cssi/SciSciGPT-SciSciNet huggingface dataset:
Escherichia coli Expression and Characterization of Cytochromes P450 2B11, 2B1, and 2B5

Abstract Dog CYP2B11 , rat CYP2B1 , and rabbit CYP2B5 have been expressed in Escherichia coli from cDNAs modified at the N-terminus (Barnes et al. , 1991, Proc. Natl. Acad. Sci. USA 88, 5597-5601). Using 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (Chaps), solubilized membranes representing >100 nmol of P450 2B11, >35 nmol of P450 2B1, and >7 nmol of P450 2B5 were efficiently extracted (40-70% yield) from a 1-liter culture. Chaps-solubilized preparations produced a reduced CO/reduced difference spectrum devoid of P420 and were used directly in a reconstituted system. The E. coli -expressed 2B enzymes retained the same functional characteristics as the purified hepatic enzymes or enzymes expressed in COS cells in terms of androstenedione metabolite profiles. Hydroxylation rates were determined under a variety of conditions, including two concentrations of NADPH-cytochrome P450 reductase (2 and 16 nmol/nmol P450) and the absence or presence of cytochrome b 5 (2 nmol/nmol P450). The androstenedione hydroxylase activities of expressed 2B1 and 2B5 were stimulated by cytochrome b 5 , whereas P450 2B11 was inhibited slightly by cytochrome b 5 . Purified expressed 2B11 (specific content, 8 nmol/mg protein) had similar activities as the Chaps-solubilized membrane preparation. The solubilized membranes containing 2B11 were also tested with 2,2′,4,4′,5,5′-hexachlorobiphenyl (245-HCB). Three major metabolites, 2-hydroxy-4,5,2′,4′,5′-pentachlorobiphenyl, 3-hydroxy-2,4,5,2′,4′,5′-hexachlorobiphenyl, and 2-hydroxy-3,4,5,2′,4′,5′-hexachlorobiphenyl were produced from 245-HCB. These metabolites are identical to those produced by 2B11 purified from liver microsomes. The 245-HCB hydroxylation rates were similar for E. coli -expressed 2B11, dog liver microsomes, and purified liver 2B11. When only the secend codon in the 2B1 was changed to GCT, >25 nmol of P450 was extracted from a 1-liter culture, suggesting that the full Barnes et al. modification scheme may not be necessary for high-level expression. An efficient method of expressing, extracting, and analyzing different P450 2B enzymes has thus been achieved. In addition, rabbit P450 2B5, which has never been purified from liver, as well as different P450 2B mutants can now be expressed at much higher levels than previously reported. The ability to express different 2B wild-type and mutant P450s in E. coli provides an excellent opportunity to study the molecular basis of species differences in substrate metabolism.
Formation of phenylethanolamine N-methyl transferase complexes as an intermediate of the methylation of norepinephrine.

Abstract The N-methylation of norepinephrine to form epinephrine involves the transient formation of a ternary complex involving S-adenosylmethionine, norepinephrine and N-methyl transferase (PNMT). Finding this complex suggests the mechanism and sequence of methylation of norepinephrine.
An approach to landscape analysis with emphasis on soils

Abstract Principal components of landscape are defined. The soils portion is termed the landscape pedoplasma, distinct geographic subdivisions of which are called soilscapes. Some concepts of morphology and fabric of soil pedons are adapted for application to entire landscapes. Terminology and numerical indices are suggested for characterizing polypedons and multi-polypedonic units, including soilscapes, as to size, shape and arrangement of the geographic units, population density of polypedons per unit area, and pedologic diversity in terms of local relief, slope, and soil drainage conditions, and in taxonomic terms. Some results of application of specific methods of soilscape analysis to published soil and topographic maps are reported. Geographic trends in soilscape variability are found on a broad regional scale as well as in local landscapes. This approach to landscape analysis is deemed useful in systematizing the great volume of cartographic data of modern published soil surveys and may help in the location of sites for detailed pedogeomorphic and land use field studies.
INTRACELLULAR INCLUSIONS IN THE GUT EPITHELIAL CELLS OF PIESMA CINEREUM SAY

Intracellular inclusions in the epithelial cells of the midgut of Piesma cinereum (Hemiptera) are described. Three types of inclusions have been observed in both viruliferous and "virus-free" insects. Two of them, α and β, are free in the cytoplasm and are of two different basic configurations: one exhibits bilateral symmetry, the other a fivefold radial symmetry. Still another type of inclusion is contained in membrane-bounded bodies and consists of elongate, irregularly shaped crystals. A description of the structure of the inclusions is given and their nature and significance are discussed.
ORBITOZYGOMATIC APPROACH TO BASILAR APEX ANEURYSMS

