cssi/SciSciGPT-SciSciNet huggingface dataset:
An Introduction to Statistical Mechanics with Applications to Nonlocal Dispersion

Theories in statistical mechanics provide the tools to go from the atomistic or molecular structure of matter to a continuum scale. Such theories allow detailed molecular data to be mapped into field (such as stress) and constitutive properties or material parameters. This approach is quite different from the continuum mechanical, wherein the molecular makeup of the fields is unknown and, to a large extent irrelevant. The advancement of computer architecture and algorithms in recent years now allows many continuum scale material parameters to be determined directly from molecular-scale computer (virtual) experiment, rather than continuum-scale experiment. It is mainly for this reason that we include this chapter in this monograph.
Más allá de las Nuevas Poblaciones de Andalucía. La estrategia de ascenso de Frey Fernando de Quintanilla en la Orden Militar de San Juan

In 1767, Carlos III entrusted Pablo de Olavide with the creation and administration of the New Settlements that were established in segregated territories of the province of La Mancha and the kingdoms of Jaen, Cordova and Seville. The scope of the project caused Olavide to appoint Fernando de Quintanilla in 1768 as a sub-delegate of the New Settlements of Andalusia. Very soon, the Enlightenment ideas of the first greatly influenced the second, who adopted and defended them until 1776. However, the arrest and subsequent inquisitorial sentence of the superintendent would make him renounce those ideas and repeatedly beg to be able to retire to his hometown. The government rejected their requests for years, but, in the meantime, Quintanilla focused on improving its position within the San Juan order; with such success that in his last two decades of life he enjoyed several encomiendas and bailiajes that, in addition, allowed him to enjoy a considerable income.
Diagnosis of pulmonary embolism.

Case 1: A 77-year-old Caucasian woman with a probable diagnosis of ovarian cancer developed an acute onset of shortness of breath two days after being discharged for a workup of symptomatic ascites. Her medical history was signifi cant for hypertension and atrial fi brillation, and she was taking therapeutic doses of coumadin. She presented to the emergency department; was found to have a large, left pleural effusion; and was admitted to the hospital. A thoracentesis removed 2.1 L of fl uid. The patient’s respiratory distress improved; however, she experienced a second episode of sudden onset shortness of breath prior to her anticipated discharge. She was afebrile, with a room air pulse oximetry of 80%, pulse of 121 beats per minute, and respiratory rate of 28. A chest x-ray (CXR) showed only a small pleural effusion remaining on the left. An electrocardiogram (EKG) showed atrial fi brillation. A chest computed tomography (CT) was performed and showed bilateral pulmonary emboli.
Quantitative concentration measurements in a turbulent helium jet using rainbow schlieren deflectometry

Rainbow schlieren deflectometry (RSD) is applied to acquire quantitative concentration measurements in a turbulent environment for the first time. RSD methodology is developed and validated using Rayleigh scattering data available in the literature. Experiments were performed in an initially laminar, momentum-driven helium jet injected into ambient air. Full-field measurements are acquired that span the laminar, transition, and fully turbulent regions of the jet. The RSD results are shown to provide accurate measurements in each region and also confirm the self-similar nature of the fully turbulent jet. Analysis shows that the transition from laminar to turbulent flow occurs across an axial span that decreases with increasing Reynolds number. Experiments with a long exposure time were conducted to evaluate the limitations of hardware averaging of the RSD signal in comparison with software averaging.
Characterization of variants of uncertain significance in isovaleryl-CoA dehydrogenase identified through newborn screening: An approach for faster analysis.

Abstract Introduction Clinical standard of care for newborn screening (NBS) is acylcarnitine metabolites quantitation by tandem mass spectrometry (MS/MS) from dried blood spots. Follow up sequencing often results in identification of one or more variants of uncertain significance (VUS). Isovaleric acidemia (IVA) is an autosomal recessive inborn error of metabolism caused by deficiency of isovaleryl-CoA dehydrogenase (IVDH) in the Leu catabolism pathway. Many IVD mutations are characterized as VUS complicating IVA clinical diagnoses and treatment. We present a testing platform approach to confirm the functional implication of VUS identified in newborns with IVA applicable to multiple inborn errors of metabolism identified by NBS. Methods An IVD null HEK293T cell culture model was generated by using a dual sgRNA CRISPR/Cas9 genome-editing strategy targeting IVD exons 2–3. Clonal cell lines were confirmed by a combination of genomic breakpoint sequencing and droplet digital PCR. The IVD null model had no IVDH antigen signal and 96% reduction in IVDH enzyme activity. The IVD null model was transfected with vectors containing control or variant IVD and functional assays were performed to determine variant pathogenicity. Results c.149G > C (p.Arg50Pro; precursor numbering), c.986T > C (p.Met329Thr), and c.1010G > A (p.Arg337Gln), c.1179del394 f. mutant proteins had reduced IVDH protein and activity. c.932C > T (p.Ala311Val), c.707C > T (p.Thr236Ile), and c.1232G > A (p.Arg411Gln) had stable IVDH protein, but no enzyme activity. c.521T > G (p.Val174Gly) had normal IVDH protein and activity. IVD variant transfection results confirmed results from IVA fibroblasts containing the same variants. Conclusions We have developed an IVD null HEK293T cell line to rapidly allow determination of VUS pathogenicity following identification of novel alleles by clinical sequencing following positive NBS results for suspected IVA. We suggest similar models can be generated via genome-editing for high throughput assessment of VUS function for a multitude of inborn errors of metabolism and can ideally supplement NBS programs.
Splash: User-friendly Programming Interface for Parallelizing Stochastic Algorithms.

