The Pros and Cons of Compressive Sensing for Wideband Signal Acquisition: Noise Folding vs. Dynamic Range

Compressive sensing (CS) exploits the sparsity present in many signals to reduce the number of measurements needed for digital acquisition. With this reduction would come, in theory, commensurate reductions in the size, weight, power consumption, and/or monetary cost of both signal sensors and any associated communication links. This paper examines the use of CS in the design of a wideband radio receiver in a noisy environment. We formulate the problem statement for such a receiver and establish a reasonable set of requirements that a receiver should meet to be practically useful. We then evaluate the performance of a CS-based receiver in two ways: via a theoretical analysis of its expected performance, with a particular emphasis on noise and dynamic range, and via simulations that compare the CS receiver against the performance expected from a conventional implementation. On the one hand, we show that CS-based systems that aim to reduce the number of acquired measurements are somewhat sensitive to signal noise, exhibiting a 3dB SNR loss per octave of subsampling, which parallels the classic noise-folding phenomenon. On the other hand, we demonstrate that since they sample at a lower rate, CS-based systems can potentially attain a significantly larger dynamic range. Hence, we conclude that while a CS-based system has inherent limitations that do impose some restrictions on its potential applications, it also has attributes that make it highly desirable in a number of important practical settings

Dietary alkaloids and the development of androconial organs in Estigmene acrea

Male salt marsh moths, Estigmene acrea (Lepidoptera: Arctiidae), possess inflatable androconial organs called coremata. Prior to mating males form aggregations and inflate their coremata en masse. The communal display attracts additional males and females for the purpose of mating. The coremata are known to carry the plant-derived dihydropyrrolizine, hydroxydanaidal. This pheromonal substance is derived from secondary plant chemicals called pyrrolizidine alkaloids found in the larval diet. When E. acrea larvae were raised on semi-synthetic diets containing different levels of the pyrrolizidine alkaloid precursors the alkaloids triggered a pronounced morphogenetic effect. Adult males that fed on high levels of the pyrrolizidine alkaloid monocrotaline N-oxide (2500 µg) developed the largest coremata. Males that fed on lower levels of monocrotaline N-oxide (500 µg) or no alkaloid, while normal in body weight, had coremata that were progressively smaller and less robust. The size of the coremata and their commensurate pheromonal charge may have behavioral consequences in the unusual mating system of this species

Identification and Characterization of Natural Compound Inhibitors of the Hsp90 Chaperone Complex

The 90 kDa Heat Shock Protein (Hsp90) has emerged as a major therapeutic target for a numberof diseases, the most notable of which is cancer. Accordingly, many groups areattempting to develop small molecules that modulate the activity of this chaperone and itsassociated co-chaperones. At the same time, many of these same diseases havetraditionally been treated using substances derived from local plant species. Recognizingthe intersection between these two medicinal strategies, our group has sought to findnovel inhibitory compounds against the Hsp90 chaperone machine by employing highthroughputscreens of natural compound libraries. In this work, we report the results offour such screens, showing that a number of potential Hsp90 inhibitors have already beenused successfully in various medical traditions for the treatment of multiple diseases.Characterization of structure-activity relationships using a 1,4- nathoquinone scaffold thatwas common to several of our natural product hits, demonstrated that the luciferaserenaturation assay that forms the basis of our screens is comparable to cell-based assays.Four compound hits, anthothecol, garcinol, rottlerin, and piperlongumine, were furthercharacterized and demonstrated to inhibit the proliferation of human cancer cells, and thematuration of an Hsp90-dependent kinase. Additionally, one of the compounds,gambogic acid, was shown to disrupt inter-molecular interactions of the Hsp90 chaperonecomplex, and to interact with Hsp90 itself. These compounds and their derivativesrepresent potential novel therapeutics against cancer and other diseases in which Hsp90plays a role.Biochemistry & Molecular Biolog

Leveraging Sanofi intensified ICB platform to enable early process development for a labile and hard-to-express molecule

Within the biopharmaceutics industry, tremendous progress has been made in the implementation of early development antibody platforms to achieve high volumetric productivity and consistent product quality for novel therapies. More recently, development of new modalities provide opportunities for advancing exciting new therapeutic possibilities. However, many of these modalities present new upstream and downstream development challenges, e.g., low expression, labile molecules, low recovery, and unreliable product quality. The resulting additional development requirements increase the timelines for demonstrating Proof of Concept and may even prohibit certain therapeutic candidates from reaching the clinic at all. The Sanofi ICB platform provides opportunities to increase productivity and improve product quality, enabling manufacture of new entities previously inaccessible. Here, we present a case study of such a situation, in which the ICB platform is applied to an early-stage, labile, hard to express molecule produced from non-CHO mammalian cells. A combination of upstream and downstream high-throughput technologies have been incorporated to rapidly define a process sufficient for first-in-human studies. Process intensification enables adequate material generation within an acceptable number of batches for both development and clinical manufacturing. This case study demonstrates the strategy of using intensified perfusion platform for non-antibody modalities to support a diverse portfolio for our evolving industry

