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Aspergillus fumigatus is the most prevalent airborne filamentous fungal pathogen in humans, causing severe and often fatal invasive infections in immunocompromised patients. Currently available antifungal drugs to treat invasive aspergillosis have limited modes of action, and few are safe and effective. To identify and prioritize antifungal drug targets, we have developed a conditional promoter replacement (CPR) strategy using the nitrogen-regulated A. fumigatus NiiA promoter (pNiiA). The gene essentiality for 35 A. fumigatus genes was directly demonstrated by this pNiiA-CPR strategy from a set of 54 genes representing broad biological functions whose orthologs are confirmed to be essential for growth in Candida albicans and Saccharomyces cerevisiae. Extending this approach, we show that the ERG11 gene family (ERG11A and ERG11B) is essential in A. fumigatus despite neither member being essential individually. In addition, we demonstrate the pNiiA-CPR strategy is suitable for in vivo phenotypic analyses, as a number of conditional mutants, including an ERG11 double mutant (erg11BDelta, pNiiA-ERG11A), failed to establish a terminal infection in an immunocompromised mouse model of systemic aspergillosis. Collectively, the pNiiA-CPR strategy enables a rapid and reliable means to directly identify, phenotypically characterize, and facilitate target-based whole cell assays to screen A. fumigatus essential genes for cognate antifungal inhibitors.

The structure and dynamics of a large segment of Ste2p, the G-protein-coupled α-factor receptor from yeast, were studied in dodecylphosphocholine (DPC) micelles using solution NMR spectroscopy. We investigated the 73-residue peptide EL3-TM7-CT40 consisting of the third extracellular loop 3 (EL3), the seventh transmembrane helix (TM7), and 40 residues from the cytosolic C-terminal domain (CT40). The structure reveals the presence of an α-helix in the segment encompassing residues 10–30, which is perturbed around the internal Pro-24 residue. Root mean-square deviation values of individually superimposed helical segments 10–20 and 25–30 were 0.91±0.33Å and 0.76±0.37Å, respectively. 15N-relaxation and residual dipolar coupling data support a rather stable fold for the TM7 part of EL3-TM7-CT40, whereas the EL3 and CT40 segments are more flexible. Spin-label data indicate that the TM7 helix integrates into DPC micelles but is flexible around the internal Pro-24 site, exposing residues 22–26 to solution and reveal a second site of interaction with the micelle within a region comprising residues 43–58, which forms part of a less well-defined nascent helix. These findings are discussed in light of previous studies in organic-aqueous solvent systems.

This article \"Predicting Future War\" by Robert Johnson provides a compelling vision for the types of challenges future forces will face and the military implications of those challenges. Although \"tours of the future\" like those found in the article are important, the author believe it is critical the military step back and understand the cultural reflexes and biases people must cultivate order to address those emerging challenges. Straight-line analysis of trends and their implications may drive them to solutions that are wrong or incomplete. Instead, the author would advocate a broader view so the force as a whole can come to terms with these challenges in a coherent way. Critically, however, the author suggest people must understand how -- in a world most agree is (as the Chairman of the Joint Chiefs of Staff is fond of saying) \"complex, uncertain, and increasingly dangerous\", they cultivate the mental agility to prepare where they can, and adjust to unanticipated conditions when they must.

