Torsional fracture of viscoelastic liquid bridges.

Short liquid bridges are stable under the action of surface tension. In applications like electronic packaging, food engineering, and additive manufacturing, this poses challenges to the clean and fast dispensing of viscoelastic fluids. Here, we investigate how viscoelastic liquid bridges can be destabilized by torsion. By combining high-speed imaging and numerical simulation, we show that concave surfaces of liquid bridges can localize shear, in turn localizing normal stresses and making the surface more concave. Such positive feedback creates an indent, which propagates toward the center and leads to breakup of the liquid bridge. The indent formation mechanism closely resembles edge fracture, an often undesired viscoelastic flow instability characterized by the sudden indentation of the fluid's free surface when the fluid is subjected to shear. By applying torsion, even short, capillary stable liquid bridges can be broken in the order of 1 s. This may lead to the development of dispensing protocols that reduce substrate contamination by the satellite droplets and long capillary tails formed by capillary retraction, which is the current mainstream industrial method for destabilizing viscoelastic liquid bridges.

Schedule-Dependent Synergy Between the Histone Deacetylase Inhibitor Belinostat and the Dihydrofolate Reductase Inhibitor Pralatrexate in T-and B-cell Lymphoma Cells in vitro.

Pralatrexate (Folotyn; PLX) and belinostat (Beleodaq; BLS) are registered for the treatment of patients with peripheral T-cell lymphoma (PTCL) and are being considered for other lymphomas. In this study we investigated whether BLS had the ability to potentiate the cytotoxicity of PLX. A panel of lymphoma cell lines was used for the combination studies: the B-cell SUDHL-4, SUDHL-5, HT, Jeko-1 and T-cell Karpas-299 and Hut-78. Uptake of PLX was mediated by the reduced folate carrier (RFC). PLX showed a 6-fold better RFC substrate affinity compared to methotrexate, and 2-fold better than levoleucovorin (l-LV). Sensitivity expressed as the concentration that resulted in 50% growth inhibition (IC50) after 72 hr exposure to PLX varied from 2.8 to 20 nM and for BLS from 72 to 233 nM, independent of the background of the cell lines. The interaction between BLS and PLX was studied using the median-drug effect analysis. At a fixed molar ratio between the drugs based on the IC50 concentration the average combination index (CI) for all cell lines showed additivity (CI: around 1.0). In three selected cell lines (SUDHL-4, SUDHL-5, and HT) sequential exposure (24 h pretreatment with BLS, followed by 48 h to PLX + BLS), did not improve interaction (CI: 0.9-1.4). As an alternative approach a non-fixed ratio was used by exposing SUDHL-4, SUDHL-5, and HT cells to IC25 concentrations of either BLS or PLX in combination with the other drug. Exposure to IC25 of PLX did not decrease the IC50 for BLS (CI from 0.6-1.2), but exposure to IC25 of BLS markedly increased PLX sensitivity (low CIs from 0.40 to 0.66). Mechanistic studies focused on induction of apoptosis, and showed cleavage of predominantly caspase-9 in HT and SUDHL-4 cells for both drugs at their IC50s, being similar in the combination setting. Moreover, at these concentrations, the drugs were shown to confer an S-phase arrest. In conclusion, the combination of PLX and BLS showed additivity in various lymphoma cell lines, with a schedule-dependent synergism in B-cell lymphoma. Based on these data, proficient inhibition of HDAC activity by BLS holds promise in sensitization of tumor cells to PLX.

Decoding the chromatin proteome of a single genomic locus by DNA sequencing.

Transcription, replication, and repair involve interactions of specific genomic loci with many different proteins. How these interactions are orchestrated at any given location and under changing cellular conditions is largely unknown because systematically measuring protein-DNA interactions at a specific locus in the genome is challenging. To address this problem, we developed Epi-Decoder, a Tag-chromatin immunoprecipitation-Barcode-Sequencing (TAG-ChIP-Barcode-Seq) technology in budding yeast. Epi-Decoder is orthogonal to proteomics approaches because it does not rely on mass spectrometry (MS) but instead takes advantage of DNA sequencing. Analysis of the proteome of a transcribed locus proximal to an origin of replication revealed more than 400 interacting proteins. Moreover, replication stress induced changes in local chromatin proteome composition prior to local origin firing, affecting replication proteins as well as transcription proteins. Finally, we show that native genomic loci can be decoded by efficient construction of barcode libraries assisted by clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9). Thus, Epi-Decoder is an effective strategy to identify and quantify in an unbiased and systematic manner the proteome of an individual genomic locus by DNA sequencing.

A Conjugate Class of Utility Functions for Sequential Decision Problems.

The use of the conjugacy property for members of the exponential family of distributions is commonplace within Bayesian statistical analysis, allowing for tractable and simple solutions to problems of inference. However, despite a shared motivation, there has been little previous development of a similar property for using utility functions within a Bayesian decision analysis. As such, this article explores a class of utility functions that appear to be reasonable for modeling the preferences of a decisionmaker in many real-life situations, but that also permit a tractable and simple analysis within sequential decision problems.

