cssi/SciSciGPT-SciSciNet huggingface dataset:
Phase Transitions in Mesoscopic Brain Dynamics – Implications for Cognition and Consciousness

Mesoscopic brain dynamics, typically studied with electro- and magnetoencephalography (EEG and MEG) display a rich complexity of oscillatory and chaotic-like states, including many different frequencies, amplitudes and phases. Presumably, these different dynamical states correspond to different mental states and functions, and to study transitions between such states could give us valuable insight in brain-mind relations that should also be of clinical interest. We use computational methods to address these problems, with an objective to find relations between structure, dynamics and function. In particular, we have developed models of paleo- and neocortical structures, in order to study their mesoscopic neurodynamics, as a link between the microscopic neuronal and macroscopic mental events and processes. In this presentation, I will describe different types of models, where the emphasis is on network connectivity and structure, but also including molecular and cellular properties at varying detail, depending on the particular problem and experimental data available. We use these models to study how phase transitions can be induced in the mesoscopic neurodynamics of cortical networks by internal (natural) and external (artificial) factors. We relate and discuss the models and simulation results to macroscopic phenomena, such as arousal, attention, anaesthesia, learning, and mental disorders.
In Defense of a Theocentric Theodicy

The problem of evil is an intellectual challenge for philosophers and theologians and an existential threat to many religious believers. It is sustained by the commitments of what is now called perfect being theology, which is above all a philosophical theology centered on the conception of God as creator of the cosmos and as omniscient, omnipotent, and perfectly good. With Kontny and Muller-Salo, I do not try to evade the problem by treating evil as illusory or subjective. I agree that there are genuine evils of horrendous proportions. The question why there is evil at all is urgent enough in a world under an omnicompetent God—‘omnicompetence’ being shorthand for the conjunction of omniscience, omnipotence, and perfect goodness. But the question why there is so much and such excruciating evil seems on the face of it unanswerable. Kontny and Muller-Salo have contributed much to our understanding of the problem, and here, rather than elaborate on all of their points, I shall simply reply to those that indicate a need to reinforce or extend major theses I have defended.
Cardiogenic shock during heart failure hospitalizations: Age-, sex-, and race-stratified trends in incidence and outcomes.

Background The objectives were to study the overall and age-, sex-, and race-stratified incidence of cardiogenic shock (CS) during heart failure hospitalizations (HFHs) not complicated by acute coronary syndromes (ACS), utilization of short-term mechanical circulatory support (MCS) and in-hospital mortality with non–ACS-related CS, and respective temporal trends. Data are lacking regarding the epidemiology of non–ACS-related CS during HFHs. Methods Retrospective observational analysis of the National Inpatient Sample 2005-2014 to identify all HFHs in adult patients without concomitant ACS. Results Of 8,333,752 HFHs, incidence rate of non–ACS-related CS was 8.7 per thousand HFHs (N = 72,668), a 4-fold increase from 4.1 to 15.6 per thousand HFHs between 2005 and 2014 (Ptrend Conclusion During HFHs in the United States, non–ACS-related CS occurred infrequently but was associated with substantial mortality. Non–ACS-related CS incidence and certain MCS utilization rates increased, and in-hospital mortality rate decreased between 2005 and 2014. These trends were generally homogenous across the age, sex, and race groups. The observed trends in incidence and mortality may be a reflection of increased identification of CS during HFHs, although further study is needed to assess whether temporal changes in care may have influenced outcomes.
Genetic polymorphisms in the Paraoxonase 1 (PON1) gene and the risk of ovarian epithelial carcinoma

1909 Background: An elevated oxidative stress has been found to play an important role in the pathogenesis of cancer. The antioxidant paraoxonase (PON1) is an endogenous free radical scavenger that can inhibit tumor cell proliferation. PON1 gene has 2 common coding polymorphisms (SNPs): rs662 in exon 6 (Gln192Arg) and rs854560 in exon 3 (Leu55Met). Both SNPs have been shown to influence PON1 activity. We investigated association of these SNPs with the risk of epithelial ovarian carcinoma. We also explored whether smoking, which is known to decrease PON1 activity, modified this association. Methods. Interviews and DNA samples were collected in a population-based case-control study of 364 women with epithelial ovarian carcinoma and 602 controls frequency-matched to cases on age and ethnicity. Genotyping was performed with the 5’ nuclease discrimination assay using TaqMan (Applied Biosystems). Samples from cases and controls were intermixed on each plate, and 144 (7.4%) randomly selected blinded were included to evaluate accuracy and reproducibility. The concordance rates among duplicates were 100% for both SNPs. Call rates were 99% and 100% for rs662 and rs854560, respectively. Unconditional logistic regression was used to test the associations between SNPs and ovarian cancer risk, while adjusting for potential confounders. Results. The distributions of the alleles among control subjects were consistent with Hardy-Weinberg equilibrium. We found that the rs854560 T allele was associated with a lower risk of ovarian cancer among Caucasian, Japanese, Hawaiian, Filipino women, and all women combined (OR=0.52; 95% CI:0.36-0.76 ; p global=0.0006; p for gene-dose effect =0.003) when compared to homozygous carriers of A allele. The interaction between this SNP and smoking exposure on risk was not statistically significant. However, among smokers, risk asociated with AA genotype was considerably higher (OR=2.42; 95%CI:1.39-4.25) than among non-smokers (OR=1.68; 95%CI:1.02-2.77). There was no evidence for effect modification of this SNP association with risk by in utero or second-hand tobacco exposure. Association of rs662 T allele with reduced risk was consistent among ethnic groups but was not statistically significant. Conclusion. In our study, women carriers of rs854560 T allele were at significant 48% decrease in ovarian cancer risk when compared to AA genotype carriers. Increased risk associated with AA genotype was considerably higher in past or current smokers when compared to women who never smoked. The biological plausibility of our findings is supported by the evidence for higher paraoxonase activity levels in T allele carriers and weakening of the antioxidant defense of PON1 by smoking.
Rapid adaptation to fully intelligible nonnative-accented speech reduces listening effort.

