury, in the form of trauma, stroke, or spontaneous hemorrhage, occurs commonly and in all age groups. Although the management of these conditions differs considerably, certain physiologic principles are shared by all and are useful in guiding the management of the most severely injured patients. This article reviews basic cerebral physiology and describes the links between physiology and management principles, emphasizing subjects relevant to the respiratory management of patients with acute brain injury.
Near-Tip Mechanics of Stress-Induced Microcracking in Brittle Materials

A continuum-mechanics description of stress-induced microcracking was developed. Modulus-reduction effects due to microcracking are taken into account through the model of Budiansky and O'Connell. This is used in conjunction with a modified microcracking criterion that stems from the work of Evans and Fu. The resulting constitutive law for a microcracking material was used in finite-element calculations to study the near-tip stress and strain fields and the size and shape of a small-scale damaged zone for a stationary mode I crack in an elastic body. The finite-element results for the stationary crack are used to predict asymptotic toughening values which correspond to a fully developed wake of microcracked material for a propagating crack. Substantial toughening can result. In contrast, the microcracking zone for a stationary crack is thought to make little or no contribution to material toughening. The theoretical results are discussed in the context of experimental observations for zirconia-toughened alumina.
Infections in the Central Nervous System

This chapter will review the epidemiology, clinical presentation, recommended evaluation and treatment of Central Nervous System (CNS) infections associated with HIV infection and Neurocysticercosis (NCC). HIV infection is frequently complicated by opportunistic infection or neoplasm of the CNS. NCC, a parasitic infection of the CNS, is the most common cause of epilepsy in the developing world and may present clinically as obstructive hydrocephalus. Most opportunistic CNS infections and neoplasms are associated with headache, fever, meningismus, altered level of consciousness, or focal neurologic deficit. NCC is diagnosed by neuroimaging and serologic testing. Treatment of these CNS infections is mainly medical, but can include surgery for diagnostic purposes and surgical removal of lesions.
A remote exposure reactor (RER) for plasma processing and sterilization by plasma active species at one atmosphere

We have developed a remote exposure reactor (RER) in which the active species of air and other gases responsible for sterilization and processing effects are generated on flat panels in a surface layer of one atmosphere uniform glow discharge plasma (OAUGDP). These active species are convected by forced airflow at one atmosphere and near room temperature to a remote exposure chamber in which the workpiece is located. This allows workpieces of any size or shape to be sterilized or processed without direct contact with the plasma. Here, we report operation of the RER as a sterilizer with both single-pass and recirculating active species flow through the remote exposure chamber. We used the RER to reduce the numbers of two genera of microorganisms (Esherichia coli and Staphylococcus aureus) on test samples of polypropylene fabric. When the recirculating airflow configuration was employed, the population both of E. coli and S. aureas cells was reduced by at least five decades after only 25 s of exposure. Tests in the single pass airflow configuration produced similar results, with the E. coli and S. aureas populations decreased by at least four decades after 25 s of exposure.
Expression of Pax-3 in the lateral neural plate is dependent on a Wnt- mediated signal from posterior nonaxial mesoderm

Abstract During early patterning of the vertebrate neuraxis, the expression of the paired-domain transcription factor Pax-3 is induced in the lateral portions of the posterior neural plate via posteriorizing signals emanating from the late organizer and posterior nonaxial mesoderm. Using a dominant-negative approach, we show in explant assays that Pax-3 inductive activities from the organizer do not depend on FGF, retinoic acid, or XWnt-8, either alone or in combination, suggesting that the organizer may produce an unknown posteriorizing factor. However, Pax-3 inductive signals from posterior nonaxial mesoderm are Wnt-dependent. We show that Pax-3 expression in the lateral neural plate expands in XWnt-8-injected embryos and is blocked by dominant-negative XWnt-8. Similarly, we show that the homeodomain transcription factor Msx-1, which like Pax-3 is an early marker of the lateral neural plate, is induced by posterior nonaxial mesoderm and blocked by dominant-negative XWnt-8. Finally, we show that Rohon–Beard primary neurons, a cell type that develops within the lateral neural plate, are also blocked in vivo by dominant-negative Xwnt-8. Together these data support a model in which patterning of the lateral neural plate by Wnt-mediated signals is an early event that establishes a posteriolateral domain, marked by Pax-3 and Msx-1 expression, from which Rohon–Beard cells and neural crest will subsequently arise.
Nonword Repetition and Speech Motor Control in Children

