cssi/SciSciGPT-SciSciNet huggingface dataset:
Hemispheric differences in protein kinase C βII levels in the rat amygdala: baseline asymmetry and lateralized changes associated with cue and context in a classical fear conditioning paradigm

The amygdala is critically important for fear learning, and specific kinases have been implicated as contributors to the mechanisms that underlie learning. We examined levels of protein kinase C betaII (PKC betaII) in the left and right lateral and basolateral nuclei (LA/BLA) of the amygdala from animals that were classically fear conditioned with tones as cues and footshocks. Groups consisted of animals that received neither tones nor shocks, paired tones and shocks, or unpaired tones and shocks. At 1 h after conditioning, some animals from each group were used for biochemical measurements of PKC betaII levels and other animals were given probe trials to assess freezing behavior to cue and context. The levels of PKC betaII were greater in the left hemisphere in animals receiving neither tones nor shocks and animals receiving paired tones and shocks. PKC betaII levels were greater in the right hemisphere of animals receiving randomly presented tones and shocks. Freezing times to cue were long (>80% of probe trial time) in both the paired tone/shock and randomly unpaired tone/shock groups. Freezing times to context were long in the unpaired tone/shock group, but not the paired tone/shock group. Correlational analyses showed that freezing times to context, but not cue, precisely predicted the right/left relation of PKC betaII levels in the LA/BLA: the greater the time spent freezing to context, the greater the increase in right hemisphere PKC betaII levels. We conclude that fear conditioning causes hemisphere and input specific increases in PKC betaII in the rat LA/BLA.
‘She says herself, “I have no future”’: love, fate and territory in Leh District, India

How and to what extent can love and desire be managed as factors in geopolitical strategy? This research expands the subject matter of geopolitical analysis and uses feminist tactics to highlight the contingent and embodied practices through which geopolitical strategies materialize in seemingly unlikely venues. In the Leh District of India's Jammu and Kashmir State, political conflict between Buddhists and Muslims has been articulated in part through women's bodies. Buddhists and Muslims are producing an embodied religious boundary through the prevention of inter-religious marriages. While in this case love has the potential to challenge political narratives, any transgressive force is blunted by the separation of intermarrying couples or their expulsion from the territory of Leh District. Drawing on interviews, survey data and participatory oral histories in Leh District, this article seeks to destabilize and complicate the global geopolitical gaze by bringing the corporeal, desiring and desired body to...
Sequence of T4, T2 and T6 bacteriophage species I RNA and specific cleavage by an E. coli endonuclease.

A phage T4 RNA species with structural similarity to tRNA, has been sequenced and its sequence compared with sequences of related molecules in T2 and T6. An E. coli endonuclease specifically cleaves these tRNAs.
Effect of Liquid Bolus Consistency and Delivery Method on Aspiration and Pharyngeal Retention in Dysphagia Patients

There is no empirically derived consensus as to what food consistency types and method of food delivery (spoon, cup, straw) should be included in the videofluoroscopic swallowing (VFSS) studies. In the present study, we examine the rates of aspiration and pharyngeal retention in 190 dysphagic patients given thin (apple juice) and thick (apricot nectar) liquids delivered by teaspoon and cup and ultrathick (pudding-like) liquid delivered by teaspoon. Each patient was tested with each of the bolus/delivery method combinations. The fractions of patients exhibiting aspiration for each bolus/method of delivery combination were (1) thick liquids (cup), 13.2%; (2) thick liquids (spoon), 8.9%; (3) thin liquids (cup), 23.7%; (4) thin liquids (spoon), 15.8%, (5) ultrathick liquids (spoon), 5.8%. In each comparison [thick liquid (cup) vs. thick liquid (spoon), thin liquid (cup) vs. thin liquid (spoon), thick liquid (cup) vs. thin liquid (cup), thick liquid (spoon) vs. thin liquid (spoon), and thick liquid (spoon) vs. ultrathick liquid (spoon)], the p value for χ2 was <0.001. These results suggest that utilizing thin, thick, and ultrathick liquids and delivery by cup and spoon during a VFSS of a patient with mild or moderate dysphagia can increase the chances of identifying a consistency that the patient can swallow without aspirating and without pharyngeal retention after swallowing.
Distal Digital Embolization from a Thrombosed Aneurysmal Hemodialysis Arteriovenous Fistula: The Benefit of a Hybrid Approach

Aneurysmal degeneration of a hemodialysis arteriovenous fistula (AVF) is common; however, distal digital embolization from an AVF is extremely rare. Even though the ultimate fate of all arteriovenous hemodialysis access is thrombosis with minimal consequences, dislodgement of thrombus at the proximal anastomosis could lead to ischemia of the distal arterial circulation. We here present a case of a renal transplant patient with a thrombosed aneurysmal AVF who presented with acute digital ischemia successfully treated with combination catheter-directed thrombolysis and open repair. No similar report was found describing this entity treated with this approach.
Phase equilibria and solidification behavior in the PbF2−AlF3 system

