cssi/SciSciGPT-SciSciNet huggingface dataset:
In Vivo Applications of CRISPR-Based Genome Editing in the Retina.

The rapidly evolving CRISPR-based genome editing technology is bringing revolutionary changes to the entirety of the life sciences. In this mini-review, we summarize the recent progress of in vivo applications of CRISPR genome editing in retinal studies. Non-viral and viral vector mediated delivery have been developed for temporary or persistent expression of CRISPR components in retinal cells. Although in theory CRISPR-based genome editing can correct a large number of mutant genes responsible for a variety of inherited retinal disorders (IRDs), precise gene modification relies on homology-directed repair (HDR) – the efficiency of which is not currently high enough for meaningful benefit. Development of CRISPR-based treatment for retinal diseases thus far has been mainly focused on gene knock-out or gene deletion in which the highly efficient non-homologous end joining (NHEJ) repair pathway is involved. Therapeutic benefits have been achieved in a few rodent models of retinal diseases following CRISPR treatment. The in vivo applications of CRISPR have also facilitated studies of gene function in the retina. As off-target events and immune responses are still the major concerns, continuous development of safer CRISPR genome editing system is prerequisite for its clinical applications.
Chimpanzees show some evidence of selectively acquiring information by using tools, making inferences, and evaluating possible outcomes

Metacognition refers to thinking about one's thinking or knowing what one knows. Research suggests that this ability is not unique to humans and may be shared with nonhuman animals. In particular, great apes have shown behaviors on a variety of tasks that are suggestive of metacognitive ability. Here we combine a metacognitive task, the information-seeking task, with tool use and variable forms of initial information provided to chimpanzees to explore how informational states impact behavioral responses in these apes. Three chimpanzees were presented with an apparatus that contained five locations where food could be hidden. If they pointed to the correct location, they received the reward, but otherwise they did not. We first replicated several existing findings using this method, and then tested novel hypotheses. The chimpanzees were given different types of information across the experiments. Sometimes, they were shown the location of the food reward. Other times, they were shown only one empty location, which was not useful information. The chimpanzees also could use a tool to search any of those locations before making a selection. Chimpanzees typically used the tool to search out the location of the reward when they could not already know where it was, but they did not use the tool when they already had been given that information. One chimpanzee made inferences about the location of hidden food, even when that food was never shown in that location. The final experiment involved hiding foods of differing preference values, and then presenting the chimpanzees with different initial knowledge states (i.e., where the best food was located, where the less-preferred food was located, or where no food was located). All chimpanzees used the tool when they needed to use it to find the best possible item on that trial, but responded by choosing a location immediately when they did not need the tool. This finding highlights that their behavior was not the result of a simple rule following such as pointing to where any food had been seen.
Learning to Use PHASER

The purpose of this chapter is to analyze the startup screen layout of PHASER, as illustrated in Figure 4.2. Along the way, we will also point out some of the general features of our animator/simulator for dynamical systems.
Tabakabhängigkeit bei psychiatrischen Patienten

Psychiatrische Patienten stellen eine Risikopopulation fur eine hohe Raucherpravalenz und starkes Rauchen dar. Die Raucherpravalenz unter allen psychiatrischen Patienten wird in den verschiedenen Arbeiten mit 35–54% angegeben und ist damit deutlich ho als in der Allgemeinbevolkerung westlicher Industrielander mit Raucherquoten zwischen 23% (z.B. Schweden), 27% (z.B. Deutschland) und 37% (z.B. Danemark) (World Health Organization 1997).
ArtiFact: Architecture and CAD Flow for Efficient Formal Verification of SoC Security Policies

Verification of security policies represents one of the most critical, complex, and expensive steps of modern SoC design validation. SoC security policies are typically implemented as part of functional design flow, with a diverse set of protection mechanisms sprinkled across various IP blocks. An obvious upshot is that their verification requires comprehension and analysis of the entire system, representing a scalability bottleneck for verification tools. The scale and complexity of industrial SoC is far beyond the analysis capacity of state-of-the-art formal tools; even simulation-based security verification is severely limited in effectiveness because of the need to exercise subtle corner-cases across the entire system. We address this challenge by developing a novel security architecture that accounts for verification needs from the ground up. Our framework, ArtiFact, provides an alternative architecture for security policy implementation that exploits a flexible, centralized, infrastructure IP and enables scalable, streamlined verification of these policies. With our architecture, verification of system-level security policies reduces to analysis of this single IP and its interfaces, enabling off-the-shelf formal tools to successfully verify these policies. We introduce a CAD flow that supports both formal and dynamic (simulation-based) verification, and is built on top of such off-the-shelf tools. Our approach reduces verification time by over 62X and bug detection time by 34X for illustrative policies.
Cold Plasma with Immunomodulatory Properties Has Significant Anti-Lymphoma Activities in Vitro and In Vivo