Alteration in corticospinal excitability, talocrural joint range of motion, and lower extremity function following manipulation in non-disabled individuals

Background: Clinical outcomes of manual therapy procedures, including manipulation, have been studied. However, mechanisms underlying observed improvements remain unclear. Objective: To determine the effect of ankle joint manipulation on corticospinal excitability, ankle dorsiflexion range of motion (DF ROM), and lower extremity functional behavior in nondisabled individuals. Method: Six nondisabled individuals (age range: 31-50 years) received the main outcomes measurements of this study, before and after long axis distraction manipulation of the talocrural joint. Main outcomes measures were motor evoked potential (MEP) amplitude of gastrocnemius (GN) and tibialis anterior (TA) using transcranial magnetic stimulation, ankle DF ROM with the knee flexed and extended using standard goniometric techniques, and unilateral anterior squat reach (ASR) distance. All subjects received the main outcomes measures. Results: Significant increase in GN MEP amplitude (P \u3c .05), but not TA MEP amplitude, were documented following intervention. Significant improvements also were noted in ankle DF ROM with knee extended and flexed (P \u3c .001) and ASR distance (P \u3c .05) Significant correlations were found between standardized change in GN MEP amplitude and ankle dorsiflexion with knee flexed (ρ = .582, ρ 2 = .339, P \u3c .01), and standardized changes in GN MEP amplitude and ASR distance (ρ = .601, ρ 2 = .361, P \u3c .01). Conclusions: Increased corticospinal excitability appears to mediate improvements in ankle DF ROM and lower extremity function following long axis distraction manipulation 1 Assistant Professor, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, to the talocrural joint in nondisabled individuals. These results establish comparative values with which to compare the corticospinal responses to manual therapy intervention in individuals with pathology. INTRODUCTION Ankle sprains are the most common injury to the ankle joint, affecting up to 2 million people and approximately 53 per 10,000 individuals per year. 1,2 Ankle sprains are common in younger and active individuals. 3-8 Certain sports and work activities may result in an even higher incidence and risk for injury. 9-15 Ankle sprains are a clinically important problem because they result in a substantial number of missed work days 8 and participation in sports activity, 3,5 as well as lead to potential early arthritic changes in the talocrural joint. 16 The prognosis for functional recovery following ankle sprain typically includes a rapid clinical improvement within the first two weeks after injury. 17 However, a series of recent studies indicate a subgroup of individuals appears predisposed to continued pain, functional deficits, and prolonged risk for additional reinjury between 6 weeks and 3 years post injury. 17-25 The prolonged disability associated with ankle sprains represents the possibility of increased direct and indirect health care costs associated with ankle sprains, and may be reduced through identification of optimal approaches to clinical management. One reason for continued pain and elevated risk for reinjury may be limited ankle joint mobility, which may occur as either a cause or consequence of ankle sprain. Limited ankle dorsiflexion has been documented as a major short-term sequel to ankle sprain. 26,27 In addition, several studies have identified limited talocrural joint dorsiflexion range of motion (DF ROM) as an important predisposing factor to ankle sprains. 28-30 Limited ankle DF ROM will position the talocrural joint in plantar flexion during weight bearing activities. This position is notable because the most common mechanism of injury for ankle sprains involves plantar flex-ion and inversion of the ankle and foot. The injury mechanism places excessive load on the anterior talofibular ligament (ATFL). With failure of ATFL, secondary restraint to inversion occurs by way of the calcaneo-fibular and posterior talofibular ligaments, placing them at similar risk for injury. Thus, limited ankle DF ROM may result in injury and consequent structural and functional compromise of the ankle lateral collateral ligaments. Physical therapists use mobilization and manipulation to improve ankle DF ROM following ankle sprains. Despite the intuitive appeal of applying these procedures to promote parallel improvements in talocrural DF ROM and functioning in individuals following ankle sprains, this notion has been the focus of relatively few prospective studies. 31 Pellow and Brantingham 32 were among the first to report reduced pain and improved function in individuals with ankle sprains receiving an ankle mortise distraction technique. Whitman and colleagues 33 reported rapid functional improvement after talocrural manipulation in a competitive volleyball player with a mild unilateral

