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We identified activin A receptor type I (ACVR1), a member of the TGF-β superfamily, as a factor favoring acute myeloid leukemia (AML) growth and a new potential therapeutic target. ACVR1is overexpressed in FLT3-mutated AML and inhibition of ACVR1expression sensitized AML cells to FLT3 inhibitors. We developed a novel ACVR1inhibitor, TP-0184, which selectively caused growth arrest in FLT3-mutated AML cell lines. Molecular docking and in vitro kinase assays revealed that TP-0184 binds to both ACVR1and FLT3 with high affinity and inhibits FLT3/ACVR1downstream signaling. Treatment with TP-0184 or in combination with BCL2 inhibitor, venetoclax dramatically inhibited leukemia growth in FLT3-mutated AML cell lines and patient-derived xenograft models in a dose-dependent manner. These findings suggest that ACVR1is a novel biomarker and plays a role in AML resistance to FLT3 inhibitors and that FLT3/ACVR1dual inhibitor TP-0184 is a novel potential therapeutic tool for AML with FLT3mutations.

Emerging GNSS applications in automobiles support regulation, security, safety, and financial transactions, as well as navigation, guidance, traffic information, and entertainment. The GNSS sub-systems and onboard applications must demonstrate robustness [...]

Suicide is a leading cause of death among service members and veterans. Among suicide methods, firearms are the most lethal and commonly used method among military populations. Limited research has compared risk factors for the various suicide methods. This study evaluated and compared risk factors for firearm versus non-firearm suicides using data from the Millennium Cohort Study, a large longitudinal military cohort.

Myelofibrosis (MF) is the deadliest form of myeloproliferative neoplasm (MPN). The JAK inhibitor Ruxolitinib can reduce constitutional symptoms but it does not substantially improve bone marrow fibrosis. Pim1 expression is significantly elevated in MPN/MF hematopoietic progenitors. Here, we show that genetic ablation of Pim1 blocked the development of myelofibrosis induced by Jak2V617F and MPLW515L. Pharmacologic inhibition of Pim1 with a second-generation Pim kinase inhibitor TP-3654 significantly reduced leukocytosis and splenomegaly, and attenuated bone marrow fibrosis in Jak2V617F and MPLW515L mouse models of MF. Combined treatment of TP-3654 and Ruxolitinib resulted in greater reduction of spleen size, normalization of blood leukocyte counts and abrogation of bone marrow fibrosis in murine models of MF. TP-3654 treatment also preferentially inhibited Jak2V617F mutant hematopoietic progenitors in mice. Mechanistically, we show that TP-3654 treatment significantly inhibits mTORC1, MYC and TGF-β signaling in Jak2V617F mutant hematopoietic cells and diminishes the expression of fibrotic markers in the bone marrow. Collectively, our results suggest that Pim1 plays an important role in the pathogenesis of MF, and inhibition of Pim1 with TP-3654 might be useful for treatment of MF.

ETS transcription factors from the ERG and ETV1/4/5 subfamilies are overexpressed in the majority of prostate cancer patients and contribute to disease progression. Here, we have developed two in vitro assays for the interaction of ETS transcription factors with DNA that are amenable to high-throughput screening. Using ETS1 as a model, we applied these assays to screen 110 compounds derived from a high-throughput virtual screen. We found that the use of lower-affinity DNA binding sequences, similar to those that ERG and ETV1 bind to in prostate cells, allowed for higher inhibition from many of these test compounds. Further pilot experiments demonstrated that the in vitro assays are robust for ERG, ETV1, and ETV5, three of the ETS transcription factors that are overexpressed in prostate cancer.

The epithelial-to-mesenchymal transition (EMT) is a highly conserved morphogenetic program essential for embryogenesis, regeneration and cancer metastasis. In cancer cells, EMT also triggers cellular reprogramming and chemoresistance, which underlie disease relapse and decreased survival. Hence, identifying compounds that block EMT is essential to prevent or eradicate disseminated tumor cells. Here, we establish a whole-animal-based EMT reporter in zebrafish for rapid drug screening, called Tg(snai1b:GFP), which labels epithelial cells undergoing EMT to produce sox10-positive neural crest (NC) cells. Time-lapse and lineage analysis of Tg(snai1b:GFP) embryos reveal that cranial NC cells delaminate from two regions: an early population delaminates adjacent to the neural plate, whereas a later population delaminates from within the dorsal neural tube. Treating Tg(snai1b:GFP) embryos with candidate small-molecule EMT-inhibiting compounds identified TP-0903, a multi-kinase inhibitor that blocked cranial NC cell delamination in both the lateral and medial populations. RNA sequencing (RNA-Seq) analysis and chemical rescue experiments show that TP-0903 acts through stimulating retinoic acid (RA) biosynthesis and RA-dependent transcription. These studies identify TP-0903 as a new therapeutic for activating RA in vivo and raise the possibility that RA-dependent inhibition of EMT contributes to its prior success in eliminating disseminated cancer cells.

