cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 312: Emodin inhibits colon cancer by modulating apoptotic and cell survival signals

Colon cancer remains a formidable health care concern and is the third most common cancer among men and women. Late diagnosis and development of resistance to chemotherapeutic regimens significantly impact overall outcome and survival. Various phytochemicals have been shown to have promising anti-cancer properties. Consequently, such natural agents are emerging as an alternative treatment modality for various cancers, including colon cancer. In this study, we have tested the effect of Emodin, an anthraquinone derivative of rhubarb, on human colon cancer cell lines. Our antibody microarray data and pathway analysis indicated that Emodin induced apoptosis in colon cancer cells by triggering both intrinsic and extrinsic apoptotic pathways. These effects of Emodin were associated with modulation of death receptor expression, changes in mitochondrial membrane integrity, and DNA degradation. Further, western blot analysis confirmed that Emodin significantly increased pro-apoptotic proteins (Bak, Bax, Bad) as well as activated caspase-3 and -8. Additionally, Emodin reduced ERK1/2, NF-κB, and STATs at transcript and protein levels, suggesting it also interferes with cell survival. Hence, the ability of Emodin to induce apoptosis and inhibit cell survival by altering molecular pathways underscore its potential as chemo-preventive as well as -therapeutic agent in combination with conventional chemotherapy. Citation Format: Ian T. Saunders, Neeraj Kapur, Hina Mir, Shailesh Singh. Emodin inhibits colon cancer by modulating apoptotic and cell survival signals [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 312.
Dysfunctional and Proinflammatory Regulatory T-Lymphocytes Are Essential for Adverse Cardiac Remodeling in Ischemic Cardiomyopathy.

Background: Heart failure (HF) is a state of inappropriately sustained inflammation, suggesting the loss of normal immunosuppressive mechanisms. Regulatory T-lymphocytes (Tregs) are considered key ...
Abstract 134: Cost-Related Nonadherence to Medication Among US Stroke Survivors After Affordable Care Act Implementation

Background and Objectives: Medication nonadherence is associated with increased risk of cardiovascular disease (CVD) events among patients with CVD. In 2014, many Americans gained the option of pur...
Safe Spaces and Safe Places: Unpacking Technology-Mediated Experiences of Safety and Harm with Transgender People

Transgender individuals in the United States face significant threats to interpersonal safety; however, there has as yet been relatively little research in the HCI and CSCW communities to document transgender individuals' experiences of technology-mediated safety and harm. In this study, we interviewed 12 transgender and non-binary individuals to understand how they find, create, and navigate safe spaces using technology. Managing safety was a universal concern for our transgender participants, and they experienced complex manifestations of harm through technology. We found that harmful experiences for trans users could arise as targeted or incidental affronts, as sourced from outsiders or insiders, and as directed against individuals or entire communities.. Notably, some violations implicated technology design, while others tapped broader social dynamics. Reading our findings through the notions of 'space" and 'place," we unpack challenges and opportunities for building safer futures with transfolk, other vulnerable users, and their allies.
Change in health-related quality of life in older women after diagnosis of a small breast cancer.

BACKGROUND Screening mammography reduces breast cancer mortality at the cost of frequent false-positive results that lead to unnecessary medical procedures, and the treatment of indolent breast cancers that would never threaten life or health. Earlier diagnosis generally permits less disruptive treatment, but it is possible that even the diagnosis of a very small breast cancer could significantly adversely impact health-related quality of life (HRQOL) in older women. METHODS The authors compared changes in HRQOL measured by either the Medical Outcomes Study 36-Item Short Form (SF-36) or the Veterans Rand 12-item Health Survey (VR-12) between 198 women diagnosed with in situ or invasive breast cancer measuring ≤1 cm and 36,814 matched controls using the National Cancer Institute's Surveillance, Epidemiology, and End Results cancer registry linked with the Medicare Health Outcomes Survey. RESULTS The mean age of the cases and controls was 75 years. The SF-36/VR-12 physical component score 12 was found to decrease by 1.6 points between the baseline and follow-up surveys for the controls compared with 3.2 points for women diagnosed with small breast cancers (P = .016). A 2-point decline is recognized as the minimally significant difference for this measure. On multivariable analysis, diagnosis of a small breast cancer was found to be one of the strongest predictors of a significant decrease in both the physical and mental domains of HRQOL (P = .012 and P = .023, respectively). CONCLUSIONS Receiving the diagnosis of even a very small breast cancer significantly impacts the physical and mental domains of HRQOL in older women. This finding can inform discussions regarding the relative benefits and costs of screening mammography in older women.
The Izapa Kingdom's Capital: Formative Period Settlement Patterns, Population, and Dating Low-Relief Stelae