In noisy settings or when listening to an unfamiliar talker or accent, it can be difficult to understand spoken language. This difficulty typically results in reductions in speech intelligibility, ...
A Note on Stein's Method for Heavy-Traffic Analysis.

In this note, we apply Stein's method to analyze the steady-state distribution of queueing systems in the traditional heavy-traffic regime. Compared to previous methods (e.g., drift method and transform method), Stein's method allows us to establish stronger results with simple and template proofs. In particular, we consider discrete-time systems in this note. We first introduce the key ideas of Stein's method for heavy-traffic analysis through a single-server system. Then, we apply the developed template to analyze both load balancing problems and scheduling problems. All these three examples demonstrate the power and flexibility of Stein's method in heavy-traffic analysis. In particular, we can see that one appealing property of Stein's method is that it combines the advantages of both the drift method and the transform method.
Drug-specific risk of severe QT prolongation following acute drug overdose

Background: Severe QT prolongation (SQTP) has been identified as a strong predictor of adverse cardiovascular events in acute drug overdose, but drug-specific causes of SQTP in the setting of acute drug overdose remain unclear. We aimed to perform the most definitive study to date describing drug-specific risk of SQTP following acute drug overdose.Methods: This was a prospective multicenter cohort study at >50 hospital sites across the US using the ToxIC Registry between 2015 and 2018. Inclusion criteria were adults (≥18 years) receiving medical toxicology consultation for acute drug overdose. The primary outcome was SQTP, which was defined using the computer automated Bazett QT correction (QTc) on the ECG with the previously validated cut point of 500 milliseconds. Mean difference in QTc was also calculated for specific drugs. Drugs associated with SQTP were analyzed using multivariable logistic regression to control for known confounders of QT risk (age, sex, race, cardiac disease).Results: From 25,303 patients screened, 6473 met inclusion criteria with SQTP occurring in 825 (13%). Drugs associated with increased adjusted odds of SQTP included Class III antidysrhythmics (sotalol), sodium channel blockers (amitriptyline, diphenhydramine, doxepin, imipramine, nortriptyline), antidepressants (bupropion, citalopram, escitalopram, trazodone), antipsychotics (haloperidol, quetiapine), and the antiemetic serotonin antagonist ondansetron.Conclusions: This large US cohort describes drug-specific risk of SQTP following acute drug overdose. Healthcare providers caring for acute drug overdoses from any of these implicated drugs should pay close attention to cardiac monitoring for occurrence of SQTP.
A Thermal/RF Hybrid Energy Harvesting System With Rectifying-Combination and Improved Fractional-OCV MPPT Method

This paper presents a thermal/RF hybrid energy harvester. The energy harvesting system can scavenge energy from a thermoelectric generator (TEG) and a radio-frequency (RF) energy source simultaneously, and deliver the combined power to a single load. Two techniques are employed in the system to increase the end-to-end efficiency; the rectifying-combination technique is proposed to eliminate the power loss associated with a dedicated AC-DC converter before the combiner and an improved fractional open-circuit voltage (FOCV) maximum power tracking (MPPT) is considered for a high average efficiency. A dynamic power path control extracts the maximum RF power from a cross-coupled differential rectifier, and also behaves as an AC/DC energy combiner. The thermal/RF harvester system achieves a measured peak end-to-end power conversion efficiency (PCE) of 63.4%. The shorter sampling time of 26ms every 16s for the proposed FOCV MPPT method reduces the long charging tail required to refresh the sampling capacitor, resulting in a an improved average efficiency of 82.2% for the thermal harvester. Fabricated in 0.18 $\mu \text{m}$ CMOS technology, the prototype operates at a thermal input voltage ranging from 40 mV to 400 mV and an RF power from −18 dBm to −3 dBm and delivers an output voltage of 1.8 V. The total area of the fabricated circuit prototype is 1.22 mm2.
Multiple weak interactions between BvgA~P and ptx promoter DNA strongly activate transcription of pertussis toxin genes in Bordetella pertussis.

