cssi/SciSciGPT-SciSciNet huggingface dataset:
Functional Somatic and Germline Variants in the NF-κB Pathway in Chronic Lymphocytic Leukemia

Abstract Abstract 560 Nuclear factor kappa B (NF-κB) encompasses a family of transcription factors involved in oncogenic processes including cellular proliferation and apoptotic inhibition. Constitutive activation of NF-κB has been observed in hematologic malignancies and is thought to confer resistance to chemotherapeutic agents. Here, we examine the role of the NF-κB pathway in chronic lymphocytic leukemia (CLL). Whole-exome sequencing was performed using tumor and matched germline DNA from 167 CLL patients. We identified 51 patients (30%) carrying 53 non-silent somatic variants in genes of the canonical NF-κB pathway, which consists of 272 genes as defined by the Ingenuity Pathway Analysis tool. Of the 99 patients whose germline sequences have been analyzed to date, 27 patients (27%) carry 34 non-silent germline variants in NF-κB pathway genes. A total of 67 patients (40%) have at least one non-silent somatic or germline variant. Variants in the NFKB1 gene, itself, were also observed: a somatic variant, H66R, found in two patients, and two germline variants, Y89F and R849W, each found in one patient. To evaluate the functional consequences of the NFKB1 variants, we performed site-directed mutagenesis to generate full-length NFKB1 cDNAs encoding these variants. We subsequently measured transcriptional activity of wild-type and mutant NFKB1 via luciferase assays in HEK293T cells using reporter cassettes containing the NFKB1 response element. Transcriptional activity of the three NFKB1 variants was found to be at least 2-fold higher than that of wild-type NFKB1 (p To test the hypothesis that deregulation of the NF-κB pathway is a key mechanism in CLL, we compared gene expression profiles of NF-κB pathway genes between CLL patient samples (n=146) and normal B cells (n=16) and found overall upregulation of the NF-κB pathway in CLL (Kolmogorov-Smirnov test, p=2.2e-16). K-means clustering and principal component analysis (PCA) further revealed that CLL patients can be divided into two subgroups exhibiting differential magnitude of NF-κB pathway upregulation. Studies in progress aim to identify the clinical significance of these subgroups. Finally, we assessed the effect of inhibiting the NF-κB pathway using the cell permeant NF-κB inhibitor, SN50. We performed Annexin V/PI staining 24 hours post-treatment in CLL cells with (n=9) or without (n=3) NF-κB pathway variants. SN50 increased cell death 1.8-fold in all cells tested (p In conclusion, our findings demonstrate that a high proportion of CLL patients harbor somatic and germline variants in NF-κB pathway genes, some of which appear to be functional. Furthermore, the NF-κB pathway is upregulated in CLL and pharmacological inhibition of the pathway leads to increased cancer cell death. Functional characterization of NF-κB pathway variants offers mechanistic insight into the disease, providing novel targets for therapy. Disclosures: No relevant conflicts of interest to declare.
Design Considerations for Insulator Metal Transition based Artificial Neurons

This work presents an Insulator Metal Transition (IMT) based Integrate-And-Fire (IAF) neuron. The proposed neuron leverages the switching mechanism of the IMT device to deliver the neuron functionality without the need for complex CMOS circuitry. The IMT neuron parameters such as the threshold voltage and the refractory period, however, are dependent on the device parameters. Design expressions for the IMT neuron are derived. These expressions can aid designers choosing the proper circuit variables given a specific IMT device with a particular set of device parameters.
Formal verification of NCL circuits

In this chapter, the author describe an equivalence checking methodology for NULL Convention Logic (NCL) circuits. Note that currently, there are no commercial equivalence checkers for quasi-delay insensitive (QDI) circuits. For commercial applications, NCL circuits, and QDI circuits in general, are often synthesized from synchronous intellectual property designs. The resulting NCL design may then be further optimized and tinkered with. Therefore, the author have designed an equivalence checker that can be used in two ways: (1) to verify the functional equivalence of two NCL designs and (2) to verify the equivalence between an NCL design and a synchronous design.
Primary Care Is an Essential Ingredient to a Successful Population Health Improvement Strategy

Primary care teams bridge health care to other sectors, making effective connections between health care and health. For health care systems to improve patient and population health, the important role of primary care must be recognized, celebrated, and strengthened. This commentary explores several of the current hot topics in policy discussions (eg, social determinants of health, population health) and gives examples of how these theoretical discussions are relevant to the real world of patient care. It concludes with a few key points on how the system can better support the important population health improvement work done by primary care teams. Changes in the way primary care is delivered, reimbursed, and measured are needed to support the health promoting and healing work that happens continuously, not just during a clinic visit or inside the clinic walls. Renewed investments must be made to strengthen delivery models that enable longitudinal, trusting relationships to develop between patients and primary care teams. Payment systems must shift away from fee-for-service models to new holistic reimbursement methods that reflect the value of a comprehensive scope of primary care practice and continuity of care. Measuring what matters in primary care will help to realign our focus on health.
Trolling as a Collective Form of Harassment: An Inductive Study of How Online Users Understand Trolling:

