Polysorbate identity and quantity dictate the extensional flow properties of protein-excipient solutions

While protein medications are promising for treatment of cancer and autoimmune diseases, challenges persist in terms of development and injection stability of high-concentration formulations. Here, the extensional flow properties of protein-excipient solutions are examined via dripping-onto-substrate extensional rheology, using a model ovalbumin (OVA) protein and biocompatible excipients polysorbate 20 (PS20) and 80 (PS80). Despite similar PS structures, differences in extensional flow are observed based on PS identity in two regimes: at moderate total concentrations where surface tension differences drive changes in extensional flow behavior, and at small PS:OVA ratios, which impact the onset of weakly elastic flow behavior. Undesirable elasticity is observed in ultra-concentrated formulations, independent of PS identity; higher PS contents are required to observe these effects than in analogous polymeric excipient solutions. These studies reveal novel extensional flow behaviors in protein-excipient solutions, and provide a straightforward methodology for assessing the extensional flow stability of new protein-excipient formulations.     

Deployment of a cloud pipeline for real-time visual inspection using fast streaming high-definition images

We investigate the challenges of building an end-to-end cloud pipeline for real-time intelligent visual inspection system for use in automotive manufacturing. Current methods of visual detection in automotive assembly are highly labor intensive, and thus prone to errors. An automated process is sought that can operate within the real-time constraints of the assembly line and can reduce errors. Components of the cloud pipeline include capture of a large set of high-definition images from a camera setup at the assembly location, transfer and storage of the images as needed, execution of object detection, and notification to a human operator when a fault is detected. The end-to-end execution must complete within a fixed time frame before the next car arrives in the assembly line. In this article, we report the design, development, and experimental evaluation of the tradeoffs of performance, accuracy, and scalability for a cloud system.     

Endometrioid carcinoma arising from endometriosis of the sigmoid colon during estrogenic treatment

A case of endometrioid carcinoma arising from endometriosis of the sigmoid colon is reported. The patient had been treated with unopposed continuous estrogen injection for twenty years after bilateral salpingo-oophorectomy because of severe endometriosis. The pathology, pertinent literature and implications of the present case are discussed.     

Influence of schedule and mode of administration on effectiveness of podofilox treatment of papillomas

We investigated the timing of podofilox delivery to see how it correlated with papilloma size. We looked at times ranging from once per week (morning and afternoon) to five times per week (morning and afternoon). We also looked at delivery systems that might enhance the effectiveness of the drug by increasing penetration of the overlying cutaneous horn. These included soaking prior to drug administration, the use of a grooved needle subsequent to drug administration, and the various possible combinations of these techniques. We found that the timing of treatments had relatively little effect on the size of the papillomas. For example, at the end of ten weeks, the geometric mean diameter (GMD) (mm) of the papillomas treated five times per week and induced by a 10(-1) dilution of the virus (group B) was 18. Likewise the GMD (mm) of papillomas treated once per week was 18 (group D). On the other hand, we found that soaking plus the use of a grooved needle plus podofilox resulted in the curing of all lesions induced by a 10(-2) virus dilution and of most induced by the 10(-1) dilution, whereas soak plus podofilox or podofilox alone were not as effective in curing the lesions. Podofilox plus needle approached the soak plus podofilox plus needle in effectiveness. Treatment schedule was not a critical determinant of podofilox effectiveness. Therapeutic benefits were enhanced by hydration of the overlying cutaneous horn and penetration with a grooved needle.     

Live animal performance, carcass traits, and meat palatability of calf- and yearling-fed cloned steers

Two groups of Brangus steers produced by nuclear transplantation cloning were used in parallel studies investigating the impact of calf- and yearling-feeding. The first group (n = 8) were fed as calves (CF; n = 4) or yearlings (YF; n = 4) to a constant age end point of 16 mo. The second group (n = 10) were fed as calves (CF; n = 5) or yearlings (YF; n = 5) to a constant live weight end point (530 kg). When slaughtered at the same age, CF and YF steers did not differ (P > .05) in feedlot ADG, but the CF steers were heavier and had higher dressing percentages, numeric yield grades, and quality grades (P < .05). Top loin steaks from the groups of steers did not differ (P > .05) in palatability traits. When fed to a constant live weight, the YF steers gained more rapidly (P < .05) and had lower (P < .05) numeric yield grades than did CF steers. Again CF steers had higher (P < .05) dressing percentages. There was no difference (P > .05) between the treatments in carcass quality grade or meat palatability characteristics. Thus, when finished to a constant weight end point, YF steers gained more rapidly, with no adverse effects on carcass quality grade or palatability traits; however, CF steers consistently produced higher dressing percentages, largely due to greater external fatness.     