In recent years, cancer immunotherapy has revolutionized cancer care. Remarkable clinical efficacy and durable responses to checkpoint blockade antibodies or to genetically engineered T-cells (CAR T cell) have been observed in patients with multiple cancers. However, not all cancer patients benefit from these therapies and as such novel immunotherapeutic approaches are needed. The cold atmospheric plasma (CAP) is a form of near room temperature ionized gas, which has shown a promising application in cancer therapy given its antitumor effects in vitro as well as in vivo. For the first time, we have shown that upon CAP treatment, the viability of the immune cells remained unaffected. Strikingly, we observed a significantly stronger immune activation of those CAP treated cells when compare with helium gas control. First, we have demonstrated that even without LPS stimulation, in vitro exposure of peritoneal elicited macrophages (PEM) to CAP for 15 or 30 seconds was sufficient to trigger the production of the pro-inflammatory cytokines IL-12 and IL-6. In addition, decreased production of anti-inflammatory cytokine IL-10 and diminished the expression of PD-L1 were observed in CAP-treated PEM as well. It indicated that CAP treatment may potentially facilitate PEMs as better activator of T cells. Second, in lieu of the stimulatory effects of CAP upon PEM, we asked whether CAP could enhance T-cell activation. So we isolated T cells from spleens of C57BL/6 mice and exposed these T cells to CAP followed by anti-CD3/CD28 stimulation. Our study shown that the production of IL-2 and IFN-g were significantly increased by T-cells treated with CAP as compared with helium gas control. Furthermore, to gain insights into effects of CAP upon immune responses in vivo, we isolated lymph nodes from OTII mice and directly exposed these LNs with CAP, helium gas control or left untreated. Then CD4+ T cells were further isolated from the LNs and cultured with macrophages in the presence or absence of OVA peptide for 48 hours, respectively. Surprisingly, CD4+ T cells isolated from CAP-treated LNs displayed enhanced function indicated by its increased production of IL-2 and IFN-g. More importantly, strong in vivo anti-tumor effects were observed when adoptively transfer CAP exposed T cells to lymphoma bearing animals. Taken together, we have shown for the first time an elevated immune-stimulatory effect of CAP upon both APCs and T cells in vitro and in vivo. Our finding may potentially shed light of a novel therapeutic approach for future cancer immunotherapy. Disclosures No relevant conflicts of interest to declare.
Association of Hypertrophic Obstructive Cardiomyopathy With Outcomes Following Transcatheter Aortic Valve Replacement

This cohort study investigates the association of hypertrophic obstructive cardiomyopathy with outcomes following transcatheter aortic valve replacement.
Roma Rights and Civil Rights: A Transatlantic Comparison

Roma Rights and Civil Rights tackles the movements for - and expressions of - equality for Roma in Central and Southeast Europe and African Americans from two complementary perspectives: law and cultural studies. Interdisciplinary in approach, the book engages with comparative law, European studies, cultural studies, and critical race theory. Its central contribution is to compare the experiences of Roma and African Americans regarding racialization, marginalization, and mobilization for equality. Deploying a novel approach, the book challenges conventional notions of civil rights and paradigms in Romani studies.
Excited States in N 14 from the Elastic Scattering of Protons by C 13

Excited states in ${\mathrm{N}}^{14}$ have been observed by measuring the differential elastic scattering cross section of ${\mathrm{C}}^{13}(p, p){\mathrm{C}}^{13}$ for proton energies from 2.6 to 5.0 Mev. Resonances were observed at proton energies of 2.743, 2.87, 3.105, 3.20, 3.78, 3.980, 4.04, and 4.14 Mev, corresponding to excited states in ${\mathrm{N}}^{14}$ at 10.092, 10.21, 10.428, 10.52, 11.05, 11.240, 11.30, and 11.39 Mev, respectively. Single-level dispersion theory analysis indicates assignments ${J}^{\ensuremath{\pi}}={1}^{+}({2}^{+}), {1}^{\ensuremath{-}}, {2}^{+}, {1}^{\ensuremath{-}}, {1}^{+}, {3}^{\ensuremath{-}}, {2}^{\ensuremath{-}}, \mathrm{and} {1}^{+}$, respectively, for these states. Analysis of previously published ${\mathrm{C}}^{13}(p, p){\mathrm{C}}^{13}$ data at lower energies confirms the assignments ${1}^{\ensuremath{-}}$, ${0}^{+}$, ${0}^{\ensuremath{-}}$, ${3}^{\ensuremath{-}}$, and ${1}^{+}$ for the states at 8.05, 8.61, 8.75, 8.90, and 8.98 Mev. A resonance at 4.265 Mev corresponding to the known narrow state at 11.504 Mev was not found in the elastic scattering data although it was found to be strong in ${\mathrm{C}}^{13}(p, {p}^{\ensuremath{'}}){\mathrm{C}}^{13*}$.
[Relationship between both duration and quality of sleep, and metabolic syndrome identified by classification tree model in midlife population in Tianjin].