Rising media and academic concerns for the social implications of online trolling require that scholars understand how everyday users conceptualize trolling. The validity of survey instruments may ...
Chapter 10 – Agarose Gels

Those who work with DNA and RNA will often need a means to verify work they have performed on these polymers, or perhaps they will need to separate sequences on the basis of size. Agarose gels are porous entities that, when placed in an electric field, provide a simple way to perform these tasks. In this chapter, we will cover the basics of agarose gels and examine three common and very important applications that utilize agarose gel electrophoresis.
Nonlinear Optimal Velocity Car Following Dynamics (II): Rate of Convergence In the Presence of Fast Perturbation

Traffic flow models have been the subject of extensive studies for decades. The interest in these models is both as the result of their important applications as well as their complex behavior which makes them theoretically challenging. In this paper, an optimal velocity dynamical model is considered and analyzed. We consider a dynamical model in the presence of perturbation and show that not only such a perturbed system converges to an averaged problem, but also we can show its order of convergence. Such understanding is important from different aspects, and in particular, it shows how well we can approximate a perturbed system with its associated averaged problem.
Refined diagnosis of hydatidiform moles with p57 immunohistochemistry and molecular genotyping: updated analysis of a prospective series of 2217 cases.

Immunohistochemical analysis of p57 expression and molecular genotyping accurately subclassify molar specimens into complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) and distinguish these from nonmolar specimens. Characteristics of a prospective series of potentially molar specimens analyzed in a large gynecologic pathology practice are summarized. Of 2217 cases (2160 uterine, 57 ectopic), 2080 (94%) were successfully classified: 571 CHMs (570 uterine, 1 ectopic), 498 PHMs (497 uterine, 1 ectopic), 900 nonmolar (including 147 trisomies, 19 digynic triploids, and 4 donor egg conceptions), and 56 androgenetic/biparental mosaics; 137 were complex or unsatisfactory and not definitively classified. CHMs dominated in patients aged 45 years and were the only kind of molar conception found in the latter group. Of 564 successfully immunostained CHMs, 563 (99.8%) were p57-negative (1 p57-positive [retained maternal chromosome 11] androgenetic by genotyping). Of 153 genotyped CHMs, 148 (96.7%) were androgenetic (85% monospermic) and 5 were biparental, the latter likely familial biparental hydatidiform moles. Of 486 successfully immunostained PHMs, 481 (99%) were p57-positive (3 p57-negative [loss of maternal chromosome 11], 2 unknown mechanism). Of 497 genotyped PHMs, 484 (97%) were diandric triploid (99% dispermic) and 13 were triandric tetraploid (all at least dispermic). Of 56 androgenetic/biparental mosaics, 37 had a p57-negative complete molar component (16 confirmed as androgenetic by genotyping). p57 expression is highly correlated with genotyping, serving as a reliable marker for CHMs, and identifies molar components and androgenetic cell lines in mosaic conceptions. Correlation of morphology, p57 expression, genotyping data, and history are required to recognize familial biparental hydatidiform moles and donor egg conceptions, as the former can be misclassified as nonmolar and the latter can be misclassified as dispermic CHM on the basis of isolated genotyping results.
Larval intelligence: Approaching AI in terms of Deleuze’s “system of the dissolved self”

In this article, the work of Gilles Deleuze, specifically in his 1968 book, Difference and Repetition, is investigated in order to make a contribution at a philosophical and conceptual level to the...
The Impact of Upper Lateral Cartilage Release on Patient-Perceived Nasal Appearance and Obstruction

Objectives/hypothesis Although upper lateral cartilages are commonly released from the dorsum of the septum during spreader graft placement in septorhinoplasty (SRP), there has been a focus on maintaining integrity of connections in the middle vault. Avoiding release of upper lateral cartilages in certain patient groups may represent an early step in this paradigm shift. We aim to assess satisfaction with nasal appearance and correction of nasal obstruction in patients who underwent SRP with spreader graft placement without upper lateral cartilage release and compared it to the traditional upper lateral cartilage release cohort. Study design Prospective cohort study. Methods A total of 559 patients who underwent SRP with spreader graft placement with upper lateral cartilage release and 30 patients who underwent SRP with spreader graft placement without release between 2012 and 2020 were administered the Nasal Obstruction Symptom Evaluation (NOSE), FACE-Q Satisfaction with Nose, and FACE-Q Social Functioning scales pre- and postoperatively. Pre- and postoperative NOSE FACE-Q, and negative inspiratory force (NIF) scores and changes were compared between groups. Results Results demonstrated clinically and statistically significant improvement at follow-up for both groups. There was no significant difference between groups in mean improvement of NOSE, FACE-Q, and NIF scores at time of last follow-up. Conclusion SRP with spreader graft placement with and without upper lateral cartilage release provide clinically and statistically significant improvement, and no significant difference in functional outcome. This suggests that upper lateral cartilages do not need to be released to achieve functional improvement and that surgeons should consider whether release is necessary to achieve goals of surgery. Level of evidence 3 Laryngoscope, 2021.
Distributed Multi-Robot Localization

