Search

Epithelial-to-mesenchymal transition (EMT) has been shown to be similarly regulated by multiple miRNAs, some displaying little or no sequence identity. While alternate models have been proposed to explain the functional convergence of sequence divergent miRNAs, little experimental evidence exists to elucidate the underlying mechanisms involved. Representative members of the miR-200 family of miRNAs and the sequence divergent miR-205 miRNA were independently over expressed in mesenchymal-like ovarian cancer (OC) cells resulting in mesenchymal-to-epithelial transition (MET). The miR-205 and the miR-200 family of miRNAs were found to coordinately induce MET in mesenchymal-like OC cells by affecting both direct and indirect changes in the expression of genes previously associated with EMT/MET. Only two direct targets of these miRNAs (ZEB 1 and WNT5A) are commonly down regulated in response to over-expression of miR-205 and/or the miR-200 family of miRNAs. Down-regulation of these genes, alone or in combination, only partially recapitulates the changes induced by the miRNAs indicating an additional contribution of indirect changes regulated by the miRNAs. Combined gene expression analyses and phylogenetic comparisons suggest an evolutionarily more recent involvement of miR-205 in the EMT/MET process.

New tools have been created to allow a superconducting design flow for schematic design, verification, and optimization. These tools integrate with the Cadence design environment. In single flux quantum superconducting electronics, individual component values, such as wire inductances, Josephson junction critical currents, and bias currents, must be optimized to allow for maximum deviance from the designer value, which is also known as the device margin. One tool is used to create a description of the proper circuit behavior. Included with this tool is the ability to automatically create the description from a Cadence netlist. The other tool is an automated device margin circuit schematic verification and optimization tool, which widens device margins while maintaining proper circuit behavior derived from the first tool. Additionally, this optimization tool can automatically correct the circuit schematic using the proper circuit behavior description. In this paper, the functionality of the language used to create the description of the proper circuit behavior is presented. Several circuits are then verified and optimized based on their correct behavior.

Isolation and analysis of circulating tumor cells (CTCs) from blood samples present exciting opportunities for basic cancer research and personalized treatment of the disease. While microchip-based negative CTC enrichment offers both sensitive microfluidic cell screening and unbiased selection, conventional microchips are inherently limited by their capacity to deplete a large number of normal blood cells. In this paper, we use 3D printing to create a monolithic device that combines immunoaffinity-based microfluidic cell capture and a commercial membrane filter for negative enrichment of CTCs directly from whole blood. In our device, stacked layers of chemically-functionalized microfluidic channels capture millions of white blood cells (WBCs) in parallel without getting saturated and the leuko-depleted blood is post-filtered with a 3 μm-pore size membrane filter to eliminate anucleated blood cells. This hybrid negative enrichment approach facilitated direct extraction of viable CTCs off the chip on a membrane filter for downstream analysis. Immunofluorescence imaging of enriched cells showed ∼90% tumor cell recovery rate from simulated samples spiked with prostate, breast or ovarian cancer cells. We also demonstrated the feasibility of our approach for processing clinical samples by isolating prostate cancer CTCs directly from a 10 mL whole blood sample.

Precision or personalized cancer medicine is a clinical approach that strives to customize therapies based upon the genomic profiles of individual patient tumors. Machine learning (ML) is a computational method particularly suited to the establishment of predictive models of drug response based on genomic profiles of targeted cells. We report here on the application of our previously established open-source support vector machine (SVM)-based algorithm to predict the responses of 175 individual cancer patients to a variety of standard-of-care chemotherapeutic drugs from the gene-expression profiles (RNA-seq or microarray) of individual patient tumors. The models were found to predict patient responses with >80% accuracy. The high PPV of our algorithms across multiple drugs suggests a potential clinical utility of our approach, particularly with respect to the identification of promising second-line treatments for patients failing standard-of-care first-line therapies.

Extremely rare circulating tumor cell (CTC) clusters are both increasingly appreciated as highly metastatic precursors and virtually unexplored. Technologies are primarily designed to detect single CTCs and often fail to account for the fragility of clusters or to leverage cluster-specific markers for higher sensitivity. Meanwhile, the few technologies targeting CTC clusters lack scalability. Here, we introduce the Cluster-Wells, which combines the speed and practicality of membrane filtration with the sensitive and deterministic screening afforded by microfluidic chips. The100,000 microwells in the Cluster-Wells physically arrest CTC clusters in unprocessed whole blood, gently isolating virtually all clusters at a throughput of25 mL/h, and allow viable clusters to be retrieved from the device. Using the Cluster-Wells, we isolated CTC clusters ranging from 2 to 100+ cells from prostate and ovarian cancer patients and analyzed a subset using RNA sequencing. Routine isolation of CTC clusters will democratize research on their utility in managing cancer.