This study examined how familiarity of word structures influenced articulatory control in children and adolescents during repetition of real words (RWs) and nonwords (NWs). A passive reflective marker system was used to track articulator movement. Measures of accuracy were obtained during repetition of RWs and NWs, and kinematic analysis of movement duration and variability was conducted. Participants showed greater consonant and vowel accuracy during RW than NW repetition. Jaw movement duration was longer in NWs compared to RWs across age groups, and younger children produced utterances with longer jaw movement duration compared to older children. Jaw movement variability was consistently greater during repetition of NWs than RWs in both groups of participants. The results indicate that increases in phonological short-term memory demands affect articulator movement. This effect is most pronounced in younger children. A range of skills may develop during childhood, which supports NW repetition skills.
ATDC/TRIM29 Phosphorylation by ATM/MAPKAP Kinase 2 Mediates Radioresistance in Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) is characterized by therapeutic resistance for which the basis is poorly understood. Here we report that the DNA and p53 binding protein ATDC/TRIM29, which is highly expressed in PDAC, plays a critical role in DNA damage signaling and radioresistance in pancreatic cancer cells. ATDC mediated resistance to ionizing radiation in vitro and in vivo in mouse xenograft assays. ATDC was phosphorylated directly by MAPKAP kinase 2 (MK2) at Ser550 in an ATM-dependent manner. Phosphorylation at Ser-550 by MK2 was required for the radioprotective function of ATDC. Our results identify a DNA repair pathway leading from MK2 and ATM to ATDC, suggesting its candidacy as a therapeutic target to radiosensitize PDAC and improve the efficacy of DNA-damaging treatment.
Opt-Out Testing: Who Can Afford to Take Care of Patients with Newly Diagnosed HIV Infection?

The appropriate adoption of a policy of opt-out universal testing for human immunodeficiency virus (HIV) will likely increase the number of new HIV-infected patients seeking care by at least 25% over the next several years. On the basis of recent analyses, this policy will save lives and reduce medical care costs. However, the majority of clinics are currently operating at maximum capacity and cannot absorb the influx of newly identified patients. Therefore, the implementation of the policy of opt-out testing will expose deficiencies in clinic capacity and will likely precipitate a crisis in health care access and delivery for patients seeking care at these clinics. A comprehensive assessment of the funding requirements of existing HIV clinics is urgently needed, and sufficient resources must be appropriated to ensure that existing clinics can expand their capacity to absorb the onslaught of HIV-infected patients newly identified via the opt-out testing policy.
Macroscopic Approach for Biofluid Transport

The macroscopic approach to biofluid transport is used to analyze fluid flow in the system as a whole. This is in contrast to the microscopic approach that we will describe in Chap. 6, which is used to predict spatial variations of shear stress, pressure, and velocity within the fluid. The macroscopic approach is appropriate when we are not interested in the spatial variations within the system, but instead are interested in average transient values or output values. Common objectives of the macroscopic approach are to find the rate of accumulation of fluid in the system, the fluid flow into or out of the system, or the forces exerted by the fluid on the system. These objectives are accomplished by applying general conservation principles to the fluid in the system.
Mechanism of lignin inhibition of enzymatic biomass deconstruction

The conversion of plant biomass to ethanol via enzymatic cellulose hydrolysis offers a potentially sustainable route to biofuel production. However, the inhibition of enzymatic activity in pretreated biomass by lignin severely limits the efficiency of this process. By performing atomic-detail molecular dynamics simulation of a biomass model containing cellulose, lignin, and cellulases (TrCel7A), we elucidate detailed lignin inhibition mechanisms. We find that lignin binds preferentially both to the elements of cellulose to which the cellulases also preferentially bind (the hydrophobic faces) and also to the specific residues on the cellulose-binding module of the cellulase that are critical for cellulose binding of TrCel7A (Y466, Y492, and Y493). Lignin thus binds exactly where for industrial purposes it is least desired, providing a simple explanation of why hydrolysis yields increase with lignin removal.
Polymorphism of human plasma apolipoprotein C-III at birth and in early neonatal life