The relationship between phase equilibria in the PbF2−AlF3 system and the solidification behavior of several ternary lead aluminum fluoride compounds was explored. A partial binary phase diagram for the PbF2−AlF3 system was determined from differential thermal analysis, annealing and directional solidification studies. The compounds AlF3, Pb3Al2F12, Pb9Al2F24, and a PbF2 solid solution were identified by x-ray diffraction, energy dispersive and microprobe analysis. The previously reported phases PbAlF5 and PbAl2F8 were not observed. Directional solidification studies showed that it is possible to grow crystals of AlF3, Pb3Al2F12, and the PbF2 solid solution from nonstoichiometric PbF2−AlF3 melts. The compound Pb9Al2F24 was found to decompose on heating by a peritectoid reaction (forming two other solids) and thus could not be solidified directly from a PbF2−AlF3 melt.
SGDBR Single-Chip Wavelength Tunable Lasers for Swept Source OCT

Sampled Grating Distributed Bragg Reflector (SGDBR) monolithic tunable lasers are now entering the production phase in telecommunications applications. These tunable lasers are unique in that they offer wide wavelength tuning (1525 to 1565 nm), fast wavelength tuning (5 ns) and high speed amplitude modulation all on the same monolithic chip 1,2,3,4 . This work studies the applicability of SGDBR monolithic tunable laser diodes for biomedical imaging using swept-wavelength or Fourier domain optical coherence tomography. This paper will present our work involved with utilizing the strengths (table 1) of this SGDBR laser class and mitigating the weaknesses (table 2) of this device for swept-wavelength imaging applications. The strengths of the laser are its small size (portable solutions), wide wavelength range (good distance resolution), fast switching speeds (improved update rates), wide choice of center wavelengths, and lower power consumption. The weaknesses being addressed are the complicated wavelength tuning mechanism (3 wavelength control currents), wider laser linewidth (10s of MHz), moderate output power (10mW ), and the need for improved laser packaging. This paper will highlight the source characterization results and discuss an initial measurement architecture utilizing the SGDBR measurement engine.
Examination of the current injection technique (distribution networks)

The limitations of the current injection technique are described. Time domain steady state simulation of the six pulse AC-DC converter in distribution systems is used as a model to determine those limitations. The simulation is able to operate under balanced or unbalanced circumstances. The time domain steady state simulation shows that the simple current injection technique is not a bad model for harmonic analysis if the converter operates under balanced conditions. If the converter is subject to irregular conditions, however, current injection might be inaccurate. >
Vertigo secondary to postlabyrinthectomy neuroma

Recurrent vertigo after ablation of vestibular sense organs is an unusual but perplexing clinical picture to the otologist. The explanation for this sequela after ablation surgery in order of decreasing frequency includes: (1) incomplete ablation of vestibular sense organs or neural input; (2) pathology in the contralatera1 labyrinth; (3) inadequate central mechanisms to compensate for unilateral vestibular ablation; and (4) a postlabyrinthectomy (amputation) neuroma. The possibility of incomplete ablation after either sense organ destruction (labyrinthectomy) or vestibular neurectomy can usually be ruled out by careful attention to the surgical ablation procedure. Complete ablation of all five vestibular sense organs, particularly the posterior canal crista, is necessary for a complete labyrinthectomy. This procedure destroys the vestibular sense organs and amputates the distal segments of vestibular neuron dendrites. Incomplete vestibular nerve transection may occur when a selective vestibular neurectomy is performed to preserve hearing. Whether by the middle fossa or posterior fossa itracranial approaches, guidance by anatomic landmarks and knowledge of the histological anatomy of the vestibular and auditory nerve components of the VIII nerve are necessary to insure complete transection of this nerve. Postoperative vestibular tests may or may not indicate persistent vestibular function after these surgical procedures. Therefore, careful reliance on the
Frontal brain volume and context effects in short-term recall in schizophrenia

In a group of schizophrenic patients, magnetic resonance imaging (MRI) measures of relative frontal brain volume (total frontal volume/total cerebral volume) correlated highly with the capacity to use context as an aid to recall in a verbal memory task. The dorsolateral area of the prefrontal cortex appears to have contributed most to this effect. Recall of simple word lists without contextual features revealed no correlation with relative frontal volume. With increasing contextual organization of the material, correlations between frontal volume and recall scores increased significantly. These findings are consistent with the general proposition that impairment in the use of informational redundancy is a significant component of schizophrenic pathology.
Convergent and parallel activation of low-conductance potassium channels by calcium and cAMP-dependent protein kinase