This article presents new settlement survey data from the Izapa center of southern Mesoamerica, a site long known for its corpus of low-relief stelae. These data, which track the changing distribution of population from 1000 BC–AD 100, indicate that the city's population peaked at 5,725 inhabitants. Izapa was the capital of a regional kingdom with more than 40 lower-order monumental centers and a territory that covered at least 450 sq. km. Recent AMS dates confirm the apogee of the kingdom at 300–100 BC, and volcanological reconstruction suggests that a Tacana volcano eruption corresponds with archaeological evidence of political and demographic disruptions to the kingdom. Patterns at Izapa are contextualized in terms of Inomata and colleagues’ (2014) call for redating Kaminaljuyu, placing the erection of stelae there to after 100 BC, as well as Love's (2018) and Mendelsohn's (2018) responses in this journal. Izapa was an integrated kingdom from 700–100 BC, and “Izapa-style” sculptures were a novel medium of political communication introduced after the polity had been functioning without them for centuries. If Inomata and colleagues' (2014) proposal is correct that low-relief stelae were erected only after 100 BC at other centers in southern Mesoamerica, this was centuries after the practice was established at Izapa.
Mentoring: Eyes to See, Ears to Hear, and a Heart to Give

The perfect mentor has been described as possessing the following characteristics: “wisdom, success, influential leadership, technical expertise, time for others, kind and able to manage their own life such that work isn’t everything” (Ibarra, Harvard Business Review 78:146–155, 2000). Mentoring can be defined as a more senior person who provides various kinds of personal and career assistance to a less senior or experienced person. This chapter explores a rare example of someone who embodies the behaviors and attitudes of a perfect mentor, Joseph F. Hair. He exhibits a genuine compassion for people and personifies the absolute principles of the perfect mentor. As a professor of over 45 years and research contributor to more than 50 books and numerous academic publications, Joe continues to positively impact lives and the discipline through service. Through the incorporation of personal experience as one of Joe Hair’s proteges, as well as his words and actions, this chapter offers guidance for mentoring doctoral students and junior faculty.
Distinct evolutionary trajectories of V1R clades across mouse species

Background: Many animals rely heavily on olfaction to navigate their environment. Among rodents, olfaction is crucial for a wide range of social behaviors. The vomeronasal olfactory system in particular plays an important role in mediating social communication, including the detection of pheromones and recognition signals. Currently, very few vomeronasal receptors have known ligands, which severely limits our understanding of chemosensory-driven social communication. In this study we examine patterns of vomeronasal type-1 receptor (V1R) evolution in the house mouse and related species within the genus Mus. By exploring the evolution of these receptors, we provide insight into the functional roles of receptor subtypes as well as the dynamics of gene family evolution. Results: We generated transcriptomes from the vomeronasal organs of 5 Mus species, and produced high quality V1R repertoires for each species. We find that V1R clades in the house mouse and relatives exhibit distinct evolutionary trajectories. Some clades are highly conserved, while others reveal patterns of rapid evolutionary change. We identify putative species-specific gene expansions, including a dramatic clade D expansion in the house mouse. While gene gains are abundant, we detect very few gene losses. We describe a novel V1R clade and highlight candidate receptors for future de-orphanization. Based on clade-level evolutionary patterns, we identify receptor families that are strong candidates for detecting social signals and predator cues. Our results further support the view that V1Rs are important for detecting the physiological status of conspecifics, particularly female estrus cues. Conclusion: Analysis of clade-level evolution is critical for understanding species9 chemosensory adaptations. This study provides clear evidence that V1R clades are characterized by distinct evolutionary trajectories. As receptor evolution is shaped by ligand identity, these results provide a framework for examining the functional roles of different receptors.
HDAC6 Regulates Radiosensitivity of Non-Small Cell Lung Cancer by Promoting Degradation of Chk1

ABSTRACT We previously discovered that HDAC6 regulates the DNA damage response via modulating the homeostasis of a DNA mismatch repair protein, MSH2, through HDAC6’s ubiquitin E3 ligase activity. Here, we have reported HDAC6’s second E3 ligase substrate, a critical cell cycle checkpoint protein, Chk1. We have found that HDAC6 and Chk1 directly interact, and that HDAC6 ubiquitinates Chk1 in vivo. Typical Chk1 protein levels fluctuate, peaking at G2 and subsequently resolving via the ubiquitin-proteasome pathway. However, in HDAC6 knockdown cells, Chk1 is constitutively active and fails to resolve post-ionizing radiation (IR), leading to increased radiation sensitivity. Upon IR treatment, a greater proportion of HDAC6 knockdown cells accumulated at G2/M phase when compared with control cells. Depletion or inhibition of Chk1 in HDAC6 knockdown cells renders those cells radiosensitive, suggesting that persistently high level of Chk1 could lead cells to arrest at G2/M phase and eventually, apoptosis. Clinically, we found that high levels of phosphorylated Chk1 (p-Ser317) are associated with a better overall survival in a cohort of non-small cell lung cancer (NSCLC) patients, suggesting a link between active Chk1 and lung cancer development. Overall, our results highlight a novel mechanism of Chk1 regulation at the protein level, and a possible strategy for sensitizing NSCLC to radiation via inhibiting the activity of HDAC6’s E3 ligase.
Risk of fatigue with the targeted therapy for renal cell carcinoma.

