Low Voltage High Precision Spatial Light ModulatorsFinal Report

The goal of this project was to make LLNL a leader in Spatial Light Modulators (SLMs) by developing the technology that will be needed by the next generation of SLMs. We would use new lower voltage actuators and bond those actuators directly to controlling circuitry to break the fundamental limitations that constrain current SLM technology. This three-year project was underfunded in the first year and not funded in the second year. With the funding that was available, we produced actuators and designs for the controlling circuitry that would have been integrated in the second year. Spatial light modulators (SLMs) are arrays of tiny movable mirrors that modulate the wave-fronts of light. SLMs can correct aberrations in incoming light for adaptive optics or modulate light for beam control, optical communication and particle manipulation. MicroElectroMechanical Systems (MEMS) is a technology that utilizes the microfabrication tools developed by the semiconductor industry to fabricate a wide variety of tiny machines. The first generation of MEMS SLMs have improved the functionality of SLMs while drastically reducing per pixel cost making arrays on the order of 1000 pixels readily available. These MEMS SLMs however are limited by the nature of their designs to be very difficult to scale above 1000 pixels and have very limited positioning accuracy. By co-locating the MEMS mirrors with CMOS electronics, we will increase the scalability and positioning accuracy. To do this we will have to make substantial advances in SLM actuator design, and fabrication

MN-ANDALUSITE, SPESSARTINE, MN-GROSSULAR, PIEMONTITE AND MN-ZOISITE/CLINOZOISITE FROM TRIKORFO, THASSOS ISLAND, GREECE

Μυλωνιτιωμένοι πλούσιοι σε μαγγάνιο σχιστόλιθοι και ασβεστοπυριτικά στρώματα που απαντούν ως ενδιαστρώσεις εντός αμφιβολιτικής έως πρασινοσχιστολιθικής φάσης μεταμόρφωσης μαρμαρυγιακούς σχιστόλιθους στο Τρίκορφο της Θάσου, 2069 χαρακτηρίζονται από μία ασυνήθιστη Mn-ούχο παραγένεση μεταμορφικών ορυκτών τα περισσότερα από τα οποία σε ιδιαίτερα μεγάλους κρυστάλλους και σε ποικιλία πολύτιμων λίθων. Τα Mn-ούχα πυριτικά ορυκτά απαντούν τόσο σε στρώσεις παράλληλα με την φύλλωση όσο και σε φλέβες που τέμνουν τη μεταμορφική δομή. Τα ορυκτά πιεμοντίτης (έως 12.7 % κ.β. Mn2O3), Mn-ούχο επίδοτο (έως 7.8 % κ.β. Mn2O3), Mn-ούχος ανδαλουσίτης (έως 15.6 % κ.β. Mn2O3), φτωχός σε Mn ροζ κλινοζοϊσίτης/επίδοτο (έως 0.87 % κ.β. Mn2O3), φτωχός σε Mn ροζ έως κόκκινος ζοϊσίτης (έως 0.21 % κ.β. Mn2O3), σπεσσαρτίνης (έως 47.7 % κ.β. MnO) και Mn-ούχος γροσσουλάριος (έως 3.6 % κ.β. MnO), συνοδεύονται από διοψίδιο, κεροστίλβη, φλογοπίτη, μοσχοβίτη, τουρμαλίνη, αιματίτη και σιδηρούχο κυανίτη. Η παραγένεση που μελετήθηκε είναι ενδεικτική υψηλών τιμών πτητικότητας του οξυγόνου λόγω της παρουσίας προϋπάρχουσας έντονα οξειδωτικής προ-μεταμορφικής ορυκτολογικής παραγένεσης πλούσιας σε μαγγάνιο. Σχηματίσθηκε κατά την πρόδρομη μεταμόρφωση ιζηματογενών πρωτόλιθων πλούσιων σε Mn, με ακόλουθη επανισσορόπηση απο τις μέγιστες συνθήκες πίεσης και θερμοκρασίας, σχηματισμό φλεβών και μετασωμάτωσης κατά την ανάδρομη μεταμόρφωση που συνόδευσε την ανάδυση της Θάσου στο Ολιγόκαινο-Μειόκαινο. Εναλλακτικά, η προσφορά ρευστών από γρανιτοειδή κατά την διάρκεια μεταμόρφωσης επαφής δεν πρέπει να αποκλειστεί. Η περιοχή μελέτης αντιπροσωπεύει μοναδικό ορυκτολογικό Γεώτοπο. Η γεωλογική-ορυκτολογική αυτή κληρονομιά μπορεί να προστατευθεί μέσω της ίδρυσης ενός Γεωπάρκου που θα συμβάλλει επιπλέον και στην προώθηση φιλικής προς το περιβάλλον ανάπτυξης της Θάσου.Mylonitized manganiferous schists and calc-silicate layers intercalated within amphibolite- to greenschist facies mica schists from the Trikorfo area (Thassos Island, Greece), host an unusual Mn-rich paragenesis of metamorphic silicate minerals, most of them in large, gemmy crystals. The silicates occur both in layers subparallel to the foliation and within discordant veins cross-cutting the metamorphic fabric. Piemontite (up to 12.7 wt. % Mn2O3), Mn-rich epidote (up to 7.8 wt. % Mn2O3), Mn-rich andalusite (up to 15.6 wt. % Mn2O3), Mn-poor pink clinozoisite-epidote (up to 0.87 wt. % Mn2O3), Mn-poor pink zoisite (up to 0.21 wt. % Mn2O3), spessartine (up to 47.7 wt. % MnO) and Mn-rich grossular (up to 3.6 wt. % MnO) are associated with diopside, hornblende, phlogopite, muscovite, tourmaline, hematite and iron-bearing kyanite. The studied assemblages are indicative of high fO2 conditions due to the presence of highly oxidized pre-metamorphic Mn-rich mineral associations. They developed during prograde metamorphism of a Mn-rich sedimentary protolith(s), followed by re equilibration to post-peak metamorphic conditions, vein formation and metasomatism during retrograde metamorphism accompanying the exhumation of the Thassos Island during the Oligocene-Miocene. Alternatively, the skarn similar mineralogy of the calc-silicate layers could have been formed by fluids released by granitoids during contact metamorphism. The studied area represents a unique mineralogical geotope. Its geological-mineralogical heritage should be protected through establishment of a mineralogical-petrological geopark that will also promote sustainable development of the area

