cssi/SciSciGPT-SciSciNet huggingface dataset:
Albumin secreted by rat liver bypasses Golgi apparatus cisternae

Albumin was isolated immunologically from various subcellular fractions from livers of adult male rats receiving an intraperitoneal injection of [3H]leucine to investigate the kinetics and pathway of subcellular transfer of newly synthesized albumin during secretion. At appropriate time intervals, livers were excised and fractionated into endoplasmic reticulum and Golgi apparatus. Golgi apparatus were further subfractionated into cisternae and secretory vesicles. In endoplasmic reticulum fractions labeled albumin appeared within 7.5 min of injection of isotope, followed by a rapid decline in specific activity. Albumin in Golgi apparatus was labeled and concentrated in secretory vesicles over 25 min. The radioactivity in albumin per mg total protein was highest in secretory vesicles and insignificant in the cisternal fraction. Labeled albumin was present in serum by 30 min and radioactivity in serum albumin reached a plateau within 60-90 min after injection of isotope. Results provide evidence for the migration of albumin from its site of synthesis on endoplasmic reticulum membrane-bound polyribosomes to its site of secretion into the circulation via the Golgi apparatus. The pathway of albumin transport to secretory vesicles is suggested to involve peripheral elements of the Golgi apparatus. Secretory vesicle formation and maturation required 20 to 30 min for completion, via a mechanism whereby the inner spaces of the central saccules may be bypassed.
A fixed point theorem for the infinite-dimensional simplex☆

We define the infinite-dimensional simplex to be the closure of the convex hull of the standard basis vectors in R∞, and prove that this space has the fixed point property: any continuous function from the space into itself has a fixed point. Our proof is constructive, in the sense that it can be used to find an approximate fixed point; the proof relies on elementary analysis and Sperner's lemma. The fixed point theorem is shown to imply Schauder's fixed point theorem on infinite-dimensional compact convex subsets of normed spaces.
Introducing Colonial Regionalism: The Case of India’s Presidencies, the View From Madras

Conventional views of regions and regionalism begin with geography, history, language or other categories of organization. In this article, I offer a new(?) concept: the colonial region and its concomitant sentiment of colonial regionalism. The colonial region is one formed under colonial rule to suit administrative needs. It may directly encompass some form of pre-existing region, or it may cobble together a variety of smaller areas—some perhaps regions of their own, others not—into one greater region. A colonial region is thus an artificial one, not necessarily taking into account local realities. Many of the presidencies, provinces, and princely states might thus be considered as forms of colonial regions. Such regions often have long lives, and over time, inhabitants within a colonial region come to take on a sense of identity and pride in that region. This article examines colonial regionalism in the Madras Presidency along the axes of pride in physical and human assets.
Structure and Thermochemical Properties of 2-Methoxyfuran, 3-Methoxyfuran, and Their Carbon-Centered Radicals Using Computational Chemistry

Methoxyfurans are known components in a number of biofuel synthesis processes and their thermochemical properties are important to the stability, reaction paths, and chemical kinetics of these species. Enthalpies (DeltaH degrees (f298)), entropies (S degrees (298)), and heat capacities (C(p)(T)) are reported for 2-methoxyfuran and 3-methoxyfuran, cyclic ethers with possible biofuel implications, and their radicals corresponding to loss of hydrogen atoms. Standard enthalpies of formation are calculated at the B3LYP/6-31G(d,p), B3LYP/6-311G(2d,2p), CBS-QB3, G3MP2B3, and G3 levels of theory with isodesmic reactions to minimize calculation errors. Structures, vibrational frequencies, and internal rotor potentials are calculated at the B3LYP/6-31G(d,p) density functional level and are used to determine the entropy and heat capacities. The recommended ideal gas phase enthalpy of formation, from the average of the CBS-QB3 and G3MP2B3 levels of theory, for 2-methoxyfuran is -45.0 kcal mol(-1) and for 3-methoxyfuran is -41.1 kcal mol(-1). Bond dissociation energies are also calculated. The C-H bonds of the furan ring are approximately 120 kcal mol(-1), which is consistent with recent data on several alkylfurans; they are significantly stronger than non-aromatic, stable heterocyclic structures. The bond energy decreases to 98 kcal mol(-1) for the methoxy-methyl C-H bonds making this methyl site a favorable abstraction target and an important site for initial decomposition paths during combustion. Group additivity for furan is discussed and groups for furan and methoxyfuran carbon radicals are derived.
Prostaglandin E1 fever in the crayfish Cambarus bartoni.

Groups of 10 crayfish were injected with prostaglandin E1, at 1 of 3 pharmacological doses (0.5, 0.1 or 0.05 mg), into the haemocoel, and individually allowed to thermoregulate in electronic shuttleboxes for 24 hr. The mean preferred temperature of each group was then compared with their mean preferred temperature for 24 hr prior to injection, and with the mean preferred temperature of 10 crayfish injected with pyrogen-free saline. Dosage-dependent increases in preferred temperature were observed in the crayfish injected with PGE1, ranging from 1°C at the lowest dosage to 3.4°C at the highest dosage, above the normal thermal preferendum for this species of 22.1°C.
Women's agency and voice: a commentary on Karpowitz, Mendelberg, and Mattioli

