cssi/SciSciGPT-SciSciNet huggingface dataset:
Investigation of the effects of storage and freezing on mixes of heavy-labeled metabolite and amino acid standards.

Rationale High-throughput metabolomics has now made it possible for small/medium-sized laboratories to analyze thousands of samples/year from the most diverse biological matrices including biofluids, cell and tissue extracts. In large-scale metabolomics studies, stable-isotope-labeled standards are increasingly used to normalize for matrix effects and control for technical reproducibility (e.g. extraction efficiency, chromatographic retention times and mass spectrometry signal stability). However, it is currently unknown how stable mixes of commercially available standards are following repeated freeze/thaw cycles or prolonged storage of aliquots. Methods Standard mixes for 13 C, 15 N or deuterated isotopologues of amino acids and key metabolites from the central carbon and nitrogen pathways (e.g. glycolysis, Krebs cycle, redox homeostasis, purines) were either repeatedly frozen/thawed for up to 10 cycles or diluted into aliquots prior to frozen storage for up to 42 days. Samples were characterized by ultra-high-pressure liquid chromatography/mass spectrometry to determine the stability of the aliquoted standards upon freezing/thawing or prolonged storage. Results Metabolite standards were stable over up to 10 freeze/thaw cycles, with the exception of adenosine and glutathione, showing technical variability across aliquots in a freeze/thaw-cycle-independent fashion. Storage for up to 42 days of mixes of commercially available standards did not significantly affect the stability of amino acid or metabolite standards for the first 2 weeks, while progressive degradation (statistically significant for fumarate) was observed after 3 weeks. Conclusions Refrigerated or frozen preservation for at least 2 weeks of aliquoted heavy-labeled standard mixes for metabolomics analysis is a feasible and time-/resource-saving strategy for standard metabolomics laboratories.
Epidemiology of mental health comorbidity in psoriasis

AbstractAim: The occurrence of mental health comorbidities such as depression, anxiety, and suicidal ideation or behavior is not uncommon in the context of psoriasis. The negative influence of psoriatic disease on a patient’s physical and mental well-being, in combination with overlapping pathophysiology, increase the risk for clinically significant psychiatric conditions. These psychiatric conditions, in turn, influence the patient’s outlook and potentially, prognosis. Although the healthcare community increasingly recognizes the association of mental health comorbidities with psoriasis, the extent of the correlation is not fully appreciated. To better understand the relationship between mental health comorbidities and psoriasis, including prevalence, risk factors, and response of psychiatric comorbidities to psoriasis treatment, a narrative review of the published literature was conducted.Methods: Data from epidemiologic, observational, and clinical studies demonstrate a substantially greater mental hea...
Actionable insights with less data: guiding early building design decisions with streamlined probabilistic life cycle assessment

Two obstacles that impede wider use of life cycle assessment (LCA) are its time- and data-intensiveness and the credibility surrounding its results—challenges that grow with the complexity of the product being analyzed. To guide the critical early-design stages of a complicated product like a building, it is important to be able to rapidly estimate environmental impacts with limited information, quantify the resulting uncertainty, and identify critical parameters where more detail is needed. The authors have developed the Building Attribute to Impact Algorithm (BAIA) to demonstrate the use of streamlined (not scope-limiting), probabilistic LCA for guiding the design of a building from early stages of the design process when many aspects of the design are unknown or undecided. Early-design uncertainty is accommodated through under-specification—characterizing the design using the available level of detail—and capturing the resulting variability in predicted impacts through Monte Carlo simulations. Probabilistic triage with sensitivity analyses identifies which uncertain attributes should be specified further to increase the precision of the results. The speed of the analyses allows for sequentially refining key attributes and re-running the analyses until the predicted impacts are precise enough to inform decision-making, such as choosing a preferable design alternative. Twelve design variants for a hypothetical single-family residential building are analyzed. As information is sequentially added to each variant, the significance of the difference in performance between each variant pair is calculated to determine when enough information has been added to resolve the designs (identify which design is preferable) with high confidence. At the sixth step in the analysis, all variant pairs whose mean impacts differ by at least 4% are resolvable with 90% confidence, even though only six attributes are specified and dozens of attributes remain under-specified. Furthermore, the comparative results for each variant pair are validated against a set of conventional LCA results, showing that BAIA identifies the correct preferable design among each resolvable pair at this step. Iterative specification guided by probabilistic triage can help identify promising early-design alternatives even when details are only provided for key attributes. The analysis of hypothetical design variants demonstrates that BAIA is both efficient (arrives at statistically defensible conclusions from design variant comparisons based on few pieces of information) and effective (identifies the same preferable design variants as conventional LCAs).
Novel hemizygous nonsense mutation in DRP2 is associated with inherited neuropathy

Mutations in DRP2 (OMIM #300052) encoding dystrophin-related protein 2, a 957 amino acid protein, were identified in a single patient with X-linked Charcot-Marie-Tooth (CMT) disease and are associated with familial autism.1,2 DRP2 is predominantly expressed in the brain and spinal cord and functionally interacts with periaxin ( PRX , OMIM #605725), a known causative CMT gene (OMIM #614895 and #145900), in the PRX-DRP2-dystroglycan (PDG) complex.3 The PDG complex supports and maintains Cajal bands, which are cytoplasmic extensions that run along the length of myelinated axons and are required for establishing a proper internodal length.4–6
Minocycline Effects on Intracerebral Hemorrhage-Induced Iron Overload in Aged Rats: Brain Iron Quantification With Magnetic Resonance Imaging