This paper presents a new approach to the cooperative localization problem, namely distributed multi-robot localization. A group of M robots is viewed as a single system composed of robots that carry, in general, different sensors and have different positioning capabilities. A single Kalman filter is formulated to estimate the position and orientation of all the members of the group. This centralized schema is capable of fusing information provided by the sensors distributed on the individual robots while accommodating independencies and interdependencies among the collected data. In order to allow for distributed processing, the equations of the centralized Kalman filter are treated so that this filter can be decomposed into M modified Kalman filters each running on a separate robot. The distributed localization algorithm is applied to a group of 3 robots and the improvement in localization accuracy is presented.
Explaining the Rising Concentration of Banking Assets in the 1990s

In recent years, the nation's largest bank holding companies have sharply increased their market share of assets. Have these institutions achieved their dominance by expanding their existing subsidiaries or by merging with other bank holding companies? A study of industry data for 1990-99 suggests that the increased market share of the largest companies is attributable almost entirely to external growth through mergers and acquisitions.
Union Organizing and Labor Outreach in the Contemporary United States

Despite their long decline, labor unions increasingly find themselves in the news. From the spirited debate over income inequality, to fights over minimum wage and the unlikely mobilization of fast food workers at the very bottom of the American labor market, labor issues are of great public interest. In this article, I review scholarship on contemporary union organizing and outreach activity. This work suggests that while innovative organizing and outreach strategies, sometimes lumped together under the rubric of “social movement unionism” and “alt-labor,” are demonstrated to be effective in advancing union causes, only a handful of unions appear to have the will and resources to utilize them. Moreover, while the implementation of new organizing and outreach strategies has been uneven and has not boosted union membership nationally, organized resistance to unions, from court rooms to state legislatures, has increased substantially.
Shape Models and Object Recognition

This paper discusses some problems that should be addressed by future object recognition systems.
Development and validation of a UPLC‐MS/MS method for the determination of 7‐hydroxymitragynine, a μ‐opioid agonist, in rat plasma and its application to a pharmacokinetic study

A simple, sensitive and specific ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine the concentrations of 7-hydroxymitragynine in rat plasma. Following a single-step liquid–liquid extraction of plasma samples using chloroform, 7-hydroxymitragynine and the internal standard (tryptoline) were separated on an Acquity UPLCTM BEH C18 (1.7 µm, 2.1 × 50 mm) column using an isocratic elution at a flow rate of 0.2 mL/min. The mobile phase consisted of 0.1% acetic acid in water and 0.1% acetic acid in acetonitrile (10:90, v/v). The run time was 2.5 min. The analysis was carried out under the multiple reaction-monitoring mode using positive electrospray ionization. Protonated ions [M + H]+ and their respective product ions were monitored at the following transitions: 415 190 for 7-hydroxymitragynine and 173 144 for the internal standard. The calibration curve was linear over the range of 10–4000 ng/mL (r2 = 0.999) with a lower limit of quantification of 10 ng/mL. The extraction recoveries ranged from 62.0 to 67.3% at concentrations of 20, 600 and 3200 ng/mL). Intra- and inter-day assay precisions (relative standard deviation) were <15% and the accuracy was within 96.5–104.0%. This validated method was successfully applied to quantify 7-hydroxymitragynine in rat plasma following intravenous administration. Copyright © 2013 John Wiley & Sons, Ltd.
Phase I Trial of Twice-Weekly Gemcitabine and Concurrent Radiation in Patients With Advanced Pancreatic Cancer

PURPOSE: To determine the maximum-tolerated dose, dose-limiting toxicities, and potential antitumor activity of twice-weekly gemcitabine and concurrent radiation in patients with locally advanced pancreatic cancer. PATIENTS AND METHODS: Nineteen patients with histologically confirmed adenocarcinoma of the pancreas were studied at the Wake Forest University Baptist Medical Center and the University of North Carolina at Chapel Hill. The initial dose of gemcitabine was 20 mg/m2 by 30-minute intravenous infusion each Monday and Thursday for 5 weeks concurrent with 50.4 Gy of radiation to the pancreas. Gemcitabine doses were escalated in 20-mg/m2 increments in successive cohorts of three to six additional patients until dose-limiting toxicity was observed. RESULTS: The dose-limiting toxicities at 60 mg/m2 given twice-weekly were nausea/vomiting, neutropenia, and thrombocytopenia. Twice-weekly gemcitabine at a 40-mg/m2 dose was well tolerated. Of the eight patients eligible for a minimum follow-up of 12 months,...
Management of hereditary thyroid cancer in children

Hereditary thyroid cancer in childhood occurs in the setting of Multiple Endocrine Neoplasia types 2A and 2B, and familial medullary thyroid carcinoma, FMTC. Prophylactic thyroidectomy in childhood has been recommended in patients found to have inherited mutations in the RET protooncogene, to prevent the development of medullary thyroid carcinoma. In this report are presented the clinical and genetic aspects of hereditary thyroid cancer in children, as well as surgical recommendations and medium-term outcome results.
Retention rates of rufinamide in pediatric epilepsy patients with and without Lennox—Gastaut Syndrome