BASILAR APEX REGION aneurysms are among the most complex cerebral aneurysms. They are not, however, among the most common aneurysms, and increased use of endovascular treatment has further decreased the number of patients with these lesions who undergo surgery. Nonetheless, not all basilar apex aneurysms are amenable to coil embolization, and neurosurgeons must be prepared to treat patients with basilar apex aneurysms surgically. We prefer an orbitozygomatic craniotomy and transsylvian approach. Meticulous exercise of the basic tenets of aneurysm surgery (proximal vascular control, sharp dissection, and preservation of perforating vessels) is crucial to optimal patient outcomes. s a group, basilar artery aneurysms are perhaps the most complex aneurysms faced by neurosurgeons. Their relative rarity and evolving endovascular treatment options mean that the frequency of surgical treatment for patients with basilar artery an- eurysms is much less than that of patients with more common aneurysms, and the rate is decreasing rapidly. However, not all of these lesions are amenable to endovascular treat- ment. Therefore, vascular neurosurgeons must maintain their skills in treating patients with these complex lesions, which may be made more complex by partial embolization. The central tenets of all aneurysm surgery apply to the treatment of patients with basilar apex aneurysms. These include proximal vas- cular control before aneurysm dissection, the use of sharp dissection techniques, adequate visualization and preservation of perforating vessels near the aneurysm, and preservation of the parent vessels. Adjuncts that include neuroanesthetic care based on cerebral protec- tion, electrophysiological monitoring, and in- traoperative angiography also are key ele- ments in the intraoperative care of patients with basilar apex aneurysms. Treatment of patients with giant basilar artery apex aneu- rysms under cardiac bypass and low blood flow or in full cardiac arrest is beyond the scope of this discussion and is not addressed. Endovascular techniques have an important role to play in the treatment of basilar artery aneurysms and are the appropriate treatment choice in selected patients. However, direct microsurgical repair is the appropriate treat- ment for many patients, which should not be supplanted by endovascular therapy simply because of the perceived difficulties and risks associated with surgery for basilar artery an- eurysms. This discussion is based on the sur- gical decision-making and technique of the senior author (RFS).
Psychosocial Trauma, Defense Strategies and Treatment Considerations in Cancer Patients and Their Families.

Abstract The psychosocial impact of cancer on the patient and the family can be almost as traumatic as the physical effects. Realistic as well as unrealistic stresses and fears are aroused which can overwhelm the individuals who have to cope with them. The patient and family must deal with marked changes in the family structure, feelings of isolation and loneliness, helplessness, and dependence on others. Because the affects associated with cancer are so painful, the utilization of defense strategies is particularly excessive and pervasive in this clinical population. Defense mechanisms such as denial, isolation of affect and rationalization are discussed. Group treatment is especially effective because of certain curative factors intrinsic to the group experience, such as instillation of hope, universality and cohesiveness, that allow the group members to lower their defensiveness and deal more adoptively with their emotional and environmental stresses.
The process of infection with bacteriophage φX174: XXVII. Removal of the Spike Proteins from the Phage Capsid

Electron microscopy of negatively stained bacteriophage φX174 has revealed a set of projections or “spikes” which protrude from the 12 vertices of the icosahedral virus particle. Urea treatment can remove these spikes, leaving an intact protein shell or capsid. Capsids produced by this procedure are readily separated from the smaller spike material by sedimentation in a sucrose gradient. Electrophoresis of dissociated phage proteins in polyacrylamide gel has shown that the φX particle contains most probably four different proteins. Only one of these is present in purified capsids prepared by the above procedure. The slow-sedimenting spike material contains the other proteins. The amino acid composition and fingerprints of the capsid and spike proteins are presented. A model of the structure of the phage particle, based on these studies of the phage proteins and electron micrographs of intact phage and spikeless capsids, is proposed. This model consists of a modified Caspar-Klug capsid in which the 12 pentamers located at the vertices of the icosahedral structure are replaced by the structurally complex spikes. Removal of the spike proteins leaves a coat structure composed solely of hexamers of a single molecular species.
Thirst in Critically Ill Patients: From Physiology to Sensation

Critically ill patients often report distressful episodes of severe thirst, but the complex biochemical, neurohormonal mechanisms that regulate this primal sensation still elude clinicians. The most potent stimuli for thirst are subtle increases in plasma osmolality. These minute changes in osmolality stimulate central osmoreceptors to release vasopressin (also known as antidiuretic hormone). Vasopressin in turn acts on the kidneys to promote the reabsorption of water to correct the increased osmolality. If this compensatory mechanism fails to decrease osmolality, then thirst is triggered to motivate drinking. In contrast, thirst induced by marked volume loss, or hypovolemic thirst, is subject to the tight osmoregulation of the renin-angiotensin aldosterone system and accompanying adrenergic agonists. Understanding the essential role that thirst plays in salt and water regulation can provide clinicians with a better appreciation for the complex physiology that underlies this intense sensation.
Multiple Genes Exhibit Phenobarbital-Induced Constitutive Active/Androstane Receptor–Mediated DNA Methylation Changes during Liver Tumorigenesis and in Liver Tumors