Stochastic algorithms are efficient approaches to solving machine learning and optimization problems. In this paper, we propose a general framework called Splash for parallelizing stochastic algorithms on multi-node distributed systems. Splash consists of a programming interface and an execution engine. Using the programming interface, the user develops sequential stochastic algorithms without concerning any detail about distributed computing. The algorithm is then automatically parallelized by a communication-efficient execution engine. We provide theoretical justifications on the optimal rate of convergence for parallelizing stochastic gradient descent. Splash is built on top of Apache Spark. The real-data experiments on logistic regression, collaborative filtering and topic modeling verify that Splash yields order-of-magnitude speedup over single-thread stochastic algorithms and over state-of-the-art implementations on Spark.
Inheritance in American Legal Thought

From the time of the Revolution, American legal thinkers viewed both the rights to transmit and to receive property at the death of its owner as positivistic, not natural rights: rights created and regulated by the state, rather than fundamental rights. In this, they were heavily influenced by William Blackstone (Ascher, 1990) who argued in his Commentaries on the Law of England that inheritance was “no natural, but merely a civil right”: For naturally speaking, the instant a man ceases to be, he ceases to have any dominion; else if he had a right to dispose of his acquisitions one moment beyond his life, he would also have a right to direct their disposal for... ages after him; which would be highly absurd and inconvenient. (Blackstone, 1803, pp. 10–11).
The undecidability of the generalized Collatz problem

The Collatz problem, widely known as the 3x + 1 problem, asks whether or not a certain simple iterative process halts on all inputs. In this paper, we build on work of J. H. Conway to show that a natural generalization of the Collatz problem is Π20 complete.
Intraductal applications of lidocaine attenuate the severity of post-ERCP acute pancreatitis (1131.2)

Endoscopic retrograde cholangiopancreatography (ERCP) is a procedure used to identify biliary duct obstruction. 5-10% of patients, however, develop acute pancreatitis (AP). AP is a severe disorder ...
When Can Formal Methods Make a Real Difference

This talk will consider a few cases from the ACM Risks Forum archives {http://www.risks.org} for which the sensible use of formal methods could have made a decisive difference in avoiding serious consequences – with respect to requirements, specifications, human interfaces, implementation, and even operation, typically in systems that were supposedly safe, reliable, or secure. This will provide a view to the future in terms of things we can learn about the past.
Alignment tolerant stripline directional couplers

The design methodology for a new type of alignment tolerant, broadside coupled, stripline, directional coupler is developed. The coupler uses an even number of cascaded, asymmetric, broadside coupled line stages that are electrically short (</spl lambda//sub g//8) and have been alternately inverted to achieve nearly symmetric coupling and return loss at all ports. The results demonstrate layer to layer alignment insensitivity that enables coupler designs where misalignment between layers is a critical parameter. Measured S-parameter results for 3 dB and 10 dB coupler designs are presented and agree well with theory. Coupling range variations less than 0.5 dB are achieved for a 3 dB alignment tolerant coupler design compared to 0.9 dB for a standard, symmetric 3 dB design with misalignments of +/-0.25 mm (+/-0.010"). An 8.4 dB alignment tolerant directional coupler displays a variation of 0.3 dB over the same layer to layer alignment range compared to an equivalent 10 dB standard design that has a coupling variation of 4.9 dB with similar misalignment between layers.
Categorical Semantics, Or Extending Data Types to Include Memory

This paper extends the algebraic theory of data types so that it can deal with issues, such as those involving memory, that can not be easily treated within the usual algebraic specification framework. The result is a simple, uniform, mathematical framework in which we can treat, not only data types and their operations, but also, the semantics of imperative languages with assignment, conditionals, while-do’s, and elementary exception handling.
The “new” policy partnership: Academic researchers and government officials partnering toward social equity

Purpose – The purpose of this paper is to introduce this special issue on “the ‘new’ policy partnership”.Design/methodology/approach – The paper highlights the significance of policy‐academic partnerships and outlines the papers included in this issue.Findings – It is important to form and maintain partnerships and collaborations with new nontraditional stakeholders. One place where this is evident is in academia.Originality/value – The special issue includes original articles that address innovative ways in which researchers and policy makers can collaborate to move policy agendas forward.
DNA damage response and tumorigenesis.