Pertussis toxin is the preeminent virulence factor and major protective antigen produced by Bordetella pertussis, the human respiratory pathogen and etiologic agent of whooping cough. Genes for its synthesis and export are encoded by the 12 kb ptx-ptl operon, which is under the control of the pertussis promoter, Pptx. Expression of this operon, like that of all other known protein virulence factors, is regulated by the BvgAS two-component global regulatory system. Although Pptx has been studied for years, characterization of its promoter architecture vis-a-vis BvgA-binding has lagged behind that of other promoters, mainly due to its lower affinity for BvgA~P. Here we take advantage of a mutant BvgA protein (Δ127-129), which enhances ptx transcription in B. pertussis and also demonstrates enhanced binding affinity to Pptx. By using this mutant protein labeled with FeBABE, binding of six head-to-head dimers of BvgA~P was observed, with a spacing of 22 bp, revealing a binding geometry similar to that of other BvgA-activated promoters carrying at least one strong binding site. All of these six BvgA-binding sites lack sequence features associated with strong binding. A genetic analysis indicated the degree to which each contributes to Pptx activity. Thus the weak/medium binding affinity of Pptx revealed in this study explains its lower responsiveness to phosphorylated BvgA, relative to other promoters containing a high affinity binding site, such as that of the fha operon.
Performance Boost Scheme with Activated Dummy Fin in 12-nm FinFET Technology for High-Performance Logic Application

This paper demonstrates performance enhancement with activated dummy fins based on a 12-nm FinFET technology definition for high-performance logic module design. The proposed scheme uses a double-height cell structure with two additional active fins enabled compared to traditional single-height cell stacking. The increase in total active fins in the proposed scheme results in higher effective transistor density and better cell performance. Through Design and Technology Co-Optimization, the parasitic capacitance of these proposed cells can be further decreased, with a NAND $2\times 4$ cell yielding about 20% lower parasitic capacitance per fin compared to a traditional single-height cell. The proposed scheme shows the highest efficacy for gate-dominant and complex module designs like CPUs.
Assessing the sensitivity of information distortion to four potential influences in studies of risky choice.

The emergence of a leading alternative during the course of a decision is known to bias the evaluation of new information in a manner that favors that alternative. We report 3 studies that address the sensitivity of predecisional information distortion and its effects in hypothetical risky decisions with regard to 4 potential influences: choice domain, repeated choice, memory requirements, and intermediate progress questions. In Experiment 1 (N = 515), the magnitude of information distortion was similar in 5 choice domains (varied between participants) involving monetary gambles, song downloads, frequent-flyer miles, political decisions, or medical decisions. Information distortion mediated the relationship between our manipulation of initial preferences and participants' final choices, with the magnitude of the indirect effect being roughly similar across domains. These results replicate and extend previous findings. Additionally, distortion decreased significantly over 4 similar decision problems (within participants), but remained significant in the fourth problem. In Experiment 2 (N = 214), information distortion increased significantly when previously viewed information remained available, apparently because reiterating that information strengthened emerging preferences. In Experiment 3 (N = 223), the removal of intermediate progress questions that measure information distortion and emerging preferences did not significantly affect final choices, again replicating previous results. We conclude that predecisional information distortion is a relatively stable and robust phenomenon that deserves a prominent role in descriptive theories of choice.
Rhythmic Physical Activity Intervention: Exploring Feasibility and Effectiveness in Improving Motor and Executive Function Skills in Children.

Introduction Increasing literature has emerged investigating the importance of considering the qualitative characteristics of physical activity (PA) interventions and sports as well as considering the role of motor competence in the exercise-cognition interplay. The purpose of this pilot study was to examine the feasibility and effectiveness of a rhythmic PA intervention compared to a standard physical education program, on motor and hot and cool executive function (EF) skills. Methods Children ages 6-11 were enrolled in one of the two programs: a rhythmic program (n = 22) and a physical education program (n = 17), both meeting for 30 min, twice per week, for 7 weeks. The rhythmic program emphasized moving to the beat of music and moving in various rhythmic patterns with whole body movements, clapping, and drumsticks. The children also created their own rhythmic patterns and socially engaged with other children by working in pairs and sharing their routines with the group. The physical education group engaged in ball skills, locomotor patterns, team sports, and moving through stations in small groups, with no emphasis on rhythm. Pretest and posttest measurements included measurement of balance (Movement ABC-2), cool and hot EF (Flanker, SWAN), and social factors, whereas throughout the implementation period data on affective valence, enjoyment, cognitive engagement, perceived exertion, and PA levels were collected at every lesson in both groups. Results The rhythmic program used in this study was feasible, scalable, affordable, and able to be implemented with minimal preparatory time. Children in both groups (rhythmic and physical education) engaged in a similar level of PA and had similar positive experiences from the programs. Both groups improved in balance and cool EF, and there were significant correlations in the change scores between balance and cool EF, as well as between cool EF with hot EF and socio-emotional factors. Discussion This study contributes to the literature by exploring the potential value of rhythmic programs as a vehicle in helping children develop motor and EF skills while deriving joy and positive social interactions from the program.
Schauer, Frederick. Social Foundations of the Law of Defamation: A Comparative Analysis, 1 J. Media L. & Prac. 3 (1980)