Karpowitz, Mendelberg, and Mattioli's research [Politics, Groups, and Identities 3 (1): 149–177. doi:10.1080/21565503.2014.999804] on women's limited participation in small discussion groups deserves close scrutiny. In School Board meetings and five-person experimental lab groups, especially those subject to majority rule, the researchers find that women speak less often than men, are interrupted more frequently, have less influence on group decisions, and are more likely than men to exercise compassionate decision-making. But there are bound to be exceptions to this conclusion and I consider the limits to Karpowitz and colleagues’ findings to better understand the conditions under which women's agency comes to the fore. I focus, first, on the role played by group identities that can subvert prevailing norms of gendered behavior and, second, raise questions about the pervasiveness and magnitude of women's different and more compassionate voice. I conclude by noting the rich research agenda revealed by Kar...
Some facets of the simple plant location polytope

We relate the simple plant location problem to the vertex packing problem and derive several classes of facets of their associated integer polytopes.
Introduction of mRNA to plant protoplasts using polyethylene glycol

A method is described to deliver mRNA to plant protoplasts using polyethylene glycol for transient expression. In order to optimize delivery and subsequent expression, we have examined a number of parameters that affect expression levels including the requirement for Mg2+ and Ca2+ ions, carrier nucleic acid, and the linearity of the dose-response. Delivery of mRNA using PEG results in levels of expression that are comparable to those obtained with electroporation. This method is particularly useful for those species in which electroporation does not work well. Moreover, the use of PEG to deliver mRNA is an inexpensive alternative to electroporation in that it does not require an electroporator.
The adaptive significance of an environmentally-cued developmental switch in an anuran tadpole.

This study investigated the proximate basis of bimodally-distributed, environmentally-induced variation that occurs in natural populations of spade-foot toad tadpoles (Scaphiopus multiplicatus). Most individuals in most populations occur as a small, slowly-developing omnivore morph. In some of these same populations, a varying number of individuals occur as a large, rapidly-developing carnivore morph (Pfennig 1989). Censuses of 37 different natural ponds revealed that the frequency of the faster-developing carnivore morph correlated significantly positively with fairy shrimp density (their chief prey) and pond drying rate. By simultaneously varying two diet components and pond drying regime in artificial pools I found that only fairy shrimp density significantly affected the proportion of carnivores. Separate experiments established that the extent to which tadpoles developed the carnivore morphology correlated with shrimp density, and that morph determination depended on the ingestion of shrimp, not simply their presence. If a critical number of shrimp were ingested, the tadpole developed into a carnivore; if not, the tadpole developed by default into an omnivore. Thus a single cue — shrimp ingestion — triggers alternative ontogenetic trajectories. Using shrimp density to induce morph differentiation enables tadpoles to respond to their environment adaptively as shrimp are most abundant in highly ephemeral ponds, where the faster developing carnivores are favored.
Immobilization of invertase in germania matrix and a study of its enzymatic activity

Invertase from baker yeast was entrapped within germania nanospheres. The enzyme was incorporated simultaneously during the precipitation of germania using the peptide sequence T-G-H-Q-S-P-G-A-Y-A-A-H that is known to catalyze the formation of germania. The efficiency of immobilization and its activity under different conditions, operation and storage stability were studied. The enzyme was entrapped efficiently and was found to be stable and retained activity over a longer period of time compared to that of the free enzyme in solution. The effect of temperature and pH on the activity of the enzyme showed that the entrapped enzyme remained stable and active over a temperature range of 15–65 °C. Optimum activity of the immobilized invertase was found to be at 60 °C. In addition, the immobilized enzyme remained active over a broader pH range (4.5–6.5). Thus germania nanospheres can efficiently immobilize enzymes and remain stable over a range of temperatures. Such immobilization techniques protect the enzyme from harsh environments required during chemical synthesis and functionalization methods. The ability to trap biomolecules such as enzymes in germania nanospheres gives rise to a new class of materials with a variety of applications such as biosensors and bioactive glasses.
Beta-1C-Globulin: Metabolism in Glomerulonephritis

The metabolism of β1C-globulin labeled with iodine-131 was studied in six normal individuals and in three individuals with glomerulonephritis who exhibited markedly reduced serum concentrations of this protein. Fractional of serum β1C-globulin in glomerulonephritis appears to be chiefly secondary to decreased synthesis.
Discrimination of pure-tone intensities by the California sea lion.

The ability of the California sea lion (Zalophus californianus) to detect intensity differences of 16‐kHz pure‐tone pulses was determined in a yes‐no signal detection task with trial by trial feedback, using a modified method of limits similar to the “staircase method.” Additionally, three prethreshold experiments were performed to determine the effect of stimulus presentation strategy on discrimination ability. Results of the prethreshold experiments suggest that a “collapse” method (i.e., symmetrically reducing the intensity of the louder tone pulse in a pair and increasing the intensity of the softer) resulted in smaller threshold estimates than either an ascending or descending staircase method. Under the collapse method, a difference threshold estimate of 3.19 dB was found for 16‐kHz pure‐tone pulses. These results support a previous hypothesis based of behavioral underwater sound localization experiments and sound‐skull measurements by Moore and Au [J. Acoust. Soc. Am. 58, 721–727 (1975)]. These exp...
Environmental Education in Jamaica: The Gap between Policymakers and Teachers