The constitutive active/androstane receptor (CAR) mediates responses to the nongenotoxic rodent liver tumor promoter phenobarbital (PB), including certain gene expression changes, hepatomegaly, and tumor formation. Aberrant DNA methylation represents epigenetic events that can play multiple roles in tumorigenesis. Previously, 146 unique PB-induced regions of altered DNA methylation (RAMs) were observed in liver tumor-susceptible CAR wild-type (WT) mice (in 23 weeks, precancerous tissue, and 32 weeks, tumor tissue), as compared to the resistant knockout (KO). We believe that at least some of these might be key for tumorigenesis. In the current study, cloning and annotation of a subset (82%) of the unique RAMs revealed 47 genes exhibiting altered methylation; 17 are already implicated in cancer or related processes and, thus, we have identified 30 "new" candidate genes that might be involved in carcinogenesis due to an epigenetic alteration. These may contribute to tumor development through their involvement in angiogenesis, apoptosis, epithelial-mesenchymal cell transition, growth/survival, and invasion/migration/metastasis. We have also, previously, discerned unique PB-elicited RAMs in liver tumor-prone B6C3F1 mice, as compared to the relatively resistant C57BL/6 strain, at 2 or 4 weeks, and identified 51 genes exhibiting altered methylation. Importantly, 11 of these genes were identified from identical, unique RAMs discerned in both the sensitive B6C3F1 and CAR WT mice, thus representing an initial, potential candidate "fingerprint" which might serve as a biomarker for PB-induced tumorigenesis. These two studies reveal "new" genes whose epigenetic statuses changed uniquely in liver tumor-susceptible mice (B6C3F1 and CAR WT), as compared to their resistant counterparts (C57BL/6 and CAR KO, respectively), within a continuum of PB-induced tumorigenesis.
Growth hormone dynamics in acromegaly.

ABSTRACT Patterns of growth hormone response to the provocative stimuli of insulininduced hypoglycemia, arginine infusion and exercise, and to the suppressive effects of hyperglycemia were studied in acromegalic subjects in order to examine the frequency of autonomous behavior of these functioning pituitary tumors. In all but one instance, non-autonomous behavior of growth hormone secretion characterized these acromegalic subjects. Persistence of a given pattern to particular physiologic manipulations indicated that such alterations in growth hormone levels were not random secretory discharges. Non-autonomous behavior of growth hormone secretion in active acromegaly would seem to imply hypothalamic control of growth hormone secretion despite elevated levels of growth hormone in these patients. These observations and the frequency with which unusual or paradoxical growth hormone responses were obtained suggest the possibility that acromegaly may begin as a primary hypothalamic disturbance with chronically ...
Extracting an explicitly data-parallel representation of image-processing programs

Our research goal is to retarget image processingprograms written in sequential languages (e.g., C) toarchitectures with data-parallel processing capabilities.Image processing algorithms are often inherently data-parallel,but the artifacts imposed by the sequentialprogramming language (e.g., loops, pointer variables,linear address spaces) can obscure the parallelism andprohibit generation of efficient parallel code. This paperproposes a program representation and pattern-recognitionapproach for generating a data-parallelprogram specification from sequential source code. Therepresentation is based on an extension of the multi-dimensionalsynchronous dataflow (MDSDF) model ofcomputation.Central to extracting this representation from code isunderstanding the mapping between iterations and arrayvariables in the source code and the operations overarray regions (e.g., rows, columns, tiled blocks) that theyimplement. Examples are presented to illustrate thismapping, and a set of patterns for recognizing theseregions are proposed. The correctness of the retargetedMDSDF specifications are validated and the potentialspeedup from parallel execution shown.
Blind channel estimation and adaptive blind equalizer initialization

The authors propose approaches to the problem of adaptive blind equalizer initialization and channel impulse response estimation for data communication systems, including telephone channels as well as digital radio channels. They propose two schemes for channel impulse response estimation that can be used for reliable initialization of the conventional decision-directed equalizers. Only batch (non-recursive) methods are considered. The proposed methods yield (globally) optimal solutions. >
Metal displacement and stoichiometry of protein-metal complexes under native conditions using capillary electrophoresis/mass spectrometry.

Increases in the study of protein-metal complexes, as well as in metal displacement in protein-metal complexes under native conditions for optimum catalytic properties in drug research and catalyst design, demands a separation/detection technology that can accurately measure metal displacement and stoichiometry in protein-metal complexes. Both nuclear magnetic resonance (NMR) and X-ray diffraction techniques have been used for this purpose; however, these techniques lack sensitivity. Electrospray ionization mass spectrometry (ESI-MS) using direct infusion offers higher sensitivity than the former techniques and provides molecular distribution of various protein-metal complexes. However, since protein-metal complexes under native conditions usually are dissolved in salt solutions, their direct ESI-MS analysis requires off-line sample clean-up prior to MS analysis to avoid sample suppression during ESI. Moreover, direct infusion of the salty solution promotes non-specific salt adduct formation by the protein-metal complexes under ESI-MS, which complicates the identification and stoichiometry measurements of the protein-metal complexes. Because of the high mass of protein-metal complexes and lack of sufficient resolution by most mass spectrometers to separate non-specific from specific metal-protein complexes, accurate protein-metal stoichiometry measurements require some form of sample clean up prior to ESI-MS analysis. In this study, we demonstrate that capillary electrophoresis/electrospray ionization in conjunction with a medium-resolution (∼10 000) mass spectrometer is an efficient and fast method for the measurement of the stoichiometry of the protein-metal complexes under physiological conditions (pH ∼7). The metal displacement of Co2+ to Cd2+, two metal ions necessary for activation in the monomeric AHL lactonase produced by B. thuringiensis, has been used as a proof of concept. Copyright © 2010 John Wiley & Sons, Ltd.
MicroRNAs as effectors of brain function

