Cancer development in the living organisms chronologically follows the cytotoxic, organotoxic and mutagenic alterations. Generally, the first symptom for chemical carcinogens is a metabolical response

in connection with the detoxification phenomenon and MDV3100 clinical trial for the infective agents the first symptom is often an immune response. Many nitrosamines similar to N-nitrosomorpholine have been considered as carcinogens. The cancerogenic effect of N-nitrosomorpholine (NMOR) on different animal species has been confirmed experimentally. The aim was to analyse the acute toxic effect of the N-nitrosomorpholine on the Rattus norvegicus race rats in this study. The administration of N-nitrosomorpholine causes alteration of some enzymes. The enzyme activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were determined for all the samples of blood serum and liver tissue. The results demonstrated that there was an increase in the levels of the ALP, ALT, AST and LDH enzyme activities regarding to the in vivo effect

of the N-nitrosomorpholine and the Nutlin-3 price increases were evaluated as the metabolic response of liver to hepatotoxic action. NMOR results in the modifications on the biological macromolecules owing to its alkylating characteristic. The degradation and turn over of the protein gains speed gradually till alkylating factor disappear. This case in the circulation

appears as the increase of the enzyme activity. These alterations are responsible for carcinogenicity and happen as liver cancer observation in the liver.”
“Background/Rationale: Guided by the need-driven dementia-compromised behavior (NDB) model, this study examined influences of the physical environment on wandering behavior. Methods: Using a descriptive, cross-sectional design, 122 wanderers from 28 long-term care (LTC) facilities were videotaped 10 to 12 times; data on wandering, light, sound, temperature and humidity levels, location, ambiance, and crowding were obtained. selleck chemicals llc Associations between environmental variables and wandering were evaluated with chi-square and t tests; the model was evaluated using logistic regression. Results: In all, 80% of wandering occurred in the resident’s own room, dayrooms, hallways, or dining rooms. When observed in other residents’ rooms, hallways, shower/baths, or off-unit locations, wanderers were likely (60%-92% of observations) to wander. The data were a good fit to the model overall (LR [logistic regression] chi(2) (5) = 50.38, P < .0001) and by wandering type. Conclusions: Location, light, sound, proximity of others, and ambiance are associated with wandering and may serve to inform environmental designs and care practices.

(C) 2013 sociedad Espanola de Neurocirugia. Published by Elsevier Espana, S.L. All Baf-A1 in vitro rights reserved.”
“Background: To determine if a standardized, non-xenogenic, reduced manipulation cultivation and surgical transplantation of limbal stem cell grafts is a safe and effective treatment option for patients with total and partial limbal stem cell deficiency. Methods: In vitro cellular outgrowth and phenotype of the limbal epithelial cell

and composite grafts were validated using a new protocol. Patients received either autologous (n = 15) or allogenic (n = 3) explants cultured using a standardized protocol free from xenogenic products. The resulting grafts were transplanted using a reduced manipulation surgical Selisistat in vivo technique. Results: The majority of cells ( bigger than 50%) displayed a progenitor phenotype typified by positive immunofluorescence for Delta Np63, CK14 and ABCG2 and low immunofluorescence for CK3/12 and desmoglein 3 proteins. The surgical protocol was designed to minimize manipulation and the graft itself was secured without sutures. The transplant recipients were followed for a mean of 24 months. Twelve of the 18 transplant recipients

were graded as anatomically successful (67%), based on the defined success parameters. There was a significant reduction in corneal neovascularization, which was accompanied by an improvement in pain though not photophobia or central corneal opacity post transplant. The transplantation protocol showed no measureable effect on visual acuity. Conclusion: We conclude that this standardized culture system and surgical approach is safe and effective in reducing corneal neovascularization. The technique is free from animal contaminants and maintains a large Quizartinib proportion of progenitor cells. Although this technique did not improve visual function, restoring a functional epithelial cell layer and reducing corneal neovascularization

provides an improved platform for a penetrating keratoplasty to ultimately improve visual function.”
“CD137 ligand (4-1BB ligand, TNFSF9, CD137L) is a member of the tumor necrosis factor family whose binding to its receptor, CD137 (4-1BB, TNFRSF9), mediates costimulatory and prosurvival signals necessary for T-cell activation and regulation of humoral immune responses. Recent studies have shown that anti-CD137 immunotherapy has promise as a treatment for solid tumors and lymphoid malignancies in preclinical models. Here, we define the tissue expression profile of CD137L, which has not been previously explored. We characterized the expression of CD137L in normal and neoplastic human hematopoietic and nonhematopoietic tissue and found that CD137L is preferentially expressed in B cells of the primary follicles, mantle zones of the secondary follicles, germinal centers, and in normal endothelial cells.