Background Machine learning has been utilized to predict cancer drug response from multi-omics data generated from sensitivities of cancer cell lines to different therapeutic compounds. Here, we build machine learning models using gene expression data from patients’ primary tumor tissues to predict whether a patient will respond positively or negatively to two chemotherapeutics: 5-Fluorouracil and Gemcitabine. Results We focused on 5-Fluorouracil and Gemcitabine because based on our exclusion criteria, they provide the largest numbers of patients within TCGA. Normalized gene expression data were clustered and used as the input features for the study. We used matching clinical trial data to ascertain the response of these patients via multiple classification methods. Multiple clustering and classification methods were compared for prediction accuracy of drug response. Clara and random forest were found to be the best clustering and classification methods, respectively. The results show our models predict with up to 86% accuracy; despite the study’s limitation of sample size. We also found the genes most informative for predicting drug response were enriched in well-known cancer signaling pathways and highlighted their potential significance in chemotherapy prognosis. Conclusions Primary tumor gene expression is a good predictor of cancer drug response. Investment in larger datasets containing both patient gene expression and drug response is needed to support future work of machine learning models. Ultimately, such predictive models may aid oncologists with making critical treatment decisions.

To improve the drug discovery yield, a method which is implemented at the beginning of drug discovery that accurately predicts drug side effects, indications, efficacy, and mode of action based solely on the input of the drug's chemical structure is needed. In contrast, extant predictive methods do not comprehensively address these aspects of drug discovery and rely on features derived from extensive, often unavailable experimental information for novel molecules. To address these issues, we developed MEDICASCY, a multilabel-based boosted random forest machine learning method that only requires the small molecule's chemical structure for the drug side effect, indication, efficacy, and probable mode of action target predictions; however, it has comparable or even significantly better performance than existing approaches requiring far more information. In retrospective benchmarking on high confidence predictions, MEDICASCY shows about 78% precision and recall for predicting at least one severe side effect and 72% precision drug efficacy. Experimental validation of MEDICASCY's efficacy predictions on novel molecules shows close to 80% precision for the inhibition of growth in ovarian, breast, and prostate cancer cell lines. Thus, MEDICASCY should improve the success rate for new drug approval. A web service for academic users is available at http://pwp.gatech.edu/cssb/MEDICASCY.

Transposable element (TE)-derived sequences comprise more than half of the human genome, and their presence has been documented to alter gene expression in a number of different ways, including the generation of alternatively spliced transcript isoforms. Alternative splicing has been associated with tumorigenesis for a number of different cancers. The objective of this study was to broadly characterize the role of human TEs in generating alternatively spliced transcript isoforms in cancer. To do so, we screened for the presence of TE-derived sequences co-located with alternative splice sites that are differentially used in normal versus cancer tissues. We analysed a comprehensive set of alternative splice variants characterized for 614 matched normal-tumour tissue pairs across 13 cancer types, resulting in the discovery of 4820 TE-generated alternative splice events distributed among 723 cancer-associated genes. Short interspersed nuclear elements (Alu) and long interspersed nuclear elements (L1) were found to contribute the majority of TE-generated alternative splice sites in cancer genes. A number of cancer-associated genes, including MYH11 , WHSC1 and CANT1 , were shown to have overexpressed TE-derived isoforms across a range of cancer types. TE-derived isoforms were also linked to cancer-specific fusion transcripts, suggesting a novel mechanism for the generation of transcriptome diversity via trans -splicing mediated by dispersed TE repeats. This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation'.

Reported crimes have declined in some major cities after the imposition of restrictions on businesses and residents to reduce the spread of the COVID-19 virus. The Balkin-McDonald (1981) model of street crime is used to explain the outcomes. Recent crime rate data from five major cities are provided.