The Anatomic Course of the First Jejunal Branch of the Superior Mesenteric Vein in Relation to the Superior Mesenteric Artery

Introduction. The purpose of this study is to determine the anatomic course of the first jejunal branch of the superior mesenteric vein (SMV) in relation to the superior mesenteric artery (SMA). Methods. Three hundred consecutive contrast-enhanced computed tomography (CT) scans were reviewed by a surgical oncologist with confirmation of findings by a radiologist. Results. The overall incidence of a first jejunal branch coursing anterior to the SMA was 41%. There was no correlation between patient gender and position of the jejunal branch. In addition, there was no correlation between size of the first jejunal branch and its location in relation to the SMA. The IMV drained into the SMV in 27% of the patients. The IMV drained into the SMV-portal vein confluence in 17% of patients and inserted into the splenic vein in 54%. An anterior coursing first jejunal branch statistically correlated with an IMV that drained into the SMV-portal vein confluence (P = 0.009). Conclusion. The first jejunal branch of the SMV has a highly variable course in relation to the SMA and has a higher incidence of an anterior location in this population than previously reported

Control and ultrasonic actuation of a gas-liquid interface in a microfluidic chip

This article describes the design and manufacturing of a microfluidic chip, allowing for the actuation of a gas-liquid interface and of the neighboring fluid. A first way to control the interface motion is to apply a pressure difference across it. In this case, the efficiency of three different micro-geometries at anchoring the interface is compared. Also, the critical pressures needed to move the interface are measured and compared to theoretical result. A second way to control the interface motion is by ultrasonic excitation. When the excitation is weak, the interface exhibits traveling waves, which follow a dispersion equation. At stronger ultrasonic levels, standing waves appear on the interface, with frequencies that are half integer multiple of the excitation frequency. An associated microstreaming flow field observed in the vicinity of the interface is characterized. The meniscus and associated streaming flow have the potential to transport particles and mix reagents

Nanoparticles for intestinal sepsis prevention synthesized via inverse miniemulsion polymerization