Abstract A 1984 study of Jamaican teachers found them to be highly supportive of the idea of including environmental studies in the high school curriculum. Eighty-nine percent thought such studies should be incorporated into existing courses, and 74.3 percent indicated that they would attend seminars to prepare them to teach such material. An examination of several course syllabi revealed that a large amount of environmental material was already incorporated into the new Caribbean Examination Council course syllabi, but interviews with curriculum planners and policymakers indicated that widespread teacher training and public education workshops were not planned because of lack of funding and miscommunication between ministries and departments.
Exercise-Induced Oxidative Stress in Patients During Thallium Stress Testing

Abstract Free radical injury is implicated ~n the ~athogenesis of coronary artery disease, ~ncludmg atherogenesis and reperfusionlinJUry. Strenuous physical exercise can cause oxidative stress by several mechanisms, includingreperfusionlinjury. We hypothesize that exercise- induced lipid peroxidation is greater among those with than those without exerciseinduced myocardial ischemia. Methods: The effect of physical exercise stress testing on plasma malonaldehyde (MDA) levels was compared between patients with (Group A, N = 8) and without (Group B) exer~ ise-i!lduced myocardial ischemia by thallium ImagIng. Analysis: Two-way ANOVA was used to compare plasma MDA levels pre- and post-exercise and paired t-test comparisons were conducted for percent MDA changes between Group A and Group B patients. Results: Two-way ANOVA revealed a significant (P = 0.002) directional difference in response to exercise between the groups' mean plasma MDA levels (Group A increased by 46 ± 12.7 percent, Group B decreased by 16.8 ± 4.6 percent). Conclusions: Differences in exercise-induced lipid peroxidation between patients with and without thallium documentation of myocar~ ial ischemia have important implications In the development of clinical markers of coronary artery disease and further research related to atherogenesis.
Arsenite suppresses Notch1 signaling in human keratinocytes.

Arsenic is a well-known human skin carcinogen whose mechanism of action remains to be elucidated. In this work using cultured human epidermal cells, arsenite suppressed accumulation of the transcriptionally active intracellular domain of Notch1. The cells responded to an active peptide from the Notch1 ligand, Jagged1, with increased levels of differentiation marker mRNAs and decreased colony-forming ability. Arsenite suppressed Jagged1 effects and expression of Jagged1 mRNA as well. Moreover, exposure of the cells to a γ-secretase inhibitor prevented Notch1 processing, decreased cell size and differentiation marker expression, and increased proliferative potential, all effects that occur with arsenite treatment. Thus, arsenite action in suppressing keratinocyte differentiation while maintaining germinative capability could be due to inhibition of Notch1 signaling subsequent to ligand binding. This work also revealed that such arsenite action depends upon epidermal growth factor receptor kinase activity. These findings may help to explain how arsenite, by decreasing generation of the tumor suppressor Notch1, contributes to skin carcinogenesis.
Application of Dual Sorption Theory to Pressure-Sensitive Paints

We describe the application of a non linear dual sorption theory for modeling the steady-state emission of pressure-sensitive paints (PSPs). Calibration comparaisons with polynomial expansion models are presented over a 1-atm pressure range for two PSP formulations
The αβ T-Cell Receptor Repertoire in Inclusion Body Myositis: Diverse Patterns of Gene Expression by Muscle-infiltrating Lymphocytes

Abstract Inclusion body myositis (IBM) is one member of a group of disorders known as idiopathic inflammatory myopathies (IIM) in which autoreactive T cells directed against muscle are thought to play a primary role in disease pathogenesis. We have utilized the polymerase chain reaction to determine the pattern of αβ T-cell receptor (TCR) variable (V) gene expression in muscle biopsies from 13 IBM patients. In the majority of biopsies, we detected oligoclonal patterns of TCR V gene expression by muscle-infiltrating lymphocytes; an average of six out of the 22 TCR Vα gene families surveyed and seven out of 24 TCR Vβ gene families surveyed were detected per biopsy. While no TCR Vα gene families were over-represented in our survey, TCR Vβ3 and Vβ6 gene usage was a prominent feature ofIBM muscle biopsies. TCR gene expression was characterized further by analysing the junctional sequence composition of both Vβ3 and Vβ6 clones from muscle biopsies of the IBM patients. A large number of structurally diverse Vβ3 and Vβ6 clonotypes were identified from these patients demonstrating a polyclonal pattern of T cell infiltration. These data, while describing prominent TCR Vβ3 and Vβ6 gene detection, do not suggest that a common antigen-driven T-cell response promotes chronic inflammation in muscle of IBM patients.
A note on the order of l1 optimal compensators

Recently, Dahleh and Pearson [1] showed that when an l1 optimal compensator for a digital single-input, single-output, time-invariant plant exists, it is rational if the plant itself is. In this note, we give an example of a one-parameter family of first order plants where the order of the optimal compensator can be arbitrarily large. However, computational experience suggests that nearly optimal controllers of reasonable degree usually exist.
Mineralization of Clay/Polymer Aerogels: A Bioinspired Approach to Composite Reinforcement

Clay aerogels, ultra low density materials made via a simple freeze-drying technique, have shown much promise in broad applications because of their low densities, often in the same range as silica aerogels (0.03−0.3 g/cm3,) but suffering from low mechanical strength. A bioinspired approach to mineralize an active polymer/clay aerogel composite is inspected, showing marked improvement of the mechanical properties with increasing modification. Further property improvement was achieved using a layer-by-layer approach to produce alternate layers of polymer and silica on the surface.
Construction and characterization of lck- and fyn-specific tRNA: ribozyme chimeras.