e20611 Background: Fatigue is one of the major side effects associated with targeted therapeutic agents in the treatment of renal cell carcinoma (RCC), and has negatively affected the optimal use o...
Fluctuations in Mean-Field Ising models

In this paper, we study the fluctuations of the average magnetization in an Ising model on an approximately $d_N$ regular graph $G_N$ on $N$ vertices. In particular, if $G_N$ is \enquote{well connected}, we show that whenever $d_N\gg \sqrt{N}$, the fluctuations are universal and same as that of the Curie-Weiss model in the entire Ferro-magnetic parameter regime. We give a counterexample to demonstrate that the condition $d_N\gg \sqrt{N}$ is tight, in the sense that the limiting distribution changes if $d_N\sim \sqrt{N}$ except in the high temperature regime. By refining our argument, we extend universality in the high temperature regime up to $d_N\gg N^{1/3}$. Our results conclude universal fluctuations of the average magnetization in Ising models on regular graphs, Erdős-Renyi graphs (directed and undirected), stochastic block models, and sparse regular graphons. In fact, our results apply to general matrices with non-negative entries, including Ising models on a Wigner matrix, and the block spin Ising model. As a by-product of our proof technique, we obtain Berry-Esseen bounds for these fluctuations, exponential concentration for the average of spins, and tight error bounds for the Mean-Field approximation of the partition function.
Complications of small-bore feeding tubes: is newer technology necessarily better?

Dear editor, Jacobson et al 1 keenly examined how a novel electromagnetic tracking system may be safely used to ensure correct placement of small-bore feeding tubes (SBFTs). Clinical practice has shifted such that SBFTs are preferred for short-term feeding due to a reduction in aspiration risk and perceived patient comfort.2 The latter, however, is largely anecdotal and may reflect provider perception rather than reality. In actuality, traditional large-bore feeding tubes (LBFTs) may be the favorable option. SBFTs are commonly placed blindly with a 1%–3% incidence of erroneous airway insertion. A pneumothorax occurs in one-third of pulmonary misplacements with an associated mortality rate reportedly exceeding 20%. Additional pulmonary complications include hemothoraces, pneumonias and broncho-pleural fistulas.1 3 SBFTs employ a rigid guidewire—the suspected culprit …
Do animal Cruelty Exposure and Positive Engagement with Pets Moderate Associations Between Children’s Exposure to Intimate Partner Violence and Externalizing Behavior Problems?

Prior research has found that co-occurring forms of family violence exacerbate the effect of intimate partner violence (IPV) exposure on children’s externalizing behaviors. Although exposure to animal cruelty (AC) is prevalent among children living in households where IPV occurs, no study to date has tested whether and to what extent AC moderates the relationship between IPV exposure and externalizing behaviors. The current study evaluates whether the associations between exposure to IPV and several indicators of externalizing behavior vary as a function of children’s AC exposure and engagement with pets. Participants included 204 mother–child dyads recruited from IPV services (children aged 7–12 years; 47% female; 77.5% ethnic minority). We conducted a separate multiple moderation analysis for each externalizing outcome (rule-breaking behavior, aggressive behavior, oppositional defiant problems, and conduct problems) using PROCESS to evaluate whether the association between exposure to IPV and externalizing behavior varied as a function of children’s engagement with pets and exposure to AC (adjusting for demographic covariates). Approximately 26% of children were exposed to AC. We did not find evidence that positive engagement with pets or AC exposure moderated the association between IPV and externalizing problems. Although prior research suggests that AC exposure and positive engagement with pets may impact the development of internalizing behavior, this study’s findings have important implications as they suggest that these aspects of human-animal interaction may play a less significant role in the development of externalizing behavior, particularly in the context of IPV.
Defining Anastomotic Leaks After Colorectal Surgery: Results of a National Survey.

Abstract Background Anastomotic leaks are a dreaded complication after colorectal surgery. Although anastomotic leak is often used as a metric to compare patient outcomes, a standard definition does not exist. Materials and methods A web-based survey was developed and distributed to US surgeons. Respondents were queried on the definition of anastomotic leaks using a 5-point Likert scale to rate different scenarios related to colorectal surgery. Results Of potential 2209 respondents, 649 (29%) responded to the survey. The majority of respondents was men (76%) and practiced colon and rectal surgery as their primary specialty (89%). Contrast extravasation at the anastomosis, regardless of timing related to the surgery, is the clinical scenario with greatest consensus (>85%). 50% of surgeons do not believe that an abscess near the anastomosis in an asymptomatic patient defines a leak. Conclusions These results highlight the pressing need for standardization of the anastomotic leak definition given the implications on outcomes measurement, research trials, and health care reimbursement.
New Advancements in Inflatable Penile Prosthesis.