SummaryIf you are ever faced with an oncoming truck, this paper could save your life. We investigate the optimal path that you should take from the middle of the road to the curb in order to avoid being hit by an oncoming truck. Although your instincts may tell you to run directly toward the curb, it turns out that this path, although the shortest, is not generally the safest.

An interview with Frank V. Cespedes of Harvard Business School in Cambridge, Massachusetts is presented. He mentions that significant value creation cannot happen without growth, so the failure to scale has managerial and investor, and social costs. He states that entrepreneurs will rely on unplanned business development opportunities without clarity on core customer characteristics. He says that customer selection affects profit margins and operating costs.

The article focuses on several brands that are used in business, marketing, and advertising worldwide. It focuses on brand marketing which is a concept that extends far beyond the marketing of brand name products. It cites several brands including Coca-Cola of Coca-Cola Co., Sony of Sony Corp. and Kodak of Eastman Kodak Co.

The article features 7th chief executive officer (CEO) of Yahoo! Inc. named Marissa Mayer. It says that Mayer was asked by recruiter Jim Citrin of Spencer Stuart to join the Yahoo! CEO search, wherein when she was asked regarding her plan for Yahoo! if she was appointed, her answer is to make their product more delightful and innovative. Moreover, it discusses the company focus of Yahoo!'s former CEOs such as media content, technology centered users, and profit enhancements.

The article focuses on the revival act of the zombie brands which are said to be much better alive. It says that zombie brands are those brands that are already non-existent and was only recalled by the buyers at present due to the impact of their television advertisements. It mentions the Pan American World Airways (Pan Am) which is the most respected brands in the era of Cold War, wherein the energy crisis in 1973 became the reason of its downturn and weakened financials.

The article reports on the mobile phones manufacturer Finland-based Nokia Corp. and Canada-based Research in Motion Ltd., the developer of Blackberry phones. It examines the Nokia's mistakes including the multi-billion costs of its research and development on the breakthroughs of mobile email, touch screens and wireless networks, failure to evolve on the operating system and the lost of focus on providing seamless Internet services. It also states that Blackberry also got lost in transmission.

The article focuses on chief executive officer (CEO) Tim Cook of Apple Inc. and his move of launching the iPad mini which outsell other iPads in the global markets. Cook has invited Apple's shareholders to patiently inform investors how Apple would grow financially in the absence of the late Steve Jobs. Along with chief financial officer (CFO) Peter Oppenheimer, Cook has disproven the belief of Jobs on the marketability of the smaller versions of iPads.

To further explore the oncogenic activity of Aurora A kinase while attempting to develop a useful mouse model for pancreatic cancer, Aurora A kinase was targeted to pancreatic duodenal homeobox gene-1 (Pdx-1)-positive cells.

Sakemura: Humanigen: Patents & Royalties. Cox:Humanigen: Patents & Royalties. Mouritsen:Sumitomo Dainippon Pharma Oncology, Inc.: Current Employment. Foulks:Tolero Pharmaceuticals, Inc.: Current Employment. Warner:Tolero Pharmaceuticals, Inc.: Current Employment. Ding:Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; DTRM: Research Funding; Astra Zeneca: Research Funding; Abbvie: Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Membership on an entity's Board of Directors or advisory committees; alexion: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees. Parikh:GlaxoSmithKline: Honoraria; Verastem Oncology: Honoraria; Genentech: Honoraria; Ascentage Pharma: Research Funding; AbbVie: Honoraria, Research Funding; Merck: Research Funding; TG Therapeutics: Research Funding; AstraZeneca: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; MorphoSys: Research Funding; Pharmacyclics: Honoraria, Research Funding. Kay:Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; MEI Pharma: Research Funding; Abbvie: Research Funding; Tolero Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squib: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Research Funding; Sunesis: Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Agios Pharma: Membership on an entity's Board of Directors or advisory committees; Cytomx: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Dava Oncology: Membership on an entity's Board of Directors or advisory committees; Juno Theraputics: Membership on an entity's Board of Directors or advisory committees. Kenderian:Mettaforge: Patents & Royalties; Lentigen: Research Funding; MorphoSys: Research Funding; Sunesis: Research Funding; Tolero: Research Funding; BMS: Research Funding; Juno: Research Funding; Gilead: Research Funding; Kite: Research Funding; Novartis: Patents & Royalties, Research Funding; Torque: Consultancy; Humanigen: Consultancy, Patents & Royalties, Research Funding.