K+ channels, which have been linked to regulation of electrogenic solute transport as well as Ca2+ influx, represent a locus in hepatocytes for the concerted actions of hormones that employ Ca2+ and cAMP as intracellular messengers. Despite considerable study, the single-channel basis for synergistic effects of Ca2+ and cAMP on hepatocellular K+ conductance is not well understood. To address this question, patch-clamp recording techniques were applied to a model liver cell line, HTC hepatoma cells. Increasing the cytosolic Ca2+ concentration ([Ca2+]i) in HTC cells, either by activation of purinergic receptors with ATP or by inhibition of intracellular Ca2+ sequestration with thapsigargin, activated low-conductance (9-pS) K+ channels. Studies with excised membrane patches suggested that these channels were directly activated by Ca2+. Exposure of HTC cells to a permeant cAMP analog, 8-(4-chlorophenylthio)-cAMP, also activated 9-pS K+ channels but did not change [Ca2+]i. In excised membrane patches, cAMP-dependent protein kinase (the downstream effector of cAMP) activated K+ channels with conductance and selectivity identical to those of channels activated by Ca2+. In addition, cAMP-dependent protein kinase activated a distinct K+ channel type (5 pS). These data represent the differential regulation of low-conductance K+ channels by signaling pathways mediated by Ca2+ and cAMP. Moreover, since low-conductance Ca(2+)-activated K+ channels have been identified in a variety of cell types, these findings suggest that differential regulation of K+ channels by hormones with distinct signaling pathways may provide a mechanism for hormonal control of solute transport and Ca(2+)-dependent cellular functions in the liver as well as other nonexcitable tissues.
A Prospective Randomized Study of Abdominal Aortic Surgery without Postoperative Nasogastric Decompression

Abstract Nasogastric decompression following abdominal aortic aneurysmectomy or bypass, for 3–4 days, is a routine part of postoperative care in many centers. A prospective randomized study of 80 patients undergoing abdominal aortic surgery was performed in order to determine the necessity of prolonged nasogastric decompression. Patients were divided evenly between removal of the nasogastric tube upon tracheal extubation and retention of the tube until the passage of flatus. Preoperative risk factors, aortic cross-clamp time, estimated blood loss, length of procedure, length of intensive care unit stay, numbers of days with nasogastric tube, number of days until clear liquid and regular diets commenced, and the length of hospital stay were recorded for all patients. There were no significant differences in any of the measured variables between the two groups. The length of hospital stay was similar in both groups and three patients in each group required a nasogastric tube or reinsertion of one. In conclusion, the routine postoperative use of nasogastric tubes for abdominal aortic procedures is unnecessary. Copyright © 1996 The International Society for Cardiovascular Surgery.
A prognostic scoring system for adult patients less than 60 years of age with acute lymphoblastic leukemia in first relapse

The outcome of patients with acute lymphoblastic leukemia (ALL) in first relapse is poor. We retrospectively evaluated patients with ALL in first relapse, 18–60 years of age, to define a prognostic score. For all patients, a scoring system of 0–3 was developed with 1 point for each of the following: age at diagnosis ≥45 years, lactate dehydrogenase (LDH) at the time of relapse ≥1.5 times upper limits of normal (ULN), not proceeding to allogeneic bone marrow transplant (BMT). A similar scoring system was developed for patients proceeding to BMT. LDH ≥1.5 times ULN at the time of relapse predicted poor overall survival. Patients with a prognostic score of greater than 1 have a poor prognosis, even with BMT, and should be considered for treatment with innovative approaches such as Phase 1 clinical trials.
A Contemporary Graduate Program in Communication in Instruction.

This article describes the masters and doctoral programs focusing on communication in instruction offered by West Virginia University. The antecedents of the programs, the beginnings at WVU, the assumptions underlying the programs, the nature of each program, and the benefits of each program are discussed.
Gene expression and cellular sources of inducible nitric oxide synthase during tumor promotion

The present studies examined the temporal sequence of inducible nitric oxide synthase (iNOS) gene expression and the cellular sources of iNOS protein and of 3-nitrotyrosine, as a marker of production of nitric oxide-derived reactive nitrogen intermediates during murine multi-stage carcinogenesis. Levels of iNOS mRNA in dorsal skin isolated from acetone-treated female Sencar mice were 2.5-fold higher than iNOS gene expression detected in cutaneous tissue isolated from Sencar mice at 1, 3, 6, 10, 16 and 22 weeks after exposure to a single topical application of 25 nmol 7,12-dimethylbenz[a]anthracene (DMBA) followed by repetitive applications of 2 microgram 17-O-tetradecanoylphorbol-13-acetate (TPA). Papillomas isolated at 16 and 22 weeks of a tumor promotion protocol also had low levels of iNOS mRNA. The diminished levels of iNOS mRNA inversely correlated with the extent of TPA-induced epidermal hyperplasia. In acetone-treated mouse skin, iNOS immunospecific antibody binding was localized to the stratum corneum and suprabasal keratinocytes. In contrast, iNOS protein was present in lower amounts and was localized to the upper-most suprabasal keratinocytes in cutaneous tissue isolated at 22 weeks following a single exposure to either 25 nmol DMBA or acetone and repetitive applications of 2 microgram TPA. At all time points examined over the 22 week time period of papilloma growth, infiltrating neutrophils within the dermis bound significant levels of anti-iNOS antibodies. The production of iNOS by neutrophils within the dermis correlated with the formation of protein nitrotyrosination within the dermal tissue, as detected by 3-nitrotyrosine-specific antibodies. The present studies indicate that NOS and reactive nitrogen intermediates, including peroxynitrite, are produced specifically by dermal neutrophils during the tumor promotion process at time points that correspond to simultaneous production of reactive oxygen intermediates. Conversely, iNOS is simultaneously down-regulated in hyperplastic epidermis and in papillomas.
How Do Coverage Policies Influence Practice Patterns, Safety, and Cost of Initial Lumbar Fusion Surgery? A Population-based Comparison of Workers’ Compensation Systems

