cssi/SciSciGPT-SciSciNet huggingface dataset:
P53, bcl-2, and Bax expression in renal cell carcinoma.

Abstract Objectives. Renal cell carcinomas often show a high degree of resistance to chemotherapy and radiation despite expressing normal function of the protein p53. The loss of control of apoptosis may also contribute to progression and resistance to treatment modalities and can be attributed to an interaction between p53 and the apoptotic regulators bcl-2 and Bax. To determine whether the expression of p53, bcl-2, or Bax could be correlated with outcome, we analyzed the expression pattern of these proteins in renal cell tumor samples. Methods. We examined 28 patients with clear cell renal cell carcinomas along with 7 patients with papillary renal cell carcinomas and 4 with renal oncocytomas. All renal cell carcinomas were clinically localized Stage pT2 with tumor size ranging from 4.0 to 10.3 cm (mean 6.23). Immunohistochemistry was performed on all samples and correlated with markers of outcome, including tumor grade, metastasis, recurrence, and overall survival rate. Results. In all clear cell tumors, the detection level of p53 expression was below the sensitivity of the assay, consistent with the reported infrequent incidence of p53 mutations in renal cell cancers. bcl-2 expression showed a significant correlation ( P = 0.018) with higher tumor grade but could not be significantly correlated with other parameters examined including tumor recurrence, metastasis, or survival rate. The expression of Bax could similarly be correlated with higher tumor grade but with none of the other parameters. Conclusions. At the present time, the combination of both tumor grade and stage represents the best prognostic markers available. Adjunctive use of bcl-2 and Bax staining currently plays a minimal role in helping to further stratify patients at high risk for disease progression or recurrence.
Differential processing of ingroup and outgroup information: the role of relative group status in permeable boundary groups

Perceivers individuate cognitively the ingroup more than the outgroup; that is, perceivers use person categories to process information about the ingroup, but use stereotypic attribute categories to process information about the outgroup. This phenomenon is labelled the differential processing effect (DPE). Is the DPE moderated by relative group status? In two experiments, either high- or low-status members of permeable-boundary groups (i.e. groups that encourage upward mobility) read through information about unfamiliar ingroup and outgroup members. Relative group status moderated the DPE. Clustering indices in recall and confusions in a name-matching task indicated that high-status members individuated the ingroup more than the outgroup, thus replicating the DPE. However, low-status members individuated the outgroup more than the ingroup, thus reversing the DPE. A third experiment suggested that these findings are predicated on the ingroup information being stereotype-consistent. © 1997 John Wiley & Sons, Ltd.
Associations between subjective sleep quality and brain volume in Gulf War veterans.

STUDY OBJECTIVES To investigate whether subjective sleep quality is associated with brain volume independent of comorbid psychiatric conditions. DESIGN Cross-sectional. SETTING Department of Veterans Affairs (VA) Medical Center. PARTICIPANTS One hundred forty-four Gulf War Veterans (mean age 45 years; range: 31-70 years; 14% female). INTERVENTIONS None. MEASUREMENTS AND RESULTS Total cortical, lobar gray matter, and hippocampal volumes were quantified from 1.5 Tesla magnetic resonance images using Freesurfer version 4.5. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Multiple linear regressions were used to determine the association of sleep quality with total and regional brain volumes. The global PSQI score was positively correlated with lifetime and current posttraumatic stress disorder (PTSD) and current depressive symptoms (P < 0.001) and was higher in veterans with Gulf War Illness, trauma exposure, and those using psychotropic medication (P ≤ 0.03). After adjusting for these comorbid variables, age, intracranial volume, and multiple comparisons, global PSQI was inversely associated with total cortical and frontal gray matter volume (adjusted P ≤ 0.03). Within the frontal lobe, total PSQI was inversely associated with the superior and middle frontal, orbitofrontal, anterior cingulate, and frontal pole volumes (adjusted P ≤ 0.02). Examination of the 3-factor structure of the PSQI revealed that the associations were driven by perceived sleep quality. CONCLUSIONS Poorer subjective sleep quality was associated with reduced total cortical and regional frontal lobe volumes independent of comorbid psychiatric conditions. Future work will be needed to examine if effective treatment of disturbed sleep leads to improved structural and functional integrity of the frontal lobes.
The nature and effects of the thermal stability of lithium hydroxide

Temperature programmed decomposition and complimentary microscopy/spectroscopy techniques were performed on lithium hydroxide with micron-sized grains. The lithium hydroxide grains thermally decomposed into Li2O, releasing H2O, following a three dimensional phase boundary moving from the surface inward. The energy barriers measured for the decomposition of surface and near-surface lithium hydroxide are noticeably smaller than those of bulk counterpart. The conversion of Li2O grains back to lithium hydroxide during moisture exposure was also found to proceed from the surface inward such that surface states are filled before bulk states. In a different set of experiments, nanometer-scale composite grains composed of LiD inner cores and LiOH outer layers were observed to form on top of pressed polycrystalline LiD upon moisture exposure. A diffusion coefficient on the order of 10−23 m2/s was measured for the diffusion controlled reaction of LiOH with LiD in the nanopowder at room temperature in a dry environment. The measured kinetics were used to model the evolution of the LiD/LiOH composite system in a dry environment.
INTRACELLULAR STUDIES OF CORTICAL NEURONS IN CHRONIC EPILEPTOGENIC FOCI IN THE MONKEY.