This study examines elevated/subway and bus ridership for the five cities in the U.S. with the largest elevated/subway systems. Data on individual trips to work from the 2010 Census are employed. The New York elevated/subway system is by far the largest system and carries 18.4% of the trips to work in the New York metro area compared to an average of 6% of trips in the metro areas of the four next-largest systems (Chicago, San Francisco-Oakland, Boston, and Washington, DC). The New York system has 245 service miles compared to an average of 92 miles for the other four and almost twice as many stations per mile as the other four. Log-odds analysis of the individual trips shows that the New York elevated/subway system carries an estimated over 40% of the work trips by certain groups of commuters. In contrast, the empirical results for the bus systems are roughly similar across the five metropolitan areas. Bus riders make up 7.7% of commuters in metro New York compared to an average of 4.7% for the other four metro areas. Unlike the elevated/subway systems, bus systems cover nearly all of these metro areas with some level of service. Log-odds results show that elevated/subway ridership increases and bus ridership decreases with income, and unmarried commuters (both female and male) are more likely to use either form of public transit.

The approach to reducing the current harm from the COVID-19 disease is to mandate or encourage an array of social distancing behaviors. These behaviors have the negative effects of reducing GDP, personal incomes, and increasing unemployment leading to calls for opening up the economy and thereby reducing social distancing. This makes more sense to do in developing economies which lack the private and public safety nets to compensate for the lost income. However, if this opening-up policy is followed, we suggest that social distancing be maintained at the level that minimizes deaths.

This paper is a study of suburbanization of African-Americans and Hispanics in metropolitan Chicago. There are at least three different types of suburbs; satellite cities with their own employment bases, spillover suburbs adjacent to the central city, and newer commuter suburbs attractive to middle-class households. The study includes data on five satellite cities and 109 spillover and other of suburbs in Cook, DuPage, Kane, Lake, McHenry, and Will Counties in metropolitan Chicago. African-American suburbanization was concentrated in spillover suburbs and the suburbs of southern Cook County – locations that already had substantial African-American populations. However, nearly all of the suburbs had an increase in African-American population. The suburbanization of Hispanics reflects the much larger growth of this group. From 1990 to 2010 the satellite cities and the suburbs generally more than doubled in their percentages of Hispanic population. Suburbs with lower income levels in 1990 tended to attract more Hispanics.

Expression levels of the miR-200 family of miRNAs are significantly reduced during the epithelial-to-mesenchymal transition (EMT) and consequent metastasis of ovarian and other cancers. Consistently, ectopic over-expression of miR-200 family miRNAs in mesenchymal-like cells reverses the process by converting treated cells to an epithelial phenotype, thereby reducing invasiveness and increasing sensitivity to chemotherapeutic drugs. To better understand the dynamics and molecular processes underlying miRNA-induced mesenchymal-to mesenchymal transition (MET), a time-course study was conducted where miRNA-induced morphological and molecular changes associated with MET were monitored over a period of 144 h. Morphological transition from an elongated mesenchymal-like to a cuboidal epithelial-like phenotype is maximized at 48 h with cells returning to the elongated phenotype by 144 h. Changes in the expression of >3000 genes, including many previously associated with epithelial-to-mesenchymal transition (EMT), are most pronounced at 48 h, and approach starting levels of expression by 144 h. The majority of these genes are not direct targets of miR-429. Targeted (siRNA) inhibition of key miR-429 regulated genes previously implicated as drivers of EMT/MET, do not recapitulate miR-429 induced MET indicating that the underlying molecular processes are complex.

The top award for research given by the American Real Estate Society is the David Ricardo Medal, and 2017 is the 200th anniversary of the publication of The Principles of Political Economy and Taxa...

This study tests for the effect of earning potential on commuting time of working husbands and wives in two-worker households in South Korea. The theoretical result obtained by Alonso (1964) and Muth (1969) is that a higher wage has offsetting effects on commuting by increasing both the demand for housing and the time cost of commuting. This study places these offsetting effects in a model of bid-rent for a two-worker household that extends the model presented by White (1977). The basic finding is that an increase in the wage rate increases the worker's commuting time by a small statistically significant amount. The result holds for both husbands and wives. The net effect of a higher wage on commuting time is positive and small. As other studies have found, commuting time is greater for husbands than for wives.

This paper examines the housing market of metropolitan Chicago from 1970 to 2015, with particular attention on the three largest minority groups – African Americans, Hispanics and Asians. The Hispanic and Asian populations of the metropolitan area have grown rapidly, while the African-American population has actually declined since 2000. Metro Chicago has a much larger Hispanic population than is typical for major northern metro areas in the USA. Suburban growth coupled with population decline in the central city has produced large minority populations in the suburbs along with sharp declines in the traditional African-American areas of the central city. African-American areas of concentrated poverty remain. Sizable mostly white population growth has occurred in and near the downtown area as most of the nearby public housing has been demolished.