Abstract Two src -family protein tyrosine kinases (PTKs), p56 lck and p59 fyn , are thought to play an important role in the antigen-specific T cell receptor (TCR)/CD3-initiated signaling pathway, but their relative contribution to these events is not clearly defined. Here, we have explored the potential of catalytic RNA molecules, or ribozymes, as tools for selectively inhibiting expression of the corresponding target genes in T cells. Several lck - or fyn -specific hammerhead ribozymes were synthesized, cloned into a bacterial transcription vector, and found to display specific catalytic activity in vitro . In order to achieve stable high-level ribozyme expression in intact cells, selected ribozymes were subsequently cloned into a retroviral vector (DC-T5T) immediately downstream of a tRNA met transcription unit. Upon retroviral transduction of a human leukemic T cell line (Jurkat), two out of four chimeric tRNA: ribozymes, fyn-1 and lck-1, were stably expressed at levels of ∼10,000 or ∼25,000 copies/cell, respectively. Ribozyme expression was associated with a reduction of up to 80% ( lck ) or 61% ( fyn ) in endogenous target mRNA by comparison to the corresponding transcript levels in control clones transfected with vector alone. By contrast, expression of the corresponding target proteins was not reduced, suggesting a post-transcriptional compensatory mechanism that increases translation or stability of the p56 lck and/or p59 fyn proteins.
Natural Cytotoxicity toward K562 Cells by Macaque Lymphocytes from Infancy through Puberty: Effects of Early Social Challenge

The consequences of a single maternal separation experience followed by reunion at 6-7 months of age was studied in socially housed pigtail (Macaca nemestrina) and bonnet (Macaca radiata) macaques. At 15 months, these subjects were removed from their natal group and placed in same species social groups, consisting of other separated and matched control subjects. Some subjects were followed until they reached an average age of 4 years while remaining in this group. Blood samples were drawn to permit assessment of the ability of peripheral blood lymphocytes to lyse, in vitro, K562 cells. Maternal separation failed to affect lysis of K562 cells acutely, although lysis by matched control subjects appeared to be transiently reduced 2 h after removal of the adult female. A longer-term influence was noted such that lysis of targets in previously separated subjects was greater than that in matched controls. Lysis rose over time regardless of species or experimental condition. A striking internal consistency in the lysis was also noted. Lysis was highly intercorrelated (r's > .60, p < or = .005) within subjects across time during baseline, separation, and reunion phases of the acute social challenge. In addition, there was a tendency for this correlation to hold over the longitudinal phases. Lysis of K562 targets by macaque lymphocytes would appear to possess trait-like stability; however, the range of lysis may be modified by early experiences.
Real-time optical detection of single human and bacterial viruses based on dark-field interferometry

Abstract The rapid and sensitive detection and characterization of human viruses and bacteriophage is extremely important in a variety of fields, such as medical diagnostics, immunology and vaccine research, and environmental contamination and quality control. We introduce an optical detection scheme for real-time and label-free detection of human viruses and bacteriophage as small as ∼24 nm in radius. Combining the advantages of heterodyne interferometry and dark-field microscopy, this label-free method enables us to detect and characterize various biological nanoparticles with unsurpassed sensitivity and selectivity. We demonstrate the high sensitivity and precision of the method by analyzing a mixture containing HIV virus and bacteriophage. The method also resolves the distribution of small nano-impurities (∼20–30 nm) in clinically relevant virus samples.
In vivo evidence for cerebral bioenergetic abnormalities in schizophrenia measured using 31P magnetization transfer spectroscopy.

Importance Abnormalities in neural activity and cerebral bioenergetics have been observed in schizophrenia (SZ). Further defining energy metabolism anomalies would provide crucial information about molecular mechanisms underlying SZ and may be valuable for developing novel treatment strategies. Objective To investigate cerebral bioenergetics in SZ via measurement of creatine kinase activity using in vivo 31 P magnetization transfer spectroscopy. Design, Setting, and Participants Cross-sectional case-control study in the setting of clinical services and a brain imaging center of an academic psychiatric hospital. Twenty-six participants with chronic SZ (including a subgroup diagnosed as having schizoaffective disorder) and 26 age-matched and sex-matched healthy control subjects (25 usable magnetic resonance spectroscopy data sets from the latter). Intervention 31 P magnetization transfer spectroscopy. Main Outcomes and Measures The primary outcome measure was the forward rate constant ( kf ) of the creatine kinase enzyme in the frontal lobe. We also collected independent measures of brain intracellular pH and steady-state metabolite ratios of high-energy phosphate-containing compounds (phosphocreatine and adenosine triphosphate [ATP]), inorganic phosphate, and the 2 membrane phospholipids phosphodiester and phosphomonoester. Results A substantial (22%) and statistically significant ( P = .003) reduction in creatine kinase kf was observed in SZ. In addition, intracellular pH was significantly reduced (7.00 in the SZ group vs 7.03 in the control group, P = .007) in this condition. The phosphocreatine to ATP ratio, inorganic phosphate to ATP ratio, and phosphomonoester to ATP ratio were not substantially altered in SZ, but a significant ( P = .02) reduction was found in the phosphodiester to ATP ratio. The abnormalities were similar between SZ and schizoaffective disorder. Conclusions and Relevance Using a novel 31 P magnetization transfer magnetic resonance spectroscopy approach, we provide direct and compelling evidence for a specific bioenergetic abnormality in SZ. Reduced kf of the creatine kinase enzyme is consistent with an abnormality in storage and use of brain energy. The intracellular pH reduction suggests a relative increase in the contribution of glycolysis to ATP synthesis, providing convergent evidence for bioenergetic abnormalities in SZ. The similar phosphocreatine to ATP ratios in SZ and healthy controls suggest that the underlying bioenergetics abnormality is not associated with change in this metabolite ratio.
Estimates for ELF effects: noise-based thresholds and the number of experimental conditions required for empirical searches.