Objective: To study the association of duration and quality of sleep with metabolic syndrome. Methods: Multi-stage cluster random sampling method was used to extract data from the '2015 adult chronic disease and nutrition monitoring population project' from 42 communities of 7 districts in Tianjin. A total of 1 388 residents aged 45 to 59 years old were selected to analyze the relationship between both duration and quality of sleep and the metabolic syndrome. χ(2) test, non-conditional logistic regression and classification tree models were used for data analysis. Result: The prevalence of metabolic syndrome appeared as 30.4%, 37.4 % and 43.1% in the poor, common or well sleep groups respectively. The prevalence rates of metabolic syndrome in the sleep time 7.5 h, 6.0-7.5 h groups were 36.5% and 30.6% respectively. After adjusting for gender and age, results from the logistic regression analysis showed that short or long sleep duration, as well as poor sleep quality all appeared as risk factors on metabolic syndrome (P<0.05). According to the classification tree model, factors as gender (importance: 0.004, standardized importance: 100%), quality of sleep (importance: 0.004, standardized importance: 99.5%), duration of sleep (importance: 0.002, standardized importance: 38.6%), education level (importance: 0.001, standardized importance: 22.3%) and salt intake (importance: 0.001, standardized importance: 22.2%) were all important on metabolic syndrome and with interactive effects. Conclusions: Both quality and duration of sleep were important influencing factors on metabolic syndrome among midlife population in Tianjin. More attention should be paid to sleep and health status among the midlife population. Ability on self-management of health should also be strengthened through health education, to prevent metabolic syndrome and other chronic diseases in this population.
Substance use screening and rates of treatment referral among justice-involved youth

Abstract Background Justice-involved youth report high rates of substance use and related problems that are associated with treatment needs; however, data on screening and linkage to treatment within the justice system is lacking. To further inform the juvenile justice behavioral health cascade of care, this study examined factors associated with identified problematic substance use and treatment referral using two screening tools. Method As part of a family court intake process, 348 justice-involved youth received two screening measures, the MAYSI-2 alcohol/drug use subscale and the CRAFFT. Both tools are designed to indicate early warning signs of substance use problems and signal referral for further clinical evaluation or treatment. Chart review analysis examined whether demographic variables (sex & race), severity of use, and type of substance used were associated with positive screens on either or both measures and subsequent treatment referral. Results Half (51.2%) of youth were identified as having problematic substance use (a positive screen) on at least one of the screeners. Overall, 38.5% positively screened on the CRAFFT with only 0.3% positively screening on just the MAYSI-2 alcohol/drug scale. Cannabis only users were less likely to positively screen on the MAYSI-2 compared to youth who reported use of both alcohol and cannabis. Positively screening on one versus both screeners was not associated with referral, yet many (28%) who positively screened were not referred for services. Conclusions The CRAFFT may be more accurate at identifying youth specifically at risk for problematic cannabis use compared to the MAYSI-2 alcohol/drug subscale. Regardless of tool used, treatment referral was low, highlighting the need for accurate identification of treatment needs of substance-using, justice-involved youth. Interventions to facilitate referrals for youth with problematic substance use are needed.
First e-cigarette flavor and device type used: Associations with vaping persistence, frequency, and dependence in young adults.

INTRODUCTION Type of e-cigarette flavoring and device during first use might differentiate later e-cigarette use and dependence. This retrospective cross-sectional study examined associations of recalled first nicotine vaping device and flavor used with current vaping frequency/dependence. METHODS A young adult cohort from Los Angeles, California, USA completed web-based surveys (N=2553). Using cross-sectional data from 971 reporting ever vaping nicotine, multivariable hurdle regressions tested associations between recalled first flavor (fruit/sweet, menthol/mint, other) and device (Juul, disposable, mod, box, pod, pen, other) vaped with past-30-day vaping status (yes/no) and frequency (1-30 days), and with any vaping dependence symptoms (yes/no) and count (1-10 symptoms). RESULTS The most common first-flavor was sweet (71%); the most common first-device was a vape pen (37%), then Juul (22%). First-flavor of mint/menthol (vs. other; adjusted odds ratio [AOR]: 2.22[95%CI=1.16-4.25]), and first-device mod (AOR=2.40[95%CI=1.34-4.31]) and non-Juul pod (2.64[95% CI=1.41-4.92]) (vs. pen) were associated with past-30-day vaping, and twice as many vaping days (ARRs [Adjusted rate ratios] range: 1.96-2.12;ps<0.05). First flavor of mint/menthol (vs. other; AOR: 1.95[95% CI=1.003-3.79) and first device mod, box, non-juul pod and other (AORs range: 2.36-4.01;ps<0.05) were associated with nicotine dependence. First device Juul, mod, box and non-Juul pod were also associated with more dependence symptoms (ARRs range:1.38-1.59;ps<0.05). CONCLUSIONS Exposure to mint/menthol and certain devices (mod, box, Juul and non-juul pods) at first e-cigarette use may be associated with more frequent e-cigarette use and nicotine dependence symptoms in young adulthood. Mint/menthol and certain devices warrant consideration in regulation of e-cigarettes based on product characteristics. IMPLICATIONS Characteristics (flavor and device type) of first e-cigarette product used were associated with higher usage and more dependence. Pending replication with prospective designs, the findings suggest certain flavors (mint/menthol) and devices (pods, mods) merit consideration in regulation because of their possible link with continued use and dependence among young people.
Basolateral protein Scribble binds phosphatase PP1 to establish a signaling network maintaining apicobasal polarity.