Background and Purpose— Brain iron overload is a key factor causing brain injury after intracerebral hemorrhage (ICH). This study quantified brain iron levels after ICH with magnetic resonance imaging R2* mapping. The effect of minocycline on iron overload and ICH-induced brain injury in aged rats was also determined. Methods— Aged (18 months old) male Fischer 344 rats had an intracerebral injection of autologous blood or saline, and brain iron levels were measured by magnetic resonance imaging R2* mapping. Some ICH rats were treated with minocycline or vehicle. The rats were euthanized at days 7 and 28 after ICH, and brains were used for immunohistochemistry and Western blot analyses. Magnetic resonance imaging (T2-weighted, T2* gradient-echo, and R2* mapping) sequences were performed at different time points. Results— ICH-induced brain iron overload in the perihematomal area could be quantified by R2* mapping. Minocycline treatment reduced brain iron accumulation, T2* lesion volume, iron-handling protein upregulation, neuronal cell death, and neurological deficits ( P Conclusions— Magnetic resonance imaging R2* mapping is a reliable and noninvasive method, which can quantitatively measure brain iron levels after ICH. Minocycline reduced ICH-related perihematomal iron accumulation and brain injury in aged rats.
Blunt cerebrovascular injury in elderly fall patients: are we screening enough?

Blunt cerebrovascular injuries (BCVI) are generally associated with high-energy injury mechanisms. Less is known regarding lower-energy injuries in elderly patients. We sought to determine the incidence of BCVI and characterize current BCVI screening practices and associated complications in elderly ground-level fall patients (EGLF, ≥ 65 years). We hypothesized that BCVI in EGLF patients would be clinically significant and screening would be less common. A retrospective study was performed utilizing the National Trauma Data Bank (NTDB, 2007–2014) and single institutional data. BCVI risk factors and diagnosis were determined by ICD-9 codes. Presenting patient characteristics and clinical course were obtained by chart review. The NTDB dataset was used to determine the incidence of BCVI, risk factors for BCVI, and outcomes in the EGLF cohort. Local chart review focused on screening rates and complications. The incidence of BCVI in EGLF patients was 0.15% overall and 0.86% in those with at least one BCVI risk factor in the NTDB. Upper cervical spine fractures were the most common risk factor for BCVI in EGLF patients. In EGLF patients, the diagnosis of BCVI was an independent risk factor for mortality (OR1.8, 95% C.I. 1.5–2.1). The local institutional data (2007–2014) had a BCVI incidence of 0.37% (n = 6487) and 1.47% in those with at least one risk factor (n = 1429). EGLF patients with a risk factor for BCVI had a very low rate of screening (44%). Only 8% of EGLF patients not screened had documented contraindications. The incidence of renal injury was 9% irrespective of BCVI screening. The incidence of BCVI is clinically significant in EGLF patients and an independent predictor of mortality. Screening is less common in EGLF patients despite few contraindications. This data suggests that using age and injury mechanism to omit BCVI screening in EGLF patients may exclude an at-risk population. IRB approval number: PRO15020269. Retrospective trial not registered
How Reliable are Children’s Memories?

In this chapter we examine the role of behavioral scientists as reporters of research findings that may be contrary to public knowledge and expectations. The research to be examined relates to the suggestibility of children’;s memory and was prompted in part by the recent flood of highly publicized and horrifying accusations of child sexual abuse in this country and abroad. Specifically, the discussion focuses on the contrast between public perceptions of children’;s testimonial competence versus actual research findings about children’;s vulner-ability to suggestion.
Health Literacy Competence of Health Education Students in Three Universities

Introduction. Limited health literacy challenges health care and perpetuates health disparities. Health agencies, such as the U.S. Department of Health and Human Services and the World Health Organ...
Psychological Needs Fulfillment and Engagement in Afterschool: “I Pay Attention Because I am Really Enjoying This.”:

This qualitative study draws on concepts from Self-Determination Theory (SDT) within a positive youth development framework to postulate that participants in an after-school program will derive a s...
An optimized InCell Western screening technique identifies hexachlorophene as a novel potent TDP43 targeting drug

TAR DNA binding protein (TDP43) is a DNA- and RNA-binding protein that is implicated in several neurodegenerative disorders termed as "TDP43 proteinopathies" including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and fronto-temporal lobe dementia (FTLD). We have developed an InCell Western (ICW) technique for screening TDP targeting drugs in 96 well plates. We tested 281 compounds and identified a novel compound hexachlorophene (referred to as B10) that showed potent reduction in TDP43 levels. The effect of B10 on TDP protein level was validated in two different cellular models: endogenous TDP43 expressing N9 microglial cells and TDP43-over-expressing HEK293 and HeLa cells. We also analyzed effect of B10 on various pathological forms of TDP such as the C25 cleaved fragment that localizes to the cytosol, insoluble high molecular weight species, and ALS-linked mutants. Our data suggest that B10 effectively reduces all forms of TDP. Overall, our data suggest that B10 could serve as a potential drug molecule for the treatment of AD, ALS and other TDP43 proteinopathies.
Vaccine Hesitancy and Low Immunization Rates in Children with Down Syndrome.