Abstract Introduction Inflatable penile prosthesis (IPP) technology is a mainstay in the treatment of erectile dysfunction refractory to medical management. Technological advancements in the design of 3-piece IPPs have been improved to optimize concealability and surgical placement since the 1980s. Recent advancements over the past 10 years include pump, reservoir, tubing, and cylinder updates. Objectives This review examines the latest updates in IPP technology, reviews recent relevant research, and is based on over 32 years of experience performing IPP surgery in addition to concurrent postoperative management. Methods A literature review was conducted for studies published over the last 10 years through March 2020 with an emphasis on technical updates of IPP, specifically the pump, reservoir, tubing, and cylinder, and their functional outcomes. Anti-infective coating and transgender innovations, in addition to postoperative management, are also reviewed. Results Technological advancements include a flat reservoir designed for improved discreteness and a prosthesis with optimized tubing length, a one-touch deflatable 3-piece system, narrow-base cylinders, a 0° angle design between the cylinders and tubing to aid in cylinder placement, a soft molding cylinder tip redesign that better mimics human anatomy, and a 3-piece IPP specifically designed for neophallus use. Furthermore, the Food and Drug Administration approved the submuscular reservoir placement. Conclusion Penile prosthesis has evolved over time to improve functional outcomes, ease of use, and minimize postoperative complications and pain. Penile prosthesis implantation continues to be a life-changing procedure for patients and it is imperative for surgeons to be up-to-date on the latest developments and research in order to provide the best functional outcomes for those they take care of. Dinerman BF, Telis L, Eid JF. New Advancements in Inflatable Penile Prosthesis. Sex Med Rev 2021;9:507–514.
The Design of a Carbon Tax

We consider the design of a tax on greenhouse gas emissions for a developed country such as the United States. We consider three sets of issues: the optimal tax base, issues relating to the rate (including the use of the revenues and rate changes over time) and trade. We show that a well-designed carbon tax can capture about 80% of U.S. emissions by taxing fewer than 3,000 taxpayers and up to almost 90% with a modest additional cost. We recommend full or partial delegation of rate setting authority to an agency to ensure that rates reflect new information about the costs of carbon emissions and of abatement. Adjustments should be made to the income tax to ensure that a carbon tax is revenue neutral and distributionally neutral. Finally, we propose an origin-based system for trade with countries that have an adequate carbon tax and a system of border taxes for imports from countries without a carbon tax. We suggest a system that imposes presumptive border tax adjustments with the ability of an individual firm to prove that a different rate should apply. The presumptive tax could be based either on average emissions for production of the item by the exporting country or by the importing country.
Distinct signatures of codon and codon pair usage in 32 primary tumor types in the novel database CancerCoCoPUTs for cancer-specific codon usage.

Background Gene expression is highly variable across tissues of multi-cellular organisms, influencing the codon usage of the tissue-specific transcriptome. Cancer disrupts the gene expression pattern of healthy tissue resulting in altered codon usage preferences. The topic of codon usage changes as they relate to codon demand, and tRNA supply in cancer is of growing interest. Methods We analyzed transcriptome-weighted codon and codon pair usage based on The Cancer Genome Atlas (TCGA) RNA-seq data from 6427 solid tumor samples and 632 normal tissue samples. This dataset represents 32 cancer types affecting 11 distinct tissues. Our analysis focused on tissues that give rise to multiple solid tumor types and cancer types that are present in multiple tissues. Results We identified distinct patterns of synonymous codon usage changes for different cancer types affecting the same tissue. For example, a substantial increase in GGT-glycine was observed in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) of the breast. Change in synonymous codon preference favoring GGT correlated with change in synonymous codon preference against GGC in IDC and IDLC, but not in ILC. Furthermore, we examined the codon usage changes between paired healthy/tumor tissue from the same patient. Using clinical data from TCGA, we conducted a survival analysis of patients based on the degree of change between healthy and tumor-specific codon usage, revealing an association between larger changes and increased mortality. We have also created a database that contains cancer-specific codon and codon pair usage data for cancer types derived from TCGA, which represents a comprehensive tool for codon-usage-oriented cancer research. Conclusions Based on data from TCGA, we have highlighted tumor type-specific signatures of codon and codon pair usage. Paired data revealed variable changes to codon usage patterns, which must be considered when designing personalized cancer treatments. The associated database, CancerCoCoPUTs, represents a comprehensive resource for codon and codon pair usage in cancer and is available at https://dnahive.fda.gov/review/cancercocoputs/ . These findings are important to understand the relationship between tRNA supply and codon demand in cancer states and could help guide the development of new cancer therapeutics.
Rhythmic heart rate variability (sinus arrhythmia) related to stages of sleep.