BACKGROUND CONTEXT: In response to increasing use of lumbar fusion for improving back pain, despite unclear efficacy, particularly among injured workers, some insurers have developed limited coverage policies. Washington State’s workers’ compensation (WC) program requires imaging confirmation of instability and limits initial fusions to a single level. In contrast, California requires coverage if a second opinion supports surgery, allows initial multilevel fusion, and provides additional reimbursement for surgical implants. There are no studies that compare population-level effects of these policy differences on utilization, costs, and safety of lumbar fusion. PURPOSE: The purpose of this study was to compare population-level data on the use of complex fusion techniques, adverse outcomes within 3 months, and costs for two states with contrasting coverage policies. STUDY DESIGN AND SETTING: The study design was an analysis of WC patients in California and Washington using the Agency for Healthcare Research and Quality’s State Inpatient Databases, 2008‐2009. PATIENT SAMPLE: All patients undergoing an inpatient lumbar fusion for degenerative disease (n54,628) were included the patient sample. OUTCOME MEASURE(S): Outcome measures included repeat lumbar spine surgery, all-cause readmission, life-threatening complications, wound problems, device complications, and costs. METHODS: Log-binomial regressions compared 3-month complications and costs between states, adjusting for patient characteristics. RESULTS: Overall rate of lumbar fusion operations through WC programs was 47% higher in California than in Washington. California WC patients were more likely than those in Washington to undergo fusion for controversial indications, such as nonspecific back pain (28% versus 21%) and disc herniation (37% versus 21%), as opposed to spinal stenosis (6% versus 15%), and spondylolisthesis (25% versus 41%). A higher percentage of patients in California received circumferential procedures (26%versus5%),fusionofthreeormorelevels(10%versus5%),andbonemorphogeneticprotein(50% versus 31%). California had higher adjusted risk for reoperation (relative risk [RR] 2.28; 95%
Aerosols produced by X-rays☆

Abstract Small proportions of organic vapors in air produce aerosols under the influence of X-rays. The particulates are generally spherical in shape and less than a micron in diameter. Those formed from acetylene and benzene vapor appear yellow and brown, respectively. They are essentially nonvolatile at room temperature and are very stable even when exposed to the high vacuum of an electron microscope. However, a substantial size reduction was attained by several hours of heating at 250°C under atmospheric pressure. The size and quantity of the particulates formed under Xirradiation depend on the organic vapor, its concentration, the humidity of the air, the intensity of the X-rays, irradiation time, and aging time after exposure. The growth and formation of particulates do not stop immediately after exposure ceases. Infrared spectrum analysis provides information on the chemical structure of the particulates.
Self-Enhancement and Learning from Performance Feedback

The theory of performance feedback views decision makers as problem solvers seeking to improve performance. By specifying how and when decision makers may instead seek to enhance their self-image by assessing performance as satisfactory, the model presented in this article specifies boundaries on performance feedback theory's critical prediction that low performance induces increased search, change, and risk taking, and it suggests one reason why decision makers sometimes fail to learn from their mistakes.
Collinear electron–helium-ion collisions: Chaotic scattering dominated by triple-collision orbits

We study the fractal scattering patterns of collinear collisions between an electron and a helium ion or a hydrogen atom. We have found that the collisional time plotted against initial energy or initial phase consists of a bi-infinite sequence of cusp-shaped regular intervals interlaced by chaotic bands and repeated enlargements of the chaotic bands show similar patterns. These patterns resemble the previous ones obtained in the retrograde region of the coplanar scattering system, however, the dynamical origin of the self-similar patterns is different and can be understood in terms of various combinations of motions perpendicular and parallel to the Wannier ridge and binary collisions. In particular, we have found that the trajectories near the cusp tips of regular intervals are strongly influenced by a set of triple-collision orbits, trajectories originate and end at the triple-collision point. Using the code and winding number for these orbits, we can organize the fractal scattering patterns into a tree structure. Furthermore, using an ensemble of trajectories with uniformly selected initial phases, we calculate the transition probabilities of excited electronic states from a certain initial state of the hydrogenlike ion or atom using the quasiclassical trajectory method. These transition probabilities illustrate that chaotic regions onmore » the average correspond to higher electronic excitation than that corresponding to the regular regions. {copyright} {ital 1996 The American Physical Society.}« less
Mental Travel and Memory Mapping in Sebald's Work