Interactions between physical fields and biological systems present difficult conceptual problems. Complete biological systems, even isolated cells, are exceedingly complex. This argues against the pursuit of theoretical models, with the possible consequence that only experimental studies should be considered. In contrast, electromagnetic fields are well understood. Further, some subsystems of cells (viz. cell membranes) can be reasonably represented by physical models. This argues for the pursuit of theoretical models which quantitatively describe interactions of electromagnetic fields with that subsystem. Here we consider the hypothesis that electric fields, not magnetic fields, are the source of interactions, From this it follows that the cell membrane is a relevant subsystem, as the membrane is much more resistive than the intra- or extracellular regions. A general class of interactions is considered: electroconformational changes associated with the membrane. Expected results of such as approach include the dependence of the interaction on key parameters (e.g., cell size, field magnitude, frequency, and exposure time), constraints on threshold exposure conditions, and insight into how experiments might be designed. Further, because it is well established that strong and moderate electric fields interact significantly with cells, estimates of the extrapolated interaction for weaker fields can be sought. By employing signal-to-noise (S/N) ratio criteria, theoretical models can also be used to estimate threshold magnitudes. These estimates are particularly relevant to in vitro conditions, for which most biologically generated background fields are absent. Finally, we argue that if theoretical model predictions are unavailable to guide the selection of experimental conditions, an overwhelmingly large number of different conditions will be needed to find, establish, and characterize bioelectromagnetic effects in an empirical search. This is contrasted with well-established chemical dosimetry, which is much simpler. Because of the large number of possible electromagnetic field conditions, we also conclude that in vitro studies, rather than in vivo studies, should be emphasized in studies aimed at discovering and characterizing mechanisms for bioelectromagnetic effects. 1992 Wiley-Liss, Inc.
RESPONSE OF THE SUPERFICIAL LYMPHATICS OF THE ARM OF INTACT MAN TO SYNTHETIC VASOPRESSIN.

SummaryPreliminary studies indicate that PLV-2 and Lys-Vp, 2 synthetic vaso-pressins, increase the rate of lymph flow in the superficial lymphatics of the forearm. The mechanism by which these polypeptides influence the rate of lymph flow is unknown.
Analysis of a GRACE global mascon solution for Gulf of Alaska glaciers

We present a high-resolution Gravity Recovery and Climate Experiment (GRACE) mascon solution for Gulf of Alaska (GOA) glaciers and compare this with in situ glaciological, climate and other remote-sensing observations. Our GRACE solution yields a GOA glacier mass balance of -65 � 11 Gt a -1 for the period December 2003 to December 2010, with summer balances driving the interannual variability. Between October/November 2003 and October 2009 we obtain a mass balance of -61 � 11 Gt a -1 from GRACE, which compares well with -65 � 12 Gt a -1 from ICESat based on hypsometric extrapolation of glacier elevation changes. We find that mean summer (June-August) air temperatures derived from both ground and lower-troposphere temperature records were good predictors of GRACE-derived summer mass balances, capturing 59% and 72% of the summer balance variability respectively. Large mass losses during 2009 were likely due to low early melt season surface albedos, measured by the Moderate Resolution Imaging Spectroradiometer (MODIS) and likely associated with the 31 March 2009 eruption of Mount Redoubt, southwestern Alaska. GRACE data compared well with in situ measurements at Wolverine Glacier (maritime Alaska), but poorly with those at Gulkana Glacier (interior Alaska). We conclude that, although GOA mass estimates from GRACE are robust over the entire domain, further constraints on subregional and seasonal estimates are necessary to improve fidelity to ground observations.
Screening, brief interventions, referral to treatment (SBIRT) for illicit drug and alcohol use at multiple healthcare sites: Comparison at intake and 6 months later

