Cryptococcus neoformans causes life-threatening meningoencephalitis in humans, but its overall biological and pathogenic regulatory circuits remain elusive, particularly due to the presence of an evolutionarily divergent set of transcription factors (TFs). Here, we report the construction of a high-quality library of 322 signature-tagged gene-deletion strains for 155 putative TF genes previously predicted using the DNA-binding domain TF database, and examine their in vitro and in vivo phenotypic traits under 32 distinct growth conditions. At least one phenotypic trait is exhibited by 145 out of 155 TF mutants (93%) and ∼85% of them (132/155) are functionally characterized for the first time in this study. The genotypic and phenotypic data for each TF are available in the C. neoformans TF phenome database (http://tf.cryptococcus.org). In conclusion, our phenome-based functional analysis of the C. neoformans TF mutant library provides key insights into transcriptional networks of basidiomycetous fungi and human fungal pathogens.

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Abstract-The current framework of network utility maximization for rate allocation and its price-based algorithms assumes that each link provides a fixed-size transmission "pipe" and each user's utility is a function of transmission rate only. These assumptions break down in many practical systems, where, by adapting the physical layer channel coding or transmission diversity, different tradeoffs between rate and reliability can be achieved. In network utility maximization problems formulated in this paper, the utility for each user depends on both transmission rate and signal quality, with an intrinsic tradeoff between the two. Each link may also provide a higher (or lower) rate on the transmission "pipes" by allowing a higher (or lower) decoding error probability. Despite nonseparability and nonconvexity of these optimization problems, we propose new price-based distributed algorithms and prove their convergence to the globally optimal rate-reliability tradeoff under readily-verifiable sufficient conditions. We first consider networks in which the rate-reliability tradeoff is controlled by adapting channel code rates in each link's physical-layer error correction codes, and propose two distributed algorithms based on pricing, which respectively implement the "integrated" and "differentiated" policies of dynamic rate-reliability adjustment. In contrast to the classical price-based rate control algorithms, in our algorithms, each user provides an offered price for its own reliability to the network, while the network provides congestion prices to users. The proposed algorithms converge to a tradeoff point between rate and reliability, which we prove to be a globally optimal one for channel codes with sufficiently large coding length and utilities whose curvatures are sufficiently negative. Under these conditions, the proposed algorithms can thus generate the Pareto optimal tradeoff curves between rate and reliability for all the users. In addition, the distributed algorithms and convergence proofs are extended for wireless multiple-inpit-multiple-output multihop networks, in which diversity and multiplexing gains of each link are controlled to achieve the optimal rate-reliability tradeoff. Numerical examples confirm that there can be significant enhancement of the network utility by distributively trading-off rate and reliability, even when only some of the links can implement dynamic reliability. IndexTerms-Mathematical programming/optimization, network control by pricing, network utility maximization, physical-layer channel coding, rate allocation.

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In this paper, we jointly consider the resource allocation and base-station assignment problems for the downlink in CDMA networks that could carry heterogeneous data services. We first study a joint power and rate allocation problem that attempts to maximize the expected throughput of the system. This problem is inherently difficult because it is in fact a nonconvex optimization problem. To solve this problem, we develop a distributed algorithm based on dynamic pricing. This algorithm provides a power and rate allocation that is asymptotically optimal in the number of mobiles. We also study the effect of various factors on the development of efficient resource allocation strategies. Finally, using the outcome of the power and rate allocation algorithm, we develop a pricing-based base-station assignment algorithm that results in an overall joint resource allocation and base-station assignment. In this algorithm, a base-station is assigned to each mobile taking into account the congestion level of the base-station as well as the transmission environment of the mobile.Index Terms-Base-station assignment, CDMA networks, nonconvex optimization, power and rate allocation, pricing.

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Cloning by somatic cell nuclear transfer has been successfully achieved by both fusing of a donor cell with and injecting an isolated donor cell nucleus into an enucleated oocyte. However, each of the above methods involves extended manipulation of either the oocytes (fusion) or the donor cells (nucleus isolation). Additionally, cloning efficiency can be reduced by low fusion rate of the cell fusion method, and specialized micromanipulation equipment and exacting nucleus isolation techniques are required for the nucleus injection method. Here we report a whole-cell injection technique for nuclear transfer in pigs and the production of cloned piglets with comparable, if not higher, efficiency than the other two nuclear transfer procedures. First, we tested the feasibility of this technique with three types of frequently used donor cells (cumulus, mural granulosa, and fibroblasts) and obtained the optimal nuclear reprogramming conditions for these cells. We further improved our protocol by avoiding ultraviolet exposure during enucleation and achieved a 37% blastocyst rate. We then conducted whole-cell injection using skin fibroblasts from the ear of a sow transgenic for two genes, the porcine lactoferrin and the human factor IX, and produced four live-born cloned transgenic piglets from three recipients. The present study demonstrated the applicability of producing normal, cloned piglets by the simple and less labor-intensive whole-cell intracytoplasmic injection.