ABSTRACT
We report the effect of shape anisotropy and material properties on the directed assembly of binary suspensions composed of magnetizable ellipsoids. In a Monte Carlo simulation, we implement the ellipsoid-dipole model to calculate the pairwise dipolar interaction energy as a function of position and orientation. The analysis explores dilute suspensions of paramagnetic and diamagnetic ellipsoids with different aspect ratios in a superparamagnetic medium. We analyze the local order of binary structures as a function of particle aspect ratio, medium permeability, and dipolar interaction strength. Our results show that local order and symmetry are tunable under the influence of a uniform magnetic field when one component of the structure is dilute with respect to the other. The simulation results match previously reported experiments on the directed assembly of binary suspension of spheres. Additionally, we report the conditions on particle aspect ratios and medium properties for various structures with rotational symmetries, as well as open and enclosed structures under the influence of a uniform magnetic field.
ABSTRACT
Microbial resistance to currently available antibiotics poses a great threat in the global fight against infections. An important step in determining bacterial antibiotic resistance can be selective DNA sequence capture and fluorescence labeling. In this paper, we demonstrate the fabrication of simple, robust, inexpensive microfluidic devices for DNA capture and fluorescence detection of a model antibiotic resistance gene sequence. We laser micromachined polymethyl methacrylate microchannels and enclosed them using pressure-sensitive adhesive tapes. We then formed porous polymer monoliths with DNA capture probes in these microchannels and used them for sequence-specific capture, fluorescent labeling, and laser-induced fluorescence detection of picomolar (pM) concentrations of synthetic and plasmid antibiotic resistance gene targets. The relative fluorescence for the elution peaks increased with loaded target DNA concentration. We observed higher fluorescence signal and percent recovery for synthetic target DNA compared to plasmid DNA at the same loaded target concentration. A non-target gene was used for control experiments and produced < 3% capture relative to the same concentration of target. The full analysis process including device fabrication was completed in less than 90 min with a limit of detection of 30 pM. The simplicity of device fabrication and good DNA capture selectivity demonstrated herein have potential for application with processes for bacterial plasmid DNA extraction and single-particle counting to facilitate determination of antibiotic susceptibility. Graphical abstract.
Subject(s)
Escherichia coli/genetics , Genes, Bacterial , Lab-On-A-Chip Devices , Plasmids/genetics , DNA Probes/genetics , Equipment Design , Escherichia coli Infections/microbiology , Fluorescence , Humans , Nucleic Acid Hybridization/methods , Porosity , Pressure , Sepsis/microbiologyABSTRACT
PURPOSE: To explore whether privacy restrictions developed to protect patients have complicated research within a 15-year surveillance study conducted with US cancer registries. METHODS: Data from enrolling 27 cancer registries over a 10-year period were examined to describe the amount of time needed to obtain study approval. We also analyzed the proportion of patients that completed a research interview out of the total reported by the registries and examined factors thought to influence this measure. RESULTS: The average length of the research review process from submission to approval of the research was 7 months (range, <1 to 24 months), and it took 6 months or more to obtain approval of the research at 41% of the cancer registries. Most registries (78%) required additional permission steps to gain access to patients for research. After adjustment for covariates, the interview response proportion was 110% greater (ratio of response proportion = 2.1; 95% confidence interval: 1.3, 3.3) when the least restrictive versus the most restrictive permission steps were required. An interview was more often completed for patients (or proxies) if patients were alive, within a year of being diagnosed, or identified earlier in the study. CONCLUSIONS: Lengthy research review processes increased the time between diagnosis and provision of patient information to the researcher. Requiring physician permission for access to patients was associated with lower subject participation. A single national point of entry for use of cancer registry data in health research is worthy of consideration to make the research approval process efficient. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.
Subject(s)
Bone Density Conservation Agents/adverse effects , Neoplasms/drug therapy , Privacy/legislation & jurisprudence , Product Surveillance, Postmarketing/methods , Adult , Aged , Bone Density Conservation Agents/administration & dosage , Female , Humans , Interviews as Topic , Male , Middle Aged , Osteoporosis/drug therapy , Registries , Teriparatide/administration & dosage , Teriparatide/adverse effects , Time Factors , United StatesABSTRACT
Infant faces readily capture adult attention and elicit enhanced neural processing, likely due to their importance evolutionarily in facilitating bonds with caregivers. Facial malformations have been shown to impact early infant-caregiver interactions negatively. However, it remains unclear how such facial malformations may impact early visual processing. The current study used a combination of eye tracking and electroencephalography (EEG) to investigate adults' early visual processing of infant faces with cleft lip/palate as compared to normal infant faces, as well as the impact cleft palate has on perceived cuteness. The results demonstrated a significant decrease in early visual attention to the eye region for infants with cleft palate, while increased visual attention is registered on the mouth region. Increased neural processing of the cleft palate was evident at the N170 and LPP, suggesting differences in configural processing and affective responses to the faces. Infants with cleft palate were also rated significantly less cute than their healthy counterparts (mean difference = .73, p < .001). These results suggest that infants' faces with cleft lip/palate are processed differently at early visual perception. These processing differences may contribute to several important aspects of development (e.g., joint attention) and may play a vital role in the previously observed difficulties in mother-infant interactions.