Abstract Objectives Alcohol screening and brief interventions in medical settings can significantly reduce alcohol use. Corresponding data for illicit drug use is sparse. A Federally funded screening, brief interventions, referral to treatment (SBIRT) service program, the largest of its kind to date, was initiated by the Substance Abuse and Mental Health Services Administration (SAMHSA) in a wide variety of medical settings. We compared illicit drug use at intake and 6 months after drug screening and interventions were administered. Design SBIRT services were implemented in a range of medical settings across six states. A diverse patient population (Alaska Natives, American Indians, African-Americans, Caucasians, Hispanics), was screened and offered score-based progressive levels of intervention (brief intervention, brief treatment, referral to specialty treatment). In this secondary analysis of the SBIRT service program, drug use data was compared at intake and at a 6-month follow-up, in a sample of a randomly selected population (10%) that screened positive at baseline. Results Of 459,599 patients screened, 22.7% screened positive for a spectrum of use (risky/problematic, abuse/addiction). The majority were recommended for a brief intervention (15.9%), with a smaller percentage recommended for brief treatment (3.2%) or referral to specialty treatment (3.7%). Among those reporting baseline illicit drug use , rates of drug use at 6-month follow-up (4 of 6 sites), were 67.7% lower ( p p p p p p p Conclusions SBIRT was feasible to implement and the self-reported patient status at 6 months indicated significant improvements over baseline, for illicit drug use and heavy alcohol use, with functional domains improved, across a range of health care settings and a range of patients.
Visual diagnosis: a 9-year-old girl who has fever, headache, and right eye pain.

1. Linda S. Nield, MD* 2. Deepak Kamat, MD, PhD† 1. *Associate Professor of Pediatrics, West Virginia University, Morgantown, WV 2. †Professor of Pediatrics; Director, Institute of Medical Education, Vice Chair of Education, Children’s Hospital of Michigan, Detroit, Mich A 9-year-old girl presents to the emergency department with a 24-hour history of fever to 103.8°F (39.9°C); headache; worsening right eye pain; and right-sided red, swollen eyelids. A day earlier, she was found to have preseptal (periorbital) cellulitis at another urgent care facility, was treated with amoxicillin/clavulanate, and was discharged from the hospital. Despite three doses of the oral antibiotic, her condition has deteriorated. The child has had multiple episodes of sinusitis in the last several years, her most recent bout occurring 3 weeks ago. Her past medical history is otherwise unremarkable. She is at the 50th percentile for height and weight for her age. Family history is noncontributory. There is no history of allergies, immunodeficiencies, or cystic fibrosis. On physical examination, the child appears ill, yet is alert and oriented. Her vital signs are: temperature, 103.8°F (39.9°C); pulse, 110 beats/min; and respiratory rate, 16 breaths/min. Her right upper and lower eyelids and surrounding facial tissue are red and swollen (Fig. 1). Vision, funduscopic, and extraocular muscle examinations cannot be completed because of her severe eye pain and eyelid swelling. Nasal mucosa is erythematous and swollen and partially obscured by dried, yellow discharge. The child has good dentition, normal tympanic membranes, and no meningismus. Findings on the rest of the physical examination are unremarkable. Figure 1. Right eyelid erythema and edema. Note that the erythema does not extend beyond the orbital ridge. Laboratory evaluation reveals a total white blood cell count of 10×103/mcL (10×109/L), with 71% polymorphonuclear cells, no bands, 18% lymphocytes, 10% monocytes, and 1% eosinophils. A blood culture and head and orbital contrast-enhanced computed tomography (CT) scan are obtained. Orbital CT reveals right periorbital soft-tissue swelling, inflammatory changes in the medial aspect of the right orbit with obvious displacement of the globe, and slight lateral displacement …
Preparation, characterization and reactions of novel vicinal dibenzotriazol-1-yl derivatives of benzotriazole and glyoxal†

A variety of novel 1,2-disubstituted-1,2-di(benzotriazol-1-yl)ethane and 1,2-di(benzotriazol-1-yl)ethylene derivatives were prepared from the adduct of benzotriazole and glyoxal.
Con: Benzodiazepines are not contraindicated as induction agents for coronary artery surgery

B ENZODIAZEPINES are not contraindicated as induction agents for coronary artery surgery; in fact, in my opinion they are indicated. It has been shown in many studies that diazepam, midazolam, and even lorazepam are effective induction agents for patients with heart disease.‘“3 The reason that benzodiazepines are effective induction agents is that they produce relatively rapid hypnotic and amnestic effects with minimal hemodynamic perturbations. The hypnotic and amnestic properties of these anesthetics are predictable, reliable, and reproducible. This combination of hypnosis and amnesia is unique to the benzodiazepines and is not a characteristic of alternative drugs such as thiopental, etomidate, and especially opioids. The relatively rapid onset of hypnosis and amnesia are important aspects of the pharmacology of benzodiazepines when used for induction in patients with coronary artery disease, and these characteristics make benzodiazepines very valuable induction agents. In contrast to opioids, benzodiazepines produce no muscle rigidity (they are muscle relaxants) and the airway is easily maintained. This makes the transition from consciousness to unconsciousness free of troublesome ventilation problems during this crucial phase of patient management. However, because benzodiazepines do not have analgesic properties, it is imperative that other anesthetic drugs be administered to provide analgesia. This can be accomplished by the judicious combination of opioids or inhalation anesthetics. This brings us to a cautionary note. It is well known that the combination of benzodiazepines and opioids can produce a supra-additive hypotension that presents a common problem in cardiac anesthesia.34 This unwanted side effect occurs in patients given
Suppression of dynamic Ca2+ transient responses to pacing in ventricular myocytes from mice with genetic calmodulin kinase II inhibition