Evidence that the excursion of rhythmic heart rate variability (sinus arrhythmia) may be manipulated by altering the subject’s state of concentration, prompted a study of effects associated with different stages of sleep. There were 9 healthy subjects, ages 16–69, and one 55-year-old subject (C.P.) with a myocardial infarction history. Awake and during sleep the excursion of heart rate variability was greatest among the younger subjects, decreasing progressively with age. C.P. displayed rhythmic heart rate variability only when asleep. In light sleep (Stages 1 and 2) all subjects, with the exception of the 69-year-old, whose rate remained almost fixed throughout the night, displayed rhythmic heart rate variability, roughly synchronous with respiration. Neither the elderly subjeot nor C.P. entered into deep sleep (Stages 3 and 4). Among the other subjects, deep sleep was marked by a precise correlation between the frequency of respiration and heart rate variability. In REM sleep, however, in all subjects, there was often a total dissociation between respiration and rhythmic heart rate variability. There were periods of no heart rate variability with continuing regular respiration and of rhythmic heart rate variability with spontaneous breath holding. In the presence of heart rate variability during REM, C.P. displayed frequent ectopic beats, but ectopic beats were nearly absent in REM periods characterized by a steady, unvarying heart rate. The range of heart rate variability at rest and during sleep (sinus arrhythmia) reflects the manner in which autonomic activity is brought to bear in regulating the heart beat. The study of the behavior of sinus arrhythmia may offer a way to anticipate the occurrence of dangerous cardiac dysarrhythmias and sudden death, especially during sleep.
Ideology, International Law, and the INS: The Development of American Asylum Politics 1948–Present

American asylum policy has developed gradually over many decades, which can be divided into five distinct eras. The relationships between the categories of refugee, asylum seeker, and undocumented immigrant have shifted frequently, and answers about which asylum seekers qualify for refugee status in the United States have been both politically constructed over time and contingent on the politics of the moment. Asylum seekers, therefore, have sometimes been assumed to be refugees, and at other times have been automatically lumped together with undocumented economic migrants. Asylum policy development has also been driven by a much larger conflict in American politics: the rise of legal institutions representing a commitment to international human rights, and the conservative backlash to that emergence. All of these forces have contributed to the current era, which is characterized by deterrence policies and litigation challenging their enforcement.
What is the impact of p2p traffic on anomaly detection

Recent studies estimate that peer-to-peer (p2p) traffic comprises 40-70% of today's Internet traffic [1]. Surprisingly, the impact of p2p traffic on anomaly detection has not been investigated. In this paper, we collect and use a labeled dataset containing diverse network anomalies (portscans, TCP floods, UDP floods, at varying rates) and p2p traffic (encrypted and unencrypted with BitTorrent, Vuze, Flashget, µTorrent, Deluge, BitComet, Halite, eDonkey and Kademlia clients) to empirically quantify the impact of p2p traffic on anomaly detection. Four prominent anomaly detectors (TRW-CB [7], Rate Limiting [8], Maximum Entropy [10] and NETAD [11]) are evaluated on this dataset. Our results reveal that: 1) p2p traffic results in up to 30% decrease in detection rate and up to 45% increase in false positive rate; 2) due to a partial overlap of traffic behaviors, p2p traffic inadvertently provides an effective evasion cover for high- and low-rate attacks; and 3) training an anomaly detector on p2p traffic, instead of improving accuracy, introduces a significant accuracy degradation for the anomaly detector. Based on these results, we argue that only p2p traffic filtering can provide a pragmatic, yet short-term, solution to this problem. We incorporate two prominent p2p traffic classifiers (OpenDPI [23] and Karagiannis' Payload Classifier(KPC) [24]) as pre-processors into the anomaly detectors and show that the existing non-proprietary p2p traffic classifiers do not have sufficient accuracies to mitigate the negative impacts of p2p traffic on anomaly detection. Given the premise that p2p traffic is here to stay, our work demonstrates the need to rethink the classical anomaly detection design philosophy with a focus on performing anomaly detection in the presence of p2p traffic. We make our dataset publicly available for evaluation of future anomaly detectors that are designed to operate with p2p traffic.
Attention Theory and Mechanisms for Skilled Performance.

Current attentional research and theory are related to the development of skilled performance. Emphasis is given to how performance changes with practice. Dual process attention theory is reviewed examining the distinctions between automatic and controlled processing. The changing interactions between automatic and controlled processing in the development of skill are discussed. It is proposed that consistent practice produces automatic productions which perform consistent transformations in a heterarchial system. Automatic productions are proposed to: be modular; show high transfer; become resource free; not be under direct control, and be fast, accurate, and coordinated. Controlled processing is assumed to develop automatic processing, maintain strategy and time varying information, and perform problem solving activities. Perceptual data, some motor data, and several motor performance examples are presented to illustrate automatic/controlled processing effects. The relationship to current theories of motor skill is discussed. New research paradigms suggested by the current approach are discussed.
Common Law Theory

Introduction Douglas E. Edlin Part I. Common Law Rules: 1. Judges as rulemakers Larry Alexander and Emily Sherwin 2. Some types of law John Gardner Part II. Common Law Reasoning: 3. The principles of legal reasoning in the common law Melvin A. Eisenberg 4. A similibus ad similia: analogical thinking in law Gerald J. Postema 5. Reasoned decisions and legal theory David Dyzenhaus and Michael Taggart Part III. Common Law Constitutionalism: 6. Common law, natural law, and the constitution James R. Stoner, Jr 7. Text, context, and constitution: the common law as public reason T. R. S. Allan 8. The myth of the common law constitution Jeffrey Goldsworthy.
Is global warming causing more, larger wildfires?