Proc Amer Assoc Cancer Res, Volume 47, 2006 SY06-02 MDC1 functions in checkpoint activation and DNA repair following DNA damage. To address the physiological role of MDC1, we disrupted the MDC1 gene in mice. MDC1−/−mice recapitulated many phenotypes of H2AX−/− mice, including growth retardation, male infertility, immune defects, chromosome instability, DNA repair defects and radiation sensitivity. At the molecular level, H2AX, MDC1 and ATM form a positive feedback loop, with MDC1 directly mediating the interaction between H2AX and ATM. MDC1 binds phosphorylated H2AX through its BRCT domain and ATM through its FHA domain. Through these interactions, MDC1accumulates activated ATM flanking the sites of DNA damage, facilitating further ATM-dependent phosphorylation of H2AX and the amplification of DNA damage signals. In the absence of MDC1, many downstream ATM signaling events are defective. These results suggest that MDC1, as a signal amplifier of the ATM pathway, is vital in controlling proper DNA damage response and maintaining genomic stability.
Talking voices: Imagining worlds: imagery and detail in conversation and other genres

The artist's life nourishes itself on the particular, the concrete: that came to me last night as I despaired about writing poems on the concept of the seven deadly sins and told myself to get rid of the killing idea: this must be a great work of philosophy. Start with the mat-green fungus in the pine woods yesterday: words about it, describing it, and a poem will come. Daily, simply, and then it won't lower in the distance, an untouchable object. Write about the cow, Mrs. Spaulding's heavy eyelids, the smell of vanilla flavouring in a brown bottle. That's where the magic mountains begin. Sylvia Plath, Journals “I wish you were here to see the sweet peas coming up.” A line of a poem? It could become one. But as it was, it was just a fragment of conversation, words uttered by a friend on one coast to a friend on the other. But these words have something in common with a poem: They spark a flash of feeling. They make us not just think about, but feel, the distance of the American continent separating two people, the longing to be in the presence of someone loved, to report not important events, but small ones, small perceptions. “I wish you were here to see the sweet peas coming up.” Why is this more moving than the simple, “I wish you were here”? Partly because “Wish you were here” is a fixed expression, a cliche. But mostly, I think, it is because of the sweet peas – small and ordinary and particular.
Charge transfer and ultrafast nuclear motions: the complex structural dynamics of an electronically excited triamine

Three ionization centers make 1,3,5-trimethyl-1,3,5-triazacyclohexane (TMTAC) an interesting model system to study intramolecular charge transfer (CT). Because the molecule assumes a Cs symmetric, axial–equatorial–equatorial (aee) conformation in the ground state, there are two distinct types of the nitrogen atoms. We discovered that either nitrogen atom can be ionized independently so that two molecular cations exist with different (localized) charge distributions in the Franck–Condon region. The initially localized charge can delocalize via CT, provided the molecule acquires a suitable structural geometry. These proper structures are all found to have a common structural motif that supports CT via through-space-interaction. The structural dynamics and the CT process in Rydberg-excited TMTAC, where the molecular ion core closely resembles the ion, were probed by time-resolved Rydberg fingerprint spectroscopy. When TMTAC is excited at 230 nm to the Franck–Condon region of the 3s Rydberg state, the two types of nitrogen atom Rydberg chromophores give rise to distinct binding energy peaks. The sequential molecular responses that follow the Rydberg excitation manifest themselves as time-dependent changes of the binding energy and are observed by ionization at 404 nm. A fast transition with 103 fs time constant was attributed to a motion that leads to a local minimum of the charge-localized state on the Rydberg potential energy surface. Because a large amount of energy is deposited into the vibrational manifolds, the molecule continues to sample the potential energy surface and eventually reaches a dynamic equilibrium between charge-localized and charge-delocalized states. The forward and backward time constants were determined to be 1.02 ps and 4.09 ps, respectively. The binding energy spectrum also reveals the existence of an equilibrium among several charge-delocalized states. Quantum chemical calculations were carried out to find the stable minima of the ground state and the ion state. The binding energies of the Franck–Condon structures and the relaxed ion structures were calculated using the Perdew–Zunger self-interaction corrected DFT (PZ-SIC) method to assign the spectra at time zero and at equilibrium, respectively.
Attributional analysis of interprofessional role conflict.

Abstract Interprofessional role conflict is often a source of job dissatisfaction for health professionals. Attributional analysis provides a methodology to better understand the health care provider's perceptions of the causes of interprofessional conflict and the influence of these causal perceptions on future behavior. This paper reports a study in which 86 physical therapists reported the attributions (perceived causes) they held for situations in which they had compromised (failure) and other instances in which they had supported (success) their best professional judgement following incidents of interprofessional conflict with physicians. Comparison of reported incidents showed that there were significant differences in subject perceptions of the nature of the causes and their future expectations following success and following failure. Therapists tended to ascribe their successes to internal, stable and controllable causes, such as their personality, effort, assertiveness or the strategies they used and held high expectations for future success. Following failure, therapists ascribed the causes of their failures to more external and uncontrollable causes such as influence of the supervisor or the receptivity of the physician. Therapist causal ascriptions for failure to external and uncontrollable sources strongly correlated with high future expectations of failure. Patterns of causal thinking following incidents of interprofessional conflict clearly influence one's future expectations to avoid, withdraw or to seek a productive resolution to role conflict.
Attraction of yellowjackets (Vespula spp.) to heptyl butyrate in Washington State (Hymenoptera: Vespidae).