Abstract The activity of cortical neurons was studied by means of intracellular recording in both normal cats and monkeys as well as in monkey cortex rendered epileptic by the intracortical injection of alumina cream. In the normal preparation, intracellular records from what was presumably soma were more readily obtained than those from what was presumably axon. In the epileptic preparations, all records obtained from cells demonstrating the firing pattern characteristics of epilepsy also had waveform characteristics typical of axons or axonlike membrane. Again, intracellular units in these epileptic preparations could rarely be evoked.
A representation theorem based analysis of two-dimensional electromagnetic scattering from materials and resistive cards

Representation-theorem-based surface integral operators are presented and used to predict electromagnetic scattering from a material body with an embedded resistive card. The integral operators are obtained from a representation theorem for the 2-D Helmholtz equation in a region with constant electrical properties characterized by complex permittivity and permeability. A resistive card embedded in the region is introduced by enforcing a resistive boundary condition on the representation theorem integrals as the thickness of a geometrically thin region surrounding an embedded card approaches zero. Surface integral operators are obtained by letting the field point in the representation theorem equations approach material boundaries and resistive cards. Multiple regions with constant electrical properties (including perfect conductors) are allowed by enforcing boundary conditions between regions. Two polarizations of normally incident plane wave radiation are considered. Prediction and experiment are in good agreement for a resistive card embedded in a bulk material. >
Mining web interactions to automatically create mash-ups

The deep web contains an order of magnitude more information than the surface web, but that information is hidden behind the web forms of a large number of web sites. Metasearch engines can help users explore this information by aggregating results from multiple resources, but previously these could only be created and maintained by programmers. In this paper, we explore the automatic creation of metasearch mash-ups by mining the web interactions of multiple web users to find relations between query forms on different web sites. We also present an implemented system called TX2 that uses those connections to search multiple deep web resources simultaneously and integrate the results in context in a single results page. TX2 illustrates the promise of constructing mash-ups automatically and the potential of mining web interactions to explore deep web resources.
A Fluorescent Sensor for 2,3‐Bisphosphoglycerate Using a Europium Tetra‐N‐oxide Bis‐bipyridine Complex for Both Binding and Signaling Purposes

Host 1 was designed and synthesized as a fluorescent sensor for 2,3-bisphosphoglycerate (BPG, 3). The design features a tris-functionalized triethylbenzene core to preorganize binding groups. The three cationic moieties, a tetra-N-oxide bipyridine - europium complex and two ammonium groups, were included to complement the three anionic functionalities on the guest. Beyond acting as a binding site, the europium complex was used to signal binding of the guest through modification of the charge transfer emission. A 1:1 complex with BPG was determined in 50% methanol/acetonitrile with a K a of 6.7×10 5 mol - 1 by monitoring the reduction of the fluorescence signal upon guest addition. In the titration of related glycolytic intermediates lacking a second phosphate (4-6) into host 1, 2:1 host to guest binding was observed. Similarly, control compound 2, which lacks the ammonium groups, binds BPG and 4-6 in a 2:1 fashion. Also, phenylphosphate 7 binds to host 1 in a 1:1 stoichiometry with a K a over three times less than 3.
Self-management: Enabling and empowering patients living with cancer as a chronic illness†‡

With recent improvements in the early detection, diagnosis, and treatment of cancer, people with cancer are living longer, and their cancer may be managed as a chronic illness. Cancer as a chronic illness places new demands on patients and families to manage their own care, and it challenges old paradigms that oncology's work is done after treatment. As a chronic illness, however, cancer care occurs on a continuum that stretches from prevention to the end of life, with early detection, diagnosis, treatment, and survivorship in between. In this article, self-management interventions that enable patients and families to participate in managing their care along this continuum are reviewed. Randomized controlled trials of self-management interventions with cancer patients and families in the treatment, survivorship, and end-of-life phases of the cancer care continuum are reviewed, and the Chronic Care Model is presented as a model of care that oncology practices can use to enable and empower patients and families to engage in self-management. It is concluded that the need for a common language with which to speak about self-management and a common set of self-management actions for cancer care notwithstanding, oncology practices can now build strong relationships with their patients and formulate mutually agreed upon care plans that enable and empower patients to care for themselves in the way they prefer.
Induction of Antimicrobial Peptides in Infected Tissues of Larval Heliothis virescens (Lepidoptera: Noctuidae)