Communication law as a whole and media law in particular tend to be country-specific rather than international or comparative. But the global twenty-first century makes us in communication law more...
XSTREME: Comprehensive motif analysis of biological sequence datasets

Abstract XSTREME is a web-based tool for performing comprehensive motif discovery and analysis in DNA, RNA or protein sequences, as well as in sequences in user-defined alphabets. It is designed for both very large and very small datasets. XSTREME is similar to the MEME-ChIP tool, but expands upon its capabilities in several ways. Like MEME-ChIP, XSTREME performs two types of de novo motif discovery, and also performs motif enrichment analysis of the input sequences using databases of known motifs. Unlike MEME-ChIP, which ranks motifs based on their enrichment in the centers of the input sequences, XSTREME uses enrichment anywhere in the sequences for this purpose. Consequently, XSTREME is more appropriate for motif-based analysis of sequences regardless of how the motifs are distributed within the sequences. XSTREME uses the MEME and STREME algorithms for motif discovery, and the recently developed SEA algorithm for motif enrichment analysis. The interactive HTML output produced by XSTREME includes highly accurate motif significance estimates, plots of the positional distribution of each motif, and histograms of the number of motif matches in each sequences. XSTREME is easy to use via its web server at https://meme-suite.org, and is fully integrated with the widely-used MEME Suite of sequence analysis tools, which can be freely downloaded at the same web site for non-commercial use.
Rhizobacteria Impact Colonization of Listeria monocytogenes on Arabidopsis thaliana Roots.

In spite of its relevance as a food-borne pathogen, we have limited knowledge about L. monocytogenes in the environment. L. monocytogenes' outbreaks have been linked to fruits and vegetables; thus, a better understanding of the factors influencing its ability to colonize plants is important. We tested how environmental factors and other soil- and plant-associated bacteria influenced L. monocytogenes' ability to colonize plant roots using Arabidopsis thaliana seedlings in a hydroponic growth system. We determined that the successful root colonization of L. monocytogenes 10403S was modestly but significantly enhanced by the bacterium being pre-grown at higher temperatures, and this effect was independent of the biofilm- and virulence-regulator PrfA. We tested 14 rhizosphere-derived bacteria for their impact on L. monocytogenes 10403S, identifying one that enhanced and ten that inhibited the association of 10403S with plant roots. We also characterized the outcomes of these interactions under both co-inoculation and invasion conditions. We characterized the physical requirements of five of these rhizobacteria to impact L. monocytogenes 10403S' association with roots, visualizing one of these interactions by microscopy. Furthermore, we determined that two rhizobacteria (one an inhibitor, the other an enhancer of 10403S root association) were able to similarly impact ten different L. monocytogenes strains, indicating that the effects of these rhizobacteria on L. monocytogenes are not strain specific. Taken together, our results advance our understanding of the parameters that effect L. monocytogenes plant root colonization, knowledge that may enable us to deter its association with, and thus downstream contamination of, food crops. IMPORTANCE Listeria monocytogenes is ubiquitous in the environment, being found in or on soil, water, plants, and wildlife. However, little is known about the requirements for L. monocytogenes' existence in these settings. Recent L. monocytogenes outbreaks have been associated with contaminated produce; thus, we used a plant-colonization model to investigate factors that alter L. monocytogenes' ability to colonize plant roots. We show that L. monocytogenes' colonization of roots was enhanced when grown at higher temperatures prior to inoculation, but did not require a known regulator of virulence and biofilm formation. Additionally, we identified several rhizobacteria that altered the ability of eleven different strains of L. monocytogenes to colonize plant roots. Understanding the factors that impact L. monocytogenes' physiology and growth will be crucial for finding mechanisms (whether chemical or microbial) that enable its removal from plant surfaces to reduce L. monocytogenes' contamination of produce and eliminate food-borne illness.
Range expansion and complete mitochondrial genome of the highfin blenny (Lupinoblennius nicholsi).

The highfin blenny, Lupinoblennius nicholsi, is a marine fish species reported in reef and rocky inshore habitats with a disjunct distribution in the southern Gulf of Mexico. Overall, there are very few studies on this species and there is a scarcity of molecular resources for genetic comparisons. We set out to report the first mitochondrial genome for L. nicholsi and report a range expansion for the species. An individual of L. nicholsi was collected from the coast of Dauphin Island, Alabama. The mitochondrial genome was sequenced, assembled, and annotated. The fragment corresponding to cytochrome oxidase I (COI) was used to compare this sample to other cryptobenthic species of the Atlantic. Finding a mature individual in the coast of Alabama implies this species has a continuous distribution throughout the northern Gulf of Mexico. The mitochondrial genome of L. nicholsi is 16,416 bp in length and comprised of 13 protein coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and a non-coding D-loop. Comparisons using COI support the species is L. nicholsi and separate it from other cryptobenthic fishes found in the area. This study represents the first mitochondrial genome for this L. nicholsi, serving as a reference for future comparative studies with marine fishes. By reporting the range expansion of this species, this study provides insights on the fish diversity of the Gulf of Mexico.
Implementing Lung Ultrasound in the Outpatient Management of COVID-19 Pneumonia: A Pilot Study to Update Local Guidelines