During 2 years of trapping with artificial attractants in the Pullman, Washington, area, 6 species of Vespula were collected. Two species, V. atropilosa (Sladen) and V. pensylvanica (Saussure), were collected in large numbers. V. atropilosa was more strongly attracted to heptyl butyrate than was V. pensylvanica . Most queens and workers collected in attractant traps were V. atropilosa . Use of artificial attractant traps for controlling yellowjackets is discussed in relation to species composition. The importance of appropriate timing is emphasized and related to the seasonal buildup and decline of worker yellowjacket populations.
Layer-by-layer 3-D constructs of adherent and non-adherent cells in hydrogel

We report a protocol for the layer-by-layer fabrication of adherent and non-adherent 3-dimensional (3-D) cell cultures. Adherent Madin Darby canine kidney (MDCK) epithelial cell cultures were patterned onto Petri dishes, and non-adherent cell cultures were physically encapsulated in alginate hydrogel layer above the adherent cells. The layer-by-layer, CAD/CAM fabrication process results in soft transfer and does not harm adherent cells. We have developed a technique to fabricate a multi-layer cell culture system to study the interactions between adherent and non-adherent cell types.
Decreases in valosin‐containing protein result in increased levels of tau phosphorylated at Ser262/356

VCP/p97 is a multifunctional AAA+-ATPase involved in vesicle fusion, proteasomal degradation, and autophagy. Reported dysfunctions of these processes in Alzheimer disease (AD), along with the linkage of VCP/p97 to inclusion body myopathy with Paget’s disease and frontotemporal dementia (IBMPFD) led us to examine the possible linkage of VCP to the AD-relevant protein, tau. VCP levels were reduced in AD brains, but not in the cerebral cortex of an AD mouse model, suggesting that VCP reduction occurs upstream of tau pathology. Genetic reduction of VCP in a primary neuronal model led to increases in the levels of tau phosphorylated at Ser262/356, indicating that VCP may be involved in regulating post-translational processing of tau in AD, demonstrating a possible functional linkage between tau and VCP.
The N-terminus of Himar1 mariner transposase mediates multiple activities during transposition.

Mariner family transposons are perhaps the most widespread transposable elements of eukaryotes. While we are beginning to understand the precise mechanism of transposition of these elements, the structure of their transposases are still poorly understood. We undertook an extensive mutagenesis of the N-terminal third of the transposase of the Himar1 mariner transposon to begin the process of determining the structure and evolution of mariner transposases. N and C-terminal deletion analyses localized the DNA binding domain of Himar1 transposase to the first 115 amino acids. Alanine scanning of 23 selected sites within this region uncovered mutations that not only affected DNA binding but DNA cleavage as well. The behavior of other mutations strongly suggested that the N-terminus is also involved in multimerization of the transposase on a single inverted terminal repeat and in paired ends complex formation which brings together the two ends of the transposon. Finally, two hyperactive mutations at conserved sites suggest that mariner transposases are under a pattern of stabilizing selection in nature with regard to how efficiently they mediate transposition, resulting in a population of “average” transposons.
A caspase homolog keeps CED-3 in check.

Apoptosis is a highly conserved form of cell death that is essential for controlling cell numbers throughout the lifetime of an organism. In Caenorhabditis elegans , the final step in the apoptotic cascade is activation of the death-inducing protease CED-3. Until now, no direct negative regulators of CED-3 had been identified, so the mechanism for maintaining a proper life–death balance was unclear. Now, a new study identifies CSP-3 as an important negative regulator of CED-3 during C. elegans development.
Abstract 5308: Id-1 gene and protein as novel therapeutic targets for metastatic cancer

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL During normal development and embryogenesis, helix-loop-helix Id proteins regulate the differentiation programs of many tissues. Moreover, recent studies have shown that dysregulated Id expression contributes to cancer progression and metastasis. Specifically, we found high levels of one of the Id family members, Id-1, in breast, prostate, brain and head and neck tumor cells which were highly aggressive, and low levels of Id-1 in non-invasive tumor cells. Ectopic expression of Id-1 in non-aggressive human cancer cells rendered them highly proliferative and invasive, and induced high levels of matrix metalloproteinase (MMP) expression. Conversely, human metastatic cancer cells became significantly less proliferative and invasive in culture when Id-1 protein expression was decreased by antisense RNA or shRNA directed against the Id-1 gene. Next, we asked whether Id-1 could be exploited as a therapeutic target to treat metastatic cancers. Using tumor-bearing animals and systemic gene targeting technique, we showed that reduction of Id-1 levels, and consequently MMP expression, could significantly decrease the metastatic spread of cancer cells. Further, several molecular pathways underlying Id-1 effects on epithelial to mesenchymal transition (EMT) and neoangiogenesis were also identified in certain types of cancer. These results suggested that Id-1 gene and/or protein could be a promising target for development of therapeutic strategies to reduce cancer metastasis. Since Id-1 expression is scarce in most mature adult tissues, a majority of normal cells would not be affected by systemic therapy targeting this gene. We determined that a cannabinoid compound, CBD, could specifically inhibit the expression of the Id-1 gene and, as a result, cancer cell proliferation and invasion in culture and tumor metastasis in vivo. In tumor-bearing mice, we observed significant anti-metastatic effects after daily treatment with CBD. Id-1 expression in tumor cells from lung foci was significantly down-regulated as well as Ki67, a marker of cell proliferation. Finally, CBD prolonged the survival of tumor-bearing mice even though the treatment was initiated after the establishment of metastases. Overall, our data suggest that Id proteins act as key regulators of tumor metastasis and suggest the use of Id genes as novel therapeutic targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5308. doi:1538-7445.AM2012-5308
CMS hadronic forward calorimeter

