High velocity impact studies on S-2 glass laminated composites

Post failure analysis of the impacted 12.7 mm thick S-2 glass composite panels (150x150 mm) was performed to study the failure modes during penetration. The panels were impacted projectiles (4.5 g) with three different nose shapes (blunt, conical and hemispherical) at velocities 250-600 m/s and impact data was reported in an earlier study. The back-face deflection of the laminates was also recorded in that study with the Imacon high speed camera at 105 f7s. Post failure analysis revealed that the laminates failed during penetration by cratering due to punching of fibers, laminate crushing, delamination and fiber stretching and breaking. The extent of failure modes varied with strike velocity of the projectile. Stress based failure criteria were proposed for these failure modes. Impact of the blunt nose projectiles on to S-2 glass laminate was simulated by incorporating the failure criteria in DYNA3D code. Simulated ballistic limit of the laminate and residual velocities o f the blunt nose projectiles agreed within 10% of the experimental results. However, the same failure criteria failed to predict the ballistic limit o f 6.4 mm thick S-2 glass laminates impacted by 5.8, 17, and 44 grain projectiles

A case of Rhizopus infection in an immunocompetent IVDA host

Introduction: Mucormycosis is a rare fungal infection most commonly seen in patients with neutropenia, diabetic ketoacidosis, or prolonged use of corticosteroids. Here we present an unusual case of isolated cerebral mucormycosis in a young, immunocompetent patient. Case: A 36 year-old female with chronic Hepatitis C and intravenous drug abuse (IVDA) presented with sudden hemiparesis of the left upper and lower extremities. Her Glasgow Coma Scale was 15. MRI brain revealed a gadolinium-enhancing lesion adjacent to the right basal ganglia and thalamus consistent with an abscess, with surrounding vasogenic edema, mass effect causing right-to-left midline shift involving her right lateral ventricle (Figures 1 and 2). The abscess was surgically debrided and biopsy of the lesion revealed multinucleated giant cells and scattered groupings of branching fungal forms consistent with Rhizopus oryzae infection. Her remaining infectious and immunologic workup was unremarkable, including undetectable Hepatitis C RNA and absent HIV antibodies. During her hospital course, she exhibited new neurological findings including right lateral gaze palsy, left facial weakness, left hemi-neglect, and left ankle clonus. This was attributed to worsening vasogenic edema despite a medical regimen including IV amphotericin B and anidulafungin. Subsequently, isavuconazole was added. She continued on this regimen for four weeks after her initial debridement and was discharged to an in-patient rehabilitation center. On follow up examinations, she has exhibited gradual improvement in her strength, however she continues to have visual field deficits and requires assistance with activities of daily living. Discussion: Mucormycosis is a rare, life-threatening fungal infection predominantly affecting immunocompromised hosts. The most significant risk factors for this infection include diabetic ketoacidosis, neutropenia, prolonged high-dose glucocorticoid therapy, bone marrow or solid organ transplantation, iron overload, and IVDA. Clinical presentation often reflects underlying risk factors for disease. For example, diabetic patients are likely to present with sinus involvement whereas patients with transplanted organs and malignancy more commonly present with pulmonary infection. Disseminated disease is most commonly seen in patients in an iron-overloaded state or those treated with deferoxamine. Isolated cerebral infection constitutes just 5% of all mucormyosis infections, but has a fatality rate exceeding 60%. Despite its rarity, however, isolated cerebral mucormycosis is the most common presentation among IVDA, constituting 62% of mucormycosis infections in this subgroup. Brain lesions are most commonly located within the basal ganglia, likely secondary to hematogenous seeding of the perforating branches of the Middle Cerebral Artery. It has been hypothesized that illicit injection drugs contaminated with mucormyosis spores enter the systemic arterial circulation before seeding the brain. Improved survival rates are seen among those patients treated with early stereotactic biopsy and aggressive amphotericin B therapy. Conclusion: For patients with a history of IVDA who present with brain abscess (especially in the basal ganglia), mucormycosis should be on the clinicians’ differential diagnosis. Early intervention with stereotactic brain biopsy and amphotericin B, as well as abscess debridement, can dramatically increase the likelihood of survival and can minimize permanent neurologic sequelae.https://scholarlycommons.henryford.com/merf2020caserpt/1076/thumbnail.jp

Volumetric, viscometric and optical study of molecular interactions in binary mixtures of diethyl malonate with ketones at 303.15, 308.15 and 313.15K