Unrestrained cell division in cancer cells is dependent upon mitosis and its related processes. Therefore, a proven effective strategy in cancer treatment has been to interfere with the function of the mitotic spindle. Despite the success of these anti-mitotic agents, tubulin itself remains the only spindle-associated protein targeted by clinically approved agents. However, in recent years major advances have been achieved in targeting proteins that associate with tubulin and the mitotic spindle. Mitotic kinases such as the Aurora and Polo families are receiving significant attention due to their vital roles in assuring proper centrosome separation and chromosome segregation. Indeed, potent and selective inhibitors of these kinases have entered clinical trials. Similarly, the kinesins, particularly kinesin spindle protein (KSP), have emerged as potential therapeutic targets and inhibitors of KSP are currently under evaluation in the clinic. Although inhibitors have not been reported, mitotic checkpoint kinases (Mad2) and separase are additional potential targets for therapeutic intervention. Continued investigation of mechanisms regulating mitotic events will likely reveal additional proteins and pathways that could be potentially targeted and thereby provide more effective therapeutic options for cancer patients.

The National Association of State Boards of Geology (ASBOG) has administered approximately fifty-one hundred examinations for the licensing of geologists since the initial examination offering in 1992. The examination consists of a fundamentals portion and a practice portion. Each portion is 4 hours in length. The average passing rate across all administrations of the fundamentals examination is 58% and is 68% for the practice examination.For each examination, the subject matter tested is divided into nine areas or subject area domains based upon the results of the task analysis (survey of the practicing profession) that guides the examination blueprint. For the fundamentals examination, the distribution of questions among domains is: field methods and remote sensing (28% of 110 examination questions), mineralogy, petrology, petrography, and geochemistry (14%), sedimentology, stratigraphy, and paleontology (10%), geomorphology (6%), structural geology and tectonics (9%), geophysics and seismology (4%), hydrogeology (25%), engineering geology (3%), and mineral, petroleum, and energy resources (1%).The candidate success in each domain on the fundamentals examinations was determined for the last five administrations of the examinations during the period 2002–2003. The average percentage of questions answered correctly in each domain was: field methods and remote sensing (67% of questions answered correctly), mineralogy, petrology, petrography, and geochemistry (58%), sedimentology, stratigraphy, and paleontology (56%), geomorphology (63%), structural geology and tectonics (64%), geophysics and seismology (60%), hydrogeology (67%), engineering geology in combination with mineral, petroleum, and energy resources (67%).Candidates are doing poorer in those subject areas traditionally believed to be the fundamental subject areas of an undergraduate geology education (mineralogy, petrology, sedimentology, etc).

A semi-empirical model is developed to predict the maximum achievable strength of a nonwoven fabric and to identify and scale the factors affecting that strength. The scope and accuracy of the model are limited by the assumptions made during its development, but they are shown to be quite reasonable. The results of the model calculations suggest that the practical potential strength of an ideal point-bonded nonwoven fabric is three to four times higher than the average tensile strength of the best available spunbonded fabric samples, and about one-third lower than the average strength of fiber samples. Weak fiber-bond interfaces, areal density variations, fiber property variations, and fiber curl or combinations of these and others factors may limit fabric strength. Of these four factors, the first two are the key ones that limit spunbonded fabric observed strength. Knowledge of the potential strength and the factors limiting strength may enable manufacturers to improve nonwoven strength.

BackgroundFMS-like tyrosine kinase 3 (FLT3), a transmembrane receptor tyrosine kinase that is frequently mutated in AML, is associated with poor prognosis. Inhibitors of FLT3 internal tandem duplication (ITD) mutants and wild-type (WT) FLT3 have been studied, but their clinical usefulness is limited owing to treatment resistance. However, the molecular factors contributing to this resistance are unknown. We reported that AML cells induce osteogenic differentiation of bone marrow-derived mesenchymal stromal cells through the bone morphogenetic protein (BMP)-mediated signaling pathway, promoting leukemic growth. However, the effects of targeting BMP signaling in patients with FLT3-mutated AML are unexplored. Here, we hypothesized that the BMP type 1 receptor ALK2 is a key biomarker and a therapeutic target in AML patients with FLT3-ITD mutations and that the FLT3-ALK2 dual inhibitor TP-0184 inhibits leukemia growth.

