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\"For nearly her entire life, Gloria Ricci has been followed by bees. They're there when her mother loses twin children; when she first meets a neighborhood girl named Isabel, who brings out feelings in her that she knows she shouldn't have; and when her parents, desperate to \"help\" her, bring her to the Belmont Institute, whose glossy brochures promise healing and peace. She tells no one, but their hum follows her as she struggles to survive against the Institute's cold and damaging methods, as she meets an outspoken and unapologetic fellow patient named Sheffield Schoeffler, and as they run away, toward the freewheeling and accepting glow of 1960s Greenwich Village, where they create their own kind of family among the artists and wanderers who frequent the jazz bars and side streets. As Gloria tries to outrun her past, experiencing profound love--and loss--and encountering a host of unlikely characters, including her Uncle Eddie, a hard-drinking former boyfriend of her mother's, to Madame Zelda, a Coney Island fortune teller, and Jacob, the man she eventually marries but whose dark side threatens to bring disaster, the bees remain. It's only when she needs them most that Gloria discovers why they're there. Moving from the suburbs of New Jersey to the streets of New York to the swamps of North Carolina and back again, Lost in the Beehive is a poignant novel about the moments that teach us, the places that shape us, and the people who change us\"-- Provided by publisher.

Actin microfilaments regulate the size, shape and mobility of dendritic spines and are in turn regulated by actin binding proteins and small GTPases. The βI isoform of spectrin, a protein that links the actin cytoskeleton to membrane proteins, is present in spines. To understand its function, we expressed its actin-binding domain (ABD) in CA1 pyramidal neurons in hippocampal slice cultures. The ABD of βI-spectrin bundled actin in principal dendrites and was concentrated in dendritic spines, where it significantly increased the size of the spine head. These effects were not observed after expression of homologous ABDs of utrophin, dystrophin, and α-actinin. Treatment of slice cultures with latrunculin-B significantly decreased spine head size and decreased actin-GFP fluorescence in cells expressing the ABD of α-actinin, but not the ABD of βI-spectrin, suggesting that its presence inhibits actin depolymerization. We also observed an increase in the area of GFP-tagged PSD-95 in the spine head and an increase in the amplitude of mEPSCs at spines expressing the ABD of βI-spectrin. The effects of the βI-spectrin ABD on spine size and mEPSC amplitude were mimicked by expressing wild-type Rac3, a small GTPase that co-immunoprecipitates specifically with βI-spectrin in extracts of cultured cortical neurons. Spine size was normal in cells co-expressing a dominant negative Rac3 construct with the βI-spectrin ABD. We suggest that βI-spectrin is a synaptic protein that can modulate both the morphological and functional dynamics of dendritic spines, perhaps via interaction with actin and Rac3.

Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic shock syndrome. Dengue vaccine development is challenging because of the need to induce protection against four antigenically distinct DENV serotypes. Recent studies indicate that tetravalent DENV vaccines must induce balanced, serotype-specific neutralizing antibodies to achieve durable protective immunity against all 4 serotypes. With the leading live attenuated tetravalent DENV vaccines, it has been difficult to achieve balanced and type-specific responses to each serotype, most likely because of unbalanced replication of vaccine viral strains. Here we evaluate a tetravalent DENV protein subunit vaccine, based on recombinant envelope protein (rE) adsorbed to the surface of poly (lactic-co-glycolic acid) (PLGA) nanoparticles for immunogenicity in mice. In monovalent and tetravalent formulations, we show that particulate rE induced higher neutralizing antibody titers compared to the soluble rE antigen alone. Importantly, we show the trend that tetravalent rE adsorbed to nanoparticles stimulated a more balanced serotype specific antibody response to each DENV serotype compared to soluble antigens. Our results demonstrate that tetravalent DENV subunit vaccines displayed on nanoparticles have the potential to overcome unbalanced immunity observed for leading live-attenuated vaccine candidates.

