cssi/SciSciGPT-SciSciNet huggingface dataset:
Fault-tolerant distributed simulation

In traditional distributed simulation schemes, the entire simulation needs to be restarted if any of the participating logical processes (LPs) crash. This is highly undesirable for long running simulations. Some form of fault tolerance is required to minimize the wasted computation. A rollback based optimistic fault tolerance scheme is integrated with an optimistic distributed simulation scheme. In rollback recovery schemes, checkpoints are periodically saved on stable storage. After a crash, these saved checkpoints are used to restart the computation. We make use of the novel insight that a failure can be modeled as a straggler event with the receive time equal to the virtual time of the last checkpoint saved on stable storage. This results in saving of implementation efforts, as well as reduced overheads. We define stable global virtual time (SGVT), as the virtual time such that no state with a lower timestamp will ever be rolled back despite crash failures. A simple change is made in existing GVT algorithms to compute SGVT. Our use of transitive dependency tracking eliminates antimessages. LPs are clubbed in clusters to minimize stable storage access time.
A slow-wave resonant electrode design for optical modulators

A slow-wave resonant electrode structure is proposed for the phase velocity matching between the RF wave and optical signal in III-V optical modulators. The resonant structure should result in reduced RF drive requirements for the modulator. For a planar structure, the proposed velocity-matched electrode configuration employs a coplanar waveguide (CPW) design, which consists of the usual center conductor segmented into a series of Z-shaped cascaded resonators. A similar electrode design may be used for III-V semiconductor ridge guides. With this design, the effective quality factor, Q, of the resonant structure will result in a decrease of the drive voltage. Thus, the power requirement can be reduced by a factor of Q/sup 2/ for a bandwidth of 10%. In addition, the bandwidth design can be improved by using Chebyshev design for coupled-line filters. Experimental results are discussed. The results indicate that, for the GaAs-AlGaAs optical waveguide, the optical phase velocity is 2.65/3.61 times smaller than RF phase velocity. With the proposed electrode design the RF phase velocity can be reduced by simply adjusting the resonator spacing. >
High-Temperature and High-Voltage Diamond Devices

High-temperature and high-voltage devices were fabricated using a bi-layer structure consisting of undoped and boron-doped diamond layers. These layers were epitaxialy grown on a synthesized single-crystal diamond of (100) orientation by a microwave plasma-assisted chemical vapor deposition (CVD) using H2, CH4 and B2H6 as reactant gases.
Packet error rate for burst-error-correcting codes in Rayleigh fading channels

In this paper, we estimate the packet error rate for data transmission over Rayleigh fading channels using burst-error correcting codes. For a certain fade margin and Doppler frequency, depending on the packet length and the fade and interfade duration statistics, bit-errors in a packet may occur in one, two or more bursts of different lengths. The packet is then considered to be lost whenever the error pattern in a packet exceeds the burst-error-correcting capability of the code. For a given data rate, these maximum tolerable bursts of errors translate to certain thresholds on the duration of fades. Thus we formulate packet loss as a level crossing problem and study the effect of Doppler frequency, fade margin, and burst error correction coding on packet error rate (PER).
Foraging in a fractal environment: Spatial patterns in a marine predator-prey system

Spatial relationships between predators and prey have important implications for landscape processes and patterns. Highly mobile oceanic birds and their patchily distributed prey constitute an accessible model system for studying these relationships. High-frequency echosounders can be used together with simultaneous direct visual observations to quantitatively describe the distributions of seabird consumers and their resources over a wide range of spatial scales, yielding information which is rarely available in terrestrial systems.
Proteostasis and the Aging Proteome in Health and Disease

The maintenance of the proteome is essential to preserve cell functionality and the ability to respond and adapt to the changing environment. This is regulated by the proteostasis network, a dedicated set of molecular components comprised of molecular chaperones and protein clearance mechanisms, regulated by cell stress signaling pathways, that prevents the toxicity associated with protein misfolding and accumulation of toxic aggregates in different subcellular compartments and tissues. The efficiency of the proteostasis network declines with age and this failure in protein homeostasis has been proposed to underlie the basis of common age-related human disorders. The current advances in the understanding of the mechanisms and regulation of proteostasis and of the different types of digressions in this process in aging have turned the attention toward the therapeutic opportunities offered by the restoration of proteostasis in age-associated degenerative diseases. Here, we discuss some of the unresolved questions on proteostasis that need to be addressed to enhance healthspan and to diminish the pathology associated with persistent protein damage.
Self-Timed Programmable Processors

Designing a self-timed programmable processor is a challenging task because of its complexity. Despite the difficulties, self-timed programmable processors have recently drawn some attention from computer architecture designers [1,2,3]. The debate over which design discipline provides the most cost-effective system has not been resolved in four decades, and is technology-dependent. However, the interest in designing fully self-timed processors stems from a very different motivation. We like to experiment with the average speed exhibited by a self-timed programmable processor, since a moderate speed-up (two to five times faster) would have tremendous impact on how high performance digital systems will be implemented in the future.
Low power light-weight embedded systems