In his article "Mental Travel and Memory Mapping in Sebald's Narratives" Jonathan White analyses several of the journeys — real and by means of the mind — by which W.G. Sebald follows what he once called "invisible connections that determine our lives." These connections are often although not always between the living and the dead "on the far side of time." In reaction against what Sebald interpreted as a conspiracy of silence in his youth over the destruction that Germany had caused and that which had been done in turn to it, Sebald attempted to reconstruct worlds and people destroyed or changed irremediably. Sometimes photographs are used in a form of communication akin to that which occurs between the living and the dead in Dante's Commedia. White suggests that Sebald's modes of real and mental travel are not only highly productive, but also capable of being followed by others in positive ways. Sebald's writing and the journeys of differing kind undertaken in it teach us negotiable routes into the uncanny. Jonathan White, "Mental Travel and Memory Mapping in Sebald's Narratives" page 2 of 9 CLCWeb: Comparative Literature and Culture 14.5 (2012): Special Issue New Work about the Journey and Its Portrayals. Ed. I-Chun Wang
NUP98–NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis

Nuclear receptor-binding SET domain protein 1 (NSD1) prototype is a family of mammalian histone methyltransferases (NSD1, NSD2/MMSET/WHSC1, NSD3/WHSC1L1) that are essential in development and are mutated in human acute myeloid leukemia (AML), overgrowth syndromes, multiple myeloma and lung cancers. In AML, the recurring t(5;11)(q35;p15.5) translocation fuses NSD1 to nucleoporin-98 (NUP98). Here, we present the first characterization of the transforming properties and molecular mechanisms of NUP98-NSD1. We demonstrate that NUP98-NSD1 induces AML in vivo, sustains self-renewal of myeloid stem cells in vitro, and enforces expression of the HoxA7, HoxA9, HoxA10 and Meis1 proto-oncogenes. Mechanistically, NUP98-NSD1 binds genomic elements adjacent to HoxA7 and HoxA9, maintains histone H3 Lys 36 (H3K36) methylation and histone acetylation, and prevents EZH2-mediated transcriptional repression of the Hox-A locus during differentiation. Deletion of the NUP98 FG-repeat domain, or mutations in NSD1 that inactivate the H3K36 methyltransferase activity or that prevent binding of NUP98-NSD1 to the Hox-A locus precluded both Hox-A gene activation and myeloid progenitor immortalization. We propose that NUP98-NSD1 prevents EZH2-mediated repression of Hox-A locus genes by colocalizing H3K36 methylation and histone acetylation at regulatory DNA elements. This report is the first to link deregulated H3K36 methylation to tumorigenesis and to link NSD1 to transcriptional regulation of the Hox-A locus.
Vasoactive Intestinal Peptide Interacts with Alpha-adrenergic-, Cholinergic-, and Substance-P-mediated Responses in Rat Parotid and Submandibular Glands:

Secretory dose-response curves were obtained with both acetylcholine and phenylephrine treatment in rat parotid and submandibular glands. Vasoactive intestinal peptide (VIP), which produced relatively low volumes of protein-rich saliva in rat salivary glands, also enhanced acetylcholine-, phenylephrine-, and substance-P-mediated fluid and protein secretion when administered in combination with these agents. The specific mechanisms involved in the synergistic actions of VIP with substances such as acetylcholine, phenylephrine, and substance P, which are primarily linked to the production of fluid secretion in rat salivary glands, have yet to be determined.
Problems of materials in mechanical heart systems.

Currently available materials for mechanical heart systems are surveyed, particularly with respect to long-term implantation, from the viewpoints of availability and workability, mechanical and biological durability, and compatibility with blood and tissue. Some materials have one or more desirable physical properties, but none offers perfect blood and tissue compatibility. Medical grade Silastic, considered best for blood handling parts, has produced promising results in auxiliary ventricle patency experiments. The insufficient tensile strength of Silastic should be increased, and it may be possible to accomplish this while maintaining the present resilience, elongation, and inertness. No long-term data on thrombus formation are available, but clot-retarding quality is essential and may perhaps be obtained by incorporating heparin. Developments in polymer chemistry may also lead to other surfaces with the requisite mechanical properties with blood.
Commentary on "a roadmap for the prevention of dementia II: Leon Thal Symposium 2008." A national registry on aging.