Blood results were censored for inpatient episodes, at the time of death, renal transplant or dialysis modality change. Multivariable multilevel mixed-effects linear regression was used and five groups of phosphate binders were compared: Group A(Calcium (Ca) and/or Aluminium (Al) binders); B(Sevelamer hydrochloride (SH) alone); C(lanthanum carbonate (LC)

alone); selleck chemicals llc D(SH and Ca/Al), E(LC and Ca/Al).\n\nResults: Of 320 patients, 292 were eligible for analysis with a mean follow-up of 15.54 (standard deviation, SD 3.98) months. Similar mean pre-dialysis serum levels of bicarbonate were observed at all 6 month-interval analyses. At 18th months, observed mean serum bicarbonate levels in mmol/L were Group B: 21.58 (SD 2.82, P<0.001), C: 23.29 (SD 2.80, P=0.02), D: 21.56 (SD 3.00, P<0.001), and E: 21.29 (SD 3.62, P=0.92) compared with Group A: 22.98 (SD 2.77). Mean serum bicarbonate was related to total SH dose in mmol/L: 22.34 (SD 2.56) for SH <2.5 g/day,

21.61 (SD 2.62) for SH 2.5-4.8 g/day, 21.04 (SD 3.31) for SH >4.8 g/day compared with 22.85 (SD 2.91) PD0332991 purchase for non-users; P-trend<0.001.\n\nConclusions: Phosphate binders’ constituents may contribute to/protect against a predisposition to pre-dialysis metabolic acidosis. This may be dose dependant in patients taking Sevelamer Hydrochloride.”
“We present the results of Monte Carlo lattice simulations of a model symmetric diblock copolymer wherein a fraction of segments of one block,

p, corresponds to ionic species, and the other block does not contain ions. We use experimentally determined Flory-Huggins interaction parameters, chi, to quantify the interactions between ionic and nonionic monomers. Analysis of the experimental data indicate that chi between poly(styrenesulfonate) and polystyrene is about 5, a value that is orders of magnitude larger than that obtained in mixtures of nonionic polymers. Our model predicts that clustering of ionic monomers in the disordered state results in stabilization of the disordered phase and the product selleck inhibitor p(2)chi N is well above the mean-field value of 10.5 at the order-disorder transition (N is the total number of monomers per chain). Network morphologies and hexagonally packed cylinders are observed in the ordered state at large p values while more traditional lamellar phases are found at small values of p.”
“Di-hydroxymethyl-di-2-(pyrrolyl)methane (DMPM) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) were dissolved in acetonitrile to form a pi-pi charge transfer complex, which exhibits a deep blue color. This complex is decomposed with the addition of captopril. It was possible to observe a change from the vivid blue color to pale orange yellow, which is related to the formation of a new n-pi complex between TCNQ and captopril.

\n\nMethods:\n\nA total of 60 sheep lumbar vertebrae were randomly divided into 3 groups. A pilot hole was made

in advance in all samples using the same method. Thereafter, the conventional pedicle screw (CPS) was inserted directly into the pilot hole in the CPS group; the hole in PMMA-PS group was first filled with polymethylmethacrylate (PMMA; 1.0 mL) and then inserted with CPS; and the EPS was inserted directly into the vertebrae in EPS group. After a period of 24 hours, biomechanical tests were performed to evaluate screw stability, and x-ray examination, micro-computerized tomography analysis, and histologic observation PLK inhibitor were performed to evaluate the interface between screw and bone.\n\nResults:\n\nCompared with the stability of CPS, those of EPS and PMMA-PS were PR171 significantly enhanced. However, no significant differences were detected between the stabilities of EPS and PMMA-PS. The PMMA surrounding the screw blocked direct contact between bone and screw and formed a “screw-PMMA-bone” interface in the PMMA-PS group. There was a “screw-bone” interface in both CPS and EPS groups. Nevertheless, the expanded anterior part of EPS formed a claw-like structure pressing the surrounding