MicroRNAs (miRNAs) are a recently discovered family of small, genome-encoded endogenous RNAs that are transcribed but are not translated into proteins. Early studies in Ceanorhabditis elegans revealed that an endogenous small RNA (lin-4) regulated translation of lin-14, a protein required for postembryonic development, through an RNA–RNA interaction.1 Small RNAs were then shown to mediate gene-silencing via a mechanism known as RNA interference (RNAi).2 Fire and Mello2 were awarded the Nobel Prize in Physiology or Medicine in 2006 for the discovery of RNAi. The term miRNA was introduced in a series of back-to-back Science articles in 2001.3–5 MiRNA genes produce primary miRNA transcripts which contain at least one, but possibly more, ≈70 nucleotide hairpin loops. These transcripts are transported into the cytoplasm where they are cleaved by the endonuclease Dicer into an imperfect duplex of 20 to 25 nucleotides. One strand of the duplex is degraded and the other mature miRNA binds to Dicer and forms a complex with argonaute proteins to form RNA-induced silencing complexes.6,7 Studies from several laboratories have revealed that the predominant role of miRNAs in RNA-induced silencing complexes is to regulate post-transcriptional gene expression by translational repression, mRNA cleavage, and mRNA decay initiated by miRNA-guided rapid deadenylation. However, emerging studies support that possible involvement of miRNAs in transcriptional and translational activation. Tremendous progress has been made in unraveling the complexities of miRNAs as meta-controllers of gene expression and their impact on cell development, survival, and function, yet miRNA research is still in its infancy. Given the enormous potential for miRNA studies to translate into novel therapeutic strategies for the diagnosis and treatment of many diseases, the quest to examine all aspects …
Weld clip design for minimization of welding-induced-alignment-distortion in butterfly laser module packages

The welding-induced-alignment-distortion (WIAD) or post-weld-shift (PWS) is a serious issue in assembling of fiberoptic components using laser welding, which may significantly affect the packaging yield. Our previous investigations have revealed that an elimination or minimization of the WIAD in butterfly laser module packaging is possible if laser welding sequence and pulse shape of the welding lasers can be optimized. This work represents our further attempt in minimizing the WIAD by design of welding tools: the weld clip. By means of numerical simulations, the influence of seven different types of weld clip on the WIAD in the assembly of the butterfly laser module packages has been investigated. A realistic physics based laser-materials interaction model is employed and the model combines the spatal and temporal characteristics of the laser beam and the thermophysical properties of the material. The results show that the design of weld clip is important in packaging of the butterfly modules and the alignment distortion induced during the laser welding process can be controlled within the minimal range by proper design of weld clip and selection of process parameters such as the welding sequence.
Seroepidemiology Of Hepatitis A In The United States

The seroepidemiology of hepatitis A depends on the biologic features of the agent. Hepatitis A virus (HAV) is shed in the stool, and infectivity titers are significantly higher for stool than for other body materials. As a consequence, the predominant mode of spread is through fecal-oral routes. Common-source vectors include contaminated foods, water, and bivalve mollusks. Risk factos include contact with a person with hepatitis A, attendance or employment at a day care center, recent international travel, exposure to infected food or water during and outbreak, homosexual activity, and injecting drug use. No known risk factors are identified in many cases. Almost 40% of individuals in the United States are seropositive for prior HAV infection, and rates increase with age, perhaps reflecting an aging cohort of persons infected in earlier times when the infection was more common. Not unexpectedly, this decrease in current infection rates has increased the number of susceptible persons
Psychiatric Symptoms in Alzheimer's Disease: Mental Status Examination Versus Caregiver Report

To examine possible reasons for conflicting prevalence data on psychiatric features of Alzheimer's disease (AD), we compared the results of a mental status examination by a physician with a questionnaire completed by caregivers in eliciting 12 different psychiatric symptoms in AD patients. There was agreement only on categories suggesting agitation. The formal examination showed more correlations with stage and severity of dementia than did the caregiver report.
Cranberry juice components act against development of urinary tract infections

The adhesion of bacteria to uroepithelial cells or urinary catheters is the first step in the development of biofilm formation and urinary tract infections (UTIs). Previous research has suggested that consumption of cranberry juice can prevent the recurrence of UTIs by decreasing bacterial adhesion to epithelial cells. However, the mechanisms of action are not well understood. Experiments were conducted at different scales to test bacterial attachment, adhesion forces and formation of biofilms after continuous exposure of bacteria to cranberry products. At the macroscale, bacteria were incubated with uroepithelial cells and the number of bacteria attached per uroepithelial cell was determined. At the nanoscale, we used atomic force microscopy (AFM) to determine the adhesion forces between E. coli and a silicon nitride AFM tip after bacterial growth in L-CJC or PACs for different numbers of culture times. Successive replacement of media and continued culture in L-CJC and PACs resulted in a significant decrease in adhesion forces for E. coli, which was correlated with a decrease in attached bacteria to uroepithelial cells during cranberry treatment. Growth of bacteria in L-CJC or PACs also inhibited the development of biofilms on polyvinyl-chloride, which can represent biofilm formation on urinary catheters.
Object-oriented configuration management technology can improve software architectural traceability