Strategy and issue frames in election campaign coverage: a social cognitive account of framing effects

This study examines how news frames in campaign coverage affect individuals' interpretation of campaigns. Framing effects are conceptualized in terms of the process by which textual features in news stories set limits on knowledge use in the construction of a discourse model - a mental model constructed through the interaction between news frames and the interpreter's social knowledge. Examining message structures in campaign news stories led to identifying two major frames in campaign coverage: strategy and issue. Narrative data collected from two field experiments were analyzed. The findings suggest that both strategy-framed and issue-framed print news stories are effective in influencing campaign interpretation.     

Context-specific adaptation of vertical vergence to correlates of eye position

Vertical phoria (vertical vergence in the absence of binocular feedback) can be trained to vary with non-visual cues such as vertical conjugate eye position, horizontal conjugate eye position and horizontal vergence. These prior studies demonstrated a low-level association or coupling between vertical vergence and several oculomotor cues. As a test of the potential independence of multiple eye-position cues for vertical vergence, context-specific adaptation experiments were conducted in three orthogonal adapting planes (midsagittal, frontoparallel, and transverse). Four vertical disparities in each of these planes were associated with various combinations of two specific components of eye position. Vertical disparities in the plane were associated with horizontal vergence and vertical conjugate eye position; vertical disparities in the frontoparallel plane were associated with horizontal and vertical conjugate eye position; and vertical disparities in the transverse plane were associated with horizontal vergence and horizontal conjugate eye position. The results demonstrate that vertical vergence can be adapted to respond to specific combinations of two different sources of eye-position information. The results are modeled with an association matrix whose inputs are two classes of eye position and whose weighted output is vertical vergence.     

Cure of malignant ascites and generation of protective immunity by monoclonal antibody-targeted activation of a glucuronide prodrug in rats

We examined the in vivo efficacy of targeting beta-glucuronidase (betaG) to activate a glucuronide prodrug (BHAMG) of p-hydroxyaniline mustard (pHAM) at hepatoma ascites in Sprague-Dawley rats. Injection i.p. of 500 microg RH1-betaG, a conjugate formed between recombinant betaG and monoclonal antibody RH1 with specificity for an antigen expressed on AS-30D rat hepatoma cells, into rats bearing AS-30D ascites resulted in the accumulation of 54 microg conjugate per 10(9) tumor cells after 2 hr. Ascites fluid and serum contained 0.53 and 0 microg/ml, respectively, RH1-betaG 2 hr after injection of the conjugate. Conjugate binding to AS-30D cells was heterogeneous and non-saturated, as determined by flow cytometry. BHAMG was less toxic than pHAM to SD rats based on measures of animal mortality, weight loss and hematological toxicity. Treatment of rats bearing established hepatoma ascites with 500 microg RH1-betaG followed 2 hr later with a single i.p. injection of 30 mg/kg BHAMG or 3 i.p. injections of 10 mg/kg BHAMG 2, 3 and 4 hr later resulted in the cure of 6/8 and 8/8 animals, respectively. Treatment with BHAMG or pHAM alone did not produce cures, whereas treatment with a control antibody-betaG conjugate and BHAMG produced significantly greater hematological toxicity compared to treatment with RH1-betaG and BHAMG. All cured rats were completely protected from rechallenge with 2 x 10(7) AS-30D cells, indicating that successful treatment of animals induced protective immunity.     

Tyrosine hydroxylase expression in primary cultures of olfactory bulb: role of L-type calcium channels

Sensory activity mediates regulation of tyrosine hydroxylase (TH), the first enzyme in the dopamine biosynthetic pathway, in the rodent olfactory bulb. The current studies established for the first time primary cultures of neonatal mouse olfactory bulb expressing TH and tested whether L-type calcium channels mediate the activity-dependent regulation of the dopamine phenotype. After 1 d in vitro (DIV), a small population of TH-immunostained neurons that lacked extensive processes could be demonstrated. After an additional 2 DIV in serum-free medium, the number of TH neurons had doubled, and they exhibited long interdigitating processes. Membrane depolarization for 48 hr with 50 mM KCl produced a further 2.4-fold increase in the number of TH-immunoreactive neurons compared with control cultures. Increased TH neuron number required at least 36 hr of exposure to KCl. Forskolin, which increases intracellular cAMP levels, induced a 1.5- to 1.6-fold increase in the number of TH-immunostained neurons. Combined treatment with KCl and forskolin was not additive. Nifedipine, an L-type calcium channel blocker, completely prevented the depolarization-mediated increase in TH expression but did not block the response to forskolin. Treatment with Bay K8644, an L-type calcium channel agonist, also significantly increased the number of TH-expressing neurons. Depolarization also induced alterations in neuritic outgrowth, resulting in a stellate versus an elongate morphology that, in contrast, was not prevented by nifedipine. These results are the first demonstration that in vitro, as in vivo, depolarization increases TH expression in olfactory bulb and that L-type calcium channels mediate this activity-dependent regulation of the dopamine phenotype.