Tests of quartz fiber prototypes, based on the detection of Cherenkov light from showering particles, demonstrate a detector possessing all of the desirable characteristics for a forward calorimeter. A prototype for the CMS experiment consists of 0.3 mm diameter fibers embedded in a copper matrix. The response to high energy (10–375 GeV) electrons, pions, protons and muons, the light yield, energy and position resolutions, and signal uniformity and linearity, are discussed. The signal generation mechanism gives this type of detector unique properties, especially for the detection of hadronic showers: Narrow, shallow shower profiles, hermeticity and extremely feast signals. The implications for measurements in the high-rate, high-radiation LHC environment are discussed.
Backbone and sidechain methyl Ile (δ1), Leu and Val resonance assignments of the catalytic domain of the yeast mRNA decapping enzyme, Dcp2

Eukaryotic mRNA decapping by Dcp2 is the penultimate step in several mRNA decay pathways. To understand regulation of Dcp2 by ligand interactions, we have assigned the backbone and sidechain methyl Ile (δ1), Leu and Val chemical shifts of the catalytic domain of the S. Cerevisiae enzyme.
Grazing incidence optics for the U.S. High-Resolution X-Ray Astronomy Program

The major telescopes in this program are the one flown on the Einstein or HEAO-B satellite in 1978 and the one planned for the AXAF which should be launched in late 1995. The x-ray performance of the Einstein mirror is reviewed briefly, and its surface properties are inferred from a combination of its x-ray properties and the information available from the limited fabrication metrology of that era. The improvements necessary for satisfying the AXAF specification are summarized. Much of this technology already has been demonstrated in the TMA program, and this progress is reviewed.
Electrochemical and Structural Characterization of cis- and trans-[Cp(CO)Ru(μ-As(C6H5)2)]2, Isomers That Undergo Two-Electron-Transfer Oxidations†

The structures and oxidations of the cis and trans isomers of the doubly bridged dinuclear species [Cp(CO)Ru(μ-AsPh2)]2 (Ph = C6H5) have been studied by X-ray crystallography, electrochemistry, and IR and NMR spectroscopies. Each complex oxidizes in a single two-electron voltammetric process, the E1/2 values being −0.36 V for the cis isomer (1) and −0.30 V for the trans isomer (2) in CH2Cl2/0.1 M [NBu4][PF6] (referenced to ferrocene). These are apparently the first comparative redox potentials published for cis and trans isomers of bridged dinuclear organometallic complexes. Oxidation of 1 to 12+ was cleanly accomplished either by electrolysis or by oxidation of 1 by 2 equiv of ferrocenium, allowing isolation of the dication. The split carbonyl absorptions in the IR spectra of 12+ (νCO = 2032, 2050 cm-1) are consistent with formation of a Ru−Ru bond in the oxidation reaction. The electrode reaction 1/1+ + e- is much slower than the reaction 1+/12+ + e-, implying that the metal−metal bond is formed in the ...
Short-term synaptic plasticity: a comparison of two synapses

During physiological patterns of activity, synaptic activity is regulated by many forms of short-term plasticity. Here, we compare the functional consequences of such plasticity at the synapse from the climbing fibre to the Purkinje cell in the cerebellum and at the synapse between the retinal ganglion cell and the thalamocortical relay neuron in the lateral geniculate nucleus. Despite superficial similarities between these two powerful synapses, they have distinctive synaptic plasticity. The climbing fibre synapse is highly reliable but accomplishes this through many synaptic specializations. However, the retinogeniculate synapse dynamically regulates the flow of visual information by using two types of receptor that have different types of plasticity. These synapses illustrate the important functional consequences of synaptic plasticity.
Activation of I-κB kinase by the HTLV type 1 Tax protein: Mechanistic insights into the adaptor function of IKKγ

The Tax protein encoded by human T cell leukemia virus type 1 (HTLV-1) induces constitutive nuclear expression of the transcription factor NF-κB, causing aberrant expression of a large array of cellular genes. Tax activates NF-κB by stimulating the activity of the I-κB kinase (IKK), which in turn leads to phosphorylation and degradation of the NF-κB inhibitor I-κBα. In normal T cells, IKK activation occurs transiently on cellular stimulation through the T cell receptor (TCR) and the CD28 costimulatory molecule. However, this inducible kinase is constitutively activated in Tax-expressing and HTLV-1-infected T cells, which contributes to the deregulated nuclear expression of NF-κB. As a genetic approach to dissect the pathways mediating IKK activation by Tax and T cell activation signals, somatic cell mutagenesis was performed to isolate signaling-defective mutant Jurkat T cell lines. One of the mutant cell lines was shown to have a defect in NF-κB activation by both T cell mitogens and Tax. Interestingly, ...
The 2-intersection number of paths and bounded-degree trees