Scribble, a member of the LAP protein family, contributes to the apicobasal polarity (ABP) of epithelial cells. The LAP-unique region of these proteins, which is essential and sufficient for ABP, includes a conserved Leucine-Rich Repeat (LRR) domain. The major binding partners of this region that could regulate ABP remain unknown. Here, using proteomics, native gel electrophoresis, and site-directed mutagenesis, we show that the concave surface of LRR domain in Scribble participates in three types of mutually exclusive interactions—(i) homodimerization, serving as an auto-inhibitory mechanism; (ii) interactions with a diverse set of polarity proteins, such as Llgl1, Llgl2, EPB41L2, and EPB41L5, which produce distinct multiprotein complexes; and (iii) a direct interaction with the protein phosphatase, PP1. Analogy with the complex between PP1 and LRR domain of SDS22, a well-studied PP1 regulator, suggests that the Scibble-PP1 complex stores a latent form of PP1 in the basolateral cell cortex. Such organization may generate a dynamic signaling network wherein PP1 could be dispatched from the complex with Scribble to particular protein ligands, achieving fast dephosphorylation kinetics.
Trees for livelihoods: Exploring the relationship between community agroforestry and community capitals in rural Haiti

For decades, various institutions have attempted to improve rural livelihoods in Haiti by implementing agroforestry. While agroforestry provides ecological and economic benefits, little is known ab...
Long-Term Dynamical Constraints on Pharmacologically Evoked Potentiation Imply Activity Conservation within In Vitro Hippocampal Networks

This paper describes a long-term study of network dynamics from in vitro, cultured hippocampal neurons after a pharmacological induction of synaptic potentiation. We plate a suspension of hippocampal neurons on an array of extracellular electrodes and record electrical activity in the absence of the drugs several days after treatment. While previous studies have reported on potentiation lasting up to a few hours after treatment, to the best of our knowledge, this is the first report to characterize the network effects of a potentiating mechanism several days after treatment. Using this reduced, two-dimensional in vitro network of hippocampal neurons, we show that the effects of potentiation are persistent over time but are modulated under a conservation of spike principle. We suggest that this conservation principle might be mediated by the appearance of a resonant inter-spike interval that prevents the network from advancing towards a state of hyperexcitability.
Towards the creation of a data-driven programming tutor

Educational data mining methods are being used to automatically generate hints to students in intelligent tutoring systems Using these methods, we hope to create a system that can give individualized instruction By analyzing time snapshot data from exams in an introductory programming course, we will write a program to construct state graphs for each student's performance, eventually resulting in a Markov decision process that represents different approaches to writing the target program, and providing feedback to students Once this system is sufficiently tested and refined, it will then be applied to subsequent semesters students in the programming course.
"Heads, You Win": Newsletters and Magazines of the Polio Nation

This article examines a range of polio rehabilitation center newsletters and polio-related quarterly publications from the late 1930s to the late 1960s. Drawing on the writings of disability and textual scholars, it determines that these print materials enabled the formation of polio-affected communities, or even a politically motivated polio nation, whose shared interests, concerns, and newly formed identities were represented in these works. The more grassroots and somacentric the orientation of these periodicals, the more therapeutic they may have been.
Clostridium difficile Infection After Subarachnoid Hemorrhage: A Nationwide Analysis.

BACKGROUND Clostridium difficile infection (CDI) is an important cause of hospital-acquired morbidity and mortality. OBJECTIVE To evaluate the incidence of, predictors for, and effects on outcome by CDI after aneurysmal subarachnoid hemorrhage. METHODS Data were extracted from the Nationwide Inpatient Sample (2002-2011). Patients with subarachnoid hemorrhage who underwent microsurgical or endovascular aneurysm repair were included. Multivariate logistic regression was used to determine the independent predictors of developing CDI. Additional models were constructed to assess the impact of CDI on mortality, length of stay, and discharge disposition. RESULTS Of the 18 007 patients who were included, 1.9% (n = 346) developed CDI. Patients who developed CDI were significantly older and had more comorbidities (P ≤ .001). Independent predictors of developing CDI were Medicaid payer status; ventriculostomy; mechanical ventilation; a greater number of noninfectious complications; and the development of a urinary tract infection; pneumonia; meningitis/ventriculitis; and sepsis (all P ≤ .02). Only 1.5% of patients with CDI required gastrointestinal surgery. Although CDI was not associated with differential mortality, it was associated with increased adjusted odds of a hospital stay of at least 24 days (odds ratio, 3.16; 95% confidence interval, 2.32-4.29; P < .001) and of a nonroutine hospital discharge (odds ratio, 1.64; 95% confidence interval, 1.13-2.39; P = .01). CONCLUSION In this nationwide analysis, both infectious and noninfectious complications, as well as ventriculostomy, mechanical ventilation, and insurance status were independent predictors of CDI. Although CDI was not associated with mortality, it was associated with a longer hospital stay and nonroutine hospital discharge.
The Spanos Attitudes Toward Hypnosis Questionnaire: Psychometric Characteristics and Normative Data

