So Much for Fond Five-Dollar Memories : Prostitution in Las Vegas, 1905-1955

Over the fifty years examined in this thesis, the interactions between federal and local officials shaped prostitution policy in Las Vegas and Clark County. At times that federal authorities were concerned about prostitution in the county, local leaders balanced tradition and economic necessity in their responses. In the early twentieth century, prostitution\u27s benefits to the local economy outweighed fear of federal reprisals, so local officials worked to protect the city\u27s brothels. By the start of World War II, the federal government\u27s increased power and presence in the West made local officials more willing to abandon the tolerance for prostitution in the community and pursue an aggressive campaign of enforcement against suspected prostitutes. In the years immediately after the war, county and city officials undertook a war on vice that targeted brothels that periodically emerged in various parts of the community. Finally, in 1954 a federal raid on one of Southern Nevada\u27s most successful brothels initiated a series of events that led to a permanent end for brothel prostitution in Clark County. This thesis illustrates the connections between two important histories: the growth of Las Vegas from a small railroad town into a modern resort city, and the expansion of the federal government\u27s power and influence during the first half of the twentieth century. Prostitution serves as a lens through which to view how these two narratives are linked

Visual Word Recognition in Deaf Readers: the interplay between orthographic, semantic and phonological information

Poor literacy is prevalent in the deaf population. This thesis assesses levels of literacy in the deaf population by investigating visual word recognition in deaf readers. For hearing readers, several studies have demonstrated that good visual word recognition skills are crucial for successful literacy attainment and poor readers are likely to have poor word recognition skills. In particular, phonology is known to play an important role in visual word recognition in hearing individuals. The role of phonology in deaf readers has also been addressed extensively. However, these have generated mixed results, which may be partly due to different methodological approaches and lack of control for reading level of participants. Studies reported in this thesis explore the role of orthography, semantics and phonology in deaf skilled readers during visual word recognition and also sentence reading using various methodologies and controlling carefully for reading level. The methodologies used include: lexical decision, masked priming, the visual world and the invisible boundary paradigm. The results from the various tasks described in this thesis show that there are similarities in the way deaf skilled and hearing readers process semantic and orthographic information. However, I found differences in how they process phonological information: deaf and hearing readers show similar effects of phonology in tasks that do not require semantic activation, however, deaf readers do not show phonological activation in tasks that require semantics while hearing readers do. This suggests qualitative differences in reading strategies for the two populations. These differences do not account for differences in literacy attainment across deaf and hearing groups (as our participants where matched for reading levels). Implications for theories of visual word recognition are discussed and in the final chapter, I introduce a proposed model of visual word recognition for deaf readers based on findings reported in this thesis

Lexical organization in deaf children who use British Sign Language: Evidence from a semantic fluency task

We adapted the semantic fluency task into British Sign Language (BSL). In Study 1, we present data from twenty-two deaf signers aged four to fifteen. We show that the same ‘cognitive signatures’ that characterize this task in spoken languages are also present in deaf children, for example, the semantic clustering of responses. In Study 2, we present data from thirteen deaf children with Specific Language Impairment (SLI) in BSL, in comparison to a subset of children from Study 1 matched for age and BSL exposure. The two groups' results were comparable in most respects. However, the group with SLI made occasional word-finding errors and gave fewer responses in the first 15 seconds. We conclude that deaf children with SLI do not differ from their controls in terms of the semantic organization of the BSL lexicon, but that they access signs less efficiently

The metabolic impact of extracellular nitrite on aerobic metabolism of Paracoccus denitrificans

Nitrite, in equilibrium with free nitrous acid (FNA), can inhibit both aerobic and anaerobic growth of microbial communities through bactericidal activities that have considerable potential for control of microbial growth in a range of water systems. There has been much focus on the effect of nitrite / FNA on anaerobic metabolism and so, to enhance understanding of the metabolic impact of nitrite / FNA on aerobic metabolism, a study was undertaken with a model denitrifying bacterium Paracoccus denitrificans PD1222. Extracellular nitrite inhibits aerobic growth of P. denitrificans in a pH dependent manner that is likely to be a result of both nitrite and free nitrous acid (FNA) (pKa = 3.25) and subsequent reactive nitrogen oxides generated from the intracellular passage of FNA into P. denitrificans. Increased expression of a gene encoding a flavohemoglobin protein (Fhp) (Pden_1689) was observed in response to extracellular nitrite. Construction and analysis of a deletion mutant established the Fhp to be involved in endowing nitrite / FNA resistance at high extracellular nitrite concentrations. Global transcriptional analysis confirmed nitrite-dependent expression of fhp and indicated that P. denitrificans expressed a number of stress response systems associated with protein, DNA and lipid repair. It is therefore suggested that nitrite causes a pH-dependent stress response that is due to the production of associated reactive nitrogen species, such as NO from the internalisation of FNA

HER2-HER3 heterodimer quantification by FRET-FILM and patient subclass analysis of the COIN colorectal trial