Light-weight embedded systems are now gaining more popularity due to the recent technological advances in fabrication that have resulted in more powerful tiny processors with greater communication capabilities that pose various scientific challenges for researchers. Perhaps the most significant challenge is the energy consumption concern and reliability, mainly due to the small size of batteries. In this tutorial, we portray a brief description of low-power, light-weight embedded systems, depict several power profiling studies previously conducted, and present several research challenges that require low-power consumption in embedded systems. For each challenge, we highlight how low-power designs may enhance the overall performance of the system. Finally, we present a several techniques that minimize the power consumption in such systems.
Formation of c1 fragment ions in collision‐induced dissociation of glutamine‐containing peptide ions: a tip for de novo sequencing

A c 1 ion was observed with significant yield in the tandem mass (MS/MS) spectra of peptide ions containing glutamine as the second amino acid residue from the N-terminus. The c 1 fragment was generated independently of the N-terminal residue of the peptide, but its abundance was strongly dependent on the side-chain identity. This ion is not a common fragmentation product in low-energy collision-induced dissociation of peptide ions, but it assists in identification of the first two amino acid residues, often difficult due to a low or absent signal from the heaviest y ion. A consecutive fragmentation mechanism is proposed, involving a b 2 ion with a six-membered ring as an intermediate, to explain the exceptional stability of the c 1 fragment ion. The utility of this information is discussed, especially in de novo sequencing of peptide ions.
Multilinear functional inequalities involving permanents, determinants, and other multilinear functions of nonnegative matrices and M-matrices

Abstract Motivated by a proof due to Fiedler of an inequality on the determinants of M -matrices and a recent paper by the authors, we now obtain various inequalities on permanents and determinants of nonsingular M -matrices. This is done by extending the multilinear considerations of Fiedler and, subsequently, of the authors, to fractional multilinear functionals on pairs of nonnegative matrices. Two examples of our results: For an n × n nonsingular M -matrix M (i) we give a sharp upper bound for det( M )+per( M ), when M is a nonsingular M -matrix, (ii) we determine an upper bound on the relative error |per( M + E )−per( M )|/|per( M )|, when M + E is a certain componentwise perturbation of M .
Preoperative Temporal Bone Computed Tomography Scan and Its Use in Evaluating the Pediatric Cochlear Implant Candidate

Preoperative computed tomography (CT) scan evaluation of the temporal bones in cochlear implant candidates plays a crucial role in determining candidacy and the side of implantation. The CT scans allow the surgeon to carefully review the anatomy of the inner ear and mastoid cavity in order to predict any potential difficulties or complications that may be encountered during the implant insertion. We retrospectively reviewed 50 preoperative CT scans of the temporal bone in children who have been successfully implanted. In these scans, we assessed the degree of mastoid pneumatization, cochlear anatomy and patency, size of the vestibular aqueduct, cochlear aqueduct, and internal auditory canal. We analyzed our findings and measurements and compared our results with the degree of difficulty noted in the insertion of the implant, the number of electrodes inserted in each case, and the overall complication rate. From this radiographic review, we have created a checklist for cochlear implant surgeons in order to highlight key features that need to be recognized in the temporal bone scan in preoperative evaluation of cochlear implant candidates.
Incidence and risk factors for HIV-1 infection—a summary of what is known and the psychiatric relevance

The human immunodeficiency virus type 1 (HIV-1) epidemic continues to grow both within the United States and worldwide. Currently, HIV-1 disease is the greatest killer of American men and third greatest killer of women aged 25–44. The major routes of HIV-1 transmission are: (i) heterosexual and (ii) homosexual sex with infected partners; (iii) injection drug use (IDU) with a needle previously used by an infected person; and (iv) transmission from an infected mother to her infant. The HIV-1 epidemic in industrial countries initially occurred largely among homosexual men, but now 53% of American AIDS cases occur in IDUs and heterosexual/infant risk groups. While the risk of infection from a single unsafe sex or IDU act may be less than one per cent, the repeated practice of these activities by participants makes overall risk quite great. Cessation of risky drug use and/or sexual behavior is the only way to prevent transmission by these routes. Use of condoms in sex, while not 100% effective, dramatically re...
Evidence for Posttranslational Protein Flavinylation in the Syphilis Spirochete Treponema pallidum: Structural and Biochemical Insights from the Catalytic Core of a Periplasmic Flavin-Trafficking Protein