bone trabeculae, which made the local bone tissue more compacted and denser than that in the CPS group.\n\nConclusions:\n\nEPS can enhance the screw stability as markedly as the traditional PMMA-PS in primary surgery, and EPS can form a better immediate interface between screw and bone compared click here with PMMA-PS. EPS also can effectively avoid thermal injury, leakage, and compression caused by PMMA. A great feasibility was proved in this study to perform comparisons between the 2 kinds

of pedicle screws in osteoporotic sheep vertebrae in vivo in the further research. In conclusion, we propose that EPS has a great application potential in augmentation of screw stability in the clinic.”
“The present study was conducted to determine the presence of enterotoxin and verotoxin levels in Turkish cheeses sold in retail stores in Istanbul, Turkey. For this purpose, 150 cheese samples (25 pieces of each: white pickled cheese, tulum cheese, mihalic cheese, hellim cheese, orgu cheese, and civil cheese) were analyzed microbiologically for Staphylococcus aureus, Escherichia coli, and E. coli O157:H7, and the presence of the toxins was identified using an ELISA test (RIDASCREEN (R) Set A, B, C, D, E and Verotoxin). Of the examined samples, 40 (26.66%) were positive for S. aureus and 55 (36.66%) were positive for E. coli, whereas E. coli O157 was isolated in 3 of these cheeses but no E. coli O157:H7 was found. However, enterotoxins and verotoxins were detected in 25 and in 3 of the cheeses, respectively. As a result, it was concluded that even though the level of microorganisms in the cheese was not sufficient to cause disease, the presence of toxins could be considered a potential risk for public health.

4% of cases. The mean patient age was 59 years, and 71.6% of the patients were male. Mean (+/- standard deviation) scene-arrival-to-drug time

was 26.2 (+/- 11.4) minutes, the mean scene-arrival-to-hospital-arrival time was 73.0 (+/- 20.6) minutes, and the mean transport time was 46.0 (+/- 11.1) minutes. Tenecteplase was administered Adriamycin chemical structure 35.9 (+/- 25.0) minutes prior to hospital arrival, and the estimated reperfusion time savings over PCI was 125.9 (+/- 25.0) minutes. Aborted infarctions were observed in 24.1% of patients, whereas 9.6% suffered reinfarction, 47.9% underwent rescue angioplasty, and 16.7% required coronary artery bypass grafting (CABG). Serious bleeding events occurred in 15 patients (20.5%), and four (5.5%) died. Conclusion. In this retrospective review of rural STEMI patients, tenecteplase was administered 36 minutes prior to hospital arrival, saving approximately two hours over typical PCI strategies and resulting in aborted infarctions in one-fourth of patients. In a rural setting with lengthy

transport times to PCI facilities, tenecteplase appears to be a feasible prehospital intervention. Randomized controlled trials are needed to fully evaluate the safety and effectiveness of this intervention prior to widespread adoption.”
“The effects of functional CA4P cell line groups and structures at the surface of biomaterials on protein adsorption were examined using direct interaction force measurements. Three kinds of surface structures were evaluated: polymer brushes, self-assembled monolayers with low molecular weight compounds, and surfaces with conventional polymer coatings. These surfaces had various functional groups including phosphorylcholine (PC) group. The surface characterization demonstrated that surface wettability and flexibility depended on both the structure of the surface and

the functional groups at the surface. The interactions of protein with these surfaces were evaluated by a force vs. distance curve using an atomic force microscope (AFM). We used fibrinogen as the protein, and the fibrinogen was immobilized on the surface of MDV3100 the AFM cantilever by a conventional technique. It was observed that the interaction force of fibrinogen was strongly related to surface hydrophobic nature and flexibility. That is, the interaction force increased with the increasing hydrophobic nature of the surface. The relationship between the amount of fibrinogen adsorbed on the surface and the interaction force showed good correlation in the range of fibrinogen adsorption from 0 to 250 ng/cm(2), that is, in a monolayered adsorption region. The interaction force decreased with increasing surface viscoelasticity. The most effective surface for preventing fibrinogen adsorption was the polymer brush surface with phosphorylcholine (PC) groups, that is, poly(2-methacryloyloxyethyl phosphorylcholine) brush. The interaction force of this sample was less than 0.