Software development is a dynamic process where engineers constantly modify and refine their systems. As a consequence, everything evolves including designs, system's architectural structure, and implementation source code. Software evolution can easily make architectural traceability relationships between software architectural entities and corresponding source code become out of date. This paper suggests the use of object-oriented software configuration (SCM) and version management technology to manage versions of architectural structure/entities, source code, and the traceability relationships among them. The resulting architectural SCM system, MolhadoArch, always keeps architectural entities version-consistent with source code. Consistent configurations are maintained not only among source code but also with the high-level software architecture. MolhadoArch supports the management of both planned and unplanned evolution of software architecture.
Lumbosacral sensory neuronal activity is enhanced by activation of urothelial purinergic receptors

Abstract Urothelial purinergic receptors are important for the regulation of afferent sensory pathways in bladder pain and overactivity. Using in vivo electrophysiological recordings we evaluated the activity of spinal dorsal horn neurons in female rats at the L6/S1 level when urinary bladder pressure was abruptly increased. Intravesical infusion of ATP and systemic application of suramin allowed us to evaluate the contribution of urothelial purinergic receptors. Rats were anesthetized with isofluorane. Suprapubic, venous and tracheal catheters were implanted. Laminectomy was performed at the L6–S1 spinal levels. The cervical spinal cord was transected, and rats were mechanically pithed. Anesthesia was stopped, rats were ventilated, and a muscle relaxant was administered. The frequency of spinal neural activity was recorded via tungsten electrodes inserted into the dorsal horn at the L6–S1 level. The signal was amplified, filtered and recorded with a data acquisition system at 10 kHz sampling rate. Vital signs as well as bladder pressure were monitored in real time. We evaluated field potentials during intravesical pressure steps ranging from 0 to 60 cm H 2 O in (A) control (saline in the bladder), (B) after stimulation of urothelial purinergic receptors (1 mM vesical ATP), and (C) after the intravenous application of the non-specific purinergic antagonist suramin (100 mg/kg). Pressure steps were maintained for 1 min followed by 3 min for recovery. Only neurons that showed an increased activity during bladder distention were evaluated. Under control conditions, the generation of field potentials increased concomitantly with bladder pressure steps, showing an activity change threshold between 20 and 40 cm H 2 O. Intravesical application of 1 mM ATP produced an increase in baseline activity, indicative of noxious stimulation, and spinal neuronal activity markedly increased above 40 cm H 2 O pressure. Systemic suramin prevented the increase in neural activity in response to pressure changes, even after intravesical ATP. These results suggest that urothelial purinergic receptors are important modulators of lumbosacral dorsal spinal neuronal activity. The inhibitory effects of suramin imply that enhanced lumbosacral neuronal signals result from activation of C-fibers during noxious bladder stimulation.
A model based excursion protection algorithm for loudspeakers

Loudspeakers in portable consumer electronic devices are frequently small in size. Due to the low sensitivity of their drive units, they are pushed to their power handling and mechanical limits by powerful amplifiers in an attempt to reach high volumes. To protect against excessive diaphragm excursions, a model based algorithm is proposed which regulates the voltage input signal to the loudspeaker while minimizing unnecessary system interventions.
A large-scale study of robots.txt

Search engines largely rely on Web robots to collect information from the Web. Due to the unregulated open-access nature of the Web, robot activities are extremely diverse. Such crawling activities can be regulated from the server side by deploying the Robots Exclusion Protocol in a file called robots.txt. Although it is not an enforcement standard, ethical robots (and many commercial) will follow the rules specified in robots.txt. With our focused crawler, we investigate 7,593 websites from education, government, news, and business domains. Five crawls have been conducted in succession to study the temporal changes. Through statistical analysis of the data, we present a survey of the usage of Web robots rules at the Web scale. The results also show that the usage of robots.txt has increased over time.
Posttranscriptionally Mediated Decreases in Folylpolyglutamate Synthetase Gene Expression in Some Folate Analogue-resistant Variants of the L1210 Cell EVIDENCE FOR AN ALTERED COGNATE mRNA IN THE VARIANTS AFFECTING THE RATE OF DE NOVO SYNTHESIS OF THE ENZYME