ABSTRACT The syphilis spirochete Treponema pallidum is an important human pathogen but a highly enigmatic bacterium that cannot be cultivated in vitro . T. pallidum lacks many biosynthetic pathways and therefore has evolved the capability to exploit host-derived metabolites via its periplasmic lipoprotein repertoire. We recently reported a flavin-trafficking protein in T. pallidum (Ftp_Tp; TP0796) as the first bacterial metal-dependent flavin adenine dinucleotide (FAD) pyrophosphatase that hydrolyzes FAD into AMP and flavin mononucleotide (FMN) in the spirochete9s periplasm. However, orthologs of Ftp_Tp from other bacteria appear to lack this hydrolytic activity; rather, they bind and flavinylate subunits of a cytoplasmic membrane redox system (Nqr/Rnf). To further explore this dichotomy, biochemical analyses, protein crystallography, and structure-based mutagenesis were used to show that a single amino acid change (N55Y) in Ftp_Tp converts it from an Mg 2+ -dependent FAD pyrophosphatase to an FAD-binding protein. We also demonstrated that Ftp_Tp has a second enzymatic activity (Mg 2+ -FMN transferase); it flavinylates protein(s) covalently with FMN on a threonine side chain of an appropriate sequence motif using FAD as the substrate. Moreover, mutation of a metal-binding residue (D284A) eliminates Ftp_Tp9s dual activities, thereby underscoring the role of Mg 2+ in the enzyme-catalyzed reactions. The posttranslational flavinylation activity that can target a periplasmic lipoprotein (TP0171) has not previously been described. The observed activities reveal the catalytic flexibility of a treponemal protein to perform multiple functions. Together, these findings imply mechanisms by which a dynamic pool of flavin cofactor is maintained and how flavoproteins are generated by Ftp_Tp locally in the T. pallidum periplasm. IMPORTANCE Treponema pallidum, the syphilis spirochete, exploits its periplasmic lipoproteins for a number of essential physiologic processes. One of these, flavin-trafficking protein (Ftp), not only exploits its catalytic center to mediate posttranslational flavinylation of proteins (to create flavoproteins) but also likely maintains the periplasmic flavin pool via its unique ability to hydrolyze FAD. This functional diversity within a single lipoprotein is quite remarkable and reflects the enzymatic versatility of the treponemal lipoproteins, as well as molecular parsimony in an organism with a limited genome. Ftp-mediated protein flavinylation in the periplasm also likely is a key aspect of a predicted flavin-dependent Rnf-based redox homeostasis system at the cytoplasmic membrane of T. pallidum. In addition to its importance in T. pallidum physiology, Ftp homologs exist in other bacteria, thereby expanding our understanding of the bacterial periplasm as a metabolically active subcellular compartment for flavoprotein biogenesis as well as flavin homeostasis.
Elevated serum creatine phosphokinase is associated with mortality and inotropic requirement in critically injured adults.

Background Hemeproteins such as free myoglobin can undergo autoxidation and catalyse lipid peroxidation, increasing oxidative stress. Creatine phosphokinase (CPK) elevation is a marker for free myoglobin after myocyte damage. Since oxidative injury is a key mechanism of injury-related organ dysfunction, we hypothesised that serum CPK levels correlate with mortality and need for inotropic medication and duration of inotropic support, i.e. shock, among critically injured patients. Methods We conducted a retrospective review of 17,847 patients admitted to a single Trauma Intensive Care Unit over 9 years. 2583 patients with serum CPK levels were included in the analysis. Patient data were collected continuously into an electronic ICU repository. Univariate analysis was accomplished using Spearman correlation and the Mann–Whitney U test. Propensity score adjustment models accounting for potential confounders were used to assess the independent effect of CPK level on mortality, need for inotropic support, and duration of inotropic support. Results Median CPK was significantly higher in patients who died (916 [IQR 332, 2472] vs. 711 [253, 1971], p = 0.004) and in those who required inotropic medications (950 [353, 2525] vs. 469 [188, 1220], p < 0.001). After adjusting for propensity score and potential confounders the odds of mortality increased by 1.10 (95% CI 1.02–1.19, p = 0.020) and the odds of inotropic medication use increased by 1.30 (95% CI 1.22–1.38, p < 0.001) per natural log unit increase in CPK. There was a significant association between CPK level and duration of inotropic support (Spearman's rho .237, p < 0.001) that remained significant in a propensity score-adjusted model. Conclusion In critically injured patients, elevated serum CPK level is independently associated with mortality, need for inotropic medication, and duration of inotropic support. This study is the first to evaluate the relationship of CPK level and mortality in addition to surrogate measures of shock in a population of critically injured patients. If these associations are verified prospectively, there may be a role for treatment with hemeprotein reductants, such as paracetamol, to mitigate the effects of shock and end-organ dysfunction.
Synthesis and analysis of fluorescence decay data using a systems theory approach

This paper shows an example of using linear systems theory for modeling a process encountered in biophysical chemistry research. A new technique using state space theory for synthesis and analysis of measured data from time-correlated single photon counting experiments is suggested in this paper. By way of this application it is demonstrated that there exist important common themes between seemingly disparate disciplines.
Spirituality, religion and palliative care.

As medical science has evolved, many conditions that once were thought to be “death sentences” have become chronic illness. In some ways, this makes death and dying more complicated, fraught with decisions about what care is appropriate and when to withhold or withdraw care. Studies have shown that most patients faced with life-threatening illness have spiritual needs that are not adequately addressed by their health care providers. The philosophy and practice of palliative care operates upon an understanding of whole person care, reflected in the muli-dimensional approach of the biopsychosocial model. One cannot provide whole-person care without giving consideration to the relevant spiritual needs held by patients with serious illness. As palliative care clinicians, we are uniquely positioned to work with teams/patients/families to explore the many variables that individuals and their families use as the guiding principles when making difficult decisions around end of life. While we are often consulted to manage physical symptoms, that is only part of our work. As we work on building relationships, both with our patients and their care team, we are often able to help facilitate communication that allows for mutually satisfactory goal setting. We are equipped to work with patients within their cultural contexts of which spirituality is a part. It is important to recognize the barriers to providing adequate spiritual care. The National Consensus Project has created clinical practice guidelines to provide a road map for the provision of quality palliative care. These guidelines delineate eight domains that are addressed through the provision of palliative care; the fifth domain gives attention to spiritual, religious and existential aspects of care. Guidelines recommend the use of standardized tools wherever possible to assess spiritual needs; referral to members of the interdisciplinary team who have specialized skills in addressing existential and spiritual concerns, and initiating contact and communication with community spiritual providers as requested by patients and their families. Palliative care providers are also called to be advocates for the spiritual and religious rituals of patients and families, especially at the time of death.
Escalation of aggressive vocal signals: a sequential playback study