Effective biological control of destructive heliothine larvae via application of microbial entomopathogens or parasitoids is limited by a robust immune response against infection and parasitization. To better understand the immune response of budworms against microbial entomopathogens, several orthologs of antibacterial response proteins were identified and extracted from a tobacco budworm, Heliothis virescens (F.) (Lepidoptera: Noctuidae), expressed sequence tag database for study of their upregulation by bacterial infection. Transcript sequences corresponding to precursors of 3 antimicrobial peptides from H. virescens hemolymph (virescein, heliomicin and heliocin) have been identified and their induction by bacterial elicitation analyzed. Further, a gloverin-like antibacterial and an H. virescens ortholog of the Lepidopteran hemocytespecific antibacterial Spod-X-Tox have been identified. Induction of these selected antibacterial protein transcripts by bacterial infection were quantitated using quantitative RT-PCR in hemocytes and fat bodies. Transcript levels of all were elevated by bacterial elicitation in both tissues as early as 3 hours post-treatment.
Modelling cardiac fibroblasts: interactions with myocytes and their impact on impulse propagation.

Aims Existence of myocyte–fibroblast coupling in the human heart is still a controversial question. This study aims at investigating in a biophysical model how much coupling would be necessary to perturb significantly the electrical propagation of the cardiac impulse. Methods and results A one-dimensional model representing a strand of myocytes covered by a layer of fibroblasts was formulated by reinterpreting the coupled myocyte–fibroblast system as a single unit and connecting these units using a monodomain approach. The myocyte membrane kinetics was described by the Bondarenko mouse cell model and the fibroblast response was based on an experimentally measured current–voltage curve and took into account the delayed activation of that current. Conduction and maximal upstroke velocities were reported for different fibroblast densities and myocyte–fibroblast coupling strengths during paced rhythm. A reduction in conduction and maximum upstroke velocities was observed for increasing coupling and fibroblast density, in agreement with cell culture experiments. This effect was because of an increase in the myocyte resting potential and of the fibroblasts acting as a current sink. At least 10 fibroblasts with capacitance 4.5 pF had to be connected to each myocyte with capacitance 153.4 pF to slow down the conduction by .10%. Conclusion Coupling with fibroblasts affects the myocyte resting potential and the impulse propagation, but microstructural changes and myocyte decoupling are needed to explain slow conduction in fibrotic tissue.
The State of the Discipline in American Political Science: Be Careful What You Wish For?

This article is an attempt to survey and analyse current developments in American political science with particuIar reference to the current wave of institutionalist theory. The main thrust of this article is to argue rhat the current concerns of the field are hardly new issues, but rather perennial. We argue that the current ‘state of the discipline’ is in many ways more a function of recurrent intellecrual dilemmas of a generai social scientific nature than they are about the particulars of the current debates in the field. Most relevant to a British journal, we shall attempt to ‘step outside the hermeneutic circle’, and suggest which aspects of contemporary American political science are most relevant to British polirical scientists. This article is an attempt both to survey and analyse current developments
CANINE HEARTWORMS IN COYOTES IN ILLINOIS

Canine heartworm (Dirofilaria immitis) disease affects wild canids and may be a factor impacting the health and population dynamics of coyotes (Canis latrans). Coyotes may serve also as a potential reservoir for transmission of these parasites to domestic dogs. We investigated 920 coyotes harvested by hunters and trappers throughout Illinois (USA) from 1995–1997. The objectives of the study were to: 1) survey the regional prevalence and intensity of heartworms in coyotes in Illinois, 2) determine whether heartworm intensity correlates with physical condition, particularly body weight and winter fat levels, and 3) evaluate the relationship between heartworm infections and the reproductive success of females. Prevalence of heartworms statewide was 16.0%. Prevalence was significantly higher in males (17.7%) than in females (14.1%; P=0.04) and was higher in the older age-classes (P<0.0001). The regional prevalence of heartworms increased from northern to southern Illinois. Intensity ranged from 1 to 111 with ...
Calanthe xhsinchuensis (Orchidaceae), a new natural hybrid from Taiwan

Natural hybridization in plants is a vital mechanism of speciation. Calanthe arisanensis and C. sieboldii occur in the same habitat in northern Taiwan, where there are a number of plants whose morphologically characters are similar in between of these two species. In this report, a new natural hybrid, Calanthe species – C. xhsinchuensis Y.I. Lee putatively derived from the natural hybridization of C. arisanensis and C. sieboldii was described and illustrated. Besides, somatic chromosome number was counted. The morphological and histological data of flowers, capsules, roots and leaves of C. xhsinchuensis show an intermediate condition between its putative parents. The chromosome number, 2n = 40, is also congruent with its putative parents. Color plates and line drawings are provided to aid in identification. Base on the morphological characteristics of reproductive and vegetative organs, and the distributions of putative parents, it is proposed that C. xhsinchuensis is a natural hybrid between C. arisanensis Hayata and C. sieboldii Decaisne ex Regel.
Achieving Accountability in Smart Grid

Smart grid is a promising power infrastructure that is integrated with communication and information technologies. Nevertheless, privacy and security concerns arise simultaneously. Failure to address these issues will hinder the modernization of the existing power system. After critically reviewing the current status of smart grid deployment and its key cyber security concerns, the authors argue that accountability mechanisms should be involved in smart grid designs. We design two separate accountable communication protocols using the proposed architecture with certain reasonable assumptions under both home area network and neighborhood area network. Analysis and simulation results indicate that the design works well, and it may cause all power loads to become accountable.
‘The artist’s piece is already in the stone’: Constructing creativity in paleontology laboratories