The multifunctional Ca 2 + and calmodulin-dependent protein kinase II (CaMKII) is important for regulating L-type Ca 2 + current (I C a ) and cytoplasmic Ca 2 + (Ca 2 + i ) uptake and release from the sarcoplasmic reticulum(SR), key elements of the 'Ca 2 + -induced Ca 2 + release' (CICR) mechanism. However, the effects of chronic CaMKII inhibition on Ca 2 + i responses during CICR are unknown. We hypothesized that chronic CaMKII inhibition significantly affects CICR in ventricular myocytes. We studied CICR by simultaneously measuring Ca 2 + i transients and I C a in voltage-clamped ventricular myocytes isolated from a recently developed genetic mouse model of cardiac CaMKII inhibition. These measurements were repeated in ventricular myocytes from novel mice with cardiac CaMKII inhibition lacking phospholamban (PLN), a known CaMKII substrate and a negative regulator of Ca 2 + i uptake into the SR Ca 2 + store. CaMKII inhibition eliminated a pattern of I C a increases called facilitation and significantly reduced beat-to-beat and cell-to-cell variability of peak Ca 2 + i transients in ventricular myocytes with PLN. PLN ablation eliminated I C a facilitation even in the absence of CaMKII inhibition and the effects of CaMKII inhibition to reduce SR Ca 2 + content and slow SR Ca 2 + uptake were lost in the absence of PLN. PLN ablation significantly reduced I C a beat-to-beat variability in cells with CaMKII inhibition. These findings show that chronic CaMKII inhibition reduces variability of CICR responses in a manner that is partly dependent on the presence of PLN.
Stress in an elastic wedge or notch loaded by a localized internal source

A study is presented of the stress inside a two-dimensional elastic solid which has a boundary surface angle and which is loaded by an internal point source of expansion. An exact analytic solution for the stress is obtained, for general surface angle and source position, and evaluated numerically for several representative cases of wedges and notches. The singular behaviour given by the leading terms near the angle vertex is found to be highly localized, and there is little or no stress enhancement near the source. For many combinations of boundary angle and source location, however, a local region of significant enhancement occurs on that part of the surface nearest the source. Implications of these results are discussed, with particular reference to surface steps.
Frontolimbic brain networks predict depressive symptoms in temporal lobe epilepsy

Psychiatric co-morbidities in epilepsy are of great concern. The current study investigated the relative contribution of structural and functional connectivity (FC) between medial temporal (MT) and prefrontal regions in predicting levels of depressive symptoms in patients with temporal lobe epilepsy (TLE). Twenty-one patients with TLE [11 left TLE (LTLE); 10 right TLE (RTLE)] and 20 controls participated. Diffusion tensor imaging was performed to obtain fractional anisotropy (FA) of the uncinate fasciculus (UF), and mean diffusivity (MD) of the amygdala (AM) and hippocampus (HC). Functional MRI was performed to obtain FC strengths between the AM and HC and prefrontal regions of interest including anterior prefrontal (APF), orbitofrontal, and inferior frontal regions. Participants self-reported depression symptoms on the Beck Depression Inventory-II. Greater depressive symptoms were associated with stronger FC of ipsilateral HC-APF, lower FA of the bilateral UF, and higher MD of the ipsilateral HC in LTLE, and with lower FA of the contralateral UF in RTLE. Regression analyses indicated that FC of the ipsilateral HC-APF was the strongest contributor to depression in LTLE, explaining 68.7% of the variance in depression scores. Both functional and microstructural measures of frontolimbic dysfunction were associated with depressive symptoms. These connectivity variables may be moderating which patients present with depression symptoms. In particular, FC MRI may provide a more sensitive measure of depression-related dysfunction, at least in patients with LTLE. Employing sensitive measures of frontolimbic network dysfunction in TLE may help provide new insight into mood disorders in epilepsy that could eventually guide treatment planning.
The reactivity of macrocyclic Fe(II) paraCEST MRI contrast agents towards biologically relevant anions, cations, oxygen or peroxide.

Abstract The reactivity of four macrocyclic Fe(II) complexes (L1–L4) is studied with the goal of developing paramagnetic chemical exchange saturation transfer (paraCEST) magnetic resonance imaging (MRI) contrast agents for in vivo studies. (L1 = 1,4,7-tris(carbamoylmethyl)-1,4,7-triazacyclononane; L2 = 1,4,7-tris[(5-methyl-2-pyridyl)methyl]-1,4,7-triazacyclononane; L3 = 1,4,7-tris[(2-pyridyl)methyl]-1,4,7-triazacyclononane; L4 = 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane). The Fe(II) complexes remain intact in the presence of 25 mM carbonate, 0.40 mM phosphate and 100 mM NaCl for 12 h at 37 °C, consistent with their moderately high formation constants (log K = 13.5, 19.2, 7.50 for [Fe(L1)]2+, [Fe(L3)]2+ and [Fe(L4)]2+, respectively). [Fe(L4)]2+, [Fe(L2)]2+ and [Fe(L3)]2+ do not dissociate over 12 h in the presence of excess Cu(II) at 37 °C. None of the complexes show appreciable redox cycling as measured by consumption of ascorbate in the presence of oxygen, corresponding to their highly stabilized Fe(II) oxidation state (Eo = 860, 930, 970, and 800 mV versus NHE for [Fe(L1)]2+, [ [Fe(L2)]2+, [Fe(L3)]2+ and [Fe(L4)]2+. None of the Fe(II) complexes produce appreciable amounts of hydroxyl radical in the presence of peroxide and ascorbate as shown by limited hydroxylation of benzoate. Fe(II) complexes of L1, L2, and L3 show 25–28% cleavage of supercoiled plasmid DNA in the presence of peroxide and ascorbate over 2 h at 37 °C while [Fe(L4)]2+ shows 6% cleavage.
Functional Expression of Horseradish Peroxidase in E.coli by Directed Evolution