Rival conspecifics often produce stereotyped sequences of signals as agonistic interactions escalate. Successive signals in sequence are thought to convey increasingly pronounced levels of aggressive motivation. Here, we propose and test a model of aggressive escalation in black-throated blue warblers, presenting subjects with two sequential and increasingly elevated levels of threat. From a speaker outside the territorial boundary, we initiated an interaction (low-threat level), and from a second speaker inside the territory, accompanied by a taxidermic mount, we subsequently simulated a territorial intrusion (escalated threat level). Our two main predictions were that signalling behaviours in response to low-threat boundary playback would predict signalling responses to the escalated within-territory threat, and that these latter signalling behaviours would in turn reliably predict attack. We find clear support for both predictions: (i) specific song types (type II songs) produced early in the simulated interaction, in response to boundary playback, predicted later use of low-amplitude ‘soft’ song, in response to within-territory playback; and (ii) soft song, in turn, predicted attack of the mount. Unexpectedly, use of the early-stage signal (type II song) itself did not predict attack, despite its apparent role in aggressive escalation. This raises the intriguing question of whether type II song can actually be considered a reliable aggressive signal. Overall, our results provide new empirical insights into how songbirds may use progressive vocal signalling to convey increasing levels of threat.
A +2.3dBm 124–158GHz Class-C frequency quadrupler with folded-transformer based multi-phase driving

This paper presents a D-band frequency quadrupler from 124GHz to 158GHz. The design leverages a folded-transformer based passive network to generate high-quality and broadband differential quadrature driving signals with low loss for the input tone centered at 35GHz. Then, the four-phase signals drive the 1st-stage frequency doublers to yield fully differential signals at the 2nd harmonic frequency (70GHz), which feed another push-push frequency doubler and generate the desired 4th harmonic output at 140GHz. The push-push doublers are designed based on 2nd harmonic load-pull with Class-C operation for optimized output power and efficiency. The quadrupler is implemented in a 32nm CMOS SOI process occupying only 530µm-by-550µm. It achieves the state-of-the-art output power of +2.3dBm, a peak DC-to-RF efficiency of 5.3%, and the best reported −3dB bandwidth of 24% at D-band under 1.1V supply.
Estimating Operational Risk Capital from Truncated Data with Constrained Optimization

In this presentation, the effect of data truncation on model stability is shown to be significant due to implied extrapolation into the region below threshold. Since the instability results from the absence of data below the truncation point, it can't be addressed by alternative fitting techniques. New information needs to be leveraged to resolve the problem. One source of information is the aggregated data of operational risk losses that fall below the truncation point, data which is often available but not used in modeling. The presentation demonstrates how to utilize this data to improve estimates of model distribution parameters and capital.
Alternative perspectives on Mild Cognitive Impairment (MCI): Broadening the definition of MCI.

Mild cognitive impairment (MCI) is a relatively newly described phenomenon representing a mild deficit on the continuum between normal aging and dementia. Although MCI is the source of much interest and research in the fields of neuroscience and medicine, its definition, prevalence, and criteria for diagnosis has yet to become standardized and is the subject of much controversy. While there is some consensus among American and European researchers about the construct of MCI, others argue that these researchers focus too much on MCI as a preclinical state of Alzheimer’s disease (Ad) and thus is too narrow. MCI must also be examined in the context of each individual patient, taking into account each person’s unique needs and the degree to which his or her life is affected by the cognitive impairment in question. As the upcoming DSM-5 criteria are still being decided, it is a particularly opportune time to focus on alternative perspectives and definitions of MCI to ensure the best clinical definition possible can be determined.
Constrained Capacity and Equilibrium Forward Premia in Electricity Markets

This paper extends the equilibrium electricity pricing model in Bessembinder and Lemmon (2002). The new model accounts for constrained capacity, an important feature in electricity markets. Explicitly including a role for capacity allows the model to reproduce the price spikes observed in wholesale electricity markets using reasonable parameter values. The model implies that the equilibrium forward premium, defined to be the forward price minus the expected spot price, is decreasing in spot price variance when the expected spot price is low, but is increasing in the spot price variance when the expected spot price is high. I extend the empirical work in Longstaff and Wang (2004) and show that data from the Pennsylvania-New Jersey-Maryland (PJM) market support these model predictions.
Heterogeneity of NH+4 transport in mouse inner medullary collecting duct cells