Density ρ, viscosity η, and refractive index nD were measured for the binary mixtures of diethyl malonate with ketones (acetophenone, cyclopentanone, cyclohexanone and 3-pentanone) at temperatures (303.15, 308.15 and 313.15) K over the entire composition range. Excess volume VE, deviation in viscosity Δη, excess Gibb’s free energy of activation for viscous flow ΔGE and deviation in molar refraction ÄR were determined from the experimental data and computed results were fitted to the Redlich-Kister polynomial equation. The values of VE, Δη, ΔGE, and ΔR were plotted against the mole fraction of diethyl malonate. The observed positive and negative values of excess parameters for all the studied binary mixtures were explained on the basis of intermolecular interactions present in these mixtures. Further different empirical relations were used to correlate the binary mixture viscosities and refractive indices

Regulation of Sonic hedgehog (Shh) expression in the zebrafish retina

Sonic hedgehog (Shh) a vertebrate homolog of the Drosophila melanogaster gene hedgehog, is a secreted protein that controls numerous differentiation processes during vertebrate development. In the vertebrate retina, Shh controls neurogenesis and its expression spreads in a wave like manner. The shh locus has been well characterised in vertebrates and the regulatory regions driving the expression in the notochord and the midline of the CNS were identified. In zebrafish, shh transgenes were established that drive GFP reporter expression very similar to that of the endogenous shh gene in the central nervous system including the retina. The cis-regulation behind shh expression in the retina was not known. This prompted me to map the region responsible for retina expression. I found it to be distinct from the previously described enhancers controlling expression in the midline of the neural tube and in the notochord. This novel regulatory region mediates expression of a GFP reporter cassette in the ganglion cell layer (GCL) and inner nuclear layer (INL) of the retina. The expression is initiated in a ventronasal patch and later spreads across the GCL and INL in a wave like pattern. A deletion approach identified a 300 bp region to be sufficient and necessary for driving expression in the retina. By a second series of mutations across this region using a linker scanning approach, a minimal 40 bp core important for expression was identified. While one clusters of point mutation impaired expression in both GCL and INL, another region was mapped that affected expression exclusively in the GCL. Thus, expression in the two layers can be separated. Pea3 and Erm factors were predicted to bind to the retinal enhancer. In vitro protein binding and morpholino studies prove that they are key regulatory factors responsible for driving expression in the retina. Pea3 and Erm are factors known to act downstream of Fgf signals. Earlier studies have demonstrated that Fgf signalling from the optic stalk is responsible for initiation of retinal neurogenesis. Moreover, shh was shown to be required for the spread of the shh expression wave in an auto-regulatory manner. Pharmacological inhibition and morpholino studies were performed to study the the role of Fgfs and Shh in the propagation of the expression. My results suggest that several distinct Fgfs and Hedgehogs act sequentially at several levels and that the propagation of the expression wave is dependent on a co-operation between FGF and Shh signalling pathways. This is reminiscent to the spread of the expression of the Drosophila hedgehog gene through the eye imaginal disc

Visualizing Data in Traditional Text Layouts with Application to Classical Latin

Scholarship in linguistics, library science, journalism, and classics has long de- pended upon reading and analyzing text in traditional printed formats. Increasingly, manual and automatic text processing techniques are being used to transform text into structured data that can be queried and visualized. Such data often consists of spreadsheets or databases that contain information extracted from the text, such as document metadata, entities and relationships, sentiment, or grammatical structure. Many techniques have been developed to visualize text as structured data. A few display that data in a recognizably traditional format. Representing data within its own text provides a common visual context that allows for more efficient reading and effective interpretation. In this thesis, we describe a design framework and a reference implementation for visually representing information in traditional text layouts. The framework provides ways to visually represent information about text directly in the text itself, including text styling, highlighting, decoration, and embedding of entire data views. By integrating data graphics into text, readers can see and interact with both the text and its associated data in a unified visual context. The implementation builds upon the declarative language in Improvise to support interactive queries including visual encoding, filtering, and sorting of data for display in the text. We present several application examples and use them to assess the expressiveness, effectiveness, and performance of the framework for navigation and query features desirable to scholars of classical Latin

Optimization of Systemic Nasal Delivery of Progesterone using Polyacrylic Acid Based Gels