Background: Lung ultrasound has a good performance with a high sensitivity and specificity for the diagnosis of pneumonia compared to chest X-ray and it has been extensively used to assess patients during the COVID-19 pandemic. This study aims to evaluate the potential advantages of the regular use of lung ultrasound for the assessment of the severity and prognosis of COVID-19 pneumonia and to propose an adapted protocol with its inclusion in current local validated and published guidelines. Methods: This is a single-center prospective study conducted during the first (April-May 2020) and second (October 2020-January 2021) waves of the SARS-CoV2 pandemic in Switzerland. All adult patients presenting to dedicated test centers with a suspicion of mild-to moderate COVID-19 pneumonia and not requiring hospitalization at the time of diagnosis were included. Patients with confirmed COVID-19 pneumonia were referred to an ambulatory follow-up unit at our institution for reassessment, with the inclusion of the use of lung ultrasound in a random selection. Descriptive statistics were calculated for demographics using percentages, means, and standard deviations, according to the distribution of variables. Results: 88 ambulatory patients with a confirmed COVID-19 pneumonia were included (male = 57 [59%]; mean age, 52.1 ± 13.5 years). Among these, 19 (21%) were hospitalized and none died. Twenty-five lung assessments by ultrasound were performed during the follow-up consultation. All were consistent with the clinical examination and confirmed the clinician’s opinion. Conclusion: Use of a standardized pleuro-pulmonary ultrasound protocol for ambulatory patients with COVID-19 could help to reduce the use of chest X-rays and improve overall management at the time of referral and eventual follow-up. However, a specific study including lung ultrasound in a systematic approach should be performed to evaluate the outcome of patients according to findings.
Attitude-translation coupling in drag-free satellites

Attitude-translation motion coupling effect on stability of gravity-stabilized drag-free satellites
Trauma Related Critical Incident Debriefing for Adolescents

Events like the tragedy at Columbine High School and the terrorists attacks on New York City in 2001 have highlighted the need for mental health practitioners to become familiar with interventions that are designed to assist young people who have survived extremely stressful events. Mental health professionals often see people who have experienced car accidents, severe abuse, rape, or other victimization, as well as survivors of natural and man-made disasters during the first critical stages of the recovery period. This article describes the process of critical incident de-briefing and provides a step-by-step primer for its application. The process is short-term (four sessions or less) and provides an intervention designed to reduce the frequency and severity of post-traumatic stress symptoms. Adolescents are particularly at risk because of issues surrounding identity formation, self- esteem, and developmental differences in coping mechanisms. Therefore, those who work with an adolescent cohort should be familiar with debriefing methods and how to apply them to the teenager.
AML-1/ETO fusion protein is a dominant negative inhibitor of transcriptional repression by the promyelocytic leukemia zinc finger protein.

The AML-1/ETO fusion protein, created by the (8;21) translocation in M2-type acute myelogenous leukemia (AML), is a dominant repressive form of AML-1. This effect is due to the ability of the ETO portion of the protein to recruit co-repressors to promoters of AML-1 target genes. The t(11;17)(q21;q23)-associated acute promyelocytic leukemia creates the promyelocytic leukemia zinc finger PLZFt/RARα fusion protein and, in a similar manner, inhibits RARα target gene expression and myeloid differentiation. PLZF is expressed in hematopoietic progenitors and functions as a growth suppressor by repressing cyclin A2 and other targets. ETO is a corepressor for PLZF and potentiates transcriptional repression by linking PLZF to a histone deacetylase-containing complex. In transiently transfected cells and in a cell line derived from a patient with t(8;21) leukemia, PLZF and AML-1/ETO formed a tight complex. In transient assays, AML-1/ETO blocked transcriptional repression by PLZF, even at substoichiometric levels relative to PLZF. This effect was dependent on the presence of the ETO zinc finger domain, which recruits corepressors, and could not be rescued by overexpression of co-repressors that normally enhance PLZF repression. AML-1/ETO also excluded PLZF from the nuclear matrix and reduced its ability to bind to its cognate DNA-binding site. Finally, ETO interacted with PLZF/RARα and enhanced its ability to repress through the RARE. These data show a link in the transcriptional pathways of M2 and M3 leukemia.
Membrane-induced helical conformation of an active candidacidal fragment of salivary histatins.

