Layerless fabrication with continuous liquid interface production

Despite the increasing popularity of 3D printing, also known as additive manufacturing (AM), the technique has not developed beyond the realm of rapid prototyping. This confinement of the field can be attributed to the inherent flaws of layer-by-layer printing and, in particular, anisotropic mechanical properties that depend on print direction, visible by the staircasing surface finish effect. Continuous liquid interface production (CLIP) is an alternative approach to AM that capitalizes on the fundamental principle of oxygen-inhibited photopolymerization to generate a continual liquid interface of uncured resin between the growing part and the exposure window. This interface eliminates the necessity of an iterative layer-by-layer process, allowing for continuous production. Herein we report the advantages of continuous production, specifically the fabrication of layerless parts. These advantages enable the fabrication of large overhangs without the use of supports, reduction of the staircasing effect without compromising fabrication time, and isotropic mechanical properties. Combined, these advantages result in multiple indicators of layerless and monolithic fabrication using CLIP technology

Jamming Model for the Extremal Optimization Heuristic

Extremal Optimization, a recently introduced meta-heuristic for hard optimization problems, is analyzed on a simple model of jamming. The model is motivated first by the problem of finding lowest energy configurations for a disordered spin system on a fixed-valence graph. The numerical results for the spin system exhibit the same phenomena found in all earlier studies of extremal optimization, and our analytical results for the model reproduce many of these features.Comment: 9 pages, RevTex4, 7 ps-figures included, as to appear in J. Phys. A, related papers available at http://www.physics.emory.edu/faculty/boettcher

Catheter-based intervention for pulmonary vein stenosis due to fibrosing mediastinitis: The Mayo Clinic experience

AbstractIntroductionFibrosing mediastinitis (FM) is a rare but fatal disease characterized by an excessive fibrotic reaction in the mediastinum, which can lead to life-threatening stenosis of the pulmonary veins (PV). Catheter-based intervention is currently the only viable option for therapy. However, the current literature on how best to manage these difficult cases, especially in regards to sequential interventions and their potential complications is very limited.MethodsWe searched through a database of all patients who have undergone PV interventions at the Earl H. Wood Cardiac Catheterization Laboratory in Mayo Clinic, Rochester. From this collection, we selected patients that underwent PV intervention to relieve stenosis secondary to FM.ResultsEight patients were identified, with a mean age of 41years (24–59years). Five were men, and three were women. Three patients underwent balloon angioplasty alone, and five patients had stents placed. The majority of patients had acute hemodynamic and symptomatic improvement. More than one intervention was required in five patients, four patients had at least one episode of restenosis, and four patients died within four weeks of their first PV intervention.ConclusionsWe describe the largest reported case series of catheter-based intervention for PV stenosis in FM. Although catheter-based therapy improved hemodynamics, short-term vascular patency, and patient symptoms, the rate of life-threatening complications, restenosis, and mortality associated with these interventions was found to be high. Despite these associated risks, catheter-based intervention is the only palliative option available to improve quality of life in severely symptomatic patients with PV stenosis and FM. Patients with PV stenosis and FM (especially those with bilateral disease) have an overall poor prognosis in spite of undergoing these interventions due to the progressive and recalcitrant nature of the disease. This underscores the need for further innovative approaches to manage this disease

A Case of Tumor Lysis Syndrome after Docetaxel Administration for Recurrent Ovarian Cancer

