Over-reaction to the CALPERS focus list?

The California Public Employees Retirement System (CalPERS) has over $ 200 billion in assets. Over the years it has gained an activist reputation. The size of investment provides it with a strong voice and the incentive to incur monitoring costs. CalPERS nudges the management and the board to act in the best interest of the shareholders. CalPERS regularly examines its portfolio and seeks change in firms that can potentially perform better. Some firms heed to this attention while those that ignore the attention end up on the focus list. This study examines the reaction of the market to the publishing of the CalPERS focus list. On one hand, an investor could interpret this news positively: A large shareholder is actively pushing management and the board, to improve operations. In the remaining sections, the literature is reviewed, we present our results and the paper ends with a discussion

Treadmill Exercise Improves Fracture Toughness and Indentation Modulus without Altering the Nanoscale Morphology of Collagen in Mice.

The specifics of how the nanoscale properties of collagen (e.g., the crosslinking profile) affect the mechanical integrity of bone at larger length scales is poorly understood despite growing evidence that collagen’s nanoscale properties are altered with disease. Additionally, mass independent increases in postyield displacement due to exercise suggest loading-induced improvements in bone quality associated with collagen. To test whether disease-induced reductions in bone quality driven by alterations in collagen can be rescued or prevented via exercise-mediated changes to collagen’s nanoscale morphology and mechanical properties, the effects of treadmill exercise and β-aminopropionitrile treatment were investigated. Eight week old female C57BL/6 mice were given a daily subcutaneous injection of either 164 mg/kg β-aminopropionitrile or phosphate buffered saline while experiencing either normal cage activity or 30 min of treadmill exercise for 21 consecutive days. Despite differences in D-spacing distribution (P = 0.003) and increased cortical area (tibial: P = 0.005 and femoral: P = 0.015) due to β-aminopropionitrile treatment, an overt mechanical disease state was not achieved as there were no differences in fracture toughness or 4 point bending due to β-aminopropionitrile treatment. While exercise did not alter (P = 0.058) the D-spacing distribution of collagen or prevent (P < 0.001) the β-aminopropionitrile-induced changes present in the unexercised animals, there were differential effects in the distribution of the reduced elastic modulus due to exercise between control and β-aminopropionitrile-treated animals (P < 0.001). Fracture toughness was increased (P = 0.043) as a main effect of exercise, but no significant differences due to exercise were observed using 4 point bending. Future studies should examine the potential for sex specific differences in the dose of β-aminopropionitrile required to induce mechanical effects in mice and the contributions of other nanoscale aspects of bone (e.g., the mineral–collagen interface) to elucidate the mechanism for the exercise-based improvements in fracture toughness observed here and the increased postyield deformation observed in other studies

In Vivo Evaluation of (-)-Zampanolide Demonstrates Potent and Persistent Antitumor Efficacy When Targeted to the Tumor Site.

Microtubule-stabilizing agents (MSAs) are a class of compounds used in the treatment of triple-negative breast cancer (TNBC), a subtype of breast cancer where chemotherapy remains the standard-of-care for patients. Taxanes like paclitaxel and docetaxel have demonstrated efficacy against TNBC in the clinic, however new classes of MSAs need to be identified due to the rise of taxane resistance in patients. (-)-Zampanolide is a covalent microtubule stabilizer that can circumvent taxane resistance in vitro but has not been evaluated for in vivo antitumor efficacy. Here, we determine that (-)-zampanolide has similar potency and efficacy to paclitaxel in TNBC cell lines, but is significantly more persistent due to its covalent binding. We also provide the first reported in vivo antitumor evaluation of (-)-zampanolide where we determine that it has potent and persistent antitumor efficacy when delivered intratumorally. Future work on zampanolide to further evaluate its pharmacophore and determine ways to improve its systemic therapeutic window would make this compound a potential candidate for clinical development through its ability to circumvent taxane-resistance mechanisms