Abstract The conformational preference of the candidacidal C-terminal 16 residue fragment (9-24; G-Y-K-R-K-F-H-E-K-H-H-S-H-R-G-Y) of salivary histatin 5 was examined in water, methanol, and dimethyl sulfoxide solutions using 500 MHz two-dimensional-NMR. Fourier transform infrared and CD spectroscopy were used to delineate its membrane-bound conformation in lipid vesicles. The peptide backbone and side-chain proton resonance assignments were accomplished by two-dimensional total correlated and nuclear Overhauser effect (NOE) spectra. The coupling constant (JNH-C alpha H) values determined from the double quantum-filtered correlated spectra, temperature coefficients of NH chemical shifts (d delta/dT), 1H/2H exchange rates on amide resonances, and the set of NOE connectivities were used to delineate backbone conformational features. The high JNH-C alpha H values (> or = 7.4 Hz), absence of any characteristic NH-NH (i, i + 1) or C alpha H-C beta H (i, i + 3) NOE connectivities, high d delta/dT values (> or = 0.004), and the fast 1H/2H amide exchange suggest that the histatin peptide favors unfolded random conformations in aqueous solution at pH 3.8. In contrast, the JNH-C alpha H values (< or = 6.5 Hz), slow 1H/2H exchange, low d delta/dT values (< or = 0.003) observed for amide resonances of residues 5-16, and the characteristic NH-NH (i, i + 1), C alpha H-C beta H (i, i + 3) NOE connectivities, provide evidence for the presence of largely alpha-helical conformations in dimethyl sulfoxide, which mimics the polar aprotic membrane environment. In methanolic solutions, 3(10)-helical conformations could exist as a minor population together with the major alpha-helical conformations. Fourier transform infrared spectroscopy and CD data indicate that lipid environments such as dimyristoylphosphatidylcholine vesicles could induce the peptide to fold into predominantly alpha-helical conformation. The results suggest that in dimethyl sulfoxide and dimyristoylphosphatidylcholine vesicles the candidacidal domain of salivary histatin 5 prefers a largely helical conformation, which could facilitate its interaction with the membrane of Candida albicans. The mechanism of antimicrobial action of this class of polypeptides appears to involve primarily electrostatic and hydrogen-bonding interaction of cationic and polar residues with the head groups of the plasma membranes of target cells.
Navigation, Organization, and Retrieval in Personal Digital Libraries of Email

Electronic mail remains the dominant application for the Internet and is the most ubiquitous type of personal digital library collection. Existing research on email includes studies of use, visualization, categorization and retrieval. [1] [4] [5] [2] This paper makes two contributions. First, I describe user interviews that revealed problems in current email systems, including role conflict, high cognitive overhead associated with organization and retrieval, inability to navigate conversations, and difficulties in addressing messages. Next, I describe a prototype system that addresses many of these problems through improvements in the message store, query interfaces, authority control, and support for identity and roles.
Exercise and Regulation of Carbohydrate Metabolism

Carbohydrates are the preferred substrate for contracting skeletal muscles during high-intensity exercise and are also readily utilized during moderate intensity exercise. This use of carbohydrates during physical activity likely played an important role during the survival of early Homo sapiens, and genes and traits regulating physical activity, carbohydrate metabolism, and energy storage have undoubtedly been selected throughout evolution. In contrast to the life of early H. sapiens, modern lifestyles are predominantly sedentary. As a result, intake of excessive amounts of carbohydrates due to the easy and continuous accessibility to modern high-energy food and drinks has not only become unnecessary but also led to metabolic diseases in the face of physical inactivity. A resulting metabolic disease is type 2 diabetes, a complex endocrine disorder characterized by abnormally high concentrations of circulating glucose. This disease now affects millions of people worldwide. Exercise has beneficial effects to help control impaired glucose homeostasis with metabolic disease, and is a well-established tool to prevent and combat type 2 diabetes. This chapter focuses on the effects of exercise on carbohydrate metabolism in skeletal muscle and systemic glucose homeostasis. We will also focus on the molecular mechanisms that mediate the effects of exercise to increase glucose uptake in skeletal muscle. It is now well established that there are different proximal signaling pathways that mediate the effects of exercise and insulin on glucose uptake, and these distinct mechanisms are consistent with the ability of exercise to increase glucose uptake in the face of insulin resistance in people with type 2 diabetes. Ongoing research in this area is aimed at defining the precise mechanism by which exercise increases glucose uptake and insulin sensitivity and the types of exercise necessary for these important health benefits.
Apoptotic and necrotic mechanisms of stress-induced human lens epithelial cell death.

Exposure to ultraviolet radiation (UVR) and reactive oxygen species (ROS) can damage the human lens and contribute to cataract formation. Recent evidence suggests that apoptosis in lens epithelial ...
Evidence for myogenic vasomotor activity in the coronary circulation.

T HAS BEEN KNOWN for many years that vascular smooth muscle will respond to the application of force by contracting. This myogenie response can be elicited by applying force and stretching an isolated strip of vascular smooth muscle or, in the case of blood vessels, by increasing the intravascular or transmural pressure. The definition of the myogenic response also includes the condition that occurs when vascular smooth muscle relaxes as the result of a decrease in applied force or intravascular pressure. This article will (1) briefly highlight the historical development of the concept of myogenitally mediated autoregulation, (2) describe the salient characteristics of myogenic activity in vascular smooth muscle, and (3) correlate these characteristics with the myogenic activity known to exist in both isolated and in situ vascular beds. The excellent review article by Johnson should be consulted for an in-depth presentation of these important topics.’ Having established the characteristics of myogenic activity, a description of our current studies related to the identification of brief myogenic activity in coronary vascular beds will be presented.
The clinical utility of Ki-67 in assessing tumor biology and aggressiveness in patients with appendiceal carcinoids.