As the field of aging and dementia evolves, it becomes apparent that there are likely multiple underlying continua of clinical and pathological substrates that characterize progression. On the clinical side, there is a natural progression from normal cognition through mild cognitive impairment (MCI) to dementia. Correspondingly, on the neuropathological side, there is a gradual accumulation of pathological markers that likely develop over years and probably decades. The challenge is to develop reliable and valid correspondences between the clinical features and the underlying neuropathological markers that are consistent and meaningful. Numerous studies have demonstrated that clinically normal individuals, late in life, can harbor significant pathology in the brain, and, conversely, some individuals who are demented have relatively little demonstrable pathology[1–3]. The correlations are imperfect. Currently, we make arbitrary distinctions among clinical categories such as normal aging, MCI and dementia. While we all recognize the artificiality of dividing a continuum into discrete categories, the exercise does serve a purpose in allowing us to communicate the clinical significance of findings to patients and also promotes interactions among physicians and scientists[4–6]. Similarly, from a neuropathological perspective, we make arbitrary distinctions regarding the meaningfulness of the development of amyloid deposits in the brain and the spread of neurofibrillary tangles throughout the brain[7]. Again, while certain demarcations are necessary for communication, the clinical significance of the development and spread of these markers needs to be clarified. As mentioned, the clinical-pathological correspondence between these two continua is variable. This type of discussion begs for the development of a collection of persons across the age spectrum on whom extensive demographic, clinical, imaging and biomarker data would be available. It is only through the longitudinal study of all of these measures in concert that we will be able to untangle these important questions regarding the development and progression of diseases of aging.
Diabetes mellitus: Exploring the challenges in the drug development process

Diabetes mellitus has reached epidemic proportions and continues to be a major burden on society globally. The International Diabetes Federation (IDF) estimated the global burden of diabetes to be 366 million in 2011 and predicted that by 2030 this will have risen to 552 million. In spite of newer and effective treatment options, newer delivery and diagnostic devices, stricter glycaemic targets, better treatment guidelines and increased awareness of the disease, baseline glycosylated hemoglobin remains relatively high in subjects diagnosed and treated with type 2 diabetes. The search continues for an ideal anti diabetic drug that will not only normalize blood glucose but also provide beta cell rest and possibly restoration of beta cell function. The development of anti diabetic drugs is riddled with fundamental challenges. The concept of beta cell rest and restoration is yet to be completely understood and proven on a long term. The ideal therapeutic approach to treating type 2 diabetes is not yet determined. Our understanding of drug safety in early clinical development is primarily limited to Type A reactions. Until marketing authorization most drugs are approved based on the principle of confirming non-inferiority with an existing gold standard or determining superiority to a placebo. The need to obtain robust pharmaco-economic data prior to marketing authorization in order to determine appropriate pricing of a new drug remains a major challenge. The present review outlines some of the challenges in drug development of anti-diabetic drugs citing examples of pulmonary insulin, insulin analogues, thiazolidinediones and the GLP1 analogues.
Regulation of expression of the valine (branched-chain amino acid) dehydrogenase-encoding gene from Streptomyces coelicolor.

Abstract Expression of the Streptomyces coelicolor (Sc) valine (branched-chain amino acid) dehydrogenase-encoding gene (vdh) is regulated by valine, glucose and NH4+ at the transcriptional level. The results of assays for the level of accumulated vdh mRNA in the Sc J802 strain by primer extension experiments and for the level of catechol dioxygenase (Xy1E) activity in Sc J802 (vdh::xylE) transformants show that transcription of the vdh gene is induced approx. 2.5-fold by valine, as compared to asparagine as the sole nitrogen source in the presence of glucose as carbon source. Valine induction is repressed by glucose, as compared to glycerol as the carbon source, and by NH4+. Glucose catabolite repression is relieved in Sc M480, a glucose kinase (glkA) deletion mutant. This suggests that glucose repression of vdh and carbohydrate metabolism are due to the same mechanism in Sc, which involves glucose kinase.
The role of stress hormones in exercise-induced suppression of alveolar macrophage antiviral function

We hypothesized that a previously observed exercise-induced suppression of alveolar macrophage antiviral resistance results from increases in corticosterone and/or epinephrine. Mice (CD-1) were run to fatigue on a treadmill (exercise), or placed in Plexiglas lanes above the treadmill (control). The role of corticosterone was assessed by further dividing mice into groups receiving one of the following treatments; sham surgery, adrenalectomy, or adrenalectomy plus corticosterone replacement. Macrophage antiviral function was suppressed in the exercised mice compared to the control mice. However, macrophage antiviral function was not suppressed in the exercised mice that underwent adrenalectomy or adrenalectomy plus corticosterone replacement. We tested whether another adrenal factor (epinephrine) may be involved by dividing mice into exercise and control groups treated with either saline or propranolol. Macrophage antiviral function was again suppressed in the saline-treated exercised mice compared to saline-treated control mice, but no differences were found between the exercised mice receiving propranolol, control mice receiving propranolol, or saline-treated control mice. Isoproterenol, when added to alveolar macrophages in culture, also suppressed antiviral resistance. These findings suggest that decreased macrophage antiviral function following exercise may be due to increased release of adrenal catecholamines.
Sterol Carrier Protein-2 Expression Modulates Protein and Lipid Composition of Lipid Droplets