In this study, CDs significantly enhanced the nasal absorption of progesterone in rabbits. From these results it is suggested that the absorption enhancing effect is mediated through the solubility enhancing and permeation enhancing properties of the CDs. Similar results have been reported by Henry131 et al in which dimethyl-β-cyclodextrin is used in nasal product containing 17-β-estradiol. The solubilized 17-β-estradiol gave significantly higher nasal bioavailability in rabbits as compared to non-suspension formulations. A similar work by Merkus145 et al demonstrated that formulation in which dimethyl-β-cyclodextrin was used to solubilize progesterone for nasal delivery has been tested in human volunteers and has been shown to result in blood levels of progesterone comparable to those after intravenous administration. In addition to the solubilizing and stabilizing effects of the cyclodextrins, these materials may also have an absorption enhancing effect on the nasal membrane. Gu72 et al investigated the solubilization of prostaglandin with hydroxypropyl β-cyclodextrin. The complex first increased the solubility and stability of the drug which lead to increase in bioavailbility to 25% on nasal administration. In this study the effect of the CDs on the integrity of nasal mucosa was evaluated and found to be safe. This was similarly demonstrated in the study by Kazunori121 et al who showed that there was no tissue damage with 1.5% β-cyclodextrin and 10% hydroxypropyl β-cyclodextrin. This work stives to show the effect of the method of addition of CDs on the absorption enhancement properties on the nasal mucosa. The progesterone absorption-enhancing effect of CDs showed a trend towards its method of addition either as a complex or as a physical mixture. Gels have been used for quite a long time as drug carriers and recent advances in gel and polymer technology have attracted researchers’ interest in these polymeric systems. The nasal route was no exception. The nasal route for administration of gels for systemic delivery of progesterone is proved to be an effective mode of drug delivery. The increased bioavailability of progesterone following nasal instillation of the gel formulation using bioadhesive PAA polymers along with beta cyclodextrin and hydroxypropyl beta cyclodextrin, together with observed minor toxicity demonstrate the potential of these nasal gels to systemically deliver the hormone. PAA polymers are a promising drug delivery system for the steroidal hormone progesterone, which enhances nasal residence time owing to increased viscosity and mucoadhesive characteristics; furthermore PAA polymers along with absorption enhancers beta cyclodextrin and hydroxypropyl beta cyclodextrin exhibit permeation enhancing effect. Gels for nasal delivery require careful study because of the special delivery required. According to this work the formulative approaches for improving nasal delivery of progesterone consist in the use of suitable absorption enhancers. As cyclodextrins were chosen for absorption enhancement, the method of addition is important to the study. Statistical optimization reveals that addition of cyclodextrins as an inclusion complex with the drug in the gels significantly affects the absorption profile. In vivo studies in rabbits for nasal absorption of progesterone show a rapid increase in plasma levels and promising bioavailability values. Hence the formulations represent a promising and novel tool for the nasal delivery of progesterone and can be used instead of injectables for the administration of the hormone. As drugs and biotechnology markets continue to grow, in the future we should expect a range of novel nasal products to escalate in the market. It is envisaged that these products will be used in crisis management as well as in treatment of long term conditions. Most of the drugs which will be available as nasal products in the future, are those, which at present are given as injections or have a low bioavailability and display unwanted pharmacological effects due to inappropriate dosing regimen. In this study detailed characterizations of the formulations along with toxicological and bioavailability studies are carried out in animals which has been promising. However there is a tendency for the absorption promoting effect to be different in larger animals. Accordingly, investigations in humans are necessary in order to prove the pharmaceutical performance and allow excellence of clinical outcome

Foix Alajouanine Syndrome Mimicking Longitudinally Extensive Transverse Myelitis

Objective: To describe an interesting case of Foix-Alajouanine Syndrome presenting as a longitudinally extensive transverse myelitis (LETM). Background: Foix-Alajouanine Syndrome is caused by a spinal dural arteriovenous malformation and presents as paraparesis and progressive walking impairment. It most commonly involves the thoracolumbar region and affects elderly men. Though treatable, it is a cause of progressive myelopathy often misdiagnosed or missed. Case Discussion: A 77-year-old man with a history of coronary artery disease presented with a one-year history of progressive lower extremity paresthesia, weakness, gait instability, and recurrent falls. He had no lumbar or lower extremity pain. He had no bladder incontinence. His symptoms were attributed to lumbar spinal stenosis and he underwent L3-L4 lumbar decompression at an outside hospital with no improvement. MRI of the lumbar spine without contrast done at the outside facility was reviewed and it showed an LETM from T8 through the tip of the conus medullaris. MRI of the entire spine was repeated with gadolinium. MRI lumbar spine with gadolinium showed flow voids at the dorsal aspect of T8-T9 consistent with a Type I spinal dural AV fistula. This was confirmed by the spinal angiogram. The patient had a negative MRI brain and cervical spine imaging. The spinal fluid analysis was unremarkable. Aquaporin-4 antibody and anti-MOG antibody tests were negative. He underwent a laminectomy with microsurgical obliteration of the AV fistula and regained 50% of his lower extremity strength within 48 hours of his surgery and continues to improve with physical therapy. Conclusion: Foix-Alajouanine Syndrome should be considered in the differential diagnosis of LETM. It is a reversible cause of progressive myelopathy and needs a careful review of imaging, laboratory data, and clinical findings.https://scholarlycommons.henryford.com/merf2020caserpt/1106/thumbnail.jp