Background/Objective To elucidate the correlation of Ki-67 with tumor biology and survival in appendiceal carcinoid tumors. Method A retrospective chart review conducted on 51 patients with appendiceal carcinoid tumors who underwent surgical intervention from 1991 to 2008. MIB-1, an antibody of Ki-67, was used to determine cell proliferation and correlated with clinical and histological parameters. MIB-1 index was categorized according to the World Health Organization (WHO) classification. Result Of the 51 patients, 32 had tumors 2 cm; and 16 with unspecified tumor size. Increased MIB proliferative index did not significantly correlate with increasing tumor size (P = 0.426). Twelve patients had metastatic disease on presentation: 9 had MIB-1 index 15%. No significant correlation between MIB index and metastasis was demonstrated (P = 0.68). Median follow-up was 40 months (range 10–183 months) with a 51% follow-up rate. Seven mortalities and three recurrences presented in 26 patients. Assessment of survival demonstrated significantly decreased survival by increasing MIB index. Survival rate by MIB index was as follows: 15% was 67% (P = 0.02). Conclusion Increased MIB index significantly correlated with decreased survival. No correlation was demonstrated by MIB index and tumor size or presentation with metastatic disease. J. Surg. Oncol. 2010;102:338–341. © 2010 Wiley-Liss, Inc.
Hormone interactions and regulation of PsPK2::GUS compared with DR5::GUS and PID::GUS in Arabidopsis thaliana

The putative pea PINOID homolog, PsPK2, is expressed in all growing plant parts and is positively regulated by auxin, gibberellin, and cytokinin. Here, we studied hormonal regulation of PsPK2::GUS expression compared with DR5::GUS and PID::GUS in Arabidopsis. PsPK2::GUS, DR5::GUS, and PID::GUS expression in Arabidopsis shoots is mainly localized in the stipules, hydathodes, veins, developing leaves, and cotyledons. Unlike DR5::GUS, PsPK2::GUS, and PID::GUS are weakly expressed in root tips. Both DR5::GUS and PsPK2::GUS are induced by different auxins and are more sensitive to methyl indole acetic acid, 4-chloro-indole acetic acid, and α-naphthalene acetic acid than others. GA(3) has no significant effect on GUS activity in DR5::GUS-transformed seedlings compared to the control, but induction by auxin and gibberellin in combination is synergistic. Cytokinin increases auxin transport in Arabidopsis seedlings. Auxin, gibberellin, and cytokinin all increase GUS activity in shoots of PsPK2::GUS transformed plants compared to the control. However, only auxin and gibberellin increase GUS activity in PID::GUS shoots. In conclusion, auxin, gibberellin, and cytokinin positively regulate PsPK2 expression in shoots, but not in roots. Auxin and gibberellin also upregulate AtPIN1 and LEAFY expression, which is similar to PsPIN1 and Uni in pea. With minor exceptions, the orthologous genes from both species are regulated similarly.
Does cancer solve an optimization problem

Many cancers are characterized by a high degree of aneuploidy, which is believed to be a result of chromosomal instability (CIN). The precise role of CIN in cancer is still the matter of a heated debate. We present a quantitative framework for examining the selection pressures acting on populations of cells and weigh the "pluses" and "minuses" of CIN from the point of view of a selfish cell. We calculate the optimal rate of chromosome loss assuming that cancer is initiated by inactivation of a tumor suppressor gene followed by a clonal expansion. The resulting rate, p* = 10(-2)per cell division per chromosome, is similar to that obtained experimentally by Lengauer et al. (1997). Our analysis further suggests that CIN does not arise simply because it allows a faster accumulation of carcinogenic mutations. Instead, CIN must arise because of alternative reasons, such as environmental factors, epigenetic events, or as a direct consequence of a tumor suppressor gene inactivation. The increased variability alone is not a sufficient explanation for the presence of CIN in the majority of cancers.
Inhibitors of Plasmin that Extend into Both the S and S‘ Binding Sites: Cooperative Interactions between S1 and S2

A new procedure for the synthesis of cyclohexanone-based inhibitors of serine proteases is reported. In this procedure the reactive ketone functionality is carried through the synthesis in masked form as a TBDMS-protected alcohol. Deprotection followed by oxidation of the alcohol generates the final form of the inhibitor. Two new inhibitors, which interact with the S1-S3 and S2' subsites of plasmin, are synthesized using this procedure. Inhibitors 1 and 2 have IC50 values against plasmin of 20 and 24 microM, respectively. The inhibition studies show that cooperative binding of inhibitors in the S1 and S2 subsites of plasmin is important for determining inhibitor selectivity.
Evaluation of the dose distribution for prostate implants using various 125I and 103Pd sources.