Previous studies from our laboratory have demonstrated that NH+4 substitutes for K+ on the Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) in rat terminal inner medullary collecting duct cells (tIMCD). To examine other NH+4 transport pathways, a transgenic mouse cell line, mIMCD-3, was employed. 86Rb+ was used as a K+ congener to explore NH+4/Rb+ (K+) competition on the extracellular K+ binding site of the Na(+)-K(+)-2Cl- cotransporter and the Na(+)-K(+)-ATPase. Addition of K+ or NH+4 reduced both bumetanide- and ouabain-sensitive Rb+ uptake. This reduction in Rb+ uptake with NH+4 addition was not due to intracellular pH-mediated changes in transporter activity. K+ and NH+4 are competitive inhibitors on both transporters. On the Na(+)-K(+)-2Cl- cotransporter, the Michaelis constant (Km) for K+ was 4.6 +/- 0.5 mM with an inhibitory constant (Ki) for NH+4 of 2.8 mM. In contrast, on the Na(+)-K(+)-ATPase, the apparent affinity for K+ was greater than for NH+4. To test Na(+)-K(+)-2Cl- cotransport-mediated NH+4 flux, bumetanide-sensitive NH+4/Rb+ exchange was measured. Bumetanide-sensitive Rb+ efflux was greater with extracellular K+ or NH+4 present relative to efflux with extracellular N-methyl-D-glucamine. This demonstrates both K+/Rb+ and NH+4/Rb+ countertransport by the Na(+)-K(+)-2Cl- cotransporter. In conclusion, NH+4 is transported in a bumetanide-sensitive Na(+)-NH+4-Cl- mode, and both NH+4 and Rb+ (K+) are competitive inhibitors for the extracellular K+ binding site. However, the kinetics of Na(+)-K(+)-2Cl(-)-mediated NH+4 transport differ from other K+ transport-mediated NH+4 pathways, such as the Na(+)-K(+)-ATPase.
Case reports: Neurenteric Cysts of the Posterior Fossa: Recognition, Management, and Embryogenesis

Neurenteric cysts are endothelium-lined structures most commonly encountered in the lower cervical or upper thoracic spinal cord. The occurrence of neurenteric cysts within the cranial vault is unusual. We present three patients with neurenteric cysts located within the posterior fossa: one near the
Politics as art

Italian Futurism emerged in the first decade of this century as a movement of both art historical and political significance. Led by impresario poet and propagandist F T. Marinetti, Futurism inaugurated the avantgardist attack on the autonomous status of art in modern bourgeois society, the repudiation of tradition, and the emphasis on formal innovation that would characterize modernist movements for decades to follow. As Renato Poggioli said, "the Futurist moment belongs to all the avant-gardes and not only to the one named for it."2 The specific political affiliations and activities of the Futurists are by now well known. In "The Founding and Manifesto of Futurism" of 1909, Marinetti upheld the glory of war, "the world's only hygiene," as an announcement of the imminent crisis that would reveal the radical foundation of a new social and aesthetic world order. Futurist art, Marinetti declared, would act as an incendiary device, upholding the new values of speed, destruction, and violence necessary for a new age of Italian national grandeur. Active propagandists and campaigners for Italy's entry into the first World War, members of the movement formed a Futurist volunteer group to the front where several were wounded and killed, as Marinetti himself often boasted.3 In 1919, Marinetti not only led a group of arditi in the burning of the offices of the Milanese Socialist newspaper Avanti but appeared, as a member of the Central Committee alongside Mussolini, on the first list of Fascist candidates. In 1929, Marinetti accepted the prestigious appointment from Mussolini to the Accademia d'Italia.4
Impressions, summary and questions raised by the IgA symposium.

During this conference, Dr. Richard Hong has referred to the IgA immunity system as an adolescent. By this, he implies that the IgA system is beginning to show signs of maturity, while at the same time being hard to understand and certainly difficult to contain. I am sure all of us can agree with him as we grapple with the huge amount of new information and attempt to sort this into a manageable understanding of IgA and its relationship to immunity in general.
Effects of charcoal-extracted, bovine follicular fluid on gonadotropin concentrations, the onset of estrus and luteal function in heifers.

A study was conducted to determine the effect of charcoal-extracted, bovine follicular fluid (CFF) on plasma follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations, the interval from luteolysis to estrus, and subsequent luteal function in heifers. Fifteen Angus, Simmental and Hereford heifers were allotted by age, weight and breed to a control (C, n = 8) or a CFF (n = 7) group. Heifers received injections of saline or CFF (iv, 8 ml/injection) every 12 h from d 1 (d 0 estrus) through d 5 of the estrous cycle. On d 6, each heifer was injected (im) with 25 mg of prostaglandin F2 alpha (PGF2 alpha). Blood samples were collected every 12 h by venipuncture starting just before the first saline or CFF injection and continuing until estrus. Thereafter, blood samples were collected every other day during the subsequent estrous cycle and assayed for FSH, LH, estradiol-17 beta and progesterone by radioimmunoassay. Injections of CFF had no effect (P greater than .05) on circulating FSH or LH concentrations from d 1 to 5 relative to the C group; however, there was a transient rise (P less than .05) in FSH concentrations 24 h following cessation of CFF injections. This transient rise in FSH was not immediately followed by an increase in plasma estradiol-17 beta concentrations. Although CFF injections did not interfere with PGF2 alpha-induced luteolysis, the interval from PGF2 alpha injection to estrus was delayed (P less than .05) by 5 d in the CFF group compared with the C group.(ABSTRACT TRUNCATED AT 250 WORDS)
Contributions of Subcortical Lacunar Infarcts to Cognitive Impairment in Older Persons