Subject(s)
Cleft Lip , Cleft Palate , Adult , Infant , Humans , Face/abnormalities , Visual Perception , Mother-Child RelationsABSTRACT
Emerging antimicrobial drug resistance is increasing the complexity involved in treating critical conditions such as bacterial induced sepsis. Methods for diagnosing specific drug resistance tend to be rapid or sensitive, but not both. Detection methods like sequence-specific single-molecule analysis could address this concern if they could be adapted to work on smaller targets similar to those produced in traditional clinical situations. In this work we demonstrate that a 120 bp double stranded polynucleotide with an overhanging single stranded 25 bp probe sequence can be created by immobilizing DNA with a biotin/streptavidin magnetic bead system, labeling with SYBR Gold, and rinsing the excess away while the probe retains multiple fluorophores. These probes with multiple fluorophores can then be used to label a bacterial plasmid target in a sequence-specific manner. These probes enabled the detection of 1 pM plasmid samples containing a portion of an antibiotic resistance gene sequence. This system shows the possibility of improving capture and fluorescence labeling of small nucleic acid fragments, generating lower limits of detection for clinically relevant samples while maintaining rapid processing times.
ABSTRACT
BACKGROUND: A major challenge in cancer chemotherapy has been developing safe and clinically efficacious chemotherapeutic agents. With its low toxicity profile, curcumin (diferuloylmethane), a naturally occurring flavinoid derived from the rhizome of Curcuma longa, has great promise. In vitro and in vivo preclinical studies have shown its inhibitory anticancer, antioxidant, anti-inflammatory, antiproliferative, and proapoptotic activities. The multiple mechanisms of the antitumor effect of curcumin putatively include down-regulating the expression of gene products such as nuclear factor-kappaB, growth suppression, inducing apoptosis, and modulating various signal transduction pathways and the expression of many oncogenes. The mechanisms underlying the antitumor activity of curcumin have not, however, been completely delineated. METHODS: An oligonucleotide microarray chip was developed and used to profile microRNA (miRNA) expressions in pancreatic cells treated with curcumin. Transcripts with regulated expression patterns on the arrays were validated by real-time PCRs. Additionally, potential mRNA targets were analyzed bioinformatically and confirmed with flow cytometry experiments. RESULTS: Curcumin alters miRNA expression in human pancreatic cells, up-regulating miRNA-22 and down-regulating miRNA-199a*, as confirmed by TaqMan real-time PCR. Upregulation of miRNA-22 expression by curcumin or by transfection with miRNA-22 mimetics in the PxBC-3 pancreatic cancer cell line suppressed expression of its target genes SP1 transcription factor (SP1) and estrogen receptor 1 (ESR1), while inhibiting miRNA-22 with antisense enhanced SP1 and ESR1 expression. CONCLUSIONS: These observations suggest that modulation of miRNA expression may be an important mechanism underlying the biological effects of curcumin.
Subject(s)
Curcumin/pharmacology , Gene Expression Profiling , MicroRNAs/genetics , Pancreatic Neoplasms/genetics , Cell Line, Tumor , Flow Cytometry , Humans , Pancreatic Neoplasms/pathology , Polymerase Chain ReactionABSTRACT
OBJECTIVES: To assess the impact of HAART use on AIDS-defining Kaposi's sarcoma and non-Hodgkin lymphoma (NHL) among adults with AIDS. DESIGN: Registry linkage study. METHODS: Adults diagnosed with AIDS from 1990 to 2000 in the San Francisco AIDS case registry were matched with cancer cases diagnosed from 1985 to 2002 in the California Cancer Registry. Multivariate Cox proportional hazard models were used to evaluate the risk and survival of AIDS-related Kaposi's sarcoma, systemic NHL, and primary central nervous system (CNS) lymphoma. RESULTS: Of the 14 183 adults with AIDS, 3028 were diagnosed with Kaposi's sarcoma, 776 with systemic NHL, and 254 with CNS NHL. After adjustment for potential confounders, more recent calendar period and use of HAART were significantly associated with a decreased risk of Kaposi's sarcoma, whereas HAART use but not calendar period was significantly associated with systemic and CNS NHL. In adjusted analysis of Kaposi's sarcoma survival time, there was strong evidence of a reduced risk of death associated with HAART use and more recent calendar period. In contrast, in adjusted analyses of systemic NHL survival time, HAART use was not associated with improved survival time; however, calendar period was associated with longer survival. In adjusted analysis of CNS NHL survival time, only cancer treatment was associated with a longer survival time. CONCLUSION: After controlling for calendar period and other confounders, use of HAART decreased the risk of Kaposi's sarcoma, systemic NHL, and CNS NHL. Use of HAART also increased Kaposi's sarcoma survival time but not NHL survival time.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Lymphoma, AIDS-Related/drug therapy , Sarcoma, Kaposi/drug therapy , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Antiretroviral Therapy, Highly Active , Female , Humans , Lymphoma, AIDS-Related/epidemiology , Male , Middle Aged , Registries , Sarcoma, Kaposi/epidemiology , Time Factors , Young AdultABSTRACT
OBJECTIVE: This study describes breast cancer stage at diagnosis among California women receiving mammograms through a state-administered screening program in comparison to other California women. METHOD: Linked data from California-administered screening programs and the California Cancer Registry were used to identify participants diagnosed with breast cancer between 1994 and 2000. Logistic regression was used to compare the adjusted likelihood of late stage disease among program participants (categorized into four subgroups based on the timing and frequency of mammograms) to non-participants in California diagnosed during the same time period. RESULTS: Program participants were significantly more likely than non-participants to be diagnosed at late stage (adjusted OR 1.2; 95% CI 1.1, 1.3), with the highest risk occurring among those diagnosed 0-1 months after initial mammogram (adjusted OR 1.8; 95% CI 1.6, 2.1). The stage distribution among regularly screened participants was similar to non-participants (adjusted OR of late stage disease 0.9; 95% CI 0.7, 1.1). CONCLUSIONS: Although program participants were more likely to be diagnosed at late stage than non-participants, their stage distribution was distinctly different according to their pattern of mammography utilization. This likely reflects differential utilization of program diagnostic and screening services, which should be taken into account in program evaluation.