L1210 cell variants resistant to edatrexate (EDX) were isolated by selection in vivo during therapy with this folate analogue. Among the variants selected, seven (L1210/EDX-4 to −7 and L1210/EDX-12 to −14) were found to exhibit 2-23-fold lower levels of folylpolyglutamate synthetase (FPGS) activity compared with parental L1210 cells. Lower levels of FPGS activity in cell-free extract from these variants using EDX as substrate were characterized by the same relative decrease in value for Vmax with no change in apparent Km. The results of an analysis of FPGS activity in mixtures of variant and parental cell extract suggested that no endogenous inhibitors in the variant cells or stimulatory factors in parental cells accounted for the differences observed. Also, FPGS from variant and parental cells showed no difference in thermostability. Decreases in a 60-61-kDa protein as shown by immunoblotting with anti-FPGS peptide antibody were found to occur commensurately with the decrease in FPGS activity in cell extract from the variants compared with parental cells. However, no evidence was obtained for a difference in turnover of FPGS protein during measurement of the decay of FPGS activity in cycloheximide-treated variant and parental cells. In addition, Northern blotting of poly(A)+ RNA did not reveal any difference in the size or level of FPGS mRNA among these various cell types. Studies of in vitro translation of hybridization-selected FPGS mRNA from L1210 cells showed that both mitochondrial and cytosolic forms of FPGS were generated during the reaction. Moreover, FPGS mRNA from the variant cells was significantly less effective in mediating formation of the FPGS peptide product in a manner correlating with FPGS activity and protein found in the cytosol of the various cell types. These results suggest that FPGS gene expression in these variants is posttranscriptionally altered at the level of the cognate mRNA itself and that this alteration constitutively down-regulates the steady-state level of FPGS in these variants.
Small Angle Neutron Scattering Study of the Structure and Formation of Ordered Mesopores in Silica

The nanoscale structure and synthesis mechanisms of a recently developed class of inorganic mesoporous materials with ordered arrays of uniform mesopores have been investigated by small angle neutron scattering (SANS). SANS measurements with solvents imbibed into the pores to vary the scattering contrast demonstrate that the low angle diffraction peaks from these materials are entirely due to the pore structure and that the pores are fully accessible to both aqueous and organic solvents. SANS measurements on the concentrated cationic surfactant and silicate precursor solutions typically used in the synthesis of the mesopore materials indicate that the existence of preassembled supramolecular arrays that mimic the final pore structure is not essential for the synthesis of these materials.
Viral infections, atopy, and asthma: Is there a causal relationship?

Respiratory syncytial virus (RSV) remains the chief cause of hospitalization for lower respiratory tract illnesses in both infants and young children, and can produce severe outcomes. In addition, several studies have suggested that infants in whom RSV bronchiolitis develops may have recurrent wheezing and asthma later in childhood. Further complicating the picture is the question of whether there is a link between RSV infection in infancy and the development of atopy later in childhood. This review will discuss existing data on RSV infection and respiratory complications later in life, as well as the link between RSV and allergic disease.
Fostering Individual Creativity Through Organizational Context: A Review of Recent Research and Recommendations for Organizational Leaders

Publisher Summary Creativity in the workplace is increasingly recognized as a valuable organizational commodity. The value of a creative workforce will only increase as organizations face an ever-expanding global nature of business, continued and rapid changes in technology, increased competition for products and/or services, and regular changes to organizational structures, strategies, and environments. Though the value of creativity grows increasingly clear, the factors that contribute to a creative and innovative workforce are more elusive. Although much attention in the creativity literature has been paid to individual characteristics related to creative potential, the business world necessarily requires an understanding of creativity that is both more considerate of organizational context and which focuses more directly on domain specific behavioral outcomes. Organizational context plays a clear role in the emergence of individual creative behaviors. Leader factors, organizational characteristics, and the social fabric of the workplace each provide mechanisms for enhancing employee creativity. Attention must always be given to factors specific to the organizational domains of interest. Within those parameters, however, organization leaders are afforded a myriad of opportunities to foster employee creativity by attending to organizational context.
The Military Use of Technology: How Benign is the Scientific Enterprise?

Throughout the nineteenth century, and well into the fourth decade of the twentieth, science was generally regarded as a progressive and benign enterprise, the main effect of which is to increase the well-being of all of humankind. However, the collaboration of scientists — especially in the medical area — in the horrendous atrocities of the Nazi regime, the Stalinist excesses in the Soviet Union (involving psychologists), the ruthless strategic bombing attacks by both sides on non-combatant civilians in World War II, culminating in the nuclear extinction of the Japanese cities of Hiroshima and Nagasaki, have led to a profound questioning of the paradigm of science as an essentially neutral and always forward-looking endeavour. (A result sometimes referred to as “paradigm lost”.)
Inter-network dynamic spectrum allocation via a Colonel Blotto game

This paper investigates a scenario where multiple network service providers (NSPs) compete to provide wireless connectivity to a set of users. The users could either be a single mobile device, a set of localized Internet-of-Things (IoT) devices, or even a campus-wide network requiring wireless backhaul. The NSPs compete with one another to provide wireless service to the users by strategically allocating the available bandwidth so as to maximize their total payoff. The NSPs present each user with an offer to provide wireless connectivity using a certain amount of bandwidth. Users then decide to connect to that NSP whose offered bandwidth maximizes their utility function. Under such an architecture, this paper focuses on the optimal bandwidth allocation strategies for the NSPs. Such a problem is best modeled using a classical problem in game theory called the Colonel Blotto game—a multidimensional strategic resource allocation game. We show that the problem of spectrum allocation can be reframed as a Colonel Blotto game and analyze the mixed strategies that achieve Nash equilibrium. Depending on whether spectrum is treated a discrete or a continuous resource, we take recourse to either existing theoretical results or rely on numerical techniques to establish the equilibrium-achieving mixed strategies. We finally discuss interesting aspects about these mixed strategies, including an intrinsic user-association mechanism that emerges when spectral efficiency is taken into consideration.
Setting up networks for transportation of critically illed children