Summary Objective To evaluate the effectiveness of rufinamide (RFM) in patients with Lennox–Gastaut Syndrome (LGS) compared to those with other epilepsy syndromes using time to treatment failure (retention rate) as the outcome measure. Methods In this retrospective cohort study, characteristics and outcomes of all patients receiving RFM in 2009 and 2010 were recorded. The primary outcome measure was RFM failure, defined as discontinuation of RFM or initiation of an additional antiepileptic therapy. The secondary outcome measure was discontinuation of RFM. Kaplan–Meier method survival curves were generated for time to RFM failure, for all patients and by the presence or absence of Lennox Gastaut Syndrome (LGS). The impact of age, seizure type, fast or slow drug titration, and concomitant therapy with valproate on retention rate were evaluated using Cox regression models. Results One hundred thirty-three patients were included, 39 (30%) of whom had LGS. For all patients, the probability of remaining on RFM without additional therapy was 45% at 12 months and 30% at 24 months. LGS diagnosis was an independent predictor of time to RFM failure (HR 0.51, 95% CI 0.31–0.83), with a median time to failure of 18 months in LGS compared to 6 months in all others ( p =0.006). Conclusions In a broad population of children with refractory epilepsy, around half will continue taking the medication for at least a year without additional therapy. Patients with LGS are two times more likely to continue RFM without additional therapy compared to those without LGS.
Patient outcomes used by advanced practice psychiatric nurses to evaluate effectiveness of practice.

Health care in the 1990s requires Advanced Practice Psychiatric Nurses (APPNs), like other health care providers, to identify and evaluate the outcomes of their practices. Many APPNs report that they are not currently engaging in outcome evaluation, and many report that they would like more resources on outcome measurement. This study identifies outcome evaluations currently in use, through an analysis of the responses of 364 Certified Clinical Nurse Specialists in a survey conducted by the Society for Education and Research in Psychiatric Nursing in 1994–1995. Specific tools that APPNs report using to assess outcomes are also identified and referenced.
Genomic Structure and Expression of the ADH7 Gene Encoding Human Class IV Alcohol Dehydrogenase, the Form Most Efficient for Retinol Metabolism in Vitro

Human alcohol dehydrogenase (ADH) consists of a family of five evolutionarily related classes of enzymes that collectively function in the metabolism of a wide variety of alcohols including ethanol and retinol. Class IV ADH has been found to be the most active as a retinol dehydrogenase, thus it may participate in retinoic acid synthesis. The gene encoding class IV ADH (ADH7) has now been cloned and subjected to molecular examination. Southern blot analysis indicated that class IV ADH is encoded by a single unique gene and has no related pseudogenes. The class IV ADH gene is divided into nine exons, consistent with the highly conserved intron/exon structure of other mammalian ADH genes. The predicted amino acid sequence of the exon coding regions indicates that a protein of 373 amino acids, excluding the amino-terminal methionine, would be translated, sharing greater sequence identity with class I ADH (69%) than with classes II, III, or V (59-61%). Expression of class IV ADH mRNA was detected in human stomach but not liver. This correlates with previous protein studies, which have indicated that class IV ADH is the major stomach ADH but unlike other ADHs is absent from liver. Primer extension studies using human stomach RNA were performed to identify the transcription initiation site lying 100 base pairs upstream of the ATG translation start codon. Nucleotide sequence analysis of the promoter region indicated the absence of a TATA box sequence often located about 25 base pairs upstream of the start site as well as the absence of GC boxes, which are quite often seen in promoters lacking a TATA box. The class IV ADH promoter thus differs from the other ADH promoters, which contain either a TATA box (classes I and II) or GC-boxes (class III), suggesting a fundamentally different form of transcriptional regulation.
Frictional behavior of sputtered TiN

Abstract In this research, reciprocating sliding experiments were conducted on films of sputtered TiN. The primary emphasis was to evaluate the effect of the applied film thickness on the friction coefficient. Other parameters namely, surface roughness, substrate hardness and applied load were also varied and their effects were studied. From the friction data and the results of the microscopy studies, the dominant mechanism responsible for the transition and steady state friction behavior were evaluated. The results show that the gradual accumulation of minute wear fragments followed by the formation of a rigid transferred layer are responsible for the transition of the friction coefficient. During the steady state, sliding is occurring between the slider and a small portion of the transferred layer. The steady state friction coefficient varies with the applied coating thickness under the light load. Under the heavy load the coating thickness has no effect on the friction coefficient, except that the friction coefficient tends to be lower for the minimum film thickness.
Laparoscopic robot‐assisted completion cholecystectomy: a report of three cases

Background Gangrenous cholecystitis remains a serious, life-threatening, surgical emergency. Surgeons are occasionally forced to perform a subtotal cholecystectomy and forego formal dissection of the cystic duct and artery, in an attempt to avoid iatrogenic injury to the common bile duct. Not infrequently, a patient may develop a persistent biliary fistula or symptomatic gall bladder remnant, which may ultimately require operative intervention. Methods Three patients were referred to the University of North Carolina Hospitals for evaluation and treatment. All patients initially presented with gangrenous cholecystitis and had undergone open cholecystectomies and placement of surgical drains at outside medical facilities. All three patients had subsequently developed persistent biliary leaks or had significant gall bladder remnants. Due to the anticipated difficulty and complexity of performing a laparoscopic completion cholecystectomy in this setting, the DaVinci® robot (Intuitive Surgical, Sunnyvale, CA, USA) was utilized for these three consecutive patients. Dissection was performed using two robotic instrument arms, as well as assistant ports for suction/irrigation devices, clips and endostaplers. Results All three patients were found to have significant gall bladder and cystic duct remnants, some with sizeable retained stones in the infundibulum. All procedures were completed laparoscopically with robotic assistance, with no complications. At follow-up, all patients were without biliary leaks or symptoms. Conclusion Laparoscopic robot-assisted completion cholecystectomy is a feasible option in the setting of a reoperative, hostile abdomen following gangrenous cholecystitis. Copyright © 2009 John Wiley & Sons, Ltd.
The Preparation of High Purity Inorganic Chlorides(1)