Several months ago, a panel of the U.S. Court of Appeals for the Federal Circuit held in Trimble Inc. v. PerDiemCo LLC that patent owners can, under certain circumstances, be subject to personal jurisdiction merely by sending communications to an accused infringer within the forum. The implications of Trimble warrant careful consideration by patent owners and accused infringers alike, as many patent professionals have recognized the nuanced consideration that may be involved in patent litigants' preferred choice of forum.6 FEDERAL CIRCUIT FINDS PATENT LETTERS INSUFFICIENT TO JUSTIFY PERSONAL JURISDICTION IN RED WING In Red Wing, Hockerson-Halberstadt, Inc. (\"HHI\"), a non-practicing entity located in New Mexico and incorporated in Louisiana, sent a cease-and-desist letter to Minnesota-based Red Wing Shoe alleging that Red Wing Shoe's products infringed HHI's patent.7 This letter also included an offer to license the allegedly infringed patent to Red Wing Shoe, and noted that HHI had previously negotiated, and was presently negotiating, a patent license with numerous other companies.8 Subsequent to that initial communication, Red Wing Shoe and HHI sent a total of five communications9 over the course of nearly nine months relating to HHI's claims of patent infringement.10 Red Wing Shoe then filed a declaratory judgment action against HHI in Minnesota district court alleging non-infringement, invalidity, and unenforceability of the patent it stood accused of infringing.11 HHI moved to dismiss the case for lack of personal jurisdiction, arguing that it lacked sufficient contacts in the forum, and the district court agreed.12 On appeal, Red Wing Shoe argued that the three letters sent by HHI, inter alia,13 gave the trial court jurisdiction over HHI under principles of minimum contacts. THE FEDERAL CIRCUIT FURTHER NARROWS ITS INTERPRETATION OF RED WING IN TRIMBLE In Trimble, the U.S. District Court for the Northern District of California dismissed an alleged infringer's (Trimble) declaratory judgment action against a patent holder (PerDiemCo), finding that \"exercising specific jurisdiction over [the patent owner] would be constitutionally unreasonable\" in view of Red Wing despite the patent owner having sufficient contacts with the forum.19 The Federal Circuit reversed the lower court's decision, holding that Red Wing did not preclude personal jurisdiction on the facts as presented.20 In rendering its decision, the Federal Circuit explained that three important Supreme Court developments had occurred since Red Wing, all of which served to clarify the scope of that case.21 First, the court recognized that the Supreme Court had, in post-Red Wing cases, repeatedly rejected special rules for patent litigation, and has made clear that patent law is governed by the same procedural rules as other areas of civil litigation in the absence of legislation to the contrary.22 Second, the court noted that, post Red Wing, the Supreme Court held that communications, depending on their nature and scope, can - by themselves - create personal jurisdiction in a foreign forum.23 Lastly, citing the Supreme Court's recent decision in Ford Motor Co. v. Mont. '\"30 Additionally, the court found the exercise of personal jurisdiction over the patent owner to be reasonable in view of the fact that the patent owner failed to set forth any compelling reason why exercising jurisdiction over the patent owner would offend the principles of fair play and substantial justice.31 TAKEAWAYS FROM TRIMBLE In view of the Trimble case, it is likely that patent owners engaged in pre-suit communications will now be faced with the difficult decision of whether to sue in their choice of forum or be sued in one where they have a limited chance of success. [...]although a patent owner can certainly challenge the ability of the case to proceed in an unfavorable forum, he may face an uphill battle in overcoming the first-to-file rule.32 As a practice point, patent owners should be wary about communicating with alleged infringers before filing suit, as communicating too much too often could create personal jurisdiction in an undesirable forum. Several months ago, a panel of the U.S. Court of Appeals for the Federal Circuit held in Trimble Inc. v. PerDiemCo LLC, that patent owners can, under certain circumstances, be subject to personal jurisdiction merely by sending communications to an accused infringer within the forum.

Over the past year or so, various lawmakers have floated a flurry of patent reform proposals aimed at curbing patent litigation abuse by so-called patent trolls, or nonpracticing patent enforcement entities. The grounds well of support for antitroll legislation motivated the House Judiciary Committee to recommend H.R. 3309, dubbed \"the Innovation Act\" to the full House of Representatives on November 20, 2013. In his article, Jeff Becker, an attorney in the Dallas office of Baker Botts LLP, discusses key provisions of the bill and analyzes how they would alter current patent jurisprudence if enacted in current form. [PUBLICATION ABSTRACT]

[...]the language of the statute has remained the same since it was first enacted in 1952.2 However, over the years courts have moved the line demarcating patentable and unpatentable concepts, especially in the technology and software fields.3 Most recently, in Alice Corp. Pty. v. CLS Bank Int'l, the U.S. Supreme Court applied a two-part framework to analyze patent eligibility for software claims, instructing courts to first ask if the claims are directed to an abstract idea.4 If the claims are directed to an abstract idea, courts must then decide whether the claims contain an inventive concept or something more that would make the claims patent eligible.5 Since its inception, the two-step patent-eligibility framework from Alice has come under scrutiny because of difficulty in uniformly applying the standard, as well as its alleged bar on important innovations. [...]various witnesses testified that under the current patent-eligibility standards, the amount of money spent by innovators on litigation against \"patent trolls\" or \"non-practicing entities\" has significantly decreased, and these savings have been used to fund additional innovation. [...]companies with significant patent exposure may consider entering comments in the record to have their voice heard on the matter. [...]because there could be a surge of patent applications filed once the legislation takes effect, companies may wish to file sooner rather than later to beat a potential influx of applications and to maintain the advantage under the first-to-file system.

Different applications have different requirements, so to ensure future flexibility, look for a system that can provide 99%+ data reliability inside the update rate availability window 4. When selecting battery-powered wireless products, determine the required reporting rate and then ask for the battery lifetime at that rate. To protect the wireless technology investment, wireless networks must support today's applications as well as future protocols.