It suggests that Tc-99m-fanolesomab can be used to evaluate renal allograft complications. Nucl Med Commun 32:925-928 (C) 2011 Wolters Kluwer

Health vertical bar Lippincott Williams & Wilkins. Nuclear Medicine Communications 2011, 32:925-928″
“The filamentous fungus Ashbya gossypii is a cotton pathogen transmitted by insects. It is readily grown and manipulated in the laboratory selleck compound and is commercially exploited as a natural overproducer of vitamin B2. Our previous genome analysis of A. gossypii isolate ATCC10895, collected in Trinidad nearly 100 years ago, revealed extensive synteny with the Saccharomyces cerevisiae genome, leading us to use it as a model organism to understand the evolution of filamentous growth. To further develop Ashbya www.selleckchem.com/screening-libraries.html as a model system, we have investigated the ecological niche of A. gossypii and isolated additional strains and a sibling species, both useful in comparative analysis. We isolated fungi morphologically similar to A. gossypii from different plant-feeding insects of the suborder Heteroptera, generated a phylogenetic tree based on rDNA-ITS sequences, and performed high coverage short read sequencing with one A. gossypii isolate from Florida, a new species, Ashbya aceri, isolated in North Carolina, and a genetically marked derivative

of ATCC10895 intensively used for functional studies. In contrast to S. cerevisiae, all strains carry four not three mating type loci, adding a new puzzle in the evolution of Ashbya species. Another surprise was the genome identity of 99.9% between the Florida strain and ATCC10895, isolated in Trinidad. The A. aceri and A. gossypii genomes show conserved gene orders rearranged by eight translocations, 90% overall sequence identity, and fewer tandem duplications in the A. aceri genome. Both

species lack transposable elements. Finally, our work identifies plant-feeding insects of the suborder Heteroptera as the most likely natural reservoir of Ashbya, and that infection of cotton and other plants buy BIX 01294 may be incidental to the growth of the fungus in its insect host.”
“Proportion of animals which developed pinch-induced catalepsy and the duration of this state were analyzed in rats of several genotypes which differed in audiogenic epilepsy proneness and compared with “audiogenic” catalepsy after a sound-induced seizure fit. The following genotypes were studied: Wistar, KM (Krushinsky -Molodkina) strain and substrains “4″ and “0″ (selected from KM and Wistar hybrid population for high “4″ and low “0″ audiogenic epilepsy proneness). Adult KM and substrain “4″ rats developed the most intense pinch induced catalepsy, whereas Wistar and 2-month-old KM showed practically no catalepsy. After a single sound exposure pinch-induced catalepsy developed in all animals which demonstrated an audiogenic seizure fit – in KM, substrain “4″, part of Wistar rats and several animals of substrain “0″, latency of the fit onset in all rats being shorter than initially.

The serum eosinophil count decreased from 460 to 270 mu L and the neutrophil count increased from

2,200 to 10,500 mu L at 6 h. The skin prick test with wheat extract, prick to prick test with whole wheat and serum-specific Ig E for wheat were negative. We conclude that FPIES can emerge with food in connection with eating habits or culture. In view of its potentially serious clinical course, it is critical to consider this diagnosis in young children presenting with acute onset of gastrointestinal symptoms or shock.”
“Pharmacology and regenerative medicine interact in two ways. One NSC23766 supplier is the use of drugs to promote tissue regeneration. The other, less obvious but with great potential, is the use of techniques developed for regenerative medicine to engineer realistic human organoids for drug screening. This review focuses on testing for nephrotoxicity, often a problem with drugs and poorly predicted in animals. Current human-based screens mainly use proximal tubule cells growing in 2D monolayers. Realism might be improved by collagen-based Daporinad inhibitor culture systems that encourage proximal tubule cells to grow as tubules. More realistic would be a recently developed technique for engineering functioning ‘mini-kidneys’ from suspensions of stem cells, a technique that works in mouse but that could also be applied to humans.”
“The protective activity of the methanolic extract of the Crataegus songarica leaves was investigated

against CCl4- and paracetamol-induced liver damage. On folklore levels, this plant is popularly used to treat various toxicological diseases. We evaluated both in vitro and ex vivo antioxidant C59 Wnt in vitro activity of C. songarica. At higher concentration of plant extract (700 mu g/ml), 88.106% inhibition on DPPH radical scavenging activity was observed and reducing power of extract