Objectives To determine the prevalence of vaccine hesitancy and refusal among parents of children with Down syndrome and to determine how well the Parent Attitudes about Childhood Vaccines Survey (PACV) is associated with vaccine receipt among children with Down syndrome. Study design We mailed the PACV to parents of children with Down syndrome who attend the Down Syndrome Clinic at Akron Children's Hospital and examined associations between PACV scores and immunization status at 19 months of age. Results Of 120 surveys sent, 63 parents completed the PACV (52% response rate) of which 60 were linked to vaccination records. Of these 60 respondents, 55 children were ≥19 months old. PACV scores were significantly correlated with days of underimmunization at 19 months of age. All parents who refused all vaccines had PACV scores of ≥50. Only 58% of children were up to date for the combined 7 vaccine series at 19 months of age. Conclusions The PACV may be a valuable tool to identify vaccine hesitancy among parents of young children with Down syndrome. Special emphasis is needed to increase adherence with on-time vaccine recommendations for children with Down syndrome to optimize their health and to potentially avoid hospitalizations.
Exploratory factor analysis of the Just Culture Assessment Tool for nursing education

BackgroundJust culture has been identified as a vital component of safety culture by national and international organisations. In a just culture, emphasis is not placed on blaming individuals for e...
Magnetite nanoparticle anchored graphene cathode enhances microbial electrosynthesis of polyhydroxybutyrate by Rhodopseudomonas palustris TIE-1.

Microbial electrosynthesis (MES) is an emerging technology that can convert carbon dioxide (CO2) into value-added organic carbon compounds using electrons supplied from a cathode. However, MES is affected by low product formation due to limited extracellular electron uptake by microbes. Herein, a novel cathode was developed from chemically synthesized magnetite nanoparticles and reduced graphene oxide nanocomposite (rGO-MNPs). This nanocomposite was electrochemically deposited on carbon felt (CF/rGO-MNPs), and the modified material was used as a cathode for MES production. The bioplastic, polyhydroxybutyrate (PHB) produced by Rhodopseudomonas palustris TIE-1 (TIE-1), was measured from reactors with modified and unmodified cathodes. Results demonstrate that the magnetite nanoparticle anchored graphene cathode (CF/rGO-MNPs) exhibited higher PHB production (91.31 ± 0.9 mg l-1). This is ∼4.2 times higher than unmodified carbon felt (CF), and 20 times higher than previously reported using graphite. This modified cathode enhanced electron uptake to -11.7 ± 0.1 μA cm-2, ∼5 times higher than CF cathode (-2.3 ± 0.08 μA cm-2). The faradaic efficiency of the modified cathode was ∼2 times higher than the unmodified cathode. Electrochemical analysis and scanning electron microscopy suggest that rGO-MNPs facilitated electron uptake and improved PHB production by TIE-1. Overall, the nanocomposite (rGO-MNPs) cathode modification enhances MES efficiency.
Lifestyle and psychosocial factors associated with maintenance of normal body mass index in college students: a cross sectional study.

The purpose of this study was to identify lifestyle and psychosocial factors associated with maintenance of normal body mass index (BMI, 18.5–24.9 kg/m2). Undergraduate students (n = 2781; 7.1% response rate) at a Big Ten university responded to a survey in 2018. BMI was calculated from the reported weight and height at the time of the survey and upon entering the university. Logistic regression analyses examined lifestyle and psychosocial health factors associated with maintenance of normal BMI by academic year. Current BMI was within normal range for 68.8% of freshmen and 60.6% of seniors. Never consuming fast food was a significant predictor for maintaining normal BMI in sophomores (OR 3.78; 95% CI 1.61, 8.88; p < 0.01) and juniors (OR 7.82; 95% CI 2.14, 28.65; p < 0.01). In seniors, better psychosocial health (OR 1.40; 95% CI 1.12, 1.76; p < 0.01) was the only significant predictor for maintaining one’s normal freshman BMI category. Among those within the normal BMI range upon entering the university, psychosocial health (OR 1.31; 95% CI 1.10, 1.55; p < 0.01) was the only predictor of retaining one’s absolute BMI within ± 3% as a senior. Prospective studies are needed to better understand the interaction between environment, behavior, and psychological health involved in retaining normal weight.
Arginase 1 Insufficiency Precipitates Amyloid-β Deposition and Hastens Behavioral Impairment in a Mouse Model of Amyloidosis.