Recently, several different models of {sup 125}I and {sup 103}Pd brachytherapy sources have been introduced in order to meet the increasing demand for prostate seed implants. These sources have different internal structures; hence, their TG-43 dosimetric parameters are not the same. In this study, the effects of the dosimetric differences among the sources on their clinical applications were evaluated. The quantitative and qualitative evaluations were performed by comparisons of dose distributions and dose volume histograms of prostate implants calculated for various designs of {sup 125}I and {sup 103}Pd sources. These comparisons were made for an identical implant scheme with the same number of seeds for each source. The results were compared with the Amersham model 6711 seed for {sup 125}I and the Theragenics model 200 seed for {sup 103}Pd using the same implant scheme.
Decagonal and related phases in Al-Mn alloys: electron diffraction and microstructure

Abstract We present the first complete stereographic projection (Kikuchi band map) of the Al-Mn decagonal phase, determined from tilting experiments using selected-area diffraction (SAD) and convergent-beam diffraction (CBD). These new crystallographic data are indexed with existing schemes. A partial stereographic projection of a phase closely related to the decagonal phase, previously identified as orthorhombic Al3Mn, is also determined with SAD and CBD. Good agreement between the stereographic projection and the SADs for Al3Mn and those for the decagonal phase is demonstrated, indicating the degree to which the Al3Mn phase is a decagonal approximate.
A Gain-of-Function Mutation in the Arabidopsis Pleiotropic Drug Resistance Transporter PDR9 Confers Resistance to Auxinic Herbicides

Arabidopsis (Arabidopsis thaliana) contains 15 genes encoding members of the pleiotropic drug resistance (PDR) family of ATP-binding cassette transporters. These proteins have been speculated to be involved in the detoxification of xenobiotics, however, little experimental support of this hypothesis has been obtained to date. Here we report our characterization of the Arabidopsis PDR9 gene. We isolated a semidominant, gain-of-function mutant, designated pdr9-1, that exhibits increased tolerance to the auxinic herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). Reciprocally, loss-of-function mutations in PDR9 confer 2,4-D hypersensitivity. This altered auxin sensitivity defect of pdr9 mutants is specific for 2,4-D and closely related compounds as these mutants respond normally to the endogenous auxins indole-3-acetic acid and indole-butyric acid. We demonstrate that 2,4-D, but not indole-3-acetic acid transport is affected by mutations in pdr9, suggesting that the PDR9 transporter specifically effluxes 2,4-D out of plant cells without affecting endogenous auxin transport. The semidominant pdr9-1 mutation affects an extremely highly conserved domain present in all known plant PDR transporters. The single amino acid change results in increased PDR9 abundance and provides a novel approach for elucidating the function of plant PDR proteins.
A type I peritrophic matrix protein from the malaria vector Anopheles gambiae binds to chitin. Cloning, expression, and characterization.

Upon feeding, mosquito midguts secrete the peritrophic matrix (PM), an extracellular chitin-containing envelope that completely surrounds the blood meal. Because the malaria parasite must cross the PM to complete its life cycle in the mosquito, the PM is a potential barrier for malaria transmission. By antibody screening of an expression library we have identified and partially characterized a cDNA encoding a putative PM protein, termed Anopheles gambiae adult peritrophin 1 (Ag-Aper1).Ag-Aper1 is the first cloned PM gene from a disease vector. Northern analysis detected an abundant Ag-Aper1 transcript only in the adult gut, and not in any other tissues or at any other stages of development. The predicted amino acid sequence indicates that it has two tandem chitin-binding domains that share high sequence similarity with each other and also with the chitin-binding domain of an adult gut-specific chitinase from the same organism. The presumed ability of Ag-Aper1 to bind chitin was verified by a functional assay with the baculovirus-expressed recombinant protein. Ag-Aper1 did bind to chitin but not to cellulose, indicating that Ag-Aper1 binds chitin specifically. The double chitin-binding domain organization of Ag-Aper1 suggests that each protein molecule is able to link two chitin polymer chains. Hence, this protein is likely to act as a molecular linker that connects PM chitin fibrils into a three-dimensional network.
Bill coloration, a flexible signal in a tropical passerine bird, is regulated by social environment and androgens

Although some group-living animals dynamically modify sexual signals in response to changes in social or reproductive status, this ability is often limited by constraints inherent in the mechanism of signal production. In birds, for example, inflexible moult schedules may restrict the ability to rapidly modify plumage-based signals. In such cases, more flexible secondary signals such as skin, eye, or bill coloration (e.g. soft parts) could potentially be used to achieve dynamic signalling. We addressed the degree to which free-living red-backed fairy-wrens, Malurus melanocephalus, can dynamically update both plumage and soft part signals when status suddenly changes, and how this may be achieved. In this cooperatively breeding passerine, dominant breeding males are distinguished from socially subordinate nonbreeding auxiliary males by the presence of nuptial plumage, dark bills and large sperm storage organs. Following an experimentally induced shift in status from auxiliary to breeder, males showed rapid increases in excreted androgen metabolites. Although they showed no overall change in nuptial plumage colour, several experimental males developed red nuptial feathers on the back following feather plucking, indicating that they had the capacity to develop bright nuptial plumage but were constrained from doing so by the moult schedule. In contrast, experimental males showed a rapid darkening of their bills, reflecting their newly acquired breeding status. These findings (1) provide experimental evidence that status affects physiologically controlled visual signals in free-living birds, (2) suggest that this linkage is mediated by testosterone and (3) illustrate how secondary ornaments may be used in dynamic signalling when the primary signalling modality is constrained.