We represent a graph by assigning each vertex a finite set such that vertices are adjacent if and only if the corresponding sets have at least two common elements. The 2-intersection number θ2(G) of a graph G is the minimum size of the union of sets in such a representation. We prove that the maximum order of a path that can be represented in this way using t elements is between (t2 - 19t + 4)/4 and (t2 - t + 6)/4, making θ2(Pn) asymptotic to 2√n. We also show the existence of a constant c depending on ϵ such that, for any tree T with maximum degree at most d, θ2(T) ≤ c(√n)1+ϵ. When the maximum degree is not bounded, there is an n-vertex tree T with θ2(T) > .945n2/3. © 1995 John Wiley & Sons, Inc.
Penicillin skin testing in advance of need: multiyear follow-up in 568 test result-negative subjects exposed to oral penicillins.

Abstract Background: There are few published data on adverse drug reactions and/or resensitization associated with oral penicillin use in penicillin allergy history-positive/penicillin skin test-negative individuals during routine clinical care with multiyear follow-up. Objectives: We sought to provide long-term follow-up data on the type, severity, and frequency of adverse reactions associated with oral penicillin use in individuals who have histories of penicillin "allergy" yet also have negative results on penicillin skin tests done in advance of need. We also aimed to repeat testing on individuals with penicillin-associated adverse reactions. Methods: Medical records were reviewed for penicillin use and associated adverse reactions in all 568 penicillin skin test-negative individuals who had received at least 1 course of oral penicillin after testing but before December 31, 2001, during routine care. These individuals were drawn from a group of 1246 penicillin skin test-negative individuals seen initially between November 16, 1994, and August 13, 2001. Results: The mean length of follow-up was 4.26 ± 1.64 years (range, 0.39-7.12 years). The mean penicillin exposure was 3.94 ± 3.91 courses (range, 1-22 courses). Only 65 (11.4%) of 568 subjects had any penicillin-associated reactions, and 6 subjects had 2 reactions each. A reaction occurred in 27 subjects (4.8%) with their first penicillin reexposure. There were 71 (3.2%) reactions with 2236 total penicillin courses. There were no serious reactions. Repeated testing was done in 33 subjects older than age 18 years. Only 1 subject was positive on repeated penicillin skin testing. Conclusion: Penicillin use after negative penicillin skin testing done in advance of need is safe, and resensitization is rare. (J Allergy Clin Immunol 2003;111:1111-5.)
STEMI complicated with serum sodium of 113 mmol/L from syndrome of inappropriate antidiuretic hormone secretion: How worse could it be?

Abstract Hyponatremia commonly occurs in acute coronary syndrome and has been recognized as a worse prognostic indicator in patients with ST-segment elevation myocardial infarction (STEMI). However STEMI with preexisting hyponatremia from syndrome of inappropriate antidiuretic hormone secretion (SIADH) has never been described in the literature. We describe a case of 59-year-old woman who presented with STEMI and received emergent percutaneous coronary intervention who also had SIADH with the lowest serum sodium measurement of 113mmol/L. Initially, she was treated with hypertonic saline to reduce central nervous system complications. Then, vasopressin receptor 2 antagonist and demeclocycline were started as well as fluid restriction and salt tablet. Her sodium level and clinical symptoms improved. Subsequently, we found cavitary right upper lung mass and a biopsy report revealed small cell lung cancer as a cause of SIADH. Severe hyponatremia from SIADH complicated with STEMI could potentially have reduced adverse outcomes by normalizing sodium level through vasopressin receptor 2 antagonist or demeclocycline. Learning objective: Hyponatremia in STEMI from SIADH, prognosis, and treatment options.>
An observation of loading path independence of fracture in rock

Abstract The effect of stress loading path on fracture or maximum stress is investigated for several rocks. A special testing apparatus constructed for this study is described. This apparatus used conventional cylindrical specimens under pressures up to 7 kb, but with the unique features that the ratio of the two independent principal stresses could be controlled by means of electrohydraulic servo-systems, thus controlling the stress loading path. The fundamental result observed is that the maximum stresses in all rocks tested are independent of the stress loading path. Results from one-dimensional strain tests, carried out by means of the servo-controlled apparatus, are also presented.
On the population biology and meiofaunal characteristics of Manayunkia aestuarina (Polychaeta: Sabellidae: Fabricinae) from a South Carolina salt marsh

The size (age) class structure of a population of Manayunkia aestuarina (Bourne) was monitored in a South Carolina salt marsh for 1 year. Reproduction in this polychaete was discontinuous; brooded embryos and juvenile recruitment were not observed in winter months (November–March). The North American population of M. aestuarina displays different reproductive traits from those reported in England although population densities from the two geographic regions appear to be stable over the period of years. M. aestuarina attains sexual maturity while in the meiofaunal size range; yet, there are marked differences in its biology compared to typical ‘interstitial polychaetes’. M. aestuarina and selected meiofaunal taxa exhibit convergent adaptations for a semi-sedentary existence.
Adenylate cyclase from term human placenta and its regulation