Higher spring and summer temperatures and earlier snowmelt are extending the wildfire season and increasing the intensity of wildfires in the western United States.
Plasma aldosterone-renin interrelationships in various forms of essential hypertension. Studies using a rapid assay of plasma aldosterone.

Plasma aldosterone measurements using a new radioimmunoassay technique were included in a component analysis of the renin-aldosterone-sodium system. The studies involved 27 normal subjects and 51 patients with essential hypertension characterized by low, normal or high plasma renin activity. Noon plasma aldosterone concentrations closely reflected the state of aldosterone secretion. Thus, in normal subjects, plasma aldosterone values exhibited a relationship to the daily urinary sodium excretion similar to that for urinary aldosterone excretion. Moreover, plasma aldosterone levels and the simultaneously measured plasma renin activity were linearly correlated over a wide range of sodium balance, again pointing to a key role for renin in the control of plasma aldosterone levels. In 21 patients with normal renin essential hypertension, the absolute levels of plasma aldosterone and their relation to plasma renin levels were similar to those observed in normal subjects. In 14 patients with high renin hypertension concurrent plasma aldosterone levels were commensurately elevated. A deflection of this renin-aldosterone interaction observed in some high renin patients appeared consequent to potassium depletion. In contrast, in 14 of 16 patients with low renin essential hypertension, noon plasma aldosterone concentrations, under conditions of normal or moderately high dietary sodium, were higher relative to simultaneous plasma renin activity, resulting in an abnormal plasma aldosterone to renin ratio above 10. This abnormal renin-aldosterone interrelation could prove useful for identifying and further characterizing patients within the low renin hypertension category. In hypertensive patients, plasma aldosterone measurements can be used interchangeably with urinary aldosterone excretion rates but for full meaning they must still be related to an index of sodium balance such as the daily rate of sodium excretion. Moreover, they have special value for short-term studies and for evaluating aldosterone secretion in states of hepatic or renal insufficiency and perhaps in edematous states in which impaired aldosterone metabolism or renal excretion occurs.
The crayfish sustaining fibers

Simultaneous intracellular and extracellular recordings were obtained from sustaining fibers (SFs) within the optic lobes of the crayfish compound eye.
Ballato electronic circuit models for programmable SAW filters

In recent years novel microelectronic technologies such as silicon-on-insulator and GaAs HBTs have advanced to near-maturity. Given the foundry availability of these technologies, it is prudent to re-evaluate the prospect of programmable SAW filters whereby IDT finger tap weights can be controlled electronically in order to achieve, for example, an adaptive filter module. To facilitate the design of these programmable SAW filters it is advantageous to use an electronic circuit model for the IDT electrodes. To this end, a SPICE-based circuit model for SAW IDTs is presented which employs the two-transformer model first presented by Ballato in 1972 for Bulk Acoustic Wave devices. The element factor for the IDT electrodes is incorporated via a frequency-dependent transformer turns ratio. Acoustic transmission line velocities and characteristic impedances can be calculated separately by such methods as the Datta-Hunsinger models for scattering coefficients from electrodes. The energy storage term can be incorporated as a velocity perturbation in the acoustic transmission line. Results of the Ballato electronic circuit model are corroborated by analytical calculations for simple IDT structures on 128°-rotated Y-cut X-propagating LiNbO3.
Analysis of multiple classifier system using product and modified product rules

One of the key factors in designing a successful multiple classifier system (MCS) is choosing an appropriate combining rule. Many theoretical and experimental efforts have been focused on estimating the probability of classification error for different combining rules. In this work, assuming N classifiers and two independent and identically distributed classes, we investigate using product and modified product rules and derive formulas to estimate their classification error probability under two class distributions, Gaussian and uniform. We also validate our derivations with computer simulations. The performance results of product, modified product, average, and majority vote rules are compared. The comparisons are done in term of probability of classification error as a function of class variance and number of classifiers. The results show that the modified product rule outperforms others while the product rule ranks last.
Comparing performance of binary-coded detectors and constraint-based detectors

Artificial immune systems can be used to detect intrusion by classifying network activities as normal or abnormal. High detection rates and low false positive rates are two necessary features of successful AIS. Strong detectors are the basis of creating a successful AIS. Some preliminary experiments showed its promise to encode detectors in the form of data triples. Currently, there are two types of detectors: binary-coded and constraint-based. This paper compares the two types of detectors using simulated network traffic data. The results show that constraint-based detectors perform better than binary-coded detectors.
Changing indications for surgery in patients with stage IV breast cancer: a current perspective.

