Anti-Lapse Statute Must Apply to a Lapsed Residuary Bequest in the Absence of Reasonably Certain Intent of the Testator: \u3cem\u3eIn re Estate of Burger\u3c/em\u3e

The Pennsylvania Supreme Court held that an intestate heir lacked standing to challenge a residuary bequest in a will contest because, in the absence of the testator\u27s contrary intent, the anti-lapse statute applied to direct the failed bequest to the other residuary legatees. In re Estate of Burger, 898 A.2d 547 (Pa. 2006)

Rewiring Neural Interactions by Micro-Stimulation

Plasticity is a crucial component of normal brain function and a critical mechanism for recovery from injury. In vitro, associative pairing of presynaptic spiking and stimulus-induced postsynaptic depolarization causes changes in the synaptic efficacy of the presynaptic neuron, when activated by extrinsic stimulation. In vivo, such paradigms can alter the responses of whole groups of neurons to stimulation. Here, we used in vivo spike-triggered stimulation to drive plastic changes in rat forelimb sensorimotor cortex, which we monitored using a statistical measure of functional connectivity inferred from the spiking statistics of the neurons during normal, spontaneous behavior. These induced plastic changes in inferred functional connectivity depended on the latency between trigger spike and stimulation, and appear to reflect a robust reorganization of the network. Such targeted connectivity changes might provide a tool for rerouting the flow of information through a network, with implications for both rehabilitation and brain–machine interface applications

Initial Active Interrogation Experiments at The University of Michigan Linear Accelerator Laboratory

To support the mission of the Countering Weapons of Mass Destruction Office of the Department of Homeland Security, the Detection for Nuclear Nonproliferation group is researching active interrogation techniques and the development of new detection algorithms for fast neutron spectroscopy. The Countering Weapons of Mass Destruction Officehas loaned us a Varian M9 linear accelerator (linac), helium-3 detectors, boron-coated straw detectors, and perfluorocarbondetectors as part of this research, providing a variety of tools to conduct our experiments.In the summer of 2018, a thorough licensing process concluded, and preliminary experiments commenced. Later in the year, the facility was approved to possess and irradiate depleted uranium, which enabledus to conduct active interrogation experiments.In the fall of 2018, we conducted our first active interrogation measurements using the linac facility. The measurements used the linac to irradiate depleted uranium,lead, and tungsten targets to induce photonuclear reactions to emit fast neutrons. The neutrons were then detected using a simple helium-3 detector. Simulations were developed using MCNPX-PoliMi and MCNP 6.1 to validate the measured results. The simulations showed close agreement for depleted uranium but indicated that additional investigation is required for the lead and tungsten data. The facility will be indispensable as the researchprogressesbyproviding a mixed-radiation field consisting of fast neutrons and photons, which is similar to the radiation environment encountered in active interrogation scenarios.Additionally, the facility is involved inresearch related toradiation damage, dosimetry, and radiation-oncology.Future activities will involve characterization of photonuclear properties of various materials, and collaborations with other university researchers

HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician's choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer.

BackgroundHuman epidermal growth factor receptor 2 (HER2)-positive breast cancer is a particularly aggressive form of the disease, and ultimately progresses in patients with metastases on standard therapies. Anthracyclines, such as doxorubicin, are an effective treatment for HER2-positive breast cancer, particularly when administered in combination with trastuzumab - however, doxorubicin-related cardiotoxicity has limited its use. Many patients are therefore never treated with anthracyclines, even upon disease progression, despite the potential for benefit. MM-302 is a novel, HER2-targeted antibody-liposomal doxorubicin conjugate that specifically targets HER2-overexpressing cells. Preclinical and Phase 1 data suggest that MM-302, as a monotherapy or in combination with trastuzumab, could be effective for managing previously treated, anthracycline-naïve, HER2-positive breast cancer, without the cardiotoxicity observed with free doxorubicin formulations.Methods/designHERMIONE is an open-label, multicenter, randomized (1:1) Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician's choice (gemcitabine, capecitabine, or vinorelbine) plus trastuzumab planned to enroll 250 anthracycline-naïve patients with locally advanced/metastatic HER2-positive breast cancer. Key inclusion criteria are: previous treatment with trastuzumab (with or without pertuzumab) in any setting; refractory or intolerant to pertuzumab (refractory to pertuzumab defined as progression in the locally advanced or metastatic setting, or disease recurrence during or within 12 months of completing pertuzumab-containing neoadjuvant and/or adjuvant therapy); and disease progression on, or intolerant to, ado-trastuzumab emtansine for locally advanced or metastatic disease. The trial is currently being conducted at sites in the USA, Canada, and Western Europe. Treatment will be administered in 21-day cycles, and will be continued until disease progression or unacceptable toxicity. The primary endpoint is independently assessed progression-free survival (PFS). Tumor response will be assessed every 6 weeks, and defined according to RECIST v1.1. Secondary endpoints include investigator-assessed PFS, overall survival (OS), OS rates at 6 months and 1 year, objective response rates, safety and tolerability, quality of life, and the pharmacokinetic profile of MM-302 plus trastuzumab.DiscussionThe HERMIONE study will evaluate the efficacy and safety of MM-302 plus trastuzumab in patients with refractory HER2-positive advanced/metastatic breast cancer for whom there are no standard of care therapies with a proven survival advantage.Trial registrationClinicaltrials.gov identifier: NCT02213744 . Registration date: 06AUG2014