Recent technological developments—in genomics, bioinformatics and high-throughput experimental techniques—are providing opportunities to study ongoing human transposable element (TE) activity at an unprecedented level of detail. It is now possible to characterize genome-wide collections of TE insertion sites for multiple human individuals, within and between populations, and for a variety of tissue types. Comparison of TE insertion site profiles between individuals captures the germline activity of TEs and reveals insertion site variants that segregate as polymorphisms among human populations, whereas comparison among tissue types ascertains somatic TE activity that generates cellular heterogeneity. In this review, we provide an overview of these new technologies and explore their implications for population and clinical genetic studies of human TEs. We cover both recent published results on human TE insertion activity as well as the prospects for future TE studies related to human evolution and health.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal of malignancies, in large measure, due to the propensity of PDAC cells to acquire resistance to chemotherapeutic agents. A better understanding of the molecular basis of acquired resistance is a major focus of contemporary PDAC research. We report here the results of a study to independently develop cisplatin resistance in two distinct parental PDAC cell lines, AsPC1 and BxPC3, and to subsequently examine the molecular mechanisms associated with the acquired resistance. Cisplatin resistance in both resistant cell lines was found to be multifactorial and to be associated with mechanisms related to drug transport, drug inactivation, DNA damage response, DNA repair and the modulation of apoptosis. Our results demonstrate that the two resistant cell lines employed alternative molecular strategies in acquiring resistance dictated, in part, by pre-existing molecular differences between the parental cell lines. Collectively, our findings indicate that strategies to inhibit or reverse acquired resistance of PDAC cells to cisplatin, and perhaps other chemotherapeutic agents, may not be generalized but will require individual molecular profiling and analysis to be effective.

Patients with spinal cord injury (SCI) have an increased risk of developing esophageal, bladder and hematologic malignancies compared with the normal population. In the present study, we aimed to identify, through in silico analysis, miRNAs and their target genes related to the three most frequent types of cancer in individuals with SCI. In a previous study, we reported a pattern of expression of miRNAs in 17 sedentary SCI males compared with 22 healthy able-bodied males by TaqMan OpenArray. This list of miRNAs deregulated in SCI patients was uploaded to miRWALK2.0 to predict the target genes and pathways of selected miRNAs. We used Cytoscape software to construct the network displaying the miRNAs and their gene targets. Among the down-regulated miRNAs in SCI, 21, 19 and 20 miRNAs were potentially associated with hematological, bladder and esophageal cancer, respectively, and three target genes (TP53, CCND1 and KRAS) were common to all three types of cancer. The three up-regulated miRNAs were potentially targeted by 18, 15 and 10 genes associated with all three types of cancer. Our current bioinformatics analysis suggests the potential influence of several miRNAs on the development of cancer in SCI. In general, these data may provide novel information regarding potential molecular mechanisms involved in the development of cancer among individuals with SCI. Further studies aiming at understanding how miRNAs contribute to the development of the major cancers that affect patients after SCI may help elucidate the role of these molecules in the pathophysiology of the disease.

The present work proposes an Automated Place and Route Methodology for asynchronous SFQ circuits using PTL lines and a commercial EDA tool, Cadence's Innovus. At the cell level, dual rail SFQ Asynchronous standard cells were developed for the MIT Lincoln Labs SFQ5ee Process to be implemented in the Place and Route methodology. Python Scripts were written that could convert single rail netlists, obtained through the synthesis tool Design Vision from Synopsys, into dual rail asynchronous cells. Automatic Place and Route of Verilog based designs using these standard cells produced layouts that passed checks for Layout vs Schematic (LVS) and Design Rule Check (DRC). Then, the transmission line lengths are back annotated from the placed and routed design into analog simulation to simulate propagation delay.

For the constellation of neurological disorders known as chemotherapy induced peripheral neuropathy, mechanistic understanding, and treatment remain deficient. Here we present the first evidence in preclinical investigation of rats that chronic sensory neuropathy depends on non-linear interactions between cancer and chemotherapy. Global transcriptional profiling of dorsal root ganglia revealed differential expression, notably in regulators of neuronal excitability, metabolism and inflammatory responses, all of which were unpredictable from effects observed with either chemotherapy or cancer alone. Systemic interactions between cancer and chemotherapy also determined the extent of deficits in sensory encoding and ion channel protein expression by single mechanosensory neurons, with the potassium ion channel Kv3.3 emerging as a potential contributor to sensory neuron dysfunction. These original findings identify novel contributors to peripheral neuropathy, and emphasize the fundamental dependence of neuropathy on the systemic interaction between chemotherapy and cancer.