BACKGROUND Evolving concepts of cancer biology and emerging evidence of a potential survival benefit from local surgery have raised the question of an expanded role for surgery in select patients with metastatic breast cancer (MBC). To determine whether such developments have influenced clinical practice, the authors evaluated surgical practice patterns in the study institution over the last 15 years. METHODS Two institutional databases were screened to identify patients with MBC who underwent breast surgery (1990–2005). Retrospective review was conducted to assess trends over time and to evaluate the role of surgery in the more modern era (1995–2005). RESULTS The overall frequency of mastectomy remained stable over time (1.7%); however, between early (1990–1995) and late (2000–2005) periods the rate of ‘symptom control’ mastectomy decreased (41% to 25%), whereas the rate of ‘local control’ mastectomy increased (34% to 66%). Conversely, the overall frequency of wide-local excision (WLE) increased over time (1995–2001), from 1% to 9% (P < .001) with no differences noted between rates of symptom control or local control procedures. In the modern era (1995–2005), 256 of 12,529 patients (2%) with MBC underwent breast surgery (33% mastectomy, 52% WLE); most frequently to ‘optimize local control’ (50%) and primarily in the setting of limited/stable distant disease. Surgery was performed for palliation in only 19% of patients. At a median follow-up of 33.9 months (range, 0–198.7 months), 136 of 256 patients (53%) in this cohort remained alive; 88% were free of local disease. CONCLUSIONS Although surgery in MBC has historically been reserved for palliation, the authors observed a decreasing rate of traditional ‘toilet mastectomy’ and a broadened surgical approach to the asymptomatic patient. When viewed in parallel with evolving concepts in cancer biology, these data reflect a change in the traditional approach to patients with MBC and warrant further investigation. Cancer 2008. ©2008 American Cancer Society.
Evolution of the performance of automatic speech recognition algorithms in transcribing conversational telephone speech

Research in the speech recognition speech-to-text conversion area has been underway for a couple of decades, and a great deal of progress has been made in reducing the word error rate. In this paper, we attempt to summarize the state of the art in speech recognition algorithms. The algorithms we describe span the areas of lexicon design, feature extraction, classifier design, combination of hypotheses, and speaker adaptation of acoustic models. We will benchmark the algorithms on two main sources of speech, the first being Voicemail (conversational telephone speech from a single speaker) and the second being Switchboard (conversational telephone speech between two speakers). We also present the results of some cross-domain experiments which highlight the "brittleness" of speech recognition systems today and illustrates the need to focus research effort on improving cross-domain performance.
Overcoming obstacles to developing new analgesics

Despite substantial investment by the pharmaceutical industry over several decades, there has been little progress in developing new, efficacious and safe analgesics. As a result, many large pharmaceutical companies are leaving the area of pain medication. Nevertheless, the chances of success could increase if analgesic drug development strategy changed. To achieve such a paradigm shift we must understand why development of drugs for pain relief is so challenging.
Existence and uniqueness of equilibrium points for concave n-person games

Existence and uniqueness of equilibrium points for concave n-person games - dynamic model for nonequilibrium situations
Low molecular weight dextran in the treatment of necrotizing enterocolitis and midgut volvulus in infants

Abstract Because of its abilities to reduce thrombus formation, low molecular-weight dextran was administered to eight newborns with necrotizing enterocolitis and two infants with midgut volvulus. The enterocolitis group which received dextran when compared with an otherwise similarly treated group which did not receive dextran, revealed the following differences: half of the dextran-treated group did not require operation while all of the patients not receiving dextran did. Although repeated perforation and late intestinal strictures occurred commonly in the group which did not receive dextran, no dextran-treated infant demonstrated either of these complications. The patients with midgut volvulus receiving dextran demonstrated remarkable recovery of bowel at reexploration, despite the widespread ischemic appearance of bowel at initial operation. No complications from the use of dextran were encountered.
The role of integrins in reproduction.

. Fertilization, implantation, and placentation are dynamic cellular events that require not only synchrony between the maternal environment and the embryo, but also complex cell-to-cell communication. This communication involves integrins, a large family of proteins involved in the attachment, migration, invasion, and control of cellular function. Over the past decade, investigators have learned that integrins participate in multiple reproductive events including fertilization, implantation, and placentation in many species. This review will describe: (i) the expression of integrins on gametes and during the establishment and development of the placenta; (ii) regulatory pathways for controlling expression of integrins in the uterus and developing placenta; (iii) the function of integrins as determined by null-mutations; and (iv) reproductive dysfunction in women related to inappropriate integrin expression in the uterus and/or placenta.
Osteoporotic bone disease in the pyridoxine-deficient rat.