Abstract Tumor Lysis Syndrome is a rare complication of the treatment of solid malignancies. A 51 year old female developed this condition one week after undergoing docetaxel chemotherapy for progressive, recurrent ovarian cancer. She was diagnosed based on classic laboratory disturbances including increased creatinine, hyperphosphatemia, hypercalcemia, hyperkalemia, and hyperuricemia. The patient was successfully treated with aggressive intravenous hydration, allopurinol, and rasburicase. Although uncommon, clinicians should be aware of this condition so that proper identification occurs and treatment can be implemented promptly. as this patient had a BMI over 25 (BMI 27.4, BSA 1.78). Creatinine clearance was calculated using the Cockroft Gault equation with a minimum creatinine value of 0.7 mg/dL. The Calvert formula was used for Carboplatin dosing. She received 6 cycles of dose-dense paclitaxel and carboplatin, with an initial improvement in her CA125. However, CT imaging at completion of 6 cycles demonstrated residual disease involving the chest, abdomen and pelvis and her CA125 plateaued. She was diagnosed with platinum resistant disease and was switched to a 28 cycle day regimen of gemcitabine (800 mg/m 2 , cycle days 1 and 8) and bevacizumab (15 mg/kg, cycle day1) of which she received 2 cycles. Her CA 125 count continued to rise despite this treatment, thus she was changed to a 28 cycle day regimen of liposomal doxorubicin (40 mg/m 2 , cycle day 1) and bevacizumab (15 mg/kg, cycle day 1). After 3 cycles of therapy, her disease failed to respond as evidenced by a rising CA 125. As a result, she was changed to docetaxel at a dose of 75 mg/m 2 and received one cycle uneventfully. Seven days after her first docetaxel administration, the patient presented with fatigue and decreased oral intake. She was admitted for supportive therapy for suspected chemotherapy-associated malaise. On the evening of hospital day #1 the patient reported increased shortness of breath. She was noted to be pale, hypotensive, and hypoxic. An EKG revealed new onset right bundle branch block. She was transferred to the ICU for critical care monitoring given her worsening clinical picture. TLS was diagnosed after laboratory evaluation revealed acute renal insufficiency (2.4 mg/dL) and severe electrolyte abnormalities (phosphorus 5.7 mg/dL, calcium 9.7 mg/dL, potassium 7.0 mmol/L and uric acid 10.1 mg/dL). Treatment with allopurinol, rasburicase, and aggressive hydration was promptly initiated. She received a single dose of intravenous rasburicase and started on allopurinol 300 mg BID. Six hours following administration of rasburicase, her uric acid had decreased to 2.9 mg/dL. She was continued on allopurinol for 3 days as her uric acid level continued to decrease. As her electrolyte

S110, a novel decitabine dinucleotide, increases fetal hemoglobin levels in baboons (P. anubis)

<p>Abstract</p> <p>Background</p> <p>S110 is a novel dinucleoside analog that could have advantages over existing DNA methyltransferase (DNMT) inhibitors such as decitabine. A potential therapeutic role for S110 is to increase fetal hemoglobin (HbF) levels to treat β-hemoglobinopathies. In these experiments the effect of S110 on HbF levels in baboons and its ability to reduce DNA methylation of the γ-globin gene promoter in vivo were evaluated.</p> <p>Methods</p> <p>The effect of S110 on HbF and γ-globin promoter DNA methylation was examined in cultured human erythroid progenitors and in vivo in the baboon pre-clinical model. S110 pharmacokinetics was also examined in the baboon model.</p> <p>Results</p> <p>S110 increased HbF and reduced DNA methylation of the γ-globin promoter in human erythroid progenitors and in baboons when administered subcutaneously. Pharmacokinetic analysis was consistent with rapid conversion of S110 into the deoxycytosine analog decitabine that binds and depletes DNA.</p> <p>Conclusion</p> <p>S110 is rapidly converted into decitabine, hypomethylates DNA, and induces HbF in cultured human erythroid progenitors and the baboon pre-clinical model.</p

Effect of Aspect Ratio and Deformability on Nanoparticle Extravasation through Nanopores