FORMAL SPECIFICATIONS AND COMMAND MODELING IN SOFTWARE SYSTEMS WITH A COMPLEX COMMAND STRUCTURE

Commands are an important part of large scale industrial software specifications, especially where the specification is separated from its implementation as in open software standards. Commands can be complex because of large numbers of parameters, dependencies among parameters, subtle side effects, and lack of abstraction. We present a formal approach for command modeling and apply it to IBM\u27s Distributed Data Management Architecture (DDM), a complex, large scale specification of data access on remote and heterogeneous IBM systems. Our approach consists of three parts: a declarative, executable command specification language, an incremental specification technique, and automated reasoning tools. The command specification language provides a formal interpretation of the structural (input-output) and behavioral properties (state constraints/change) of commands. To manage the details of complex commands with numerous inter-dependent arguments, a novel incremental specification technique and several tools for incremental definition and browsing are presented. Two forms of automated reasoning are also demonstrated: type checking to ensure well-typed expressions and target system tracing to simulate command execution. Lessons learned from our experience with the DDM are also discussed

Open Access High Throughput Drug Discovery in the Public Domain: A Mount Everest in the Making

High throughput screening (HTS) facilitates screening large numbers of compounds against a biochemical target of interest using validated biological or biophysical assays. In recent years, a significant number of drugs in clinical trails originated from HTS campaigns, validating HTS as a bona fide mechanism for hit finding. In the current drug discovery landscape, the pharmaceutical industry is embracing open innovation strategies with academia to maximize their research capabilities and to feed their drug discovery pipeline. The goals of academic research have therefore expanded from target identification and validation to probe discovery, chemical genomics, and compound library screening. This trend is reflected in the emergence of HTS centers in the public domain over the past decade, ranging in size from modestly equipped academic screening centers to well endowed Molecular Libraries Probe Centers Network (MLPCN) centers funded by the NIH Roadmap initiative. These centers facilitate a comprehensive approach to probe discovery in academia and utilize both classical and cutting-edge assay technologies for executing primary and secondary screening campaigns. The various facets of academic HTS centers as well as their implications on technology transfer and drug discovery are discussed, and a roadmap for successful drug discovery in the public domain is presented. New lead discovery against therapeutic targets, especially those involving the rare and neglected diseases, is indeed a Mount Everestonian size task, and requires diligent implementation of pharmaceutical industry’s best practices for a successful outcome

Clinical study of chemotherapy induced febrile neutropenia: talcott’s versus multinational association for supportive care in cancer risk assessment scoring systems

Background: Cancer is a leading cause of death worldwide, accounting for 8.2 million deaths in 2012. Febrile neutropenia (FN) is fever associated with abnormally low neutrophil count signifying an immunocompromised state secondary to malignancy or its treatment. The aim of this study was to evaluate clinical outcome of chemotherapy induced febrile neutropenia.Methods: This was a hospital based prospective, descriptive observational study. Patients of either sex, age (18-90 years), with cancer on chemotherapy, single oral temperature ≥101°Fahrenheit (38.3°C) or a temperature ≥100.4° Fahrenheit (38.0° C) for ≥ one hour with absolute neutrophil counts <500 cells/mm3 or <1000 cells/mm3 with a predicted decrease to less than 500 cells/mm3 in the next 24 hours, only with first febrile episode occurring during study period and prior or concurrent radiation therapy were included in this study.Results: Among 87 patients, 70 (80.5%) were less than 60 years and 17 (19.5%) were ≥60 years. The mean age of study patients was 44.46±15 years, (range 18 to 77 years), 31(35.6%) were male and 56 (64.4%) were female. Talcott’s and MASCC risk predicting tool versus outcome, p values for Talcott’s and MASCC were significant (<0.05).Conclusions: Neutropenic fever is a potentially life-threatening complication of cancer chemotherapy. MASCC and Talcott’s model can be used to identify low and high risk patients. MASCC risk index may have a better performance than the Talcott’s model in risk classification