Studies were carried out to investigate potential changes in apolipoprotein C-III (apoC-III) polymorphism from birth through the first month of life. Maternal serum at term and neonatal serum at birth, 3, 14, and 28 days were analyzed for the three principal polymorphic forms of apoC-III: apoC-III-0, apoC-III-1, and apoC-III-2. A two-dimensional electrophoretic procedure combining isoelectric focusing and electroimmunoassay was developed for this purpose. In maternal serum (n = 28), apoC-III-1 to apoC-III-2 ratios (1.45) were typical of normolipidemic adult serum, while the corresponding cord sera (n = 32) had a reversal of the apoC-III-1 to apoC-III-2 ratio (0.55). Basic polyacrylamide gel electrophoretic patterns of isolated cord sera lipoprotein density classes confirmed the reversal of the apoC-III-1 to apoC-III-2 ratio in each class. Following birth, the apoC-III-1 to apoC-III-2 ratio reached unity (1.04) at 3 days and did not change significantly thereafter. It can be concluded that the apoC-III-1 to apoC-III-2 ratio in the normal newborn increases shortly after birth primarily due to an increase in apoC-III-1, and this change appears to be associated with oral feeding, suggesting that intestinal factors may play a role in controlling the ratio of plasma apoC-III-1 to apoC-III-2.
The efficacy of local anesthetics in blocking the sensations of itch, burning, and pain in normal and "sunburned" skin.

Satisfactory methods to determine the efficacy of topical anesthetics in relieving cutaneous itch, pricking, burning, and pain in unbroken skin have not been available. A technique with the use of an alternating current of low amperage and voltage that selectively induces these sensations without apparent in;ury to the skin is described. The efficacy of local anesthetics in obtunding itching and pricking induced experimentally and by exposure of the skin to ultraviolet light was evaluated. Studies in 150 volunteers indicate that salts of local anesthetics are ineffective in obtunding itching and burning in intact normal or ultraviolet burned skin; bases in concentrated solutions are effective.
Renal insufficiency predicts mortality in geriatric patients undergoing emergent general surgery.

Clinical predictors of perioperative mortality in geriatric patients undergoing emergent general surgery have not been well described. The purpose of this study was to determine the incidence of po...
Current Management of Neonatal Liver Tumors

This review is focused on the special issues and challenges confronting physicians and surgeons caring for an unborn child, or a newborn with a liver tumor. Liver tumors at this age are very rare and they make it difficult for pediatric surgeons to gain experience necessary to obtain good results. On the other hand, adult hepatobiliary surgeons faced with a fetus or infant with a liver mass are ill equipped to care for the patient even if they have done a high volume of adult liver surgery and are expert in the field. Often a team approach is the best solution.
Protein-protein interactions among ion channels regulate ion transport in the kidney.

Le transport epithelial d'ions au niveau de divers organes est regule par des agonistes extracellulaires qui agissent via des recepteurs membranaires ou des messagers intracellulaires. Divers arguments suggerent que des interactions directes entre les proteines membranaires ou entre une proteine de transport et des proteines attachees a la membrane peuvent reguler le transport epithelial. La proteine CFTR (Cystic Fibrosis Transmembrane Conductance Regulator, mutee dans la mucoviscidose) est abondamment exprimee dans le nephron, mais son role de canal chlorure ne semble pas critique pour le transport d'eau et de sel au niveau de cet organe. Il est bien etabli que le canal potassique ROMK (egalement appele Kir 1.1), localise dans le segment epais ascendant de l'anse de Henle et dans les cellules principales du canal collecteur, est inhibe par des concentrations millimolaires de Mg-ATP cytosolique. Le mecanisme de cette inhibition est longtemps reste enigmatique. Sur base de nos resultats, nous proposons que la proteine ABC (ATP-binding cassette) CFTR est un cofacteur pour la regulation de Kir 1.1. En effet, la sensibilite Mg-ATP de Kir 1.1 est completement absente dans deux modeles murins deficients en CFTR. L'ouverture ou la fermeture du canal CFTR pourrait constituer un mecanisme moleculaire qui empeche ou facilite la capacite de detection de l'ATP de Kir 1.1. La detection du Mg-ATP par le complexe CFTR-Kir 1.1 pourrait-elle participer au couplage du metabolisme avec le transport d'ions? Les concentrations intracellulaires d'ATP dans les cellules tubulaires sont de l'ordre du millimolaire, donc saturantes pour l'ouverture de Kir 1.1 par le Mg-ATP. Par consequent, les canaux Kir 1.1 seraient fermes et incapables de contribuer a la regulation de la secretion de potassium a moins que d'autres phenomenes ne modulent la sensibilite a l'ATP (CFTR-dependante) de Kir 1.1. Le troisieme element du complexe de detection metabolique affectant la regulation de Kir 1.1 est sans doute la serine-threonine kinase regulee par l'AMP (AMPK). Les modifications du niveau d'AMP plutot que d'ATP representent le signal metabolique detecte par les cellules tubulaires. Etant donne que l'AMPK inhibe le CFTR en modulant son ouverture, nous proposons que la secretion renale de potassium est regulee par des interactions impliquant Kir 1.1, CFTR et AMPK.
Incidence of Venothromboembolism (VTE) in Patients (pts) with Acute Lymphocytic Leukemia (ALL), Burkitt’s Leukemia/Lymphoma (BL) or Lymphoblastic Leukemia (LL).