Transportation of critically illed patients,also called transport network,is a special medical system radiating from a children’s emergent center to those facilities regarding communication and training. With the establishment of NICU and PICU,the transportation of critically illed children and neonates gradually formed and developed in the past years. This article proposes a pattern of transport network,organization type and its mode,focuses on introducing transport region and combination during every conveying link. Tasks before transportation,on the way and arrival at the center were described. Transport evaluation and quality control were brought into transport system management;moreover,setting up regional critically illed children transport network and experience in developing transport network were introduced.
Protein-Assembled Nanocrystal-Based Vertical Flash Memory Devices with Al2O3 Integration

This work presents vertical flash memory devices with protein-assembled PbSe nanocrystals as a floating gate and Al2O3 as a control oxide. The advantage of a vertical structure is that it improves cell density. Protein assembly improves uniformity of nanocrystals, which reduces threshold voltage variation among devices. The introduction of Al2O3 as a control oxide provided lower voltage/faster operation and hence less power consumption compared with the devices fabricated with SiO2. The integration of Al2O3 appeared to be compatible with the protein assembly approach. In conclusion, Al2O3 has the potential to become the high-k control oxide due to its relatively high electron/hole barrier heights, and high permittivity.
Mass Transport Properties

This chapter explains the effect of structure on grain boundary diffusion. Grain boundaries control the following mass transport properties of thin films, at least at temperatures less than one-half of the absolute melting temperature: conductivity during electromigration, reaction temperatures, and hillock formation. However, mass transport also occurs in mono-crystalline films where the point defect structure controls the rate of transport through the lattice. The chapter examines the effect of structure on all three modes of transport. It also reviews some thin films that are amorphous and the way mass transport in some of them has practical importance. Diffusion barriers are used to prevent diffusion between two layers. The chapter examines the ways the aspects of structure affect the ability of diffusion barrier materials to prevent atom transport and to prevent chemical reactions with the adjacent layers. The chapter also discusses the effect of pre-existing structure on the course of reactions between layers and the effect of defects introduced via radiation on the rates of reactions.
Racial and Ethnic Influences on Mental Health and Substance Use Disorders: The Case of Caribbean Blacks

The scientific literature supports that differences in socioeconomic status and poor living arrangements influence health outcomes. The fact that the nature of health inequalities differ by their sources raises important questions about causal factors related to substance abuse disorders. Prior studies have generally grouped respondents of African American and Caribbean black ethnicities into one global category of “Black” or African American. This aggregation may obscure important differences in substance use patterns. This study examines in- and out-of country Caribbean Blacks, in comparison to African Americans, at the population and individual levels and how processes of migration might influence substance use disorders. The study is based upon national household probability samples of non-institutionalized African Americans and Blacks from Caribbean countries living in the U.S., conducted between February 2001 and June 2003, with a slightly modified version of the World Mental Health version of the World Health Organization’s Composite International Diagnostic Interview. A total of 3570 African Americans and 1623 Caribbean Blacks, aged 18 and over were interviewed in the United States and an additional 2068 adults in Guyana and 1216 in Jamaica. In this study we found that prevalence of substance disorders vary by national context, with higher rates within the U.S. Rates of substance misuse were lower overall for women, but differ across cohorts by other socio-demographic factors. Nativity and length of time in the U.S. were also associated with mental health disorders. The needs and directions for future research are discussed.
Comparison of crosstalk for amplitude and phase modulation in an analog fiber optic link

We investigated analog rf crosstalk levels in a 25 km, wavelength-division multiplexed, Er-amplified fiber optic link for both a) amplitude modulation with direct photodetection and b) phase modulation with differential interferometric demodulation and photodetection. Experimental results are presented for optical channel spacing in the range 50 GHz to 200 GHz.
High-risk and poorly differentiated thyroid cancer

Follicular cell-derived thyroid carcinomas are classified based on their histology and cellular architecture, as well differentiated (papillary carcinoma and follicular carcinoma), poorly differentiated, and undifferentiated thyroid carcinomas (Pathology and genetics of tumors of endocrine organs. Lyon: IARC Press, 2004). Although the majority of clinically diagnosed thyroid cancers today are of the well-differentiated variety arising from follicular thyroid cells, dedifferentiation results in an aggressive phenotype which is responsible for an inordinate number of deaths from thyroid cancer.
Regulation of Plant Metabolism by Protein Phosphorylation. Possible Regulation of Sucrose-Phosphate Synthase by 14-3-3 Proteins

