Genomic perspectives on the evolution of fungal entomopathogenicity in Beauveria bassiana

The ascomycete fungus Beauveria bassiana is a pathogen of hundreds of insect species and is commercially produced as an environmentally friendly mycoinsecticide. We sequenced the genome of B. bassiana and a phylogenomic analysis confirmed that ascomycete entomopathogenicity is polyphyletic, but also revealed convergent evolution to insect pathogenicity. We also found many species-specific virulence genes and gene family expansions and contractions that correlate with host ranges and pathogenic strategies. These include B. bassiana having many more bacterial-like toxins (suggesting an unsuspected potential for oral toxicity) and effector-type proteins. The genome also revealed that B. bassiana resembles the closely related Cordyceps militaris in being heterothallic, although its sexual stage is rarely observed. A high throughput RNA-seq transcriptomic analysis revealed that B. bassiana could sense and adapt to different environmental niches by activating well-defined gene sets. The information from this study will facilitate further development of B. bassiana as a cost-effective mycoinsecticide

Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative condition where loss of motor neurons within the brain and spinal cord leads to muscle atrophy, weakness, paralysis and ultimately death within 3–5 years from onset of symptoms. The specific molecular mechanisms underlying the disease pathology are not fully understood and neuroprotective treatment options are minimally effective. In recent years, stem cell transplantation as a new therapy for ALS patients has been extensively investigated, becoming an intense and debated field of study. In several preclinical studies using the SOD1G93A mouse model of ALS, stem cells were demonstrated to be neuroprotective, effectively delayed disease onset and extended survival. Despite substantial improvements in stem cell technology and promising results in preclinical studies, several questions still remain unanswered, such as the identification of the most suitable and beneficial cell source, cell dose, route of delivery and therapeutic mechanisms. This review will cover publications in this field and comprehensively discuss advances, challenges and future direction regarding the therapeutic potential of stem cells in ALS, with a focus on mesenchymal stem cells. In summary, given their high proliferation activity, immunomodulation, multi-differentiation potential, and the capacity to secrete neuroprotective factors, adult mesenchymal stem cells represent a promising candidate for clinical translation. However, technical hurdles such as optimal dose, differentiation state, route of administration, and the underlying potential therapeutic mechanisms still need to be assessed

The workload in the M/G/1 queue with work removal

We consider an M/G/1 queue with the special feature of additional negative customers, who arrive according to a Poisson process. Negative customers require no service, but at their arrival a stochastic amount of work is instantaneously removed from the system. We show that the workload distribution in this M/G/1 queue with negative customers equals the waiting time distribution in a GI/G/1 queue with ordinary customers only; the effect of the negative customers is incorporated in the new arrival process

A note on negative customers, GI/G/1 workload, and risk processes

This note illustrates that a combination of the approach in our previous papers (Boucherie and Boxma, 1996, Probability in the Engineering and Informational Sciences10: 261–277; Jain and Sigman, 1996, Probability in the Engineering and Informational Sciences 10: 519–531) directly leads to a Pollaczek-Khintchine form for the workload in a queue with negative customers. The same technique is also applied to risk processes with lump additions

A two-echelon spare parts network with lateral and emergency shipments: a product-form approximation

We consider a single-item, two-echelon spare parts inventory model for repairable parts for capital goods with high downtime costs. The inventory system consists of multiple local warehouses, a central warehouse, and a central repair facility. When a part at a customer fails, if possible his request for a\u3cbr/\u3eready-for-use part is fulfilled by his local warehouse. Also, the failed part is sent to the central repair facility for repair. If the local warehouse is out of stock, then, via an emergency shipment, a ready-for-use part is sent from the central warehouse if it has a part in stock. Otherwise, it is sent via a lateral\u3cbr/\u3etransshipment from another local warehouse, or via an emergency shipment from the external supplier. We assume Poisson demand processes, generally distributed leadtimes for replenishments, repairs, and emergency shipments, and a basestock policy for the inventory control. \u3cbr/\u3e\u3cbr/\u3eOur inventory system is too complex to solve for a steady-state distribution in closed form. We approximate it by a network of Erlang loss queues with hierarchical jump-over blocking. We show that this network has a product-form steady-state distribution. This enables an efficient heuristic for the optimization of basestock levels, resulting in good approximations of the optimal costs

Batch scheduling in the histopathology laboratory

\u3cp\u3eHistopathology laboratories aim to deliver high quality diagnoses based on patient tissue samples. Timely and high quality care are essential for delivering high quality diagnoses, for example in cancer diagnostics. However, challenges exist regarding employee workload and tardiness of results, which both impact the diagnostic quality. In this paper the histopathology operations are studied, where tissue processors are modeled as batch processing machines. We develop a new 2-phased decomposition approach to solve this NP-hard problem, aiming to improve the spread of workload and to reduce the tardiness. The approach embeds ingredients from various planning and scheduling problems. First, the batching problem is considered, in which batch completion times are equally divided over the day using a Mixed Integer Linear Program. This reduces the peaks of physical work available in the laboratory. Second, the remaining processes are scheduled to minimize the tardiness of orders using a list scheduling algorithm. Both theoretical as well as historical data were used to assess the performance of the method. Results show that using this decomposition method, the peaks in histopathology workload in UMC Utrecht, a large university medical center in The Netherlands, may be reduced with up to 50 % by better spreading the workload over the day. Furthermore, turnaround times are reduced with up to 20 % compared to current practices. This approach is currently being implemented in the aforementioned hospital.\u3c/p\u3

Evaluating the GPRS Radio Interface for Different Quality of Service Profiles

. This paper presents a discrete-event simulator for the General Packet Radio Service (GPRS) on the IP level. GPRS is a standard on packet data in GSM systems that will become commercially available by the end of this year. The simulator focuses on the communication over the radio interface, because it is one of the central aspects of GPRS. We study the correlation of GSM and GPRS users by a static and dynamic channel allocation scheme. In contrast to previous work, our approach represents the mobility of users through arrival rates of new GSM and GPRS users as well as handover rates of GSM and GPRS users from neighboring cells. Furthermore, we consider users with different QoS profiles modeled by a weighted fair queueing scheme. The simulator considers a cell cluster comprising seven hexagonal cells. We provide curves for average carried traffic and packet loss probabilities for different channel allocation schemes and packet priorities as well as curves for average throu..