Despite the critical role lipid droplets play in maintaining energy reserves and lipid stores for the cell, little is known about the regulation of the lipid or protein components within the lipid droplet. Although immunofluorescence of intact cells as well as Western analysis of isolated lipid droplets revealed that sterol carrier protein-2 (SCP-2) was not associated with lipid droplets, SCP-2 expression significantly altered the structure of the lipid droplet. First, the targeting of fatty acid and cholesterol to the lipid droplets was significantly decreased. Second, the content of several proteins important for lipid droplet function was differentially increased (perilipin A), reduced severalfold (adipose differentiation-related protein (ADRP), vimentin), or almost completely eliminated (hormone-sensitive lipase and proteins >93 kDa) in the isolated lipid droplet. Third, the distribution of lipids within the lipid droplets was significantly altered. Double labeling of cells with 12-(N-methyl)-N-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-octadecanoic acid (NBD-stearic acid) and antisera to ADRP showed that 70, 24, and 13% of lipid droplets contained ADRP, NBD-stearic acid, or both, respectively. SCP-2 expression decreased the level of ADRP in the lipid droplet but increased the proportion wherein ADRP and NBD-stearic acid colocalized by 3-fold. SCP-2 expression also decreased the lipid droplet fatty acid and cholesterol mass (nmol/mg protein) by 5.2- and 6.6-fold, respectively. Finally, SCP-2 expression selectively altered the pattern of esterified fatty acids in favor of polyunsaturated fatty acids within the lipid droplet. Displacement studies showed differential binding affinity of ADRP for cholesterol and fatty acids. These data suggested that SCP-2 and ADRP play a significant role in regulating fatty acid and cholesterol targeting to lipid droplets as well as in determining their lipid and protein components.
Tailoring Architecture of Nanothin Hydrogels: Effect of Layering on pH-Triggered Swelling

We have tailored the internal architecture of ultrathin poly(methacrylic acid) (PMAA) hydrogels from well stratified to highly intermixed by controlling the internal structure in layer-by-layer templates used for hydrogel fabrication. We have found pH-triggered swelling properties of these hydrogels to be significantly affected by hydrogel architecture. Well-stratified hydrogels exhibited a dramatic 10-fold increase in thickness when transitioned between pH = 5 and 7.5, unlike the 2-fold swelling observed in less-organized hydrogels.
On-line chemical analysis of aerosols by rapid single-particle mass spectrometry

Abstract The design and performance of an instrument for rapid single-particle mass spectrometry (RSMS) is described. Aerosols are sampled directly into a mass spectrometer where individual particles are detected by light scattering from a continuous laser beam. The scattered radiation from each particle triggers an excimer laser which ablates the particle in-flight. Ions produced from the particle are analyzed by time-of-flight mass spectrometry. The chemical composition of the particle is inferred from the distribution of ions in the mass spectrum. Since the chemical composition is determined approximately 1 ms after a particle enters the sampling inlet, chemical transformation by reaction, condensation, evaporation, or phase change is minimized. Since the ion formation process in RSMS is similar to that in laser microprobe mass spectrometry, RSMS exhibits similar attributes for single-particle analysis. These include detection of trace organic and inorganic species, speciation of inorganic materials, and the ability to distinguish the surface versus total volume composition of a particle. RSMS extends these capabilities to include semivolatile compounds and surface chemical reactions. Potential applications of RSMS to atmospheric aerosols are discussed including speciation of semivolatile and nonvolatile sulfur compounds, source apportionment through isotopic ratio measurements, and the detection of thin coatings on particles produced by condensation of reactive gases.
The Use of Bole Surface in the Estimation of Woodland Production

The biological potential for timber production is defined as the accumulated fractions of net primary production expected to become timber. It is proposed that the timber fraction of ecosystem production can be expressed as a matrix of primary units of measure. The primary matrix is a set of values for volume, bole surface, and length arrayed by top diameters of stem segments and aggregated from the largest to the smallest. From this matrix one may estimate the potential production of a multitude of timber products. It is proposed that this primary matrix also is practical for estimating biomass, energy, water and nutrient flows, and the distribution of organic matter among trees, shrubs, and herbaceous plants. These relations can provide a basis for practical choices among alternative silvicultural actions and for estimating how much organic matter can be harvested as a crop in relation to other forest goods and services.
Hydroclimate of the Western United States Based on Observations and Regional Climate Simulation of 1981–2000. Part I: Seasonal Statistics

The regional climate of the western United States shows clear footprints of interaction between atmospheric circulation and orography. The unique features of this diverse climate regime challenges climate modeling. This paper provides detailed analyses of observations and regional climate simulations to improve our understanding and modeling of the climate of this region. The primary data used in this study are the 1/88 gridded temperature and precipitation based on station observations and the NCEP‐NCAR global reanalyses. These data were used to evaluate a 20-yr regional climate simulation performed using the fifth-generation Pennsylvania State University‐National Center for Atmospheric Research (Penn State‐NCAR) Mesoscale Model (MM5) driven by large-scale conditions of the NCEP‐NCAR reanalyses. Regional climate features examined include seasonal mean and extreme precipitation; distribution of precipitation rates; and precipitation intensity, frequency, and seasonality. The relationships between precipitation and surface temperature are also analyzed as a means to evaluate how well regional climate simulations can be used to simulate surface hydrology, and relationships between precipitation and elevation are analyzed as diagnostics of the impacts of surface topography and spatial resolution. The latter was performed at five east‐west transects that cut across various topographic features in the western United States. These analyses suggest that the regional simulation realistically captures many regional climate features. The simulated seasonal mean and extreme precipitation are comparable to observations. The regional simulation produces precipitation over a wide range of precipitation rates comparable to observations. Obvious biases in the simulation include the oversimulation of precipitation in the basins and intermountain West during the cold season, and the undersimulation in the Southwest in the warm season. There is a tendency of reduced precipitation frequency rather than intensity in the simulation during the summer in the Northwest and Southwest, which leads to the insufficient summer mean precipitation in those areas. Because of the general warm biases in the simulation, there is also a tendency for more precipitation events to be associated with warmer temperatures, which can affect the simulation of snowpack and runoff.
Child development and evolutionary psychology.