In an effort to develop a bacterial expression system for horseradish peroxidase (HRP), we inserted the gene encoding HRP into the pET-22b(+) vector (Novagen) as a fusion to the signal peptide PelB. A similar construct for cytochrome c peroxidase (CcP) leads to high CcP activity in the supernatant. Expression of the wild-type HRP gene in the presence of isopropyl-beta-D-thiogalactopyranoside (IPTG) yielded no detectable activity against ABTS (azinobis(ethylbenzthiazoline sulfonate)). However, weak peroxidase activity was detected in the supernatant in the absence of IPTG. The HRP gene was subjected to directed evolution: random mutagenesis and gene recombination followed by screening in a 96-well microplate format. From 12 000 clones screened in the first generation, one was found that showed 14-fold higher HRP activity than wild-type, amounting to approximately 110 microg of HRP/L, which is similar to that reported from laborious in vitro refolding. No further improvement was obtained in subsequent generations of directed evolution. This level of expression has nonetheless enabled us to carry out further directed evolution to render the enzyme more thermostable and more resistant toward inactivation by H2O2. These results show that directed evolution can identify mutations that assist proteins to fold more efficiently in Escherichia coli. This approach will greatly facilitate efforts to "fine-tune" those many enzymes that are promising industrial biocatalysts, but for which suitable bacterial or yeast expression systems are currently lacking.
Pervious Concrete Performance in Eastern Washington: Surface Infiltration

Due to slow draining soils, winter conditions and hilly terrain, Eastern Washington is considered to be a challenging region for implementation of permeable pavements. Four pervious concrete placements have been installed on the Washington State University campus in Pullman, WA. They have already weathered from two to four winters and are all functioning hydraulically. This paper provides information on the effectiveness of these facilities, and their current hydraulic functionality.
A Simple Friction and Diffusion Scheme for Planetary Geostrophic Basin Models

A simple friction and diffusion scheme is proposed for use with the time-dependent planetary geostrophic equations, which in their proper asymptotic form cannot be solved in a closed basin. The resulting set of equations admits boundary conditions of no-normal flow and no-normal heat flux at all rigid boundaries, is amenable to efficient numerical solution, and may be solved with small heat (and salt) diffusivities. The scheme is formally a minor modification of several others that have recently been proposed but differs in significant details. Friction is represented by linear drag in the horizontal momentum equations, while the hydrostatic balance is retained exactly. The Laplacian vertical and horizontal heat (and salt) diffusion are supplemented by biharmonic horizontal diffusion. The latter is necessary in order that the smoothness of the solution can be maintained up to and along the boundary, which is particularly important because the no-normal-flow condition is enforced as a differential equation that must be solved along the boundary. The equations support a frictional western boundary current that is nearly adiabatic.
The naive rule for reconstructing a noisy Markov chain

SUMMARY An observer desires to record a realization of a stationary two-state Markov chain X, but experimental conditions are such that he instead sees a realization of a sequence Y subject to error. The objective is to reconstruct X. The naive reconstruction rule is that rule which assumes that X is a sequence of independent random variables and selects Ai the reconstructed Xi, using only Yi. A necessary and sufficient condition is given for the naive rule to be the optimal reconstruction rule.
Optimum polarizations for radar meteorology

Specular null polarization theory has recently been introduced for the case of coherent scattering where a 2/spl times/2 scattering is sufficient to describe the scattering process (Hubbert, 1994). In this paper specular null polarization theory is extended to the case of incoherent scattering. Optimum polarization states are derived and the results are discussed in relation to the established radar optimum polarization states. Modeling of ensembles of precipitation particles using the transition (T-) matrix approach is used to illustrate the results of the analysis. >
Halothane binds to druggable sites in the [Ca2+]4-calmodulin (CaM) complex, but does not inhibit [Ca2+]4-CaM activation of kinase.

The mechanism(s) of volatile anesthetics (VAs) are poorly under- stood. High-resolution NMR spectroscopy was used to determine the structure of the halothane-(Ca 2+ )4-calmodulin ((Ca 2+ )4- CaM) complex, and it was found that halothane molecules bind in the druggable sites. Then it was examined whether VAs binding to druggable sites in calmodulin would affect the (Ca 2+ )4-CaM dependent activity of myosin light chain kinase. Fluorescence assays were used to determine that VA mediate (Ca 2+ )4-CaM activation of smooth-muscle-myosin-light-chain-kinase (smMLCK), but do not alter signi- ficantly the Kd of (Ca 2+ )4-CaM binding to skeletal-myosin-light-chain-kinase- peptide recognition sequence (skMLCKp). The results suggested that VAs do not alter (Ca 2+ )4-CaM dependent MLCK activity via direct interactions with (Ca 2+ )4-CaM.
Mary Parker Follett—Prophet of Management: A Celebration of Writings from the 1920s

The article reviews the book “Mary Parker Follett: Prophet of Management: A Celebration of Writings From the 1920s,” edited by Pauline Graham.