Multi-electrode stimulation in somatosensory cortex increases probability of detection

Objective. Brain machine interfaces (BMIs) that decode control signals from motor cortex have developed tremendously in the past decade, but virtually all rely exclusively on vision to provide feedback. There is now increasing interest in developing an afferent interface to replace natural somatosensation, much as the cochlear implant has done for the sense of hearing. Preliminary experiments toward a somatosensory neuroprosthesis have mostly addressed the sense of touch, but proprioception, the sense of limb position and movement, is also critical for the control of movement. However, proprioceptive areas of cortex lack the precise somatotopy of tactile areas. We showed previously that there is only a weak tendency for neighboring neurons in area 2 to signal similar directions of hand movement. Consequently, stimulation with the relatively large currents used in many studies is likely to activate a rather heterogeneous set of neurons. Approach. Here, we have compared the effect of single-electrode stimulation at subthreshold levels to the effect of stimulating as many as seven electrodes in combination. Main results. We found a mean enhancement in the sensitivity to the stimulus (d′) of 0.17 for pairs compared to individual electrodes (an increase of roughly 30%), and an increase of 2.5 for groups of seven electrodes (260%). Significance. We propose that a proprioceptive interface made up of several hundred electrodes may yield safer, more effective sensation than a BMI using fewer electrodes and larger currents

LinkedIn Blunders: A Mixed Method Study of College Students’ Profiles

Although a significant need exists for college students to market their job skills effectively to potential employers, no prior research systematically analyzed the quality of information included in college students’ LinkedIn profiles. This study used a marketing framework to evaluate the effectiveness of information in LinkedIn profiles posted by current and former community college students. The mixed method study analyzed 340 publicly available LinkedIn profiles for students who reported attending 89 community colleges in the United States. The results suggest many college students may not understand how to use a LinkedIn profile to market their skills to potential employers. Key sections were often left blank and profiles failed to communicate students’ unique value proposition. Content analysis revealed 75% of profiles contained an experience section with poor to below average descriptions. Comparative analysis found profiles for unemployed individuals and those seeking a new position were significantly worse than profiles for their employed counterparts. Additionally, LinkedIn profiles for students from large community colleges had significantly more writing errors than profiles for students attending medium-size community colleges. After discussing implications of the research, recommendations based on the study’s results are suggested for career service staff, educators, and students

Nuclear-localized focal adhesion kinase regulates inflammatory VCAM-1 expression.

Vascular cell adhesion molecule-1 (VCAM-1) plays important roles in development and inflammation. Tumor necrosis factor-α (TNF-α) and focal adhesion kinase (FAK) are key regulators of inflammatory and integrin-matrix signaling, respectively. Integrin costimulatory signals modulate inflammatory gene expression, but the important control points between these pathways remain unresolved. We report that pharmacological FAK inhibition prevented TNF-α-induced VCAM-1 expression within heart vessel-associated endothelial cells in vivo, and genetic or pharmacological FAK inhibition blocked VCAM-1 expression during development. FAK signaling facilitated TNF-α-induced, mitogen-activated protein kinase activation, and, surprisingly, FAK inhibition resulted in the loss of the GATA4 transcription factor required for TNF-α-induced VCAM-1 production. FAK inhibition also triggered FAK nuclear localization. In the nucleus, the FAK-FERM (band 4.1, ezrin, radixin, moesin homology) domain bound directly to GATA4 and enhanced its CHIP (C terminus of Hsp70-interacting protein) E3 ligase-dependent polyubiquitination and degradation. These studies reveal new developmental and anti-inflammatory roles for kinase-inhibited FAK in limiting VCAM-1 production via nuclear localization and promotion of GATA4 turnover

MISSE 6 Polymer Film Tensile Experiment

The Polymer Film Tensile Experiment (PFTE) was flown as part of Materials International Space Station Experiment 6 (MISSE 6). The purpose of the experiment was to expose a variety of polymer films to the low Earth orbital environment under both relaxed and tension conditions. The polymers selected are those commonly used for spacecraft thermal control and those under consideration for use in spacecraft applications such as sunshields, solar sails, and inflatable and deployable structures. The dog-bone shaped samples of polymers that were flown were exposed on both the side of the MISSE 6 Passive Experiment Container (PEC) that was facing into the ram direction (receiving atomic oxygen, ultraviolet (UV) radiation, ionizing radiation, and thermal cycling) and the wake facing side (which was supposed to have experienced predominantly the same environmental effects except for atomic oxygen which was present due to reorientation of the International Space Station). A few of the tensile samples were coated with vapor deposited aluminum on the back and wired to determine the point in the flight when the tensile sample broke as recorded by a change in voltage that was stored on battery powered data loggers for post flight retrieval and analysis. The data returned on the data loggers was not usable. However, post retrieval observation and analysis of the samples was performed. This paper describes the preliminary analysis and observations of the polymers exposed on the MISSE 6 PFTE