Probing a Set of Trajectories to Maximize Captured Information

We study a trajectory analysis problem we call the Trajectory Capture Problem (TCP), in which, for a given input set T of trajectories in the plane, and an integer k? 2, we seek to compute a set of k points ("portals") to maximize the total weight of all subtrajectories of T between pairs of portals. This problem naturally arises in trajectory analysis and summarization. We show that the TCP is NP-hard (even in very special cases) and give some first approximation results. Our main focus is on attacking the TCP with practical algorithm-engineering approaches, including integer linear programming (to solve instances to provable optimality) and local search methods. We study the integrality gap arising from such approaches. We analyze our methods on different classes of data, including benchmark instances that we generate. Our goal is to understand the best performing heuristics, based on both solution time and solution quality. We demonstrate that we are able to compute provably optimal solutions for real-world instances

Effects of Caffeinated and Non-Caffeinated Gum on Premotor, Motor, and Overall Reaction Time

Chewing gum and caffeine when used independently and concurrently increase neural activity ultimately improving reaction time but less is known about how caffeinated gum influences distinct phases of the reaction time response. Physically active college females (n=14) completed a 60-second reaction time test on a visuomotor board under the following counterbalanced conditions: 1) Baseline, 2) Non-caffeinated gum, 3) Caffeinated gum (300 mg caffeine). Point of application #1: Chewing gum improved premotor reaction time compared to baseline, but caffeine did not provide additional benefit. Point of application #2: Neither non-caffeinated nor caffeinated gum improved motor reaction times from baseline. Point of application #3: Chewing gum improved overall reaction time compared to baseline, but caffeine did not provide additional benefit. Keywords: Chewing, Visuomotor, Visual processin

Development and Validation of a Simple Method for the Detection of Fascaplysin in Plasma

Fascaplysin is a cytotoxic natural product isolated from a variety of Indo-Pacific marine organisms, primarily Fascaplysinopsis sponges and Didemnum tunicates. Positive xenograft studies involving this alkaloid structural class have indicated that fascaplysin may serve as an important lead compound for preclinical development. This study was undertaken as a prelude to a full pharmacokinetics and therapeutic assessment of fascaplysin. We describe here a simple plasma preparation and a rapid HPLC method for the detection of fascaplysin in mice. The method was validated by parameters including good linear correlation, a limit of quantification of 107.1 μg/ mL, and a good precision with a coefficient of variation of 0.92% for 10 μg/mL. This method provides excellent sensitivity and visualization of fascaplysin as a single peak allowing for rapid analysis of plasma samples involving absorption, distribution, and metabolism studies. A preliminary pharmacokinetics study in C57Bl/6 mice using 20.6 mg/kg fascaplysin yielded a biphasic curve with T½α=16.7 min, T½β=11.7 h, and C0 of 17.1 μg/mL

Comparative Population Genomics of African Montane Forest Mammals Support Population Persistence across a Climatic Gradient and Quaternary Climatic Cycles

The Eastern Afromontane biodiversity hotspot (EABH) has the highest concentration of biodiversity in tropical Africa, yet few studies have investigated recent historical diversification processes in EABH lineages. Herein, we analyze restriction-site associated DNA-sequences (RAD-Seq) to study recent historical processes in co-distributed mouse (Hylomyscus) and shrew (Sylvisorex) species complexes, with an aim to better determine how historical paleoenvironmental processes might have contributed to the EABH’s high diversity. We analyzed complete SNP matrices of \u3e 50,000 RAD loci to delineate populations, reconstruct the history of isolation and admixture, and discover geographic patterns of genetic partitioning. These analyses demonstrate that persistently unsuitable habitat may have isolated multiple populations distributed across montane habitat islands in the Itombwe Massif and Albertine Rift to the west as well as Mt Elgon and Kenyan Highlands to the east. We detected low genetic diversity in Kenyan Highland populations of both genera, consistent with smaller historical population sizes in this region. We additionally tested predictions that Albertine Rift populations are older and more persistently isolated compared to the Kenyan Highlands. Phylogenetic analyses support greater historical isolation among Albertine Rift populations of both shrews and mice compared to the Kenyan Highlands and suggest that there are genetically isolated populations from both focal genera in the Itombwe Massif, Democratic Republic of Congo. The Albertine Rift ecoregion has the highest mammalian tropical forest species richness per unit area on earth. Our results clearly support accelerating efforts to conserve this diversity