Background: Pts with cancer are at increased risk of thromboembolic events with potentially life-threatening consequences. The incidence of VTE in cancer pts has been estimated at 1 in 250. Although most of these episodes are associated with solid tumors, VTE is also observed in pts with acute leukemias, even in the presence of thrombocytopenia. Anticoagulation in this pt population can be particularly problematic if pts are undergoing myelosuppressive chemotherapy. VTE prophylaxis is often not given because of the perceived high risk of bleeding with a presumed low risk of VTE. Method: As little is known about the incidence and significance of VTE in pts with acute leukemia, we conducted a retrospective chart review of 223 pts with ALL, BL, or LL who received a hyper-CVAD regimen (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and cytarabine) with or without rituximab, maintenance chemotherapy (with L-asparaginase only months #7 & 18), allogeneic stem cell transplant (SCT), or salvage chemotherapy at our institution from November 1999 to May 2005. The median observation period was 112 weeks (range 1–328). Results: The median age was 51 yrs (range 19–75). 70% were ALL, (50% were Philadelphia positive ALL), 20% Burkitt’s or Burkitt’s-like, and 10% LL. Thirty nine of 223 pts (18%) had confirmed VTE by imaging studies: 12.5% prior to or at the time of diagnosis, 57.5% during consolidation chemotherapy, and 27.5% during maintenance chemotherapy, SCT, or supportive care. Location of VTE varied by site: 3/39 (8%) pulmonary embolus, 16/39 (41%) lower extremity, 2/39 (5%) central venous catheter (CVC), and 18/39 (46%) upper extremity. Two of the 18 with upper extremity VTEs did not have CVC, and an additional 2 had bilateral upper extremity thromboses. The platelet counts were reviewed near the time of VTE diagnosis: 22/39 (56%) had greater than 100 × 10 9 /L, 17/39 (44%) were less than that value, with 76% below 50,000 × 10 9 /L. Conclusion: Pts with ALL, BL, and LL undergoing therapy are at risk for developing VTE. Thrombocytopenia does not preclude development of VTE. A more detailed analysis will be forthcoming regarding the risk factors for VTE in this pt population, the current medical practices and bleeding complications with VTE prophylaxis and treatment, and the effect on therapy administration and overall survival. Practice guidelines for management of acute leukemia pts with thromboembolic events should be pursued.
Predicting Economic, Social, and Foreign Policy Conservatism: the Role of Right-Wing Authoritarianism, Social Dominance Orientation, Moral Foundations Orientation, and Religious Fundamentalism

The current research examined the capability of Right-Wing Authoritarianism (RWA), Social Dominance Orientations (SDO-D and SDO-E), the five Moral Foundations Orientation (MFO), and Religious Fundamentalism (RF) to predict economic conservatism, social conservatism, and foreign policy conservatism. Based on data gathered from a sample of students attending a public university located in the northeast U.S., multiple regression analyses indicated: 1) RWA and SDO-D were predictors of economic conservatism; 2) only RWA predicted social conservatism; and 3) RWA and RF predicted foreign policy conservatism. In all cases, RWA was the strongest predictor of economic, social, and foreign policy conservatism. We discuss the reasons RWAs endorse conservative economic, social and foreign policies.
Habitus, doxa, and saga: applications of Bourdieu’s theory of practice to organizational history