Laboratory technicians are typically portrayed as manual workers following routine procedures to produce scientific data. However, technicians in vertebrate paleontology laboratories often describe their work in terms of creativity and artistry. Fossil specimens undergo extensive preparation – including rock removal, damage repair, and reconstruction of missing parts – to become accessible to researchers. Technicians called ‘fossil preparators’ choose, apply, and sometimes invent these preparation methods. They have no formal training, no standard protocols, and few publications to consult on techniques. Despite the resulting diversity of people and practices, preparators and their work are usually absent from research publications, making them ‘invisible technicians’ in Steven Shapin’s sense. But preparators reject the view of their work as predictable or simple; in particular, many preparators value art training, the aesthetics of prepared fossils, and the process of creative problem-solving in their wo...
Direct extraction of mobility in pentacene OFETs using C-V and I-V measurements

Mobility was extracted from top-contact pentacene organic field effect transistors with minimal assumptions. Low-frequency capacitance-voltage (C-V) measurements were used to calculate the sheet charge density of the channel, and current-voltage measurements with low drain-to-source voltage were used to extract mobility. The separation of charge and mobility with the use of C-V measurements illustrates that the mobility increases with gate voltage, differing significantly from mobility dependence on gate voltage in crystal silicon MOSFETs. The physical meaning of this mobility and the possible mechanism for the increase in mobility as a function of gate bias are discussed.
Arbutus: Network-Layer Load Balancing for Wireless Sensor Networks

The hot spot problem is a typical byproduct of the many-to-one traffic pattern that characterizes most wireless sensor networks: the nodes with the best channel to the sink are overloaded with traffic from the rest of the network and experience a faster energy depletion rate than their peers. Routing protocols for sensor networks typically use a reliability metric to avoid lossy links and thus directly exacerbate the problem. Significant advantages can be obtained by embedding a load balancing scheme at the network layer, as we show with the design and implementation of Arbutus, a novel routing protocol for wireless sensor networks with a built-in load balancing scheme. By imposing a special structure on the collection tree, privileging longer hops, and accounting for network load in the route selection process, Arbutus reduces the impact of hot spots on network lifetime without a deterioration of the end-to-end reliability performance. An implementation of Arbutus on Berkeley motes and the MoteLab testbed shows a 30% reduction in the network traffic load needed to achieve the same packet delivery rate as an existing mote-oriented protocol. This provides key benefits such as a significant lifetime gain and increased fault tolerance.
Emotional approach coping and self-efficacy moderate the effects of written emotional disclosure and relaxation training for people with migraine headaches.

Objectives—We tested whether emotional skills and headache management self-efficacy (HMSE) moderated effects of written emotional disclosure (WED) compared to control writing and a different intervention, relaxation training (RT). Design/Methods—Undergraduates with migraine headaches reported emotional approach coping (EAC) and HMSE; were randomized to WED, RT, or control; and assessed on health measures at baseline and 3-month follow-up. Results—Greater EAC predicted improvement following WED compared to RT and control, whereas low HMSE predicted improvement following both WED and RT, compared to control. Conclusions—Emotional skill may specifically—and low health management self-efficacy may generally—predict positive responses to WED. Written emotional disclosure (WED) has modest benefits for people with health problems, but personality differences likely moderate its effects. Also, comparing WED to another intervention can test whether moderators are specific to WED or general to various interventions. Relaxation training (RT) may be an ideal comparison intervention. We hypothesized that having emotional skills predicts benefits of WED, but may be irrelevant for RT. In contrast, being low in self-efficacy to manage health problems may predict benefits of both interventions. We tested these two moderators on the effects of WED, RT, and neutral control writing in young adults with migraine headaches.
A2-5: Addressing Missing Data and Clinical Relapse Can Improve Composite Diabetes Quality of Care Measure

Background/Aims To identify strategies likely to improve composite measures of diabetes care quality.
Using scratchpad to exploit object locality in Java

Performance of modern computers is tied closely to the effective use of cache because of the continually increasing speed discrepancy between processors and main memory. We demonstrate that generational garbage collection employed by a system with cache and scratchpad memory can take advantage of the locality of small short-lived objects in Java and reduce memory traffic by as much as 20% when compared to a cache-only configuration. Converting half of the cache to scratchpad can be more effective at reducing memory traffic than doubling or even quadrupling the size of the cache for several of the applications in SPECjvm98.
Overview of curricular approaches

Institutions use both programmatic and curricular approaches to address students' transition to life after college. While Chapter Four discusses the programmatic approaches, this chapter provides an overview of the curricular approaches.
WDM protocol-transparent distance extension using R2 remodulation