Bayesian Inference for Reliability of Systems and Networks Using the Survival Signature.

The concept of survival signature has recently been introduced as an alternative to the signature for reliability quantification of systems. While these two concepts are closely related for systems consisting of a single type of component, the survival signature is also suitable for systems with multiple types of component, which is not the case for the signature. This also enables the use of the survival signature for reliability of networks. In this article, we present the use of the survival signature for reliability quantification of systems and networks from a Bayesian perspective. We assume that data are available on tested components that are exchangeable with those in the actual system or network of interest. These data consist of failure times and possibly right-censoring times. We present both a nonparametric and parametric approach.

Pain exposure physical therapy may be a safe and effective treatment for longstanding complex regional pain syndrome type 1: a case series.

OBJECTIVE: To determine if treatment of longstanding complex regional pain syndrome type 1, focusing on functional improvement only while neglecting pain, results in clinical improvement of this syndrome. DESIGN: Prospective description of a case series of 106 patients. SETTING: Outpatient clinic for rehabilitation. INTERVENTIONS: Physical therapy of the affected limb directed at a functional improvement only while neglecting the pain, was performed following an extensive explanation. Normal use of the limb between the treatments was encouraged despite pain. A maximum of five of these sessions were performed in three months. MEASURES: Radboud Skills Test was used to monitor functional improvement of the arms. Speed and walking distance was used as the measure of outcome for the legs. RESULTS: The function of the affected arm or leg improved in 95 patients. Full functional recovery was experienced in 49 (46%) of them. A reduction in pain presented in 75 patients. In 23 patients functional recovery was reached despite an increase in pain. Four patients stopped early due to pain increase. CONCLUSIONS: Our results suggest that 'pain exposure physical therapy' is effective and safe for patients who are unresponsive to accepted standard therapies. Avoiding the use of a limb due to pain will result in loss of function. Forced usage of limbs restores the function, reverses these adaptive processes and leads to regain of control by practice with a reduction of pain in most cases.

Mechanism of the photochemical ligand substitution reactions of fac-[Re(bpy)(CO)(3)(PR(3))](+) complexes and the properties of their triplet ligand-field excited states.

We report herein the mechanism of the photochemical ligand substitution reactions of a series of fac-[Re(X(2)bpy)(CO)(3)(PR(3))](+) complexes (1) and the properties of their triplet ligand-field ((3)LF) excited states. The reason for the photostability of the rhenium complexes [Re(X(2)bpy)(CO)(3)(py)](+) (3) and [Re(X(2)bpy)(CO)(3)Cl] (4) was also investigated. Irradiation of an acetonitrile solution of 1 selectively gave the biscarbonyl complexes cis,trans-[Re(X(2)bpy)(CO)(2)(PR(3))(CH(3)CN)](+) (2). Isotope experiments clearly showed that the CO ligand trans to the PR(3) ligand was selectively substituted. The photochemical reactions proceeded via a dissociative mechanism from the (3)LF excited state. The thermodynamical data for the (3)LF excited states of complexes 1 and the corrective nonradiative decay rate constants for the triplet metal-to-ligand charge-transfer ((3)MLCT) states were obtained from temperature-dependence data for the emission lifetimes and for the quantum yields of the photochemical reactions and the emission. Comparison of 1 with [Re(X(2)bpy)(CO)(3)(py)](+) (3) and [Re(X(2)bpy)(CO)(3)Cl] (4) indicated that the (3)LF states of some 3- and 4-type complexes are probably accessible from the (3)MLCT state even at ambient temperature, but these complexes were stable to irradiation at 365 nm. The photostability of 3 and 4, in contrast to 1, can be explained by differences in the trans effects of the PR(3), py, and Cl(-) ligands.

Influence of endothelin ET(A) and ET(B) receptor antagonists on endothelin-induced contractions of the guinea pig isolated gall bladder.

The receptors mediating guinea pig gall bladder (GPGB) contractions induced by endothelin-1 (ET-1) and related peptides were characterized using various ET receptor antagonists. As all ET-receptor agonists used, except sarafotoxin S6c (SRTX), failed to induce a clear-cut maximal response at the highest concentration tested (i.e. 100 nM), their potencies are expressed in terms of a CK50 (i.e. the concentration causing 50% of the response to 80 mM KCl). ET-1 (CK50 0.8 nM) was equipotent to ET-2 and SRTX (selective ET(B) receptor agonist), but more potent than ET-3 (5-fold) or IRL 1620 (selective ET(B) receptor agonist). BQ-123 (0.3 microM, peptidic ET(A) receptor antagonist) did not alter responses to ET-1, ET-3 or SRTX. BQ-788 (1 microM, peptidic ET(B) receptor antagonist) reduced the potency of ET-3 (9-fold at the CK50 level) and SRTX ( > 20-fold), but not ET-1. SRTX responses were unaffected by RES-701-1 (3 microM, peptidic ET(B) receptor antagonist). The combination BQ-123 (0.3 microM) plus BQ-788 (1 microM) did not modify responses to ET-1, inhibited SRTX responses similarly to BQ-788 alone and abolished ET-3 responses. Bosentan (1 microM, non-peptidic ET(A)/ET(B) receptor antagonist) reduced the potency of ET-1 (15-fold). ET-3 (9-fold) and SRTX (4-fold). In rat aorta, the antagonists blocked ET-1-induced contractions (BQ-123 and bosentan) or SRTX-induced endothelium-dependent relaxations (BQ-788, RES-701-1 and bosentan). Thus, the GPGB expresses both ET(A) and ET(B) receptors. As BQ-123 only blocked responses to ET-3 in the presence of BQ-788, there appears to be cross-talk between both receptor types. Also, the binding sites of ET-1 and ET-3 on the ET(A) receptor may not coincide entirely, as BQ-123, even in presence of BQ-788, did not affect ET-1-induced contractions.