Gambogic Acid, a Natural Product Inhibitor of Hsp90

A high-throughput screening of natural product libraries identified (−)-gambogic acid (1), a component of the exudate of Garcinia harburyi, as a potential Hsp90 inhibitor, in addition to the known Hsp90 inhibitor celastrol (2). Subsequent testing established that 1 inhibited cell proliferation, brought about the degradation of Hsp90 client proteins in cultured cells, and induced the expression of Hsp70 and Hsp90, which are hallmarks of Hsp90 inhibition. Gambogic acid also disrupted the interaction of Hsp90, Hsp70, and Cdc37 with the heme-regulated eIF2α kinase (HRI, an Hsp90-dependent client) and blocked the maturation of HRI in vitro. Surface plasmon resonance spectroscopy indicated that 1 bound to the N-terminal domain of Hsp90 with a low micromolar Kd, in a manner that was not competitive with the Hsp90 inhibitor geldanamycin (3). Molecular docking experiments supported the posit that 1 binds Hsp90 at a site distinct from Hsp90s ATP binding pocket. The data obtained have firmly established 1 as a novel Hsp90 inhibitor and have provided evidence of a new site that can be targeted for the development of improved Hsp90 inhibitors

The Grizzly, January 24, 1995

Ursinus College and the U.S. News and World Report Rating System • Ursinus Concludes The Next Step Campaign • 4,000 Casualties in Japanese Earthquake • Newt Confronts Ethics Issues • Local Bank Robber Brought Up on Federal Charges • Politics Department Update • Servant-Leadership Program Comes to Ursinus • St. Andrew\u27s Society of Philadelphia Scholarships • An Afternoon with Picasso and Moore • Thirdgill Kicks Off This Semester\u27s Comedy • Star Trek: Voyager Launches • Support Your Coffee House • Not-So-Super Super Bowl • Alumnus Expresses Concern Over Oversight • Men\u27s B-Ball Snaps Two-Game Skid • Bears Ready For Conference Showdown with Muhlenberg • Gymnasts Off to a Raging Start • Bears Win Triangular Meet • Aqua Bears Swept by Gettysburg • Lady Bears are Ranked For the First Timehttps://digitalcommons.ursinus.edu/grizzlynews/1350/thumbnail.jp

Accuracy of tumor segmentation from multi-parametric prostate MRI and 18F-choline PET/CT for focal prostate cancer therapy applications

Abstract Background The study aims to assess the accuracy of multi-parametric prostate MRI (mpMRI) and 18F-choline PET/CT in tumor segmentation for clinically significant prostate cancer. 18F-choline PET/CT and 3 T mpMRI were performed in 10 prospective subjects prior to prostatectomy. All subjects had a single biopsy-confirmed focus of Gleason ≥ 3+4 cancer. Two radiologists (readers 1 and 2) determined tumor boundaries based on in vivo mpMRI sequences, with clinical and pathologic data available. 18F-choline PET data were co-registered to T2-weighted 3D sequences and a semi-automatic segmentation routine was used to define tumor volumes. Registration of whole-mount surgical pathology to in vivo imaging was conducted utilizing two ex vivo prostate specimen MRIs, followed by gross sectioning of the specimens within a custom-made 3D-printed plastic mold. Overlap and similarity coefficients of manual segmentations (seg1, seg2) and 18F-choline-based segmented lesions (seg3) were compared to the pathologic reference standard. Results All segmentation methods greatly underestimated the true tumor volumes. Human readers (seg1, seg2) and the PET-based segmentation (seg3) underestimated an average of 79, 80, and 58% of the tumor volumes, respectively. Combining segmentation volumes (union of seg1, seg2, seg3 = seg4) decreased the mean underestimated tumor volume to 42% of the true tumor volume. When using the combined segmentation with 5 mm contour expansion, the mean underestimated tumor volume was significantly reduced to 0.03 ± 0.05 mL (2.04 ± 2.84%). Substantial safety margins up to 11–15 mm were needed to include all tumors when the initial segmentation boundaries were drawn by human readers or the semi-automated 18F-choline segmentation tool. Combining MR-based human segmentations with the metabolic information based on 18F-choline PET reduced the necessary safety margin to a maximum of 9 mm to cover all tumors entirely. Conclusions To improve the outcome of focal therapies for significant prostate cancer, it is imperative to recognize the full extent of the underestimation of tumor volumes by mpMRI. Combining metabolic information from 18F-choline with MRI-based segmentation can improve tumor coverage. However, this approach requires confirmation in further clinical studies.https://deepblue.lib.umich.edu/bitstream/2027.42/142871/1/13550_2018_Article_377.pd