In computer networks using wavelength-division multiplexing (WDM), it is often necessary to extend the length of a given WDM path beyond that of a single segment whose length Is limited by the link budget. While wavelength-flattened optical amplifiers are the most obvious solution, this paper calls attention to a simple (albeit less efficient) alternative that works for any number of wavelength channels, but only a modest number of segments and modest bit rates. This scheme substitutes for each optical amplifier stage a multiwavelength 2R remodulator consisting of a WDM demultiplexor, followed by wavelength-by-wavelength zero-crossing detectors, then remodulation wavelength by wavelength, and finally wavelength-division multiplexing back onto a single fiber. Theory and experimental results confirm the usefulness of this primitive technique, which can also be used for add-and-drop links, for wavelength routing or wavelength conversion in scalable wavelength routing networks, for internetwork gateways, and for other applications.
Responses to robot social roles and social role framing

Promoting dependents' perceptions of point-of-injury care robots as social actors may elicit feelings of companionship and diminish stress. However, numerous rescuers may control these robots and communicate with dependents through the robot, creating communication and interaction challenges that may be best addressed by creating a pure medium robot expressing no social identity. In addition, setting dependents' expectations regarding the robot's social role may improve perceptions of the robot and trust in the robot's suggestions. In a 3 (role: pure medium vs. social medium vs. social actor) × 2 (framing: framed vs. unframed) between-participants design, participants interacted with a simulation of a robot in a search and rescue context (N=84). Robot social behavior decreased participants' fear, yet made participants feel more isolated. Framing generated increased trust in the robot. Implications for the theory and design of robots and human-robot interaction are discussed.
Analysis of Multiparameter Flow Cytometric Data

Today, most flow cytometric (FCM) measurements are multiparameter measurements of cells or cellular components. Analysis of these complex data requires that the experimenter become intimately familiar with the data in order to extract meaningful information. Here we will discuss some aspects of the analysis of multivariate flow cytometric data. However, drawing conclusions through the statistical analysis of measurements made on numerous samples will not be discussed. The statistics of intra-sample comparisons are discussed in numerous nonparametric statistics texts. As will become clear, the approach presented here will be primarily graphical versus statistical.
Cyclic homology, Serre's local factors and the -operations

We show that for a smooth, projective variety X defined over a number field K, cyclic homology with coefficients in the ringA∞ = Q ν|∞ Kν, provides the right theory to obtain, using the λ-operations, Serre’s archimedean local factors of the complex Lfunction of X as regularized determinants. Contents
Preliminary pharmacokinetic evaluation of Albuleukin; an interleukin-2 human serum albumin fusion protein, in solid tumor patients

4757 Albuleukin is a novel therapeutic protein generated by the fusion of the human serum albumin and interleukin-2 genes. It was hypothesized that fusion to albumin would combine the short-acting but potent pharmacological activity of interleukin-2 and the favorable pharmacokinetic properties of albumin. Two Phase 1 clinical trials of Albuleukin are ongoing in patients with solid tumors. The objective of these studies is to determine the safety, tolerability, and pharmacokinetics of subcutaneously administered Albuleukin. In the first trial, doses of 2.0, 6.6, 22and 44 μg/kg of Albuleukin have been given every 2 weeks. In the second study, doses of 1.0, 3.3, 11 and 22 μg/kg have been administered weekly. Plasma samples for pharmacokinetic analysis were obtained at times out to one week following dosing. Plasma Albuleukin concentrations following the 1.0 μg/kg dose were below the 2 ng/mL limit of quantitation. Albuleukin was detectable in 4/5 patients given a 2.0 μg/kg dose, and in all patients at higher doses. Absorption of Albuleukin was prolonged with the Cmax occurring approximately 24-48 hours after dosing. The Cmax increased linearly with increasing dose, from a low of 6.4 ± 4.7 ng/mL after a 2.0 μg/kg dose to a high of 149 ± 76 ng/mL following a dose of 44 μg/kg. Plasma concentration curves suitable for calculation of terminal phase parameters were obtained following doses of 11, 22 and 44 μg/kg. The terminal half-life (t1/2) is 14 to 15 hours following the first SC dose of Albuleukin and is considerably longer than the reported 85-minute t1/2 for IV IL-2. The average mean residence time was between 46 and 50 hours. In most patients receiving more than one cycle of treatment, Cmax was 40-80% lower in the second and subsequent courses of Albuleukin than in the first course. Immunogenicity testing showed that subjects had not developed anti-Albuleukin antibodies that could account for the altered PK. Decreases in Cmax following multiple doses of IL-2 have been previously reported in the literature and were associated with increases in soluble IL-2 receptors. Increases in soluble IL-2 receptors have been observed following dosing with Albuleukin. The relationship between the decreased Albuleukin plasma concentrations and increased soluble IL-2 receptors will be further explored as more data become available.
Analysis of FPGA-Based Reconfiguration Methods for Mobile and Embedded Applications

As mobile and handheld devices are gaining popularity, many applications have found their way into these devices. Apart from optimized hardware-software architectures, new techniques and design methodologies are needed to support applications running on mobile systems. FPGA-based dynamic reconfigurable systems are currently the most feasible option to deliver embedded applications that have stringent requirements. There are different methods of reconfiguring the hardware on chip dynamically. Selecting a specific reconfiguration method and designing the corresponding hardware architectures for an application are important and challenging tasks in reconfigurable computing systems. In this work, we investigate different FPGA-based reconfiguration methods; study their features, advantages and disadvantages; and analyze the reconfiguration time and space overhead for each method.
Case Study Research Putting the Quant Into the Qual

Case studies are usually considered a qualitative method. However, some aspects of case study research—notably, the selection of cases—may be viewed through a quantitative template. In this symposium, we invite authors to contemplate the ways in which case study research might be conceived, and improved, by applying lessons from large-n cross-case research.
Electrical events during activation and inhibition of gastric HCl secretion.