An integrated, parallel-plate microfluidic device was engineered to interrogate and fractionate cells based on their adhesivity to a substrate surface functionalized with adhesive ligand in a tightly controlled flow environment to elucidate associated cell-intrinsic pathways. Wall shear stress levels and endothelial presentation of E-selectin were modeled after the inflamed vasculature microenvironment in order to simulate in vitro conditions under which in vivo hematogenous metastasis occurs. Based on elution time from the flow channel, the collection of separate fractions of cells – non-interacting and interacting – at high yields and viabilities enabled multiple post-perfusion analyses, including flow cytometry, in vivo metastasis modeling, and transcriptomic analysis. This platform enabled the interrogation of flow-regulated cell molecular profiles, such as (co)expression levels of natively expressed selectin ligands sLe(x), CD44, and carcinoembryonic antigen, and cancer stem cell marker CD24. This additionally revealed E-selectin adhesivity exhibited by metastatic human colon carcinoma cells to be a transient phenotype. Facile and rapid, this methodology for unbiased, label free sorting of large populations of cells based on their adhesion in flow represents a method of studying flow-regulated adhesion in vitro for the identification of molecular drug targets for development as anti-metastatic cancer therapeutics.

International audience; Spherical proportional counters (SPCs) are a novel gaseous detector technology employed by the NEWS-G low-mass dark matter search experiment for their high sensitivity to single electrons from ionization. In this paper, we report on the first characterization of the single electron response of SPCs with unprecedented precision, using a UV-laser calibration system. The experimental approach and analysis methodology are presented along with various direct applications for the upcoming next phase of the experiment at SNOLAB. These include the continuous monitoring of the detector response and electron drift properties during dark matter search runs, as well as the experimental measurement of the trigger threshold efficiency. We measure a mean ionization energy of W=27.6±0.2 eV in Ne+CH4 (2%) for 2.8 keV x-rays, and demonstrate the feasibility of performing similar precision measurements at sub-keV energies for future gas mixtures to be used for dark matter searches at SNOLAB.

Cancer incidence and mortality rates in the United States (US) are not equitably distributed among all population groups, especially for racial and ethnic minorities. While non-genetic factors, including socioeconomic and environmental differences, have long been cited as the main contributors to cancer health disparities (CHD), new evidence points to a possible role of genetic and biological differences in CHD but with limited understanding and remain largely undiscovered. In this study, disparities in cancer survival outcome among US population groups were characterized based on self-identified race and ethnicity (SIRE) and genetic ancestry (GA), using univariate and multivariate survival analyses. Moreover, group-specific gene expression and mutation signatures that contribute to cancer survivorship disparities were systematically analyzed using feature selection and multiple and generalized linear regression models. Kaplan-Meier analysis of overall survival of The Cancer Genome Atlas (TCGA) cohort showed significantly different survival probability for the following GA groups: East Asian (EA) vs. European (EU) in head and neck squamous cell carcinoma (HNSC), African (AF), EA and EU vs. Admixed American (AA) in kidney renal clear cell carcinoma (KIRC), and EA, AA vs. EU and EA vs. AA in skin cutaneous carcinoma (SKCM). Multivariate Cox proportional hazard modeling using GA showed significantly greater risk of mortality for AF compared to EU (hazard ratio(HR)= 1.838, p= 0.021) with breast invasive carcinoma (BRCA) and HNSC (HR= 2.01, p= 0.005), Native Americans (NA) compared to EU (HR= 1.36, p= Citation Format: Kara Keun Lee, John F. McDonald, King I. Jordan. The effect of genetic ancestry and molecular signatures on cancer survival disparities: A pan-cancer analysis [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-002.

