RELAX, DON\u27T DO IT: UNDERSTANDING HOW TECHNOLOGY USE AND AWARENESS AFFECT YOUR LIFE ORIENTATION

This study examines whether or not the social norm of using technology alongside with the awareness of one’s environment impacts how optimistically people view the world. We conducted a Mechanical Turk survey designed to measure a person’s technology use, mindful awareness, personality constructs, and life orientation. After analyzing our data in SPSS, we found that, though there is a negative relationship between technology use and mindful awareness, but a positive relationship between mindful awareness and life orientation. This suggests that the more a person uses technology the less mindfully aware they become, but their increased technology use and increased awareness also causes them to having a higher life orientation. This could mean that, as opposed to the popular opinion, technology could either be improving our perceptions of life orientation or biasing the self-reports of one’s awareness. Rationale for the findings is provided and future recommendations are made

Human-centered Electric Prosthetic (HELP) Hand

In developing countries such as India, there is a higher rate of amputations among the population but a lack of viable, low cost solutions. Through a partnership with Indian non-profit Bhagwan Mahaveer Viklang Sahayata Samiti (BMVSS), the team designed a functional, robust, and low cost electrically powered prosthetic hand that communicates with people with unilateral, transradial amputations in urban India through a biointerface. The device uses compliant tendon actuation, small linear servos, and a wearable sleeve outfitted with electromyography (EMG) sensors to produce a device that, once placed inside a prosthetic glove, is anthropomorphic in both look and feel. The hand is capable of forming three grips through the use of a manually adjustable opposable thumb: the key, pinch, and wrap grips. The hand also provides vibrotactile user feedback upon completion of a grip. The design includes a prosthetic gel liner to provide a layer of cushion and comfort for safe use by the user. These results show that it is possible to create a low cost, electrically powered prosthetic hand for users in developing countries without sacrificing functionality. In order for this design to be truly adjustable to each user, the creation of an easily navigable graphical user interface (GUI) will have to be a future goal. The prosthesis prototype was developed such that future groups can design for manufacturing and distribution in India

RAG-induced DNA double-strand breaks signal through Pim2 to promote pre-B cell survival and limit proliferation

Interleukin 7 (IL-7) promotes pre–B cell survival and proliferation by activating the Pim1 and Akt kinases. These signals must be attenuated to induce G1 cell cycle arrest and expression of the RAG endonuclease, which are both required for IgL chain gene rearrangement. As lost IL-7 signals would limit pre–B cell survival, how cells survive during IgL chain gene rearrangement remains unclear. We show that RAG-induced DNA double-strand breaks (DSBs) generated during IgL chain gene assembly paradoxically promote pre–B cell survival. This occurs through the ATM-dependent induction of Pim2 kinase expression. Similar to Pim1, Pim2 phosphorylates BAD, which antagonizes the pro-apoptotic function of BAX. However, unlike IL-7 induction of Pim1, RAG DSB-mediated induction of Pim2 does not drive proliferation. Rather, Pim2 has antiproliferative functions that prevent the transit of pre–B cells harboring RAG DSBs from G1 into S phase, where these DNA breaks could be aberrantly repaired. Thus, signals from IL-7 and RAG DSBs activate distinct Pim kinase family members that have context-dependent activities in regulating pre–B cell proliferation and survival

Genome-wide mapping of cystitis due to Streptococcus agalactiae and Escherichia coli in mice identifies a unique bladder transcriptome that signifies pathogen-specific antimicrobial defense against urinary tract infection