A brief review of some of the relationships between the secretory rate and the electrophysiological characteristics of the canine and frog gastric mucosa is presented. There is no simple relationship between the potential difference (PD) and H+ rate in the in vitro frog gastric mucosa with standard Cl– bathing solutions. In contrast, with Cl– - free solutions (PD is inverted) there is a precise linear relationship between the PD and the H+ rate. This linear relationship is strong support for the concept that the H+ mechanism under these conditions is electrogenic. In the past it has been difficult rigorously to exclude the possibility that the inverted PD is due to a liquid junction potential between acid fluid in the lumina and the secretory bathing solution. Use of aminopyrine or imidazole essentially eliminates the possibility that the inverted PD is due to a liquid junction potential. Hence the linear relationship is solid evidence for the electrogenicity of the H+ mechanism. Recently we have shown that aminopyrine or imidazole can reverse thiocyanate inhibition of H+ secretion.
Attempts to overcome the anti-fertility effect of intrauterine plastic spirals in the ewe.

A study was conducted to determine whether the antifertilization of intrauterine devices in ewes could be overcome by the use of hormones or drugs that either stimulate or inhibit uterine motility. 44 parous western ewes were unilaterally ovariectomized and a plastic spiral was inserted into the uterine horn opposite the remaining ovary. Spirals were immediately removed from 5 ewes. At the time of mating 2 weeks to 3 months post surgery sham-operated and spiral control ewes were injected with saline solution. Ewes with spirals were injected with either estradiol epinephrine oxytocin oxytocin and acetylcholine or oxytocin acetylcholine and physostigmine. Other ewes with spirals were laparotomized and either the uterus was massaged or the cervical lumen was cleaned. 3 days postmating 8 ova recovered from 5 sham-operated ewes were all cleaved with a mean of 90 accessory sperm in the zonae pellucidae. 3 of 12 ova recovered from 8 spiral control ewes were cleaved. Only 1 of 40 ova recovered from 28 treated ewes was cleaved. Accessory sperm were not found in either cleaved or uncleaved ova from any spiral ewe. None of the treatments overcame the antifertilization effect of the spiral.
Determinants of mental health treatment seeking among soldiers who recognize their problem: implications for high-risk occupations

ABSTRACTAlthough research has documented an increased risk of mental health problems among employees in high-stress occupations, little attention has been devoted to the process by which employees seek treatment for these problems. Using components of the Stages of Change Model (Prochaska & DiClemente, 1982), this study examined the correlates of considering and receiving treatment for such problems among active-duty military personnel in the U.S. Army. A multidimensional assessment of determinants of treatment seeking was administered to 1725 military personnel, along with measures of mental health symptoms and treatment seeking. These determinants were examined as predictors of considering and receiving treatment among a sub-sample of 466 personnel who recognized having a current mental health problem. Multinomial logistic regressions indicated that attitudes towards treatment and a preference for self-reliance distinguished those considering treatment from those who had not sought treatment. A larger n...
Newly Designed Quinolinol Inhibitors Mitigate the Effects of Botulinum Neurotoxin A in Enzymatic, Cell-Based, and ex Vivo Assays.

Botulinum neurotoxin A (BoNT/A) is one of the most deadly toxins and is the etiological agent of the potentially fatal condition, botulism. Herein, we investigated 8-hydroxyquinoline (quinolin-8-ol) as a potential inhibitor scaffold for preventing the deadly neurochemical effects of the toxin. Quinolinols are known chelators that can disrupt the BoNT/A metalloprotease zinc-containing active site, thus impeding its proteolysis of the endogenous protein substrate, synaptosomal-associated protein 25 (SNAP-25). By use of this information, the structure–activity relationship (SAR) of the quinolinol-5-sulfonamide scaffold was explored through preparation of a crude sulfonamide library and evaluation of the library in a BoNT/A LC enzymatic assay. Potency optimization of the sulfonamide hit compounds was undertaken as informed by docking studies, granting a lead compound with a submicromolar Ki. These quinolinol analogues demonstrated inhibitory activity in a cell-based model for SNAP-25 cleavage and an ex vivo a...
Abstract A31: 14-3-3 binding sites in full-length and splice variant forms of BRAF V600E modulate the response to RAF inhibitors