Alzheimer's disease (AD) includes several hallmarks comprised of amyloid-β (Aβ) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines. However, currently, it remains unknown if the reduction of arginase 1 (Arg1) in myeloid cell impacts amyloidosis. Herein, we produced haploinsufficiency of Arg1 by the hemizygous deletion in myeloid cells using Arg1fl/fl and LysMcreTg/+ mice crossed with APP Tg2576 mice. Our data indicated that Arg1 haploinsufficiency promoted Aβ deposition, exacerbated some behavioral impairment, and decreased components of Ragulator-Rag complex involved in mechanistic target of rapamycin complex 1 (mTORC1) signaling and autophagy. Additionally, Arg1 repression and arginine supplementation both impaired microglial phagocytosis in vitro. These data suggest that proper function of Arg1 and arginine metabolism in myeloid cells remains essential to restrict amyloidosis.
Endgames: military responses to protests in Arab Autocracies

Since the Arab Spring, there has been a plethora of studies devoted to how militaries affiliated with autocratic regimes respond to mass protests. Endgames: Military Responses to Protests in Arab A...
Peginterferon Beta-1a Demonstrated Better Clinical Outcomes than Teriflunomide in Patients with Relapsing MS, Using a Matching-adjusted Comparison of Phase 3 Trials (P6.368)

Objective: To determine indirect comparative efficacy for proportion of patients with 24-week confirmed disability worsening (CDW) at 108 weeks and annualized relapse rate (ARR) in patients with relapsing forms of multiple sclerosis (RMS) treated with subcutaneous (SC) peginterferon beta-1a every two weeks or oral teriflunomide 14 mg once daily. Background: Peginterferon beta-1a and teriflunomide are two first-line therapies for the treatment of RMS. There are no direct head-to-head trials comparing their efficacy. A matching-adjusted indirect comparison of weighted individual patient data with aggregate data from published Phase 3 trials can provide relevant information for clinicians on the comparative efficacy of these two agents. Design/Methods: Individual relapsing-remitting MS (RRMS) patient data from studies of peginterferon beta-1a 125 mcg every two weeks (ADVANCE/ATTAIN) and pooled summary data of RMS (>90% RRMS) patients from 2 published studies of teriflunomide 14 mg (TEMSO, TOWER) were utilized. The designs and populations of patients in the TEMSO and TOWER trials were sufficiently similar to allow data from the two studies to be pooled. A matching-adjusted indirect comparison of efficacy outcomes was conducted by weighting individual peginterferon-beta-1a-treated patients to match multiple key aggregate baseline characteristics of teriflunomide-treated patients. Results: After matching, baseline characteristics were well balanced across treatment groups. At 108 weeks, peginterferon beta-1a (effective n=382) had a significantly lower proportion of patients with 24-week CDW compared with teriflunomide (n=728) (after matching 8.4% vs. 12.6%; p=0.032). ARR was also numerically lower in patients receiving peginterferon beta-1a vs. teriflunomide (after matching 0.257 vs. 0.354; p=0.051). Conclusions: In this matching-adjusted indirect comparison utilizing three Phase 3 trials, treatment with SC peginterferon beta-1a 125 mcg every 2 weeks resulted in a significantly lower proportion of patients with 24-week CDW compared with oral teriflunomide 14 mg once daily in patients with RMS. Study Supported by: Biogen Disclosure: Dr. Newsome has received personal compensation for activities with Biogen Idec, Novartis, and Genzyme. Dr. Naylor has received personal compensation for activities with Biogen as an employee. Dr. Shang has nothing to disclose. Dr. Castrillo-Viguera has received personal compensation for activities with Biogen as an employee. Dr. Castrillo-Viguera holds stock and/or stock options in Biogen.
Isolation and Characterization of the Cells of the Cerebral Microvessels

Publisher Summary This chapter describes the isolation and characterization of the cells of the cerebral microvessels. The principal steps in isolating microvessels are (1) tissue preparation, (2) dissociation, and (3) separation of the desired elements from the often homogeneous tissue dispersion. The methods used in each of the principal steps vary, sometimes significantly, depending upon the intended use of the isolated microvessels. The details to be considered are the types of isolation media, the control of temperature during isolation, the use of enzymatic digestion or lack of it, the methods of mechanical dispersion (if used), the methods of separation and/or harvest, and, finally, the conditions for holding or maintaining the isolated microvessels until they are utilized. The chapter presents the literature on microvessel isolation from brain and retina. It discusses the range of species and methods of isolation used, as well as the studies performed on the isolated microvessels. The isolation procedure for deriving cells in culture that was successfully used on mouse cerebral microvessels was a mechanical dispersion and filtration technique.
Other Developments and Trends in the Application of Chaos

Suppose we are given the mapping x n +1 = f(x n ), which for some initial condition x0 corresponds to a purely deterministic orbit or sequence {x n } x 1 , x 2 ,..., x n . Due to roundoff and/or truncation errors, however, the sequence that we might observe when this mapping is iterated will be {y n }: y1, y2..., y n (see Fig. 131).
Rapid Multiplexed Imaging of Cell-Surface Cancer Biomarkers in Fresh Tissues with Targeted SERS Nanoparticles