Alzheimer’s disease (AD) and cerebrovascular disease (CVD) are generally considered the most common causes of cognitive impairment and dementia in older persons and are independent but frequently comorbid pathological processes. It is well established that AD is a major contributor to cognitive impairment and dementia, but the effects of CVD are less clear. Not only is there controversy about the magnitude of CVD effects in general, but CVD is also pathologically heterogenous and there also are important questions about how specific manifestations of CVD relate to cognition.
Abstract A15: Sin3B: a non-classical tumor suppressor

Perturbations in cell cycle regulators elicit hyperproliferation and the inability of cells to exit the cell cycle, which are common occurrences in cancer. Recently, we have demonstrated that Sin3B, an essential component of the mammalian histone deacetylase repressor complex, is required for oncogene-induced senescence both in vitro and in vivo. Surprisingly, primary Sin3B-null cells are not readily transformed upon ectopic expression of oncogenic Ras. Thus, these observations indicate that loss of Sin3B uncouples the ability to undergo senescence from the sensitivity to transformation in primary cells. To better understand the relationship between Sin3B, senescence and transformation, we have generated novel immortalized cell lines genetically inactivated for Sin3B. Our results indicate that in these Sin3B-deleted cells, expression of oncogenic Ras promotes transformation and provides a proliferative advantage. Interestingly, we have demonstrated that the paired amphipathic helix 2 (PAH2) domain is crucial for the tumor suppressive nature of Sin3B. To elucidate the molecular bases for these effects, immunoprecipitation and mass-spectrometry was performed to identify the proteins associated with Sin3B and its loss-of-function mutants. We have now identified novel interactors of the Sin3B complex and defined crucial domains responsible for the complex9s assembly. These observations suggest that Sin3B functions as a non-classical tumor suppressor which serves to limit the transformative potential of cancer cells. The restoration of Sin3B functionality and downstream pathways may prove useful in the design of targeted therapies to treat advanced disease. Citation Format: Anthony J. Bainor, Beatrix Ueberheide, Gregory David. Sin3B: a non-classical tumor suppressor. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Cancer Cell Cycle - Tumor Progression and Therapeutic Response; Feb 28-Mar 2, 2016; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(11_Suppl):Abstract nr A15.
IL-10 enhances IgE-independent IL-33-mediated mast cell cytokine production

IgE antibodies play a critical role in antigen-mediated mast cell activation. However, mast cells can be activated via IgE-independent mechanisms including signaling via the IL-33 receptor ST2. We have previously shown that the Th2-derived cytokine IL-10 can enhance IgE-dependent mucosal mast cell activation and promote mast cell function and survival. However, whether the effects of IL-10 on mast cells are global in nature and not limited to IgE-mediated signaling is not clear. To determine whether IL-10 can prime the activation of mast cells mediated by IgE-independent signals such as IL-33, we assessed the effects of rIL-10 exposure on IL-33-stimulated mast cells and their subsequent activation via IgE. Bone marrow-derived mast cells (BMMCs) from wild-type (WT) and IL-10 −/− mice were cultured with rIL-33 with or without rIL-10 and activated with DNP-IgE and antigen. Exposure to IL-10 enhanced cytokine production in both WT and IL-10 −/− BMMCs, and this was significantly increased after activation via IgE. IL-10 −/− BMMCs exhibited decreased cytokine production, but this was restored upon culture with rIL-10. Interestingly, IL-33 stimulation (and subsequent activation with IgE) induced comparably enhanced levels of cytokine production, specifically IL-13 and IL-6, in both WT and IL-10 −/− cells, suggesting that ST2-mediated signals can overcome the lack of IL-10. However, the addition of exogenous IL-10 to IL-33-stimulated cultures further enhanced the levels of these cytokines not only in IgE-activated cells, but also in cells stimulated with IL-33 alone. Our observations therefore suggest that IL-10 can play critical roles in enhancing mast cell function both via IgE-dependent and independent mechanisms.
Dynamic fracture and hot-spot modeling in energetic composites

Defects such as cracks, pores, and particle-matrix interface debonding affect the sensitivity of energetic materials by reducing the time-to-ignition and the threshold pressure to initiate an explosion. Frictional sliding of preexisting cracks is considered to be one of the most important causes of localized heating. Therefore, understanding the dynamic fracture of crystalline energetic materials is of extreme importance to assess the reliability and safety of polymer-bonded explosives. Phase field damage model simulations, based on the regularization of the crack surface as a diffuse delta function, are used to describe crack propagation in cyclotetramethylene-tetranitramine crystals embedded in a Sylgard matrix. A thermal transport model that includes heat generation by friction at crack interfaces is coupled to the solution of crack propagation. 2D and 3D dynamic compression simulations are performed with different boundary velocities and initial distributions of cracks and interface defects to underst...
EGFR-related genomic abundance associates with EGFR mutation in non-small cell lung cancer and is accurately detected by interphase FISH