The Attitudes Toward Hypnosis Questionnaire (ATHQ) is a 14-item, self-report measure of positive versus negative attitudes about hypnosis. It is composed of three subscales identified via factor analysis: Positive Beliefs, Fearlessness, and Mental Stability. The purpose of this study was to evaluate the generalizability of the original factor structure of the ATHQ and to provide normative data based on a large sample of 925 introductory psychology students. Internal consistency analysis and factor analysis did not support the scale's original factor structure. Accordingly, it is recommended that the subscales be abandoned and that the 14 items of the ATHQ be utilized as a unidimensional scale. Although attitudes toward hypnosis have been described as an important determinant of hypnotic responding, there has been very little research evaluating this association. If employed as a unidimensional scale, the ATHQ could be a very useful tool in future studies on this topic.
Apoe ε4 as a Predictor of Subjective Quality of Life in a Biracial Older Person Community Sample

>> Objectives: The e4 allele of apolipoprotein E (APOE) has been associated with health-related outcomes that may adversely affect quality of life (QOL) in older adults. In the absence of published information, we sought to determine whether the e4 allele was associated with subjective QOL across 5 parameters in a community sample of older adults. Design: Prospective cohort study. Setting: Community-based sample of older adults in North Carolina (Duke site of the Established Populations for Epidemiologic Studies of the Elderly [Duke EPESE]). Participants: Self-responding genotyped sample members (n = 1,880) of whom 1,254 provided longitudinal data. Measurements: APOE genotype and five newly constructed, reliable, and valid measures of subjective QOL derived from the Duke EPESE questionnaire. The 5 parameters measured were social, economic, mental and physical health, and functional
Oxytocin antagonist inhibitory effect on the rat and baboon uterus may be overcome by prostaglandins

Objective: A potent, long-acting oxytocin antagonist produced in our laboratory (ANTAG-III) can inhibit uterine response to oxytocin in the rat and baboon for hours and even days. The purpose of this study was to evaluate uterine response to prostaglandins subsequent to the administration of ANTAG-III. Study Design: For the rat study one cannula was inserted in the jugular vein, and another cannula to measure uterine activity was inserted in the uterus. In study 1 saline solution or 5 μg of ANTAG-III was administered to five rats each, followed by 100 mU of oxytocin at 0.1, 1, and 2 hours. In study 2 six rats each were infused with saline solution of 5 μg of ANTAG-111, followed 1 hour later by 5 μg of 15-methyl-prostaglandin F 2α and uterine activity monitored. After baseline activity returned to normal 100 mU of oxytocin was infused and the uterine response reassessed. For the baboon study ANTAG-III was administered into the aorta of tethered pregnant baboons ( n = 2). An oxytocin challenge test was performed starting with 10 mU/min and going up to 400 mU/min. After a significant uterine contractile response was established and activity returned to baseline, a 15-methyl-prostaglandin F2a challenge test was performed. Results: During the period in which the response to oxytocin was inhibited the uterine response to 15-methyl-prostaglandin F 2α of the estrous rat and pregnant baboon was maintained. Conclusions: The inhibition of the estrous rat and pregnant baboon uterus to oxytocin caused by ANTAG-III may be prolonged. During this period uterine response to prostaglandins is not altered.
The impact of litigants' baby-facedness and attractiveness on adjudications in small claims courts

The effects of litigants' facial appearance on judicial decisions were investigated in 506 cases heard in small claims courts. Replicating previous laboratory studies, both baby-facedness and attractiveness exerted a significant impact on adjudications. As plaintiffs increased in attractiveness, defendants were more likely to lose the case. Also, as defendants increased in baby-facedness, they were more likely to win cases involving intentional actions and less likely to win cases involving negligent actions, although the latter simple effect was not significant. Finally, as defendants increased in facial maturity, they were required to pay larger monetary awards to baby-faced plaintiffs, albeit not to average or mature-faced plaintiffs. This pattern of decisions was interpreted as reflecting assumptions about the psychological attributes of baby-faced versus mature-faced individuals. The effects of the extralegal variables of litigant attractiveness and baby-facedness were sufficiently large to have practical as well as statistical significance, and they were independent of each other and the age of the litigants as well as of legal variables predicting adjudications.
Antilipolytic effects of growth hormone.

Abstract When added in vitro to adipose tissue from hypophysectomized rats, growth hormone (0.1–1.0 μg./ml.) antagonized the lipolytic action of epinephrine. Glycerol production in response to 0.05 μg./ml. of epinephrine was reduced by 50–70 per cent. Glucose was not required. This antilipolytic response is transient, lasts less than 3 hours and once passed cannot be reinitiated by further addition of growth hormone. Incubation with actinomycin d (5 μg./ml.) plus growth hormone caused the antilipolytic response to growth hormone to persist for at least 4 hours. Growth hormone did not antagonize the lipolytic response to N6,2′-0-dibutyryl cyclic AMP (2 × 10−3 M), suggesting that growth hormone may interfere with some aspect of the formation of cyclic AMP rather than the ability of the tissues to respond to the cyclic nucleotide. The characteristics of the antilipolytic effect of growth hormone parallel those reported previously for the stimulatory effects of growth hormone on glucose transport and metabolism. It is concluded that the antilipolytic effect of growth hormone represents another facet of the acute insulin-like action of the hormone.
Autoimmune disease: the consequence of deficient T-cell function?