The serine/threonine kinase BRAF is mutated in 7% of human cancers, the most frequent alteration being a valine to glutamic acid substitution at amino acid 600 (V600E). BRAF V600E melanomas are highly sensitive to RAF inhibitors but the expression of aberrantly spliced BRAF V600E (BRAF V600E ΔEx) isoforms are associated with resistance in 13-30% of progressing patients. Compared to full-length BRAF V600E, BRAF V600E ΔEx exhibit enhanced dimerization and signaling via ERK1/2 during RAF inhibitor therapy; however, much remains unknown regarding their mechanism of action. The 14-3-3 protein binding sites, serine 365 (S365) and serine 729 (S729), play a complex role in regulating the activity and dimerization of RAF isoforms. All reported BRAF V600E ΔEx isoforms lose the N-terminal 14-3-3 binding site (S365) but retain the C-terminal site (S729); therefore, we analyzed the involvement of 14-3-3 binding sites in response to RAF inhibitor therapy. In full-length BRAF V600E, mutation of S365 to alanine promotes elevated MEK-ERK1/2 signaling and growth in the presence of RAF inhibitor. BRAF V600E ΔEx exhibits increased phosphorylation on S729 during RAF inhibitor therapy. Mutation of S729 to alanine renders the BRAF V600E ΔEx isoforms sensitive to RAF inhibitor, measured by reduced ERK1/2 phosphorylation and cell growth in vitro and in vivo. These data highlight the importance of BRAF V600E 14-3-3 binding sites in mediating targeted therapy resistance in mutant BRAF-driven melanoma. Citation Format: Michael J. Vido, Kaitlyn Le, Justin Rock, Edward J. Hartsough, Neda Dadpey, Andrew E. Aplin. 14-3-3 binding sites in full-length and splice variant forms of BRAF V600E modulate the response to RAF inhibitors. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A31.
Mitochondrial proteostasis as a shared characteristic of slowed aging: the importance of considering cell proliferation

Proteostasis is one of the seven "pillars of aging research" identified by the Trans-NIH Geroscience Initiative and loss of proteostasis is associated with aging and age-related chronic disease. Accumulated protein damage and resultant cellular dysfunction are consequences of limited protein repair systems and slowed protein turnover. When relatively high rates of protein turnover are maintained despite advancing age, damaged proteins are more quickly degraded and replaced, maintaining proteome fidelity. Therefore, maintenance of protein turnover represents an important proteostatic mechanism. However, measurement of protein synthesis without consideration for cell proliferation can result in an incomplete picture, devoid of information about how new proteins are being allocated. Simultaneous measurement of protein and DNA synthesis provides necessary mechanistic insight about proteins apportioned for newly proliferating cells versus for somatic maintenance. Using this approach with a number of murine models of slowed aging shows that, compared to controls, energetic resources are directed more toward somatic maintenance and proteostasis, and away from cell growth and proliferation. In particular, slowed aging models are associated with heightened mechanisms of mitochondrial proteostatic maintenance. Taking cell proliferation into account may explain the paradoxical findings that aging itself and slowed aging interventions can both be characterized by slower rates of protein synthesis.
Pre-existing malignancy results in increased prevalence of distinct populations of CD4+ T cells during sepsis.

The presence of pre-existing malignancy in murine hosts results in increased immune dysregulation and risk of mortality following a septic insult. Based on the known systemic immunologic changes that occur in cancer hosts, we hypothesized that the presence of pre-existing malignancy would result in phenotypic and functional changes in CD4+ T cell responses following sepsis. In order to conduct a non-biased, unsupervised analysis of phenotypic differences between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor cells and tumors were allowed to grow for 3 weeks. These cancer hosts and age-matched non-cancer controls were then subjected to CLP. Splenocytes were harvested at 24h post CLP and flow cytometry and SPADE (Spanning-tree Progression Analysis of Density-normalized Events) were used to analyze populations of CD4+ cells most different between the two groups. Results indicated that relative to non-cancer controls, cancer mice contained more resting memory CD4+ T cells, more activated CD4+ effectors, and fewer naive CD4+ T cells during sepsis, suggesting that the CD4+ T cell compartment in cancer septic hosts is one of increased activation and differentiation. Moreover, cancer septic animals exhibited expansion of two distinct subsets of CD4+ T cells relative to previously healthy septic controls. Specifically, we identified increases in both a PD-1hi population and a distinct 2B4hi BTLAhi LAG-3hi population in cancer septic animals. By combining phenotypic analysis of exhaustion markers with functional analysis of cytokine production, we found that PD-1+ CD4+ cells in cancer hosts failed to make any cytokines following CLP, while the 2B4+ PD-1lo cells in cancer mice secreted increased TNF during sepsis. In sum, the immunophenotypic landscape of cancer septic animals is characterized by both increased CD4+ T cell activation and exhaustion, findings that may underlie the observed increased mortality in mice with pre-existing malignancy following sepsis.
Seeing cilia: imaging modalities for ciliary motion and clinical connections