2419 Members of the EGFR family of receptors are important players in lung tumorigenesis and ideal targets for molecular therapy. EGFR tyrosine kinase inhibitors (TKIs) are effective in non-small cell lung carcinoma (NSCLC) and mutations in EGFR as well as EGFR and HER2 high copy numbers have been associated with sensitivity to TKIs. The association of EGFR mutation, gene amplification and sensitivity to TKIs was investigated in NSCLC cell lines and a comprehensive cytogenetic evaluation (metaphase and interphase fluorescence in situ hybridization - FISH, GTL banding, spectral karyotyping - SKY and comparative genomic hybridization - CGH) was performed to verify whether interphase FISH analysis was technically accurate to represent genomic status. Gene amplification was found in higher frequency among 8 lines carrying EGFR mutations (6, 2 and 1 for EGFR, HER2 and HER3 respectively) than in 26 lines without mutation (0, 1 and 0, respectively). Sensitivity to TKIs increased according to the sum of the mean copy number per cell of the EGFR, HER2 and HER3 genes. All sensitive lines had >15 copies of these genes per cell. Metaphase FISH analysis has not detected gene amplification in cases of small amplicons. Small gene clusters identified by interphase FISH were confirmed as gene amplification by CGH when present in the majority of nuclei (EGFR in H820, HER2 in HCC827) but not when observed in
Diagnosing and treating postpartum uterine artery pseudoaneurysm

Uterine artery pseudoaneurysm (UAP) is an uncommon cause of postpartum hemorrhage. We present a case of a 19-year-old woman 6 weeks postpartum after low transverse cesarean delivery with recurrent ...
Abstract P4-11-06: The role of patient perceptions in under reporting chemotherapy induced peripheral neuropathy (CIPN)

Background: Although paclitaxel remains one of the most efficacious and commonly used agents in the treatment of breast cancer, it can cause a number of side effects. Decisions to delay, decrease, or discontinue treatment are made based on the severity of chemotherapy induced peripheral neuropathy (CIPN), which is not objectively measured but relies on patient9s accurately reporting symptoms to their clinical team. There is some concern that patients do not accurately or completely report CIPN symptoms during treatment. A previous study reported that 3 of 24 patients (12.5%) considered or could understand another patient9s decision to under-report CIPN symptoms to avoid treatment disruption. The objective of this follow-up study was to determine whether under-reporting occurred and to understand patient perspectives on topics previously found relevant to a patient9s decision to under-report CIPN. Methods: Ten patients with early stage breast cancer who received adjuvant paclitaxel 80 mg/m2 for up to 12 weeks, who had no prior neuropathy or neurotoxic chemotherapy participated in a recorded, semi-structured, phone-based interview that followed an interview guide designed to cover topics relevant to patient under-reporting . The interviews were then transcribed and qualitatively analyzed using NVivo software to identify common themes. Results: No patients in this study admitted to under-reporting neuropathy. Themes that emerged from the interviews are presented in Table 1. Conclusion: Insight as to how patients perceive various aspects of paclitaxel treatment revealed that comfort level with providers, inclusion in the decision-making process, and encouragement to fully disclose all symptoms played an important role when patients considered whether to report adverse effects. Future research may focus on whether a lack of health literacy and/or health care related work experience predisposes to CIPN under-reporting. Citation Format: Hertz DL, Krumbach E, Nobles B, Erickson S, Farris KB. The role of patient perceptions in under reporting chemotherapy induced peripheral neuropathy (CIPN) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-11-06.
Advances in surface-coated single-walled carbon nanotubes as near-infrared photoluminescence emitters for single-particle tracking applications in biological environments

Single-particle tracking (SPT) represents a powerful tool for revealing the single-molecule dynamics in a number of biological processes in live cells and biological tissue. Single-walled carbon nanotubes (SWCNTs) are promising photoluminescence emitters for SPT applications in various biological environments due to their characteristic large-aspect-ratio structures along with their bright and stable near-infrared (NIR) photoluminescence, which are invaluable for long-term video-rate imaging and tracking applications at the single-molecule level with high signal-to-noise ratios (SNRs). Recent advances in applying SWCNTs as NIR photoluminescence emitters have highlighted the understanding of brain tissue organization at the nanometer scale. In the first section, this review article summarizes the latest advances in different surface coatings commonly used for encapsulating SWCNT surfaces via molecular self-assembly in order to obtain surface-coated nanotubes with low cytotoxicity and minimal nonspecific interactions with live cells while maintaining their emission of bright photoluminescence to enable long-term photoluminescent imaging and tracking at the single-nanotube level in biological environments. The second section offers a comparison of different excitation strategies of (6,5) SWCNTs to determine the best excitation wavelength for efficient video-rate imaging and tracking of individual nanotubes in live brain tissue for up to tens of minutes without inducing unacceptable phototoxicity or temperature increases. Finally, this review showcases that, by utilizing the photoluminescence tracking of single nanotubes combined with super-resolution single-molecule localization microscopy technologies, it is practical to elucidate the ultrafine nanometer-scale organization of the brain extracellular space (ECS) and probe the local rheological properties of young rat brain with a subdiffraction optical resolution down to 50 nm at a subwavelength accuracy of ~40 nm. The findings primarily indicate the great diversity of the brain ECS and the inhomogeneous properties of the local viscosity in live brain tissue. Overall, because of their advantages of low cytotoxicity, bright photoluminescence, high SNRs (~25), and deep tissue penetration (~100 μm) for long-term video-rate imaging and tracking at the single-nanotube level under 845 nm excitation (K-momentum exciton–phonon sideband, KSB), phospholipid-polyethylene glycol-coated SWCNTs hold great potential as NIR photoluminescence emitters for single-particle tracking in biological environments, as exemplified here in live brain tissue, and may find extended applications in elucidating the fundamental roles of the brain ECS in various biological processes, such as sleep, memory, aging, brain tumor progression, and neurodegenerative disease development.
The scale of life and its lessons for humanity.