: The age-related decrease in T-lymphocyte function is discussed in relation to the onset of autoimmune disease. It is postulated that the decrease in T-cell “immune surveillance” permits: a) the ingress of viruses whose enzymes modify host glycoproteins and render them immunogenic, and b) the replication of viruses incorporated into the genome of cells during infections in early life. The existence of immunodeficiencies too subtle to be detected by our present laboratory methods is postulated and discussed in relation to diseases observed in geriatric patients. It would seem that the prevention of some geriatric diseases should begin in the pediatrician's office.
UV Resonance Raman Spectroscopy Monitors Polyglutamine Backbone and Side Chain Hydrogen Bonding and Fibrillization

We utilize 198 and 204 nm excited UV resonance Raman spectroscopy (UVRR) and circular dichroism spectroscopy (CD) to monitor the backbone conformation and the Gln side chain hydrogen bonding (HB) of a short, mainly polyGln peptide with a D(2)Q(10)K(2) sequence (Q10). We measured the UVRR spectra of valeramide to determine the dependence of the primary amide vibrations on amide HB. We observe that a nondisaggregated Q10 (NDQ10) solution (prepared by directly dissolving the original synthesized peptide in pure water) exists in a β-sheet conformation, where the Gln side chains form hydrogen bonds to either the backbone or other Gln side chains. At 60 °C, these solutions readily form amyloid fibrils. We used the polyGln disaggregation protocol of Wetzel et al. [Wetzel, R., et al. (2006) Methods Enzymol.413, 34-74] to dissolve the Q10 β-sheet aggregates. We observe that the disaggregated Q10 (DQ10) solutions adopt PPII-like and 2.5(1)-helix conformations where the Gln side chains form hydrogen bonds with water. In contrast, these samples do not form fibrils. The NDQ10 β-sheet solution structure is essentially identical to that found in the NDQ10 solid formed upon evaporation of the solution. The DQ10 PPII and 2.5(1)-helix solution structure is essentially identical to that in the DQ10 solid. Although the NDQ10 solution readily forms fibrils when heated, the DQ10 solution does not form fibrils unless seeded with the NDQ10 solution. This result demonstrates very high activation barriers between these solution conformations. The NDQ10 fibril secondary structure is essentially identical to that of the NDQ10 solution, except that the NDQ10 fibril backbone conformational distribution is narrower than in the dissolved species. The NDQ10 fibril Gln side chain geometry is more constrained than when NDQ10 is in solution. The NDQ10 fibril structure is identical to that of the DQ10 fibril seeded by the NDQ10 solution.
Meteorologic and isotopic characteristics of precipitation events with implications for groundwater recharge, Southern High Plains

Abstract Recharge estimates for the Ogallala aquifer in the Southern High Plains vary by two orders of magnitude (0.01 to 1.6 inches/yr or 0.25 to 41 mm/yr) because of differing interpretations of the contribution of the area's numerous playa lakes to the recharge of the aquifer. Higher rates are suggested by studies in which the playa lakes are assumed to be a major source of recharge. To reevaluate the recharge potential of precipitation, we measured meteorologic and isotopic properties of single precipitation events at five stations for one year. Values of precipitation for δ18O (−22.7‰ to −4.7‰) and δD (−162% to +35%) plot along the world meteoric water line. Mean annual weighted values of δ18O and δD are −7.5‰ and −48‰, respectively. Air masses from the Gulf of Mexico account for most summer precipitation, which is more isotopically enriched than winter precipitation, mainly derived from air masses from the eastern Pacific Ocean. Precipitation is more depleted in δ18O and δD toward the northwestern part of the Southern High Plains, becoming isotopically enriched toward the southeast. These isotopic differences reflect temperature, continental, and altitude effects. Isotopic composition of Ogalla ground water has a spatial distribution similar to that of precipitation. Ground water, however, is consistently more enriched than precipitation sampled in the same area, suggesting evaporation during recharge. Evaporation can occur either in playa lakes prior to infiltration or in the vadose zone. Tritium in precipitation ranges from 1.1 to 14.7 TU, and in groundwater it ranges from zero where the vadose zone is thick, to 73 TU, where the zone is thin. The calculated recharge rate (using tritium as a tracer) ranges from 0.5 to 3.24 inches/yr, or 12.7 to 82 mm/yr. Such high recharge rates were only measured below playa lakes. Because of the fast recharge rates and the slightly enriched values of δ18O and δD in ground water, the Ogalla a aquifer is most likely recharged by focused percolation of partly evaporated playa lake water, rather than by slow regional diffusive percolation of precipitation.
The Lysine Requirement of White Chinese Goslings