Actin microfilaments regulate the size, shape and mobility of dendritic spines and are in turn regulated by actin binding proteins and small GTPases. The [beta]I isoform of spectrin, a protein that links the actin cytoskeleton to membrane proteins, is present in spines. To understand its function, we expressed its actin-binding domain (ABD) in CA1 pyramidal neurons in hippocampal slice cultures. The ABD of [beta]I-spectrin bundled actin in principal dendrites and was concentrated in dendritic spines, where it significantly increased the size of the spine head. These effects were not observed after expression of homologous ABDs of utrophin, dystrophin, and [alpha]-actinin. Treatment of slice cultures with latrunculin-B significantly decreased spine head size and decreased actin-GFP fluorescence in cells expressing the ABD of [alpha]-actinin, but not the ABD of [beta]I-spectrin, suggesting that its presence inhibits actin depolymerization. We also observed an increase in the area of GFP-tagged PSD-95 in the spine head and an increase in the amplitude of mEPSCs at spines expressing the ABD of [beta]I-spectrin. The effects of the [beta]I-spectrin ABD on spine size and mEPSC amplitude were mimicked by expressing wild-type Rac3, a small GTPase that co-immunoprecipitates specifically with [beta]I-spectrin in extracts of cultured cortical neurons. Spine size was normal in cells co-expressing a dominant negative Rac3 construct with the [beta]I-spectrin ABD. We suggest that [beta]I-spectrin is a synaptic protein that can modulate both the morphological and functional dynamics of dendritic spines, perhaps via interaction with actin and Rac3.

The effects of fluency-based instruction and accuracy-based instruction on contingency adduction were assessed using an alternating treatments design. Stimulus equivalence tasks were used to measure contingency adduction. Stimulus classes were composed of arbitrary visual forms. One treatment condition consisted of teaching fast, fluent responding with mastery criteria that included both accuracy and speed. This condition provided learning experiences similar to those encountered when receiving precision teaching or fluency-based instruction. The other treatment condition consisted of teaching in a manner that required slow, constrained responding, with a mastery criterion that only included accuracy. This condition provided learning experiences similar to those encountered in a traditional classroom educational setting. After mastery criteria were met in either condition, contingency adduction was tested. The dependent variables were number of errors prior to contingency adduction, average errors by adduction complexity, total time in teaching trials prior to adduction, number of teaching blocks prior to mastery of adduction relation, number of adduction testing blocks prior to mastery, number of relations mastered in the first adduction testing block, and number of errors in adduction testing blocks prior to mastery. Results indicated that participants made more errors prior to contingency adduction in fluency-based teaching than in accuracy-based teaching. However, participants also took less total time in teaching trials prior to contingency adduction in fluency-based teaching than in accuracy-based teaching.

Complete vaccine-mediated immune control of highly pathogenic Mycobacterium tuberculosis is possible if immune effector responses can intercept the infection at its earliest stages. Despite widespread use of the bacille Calmette–Guérin (BCG) vaccine, tuberculosis (TB) remains a leading cause of global mortality from a single infectious agent ( Mycobacterium tuberculosis or Mtb). Here, over two independent Mtb challenge studies, we demonstrate that subcutaneous vaccination of rhesus macaques (RMs) with rhesus cytomegalovirus vectors encoding Mtb antigen inserts (hereafter referred to as RhCMV/TB)—which elicit and maintain highly effector-differentiated, circulating and tissue-resident Mtb-specific CD4 + and CD8 + memory T cell responses—can reduce the overall (pulmonary and extrapulmonary) extent of Mtb infection and disease by 68%, as compared to that in unvaccinated controls, after intrabronchial challenge with the Erdman strain of Mtb at ∼1 year after the first vaccination. Fourteen of 34 RhCMV/TB-vaccinated RMs (41%) across both studies showed no TB disease by computed tomography scans or at necropsy after challenge (as compared to 0 of 17 unvaccinated controls), and ten of these RMs were Mtb-culture-negative for all tissues, an exceptional long-term vaccine effect in the RM challenge model with the Erdman strain of Mtb. These results suggest that complete vaccine-mediated immune control of highly pathogenic Mtb is possible if immune effector responses can intercept Mtb infection at its earliest stages.

Non-covalent inclusion complexes formed between amino acids and derivatized calix[6]arenes are observed in MALDI mass spectrometry. The methyl, ethyl, and propyl ester derivatives of calix[6]arene yielded amino acid complexes, while the smaller calix[4]arene analogs did not. Similarly the underivatized calix[6]arene and calix[4]arene did not produce complexes. Amino acid complexes were observed for nearly all 20 amino acids in time-of-flight (TOF) analysis. In Fourier transform mass spectrometry (FTMS) analysis, however, only the most basic amino acids arginine, histidine, and lysine formed stable adducts. The complexes were abundant under matrix-assisted laser desorption ionization (MALDI) conditions, which suggested favorable interactions between host and guest.

Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic shock syndrome. Dengue vaccine development is challenging because of the need to induce protection against four antigenically distinct DENV serotypes. Recent studies indicate that tetravalent DENV vaccines must induce balanced, serotype-specific neutralizing antibodies to achieve durable protective immunity against all 4 serotypes. With the leading live attenuated tetravalent DENV vaccines, it has been difficult to achieve balanced and type-specific responses to each serotype, most likely because of unbalanced replication of vaccine viral strains. Here we evaluate a tetravalent DENV protein subunit vaccine, based on recombinant envelope protein (rE) adsorbed to the surface of poly (lactic-co-glycolic acid) (PLGA) nanoparticles for immunogenicity in mice. In monovalent and tetravalent formulations, we show that particulate rE induced higher neutralizing antibody titers compared to the soluble rE antigen alone. Importantly, we show the trend that tetravalent rE adsorbed to nanoparticles stimulated a more balanced serotype specific antibody response to each DENV serotype compared to soluble antigens. Our results demonstrate that tetravalent DENV subunit vaccines displayed on nanoparticles have the potential to overcome unbalanced immunity observed for leading live-attenuated vaccine candidates.

Using Baltimore as a case study, this dissertation argues that newspaper editors played a formative role in the changing political environment of the early American republic. In the late 1790s, Republican editors began producing and disseminating highly partisan print to mobilize readers under the Republican banner. Following the Republicans' ascension to national power in 1800, Federalist editors adopted the rhetorical weapons that Republican editors had used against them. In the first two decades of the nineteenth century, partisan conflict escalated as political editors refined their campaign tactics and reacted to the machinations of their opponents. Political historians have often told a story in which Republican editors pioneered the creation of a partisan press network. According to this interpretation, Federalist editors failed to respond, leading to their party's ultimate political downfall. I argue instead that Federalist and Republican editors engaged in an ongoing dialogue with one another and their audience. These editors transformed political discussion by adopting highly partisan and oftentimes abrasive editorial rhetoric, each side continually adapting its tactics in order to retaliate against its opponents. Significantly, they also embedded themselves within a larger, bipartisan newspaper network. Their political discussion became national in scope as editors outside of their cities reproduced their political writings and used their language to facilitate their own local political discussions. By providing the vocabulary for political debate, some editors acted as cultural gatekeepers, holding spheres of influence within the larger national newspaper network and therefore defining the boundaries of public political discourse. In the process, political editors helped legitimize the existence of a two party system through their promotion of partisan conflict. By providing new insights on the inner workings of the national newspaper network, this dissertation contributes to studies on the formation and influence of political information networks. It is comprised of six chapters that chronologically follow the back-and-forth political struggle between Maryland's political parties and their editors between 1798 and 1820. In the 1790s, Republican editors embraced tactics of character defamation and aggressive partisanship, mobilizing the populace in their favor for the presidential election of 1800. After Republicans achieved national power in 1801, Federalist editors responded to the Republicans' taunting by turning their polemical rhetoric against them. The political battle continued to escalate throughout the first two decades of the nineteenth century, culminating during the War of 1812. With the decline of the Federalist Party following the war, the nation entered the so-called Era of Good Feelings. Without an active opposition to unite them, however, the Republican Party disintegrated into multiple factions. By 1820, Republican editors despaired of their party's growing disunity and began to recognize that party competition and partisan dialogue were vital for their careers. They cast aside attempts at party reconciliation, renewing their use of old party labels and picking partisan fights as a means to salvage their position as cultural gatekeepers within the emerging second party system.

\"The situation will be changed for the better now,\" said [Raymond Ayad], who knew [Yasser Arafat] when the future leader was an engineer in Kuwait in 1965. \"There is no excuse for Israel and America now that they can't blame Arafat. . . . If they really believe in peace, they will have to work with this new government.\" At the Muqata compound where Arafat was a virtual prisoner for the last 21/2 years of his life and where he will be buried today, the mood was vengeful. Many said they believed that Israel poisoned Arafat or, at the least, contributed to his death by keeping him penned up in the airless, unsanitary compound. Morris Arbel, a secular security guard at a supermarket in the trendy German Colony, thought Arafat's death would lead to \"a new page\" between Israel and the Palestinians. \"Arafat never changed, despite what others thought,\" Arbel, 48, said. \"If he had, the Palestinians would have had a state by now.\"