Our lab is developing miniature Raman imaging systems and topical-staining protocols to rapidly image cell-surface biomarkers in fresh tissues. In particular, this work employs targeted surface-enhanced Raman scattering (SERS) nanoparticles (NPs) to enable the sensitive and multiplexed detection of a large number of cell-surface biomarkers of cancer. The SERS NPs were functionalized with different targeting antibodies, and their biomarker detection capability was investigated via in vitro and ex vivo experiments with cells and tissues. Here, we design SERS NPs to specifically target the cancer biomarker EGFR upon topical application on cells and tissues. In vitro flow cytometry with fluorescent SERS NPs reveals a high ratio of specific versus nonspecific binding for the tumor cell lines A431 (skin cancer), U251 (glioma) and SkBr3 (breast cancer). For tissue imaging, we have developed a fiber-optic-based spectral detection probe, with 785-nm laser illumination, for rapid detection of SERS NPs with sub-millimeter spatial resolution. Based on the spectral detection probe, multiple imaging systems were customized for rapid tissue phenotyping such as a comprehensive rotational scanning endoscope for in vivo imaging of the rat esophagus and a raster-scanning device for intraoperative imaging of breast tissue margins. Ex vivo experiments were performed to develop a strategy for the rapid detection of multiple cell-surface biomarkers following a brief (5-10 min) topical application of SERS NPs on tissues. By developing high-affinity targeted SERS NPs, sensitive spectral-imaging devices, and an optimized topical-delivery protocol, we demonstrate a ratio metric method to rapidly quantify the specific binding of biomarker-targeted NPs on fresh tissues, thereby eliminating the ambiguities that often arise due to nonspecific sources of contrast. These tools will enable multiplexed molecular imaging for the early detection of epithelial cancers, rapid surgical guidance, and monitoring the molecular response to treatments.
A Survey on Service Creation by End Users

We conducted a survey on end users’ willingness and capability to create their desired communication services. The survey is based on the graphical service creation tool we implemented for the Language for End System Services (LESS). We call the tool CUTE, which stands for Columbia University Telecommunication service Editor. This report demonstrates our survey result and shows that relatively inexperienced users are willing and capable to create their desired communication services, and CUTE fits their needs.
Effect of Operating Conditions on Gearbox Noise

Low contact ratio spur gears were tested in the NASA gear noise rig to study the noise radiated from the top of the gearbox. The measured sound power from the gearbox top was obtained from a near field acoustic intensity scan taken at 63 nodes just above the surface. The sound power was measured at a matrix of 45 operating speeds and torque levels. Results are presented in the form of a spectral speed map and as a plot of sound power versus torque (at constant speed) and as sound power versus speed (at constant torque). Because of the presence of vibration modes, operating speed was found to have more impact on noise generation than torque level. A NASA gear dynamics code was used to compute the gear tooth dynamic overload at the same 45 operating conditions used for the experiment. Similar trends were found between the analytical results for dynamic tooth overload and experimental results for sound power. Dynamic analysis may be used to design high quality gears with profile relief optimized for minimum dynamic load and noise.
High-Throughput Differentiation and Screening of a Library of Mutant Stem Cell Clones Defines New Host-Based Genes Involved in Rabies Virus Infection.

We used a genomic library of mutant murine embryonic stem cells (ESCs) and report the methodology required to simultaneously culture, differentiate, and screen more than 3,200 heterozygous mutant clones to identify host-based genes involved in both sensitivity and resistance to rabies virus infection. Established neuronal differentiation protocols were miniaturized such that many clones could be handled simultaneously, and molecular markers were used to show that the resultant cultures were pan-neuronal. Next, we used a green fluorescent protein (GFP) labeled rabies virus to develop, validate, and implement one of the first host-based, high-content, high-throughput screens for rabies virus. Undifferentiated cell and neuron cultures were infected with GFP-rabies and live imaging was used to evaluate GFP intensity at time points corresponding to initial infection/uptake and early and late replication. Furthermore, supernatants were used to evaluate viral shedding potential. After repeated testing, 63 genes involved in either sensitivity or resistance to rabies infection were identified. To further explore hits, we used a completely independent system (siRNA) to show that reduction in target gene expression leads to the observed phenotype. We validated the immune modulatory gene Unc13d and the dynein adapter gene Bbs4 by treating wild-type ESCs and primary neurons with siRNA; treated cultures were resistant to rabies infection/replication. Overall, the potential of such in vitro functional genomics screens in stem cells adds additional value to other libraries of stem cells. This technique is applicable to any bacterial or virus interactome and any cell or tissue types that can be differentiated from ESCs. Stem Cells 2015;33:2509–2522
Molecular Analysis of Root Induction by Agrobacterium rhizogenes

Agrobacterium rhizogenes incites hairy root disease of plants. The disease is closely related to crown gall disease due to strains of Agrobacterium tumefaciens. The ability of both bacteria to cause plant tumors is encoded by the large virulence plasmids in the respective strains. The virulence plasmid of A. rhizogenes has become known as the root-inducing (Ri) plasmid, to distinguish the plasmid from the tumor-inducing (Ti) plasmid of A. tumefaciens. The underlying mechanisms for hairy root and crown gall disease are very similar. Therefore, this review will not discuss the extensive literature pertaining to the Ti plasmid except where necessary for comparison to the Ri plasmid. However, an understanding of the Ri plasmid as permitted by present knowledge is incomplete without consideration of the Ti plasmid, and the reader is referred to other chapters in this book and recent reviews (Zambryski et al., 1983; Nester et al., 1984).
A bacterial toxin and a nonenveloped virus hijack ER-to-cytosol membrane translocation pathways to cause disease