The most common causes of urinary tract infections (UTIs) are Gram-negative pathogens such as Escherichia coli; however, Gram-positive organisms, including Streptococcus agalactiae, or group B streptococcus (GBS), also cause UTI. In GBS infection, UTI progresses to cystitis once the bacteria colonize the bladder, but the host responses triggered in the bladder immediately following infection are largely unknown. Here, we used genome-wide expression profiling to map the bladder transcriptome of GBS UTI in mice infected transurethrally with uropathogenic GBS that was cultured from a 35-year-old women with cystitis. RNA from bladders was applied to Affymetrix Gene-1.0ST microarrays; quantitative reverse transcriptase PCR (qRT-PCR) was used to analyze selected gene responses identified in array data sets. A surprisingly small significant-gene list of 172 genes was identified at 24 h; this compared to 2,507 genes identified in a side-by-side comparison with uropathogenic E. coli (UPEC). No genes exhibited significantly altered expression at 2 h in GBS-infected mice according to arrays despite high bladder bacterial loads at this early time point. The absence of a marked early host response to GBS juxtaposed with broad-based bladder responses activated by UPEC at 2 h. Bioinformatics analyses, including integrative system-level network mapping, revealed multiple activated biological pathways in the GBS bladder transcriptome that regulate leukocyte activation, inflammation, apoptosis, and cytokine-chemokine biosynthesis. These findings define a novel, minimalistic type of bladder host response triggered by GBS UTI, which comprises collective antimicrobial pathways that differ dramatically from those activated by UPEC. Overall, this study emphasizes the unique nature of bladder immune activation mechanisms triggered by distinct uropathogens

Bacteria-Induced Uroplakin Signaling Mediates Bladder Response to Infection

Urinary tract infections are the second most common infectious disease in humans and are predominantly caused by uropathogenic E. coli (UPEC). A majority of UPEC isolates express the type 1 pilus adhesin, FimH, and cell culture and murine studies demonstrate that FimH is involved in invasion and apoptosis of urothelial cells. FimH initiates bladder pathology by binding to the uroplakin receptor complex, but the subsequent events mediating pathogenesis have not been fully characterized. We report a hitherto undiscovered signaling role for the UPIIIa protein, the only major uroplakin with a potential cytoplasmic signaling domain, in bacterial invasion and apoptosis. In response to FimH adhesin binding, the UPIIIa cytoplasmic tail undergoes phosphorylation on a specific threonine residue by casein kinase II, followed by an elevation of intracellular calcium. Pharmacological inhibition of these signaling events abrogates bacterial invasion and urothelial apoptosis in vitro and in vivo. Our studies suggest that bacteria-induced UPIIIa signaling is a critical mediator of bladder responses to insult by uropathogenic E. coli

Tobacco Upregulates P. gingivalis Fimbrial Proteins Which Induce TLR2 Hyposensitivity

Tobacco smokers are more susceptible to periodontitis than non-smokers but exhibit reduced signs of clinical inflammation. The underlying mechanisms are unknown. We have previously shown that cigarette smoke extract (CSE) represents an environmental stress to which P. gingivalis adapts by altering the expression of several virulence factors - including major and minor fimbrial antigens (FimA and Mfa1, respectively) and capsule - concomitant with a reduced pro-inflammatory potential of intact P. gingivalis.We hypothesized that CSE-regulation of capsule and fimbrial genes is reflected at the ultrastructural and functional levels, alters the nature of host-pathogen interactions, and contributes to the reduced pro- inflammatory potential of smoke exposed P. gingivalis. CSE induced ultrastructural alterations were determined by electron microscopy, confirmed by Western blot and physiological consequences studied in open-flow biofilms. Inflammatory profiling of specific CSE-dysregulated proteins, rFimA and rMfa1, was determined by quantifying cytokine induction in primary human innate and OBA-9 cells. CSE up-regulates P. gingivalis FimA at the protein level, suppresses the production of capsular polysaccharides at the ultrastructural level, and creates conditions that promote biofilm formation. We further show that while FimA is recognized by TLR2/6, it has only minimal inflammatory activity in several cell types. Furthermore, FimA stimulation chronically abrogates the pro-inflammatory response to subsequent TLR2 stimulation by other TLR-2-specific agonists (Pam3CSK4, FSL, Mfa1) in an IkappaBalpha- and IRAK-1-dependent manner.These studies provide some of the first information to explain, mechanistically, how tobacco smoke changes the P. gingivalis phenotype in a manner likely to promote P. gingivalis colonization and infection while simultaneously reducing the host response to this major mucosal pathogen