Summary The activation of placental AC by either Mg 2+ or Mn 2+ , in the presence and absence of NaF, followed sigmoidal saturation kinetics. Mn 2+ enhanced maximally the NaF-stimulated Mg 2+ -dependent AC activity. The apparent K m of Mg 2+ -dependent AC for ATP was 0.4 m M , with and without NaF addition. GTP and GMP-P(NH)P stimulated the Mg 2+ -dependent AC in a dose-dependent manner with half-maximal stimulation taking place at concentrations of approximately 2 μM. In the presence of GMP-P(NH)P (10 μm) the kinetics of the AC dependence on Mg + ion concentration changed from sigmoidal to hyperbolic. Most of the AC activity (> 83 per cent) was associated with the particulate fractions of placental homogenate. For better reproducibility, the AC assay was performed using sonicated particulate fraction preparations; sonication did not alter the response of AC to stimuli to a variety of agents used in these experiments; freezing and thawing, however, obliterated the stimulation by β-adrenergic agonists. Placental AC activity was inhibited by p -hydroxymercuriphenyl sodium sulphonate in a dose-dependent fashion, and the inhibition was reversed by dithiothreitol. Mg 2+ -dependent AC was inhibited by 0.5 mm phenylhydrazine (95 per cent). Mg 2+ -dependent AC activity was responsive to stimulation by epinephrine, without and with GTP addition, with half-maximal stimulation taking place at a concentration of 2 μm. The stimulatory effect of epinephrine was blocked by propranolol in a dose-dependent manner but was not blocked by phentolamine. Oestrone, oestradiol-17β, 2-hydroxyoestreone, 2-hydroxyoestradiol-17β, dehydroepiandrosterone sulphate, and progesterone, as well as oxytocin, did not alter either the basal or GMP-P(NH)P-stimulated Mg 2+ -dependent AC activities. Preincubation of 20 000 g particulate fraction with either NaF or GMP-P(NH)P, followed by washing, resulted in preparations that remained stimulated without the requirement of any further additions.
Diminished activation of the MAP kinase pathway in CD3-stimulated T lymphocytes from old mice.

Abstract Stimulation of the ERK family of protein kinases (`extracellular signal regulated kinases', also known as MAP kinases) plays an important role in the activation of many cell types, including T lymphocytes. ERKs are activated when they are phosphorylated by an upstream activator, the dual-specific protein kinase MEK. To see if aging leads to an impairment of MEK activation in mouse T cells, we used a mobility shift assay in which activation of MEK leads to phosphorylation and altered mobility of ERK-2 kinase. Similarly, we monitored mobility of pp90rsk, a known ERK substrate, as an indication of ERK function. We found an age-related decline in the ability of mouse T cells to activate both MEK and ERK function in response to stimulation by antibodies to the CD3 chain of the T cell receptor. Aging did not alter the kinetics of enzyme activation, but did diminish (by about 2-fold) the maximal level of substrate converted into the slower migrating form. Naive and memory CD4 T cells from young mice were equally able to convert ERK2 to its slower migrating form, suggesting that the decline in MEK function is not likely to be attributable to the shift, with age, from naive to memory T cell predominance. Our data suggest that age-dependent declines in gene activation, including genes for key cytokines like IL-2, may be due to declines in the upstream signals that lead to activation of the MEK/ERK protein kinase cascade.
Some additional light on the childhood sexual abuse-psychopathology axis

Abstract This exposition is an attempt to unravel the complexities of the relationship between childhood sexual abuse and adult psychopa-thology. Four facets of the relationship are examined in some detail: (a) the extent of childhood sexual abuse; (b) the probability that sexual abuse in childhood will result in psychopathology in the adult; (c) the reliability of early life memories in later life; and (d) the role of recovered memory of trauma in the healing process. The conclusions of this logico-empirical analysis are that first, government statistics tend to underestimate the extent of childhood sexual abuse, whereas independent surveys tend to overestimate it. Estimating prevalence is further complicated by variations in the definitions of key terms. Possibly the only safe conclusion is that true prevalence cannot be reliably determined. Second, empirical investigations of childhood sexual abuse conclude that not all victims are emotionally injured. A substantial number of these investigations find ...
Discrepancies between flow cytometric and cytogenetic studies in the detection of aneuploidy in human solid tumors

Parallel flow cytometric (FCM) cell DNA studies and cytogenetic studies were performed on clinical samples from twenty human solid tumors of various types and on cell lines established in tissue culture from three of these tumors. Six of twenty clinical samples (30%) showed concordance between flow cytometry and cytogenetics with respect to the presence or absence of aneuploidy. Among the fourteen cases with discrepancies between the two methods, 8 (40% of all cases) showed hypodiploidy by cytogenetics and had diploid DNA histograms. Three cases (15%) had prominent discrete peaks in the triploid to tetraploid region by cytogenetics but had only barely discernible corresponding peaks in the DNA histogram. In two cases (10%) cytogenetic studies revealed diffuse aneuploidy. Cytogenetic studies demonstrated near-tetraploidy in three samples, but only one of these was detected by FCM; all three cases exhibited other numerical chromosomal abnormalities. In one case aneuploidy was demonstrated by FCM and not by cytogenetics. Among the tumor cell lines established in culture, the DNA Index was often higher than the cytogenetic index. Overall, 13/20 or 65% of patients with solid tumors in this study had numerical chromosomal abnormalities that were not detected by flow cytometry. Eleven of these patients had distant metastases at the time of tumor sampling, and nine of these died of their disease within 1-11 months of the time of study.
Coronary heart disease in women: update 2008.