A dedicated network of cellular factors ensures that proteins translocated into the endoplasmic reticulum (ER) are folded correctly before they exit this compartment en route to other cellular destinations or for secretion. When proteins misfold, selective ER-resident enzymes and chaperones are recruited to rectify the protein-misfolding problem in order to maintain cellular proteostasis. However, when a protein becomes terminally misfolded, it is ejected into the cytosol and degraded by the proteasome via a pathway called ER-associated degradation (ERAD). Strikingly, toxins and viruses can hijack elements of the ERAD pathway to access the host cytosol and cause infection. This review focuses on emerging data illuminating the molecular mechanisms by which these toxic agents co-opt the ER-to-cytosol translocation process to cause disease.
Do cigarette prices motivate smokers to quit? New evidence from the ITC survey.

Aims To examine the importance of cigarette prices in influencing smoking cessation and the motivation to quit. Design We use longitudinal data from three waves of the International Tobacco Control Policy Evaluation Survey (ITC). The study contrasts smoking cessation and motivation to quit among US and Canadian smokers and evaluates how this relationship is modified by cigarette prices, nicotine dependence and health knowledge. Different price measures are used to understand how the ability to purchase cheaper cigarettes may reduce the influence of prices. Our first model examines whether cigarette prices affect motivation to quit smoking using Generalized Estimating Equations to predict cessation stage and a least squares model to predict the change in cessation stage. The second model evaluates quitting behavior over time. The probability of quitting is estimated with Generalized Estimating Equations and a transition model to account for the ‘left-truncation’ of the data. Settings US and Canada. Participants 4352 smokers at Wave 1, 2000 smokers completing all three waves. Measurements Motivation to quit, cigarette prices, nicotine dependence and health knowledge. Findings Smokers living in areas with higher cigarette prices are significantly more motivated to quit. There is limited evidence to suggest that price increases over time may also increase quit motivation. Higher cigarette prices increase the likelihood of actual quitting, with the caveat that results are statistically significant in one out of two models. Access to cheaper cigarette sources does not impede cessation although smokers would respond more aggressively (in terms of cessation) to price increases if cheaper cigarette sources were not available. Conclusions This research provides a unique opportunity to study smoking cessation among adult smokers and their response to cigarette prices in a market where they are able to avoid tax increases by purchasing cigarettes from cheaper sources. Higher cigarette prices appear to be associated with greater motivation to stop smoking, an effect which does not appear to be mitigated by cheaper cigarette sources. The paper supports the use of higher prices as a means of encouraging smoking cessation and motivation to quit.
The impact of neogene grassland expansion and aridification on the isotopic composition of continental precipitation

The late Cenozoic was a time of global cooling, increased aridity, and expansion of grasslands. In the last two decades numerous records of oxygen isotopes have been collected to assess plant ecological changes, understand terrestrial paleoclimate, and to determine the surface history of mountain belts. The δ18O values of these records, in general, increase from the mid-Miocene to the Recent. We suggest that these records record an increase in aridity and expansion of grasslands in midlatitude continental regions. We use a nondimensional isotopic vapor transport model coupled with a soil water isotope model to evaluate the role of vapor recycling and transpiration by different plant functional types. This analysis shows that increased vapor recycling associated with grassland expansion along with biomechanistic changes in transpiration by grasses themselves conspires to lower the horizontal gradient in the δ18O of atmospheric vapor as an air mass moves into continental interiors. The resulting signal at a given inland site is an increase in δ18O of precipitation with the expansion of grasslands and increasing aridity, matching the general observed trend in terrestrial Cenozoic δ18O records. There are limits to the isotopic effect that are induced by vapor recycling, which we refer to here as a “hydrostat.” In the modern climate, this hydrostatic limit occurs at approximately the boundary between forest and grassland ecosystems.
2,3-Dihydrofarnesyl and citronellyl esters in the paracloacal gland secretions of the brown caiman (Caiman crocodilus fuscus) from Costa Rica

Abstract The paracloacal gland secretions of a male and a female brown caiman (Caiman crocodilus fuscus) from Costa Rica were analyzed by gas chromatography-mass spectrometry. 3,7,11-Trimethyldodeca-6,10-dien-1-ol (2,3-dihydrofarnesol) and 20 of its esters, with acid moieties ranging in carbon-chain length from two to 18, were observed in one or both sexes. Most of these compounds have not previously been described from a natural source. 3,7-Dimethyl-6octen-1-yl (citronellyl) acetate, citronellyl butanoate, and citronellyl hexanoate were observed in the secretions of the female caiman. Squalene was observed in both sexes.
Toxicity of dimethyl sulfoxide and magnesium as a function of temperature.

