A New Linear Logic for Deadlock-Free Session-Typed Processes

The π -calculus, viewed as a core concurrent programming language, has been used as the target of much research on type systems for concurrency. In this paper we propose a new type system for deadlock-free session-typed π -calculus processes, by integrating two separate lines of work. The first is the propositions-as-types approach by Caires and Pfenning, which provides a linear logic foundation for session types and guarantees deadlock-freedom by forbidding cyclic process connections. The second is Kobayashi’s approach in which types are annotated with priorities so that the type system can check whether or not processes contain genuine cyclic dependencies between communication operations. We combine these two techniques for the first time, and define a new and more expressive variant of classical linear logic with a proof assignment that gives a session type system with Kobayashi-style priorities. This can be seen in three ways: (i) as a new linear logic in which cyclic structures can be derived and a CYCLE -elimination theorem generalises CUT -elimination; (ii) as a logically-based session type system, which is more expressive than Caires and Pfenning’s; (iii) as a logical foundation for Kobayashi’s system, bringing it into the sphere of the propositions-as-types paradigm

EVALUATION OF THE CONTRIBUTION OF CYTOCHROME P450 3A4 TO HUMAN LIVER MICROSOMAL BUPROPION HYDROXYLATION

This paper is available online at http://dmd.aspetjournals.org ABSTRACT: The purpose of this investigation was to evaluate the role of cytochrome P450 (CYP) 3A4 in human liver microsomal bupropion (BUP) hydroxylation. Across the BUP concentration range of 0.075 to 12 mM, cDNA-expressed CYP3A4 demonstrated BUP hydroxylase activity only when incubated with concentrations >4 mM. When assayed at 12 mM BUP, cDNA-expressed CYP3A4 catalyzed BUP hydroxylation at a 30-fold lower rate than cDNA-expressed CYP2B6 (0.2 versus 7 pmol/min/pmol of P450 Bupropion (BUP) 1 is a second-generation antidepressant agent that is also used in the management of smoking cessation. This drug undergoes extensive hepatic metabolism in humans via oxidative and reductive pathways Clinical pharmacokinetic studies have demonstrated 3-to 10-fold interindividual differences in HBUP C max and AUC In a prior in vitro study reported in abstract form, CYP3A4 demonstrated the second highest rate of BUP hydroxylation among a panel of cDNA-expressed P450 isozyme

An evaluation of the combination effect of zoledronate and chemotherapeutic agents in canine osteosarcoma cells

IntroductionOsteosarcoma (OSA) is an aggressive form of bone cancer in both dogs and humans. The treatment options for metastatic (stage III) OSA are currently limited and the prognosis is poor. Zoledronate, a second generation amino-bisphosphonate, is commonly used for palliation of cancer induced bone pain. Zoledronate has also demonstrated anti-cancer properties and possibly enhances the cytotoxicity of doxorubicin in a canine histiocytosis cell line and human prostatic cancer cell line. The goal of this study was to evaluate the combination effect of zoledronate and various chemotherapeutic drugs in canine OSA cells.MethodsCanine OSA cell line (D17), cells from two canine primary OSAs, and MDCK, a canine kidney cell line, were used to evaluate the therapeutic potential of these drugs. Carboplatin, doxorubicin, vinorelbine, toceranib, and isophosphoramide mustard (active metabolite of ifosfamide) were used as chemotherapeutic agents. First, cells were treated with either zoledronate or chemotherapy drug alone for 72 hours. Cell viability was assessed using CellTiter Glo and IC5, IC10, IC20, and IC50 were calculated. Second, cells were treated with a combination of zoledronate and each chemotherapeutic agent at their IC5, IC10, IC20, and IC50 concentrations. After 72 hours, cell viability was assessed by CellTiter Glo.Results and discussionZoledronate, carboplatin, doxorubicin, vinorelbine, and isophosphoramide mustard showed concentration dependent decrease in cell viability. Toceranib showed decreased cell viability only at higher concentrations. When zoledronate was used in combination with chemotherapy drugs, while it showed potential synergistic effects with toceranib, potential antagonistic effects with vinorelbine and isophosphoramide mustard were observed. However, the results differed by cell line and thus, further evaluation is warranted to understand the exact mechanism of action

Exploiting open source 3D printer architecture for laboratory robotics to automate high-throughput time-lapse imaging for analytical microbiology

Growth in open-source hardware designs combined with the low-cost of high performance optoelectronic and robotics components has supported a resurgence of in-house custom lab equipment development. We describe a low cost (below USD700), open-source, fully customizable high-throughput imaging system for analytical microbiology applications. The system comprises a Raspberry Pi camera mounted on an aluminium extrusion frame with 3D-printed joints controlled by an Arduino microcontroller running open-source Repetier Host Firmware. The camera position is controlled by simple G-code scripts supplied from a Raspberry Pi singleboard computer and allow customized time-lapse imaging of microdevices over a large imaging area. Open-source OctoPrint software allows remote access and control. This simple yet effective design allows high-throughput microbiology testing in multiple formats including formats for bacterial motility, colony growth, microtitre plates and microfluidic devices termed ‘lab-on-a-comb’ to screen the effects of different culture media components and antibiotics on bacterial growth. The open-source robot design allows customization of the size of the imaging area; the current design has an imaging area of ~420 × 300mm, which allows 29 ‘lab-on-a-comb’ devices to be imaged which is equivalent 3480 individual 1μl samples. The system can also be modified for fluorescence detection using LED and emission filters embedded on the PiCam for more sensitive detection of bacterial growth using fluorescent dyes