New Landscapes and Horizons in Hepatocellular Carcinoma Therapy

Hepatocellular carcinoma (HCC), is the sixth most frequent form of cancer and leads to the fourth highest number of deaths each year. HCC results from a combination of environmental factors and aging as there are driver mutations at oncogenes which occur during aging. Most of HCCs are diagnosed at advanced stage preventing curative therapies. Treatment in advanced stage is a challenging and pressing problem, and novel and well-tolerated therapies are urgently needed. We will discuss further advances beyond sorafenib that target additional signaling pathways and immune checkpoint proteins. The scenario of possible systemic therapies for patients with advanced HCC has changed dramatically in recent years. Personalized genomics and various other omics approaches may identify actionable biochemical targets, which are activated in individual patients, which may enhance therapeutic outcomes. Further studies are needed to identify predictive biomarkers and aberrantly activated signaling pathways capable of guiding the clinician in choosing the most appropriate therapy for the individual patient

Harriette Simpson Arnow\u27s Out-Migration: From Burnside, Kentucky to Ann Arbor, Michigan

Although Harriette Simpson Arnow remains best known today for her so called “Kentucky trilogy, the novels Mountain Path (1936), Hunter’s Horn (1949), and her classic—and tragic—story of Appalachian out-migration The Dollmaker (1954), she spent much of her life outside her native region of southeastern Kentucky, living at various times in upper-Michigan, Louisville, Cincinnati, Detroit, and beginning in 1950, on a small, forty-acre farm near Ann Arbor. This “Kentucky author,” then, spent the last three and a half decades of her life as a Michigan resident. Drawing largely from autobiographical writing found in the University of Kentucky archives, as well as interviews with Arnow and others about this “Michigan” period of her life—during which she produced relatively little fiction compared to her earlier career—this paper proposes to explore her complex feelings about her native state, her despair at the creeping of “exurbia” into the once rural area around the Ann Arbor farm, her struggles with health as well as her determination to continue writing—all to offer a more complete view of this complicated woman and her own experience of migration. Arnow continued to identify as a Kentuckian while in Michigan, and participated in the organization Kentuckians of Michigan—the non-profit group, not the bluegrass music venue—yet she did not write any contemporary Kentucky fiction during the last decades of her life. This presentation will also explore how her own “un-stitching of the seams” by relocating from Kentucky to Michigan might have contributed to this change in the subject matter of her fiction

Unruly Women: Music and Madness in Lee Smith\u27s _The Devil\u27s Dream_

Traditional mountain music, along with its descendant, country music, frequently appear in the work of Appalachian writer Lee Smith, but nowhere do they occupy a more central position than in her 1992 novel The Devil’s Dream. This polyphonic work tells the story of five generations of a “singing family” modeled loosely on the Carter clan; it includes a fictional treatment of the famous Bristol Sessions of 1927; and it begins and ends in the lobby of the Opryland Hotel in Nashville. Given the centrality of music to the novel, it perhaps should come as no surprise that one of the best critical treatments of it appears not in a literary journal but in the Country Music Annual of 2000. The Devil’s Dream also treats another frequent subject in Smith’s fiction, however: that of female madness, institutionalization, and silencing. The novel includes a striking number of unruly, depressed, and unconventional women; many of them end up institutionalized in mental hospitals, prisons, or nursing homes. This paper will examine the way that one female character, the successful musician Katie Cocker, uses music and the production of the album “Shall We Gather at the River” to free her institutionalized relatives and to give them, quite literally, a voice on the recording. Through this recording, mountain music becomes a means of emptying the asylums and giving, at least temporarily, some agency to previously silenced and disempowered female characters