was increased in a concentration-dependent manner. We also observed its inhibition on Fe2+/ascorbic acid-induced lipid peroxidation on rat liver microsomes in vitro. In addition, C. songarica extract exhibited antioxidant effects on calf thymus DNA damage induced by Fenton reaction. Hepatotoxicity was induced by challenging the animals with CCl4 (1 ml/kg body weight, i.p.) and paracetamol (500 mg/kg body weight) and the extract was administered at three concentrations (100, 200, and 300 mg/kg body weight). Hepatoprotection was evaluated by determining the activities of liver function marker enzymes and antioxidant status of liver. Administration of CCl4 elevated the levels of liver function enzymes, SGOT, SGPT, and LDH. We also observed a dramatic increase in ALT, AST, bilirubin, and alkaline phosphatase levels in rats administered 500 mg/kg body weight of paracetamol. Decreased antioxidant defense system as glutathione (GSH), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione-S-transferase (GST), and superoxide dismutase (SOD) were observed in rats treated with CCl4 and paracetamol.

However, we still have some problems with cutaneous leishmaniasis, hepatitis similar to C, human immunodeficiency virus, tuberculosis, infections among immunocompromised hosts, hospital-acquired infections, and antibiotic-resistant bacterial strains. We need to emphasize improvements

in sanitation, good clinical practice, and education about the rational administration of antibiotics.”
“An endophytic fungus Aspergillus terreus, var. boedijnii (Blochwitz) was isolated from red marine alga Laurencia ceylanica, J. Agardh, cultured in large scale and extracted with EtOAc. The above-mentioned extract yielded a new butyrolactone, 3-hydroxy-4-(4-hydroxyphenyl)-5-methoxycarbonyl-5-(4-hydroxy-3-formylbenzyl)-2,5-dihydro-2-furanone (1), along with the previously reported nine compounds, butyrolactone-1 (2), 6-hydroxymellin (3), (3R, 4R)-6,7-dimethoxy-4-hydroxymellin Selleck SRT2104 (4), (+)-territonin (5), (+)-territonin-A (6), (+)-asterrelenin (7), (+)-terrein (8), oleic acid (9) and glucopyranosyl–sitosterol (10), on column and preparative thin-layer chromatography. Compounds 1-8 were subjected to -glucuronidase inhibitory activity test, and 1 showed a remarkable activity, while 2 and 7 showed moderate activity.”
“In this work,

the hydrodynamic characteristics in tubular photobioreactors with a series GSI-IX ic50 of helical static mixers built-in were numerically investigated using computational fluid dynamics (CFD). The influences of height and screw pitch of the helical static mixer and fluid inlet velocity on the cell trajectories, swirl numbers and energy consumption were examined. In order to verify the actual results for cultivation of microalgae, cultivation experiments of freshwater Chlorella sp. were carried out in photobioreactor with and without helical static mixer built-in at the same time. It was shown that find more with built-in helical static mixer, the mixing of fluid could be intensified, and the light/dark cycle could also be achieved which is of benefit for the growth of microalgae. The biomass productivity of Chlorella

sp. in tubular photobioreactor with helical static mixer built-in was 37.26 % higher than that in the photobioreactor without helical static mixer.”
“Severe mitral valve regurgitation is a serious condition with significant morbidity and mortality. It is not uncommon recently, to see patients with significant mitral valve regurgitation that are considered “non-surgical candidates” due to their comorbidities. MitraClip is a new percutaneous approach for treating mitral valve regurgitation which involves mechanical edge-to-edge coaptation of the mitral leaflets. In October of 2013, The US Food and Drug Administration (FDA) approved the MitraClip for patients with symptomatic degenerative mitral regurgitation deemed high risk for mitral-valve surgery. Several large clinical trials confirmed the safety and efficacy of MitraClip.

Methods: We collected visit diagnoses from all 107 public health facilities in Leon between 2008 and 2012. We compared rates of pneumonia hospitalizations, ambulatory visits for pneumonia and infant mortality during the prevaccine (2008-2010) and vaccine (2011-2012) periods among different age groups