Coronary heart disease (CHD) remains the leading cause of mortality for US women, responsible for almost 250,000 deaths annually. Preventive heart-health behavioral changes by women and aggressive coronary risk reduction can decrease the number of women disabled and killed by CHD. Angina is the predominant initial and subsequent presentation of CHD in women; categorization of chest pain and risk stratification of women assume pivotal roles. A robust evidence-based algorithm can guide cardiovascular imaging techniques to evaluate women with suspected myocardial ischemia to detect those with worsened survival. Restricted functional capacity (<5 METs) is a consistent marker of worsened prognosis. Younger women have substantially higher mortality rates than men following myocardial infarction and coronary bypass surgery. Although these women have more comorbidity and risk factors, other issues including biological differences, treatment differences, and psychosocial factors require management strategies tailored to the unique needs of women. Clinical Pharmacology & Therapeutics (2008) 83, 37–51; doi:10.1038/sj.clpt.6100447; published online 28 November 2007
Notes on Cladoniaceae in New Zealand

Abstract Australasia is a center of endemism for the lichen genus Cladonia and its allies. The taxonomic diversity of this genus in New Zealand is remarkable, with approximately 60 species recognized. This paper treats 21 species of Cladonia, including eight new taxa: C. cyanopora, C. darwinii, C. fuscofunda, C. gallowayi, C. incerta, C. pulchra, C. nitidella, and C. strangulata. Eight additional species not previously known from New Zealand are also discussed.
AMPA-induced dark cell degeneration of cerebellar Purkinje neurons involves activation of caspases and apparent mitochondrial dysfunction.

Cerebellar Purkinje neurons (PNs) are selectively vulnerable to AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepriopionic acid)-induced delayed neurotoxicity known as dark cell degeneration (DCD) that is expressed as cytoplasmic and nuclear condensation, neuron shrinkage, and failure of physiology. The present study was initiated to determine whether AMPA-receptor-induced DCD in PNs is associated with Bax translocation to the mitochondria, cytochrome C release from the mitochondria, changes in mitochondrial potential, and activation of representative initiator and executor caspases that include caspase-9, caspase-3, and caspase-7. AMPA consistently and rapidly hyperpolarized mitochondria as reflected by an increase in MitoTracker Red CMS Ros fluorescence. Increases in Bax immunoreactivity were quantitatively and temporally variable and Bax failed to localize to mitochondria. Additionally, we observed a marked increase in immunoreactivity of cytochrome C although its release from mitochondria was not apparent. Mitochondrial membrane hyperpolarization and increases in cytochrome C immunoreactivity preceded caspase activation. Immunohistochemical analyses revealed the active form of caspases-3 and -9 were markedly and significantly increased in PNs following 30 μM AMPA, and caspase-9 activation preceded caspase-3. Increases in active caspase-7 immunoreactivity were less frequently encountered in PNs. Thus DCD shares some characteristics of apoptotic programmed cell death, but lacks typical mitochondrial pathophysiology associated with classic apoptosis. These findings suggest that AMPA-induced DCD is a form of active PCD that lies on a spectrum between classical apoptosis and passive necrosis.
A role for calcitonin gene-related peptide in protection against gastric ulceration

OBJECTIVE: The goal of this investigation was to determine the role of calcitonin gene-related peptide (CGRP) in gastric mucosal resistance to ulceration. SUMMARY BACKGROUND DATA: CGRP is a 37-amino acid peptide found in the peripheral ends of afferent gastric neurons. CGRP is known to inhibit acid secretion, stimulate mucosal blood flow, and stimulate release of somatostatin. METHODS: The release of CGRP in response to intragastric and intra-arterial administration of capsaicin in the isolated, vascularly perfused rat stomach was measured by radioimmunoassay. The molecular forms of CGRP released were analyzed by gel filtration chromatography. The effect of intravenous CGRP or intragastric capsaicin on gastric ulceration induced by 100 mmol/L HCl and indomethacin was studied in intact and endogenous CGRP-depleted rats. RESULTS: Intra-arterial capsaicin (concentration range, 10(-7) to 10(-5) mol/L) stimulated a prompt and sustained release of immunoreactive CGRP, of which 84% coeluted with rat 1-37 CGRP I by gel filtration. Intragastric capsaicin (range, 10(-5) to 10(-4) mol/L) failed to release CGRP into the vascular perfusate. In intact rats, intragastric capsaicin (10(-6) mol/L) or intravenous CGRP I (10 micrograms/kg/hr) reduced the number and area of mucosal lesions caused by HCl and indomethacin compared with the findings in control rats. Rats depleted of endogenous CGRP were more susceptible to gastric ulceration than were normal rats. Intragastric capsaicin failed to protect the mucosa of CGRP-depleted rats, whereas exogenous intravenous CGRP was effective. CONCLUSIONS: These data support the hypothesis that CGRP released from gastric enteric neurons mediates gastric mucosal resistance to ulceration by noxious agents.