Reversible protein phosphorylation is known to be an important regulatory mechanism for several plant enzymes involved in primary carbon and nitrogen metabolism (1,2). Our laboratory has been studying two enzymes of sucrose metabolism, sucrose-phosphate synthase (SPS) and sucrose synthase (SuSy), and an enzyme of N-metabolism, NADH:nitrate reductase (NR), which are known to be phosphorylated in vivo. Interestingly, the effect of phosphorylation is somewhat different for the three enzymes. With SuSy, phosphorylation of the single, major phosphorylation site (Ser-15; ref. 3) has little effect on activity but appears to be one of the factors that controls its association with the plasma membrane (4) and actin cytoskeleton (5). Thus, phosphorylation affects intracellular localization of the enzyme. With NR, phosphorylation of Ser-543 has no direct effect on activity but completes the motif required for binding of a 14-3-3 inhibitor protein (6,7). Thus, phosphorylation affects enzyme activity indirectly by affecting protein:protein interactions. With SPS, phosphorylation appears to directly affect enzyme activity, at least in some cases. Current work suggests that SPS may have three regulatory phosphorylation sites: i) Ser-158, which is largely (or solely) responsible for light/dark modulation (8); ii) Ser-424, which is thought to be responsible for osmotic stress activation of SPS (9), and iii) Ser-229, which may constitute a binding site for a 14-3-3 inhibitor protein (10).
THE GROWTH OF A MANAGER: From Pure Research to Policy Administration

Publisher Summary This chapter presents an analysis on the growth of a manager from pure research to policy administration. The analysis is presented by Philip W. Hammer, Ph.D., Vice President, The Franklin Center, Franklin Institute Science Museum; Former Director of the Society of Physics Students; and Assistant Director of the Education Division, American Institute of Physics. He says, besides training for research, studying to obtain a Ph.D. is also a socialization process whereby one becomes a member of a community with common traditions, mores, and ways of communicating. Thus, to be effective in the physics community and to have credibility, a person should be a part of the physics culture. Congressional fellows are sponsored by a large number of professional societies. The program is designed to bring scientific expertise into the legislative process, while simultaneously exposing the science community to the intricacies of how policy is made at the federal level. Physics management fellowship is an opportunity to positively impact an organization in which there are opportunities for professional growth into permanent positions. Administration is a high-wattage activity, requiring lots of motion and human interaction. In contrast, projects get done at more of a slow burn, with much intellectual energy expended in the process of developing ideas and making plans. The work style is intense but steady for 8 to 9 hours per day.
Mechanism of the G-protein mimetic nanobody binding to a muscarinic G-protein-coupled receptor.

Protein-protein binding is key in cellular signaling processes. Molecular dynamics (MD) simulations of protein-protein binding, however, are challenging due to limited timescales. In particular, binding of the medically important G-protein-coupled receptors (GPCRs) with intracellular signaling proteins has not been simulated with MD to date. Here, we report a successful simulation of the binding of a G-protein mimetic nanobody to the M2 muscarinic GPCR using the robust Gaussian accelerated MD (GaMD) method. Through long-timescale GaMD simulations over 4,500 ns, the nanobody was observed to bind the receptor intracellular G-protein-coupling site, with a minimum rmsd of 2.48 A in the nanobody core domain compared with the X-ray structure. Binding of the nanobody allosterically closed the orthosteric ligand-binding pocket, being consistent with the recent experimental finding. In the absence of nanobody binding, the receptor orthosteric pocket sampled open and fully open conformations. The GaMD simulations revealed two low-energy intermediate states during nanobody binding to the M2 receptor. The flexible receptor intracellular loops contribute remarkable electrostatic, polar, and hydrophobic residue interactions in recognition and binding of the nanobody. These simulations provided important insights into the mechanism of GPCR-nanobody binding and demonstrated the applicability of GaMD in modeling dynamic protein-protein interactions.
Subungual atypical lentiginous melanocytic proliferations in children and adolescents: A clinicopathologic study.

Background Most subungual melanocytic lesions in children are benign, but some are difficult to classify due to prominent lentiginous growth and high-grade cytologic atypia. Objective To characterize the clinicopathologic features of these rare lesions. Methods Subungual atypical lentiginous melanocytic proliferations from patients Results Eleven patients aged 2-19 years had expanding or darkening longitudinal pigmented streak(s) with or without Hutchinson sign. Microscopically, all revealed predominantly single-cell growth, pagetoid scatter, and poor circumscription. Eight (73%) cases showed focal or poor nesting, and 3 (27%) demonstrated confluence. Nuclear enlargement, hyperchromasia, and angulation were present in 8 (73%) cases, 7 (64%) cases, and 6 (55%) cases, respectively. One of 4 cases tested by FISH was positive. Three lesions recurred locally without other adverse outcome. Limitations Small sample size and short clinical follow-up. Two cases were examined in partial biopsies only. Conclusion Some subungual melanocytic lesions in children and adolescents are histologically indistinguishable from adult subungual melanoma in situ. While the biologic potential remains elusive, FISH might aid in risk stratification. Awareness of this rare group of lesions is crucial for facilitating future investigation into its biologic behavior.