Abstract AIKENS et al. (1954) suggested that a protein level of 21% was adequate for Pilgrim goslings. Snyder (1959) reported that a ration containing approximately 20% protein was optimum for Pilgrim goslings. Yacowitz et al. (1954) and Waibel (1958) observed that goslings grew most rapidly on protein levels higher than 20% of the ration. Roberson and Francis (1963) reported that White Chinese goslings grew more rapidly on 24% protein level than on lower levels, but the advantage was lost when the geese were raised beyond the stage of rapid growth. Although the protein requirement of goslings has been estimated, the requirement for individual amino acids has not been estimated. PROCEDURE White Chinese goslings of both sexes or sexed were received from the hatchery and wingbanded. The goslings in three of the experiments were placed on a practical starting ration (Roberson and Francis, 1963) for the first seven days, and those in …
Port-site recurrence of pancreatic adenocarcinoma following laparoscopic pancreaticoduodenectomy.

Introduction Minimally invasive surgical approaches have only recently been applied to pancreatic adenocarcinoma.
Model experiments on the poisoning of Pt catalysts by sulfur

Abstract Surface reactions have been studied in high vacuum on the (100) surface of platinum that was clean or covered with various amounts of sulfur. This system was chosen for its simplicity in order to observe the mechanisms by which sulfur poisons catalytic activity. Three different poisoning mechanisms were identified: (i) When the surface is covered with one S atom per two surface Pt atoms, it is chemically inert, (ii) At lower coverages, the strong chemical bond to sulfur modifies the chemical properties of the platinum surface and weakens its interaction with adsorbates. (iii) When the sulfur coverage is one S per four Pt, a regular sulfur overlayer is established; molecules can adsorb on the surface but are prevented by the sulfur structure from participating in Langmuir-Hinshelwood reactions. The reactions on which these observations were made are the dissociation of H2S, the adsorption and desorption of CO, the reduction of NO by CO, the dissociation and desorption of NO, and the adsorption and dehydrogenation of benzene and acetylene.
Dorsolateral Prefrontal Cortex Magnetic Resonance Imaging Measurements and Cognitive Performance in Autism

This study examined the relationships between volumetric measurements of frontal lobe structures and performance on executive function tasks in individuals with autism. Magnetic resonance imaging (MRI) scans were obtained from 38 individuals with autism and 40 matched controls between the ages of 8 and 45 years. Executive function was assessed using neuropsychological measures including the Wisconsin Card Sorting Test and Tower of Hanoi. Differences in performance on the neuropsychological tests were found between the 2 groups. However, no differences in dorsolateral prefrontal cortex volumes were observed between groups. No correlations between volumetric measurements and performance on the neuropsychological tests were found. Findings from this study suggest that executive function deficits observed in autism are related to functional but not anatomical abnormalities of the frontal lobe. The absence of correlations suggests that executive dysfunction is not the result of focal brain alterations but, rather, is the result of a distributed neural network dysfunction.
Chair-boat transitions in single polysaccharide molecules observed with force-ramp AFM

Under a stretching force, the sugar ring of polysaccharide molecules switches from the chair to the boat-like or inverted chair conformation. This conformational change can be observed by stretching single polysaccharide molecules with an atomic force microscope. In those early experiments, the molecules were stretched at a constant rate while the resulting force changed over wide ranges. However, because the rings undergo force-dependent transitions, an experimental arrangement where the force is the free variable introduces an undesirable level of complexity in the results. Here we demonstrate the use of force-ramp atomic force microscopy to capture the conformational changes in single polysaccharide molecules. Force-ramp atomic force microscopy readily captures the ring transitions under conditions where the entropic elasticity of the molecule is separated from its conformational transitions, enabling a quantitative analysis of the data with a simple two-state model. This analysis directly provides the physico-chemical characteristics of the ring transitions such as the width of the energy barrier, the relative energy of the conformers, and their enthalpic elasticity. Our experiments enhance the ability of single-molecule force spectroscopy to make high-resolution measurements of the conformations of single polysaccharide molecules under a stretching force, making an important addition to polysaccharide spectroscopy.
40Ar/39Ar dating of Apollo 12 impact spherules

[1] We have used the 40Ar/39Ar isochron technique to determine ages of 81 lunar spherules from Apollo 12 soil sample 12023. Most spherules are created in meteoroid impacts, and their ages correspond to the timing of the impacts that formed them. Of the 81 impacts we have dated, most occurred in the last 500 million years. The abundance of spherules from the most recent ∼10% of the history of the Moon is consistent with an increase in the meteoroid bombardment of the inner Solar System, but does not require this explanation. The soil sample from which we extracted our spherules was from the ejecta of a recent impact; our spherule age measurements support models of lunar soil mechanics and impact cratering in which ejecta are stratified and inverted relative to the stratigraphy that was present before the impact.
A Hill of Beans

Alexander L. Densmore et al . (Reports,[17 Jan., p. 369][1]) address an important geomorphologic question: What is the relative importance of large, infrequent, slope-clearing events (SCEs) in determining hillslope longitudinal profiles? To model the frequency and magnitude distribution of SCEs,
Influences of question wording on levels of support for genetically modified organisms