Abstract The purification or synthesis of AgCl, AlCl3, BiCl3, CrCl3, CuCl, CuCl2, FeCl3, NaCl, NiCl3, SbCl3, and ZnCl2 is described. Great care was exercised in order to reduce anionic as well as cationic impurities. Therefore, the salts were analyzed for metallic impurities by emission spectroscopy and also for nonmetallic impurities, mainly oxygen, carbon, hydrogen, sulfur and bromine, by spark source mass spectrometry. The purified salts were found, with few exceptions, to contain no impurity, cationic or anionic (including oxygen), greater than 100 ppm.
A conceptual framework and open research questions for chat-based reference service

This article seeks to shift the literature on chat-based reference services beyond the current spate of case studies and discussions of emerging standards and best practices in providing chat-based reference, to a higher level of discussion on the creation and discussion of theoretical frameworks to unite these standards and practices. The article explores the various steps in the process of providing synchronous, chat-based reference, as well as issues involved in providing such service at each step. The purpose of this exploration is twofold: First, this article presents some open research questions at each step in the process of providing chat-based reference service. Second, the entire process of providing chat-based reference is viewed as a whole, and a model of the provision of chat-based reference service is developed at a high level of abstraction. It is hoped that this model may serve as a conceptual framework for future discussions of and development of applications for chat-based reference.
Growth dynamics of pentacene thin films

The recent demonstration of single-crystal organic optoelectronic devices has received widespread attention1,2,3,4. But practical applications of such devices require the use of inexpensive organic films deposited on a wide variety of substrates. Unfortunately, the physical properties of these organic thin films do not compare favourably to those of single-crystal materials. Moreover, the basic physical principles governing organic thin-film growth and crystallization are not well understood. Here we report an in situ study of the evolution of pentacene thin films, utilizing the real-time imaging capabilities of photoelectron emission microscopy. By a combination of careful substrate preparation and surface energy control, we succeed in growing thin films with single-crystal grain sizes approaching 0.1 millimetre (a factor of 20–100 larger than previously achieved), which are large enough to fully contain a complete device. We find that organic thin-film growth closely mimics epitaxial growth of inorganic materials, and we expect that strategies and concepts developed for these inorganic systems will provide guidance for the further development and optimization of molecular thin-film devices.
Anay's will to learn: a woman's education in the shadow of the maquiladoras

Anay's Will to Learn: A Woman's Education in the Shadow of the Maquiladoras, by Elaine Hampton and Anay Palomenque de Carrillo, explores the contemporary struggles of Mexican women in obtaining edu...
Laboratory Measurements of the Microwave Opacity of Phosphine: Opacity Formalism and Application to the Atmospheres of the Outer Planets

Abstract Preliminary room-temperature measurements of the microwave opacity of phosphine (Hoffman and Steffes 1999). Icarus 140 , 235–238, suggested that phosphine (PH 3 ) may contribute significantly to the microwave emission spectrum of Neptune, and to the centimeter-wavelength opacity measured by the Voyager 2 spacecraft at Neptune and Saturn. As a result, new laboratory measurements of the microwave opacity of PH 3 in an H 2 /He atmosphere have been conducted at frequencies (wavelengths) of 1.5 GHz (20 cm), 2.2 GHz (13.3 cm) 8.3 GHz (3.6 cm), 13.3, GHz (2.3 cm), 21.6 GHz (1.4 cm), and 27 GHz (1.1 cm) over a range of temperatures (175–298 K) and pressures (1–6 bars). A measurement-based centimeter-wavelength opacity formalism for phosphine has been developed and provides an order of magnitude improvement over previous models. The resulting model is applied to results from the Voyager 2 radio science experiments at Saturn and Neptune and to disk-averaged, centimeter-wavelength observations of Neptune and Saturn. Future uses will include application to spatially resolved microwave images of the outer planets from radio telescopes and spacecraft radiometry and to future radio occultation measurements, including Cassini–Saturn.
On building special-purpose social networks for emergency communication

In this paper we propose a system that will allow people to communicate their status with friends and family when they find themselves caught up in a large disaster (e.g., sending "I'm fine" in the immediate aftermath of an earthquake). Since communication between a disaster zone and the non-affected world is often highly constrained we design the system around lightweight triggers such that people can communicate status with only crude infrastructure (or even sneaker-nets). In this paper we provide the high level system design, discuss the security aspects of the system and study the overall feasibility of a purpose-built social networking system for communication during an emergency.
Genetic Analysis of Bacteriophage P4 Using P4-Plasmid ColE1 Hybrids