Two techniques, liquid extrusion with water and optical microscopy on embedded carpet samples, are used to assess pore size distribution and location within the pile of a cut pile carpet manufactured from a polypropylene backing, crosslinked styrene butadiene rubber adhesive, and nylon pile. The results from the two techniques agree where the resulting data overlap and are complimentary in other pore size ranges. The carpet is able to absorb 6.1 times its weight in water. When the water content is reduced to roughly 50-60% by mechanical extraction, free water is probably situated in pores with an effective capillary diameter of up to 200 micrometers. The occupied pores are distributed throughout the carpet pile thickness and largely within the yams. This in formation may be used to develop an economical technique for drying carpets.

This article describes how The University of Iowa College of Nursing Instructional Design Services uses MS-DOS computer technology to create presentation graphics to support nursing education, research, scholarly productivity, and service. Hardware and software are described and examples are presented to illustrate the use of software to create alphanumeric, schematic, and freeform pictures. The authors stress that the use of computer-aided design and production does not eliminate the use of traditional principles of visual design, but rather necessitates their application.

A simple method for predicting the bending behavior of point bonded nonwoven fabrics has been developed. Proven theories found in the literature have been combined using elementary geometry and probability to produce a method to calculate the bend ing rigidity of nonwoven fabrics based on the properties of the constituent fibers and the fabric's construction. Pattern-bonded polypropylene and polyester fabrics, both spunbonded and bonded carded web, have been analyzed. The theoretical results agree with experimental values of bending stiffness.

This review is directed toward the study of the physiology and biochemistry of parasitic fungi on insects and stresses the usefulness and utility of these organisms from the standpoint of applied research and biotechnology. The review covers the principal contributions made by investigators toward elucidation of the infective mechanisms of the entomogenous fungi, and the various biochemical attributes of these organisms. The interplay of the various enzymes and associated biochemical substances which are involved in the infective process is discussed as well as the important studies of the peculiar physiology frequently associated with these microorganisms.

Selected species of the order Peronosporales, which are unable to epoxidize squalene and thus synthesize sterols, are able to metabolize exogenous cycloartenol to lanosterol and in some organisms to fucosterol, ergosterol, and cholesterol. Lanosterol was less effectively utilized but some ergosterol and cholesterol were yielded. Fucosterol was very efficiently metabolized by most species to ergosterol, Δ7-ergostenol, Δ5-ergostenol, cholestanol, and cholesterol. Several unknown sterols were observed in most trials. These data suggest a vestigial sterol synthetic pathway derived from cycloartenol, followed by possible isomerization to lanosterol and then to other sterols.

The article assesses the effects, direct and indirect, intended and unintended, of the 1993 national electoral reform and the results of the 1994 general elections in Italy. It shows that the new system is not an eccentric compromise, and that those who forecast either its unworkability or its evil consequences were mistaken. However, in evaluating the success of the reform with respect to the ambitions which were held for it, it concludes that the reform was a predictable failure. The article then explores the role played by the electoral reform in the unexpected electoral success of the Polo della Libertà, the emergence of Forza Italia, and the ability of Berlusconi to strike a compromise with two such different parties as La Lega and the AN.

An interview with S. Premkumar, chief executive officer (CEO) at India-based hospital chain Apollo Hospitals Enterprise Ltd., is presented. Premkumar discusses working in the technology company HCL Technologies Ltd. for 29 years, his plan to expand in Trichy and Balangore, and how the hospital management keeps the quality of managed services. He also emphasizes the need for the healthcare industry to be recognised as a sector just like a software.

Presents the short story 'Nietzsche Would Have Been a Great Dart Player.'