Abstract Weanling rats develop osteoporosis on a high protein pyridoxine-deficient diet. Urinary o -phosphoethanolamine (OPE) levels are elevated in deficient animals and there is decrease in several hepatic enzymes which require pyridoxal phosphate as cofactor, including OPE phospholyase, an enzyme which degrades OPE. Serum alkaline phosphatase levels do not differ from control animals. Osteoporotic bone disease in the pyridoxine-deficient rat may be responsible in part for the growth failure in these animals, and may be related to the bone disease seen in some human metabolic disorders.
Mechanisms for the modulation of native glycine receptor channels by ethanol.

Previously, we showed that ethanol increases synaptic glycine currents, an effect that depends on ethanol concentration and developmental age of the preparation. Glycine receptor (GlyR) subunits un...
MyRIP Anchors Protein Kinase A to the Exocyst Complex

The movement of signal transduction enzymes in and out of multi-protein complexes coordinates the spatial and temporal resolution of cellular events. Anchoring and scaffolding proteins are key to this process because they sequester protein kinases and phosphatases with a subset of their preferred substrates. The protein kinase A-anchoring family of proteins (AKAPs), which target the cAMP-dependent protein kinase (PKA) and other enzymes to defined subcellular microenvironments, represent a well studied group of these signal-organizing molecules. In this report we demonstrate that the Rab27a GTPase effector protein MyRIP is a member of the AKAP family. The zebrafish homolog of MyRIP (Ze-AKAP2) was initially detected in a two-hybrid screen for AKAPs. A combination of biochemical, cell-based, and immunofluorescence approaches demonstrate that the mouse MyRIP ortholog targets the type II PKA holoenzyme via an atypical mechanism to a specific perinuclear region of insulin-secreting cells. Similar approaches show that MyRIP interacts with the Sec6 and Sec8 components of the exocyst complex, an evolutionarily conserved protein unit that controls protein trafficking and exocytosis. These data indicate that MyRIP functions as a scaffolding protein that links PKA to components of the exocytosis machinery.
Cell-free translation of proline-rich protein mRNAS from human submandibular gland.

Summary RNA was isolated from a human submandibular gland and separated into poly A-enriched and poly A-deficient fractions by chromatography on oligo(dT) cellulose. Both of these RNA fractions stimulated methionine incorporation into polypeptides in a reticulocyte lysate translation system. Two in vitro translation products templated by poly A-enriched mRNA were isolated by immunoprecipitation with immune serum directed against human salivary anionic proline-rich protein I. These polypeptides were shown to be precursors of proline-rich proteins on the basis of M r , affinity for the antiserum, and preferential incorporation of proline. This study is the first to demonstrate cell-free translation of the mRNAs for human proline-rich salivary protein precursors.
A direct method for recording tension changes in the wall of small blood vessels in vitro.

A method is described for the direct recording of tension changes in the wall of blood vessels of 100 μm i.d. or less in vitro. Most vessels tested exhibited spontaneous rhythmic activity and responded tol-norepinephrine by an increase in tension. The response to transmural stimulation of the intramural nerves was variable.
Metabolism of progesterone in the canine feto-placental unit.

AbstractProgesterone (P), a major hormone of pregnancy, was selected for study under the conditions of an intact utero-placental-fetal unit. A preparation of the canine gravid uterus, near term, is described and shown to permit observation of the metabolic relationships of the steroid hormone P between maternal and fetal organisms. [1,2-3H] P or [7α-3H]P was injected into pups, while [4-14C]P was injected into the uterine circulation. Perfusion was continued for 1 hr with excellent survival of the pups. Identified metabolites in the fetal and maternal tissues suggest a metabolic pool that is shared throughout the unit.
Imaging of the aging brain. Part I. Normal findings.

A thorough knowledge of the normal changes that occur in the brain with age is critical before abnormal findings are analyzed. Magnetic resonance (MR) imaging improves the ability to distinguish normal and abnormal findings in the brain. The major changes that may occur in elderly individuals without neurologic deficits include enlargement of the ventricles, cortical sulci, and vermian subarachnoid spaces; multifocal areas of hyperintensity in the white matter and basal ganglia; a progressive prominence of hypointensity on T2-weighted images of the putamen, almost equal to that of the globus pallidus; an increase in the oxygen extraction ratio with normal or mildly decreased neuron metabolism; arteriosclerosis in large and small arteries and amyloid angiopathy in leptomeningeal cortical vessels; and decreased dopamine receptor binding in the corpus striatum. Since approximately half of the elderly population exhibits only negligible brain alterations, MR imaging may facilitate the distinction between usua...
Ontology and Method in Cognitive Sociology

The sociology of cognition could serve as a more effective bridge between sociology and other disciplines, and more of a two-way thoroughfare, if we would consider doing the following two things, which we are already doing here and there. First, we need to take a stand in philosophy of social science debates. Second, we need to show how what we do contributes to sociological methods, and not only say that what we do contributes to sociological theory, however fundamental that contribution may be.