A study was made in isolated left atria (rabbit) of the toxicity of various concentrations of dimethyl sulfoxide (DMSO) and magnesium (MgCl2.6H2O) at 5, 15 and 25°C. The cryoprotectants (DMSO, Mg++) are less toxic at 15°C as shown by Q10 values calculated from ouabain responses at different temperatures. Magnesium is shown to be less toxic than dimethyl sulfoxide and to give best results at concentrations around 20–60 mM.
Thermal analysis of LN2-cooled silicon crystals for Energy Recovery Linac monochromators

We discuss major features of the predicted power distribution in undulator beams at the proposed Cornell Energy Recovery Linac, and the anticipated consequences for monochromator performance. Finite element analysis of thermal deformation of LN2-cooled Si crystal monochromators for the ERL is summarized. A new metric, the modified linear power density, is found to provide a clear description of crystal thermal deformation.
Theoretical Considerations Concerning the D + D Reactions

Some possibilities are explored for the theoretical explanation of the angular distribution of $D+D$ reaction products. The variation with energy is ascribed entirely to differences in the centrifugal barriers encountered by the bombarding particles responsible for the isotropic and non-isotropic components. The detailed data on the proton distributions at low energies appear to be explained in terms of an asymmetric part produced by $P$-waves superposed on isotropic emissions caused by $S$-waves. However, ordinary extrapolation of this to higher energies gives much less symmetric distributions than experimentally found at such energies for the emission of neutrons. If the experiments are correct as interpreted, then they appear to show that spin-orbit coupling plays a large part in the reactions. In that case, an isotropic component produced by incoming $P$-waves grows in importance with energy and accounts for the increasingly parallel growth of the isotropic and asymmetric emissions.
A new high temperature ISOL ion source with an electron-extracting grid

Abstract The recently developed UNISOR high temperature ISOL ion source has been significantly improved with the addition of an electron-extracting grid. The use of a tungsten wire mesh anode of cylindrical geometry in close proximity to the hot cathode allows the source to run on pure He gas and at a lower overall pressure. A much wider range of cathode heating currents are now possible. Initial on-line tests indicate a six-fold increase in efficiency.
High-level expression of tamavidin 2 in human cells by codon-usage optimization

Tamavidin 2 is a fungal protein that binds to biotin with an extremely high affinity. Tamavidin 2 is superior to avidin or streptavidin in terms of its low-level non-specific binding and high-level thermal stability. However, the gene for tamavidin 2 is highly expressed in Escherichia coli but not in mammalian cells, restricting its application as an affinity tag in mammalian cells. Here, we optimized the codon usage of tamavidin 2 for human cells and found that the resultant mutant expressed tamavidin 2 at approximately 30-fold higher level compared with the native gene. The protein thus produced in human cells could be purified by iminobiotin affinity chromatography, bound tightly to biotin, and was stable at high temperature (82 °C). This powerful technology for high-level expression of tamavidin 2 in mammalian cells will be of value in evaluating various fusion proteins produced in mammalian cells for numerous applications.
Stimulation of mutation in phage T 4 by lesions in gene 32 and by thymidine imbalance.

Summary In bacteriophage T 4 , temperature-sensitive ( ts ) mutations in gene 32 as well as in gene 43 have previously been shown to stimulate reversion of frame-shift mutations. We show here that two ts mutations in gene 32 increase reversion of base substitution mutations. ts mutations in several other genes with DNA-related functions were not observed to have significant mutator or antimutator effects. A recombinational map of gene 32 was constructed using II mutations including the two ts alleles with mutator effects. The length of the map suggests that gene 32 specified a protein of roughly 30 000 molecular weight. It was also shown that a phage mutant with defective thymidylate synthetase has a mutator effect on base substitution mutation when grown under conditions of limiting thymine or thymidine. In addition, these experiments suggested that high levels of exogenous thymine or thymidine stimulate mutation if added to phage with a normal thymidylate synthetase.
Learning Best Concept Approximations from Examples

This paper addresses the problem of learning the best approximation of a concept from examples, when the concept cannot be expressed in the learner’s representation language. It presents a method that determines the version space of the best approximations and demonstrates that for any given approximation of the target concept there is a better approximation in this version space. The method does not depend on the order of examples and has an almost monotonic convergence. This method was developed for the Disciple learning agent that can be taught by a subject matter expert how to perform complex problem solving tasks.
Synthesis and dihydrogen phosphate binding properties of pyrrole containing ansa-ferrocenes

Abstract Pyrrole-substituted α,ω-diamines varying in length and number of heteroatoms between the amine functionalities were reacted with 1,1′-ferrocenedimethanol to form ansa -ferrocenes. 1 H-NMR binding studies in a 2% dimethylsulfoxide- d 6 solution of dichloromethane- d 2 establish a correlation between the affinity for tetrabutylammonium dihydrogen phosphate and the number of heteroatoms in the diamine. Further support for this conclusion came from electrochemical analyses.
Radiative Recombination Rate Coefficients for Bare through F-like Isosequences of Mg, Si, S, Ar, Ca, Fe, and Ni

We present distorted-wave calculations and analytic fits to the radiative recombination rate coefficients of bare to F-like isosequences of seven abundant astrophysical elements, including Mg, Si, S, Ar, Ca, Fe, and Ni. The fits are valid over a wide range of temperature, from 10-4 to 104 eV. Extensive comparisons with existing data are made.
Learning Verb-Noun Relations to Improve Parsing

The verb-noun sequence in Chinese often creates ambiguities in parsing. These ambiguities can usually be resolved if we know in advance whether the verb and the noun tend to be in the verb-object relation or the modifier-head relation. In this paper, we describe a learning procedure whereby such knowledge can be automatically acquired. Using an existing (imperfect) parser with a chart filter and a tree filter, a large corpus, and the log-likelihood-ratio (LLR) algorithm, we were able to acquire verb-noun pairs which typically occur either in verb-object relations or modifier-head relations. The learned pairs are then used in the parsing process for disambiguation. Evaluation shows that the accuracy of the original parser improves significantly with the use of the automatically acquired knowledge.
The interstitial cell stimulating activity of ovine, equine and human luteinizing hormone preparations in the hypophysectomized male rhesus monkey.