Evolutionary developmental psychology involves the expression of evolved, epigenetic programs, as described by the developmental systems approach, over the course of ontogeny. There have been different selection pressures on organisms at different times in ontogeny, and some characteristics of infants and children were selected in evolution to serve an adaptive function at that time in their life history rather than to prepare individuals for later adulthood. Examples of such adaptive functions of immaturity are provided from infancy, play, and cognitive development. Most evolved psychological mechanisms are proposed to be domain specific in nature and have been identified for various aspects of children’s cognitive and social development, most notably for the acquisition of language and for theory of mind. Differences in the quality and quantity of parental investment affect children’s development and influence their subsequent reproductive and childcare strategies. Some sex differences observed in childhood, particularly as expressed during play, are seen as antecedents and preparations for adult sex differences. Because evolved mechanisms were adaptive to ancestral environments, they are not always adaptive for contemporary people, and this mismatch of evolved mechanisms with modern environments is seen in children’s maladjustment to some aspects of formal schooling. We argue that an evolutionary perspective can be valuable for developing a better understanding of human ontogeny in contemporary society and that a developmental perspective is important for a better understanding of evolutionary psychology.
High-resolution human cervical spinal cord imaging at 7 T

We present high-resolution anatomical imaging of the cervical spinal cord in healthy volunteers at the ultrahigh field of 7T with a prototype four-channel radiofrequency coil array, in comparison with 3-T imaging of the same subjects. Signal-to-noise ratios at both field strengths were estimated using the rigorous Kellman method. Spinal cord crosssectional area measurements were performed, including whole-cord measurements at both fields and gray matter segmentation at 7T. The 7-T array coil showed reduced sagittal coverage, comparable axial coverage and the expected significantly higher signal-to-noise ratio compared with equivalent 3-T protocols. In the cervical spinal cord, the signal-to-noise ratio was found by the Kellman method to be higher by a factor of 3.5 with the 7-T coil than with standard 3-T coils. Cervical spine imaging in healthy volunteers at 7T revealed not only detailed white/gray matter differentiation, but also structures not visualized at lower fields, such as denticulate ligaments, nerve roots and rostral–caudal blood vessels. Whole-cord cross-sectional area measurements showed good agreement at both field strengths. The measurable gray/white matter cross-sectional areas at 7T were found to be comparable with reports from histology. These pilot data demonstrate the use of higher signal-to-noise ratios at the ultrahigh field of 7T for significant improvement in anatomical resolution of the cervical spinal cord, allowing the visualization of structures not seen at lower field strength, particularly for axial imaging. Copyright © 2011 John Wiley & Sons, Ltd.
Evaluative Pressure in Mothers: Effects of Situation, Maternal, and Child Characteristics on Autonomy Supportive Versus Controlling Behavior

This study examined the effects of situational pressure and maternal characteristics (social contingent self-worth, controlling parenting attitudes) on mothers' autonomy support versus control in the social domain. Sixty 4th-grade children and their mothers worked on a laboratory task in preparation for meeting new children, with mothers in either an evaluation (mothers told their child would be evaluated by other children) or no-evaluation (no mention of evaluation) condition. Mothers in the evaluation condition spent more time giving answers to their children. Mothers with controlling parenting attitudes exhibited more controlling behavior. Further, mothers with high social contingent self-worth in the evaluation condition were most controlling. Results suggest the importance of interactions between situations and maternal characteristics in determining levels of mothers' autonomy support versus control and have implications for helping parents support children's autonomy.
Ag i-like array 4d 10 5s–4d 9 5s5p of I vii through Eu xvii

The spectra were produced with a high-voltage spark discharge and photographed with the National Bureau of Standards’ 10.7-m grazing-incidence spectrograph. The Ag i-like transition array 4d105s–4d95s5p was first identified by comparison with the analogous array in the Cu i isoelectronic sequence, then by comparison with a calculated spectrum. The latter was obtained with scaled Hartree–Fock radial energy integrals. The array has been observed most completely in I vii and Xe viii and, with decreasing strength, to higher sequence members. In Sm xvi and Eu xvii only the strongest line was found. The energy levels and the fitted parameter values for I vii and Xe viii are given.