This paper examines the influences of question wording on consumers’ levels of support for genetically modified organisms (GMOs) in food products. Pairs of questions, offering varied amounts of information on the benefits and risks of GMOs, are posed to consumers in a specific geographic area (Vermont, USA) to ascertain the factors that impact on levels of support for this technology. A multivariate analysis is conducted to examine how knowledge, attitudes, and behavioural intentions affect changes in levels of support. The findings suggest that consumers’ levels of support do vary based on question wording. It is further found that knowledge and behavioural intentions play a consistently significant role in influencing change in support for GMOs. Implications for both consumer advocacy groups and industry groups are discussed.
Conventional Strain Energy in Dimethyl-Substituted Cyclobutane and the gem-Dimethyl Effect

The gem-dimethyl effect is the acceleration of cyclization by substituents in the chain and is often used in organic synthesis as a ring-closing effect. Calculations on cyclobutane, methylcyclobutane, and 1,1-dimethylcyclobutane are performed. 1,1-Dimethylcyclobutane is a four-membered carbon ring with gem-dimethyl substituents. Optimum equilibrium geometries, harmonic vibrational frequencies, and corresponding electronic energies are computed for all pertinent molecular systems using SCF theory, density functional theory (DFT), and second-order perturbation theory (MP2) with two triple-ζ quality basis sets, 6-311G(d,p) and 6-311G+(2df,2pd). Additional single-point calculations are performed using the optimized MP2/6-311G+(2df,2pd) geometries and coupled-cluster theory including single and double excitations and noniterative, linear triple excitations (CCSD(T)). Calculations indicate that 1,1-dimethylcyclobutane is more than 8 kcal mol-1 less strained than cyclobutane, that is, there is at least some ther...
Synthesis and manipulation of multifunctional, fluorescent-magnetic nanoparticles for single molecule tracking

Heterogeneous nanostructures that possess multiple properties as a result of their differing constituent materials have attracted significant interest in the last few years. In particular, fluorescent-magnetic nanostructures have potential applications in imaging, separations, and single molecule tracking as a result of their fluorescent and magnetic properties. Here we report the synthesis of fluorescent-magnetic nanocomposites composed of fluorescent semiconductor quantum dots or graphitic carbon nanoparticles and magnetic iron oxide nanoparticles. We have developed synthetic strategies using either micellular or polymer encapsulation, yielding composites from ~10 - 100s of nms. Composites maintain the fluorescent and magnetic properties of their constituent materials. These composites can be used for in vitro and in vivo imaging using fluorescent or magnetic (e.g., MRI) modalities. Additionally, we describe the manipulation of these composites using magnetic instrumentation. In particular, we have designed a magnetic needle that can be used to manipulate nanocomposites. Particles as small as 30 nm can be manipulated while simultaneous observed through their fluorescent property. Single particle status can be confirmed through quantum dot blinking, demonstrating the potential of these composites for single molecule tracking.
Correlation of loss of hyaluronic acid and chondroitin sulphate in skin of mice with carcass nitrogen loss during starvation.

THE constituents of the ground substance of connective tissue respond dynamically to loss of systemic nitrogen. Marked changes have been reported to occur in the composition of the skin of mice during starvation1. This is accompanied by a significant reduction in hyaluronic acid (HA) and chondroitin sulphate (CS). Earlier studies2 with rats suggested that hexosamine-containing materials in the skin decreased rapidly with small losses of carcass nitrogen (N), but when large losses occurred the additional decrement in the former was small. No attempt, however, was made to quantitate this relationship. In this work, decrement in HA and CS during starvation was correlated with loss of N in mice.
Do Job Applicant Credit Histories Predict Performance Appraisal Ratings or Termination Decisions

In this study the authors investigated the criterion validity of job applicant credit report history in predicting subsequent performance appraisal ratings and termination decisions for 178 employees at a large financial services corporation. Predictors extracted from applicant credit reports, such as number of times late with payments, had no relationship with either performance appraisal ratings or termination decisions. The authors therefore recommend caution in using credit report data for making selection decisions.
The effect of processing instruction and dictogloss tasks on acquisition of the English passive voice

This study was intended to compare processing instruction (VanPatten, 1993, 1996, 2000), an input-based focus on form technique, to dictogloss tasks, an output-oriented focus-on-form type of instruction to assess their effects in helping beginning-EFL (English as a Foreign Language) learners acquire the simple English passive voice. Two intact classes of Grade 7 beginning EFL learners (n = 110) in China were randomly assigned to each type of instruction: Group A (n = 55) to processing instruction (PI), and Group B (n = 55) to dictogloss tasks (DG). A pretest and posttest (immediate and delayed) design was used, where participants' ability to comprehend and produce the target feature was assessed. Results showed that the PI group performed significantly better than the DG group in comprehension, and as well as the DG group in production on the immediate posttest. One month later, the two groups' performances were similar in terms of both comprehension and production on the delayed posttest. Both groups imp...