The respiratory tract is lined with multiciliated epithelial cells that function to move mucus and trapped particles via the mucociliary transport apparatus. Genetic and acquired ciliopathies result in diminished mucociliary clearance, contributing to disease pathogenesis. Recent innovations in imaging technology have advanced our understanding of ciliary motion in health and disease states. Application of imaging modalities including transmission electron microscopy, high-speed video microscopy, and micron-optical coherence tomography could improve diagnostics and be applied for precision medicine. In this review, we provide an overview of ciliary motion, imaging modalities, and ciliopathic diseases of the respiratory system including primary ciliary dyskinesia, cystic fibrosis, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis.
A Brief History of the Cochlear Implant and Related Treatments

Abstract The first cochlear implants (CIs) provided an awareness of environmental sounds and some assistance in speechreading (including lipreading), but no recognition of speech was possible with the CI alone. In contrast, modern CIs enable high levels of speech recognition with the CI alone for the great majority of users. Indeed, most of today’s users converse routinely via the telephone, even with previously unfamiliar persons at the other end and discussing unpredictable and changing topics. That ability is a long trip from total or nearly total deafness, and represents the first substantial restoration of a human sense using a medical intervention. In this chapter we describe five large steps forward that in retrospect led to the modern CI and related treatments. The CI is now widely regarded as one of the great advances in medicine and is a triumph of bioengineering, medicine, and neuroscience, among other disciplines.
Multi-aperture phased arrays versus multi-beam lens arrays for mmW multiuser MIMO

Multi-beamforming and data multiplexing is a key functionality for realizing the spatial multiplexing gains in multiuser MIMO systems at millimeter-wave (mmW) frequencies. Due to prohibitive complexity of conventional digital beamforming, two main approaches to hybrid analog-digital beamforming are being investigated that use either phased arrays or lens arrays for analog beamforming. While the two approaches are equivalent from a purely communication-theoretic perspective, they offer very different tradeoffs in terms of performance, complexity and power consumption. In particular, all existing phased array-based prototypes are limited to a single beam per aperture, due to hardware constraints, thereby necessitating the use of multiple smaller sub-arrays for multi-beam operation. On the other hand, the beam switching network presents a hardware challenge in lens array-based systems, thereby limiting the coverage achieved by particular radio-frequency chain. In this paper, we apply the beamspace MIMO framework to compare the achievable sum-rates in a small cell served by an access point using a lens array-based or phased array-based architecture. We also discuss the hardware complexity of the two architectures to enable performance-complexity-energy optimization.
Fit-for-purpose block polymer membranes molecularly engineered for water treatment

Continued stresses on fresh water supplies necessitate the utilization of non-traditional resources to meet the growing global water demand. Desalination and hybrid membrane processes are capable of treating non-traditional water sources to the levels demanded by users. Specifically, desalination can produce potable water from seawater, and hybrid processes have the potential to recover valuable resources from wastewater while producing water of a sufficient quality for target applications. Despite the demonstrated successes of these processes, state-of-the-art membranes suffer from limitations that hinder the widespread adoption of these water treatment technologies. In this review, we discuss nanoporous membranes derived from self-assembled block polymer precursors for the purposes of water treatment. Due to their well-defined nanostructures, myriad chemical functionalities, and the ability to molecularly-engineer these properties rationally, block polymer membranes have the potential to advance water treatment technologies. We focus on block polymer-based efforts to: (1) nanomanufacture large areas of high-performance membranes; (2) reduce the characteristic pore size and push membranes into the reverse osmosis regime; and (3) design and implement multifunctional pore wall chemistries that enable solute-specific separations based on steric, electrostatic, and chemical affinity interactions. The use of molecular dynamics simulations to guide block polymer membrane design is also discussed because its ability to systematically examine the available design space is critical for rapidly translating fundamental understanding to water treatment applications. Thus, we offer a full review regarding the computational and experimental approaches taken in this arena to date while also providing insights into the future outlook of this emerging technology.
Relationship Satisfaction: Impact and Consequences for Women's Emotional Health and Treatment

This study uses feminist theory to examine the variables of relationship length and relationship satisfaction as predicators of both self-esteem and emotional functioning for women. Using a national sample of data gathered from 1,257 female survey respondents this study found significant relationships between emotional functioning, self-esteem, and self-reported relationship satisfaction which was supported by regression testing and path analysis. In addition, a significant negative relationship was noted between a woman's self-esteem and her with-holding of verbalized displeasure or disagreement with her partner. Implications for women in therapy were discussed.
Untangling the web from DNS

The Web relies on the Domain Name System (DNS) to resolve the hostname portion of URLs into IP addresses. This marriage-of-convenience enabled the Web's meteoric rise, but the resulting entanglement is now hindering both infrastructures--the Web is overly constrained by the limitations of DNS, and DNS is unduly burdened by the demands of the Web. There has been much commentary on this sad state-of-affairs, but dissolving the ill-fated union between DNS and the Web requires a new way to resolve Web references. To this end, this paper describes the design and implementation of Semantic Free Referencing (SFR), a reference resolution infrastructure based on distributed hash tables (DHTs).