AbstractUsing the concept of ‘organizational saga’ as a guide, this article presents Pierre Bourdieu’s theory of practice as an analytical tool capable of advancing insights into organizational behavior and related social phenomena. Responding to the question of what makes an organization’s inherently historical saga ‘knowable’, illustrated are conceptual and methodological considerations derived from key concepts in Bourdieusian social theory, namely habitus and doxa, that offer lenses with which organizational culture, identity, and belief can be more thoughtfully engaged. Expanding the theoretical scope beyond saga, recent contributions to management and organizational history are presented throughout as topical and methodological frameworks for future analytical application of habitus, doxa and other concepts. As such, it is argued that Bourdieu can reformulate or uncover knowledge of specific case studies in management and organizational history, as well as reexamine theories of history and instituti...
Dancing Together: The Lakota Sun Dance and Ethical Intercultural Exchange

Reflecting upon my twenty years of participation in several Lakota Sun Dance ceremony communities, this article explores ethical questions that arise from non-Native people practicing traditional Native American ceremonies, especially the Lakota Sun Dance. Through personal stories of lessons learned attending twenty Lakota Sun Dances, being taught for many years to sing ceremonial songs by a fluent Lakota singer/elder, and a historical overview of the Sun Dance, I discuss paths toward mutually enhancing intercultural communication based on respect, shared sacrifice, generosity, integrity, and the cultivation of long-term thinking for the well-being of people and the planet, now, and for generations to come.
Somatic mosaicism of an intragenic FANCB duplication in both fibroblast and peripheral blood cells observed in a Fanconi anemia patient leads to milder phenotype

Background Fanconi anemia (FA) is a rare disorder characterized by congenital malformations, progressive bone marrow failure, and predisposition to cancer. Patients harboring X-linked FANCB pathogenic variants usually present with severe congenital malformations resembling VACTERL syndrome with hydrocephalus. Methods We employed the diepoxybutane (DEB) test for FA diagnosis, arrayCGH for detection of duplication, targeted capture and next-gen sequencing for defining the duplication breakpoint, PacBio sequencing of full-length FANCB aberrant transcript, FANCD2 ubiquitination and foci formation assays for the evaluation of FANCB protein function by viral transduction of FANCB-null cells with lentiviral FANCB WT and mutant expression constructs, and droplet digital PCR for quantitation of the duplication in the genomic DNA and cDNA. Results We describe here an FA-B patient with a mild phenotype. The DEB diagnostic test for FA revealed somatic mosaicism. We identified a 9154 bp intragenic duplication in FANCB, covering the first coding exon 3 and the flanking regions. A four bp homology (GTAG) present at both ends of the breakpoint is consistent with microhomology-mediated duplication mechanism. The duplicated allele gives rise to an aberrant transcript containing exon 3 duplication, predicted to introduce a stop codon in FANCB protein (p.A319*). Duplication levels in the peripheral blood DNA declined from 93% to 7.9% in the span of eleven years. Moreover, the patient fibroblasts have shown 8% of wild-type (WT) allele and his carrier mother showed higher than expected levels of WT allele (79% vs. 50%) in peripheral blood, suggesting that the duplication was highly unstable. Conclusion Unlike sequence point variants, intragenic duplications are difficult to precisely define, accurately quantify, and may be very unstable, challenging the proper diagnosis. The reversion of genomic duplication to the WT allele results in somatic mosaicism and may explain the relatively milder phenotype displayed by the FA-B patient described here.
Affecting mobility: Consuming driving and driving consumption in Southeast Asian emerging markets:

This article examines emergent consumption patterns in Vietnam’s shifting transportation market and then considers them within broader design and marketing infrastructures shaping emerging markets ...
The Future of Making for Designers, Makers, and Users: A Conversation Between Industry and Academia

In recent years, the apparel industry has been integrating a number of emerging technologies. Methods such as automated production and 3D printing or additive manufacturing are shifting the dynamic for traditional apparel designers. Such evolution is leading to a shift in paradigm as various industry companies are actively exploring and applying such emerging technology in commercial products and manufacturing processes. This study examined the perception of both industry and academia in the changing environment for designers, makers, and users and explored approaches in locating resources for supporting both industry and academia in future growth. Data suggests that roles of designer, makers, and users are quickly changing with reconfigured knowledge base and new skill sets in the age of novel technology. Much disconnect still exists between industry and academia and among groups of designers, makers, and users in realizing the best mechanism in transitioning to the new ways.