A set of plasmids that contain fragments of the bacteriophage P4 genome has been constructed by deleting portions of a P4-ColE1 hybrid. A P4 genetic map has been established and related to the physical map by examining the ability of these plasmids to rescue various P4 mutations. The P4 virl mutation and P4 genes involved in DNA replication (alpha), activation of P2 helper genes (delta and epsilon), polarity suppression (psu) and head size determination (sid) have been mapped, as has the region responsible for synthesis of a nonessential P4 protein. One of the deleted plasmids contains only 5900 base pairs (52%) of P4 but will form plaques if additional DNA is added to increase its total size to near that of P4. This plasmid is also unique in that it will not form stable associations with P2 lysogens of E. coli which are recA+. P4 alpha mutants can be suppressed as a result of replication under control of the ColE1 part of the hybrid.
Context matters: Design guidance for maximizing success of storytelling sessions during a user-centered design task

Empirical comparisons of elicitation methods provide guidance to engineers for the selection of the best method for a given design goal. This work explores how alterations to the context (i.e, setting, prompts) of storytelling sessions impacted the types of user needs collected from 22 emergency room (ER) nurses. Six user need sets, comprised of 477 narratives detailing an experience relating to a healthcare quality aim, were quantitatively compared. The results of the study yielded a set of decision rules and decision trees to aid the selection of an appropriate storytelling protocol that facilitates formative usability design.
Brain Angiotensin II Receptor Subtypes and the Control of Luteinizing Hormone and Prolactin Secretion in Female Rats.

The present experiments examined the role of the two recently identified angiotensin II (Ang II) receptor subtypes, AT, and AT(2) , in the central nervous system regulation of luteinizing hormone (LH) and prolactin secretion in estrogen- and progesterone-treated ovariectomized rats. In this animal model, intracerebroventricular (icv) injection of Ang II stimulates LH and inhibits prolactin release. The specific Ang II receptor subtype antagonists losartan (AT(1) ) or PD123177 (AT(2) ) were administered (icv) in various doses (10 ng to 1,000 ng) 10 min prior to icv injection of Ang II (100 ng). Control animals were pretreated with artificial cerebrospinal fluid prior to Ang II administration. Blood samples for LH and prolactin determinations were taken from conscious, freely-moving rats prior to and following injection of the antagonists and Ang II. Water intake was measured. Ang ll-induced water intake was attenuated 62% by 1,000 ng losartan; water intake was not affected by lower doses of losartan or by any dose of PD123177. Ang ll-induced stimulation of LH release was abolished by the 1,000 ng doses of losartan and PD123177 and attenuated by the 500 ng doses of both drugs. Lower doses did not affect Ang ll-induced LH secretion. Ang ll-induced inhibition of prolactin release was significantly reduced by the 1,000 ng doses of both losartan and PD123177. Lower doses of either drug did not affect the Ang II inhibition of prolactin release. Previous studies had shown that Ang II administration into the anterior hypothalamus-medial preoptic (AHPO) area stimulated LH release. This brain area contains AT(1) receptors. To investigate the potential brain site where the AT(2) receptor may influence LH release, Ang II was injected into the locus ceruleus, a brain nucleus which contains predominately the AT(2) receptor subtype. Ang II administration into the locus ceruleus was paired with an injection of artificial cerebrospinal fluid or Ang II into the AHPO area. Injection of Ang II into the AHPO area stimulated LH release. Injection into the locus ceruleus did not affect LH secretion, nor did it modify the rise in LH elicited by administration of Ang II into the AHPO area. Plasma levels of prolactin were not altered by any of these injections. Taken together, these data demonstrate that, in estrogen- and progesterone-treated female rats, icv Ang ll-induced water intake is mediated by the AT, receptor subtype, while Ang ll-induced changes in LH and prolactin secretion appear to be mediated by both the AT(2) and AT(2) receptor subtypes. The latter observations are one of the first suggesting a potential function for the AT(2) subtype in vivo, although the physiological relevance of this observation, as well as the site of action for the effects on LH and prolactin, remain to be established.
Direct effects of glucose on proinsulin synthesis and processing during desensitization.

Prolonged exposure of isolated islets to glucose (11 mM) results in desensitization of insulin secretion. In this study, both glucose-regulated proinsulin biosynthesis and its processing during glucose-induced desensitization were examined at critical periods during 24 h. Although insulin secretion declined at 24 h to one third the 3 h maximum rate, the total rate of proinsulin biosynthesis, assessed by [3H]leucine incorporation, was unchanged at 0, 3, and 24 h of glucose (11 mM) exposure. Total insulin recovery measured by immunoreactive insulin in islets and media after 24 h was approximately 172% of the initial islet content. After correction for insulin degradation, and since proinsulin biosynthesis was unchanged, the synthesis rate was calculated to be a constant 3.5 ± 1.1 %/h of the initial islet content. Results suggest that desensitization may occur at the release mechanism rather than at a step in glucose metabolism common for the stimulation of synthesis and secretion. In contrast, the conversio...
Invited Editorial: The Four Theories of Profit and Their Joint Effects