Previous research has shown that phosphate becomes depleted in the intestinal mucosa following local surgical injury or disease, triggering bacterial virulence and sepsis. Consequently, replenishment of depleted phosphate levels has been shown to prevent bacterial virulence in vitro[3] and sepsis in vivo[1]. Inverse phase miniemulsion polymerization (IPMP) has been extensively used in recent years in the production of nanocapsules for drug delivery of water-soluble therapeutic compounds that can be rendered degradable with time while allowing for sustained release of the encapsulated agent. In previous work we have successfully encapsulated inorganic phosphate salts, such as potassium monophosphate[2], into nanoparticles formed using IPMP. Our in vitro studies, however, have shown that polyphosphate salts, specifically sodium hexametaphosphate (PPi), are more effective at suppressing bacterial virulence[3]. This study focuses on the production and encapsulation of sodium hexametaphosphate into nanoparticles for controlled and extended release. Previous studies demonstrated[3] that encapsulation of sodium hexametaphosphate presents a series of challenges affecting the reproducibility of the IPMP process. Sodium hexametaphosphate is a strong lipophobe whose presence induces a high degree of order for water molecules. This modification in water structure weakens the surfactant interaction with water molecules, actively affecting the stability of the emulsion. This process, known as “salting-out”, has been shown to shift the hydrophilic-lipophilic balance (HLB) of nonionic surfactants towards a more lipophilic value[4]. While this issue has been addressed in a variety of previous studies, no mathematical correlation currently exists describing the effect of salt concentration on the HLB of a specific surfactant. Since miniemulsions require combinations of different phase-soluble surfactants, this adds to the complexity in predicting the extent and strength of the electrolyte effect on the stability of the emulsion system. In this study, we adjusted the IPMP process to counter the unstabilizing force created by the presence of sodium hexametaphosphate in the aqueous phase of the system. A precursor solution containing PEG diacrylate (PEGDA) macromer and NVP comonomer were chosen to create the hydrogel matrix, due to its biocompatibility and the ability to control the crosslinking density. The emulsion was formed of water in cyclohexane with the help of two nonionic surfactants, Tween 20 and SPAN 80. The effect of variations in HLB ranging from 4.0 to 9.5 on emulsion droplet size was investigated, for which the optimum overall HLB occurred at 6.5, an increase of two HLB points over the theoretical required value without salt interference[2, 3]. The effects of total surfactant amounts, reaction time, temperature and initiator concentration on nanoparticle yield were also explored. A final emulsion with 3.2% w/v of surfactants, 2 hours of reaction time, 64ºC and an initiator concentration equal to 1% of the initial double concentration resulted in a maximum nanoparticle mass yield of ~39%. Finally, the particles were characterized in terms of crosslink density, showing an efficient encapsulation of the studied salt and a promising path for in-vivo testing. This study helped us develop a reproduceable formulation of an IPMP process that yields stable nanoparticles with suitable therapeutic levels of phosphates. [1] Hyoju, S.K. et al, “Oral Polyphosphate Suppresses Bacterial Collagenase Production and Prevents Anastomotic Leak Due to Serratia marcescens and Pseudomonas aeruginosa”, Annals of Surgery, Feb, 2017. [2]Vadlamudi, S. et al., “Inverse miniemulsion polymerization of phosphate-loaded hydrogel nanoparticles for sepsis prevention”, Unpublished master dissertation, Illinois Institute of Technology, Chicago, Illinois (2014) [3] Yin Y et al, “De Novo Synthesis and Functional Analysis of Polyphosphate-Loaded Poly(Ethylene) Glycol Hydrogel Nanoparticles Targeting Pyocyanin and Pyoverdin Production in Pseudomonas aeruginosa as a Model Intestinal Pathogen”. Annals of Biomedical Engineering. 45(4):1058-1068, 2017. [4] Shinoda, K., & Takeda, H. “The effect of added salts in water on the hydrophile-lipophile balance of nonionic surfactants: The effect of added salts on the phase inversion temperature of emulsions”. Journal of Colloid And Interface Science, 32(4), 642–646, 1970

Impact of preoperative therapy on patterns of recurrence in pancreatic cancer

AbstractBackgroundA theoretical advantage of preoperative therapy in pancreatic adenocarcinoma is that it facilitates the early treatment of micrometastases and reduces postoperative systemic recurrence.MethodsMedical records of 309 consecutive patients undergoing resection of adenocarcinoma in the head of the pancreas were reviewed. Survival was calculated using the Kaplan–Meier method. Associations between preoperative therapy and patterns of recurrence were determined using chi-squared analysis.ResultsPreoperative therapy was administered to 108 patients and upfront surgery was performed in 201 patients. Preoperative therapy was associated with a significantly longer median disease-free survival of 14 months compared with 12 months in patients submitted to upfront surgery (P = 0.035). The rate of local disease as a component of first site of recurrence was significantly lower with preoperative therapy (11.3%) than with upfront surgery (22.9%) (P = 0.016). Preoperative therapy was associated with a lower rate of hepatic metastasis (21.7%) than upfront surgery (34.3%) (P = 0.026). Preoperative therapy did not affect rates of peritoneal or pulmonary metastasis.ConclusionsPreoperative therapy for pancreatic cancer was associated with longer disease-free survival and lower rates of local and hepatic recurrences. These data support the use of preoperative therapy to reduce systemic and local failures after resection

Condensation properties of stress granules and processing bodies are compromised in Myotonic Dystrophy Type 1

RNA regulation in mammalian cells requires complex physical compartmentalisation, using structures thought to be formed by liquid-liquid phase separation. Disruption of these structures is implicated in numerous degenerative diseases. Myotonic dystrophy type 1 (DM1) is a multi-systemic trinucleotide repeat disorder resulting from an expansion of nucleotides CTG (CTGexp) in the DNA encoding DM1 protein kinase (DMPK). The cellular hallmark of DM1 is the formation of nuclear foci that contain expanded DMPK RNA (CUGexp) (with thymine instead of uracil). We report here the deregulation of stress granules (SGs) and processing bodies (P-bodies), two cytoplasmic structures key for mRNA regulation, in cell culture models of DM1. Alterations to the rates of formation and dispersal of SGs suggest an altered ability of cells to respond to stress associated with DM1, while changes to the structure and dynamics of SGs and P-bodies suggest that a widespread alteration to the biophysical properties of cellular structures is a consequence of the presence of CUGexp RNA.</p

Maximum Likelihood Estimator for Hidden Markov Models in continuous time

The paper studies large sample asymptotic properties of the Maximum Likelihood Estimator (MLE) for the parameter of a continuous time Markov chain, observed in white noise. Using the method of weak convergence of likelihoods due to I.Ibragimov and R.Khasminskii, consistency, asymptotic normality and convergence of moments are established for MLE under certain strong ergodicity conditions of the chain.Comment: Warning: due to a flaw in the publishing process, some of the references in the published version of the article are confuse