Recent evidence has implicated microRNAs (miRNAs) as potentially significant players in the acquisition of cancer-drug resistance in pancreatic and other cancers. To evaluate the potential contribution of miRNAs in acquired resistance to cisplatin in pancreatic cancer, we compared levels of more than 2000 human miRNAs in a cisplatin-resistant cell line (BxPC3-R) derived from parental (BxPC3) cells by step-wise exposure to increasing concentrations of the drug over more than 20 passages. The acquired drug resistance was accompanied by significant changes in the expression of 57 miRNAs, of which 23 were downregulated and 34 were upregulated. Employing a hidden Markov model (HMM) algorithm, we identified downregulation of miR-374b as likely being directly involved in acquisition of the drug-resistant phenotype. Consistent with this prediction, ectopic overexpression of miR-374b in the resistant BxPC3-R cells restored cisplatin sensitivity to levels approaching those displayed by the BxPC3 parental cells. The results are consistent with a growing body of evidence implicating miRNAs in acquired cancer-drug resistance and with the potential therapeutic value of these small regulatory RNAs in blocking and/or reversing the process.

Many design challenges exist in achieving high frequency clocking for high-speed applications. This paper describes a new clock distribution technique and clocking approach with the use of clock doublers in close proximity to sub-circuits to achieve higher data rates, and in many cases, reduce design complexity and power in serializers. A half-rate 4:1 serializer using this unique frequency doubling clock distribution technique has been implemented in a 90 nm BiCMOS process. The design includes a $2^{10}-1$ pattern length LFSR with phase shifting logic as the testing circuit and a high bandwidth cascoded output driver. The chip has the dimensions of 1.8 $\,\times\,$ 2.2 mm $^{2}$ and consumes 5.78 W from a ${-}$ 3.4 V supply voltage at 140 Gb/s.

Transposable element (TE) derived sequences comprise more than half of the human genome, and their presence has been documented to alter gene expression in a number of different ways, including the generation of alternatively spliced transcript isoforms. Alternative splicing has been associated with tumorigenesis for a number of different cancers. The objective of this study was to broadly characterize the role of human TEs in generating alternatively spliced transcript isoforms in cancer. To do so, we screened for the presence of TE-derived sequences co-located with alternative splice sites that are differentially utilized in normal versus cancer tissues. We analyzed a comprehensive set of alternative splice variants characterized for 614 matched normal-tumor tissue pairs across 13 cancer types, resulting in the discovery of 4,820 TE-generated alternative splice events distributed among 723 cancer-associated genes. SINEs (Alu) and LINEs (L1) were found to contribute the majority of TE-generated alternative splice sites in cancer genes. A number of cancer-associated genes - including MYH11, WHSC1, and CANT1 - were shown to have overexpressed TE-derived isoforms across a range of cancer types. TE-derived isoforms were also linked to cancer-specific fusion transcripts, suggesting a novel mechanism for the generation of transcriptome diversity via trans-splicing mediated by dispersed TE repeats. Citation Format: Evan A. Clayton, Lavanya Rishishwar, Tzu-Chuan Huang, Saurabh Gulati, Dongjo Ban, John F. McDonald, I. King Jordan. An atlas of transposable element derived alternative splicing in cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2115.

The paper specifies a model of the urban housing market that includes the possibility of asymmetric responses to decreases and increases in housing demand. The model includes an occupancy rate and permits the number housing units to increase or decrease. The occupancy rate and the change in housing units are critical dependent variables. As predicted by the model, the empirical results for 1970 to 2010 show that the occupancy rate in declining central cities fell when population declined and increased when housing units were removed from the stock. The suburbs of those same central cities experienced fairly smooth expansions of the housing market with only small variations in occupancy rates.

JunD, a member of the AP-1 family, is essential for cell proliferation in prostate cancer (PCa) cells. We recently demonstrated that JunD knock-down (KD) in PCa cells results in cell cycle arrest in G1-phase concomitant with a decrease in cyclin D1, Ki67, and c-MYC, but an increase in p21 levels. Furthermore, the over-expression of JunD significantly increased proliferation suggesting JunD regulation of genes required for cell cycle progression. Here, employing gene expression profiling, quantitative proteomics, and validation approaches, we demonstrate that JunD KD is associated with distinct gene and protein expression patterns. Comparative integrative analysis by Ingenuity Pathway Analysis (IPA) identified 1) cell cycle control/regulation as the top canonical pathway whose members exhibited a significant decrease in their expression following JunD KD including PRDX3, PEA15, KIF2C, and CDK2, and 2) JunD dependent genes are associated with cell proliferation, with MYC as the critical downstream regulator. Conversely, JunD over-expression induced the expression of the above genes including c-MYC. We conclude that JunD is a crucial regulator of cell cycle progression and inhibiting its target genes may be an effective approach to block prostate carcinogenesis.