As a theory of profit, resource-based theory is focused on a single causal mechanism—competitive advantage. Although this focus has been useful in helping to understand some sources of interfirm profit differentials, it is nevertheless highly limiting because competitive advantage is not the only causal mechanism by which profit can be generated. Three other mechanisms, labeled here as rivalry restraint, information asymmetry, and commitment timing, have also been extensively studied as sources of profit. Rather than continuing to examine each of these four mechanisms’ main effects on profit in isolation, and thereby generate increasingly incremental knowledge over time, the author proposes an alternative agenda for future research—namely, to synthesize multiple mechanisms in order to focus on their relatively unexplored interaction effects on profit. This article reviews the small but emerging literature of research that has already begun to pursue this agenda and outlines some logical next steps for fur...
S100A10: a complex inflammatory role.

In this issue of Blood , O'Connell and colleagues demonstrate that macrophage recruitment in response to an inflammatory stimulus is markedly decreased in S100A10-deficient mice compared with wild-type mice, establishing the plasminogen receptor, S100A10, as a major mediator of this key plasmin-
Effects of anions on amiloride-sensitive, active sodium transport across rabbit colon, in vitro. Evidence for "trans-inhibition" of the Na entry mechanism.

replacement of Cl in the solutions bathing partial mucosal strips of rabbit descending colon with sulfate, isethionate, hydroxypropane-sulfonate and, to a lesser degree, ethanesulfonate stimulates active Na absorption (JnetNa) when the baso-lateral pump mechanism is not saturated. These effects are rapid in onset and are readily reversible. Our findings indicate that these stimulatory anions decrease the resistance of the amiloridesensitive Na entry step at the mucosal membrane (RNam). However, when the active Na pump mechanism at the baso-lateral membrane is saturated these stimulatory anions do not decrease the resistance of the Na entry process. These findings suggest the presence of a negative feedback between the activity of the pump mechanism and the resistance of the Na entry step which may be mediated by the size of the intracellular Na transport pool. In other words, it seems that when the baso-lateral pump is operating at its maximal rate the resistance to Na entry across the mucosal membrane through the amiloride-sensitive pathway is at a minimum and cannot be further decreased.
Deployment of tensegrity structures

In this paper we present a strategy for tensegrity structures deployment. The main idea is to use a certain set of equilibria to which the undeployed and deployed configurations belong. In the state space this set is represented by an equilibrium manifold. The deployment is conducted such that the deployment trajectory is close to this equilibrium manifold.
Adoption complexity and economies of scope for new process technology in manufacturing

Abstract In a study of 39 domestic, durable goods plants, justifications for purchase of new process technology varied from the simple, single-goal approach to the complex, multiple-objective strategy. This variety contributes to a larger construct of adoption complexity, which was found to be a function of flexible manufacturing systems (FMS) (vs. cellular) purchase choice and plant size in a significant path model. Adoption complexity, in turn, significantly influences intrafirm personnel flows for implementation (e.g., mobility and job rotation). Flexible outcomes are not automatic with FMS purchase, however. Part family variety was significantly higher in larger plants and part variety was significantly promoted by personnel flows. Suggestions for further research and policy implications are discussed.
DENTURE ADHESIVES: CHANGING ATTITUDES

Since people began using denture adhesives more than 200 years ago, dentists have been slow to acknowledge their place in prosthetic dentistry. The author maintains that if properly used, denture adhesives can be an asset to the dentist's armamentarium. This article reviews much of the recent research on adhesives and outlines the conditions under which they should be used.
House fly head GABA‐gated chloride channel: [3 H] α‐Endosulfan binding in relation to polychlorocycloalkane insecticide action

This study attempts to use [3H] α-endosulfan to examine directly the binding site(s) for cyclodienes, lindane and toxaphene (collectively referred to as the polychlorocycloalkane or PCCA insecticides) in the 4-aminobutyric acid (GABA)-gated chloride channel. [3H] α-Endosulfan was prepared by reduction of hexachloronorbornenedicarboxylic anhydride with sodium borotritide, then coupling the labelled alcohol with thionyl chloride followed by HPLC purification (35 Ci mmol−1, > 99% radiochemical purity). This new candidate radioligand readily partitions into lipid membranes and undergoes indiscriminate adsorption to surfaces resulting in high levels of non-specific binding. This makes it very difficult to differentiate the small portion of specific binding at the site relevant to toxic action. This problem was partially circumvented by incubating [3H] α-endosulfan (0.1 nM) with house-fly head membranes (0.2 mg protein) for 70 min at 22°C giving 23 (±4)% specific binding (40 fmol mg−1 protein) determined as the difference between the radioligand alone and on preincubation for 15 min with unlabelled α-endosulfan (final concentration 100 nM). This procedure is not appropriate for determination of saturation isotherms and standard binding kinetics. However, the effectiveness of 16 PCCAs (also at 100 nM final concentration) in blocking the specific binding of [3H] α-endosulfan is generally consistent with their relative potencies as inhibitors of 4-[3H] propyl-1-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2.2.2] octane ([3H]EBOB) binding suggesting that the binding site for both [3H]α-endosulfan and the PCCAs is part of the GABA-gated chloride channel. Insecticidal channel blockers of other types (e.g. picrotoxinin, trioxabicyclooctanes, a dithiane, and phenylpyrazoles) and GABA are poor inhibitors of [3H] α-endosulfan binding relative to their potencies as inhibitors of [3H] EBOB binding. It therefore appears that the PCCAs compete directly for the [3H] α-endosulfan site, whereas the other channel blockers bind with different inhibition kinetics or at a site more closely coupled to the EBOB than the α-endosulfan binding domain.
JAKs and STATs in invertebrate model organisms