Market-dependent production set

A country’s production possibility frontier or PPF is defined as the boundary of its economy’s production set in the net output space for a given technology and fixed quantities of primary factors of production. In general equilibrium theory, exogenous changes in technology or primary-factor supplies alter equilibrium prices; however, government-policy induced domestic relative commodity price changes do not alter the shape of an economy’s production set. We show that, under international capital mobility, which is empirically significant, the shape of a country’s production set does, in fact, depend on market forces and this shape can be manipulated by government policy

Multimodal non-surgical treatment of a feline tracheal adenocarcinoma

Case summary A 10-year-old, castrated male domestic shorthair cat presented with a 2–3 month history of weight loss, lethargy and coughing. Thoracic radiographs revealed a soft tissue opacity overlying the dorsal trachea from the first rib to second rib and the ventral aspect of the trachea extending from the second rib to approximately the fourth rib. CT confirmed a mass involving the dorsal, right lateral and ventral aspects of the trachea narrowing the lumen and extending from vertebra C7 through T4. Bronchoscopy revealed a partially circumferential irregular and multilobulated tracheal mass, which was biopsied. The histopathological diagnosis was tracheal adenocarcinoma. The cat was treated with a definitive course of external beam radiation therapy (RT; 3 Gy × 18), cytotoxic chemotherapy, a tyrosine kinase inhibitor and palliative RT. The cat remained asymptomatic for 2 months and the mass remained stable radiographically for 11 months after RT. Relevance and novel information With multimodal treatment the cat had a survival time of 755 days. Initial treatment included definitive RT, carboplatin and piroxicam, followed by toceranib phosphate and palliative RT when the mass recurred. This case report describes the first documented use of non-surgical treatment and long-term outcome of tracheal adenocarcinoma in a cat. This case report is an indication that prolonged survival can be achieved with multimodal therapy

Challenges for Designing new Technology for Health and Wellbeing in a Complex Mental Healthcare Context

This paper describes the challenges and lessons learned in the experience-centered design (ECD) of the Spheres of Wellbeing, a technology to promote the mental health and wellbeing of a group of women, suffering from significant mental health problems and living in a medium secure hospital unit. First, we describe how our relationship with mental health professionals at the hospital and the aspirations for person-centric care that we shared with them enabled us, in the design of the Spheres, to innovate outside traditional healthcare procedures. We then provide insights into the challenges presented by the particular care culture and existing services and practices in the secure hospital unit that were revealed through our technology deployment. In discussing these challenges, our design enquiry opens up a space to make sense of experience living with complex mental health conditions in highly constrained contexts within which the deployment of the Spheres becomes an opportunity to think about wellbeing in similar contexts

The need for sexual health clinics, their future role, and contribution to public health

Specialised sexual health clinics (SHCs) play an important role in addressing the staggering rates of STIs seen in many high-income nations. Despite increasing healthcare coverage in the US and nationalised health care in some countries, there is a continued need for SHCs to meet the needs of patients and the community, especially for high-priority populations: those at high risk of STI acquisition and/or groups historically marginalised and underserved in the traditional healthcare system. We need to mobilise resources to support a stronger clinical infrastructure in specialised SHCs. This review describes the importance of SHCs, their future role, and some of the innovative programs housed within SHCs in the US, Australia, and the Netherlands to address both STI and HIV prevention for the populations they serve

Evaluation of zoledronate for the treatment of canine stage III osteosarcoma: A phase II study

Abstract Background Greater than 90% of dogs with appendicular osteosarcoma will develop pulmonary metastasis despite the standard of care. Available treatments have limited efficacy for stage III disease. Zoledronate, a bisphosphonate, induces apoptosis of canine osteosarcoma cells and appears to modulate the tumour microenvironment. Objectives This prospective, single institutional phase IIa trial investigated the use of single agent zoledronate in dogs with pulmonary metastases from osteosarcoma. Methods Zoledronate was administered once monthly, and thoracic radiographs were used to assess response. Results Eleven dogs were enrolled. Stable disease was achieved in two of eight dogs available for response assessment. The median progression‐free survival was 28 days (range: 4–93 days). The median stage III‐specific survival time was 92 days. Adverse events were reported in four dogs; two dogs developed grade III or higher toxicities. Notable adverse events included conjunctivitis, fever, hypocalcaemia, and hypophosphatemia. Conclusions Zoledronate appears to have limited efficacy as a single agent for stage III osteosarcoma and may be associated with unexpected toxicity in this population. This clinical trial was registered on the AVMA Animal Health Studies Database (AAHSD004396)