Concomitant rotator cuff repair and instability surgery provide good patient-reported functional outcomes in patients aged 40 years or older with shoulder dislocation

Background: Recurrent anterior shoulder dislocation in patients aged \u3e /= 40 years is not as rare as once thought. The mechanism of instability in this patient population is different-more likely to be attributed to rotator cuff pathology-compared with that in younger individuals. With an increasingly aging active population, surgical management has a rising role in preventing morbidity associated with recurrent instability. Our purpose was to evaluate outcomes of anterior shoulder instability repair (ie, Bankart or bony Bankart repair) with and without rotator cuff repair (RCR) in patients aged \u3e /= 40 years. Methods: We conducted a retrospective chart review of all patients aged \u3e /= 40 years who underwent surgical repair for anterior shoulder instability from 2008-2016. Patients were categorized into 4 cohorts: Bankart repair only, bony Bankart repair only, Bankart repair with concomitant RCR, and bony Bankart repair with concomitant RCR. Demographic and history-of-instability data were collected. Clinical and functional outcomes assessed included the Single Assessment Numeric Evaluation score, American Shoulder and Elbow Surgeons score, Penn Shoulder Score, visual analog scale score for pain, Western Ontario Shoulder Instability Index score, and patient satisfaction score. Results: A total of 146 patients were included in this study, with 103 patients (71%) having \u3e /=2-year outcome scores. Outcome scores were not significantly different among groups. For patients who underwent Bankart repair only, bony Bankart repair only, Bankart repair with RCR, and bony Bankart repair with RCR, the Single Assessment Numeric Evaluation scores were 80.8 +/- 19.7, 90.0 +/- 10.7, 79.3 +/- 29.4, and 87.2 +/- 10.6, respectively (P = .284); American Shoulder and Elbow Surgeons scores, 83.8 +/- 19.7, 92.4 +/- 17.4, 82.5 +/- 25.6, and 85.6 +/- 12.7, respectively (P = .114); Penn Shoulder Scores for function, 84.5 +/- 17.9, 90.9 +/- 15.3, 83.6 +/- 25.1, and 95.7 +/- 13.0, respectively (P = .286); and Western Ontario Shoulder Instability Index scores, 481.0 +/- 519.5, 292.1 +/- 414.3, 548.9 +/- 690.5, and 320.6 +/- 258.7, respectively (P = .713). Age at the time of surgery significantly differed between cohorts (P \u3c .001). No patients had recurrence of instability during the study period. Conclusion: Similar functional outcomes can be achieved in the surgical management of anterior instability in patients aged \u3e /= 40 years. Rotator cuff tears should be suspected and repaired in patients with anterior instability, especially those aged \u3e /= 50 years

Fluorogenic Atom Transfer Radical Polymerization in Aqueous Media as a Strategy for Detection

The development of novel approaches to signal amplification in aqueous media could enable new diagnostic platforms for the detection of water-soluble analytes, including biomolecules. This paper describes a fluorogenic polymerization approach to amplify initiator signal by the detection of visible fluorescence upon polymerization in real-time. Fluorogenic monomers were synthesized and co-polymerized by atom transfer radical polymerization (ATRP) in water to reveal increasing polymer fluorescence as a function of both reaction time and initiator concentration. Optimization of the fluorogenic ATRP reaction conditions allowed for the quantitative detection of a small-molecule initiator as a model analyte over a broad linear concentration range (pM to mM). Raising the reaction temperature from 30 C to 60 C facilitated sensitive initiator detection at sub-picomolar concentrations in as little as 1 h of polymerization. This method was then applied to the detection of streptavidin as a model biological analyte by fluorogenic polymerization from a designed biotinylated ATRP initiator. Taken together, these studies represent the first example of a fluorogenic ATRP reaction and establish fluorogenic polymerization as a promising approach for the direct detection of aqueous analytes and biomolecular recognition events