of children using generalized estimating equations, accounting for clustering by municipality. Exposure time was estimated by official municipality ABT-263 mw population estimates. Results: The adjusted incidence rate ratio for pneumonia hospitalization in the vaccine versus prevaccine period was 0.67 (0.59-0.75) among infants and 0.74 (0.67-0.81) among 1-year olds. The adjusted incidence rate ratio for ambulatory visits for pneumonia was 0.87 (0.75-1.01) among infants, and 0.84 (0.74, 0.95) among 1-year olds. The adjusted incidence rate ratio for infant mortality was 0.67 (0.57-0.80). We also observed lower rates of health facility visits for pneumonia among age groups (2- to 4-year old and 5- to 14-year old) not eligible to receive Bafilomycin A1 cell line PCV-13. Conclusions: Within the first 2 years of a PCV-13 immunization program in Nicaragua, we observed lower rates of hospitalizations and ambulatory visits for pneumonia among children of all ages and a lower infant mortality rate. Lower rates of pneumonia among age groups not eligible to receive PCV-13

suggest an indirect effect of the vaccine.”
“MYC dysregulation initiates a dynamic process of genomic instability that is linked to tumor initiation. Early studies using MYC-carrying retroviruses showed that these viruses were potent transforming agents. Cell culture models followed that addressed the role of MYC in transformation. With the advent of MYC transgenic mice, it became obvious that MYC deregulation alone was sufficient to initiate B-cell neoplasia in mice. More than 70% of all tumors have some form of c-MYC gene dysregulation, which affects gene regulation, microRNA expression profiles, large genomic amplifications, and the overall organization of the nucleus.

These changes CAL-101 mouse set the stage for the dynamic genomic rearrangements that are associated with cellular transformation.”
“Adequate tissue oxygenation is an essential factor in diabetic foot management. Hyperbaric oxygen (HBO) therapy has been successfully used as adjunctive treatment to improve the healing of diabetic foot ulcers. However, the clinical uses of HBO therapy are limited due to the low availability of HBO chambers, poor patient compliance, and high oxidative potential. Normobaric hyperoxic (NBO) therapy may be a potentially attractive alternative to HBO therapy because of its high availability, good patient compliance, and few technical requirements. Several studies on NBO therapy to attenuate infarct volume after stroke have provided compelling evidence.

Conclusions: Individuals with traumatic brain injury may benefit from memory group intervention focusing on internal strategy use. Study hypotheses should be retested using a randomized, controlled design, and further research is needed to better delineate influences on intervention GW4869 research buy candidacy and outcomes.”
“An effective hydrolytic degradation of PDLLA, PCL and their blends in a phosphate-buffered solution of pH 4.0 at 37 degrees C for 18 weeks was achieved, observing a considerably faster degradation of PDLLA as compared to PCL due to the hydrophobic and semicrystalline nature

of PCL matrix, able to partially prevent water diffusion into the bulk specimen.\n\nDSC and FTIR results indicated that PCL phase, in compositions rich in PCL, find more was very stable against hydrolysis, but the presence of PDLLA in the PDLLA/PCL blends seemed to catalyze the hydrolytic degradation of the PCL phase, probably associated to

easier diffusion of water into the PCL domains by the presence of PDLLA amorphous regions. This last trend was proportional to the content of PDLLA in the blends, excepting for the composition 64%PDLLA/36%PCL It was confirmed that PCL molecules partially delayed hydrolysis of PDLLA molecules, according to FTIR analysis, and the water diffusion prevention level was proportional to the content of PCL in the blends, except for the system 64%PDLLA/36%PCL, which presented a lower extent of degradation than neat PDLLA but higher than the blend 80% PDLLA/20%PCL. This indicated that PCL molecules did not significantly

impede hydrolysis of PDLLA molecules in this blend, possibly due to the achievement of a particular structure of the PDLLA/PCL interphase in this blend. In general, hydrolysis of PDLLA/PCL Rabusertib order blends was found to be a complex phenomenon depending not only on the content of both polymer phases, but also on the polymer phase crystallinity and morphology. (C) 2012 Elsevier Ltd. All rights reserved.”
“Background: Dynamic activation and inactivation of gene regulatory DNA produce the expression changes that drive the differentiation of cellular lineages. Identifying regulatory regions active during developmental transitions is necessary to understand how the genome specifies complex developmental programs and how these processes are disrupted in disease. Gene regulatory dynamics are mediated by many factors, including the binding of transcription factors (TFs) and the methylation and acetylation of DNA and histones. Genome-wide maps of TF binding and DNA and histone modifications have been generated for many cellular contexts; however, given the diversity and complexity of animal development, these data cover only a small fraction of the cellular and developmental contexts of interest. Thus, there is a need for methods that use existing epigenetic and functional genomics data to analyze the thousands of contexts that remain uncharacterized.