The scale of life on Earth is shaped by a confluence of biophysical, evolutionary, ecological, and, recently, human forces. Measuring the scale of life offers insights about these forces and raises many more questions. In PNAS, Bar-On et al. (1) offer the most comprehensive quantification to date of the biomass of life on Earth, broken down by major taxonomic groups, ecological strategies, and environments. Despite high uncertainty in some estimates, their findings shed fascinating light on how biomass is distributed. Although many of the detailed findings will likely surprise most readers, the study also builds a foundation for exploring major ecological, evolutionary, and environmental questions. We highlight two such questions as examples of the future impact of this work. One of the findings is the striking contrast between marine and terrestrial biomes. Can we account for the differences on the basis of what we know about how these disparate ecosystems function? The findings also raise important questions about the future. What scale of human activities can be supported by marine and terrestrial environments, looking forward? How will climate change alter the answers? Total primary productivity in the oceans [48.5 Gt C/y net primary production (NPP)] is similar to that on land (56.4 Gt C/y NPP), even though the oceans have more than twice as much surface area (2). However, despite similar total primary productivity, Bar-On et al. (1) estimate that there is roughly 80 times more biomass on land than in the oceans. Terrestrial plants—which comprise ∼80% of the total biomass on Earth—make up most of this difference. In striking contrast to the land’s dominance of producer biomass, Bar-On et al. (1) estimate that more than 70% of global animal biomass is found in the ocean. Earth has a plant-dominated landscape and an animal-dominated seascape. What could explain these fundamental … [↵][1]1To whom correspondence may be addressed. Email: mburgess{at}ucsb.edu or gaines{at}ucsb.edu. [1]: #xref-corresp-1-1
Towards a greater understanding of anxiety sensitivity across groups: The construct validity of the Anxiety Sensitivity Index-3.

Abstract The present study examined the factor structure, invariance properties, reliability, and validity of the Anxiety Sensitivity Index-3 (ASI-3, Taylor et al., 2007). Participants were recruited from a large, ethnically diverse southwestern university (n = 3651; 77.8% female; Mage = 22.06 years; 28% non-Hispanic White). Findings supported a bifactor structure for the ASI-3, which demonstrated measurement invariance across sex, race/ethnicity, age, and sexual minority status. Furthermore, the ASI-3 demonstrated strong reliability and validity, with the anxiety sensitivity general and specific factors (physical, cognitive, and social concerns) evidencing unique patterns of relations with symptoms of depression, suicidality, anxious arousal, and social anxiety. Clinically, these findings generally support the validity of the ASI-3 in measuring anxiety sensitivity across sex, age, race/ethnicity, and sexual minority status. Future work is needed to better understand the role anxiety sensitivity plays within specific demographic subgroups, particularly African–Americans, Asian Americans, and sexual minorities.
Myocardial Contraction Fraction by M-Mode Echocardiography Is Superior to Ejection Fraction in Predicting Mortality in Transthyretin Amyloidosis.

ABSTRACT Background Transthyretin amyloidosis (ATTR) is often associated with cardiac involvement manifesting as conduction disease as well as restrictive cardiomyopathy causing heart failure and death. Myocardial contraction fraction (MCF), the ratio of left ventricular stroke volume (SV) to myocardial volume (MV), is a volumetric measure of myocardial shortening that is superior to ejection fraction (EF) in predicting mortality in patients with primary amyloid light chain cardiac amyloidosis. We hypothesized that MCF would be an independent predictor of survival in TTR-CA. Methods and Results MCF was derived from 2-dimensional echocardiography-guided M-mode data for 530 subjects in the Transthyretin Amyloidosis Outcomes Survey (THAOS) database: age 61 ± 16years, 74% male, 158 wild-type (ATTRwt) and 372 mutant (ATTRm), follow-up 1.5 ± 1.7years. Using multivariate Cox proportional hazard regression models, MCF Conclusions MCF was superior to EF in predicting mortality in patients with ATTR. A predictive model combining MCF with systolic blood pressure, renal function, NYHA functional class, and health status was strongly associated with survival in patients with ATTR. ClinicalTrials.gov identifier NCT00628745