BACKGROUND: The phase 3 MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based chemotherapy in first-line treatment of advanced colorectal cancer. This study exploits additional information on HER2-HER3 dimerization to achieve patient stratification and reveal previously hidden subgroups of patients who had differing disease progression and treatment response. METHODS: HER2-HER3 dimerization was quantified by 'FLIM Histology' in primary tumor samples from 550 COIN trial patients receiving oxaliplatin and fluoropyrimidine chemotherapy +/-cetuximab. Bayesian latent class analysis (LCA) and covariate reduction was performed to analyze the effects of HER2-HER3 dimer, RAS mutation and cetuximab on progression-free survival (PFS) and overall survival (OS). All statistical tests were two-sided. RESULTS: LCA on a cohort of 398 patients revealed two patient subclasses with differing prognoses (median OS: 1624 days [95%CI=1466-1816] vs 461 [95%CI=431-504]): Class 1 (15.6%) showed a benefit from cetuximab in OS (HR = 0.43 [95%CI=0.25-0.76]; p = 0.004). Class 2 showed an association of increased HER2-HER3 with better OS (HR = 0.64 [95%CI=0.44-0.94]; p = 0.02). A class prediction signature was formed and tested on an independent validation cohort (N = 152) validating the prognostic utility of the dimer assay. Similar subclasses were also discovered in full trial dataset (N = 1,630) based on 10 baseline clinicopathological and genetic covariates. CONCLUSIONS: Our work suggests that the combined use of HER dimer imaging and conventional mutation analyses will be able to identify a small subclass of patients (>10%) who will have better prognosis following chemotherapy. A larger prospective cohort will be required to confirm its utility in predicting the outcome of anti-EGFR treatment

How do face masks impact communication amongst deaf/HoH people?

Face coverings have been key in reducing the spread of COVID-19. At the same time, they have hindered interpersonal communication, particularly for those who rely on speechreading to aid communication. The available research indicated that deaf/hard of hearing (HoH) people experienced great difficulty communicating with people wearing masks and negative effects on wellbeing. Here we extended these findings by exploring which factors predict deaf/HoH people’s communication difficulties, loss of information, and wellbeing. We also explored the factors predicting perceived usefulness of transparent face coverings and alternative ways of communicating. We report the findings from an accessible survey study, released in two written and three signed languages. Responses from 395 deaf/HoH UK and Spanish residents were collected online at a time when masks were mandatory. We investigated whether onset and level of deafness, knowledge of sign language, speechreading fluency, and country of residence predicted communication difficulties, wellbeing, and degree to which transparent face coverings were considered useful. Overall, deaf/HoH people and their relatives used masks most of the time despite greater communication difficulties. Late-onset deaf people were the group that experienced more difficulties in communication, and also reported lower wellbeing. However, both early- and late-onset deaf people reported missing more information and feeling more disconnected from society than HoH people. Finally, signers valued transparent face shields more positively than non-signers. The latter suggests that, while seeing the lips is positive to everyone, signers appreciate seeing the whole facial expression. Importantly, our data also revealed the importance of visual communication other than speechreading to facilitate face-to-face interactions

Targeted next-generation sequencing of DNA regions proximal to a conserved GXGXXG signaling motif enables systematic discovery of tyrosine kinase fusions in cancer

Tyrosine kinase (TK) fusions are attractive drug targets in cancers. However, rapid identification of these lesions has been hampered by experimental limitations. Our in silico analysis of known cancer-derived TK fusions revealed that most breakpoints occur within a defined region upstream of a conserved GXGXXG kinase motif. We therefore designed a novel DNA-based targeted sequencing approach to screen systematically for fusions within the 90 human TKs; it should detect 92% of known TK fusions. We deliberately paired ‘in-solution’ DNA capture with 454 sequencing to minimize starting material requirements, take advantage of long sequence reads, and facilitate mapping of fusions. To validate this platform, we analyzed genomic DNA from thyroid cancer cells (TPC-1) and leukemia cells (KG-1) with fusions known only at the mRNA level. We readily identified for the first time the genomic fusion sequences of CCDC6-RET in TPC-1 cells and FGFR1OP2-FGFR1 in KG-1 cells. These data demonstrate the feasibility of this approach to identify TK fusions across multiple human cancers in a high-throughput, unbiased manner. This method is distinct from other similar efforts, because it focuses specifically on targets with therapeutic potential, uses only 1.5 µg of DNA, and circumvents the need for complex computational sequence analysis

Sentence Repetition in Deaf Children with Specific Language Impairment in British Sign Language

Children with specific language impairment (SLI) perform poorly on sentence repetition tasks across different spoken languages, but until now, this methodology has not been investigated in children who have SLI in a signed language. Users of a natural sign language encode different sentence meanings through their choice of signs and by altering the sequence and inflections of these signs. Grammatical information is expressed through movement and configurational changes of the hands and face. The visual modality thus influences how grammatical morphology and syntax are instantiated. How would language impairment impact on the acquisition of these types of linguistic devices in child signers? We investigated sentence repetition skills in a group of 11 deaf children who display SLI in British Sign Language (BSL) and 11 deaf controls with no language impairment who were matched for age and years of BSL exposure. The SLI group was significantly less accurate on an overall accuracy score, and they repeated lexical items, overall sentence meaning, sign order, facial expressions, and verb morphological structures significantly less accurately than controls. This pattern of language deficits is consistent with the characterization of SLI in spoken languages even though expression is in a different modality. We conclude that explanations of SLI, and of poor sentence repetition by children with this disorder, must be able to account for both the spoken and signed modalities