Luteinizing hormone preparations of non-primate (sheep and horse) as well as of primate origin (human pituitary and placental) were found to stimulate the interstitial cells of Leydig in hypophysectomized male rhesus monkeys. Although quantitative differences in the efficacy of the various LH preparations were noted, it is concluded that an absolute “species specificity” as described for the actionof growth hormone in primates is not attributable to theinterstitial cell stimulating activity of luteinizing hormone.
Decoupling with state feedback and precompensation

Two algorithms for decoupling invertible systems via state feedback and precompensation are presented. The first is a generalization of the Falb-Wolovich procedure, while the second utilizes simple transfer function technique and yields a stable decoupled system.
NK cells in HIV infection: Paradigm for protection or targets for ambush

Natural killer cells are a crucial component of the innate immune response to certain tumours and to various viruses, fungi, parasites and bacteria. HIV has infected more than 60 million people worldwide and has led to more than 23 million deaths. At present, there are approximately 40 million people who are living with HIV infection, and there were 5 million new infections in 2004. As part of the innate immune system, natural killer cells might have an important role in host defence against HIV infection, as well as in the control of HIV replication in vivo. In this regard, it is important to understand how natural killer cells and HIV interact. This Review focuses on the role of natural killer cells in controlling HIV infection and on the impact of HIV and HIV-viraemia-induced immune activation on natural-killer-cell function.
Calorimetric unfolding of the bimolecular and i-motif complexes of the human telomere complementary strand, d(C3TA2)4

A combination of spectroscopic and calorimetric techniques is used to determine the unfolding thermodynamics of the complexes formed by the complementary sequence of the human telomere, d(C(3)TA(2))(4), in the pH range of 4.2 to 6. Calorimetric melting curves show biphasic transitions; both transitions are shifted to higher temperatures as the pH is decreased, indicative of cytosine protonation, which favors the formation of C*C(+) base pairs. Furthermore, the transition temperature, T(M), of the lower transition depends on strand concentration, while the T(M) of the higher transition is independent of strand concentration, indicating the following sequential melting: bimolecular complex(s)-->intramolecular complex-->random coil. The thermodynamic profiles for the formation of each complex, bimolecular and i-motif reveals small favorable free energy terms resulting from favorable enthalpy-unfavorable entropy compensations, uptake of protons, marginal uptake of counterions (i-motif) and marginal release of water molecules (i-motif). Furthermore, an enthalpy of 3.2 kcal/mol (bimolecular complex) and 5.0 kcal/mol (i-motif) is estimated for a single C*C(+)/C*C(+) base-pair stack.
[Investigations on neutralization and inhibition of hemagglutination by the parapoliomyelitis virus (Col SK strain) with sera from cases of encephalitis, aseptic meningitis and poliomyelitis].

Es wird berichtet uber die Untersuchung einer Anzahl von Patienten mit der klinischen Diagnose Encephalitis, aseptischer Meningitis oder Poliomyelitis, sowie deren Kontaktpersonen, auf die Gegenwart neutralisierender und hamagglutinationshemmender Antikorper gegen Parapoliomyelitisvirus (Col SK-Stamm). Einwandfrei positive Ergebnisse mit beiden Untersuchungsmethoden betrugen bei einer Gruppe von insgesamt 23 Patienten 8,7% fur Neutralisation und 17,3% fur Hamagglutinationshemmung; bei einer Gruppe von insgesamt 30 klinisch gesunden Kontaktpersonen 16,7 fur Neutralisation und 0% fur Hamagglutinationshemmung. Die atiologische Bedeutung der serologischen Reaktionen fur die verschiedenen Krankheitsbilder wird diskutiert.
Growth habits and kinetics of crystallization of poly(ethylene 2,6-naphthalate) under isothermal and nonisothermal conditions

Abstract Poly(ethylene 2,6-naphthalate) (PEN) can be formed into the glassy state by rapid quenching, or it can form semicrystalline structure by either annealing the amorphous precursor at elevated temperature or slow cooling from the melt. During isothermal crystallization, relatively high crystallinity develops, with a time dependence described by the Avrami equation with the exponent n = 2.5. The activation energy for isothermal crystallization was determined to be 60 kcal/mol. The modified Avrami equation proposed by Velisaris was found to describe the primary and secondary crystallization reasonably well. For nonisothermal studies, PEN was crystallized by cooling at rates ranging from 1°C/min to 5°C/min from the melt. The models proposed by Ozawa and Nakamura were used to describe the nonisothermal crystallization kinetics of PEN. The exponent n and rate constant k of the nonisothermal crystallization determined by Ozawa analysis showed good agreement with those of isothermal crystallization. The Na...