Invertebrate organisms provide systems to elucidate the developmental roles of Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathways, thereby complementing research conducted with mammalian cells and animals. Components of the JAK/STAT protein pathway have been identified and characterized in the fruit fly Drosophila melanogaster and the cellular slime mold Dictyostelium discoideum. This review summarizes the molecular and genetic data obtained from these model organisms. In particular, a Drosophila JAK/STAT pathway regulates normal segmentation, cell proliferation, and differentiation, and hyperactivation of the pathway leads to tumor formation and leukemia-like defects. A Dictyostelium STAT regulates the development of stalk cells during the multicellular part of the life cycle. Future research utilizing these organisms should continue to provide insights into the roles and regulation of these proteins and their signaling pathways.
Decreasing Pancreatic Leak After Distal Pancreatectomy: Saline-coupled Radiofrequency Ablation in a Porcine Model

Despite marked improvements in pancreatic surgery, the high incidence and morbidity of pancreatic leak after resection has remained unchanged. The objective of this study was to evaluate the role of saline-coupled radiofrequency ablation (TissueLink) as an alternative to traditional methods of stump closure in an animal model of distal pancreatectomy. Forty swine were randomized after pancreatic transection and remnant stump was either oversewn in a traditional fashion (control) or treated with the device alone (TissueLink). Animals were killed and necropsied at 3 or 5 weeks postoperatively. Primary endpoints were the development of a pancreatic fistula defined as dye extravasation from the remnant duct, presence of undrained amylase-rich fluid collections/abscess, and greater than threefold drain/serum amylase after the third postoperative day. The incidence of pancreatic leak in the TissueLink group was 5.5 vs 42% in the control group (p = 0.01). There were no differences in operative time or other clinical parameters measured. Histologic analysis of the remnant pancreatic stumps confirmed our results. These data support our hypothesis that saline-coupled radiofrequency ablation leads to obliteration of ducts with a resultant decrease in pancreatic leak and subsequent complications. This technology may play a substantial role in preventing this dreaded complication in the clinical setting.
Geometric and temperature compensating effects of the MOS enhanced capacitor

Geometric and temperature effects of the MOS enhanced capacitor are shown to be valuable for MOS D to A conversion and for temperature compensation of MOS oscillators. It is also shown that these effects may be deleterious in one transistor memory and high speed bootstrap circuits.
Distributed database concurrency controls using before-values

Associated with the write of a database entity is both the "before" or old value, and the "after" or new value. Concurrency can be increased by allowing other transactions to read the before values of a given transaction. The ramifications of allowing this, particularly on a distributed system in which limited communications is desirable, are investigated. A careful distinction is made between design decisions concerning communications and design decisions concerning the responses to read/write requests. Two schemes for producing such controls are given, one scheme for systems where processes are committed on termination, and the other for systems where committment is made later.
Changes of the outer to inner heliospheric intensity ratios of >70 MeV galactic cosmic rays as a function of solar magnetic polarity

[1] We have examined the temporal history of the outer to inner heliospheric intensity ratios of >70 MeV cosmic rays using the Voyager, Pioneer, and IMP spacecraft during the time period from 1984 to 2001. This ratio effectively measures the changes in the integral radial cosmic ray gradient between the outer heliosphere and the Earth. In the time period from 1984 to 1990, when the solar magnetic polarity was negative, this outer to inner heliospheric ratio out to ∼50 AU changed temporally in such a way that an average radial gradient ∼2%/AU near the ecliptic plane was maintained throughout this entire period. After 1990, when the solar magnetic polarity became positive, this average ratio began to slowly decrease, as measured at all three spacecraft throughout the heliosphere out to 50–70 AU, reaching a minimum value corresponding to an average 0.5%/AU radial gradient in 1996. In 1997–1998, in conjunction with the first large transient decreases in the new 11-year solar cycle, the intensity ratios between the outer heliosphere spacecraft and the Earth began to increase rapidly. By the time the Bastille Day transient in 2000 at the Earth had propagated to V2 and V1, which were now between 65 and 82 AU, the outer to inner heliospheric intensity ratios had increased from a value ∼1.4 in 1997 to between 3.0 and 4.0, respectively, at V2 and V1 in 2001. Therefore this time period represents a transition back to a negative solar magnetic polarity and to the reestablishment of a ∼2%/AU average radial gradient similar to that of the previous negative polarity cycle in the heliosphere, but now observed out to ∼80 AU in 2001. This particularly simple pattern for the temporal changes in the average radial gradient in alternate solar magnetic polarity cycles can thus be followed through almost a complete 22-year solar magnetic cycle.