Bronchoalveolar eosinophilia in random-source versus purpose-bred dogs.

Eosinophils (EOS) have been implicated in changes in airway and vascular reactivity in a variety of disease states. Analysis of cells in bronchoalveolar lavage samples from chronic, heartworm-free random-source (RS) dogs indicated higher leukocyte counts with markedly higher percent and total numbers of EOS than were present in purpose-bred (PB) animals. Bronchoalveolar lavage fluid (BALF) obtained from RS dogs had a significantly elevated total nucleated cell count: 0.8 x 10(6) vs 0.4 x 10(6) for the PB dogs. RS dogs had 24% +/- 5% and PB dogs had 3% +/- 0.7% EOS. The RS animals with elevated EOS had similar percentages of neutrophils: 4% +/- 0.6% as the PB animals. Despite aggressive anthelminthic treatment, the abnormal BALF cellular profile of the RS animals persisted even though circulating levels of EOS in this group decreased. Analysis of BALF for thromboxane B2 (TxB2) and 6-keto-prostaglandin F1(1a) (6-keto-PGF1a) indicated that only the TxB2 levels were significantly different between groups. The RS BALF TxB2 levels were 73 +/- 14 pg/ml vs 23 +/- 3 pg/ml for the PB group (P < 0.05). Regression analysis of the relationship between increasing TxB2 levels and the absolute number of EOS per milliliter of BALF obtained from the RS dogs indicated a significant correlation (r = 0.83, P < 0.0001). No difference in plasma levels of these mediators was observed. Other physiologic parameters also differed between the two groups: the RS group had significantly increased heart rates and cardiac output under baseline conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro cyanide release from sodium nitroprusside in various intravenous solutions.

The concentration of cyanide, a toxic metabolite of sodium nitroprusside, in solutions other than 5% dextrose in water, has not been reported. In this study, cyanide ion levels were measured by a cyanide ion-specific electrode in 250 ml of six different intravenous solutions (5% dextrose in water, 10% dextrose in water, distilled water, 0.9% sodium chloride, and lactated Ringer's solution with and without 5% dextrose) exposed to 300 foot candles of fluorescent light for 72 hours after sodium nitroprusside was dissolved in each solution. The rates of the increase in cyanide ion concentration in all six solutions were fairly constant between 4 and 24 hours. At 24 hours, there were no statistically significant differences in cyanide ion concentration among the six solutions. After 24 hours, the rate of the increase in cyanide ion concentration in the electrolyte solutions decreased more than that in the nonelectrolyte solutions. At 72 hours, the electrolyte-containing solutions had statistically significant lower mean cyanide ion concentrations than 5% dextrose, often the recommended diluent for sodium nitroprusside. There was no difference in mean cyanide ion concentration between lactated Ringer's solution with and without 5% dextrose. Solutions containing electrolytes are preferable to 5% dextrose for the dilution of sodium nitroprusside.

In vitro cyanide release from sodium nitroprusside.

In vitro release of cyanide from sodium nitroprusside in 5% dextrose in water solution following exposure or non-exposure to fluorescent light (500 ft candles or 791 microwatt per square cm [muWcm-2]), was measured by a cyanide-specific ion electrode at 4, 8, 24, 48, and 72 h. The cyanide concentrations were significantly increased at 24 h in the light-exposed solution. In this group, 100% of the cyanide was released from sodium nitroprusside at 72 h exposure to light. However, cyanide concentrations showed no significant changes for 72 h in the light-protected solutions, which were either exposed to 500 foot candles fluorescent light or stored in a dark room. Less than 2.5% of the cyanide was released from sodium nitroprusside at 72 h in both of the light-protected groups. No significant differences in cyanide concentrations were observed at 8 h among the exposed or non-exposed solutions. After 24 h of exposure, the cyanide concentrations in the exposed group were significantly higher than those of the two light-protected solutions. However, there were no significant differences between the cyanide concentration in the light-protected solutions. These results substantiate the safety of sodium nitroprusside solution for 24 h if the sodium nitroprusside containing solutions are properly protected from light. An additional study performed showed that a significant amount of cyanide released from sodium nitroprusside was adsorbed to the surface of polyvinylchloride.