We describe the fabrication of filamentous hydrogel nanoparticles using a unique soft lithography based particle molding process referred to as PRINT (Particle Replication in Non-wetting Templates). The nanoparticles possess a constant width of 80 nm, and we varied their lengths ranging from 180 nm to 5000 nm. In addition to varying the aspect ratio of the particles, the deformability of the particles was tuned by varying the cross-link density within the particle matrix. Size characteristics such as hydrodynamic diameter and persistence length of the particles were analyzed using dynamic light scattering and electron microscopy techniques, respectively, while particle deformability was assessed by atomic force microscopy. Additionally, the ability of the particles to pass through membranes containing 0.2 μm pores was assessed by means of a simple filtration technique, and particle recovery was determined using fluorescence spectroscopy. The results show that particle recovery is mostly independent of aspect ratio at all cross-linker concentrations utilized, with the exception of 96 wt% PEG diacrylate 80 × 5000 nm particles, which showed the lowest percent recovery

Multiscale computational analysis of Xenopus laevis morphogenesis reveals key insights of systems-level behavior

<p>Abstract</p> <p>Background</p> <p>Tissue morphogenesis is a complex process whereby tissue structures self-assemble by the aggregate behaviors of independently acting cells responding to both intracellular and extracellular cues in their environment. During embryonic development, morphogenesis is particularly important for organizing cells into tissues, and although key regulatory events of this process are well studied in isolation, a number of important systems-level questions remain unanswered. This is due, in part, to a lack of integrative tools that enable the coupling of biological phenomena across spatial and temporal scales. Here, we present a new computational framework that integrates intracellular signaling information with multi-cell behaviors in the context of a spatially heterogeneous tissue environment.</p> <p>Results</p> <p>We have developed a computational simulation of mesendoderm migration in the <it>Xenopus laevis </it>explant model, which is a well studied biological model of tissue morphogenesis that recapitulates many features of this process during development in humans. The simulation couples, via a JAVA interface, an ordinary differential equation-based mass action kinetics model to compute intracellular Wnt/β-catenin signaling with an agent-based model of mesendoderm migration across a fibronectin extracellular matrix substrate. The emergent cell behaviors in the simulation suggest the following properties of the system: maintaining the integrity of cell-to-cell contact signals is necessary for preventing fractionation of cells as they move, contact with the Fn substrate and the existence of a Fn gradient provides an extracellular feedback loop that governs migration speed, the incorporation of polarity signals is required for cells to migrate in the same direction, and a delicate balance of integrin and cadherin interactions is needed to reproduce experimentally observed migratory behaviors.</p> <p>Conclusion</p> <p>Our computational framework couples two different spatial scales in biology: intracellular with multicellular. In our simulation, events at one scale have quantitative and dynamic impact on events at the other scale. This integration enables the testing and identification of key systems-level hypotheses regarding how signaling proteins affect overall tissue-level behavior during morphogenesis in an experimentally verifiable system. Applications of this approach extend to the study of tissue patterning processes that occur during adulthood and disease, such as tumorgenesis and atherogenesis.</p

Salience-based selection: attentional capture by distractors less salient than the target

Current accounts of attentional capture predict the most salient stimulus to be invariably selected first. However, existing salience and visual search models assume noise in the map computation or selection process. Consequently, they predict the first selection to be stochastically dependent on salience, implying that attention could even be captured first by the second most salient (instead of the most salient) stimulus in the field. Yet, capture by less salient distractors has not been reported and salience-based selection accounts claim that the distractor has to be more salient in order to capture attention. We tested this prediction using an empirical and modeling approach of the visual search distractor paradigm. For the empirical part, we manipulated salience of target and distractor parametrically and measured reaction time interference when a distractor was present compared to absent. Reaction time interference was strongly correlated with distractor salience relative to the target. Moreover, even distractors less salient than the target captured attention, as measured by reaction time interference and oculomotor capture. In the modeling part, we simulated first selection in the distractor paradigm using behavioral measures of salience and considering the time course of selection including noise. We were able to replicate the result pattern we obtained in the empirical part. We conclude that each salience value follows a specific selection time distribution and attentional capture occurs when the selection time distributions of target and distractor overlap. Hence, selection is stochastic in nature and attentional capture occurs with a certain probability depending on relative salience