IMPORTANCE: The definition of posttraumatic stress disorder (PTSD) changed markedly between the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and DSM-5, creating challenges for studies and in medical settings spanning this transition. OBJECTIVE: To evaluate the ability to compare and assess PTSD, based on DSM-IV and DSM-5 criteria, using PTSD Checklists (PCLs). DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study was conducted with survey data collected in October 2019, from the Millennium Cohort Study, a population-based US military cohort study. The population for the present study was restricted to a subset of initial web responders of the 2019 survey cycle, randomly assigned to 1 of 4 survey groups. EXPOSURES: Each group received the DSM-IV and DSM-5 PCL (PCL–Civilian [PCL-C] version and PCL for DSM-5 [PCL-5]). PCL instruments were counterbalanced to control for order effects. MAIN OUTCOMES AND MEASURES: Survey data were used to assess PTSD (using the PCL-C and PCL-5), major depressive disorder (using the Patient Health Questionnaire), generalized anxiety (using the Generalized Anxiety Disorder scale), and problem drinking (using the Patient Health Questionnaire). Demographic and military characteristics included age, sex, race/ethnicity, marital status, education, service branch, pay grade, enrollment panel, and military service status. RESULTS: Among the 1921 participants (mean [SD] age, 50.1 [12.5] years), 1358 (70.7%) were men, 1638 (85.3%) were non-Hispanic White individuals, 1440 (75.0%) were married, and 1190 (61.9%) had at least a bachelor’s degree; 295 (15.4%) had probable PTSD according to DSM-IV criteria with PCL-C compared with 286 (14.9%) using DSM-5 criteria with PCL-5 (??=?0.77). There was substantial agreement between PCLs for probable PTSD based on DSM-IV criteria (295 [15.4%] with PCL-C; 316 [16.4%] with PCL-5; ??=?0.80) and DSM-5 criteria (286 [14.9%] with PCL-5; 258 [13.4%] with PCL-C; ??=?0.77). Estimated PTSD sum scores showed excellent agreement with observed scores. Using an established crosswalk, PCL-5 sum scores estimated with the PCL-C were similar to observed PCL-5 scores. Of the 17 corresponding items between the 2 instruments, 16 had substantial agreement. Appending 2 additional PCL-C items to the PCL-5 did not significantly alter estimates. The PCL-C and PCL-5 had nearly identical associations with comorbid conditions. CONCLUSIONS AND RELEVANCE: The findings of this diagnostic study suggest that PTSD can be successfully assessed and compared over time with either PCL instrument in veteran and military populations.

The article discusses the six-level purpose-driven model of leadership. It explains that the sociopath level means that the leader serves no one and exhibits abnormally low empathy while the chameleon leader is the one that strive to please may people. It notes that leadership style is composed of the different types with one dominant type and leadership development programs must be designed to help leaders find their own path.

The article reports on a study by professor Sunil Gupta and colleagues on the influence of peers for purchases in a social networking sites like Facebook, Myspace, and Google. The findings indicate that the business viability of the online social networks remain in question despite the cultural and social revolution. However, many of the online social sites are following Google in generating revenues from advertising.

In an interim application, Pumfrey J has held that serving a notice of experiments in the course of patent litigation is likely to amount to a waiver of any privilege that subsists in respect of any preliminary or work-up investigations conducted in the course of devising those experiments.

Warner: Tolero Pharmaceuticals: Employment. Bearss:Tolero Pharmaceuticals: Employment. Kay:Agios: Other: DSMB; Infinity Pharmaceuticals: Other: DSMB; Celgene: Other: Data Safety Monitoring Board; MorphoSys: Other: Data Safety Monitoring Board.

Introduction:Bone marrow stromal cells (BMSCs), a major component of CLL microenvironment influences CLL B-cell survival. We have utilized an in vitroBMSC model system and found unique alterations in CLL B-cells with short term BMSC co-culture that point to previously unidentified biologic changes in the CLL B-cells that may influence CLL B-cell signaling and their drug resistance.

Kim: Tolero Pharmaceuticals, Inc: Employment. Whatcott:Tolero Pharmaceuticals, Inc: Employment. Siddiqui-Jain:Tolero Pharmaceuticals, Inc: Employment. Anthony:Tolero Pharmaceuticals, Inc: Employment. Bearss:Tolero Pharmaceuticals, Inc: Employment. Warner:Tolero Pharmaceuticals: Employment.

Introduction

Despite the remarkable outcomes and recent FDA approval of CD19 directed chimeric antigen receptor T (CART19) cell therapy in B cell malignancies, the durable responses in diffuse large B cell lymphoma are less than 40% and CART activity in chronic lymphocytic leukemia (CLL) is further limited. This is thought to be related to loss of CART persistence, poor trafficking to lymph nodes and inhibition by the leukemic microenvironment. Therefore, strategies to enhance CART cell function to overcome these limitations are needed. Recent studies have shown that abnormal expression of the receptor tyrosine kinase (RTK) AXL is associated with poor prognosis in human cancers. AXL signaling is associated with tumor proliferation, survival, metastasis, and drug resistance. Inhibition of AXL RTK with TP-0903, a high affinity AXL inhibitor has been found to induce robust apoptosis of CLL B cells. Based on the significant modulation of T cell functions observed with BTK inhibitor, we examined the role of AXL RTK inhibition with TP-0903 on T cell function in CLL and other B cell malignancies.

Whatcott: Tolero Pharmaceuticals, Inc: Employment. Warner:Tolero Pharmaceuticals: Employment.

Tyagi: Tolero Pharmaceuticals, Inc: Employment. Whatcott:Tolero Pharmaceuticals, Inc: Employment. Foulks:Tolero Pharmaceuticals, Inc: Employment. Siddiqui-Jain:Tolero Pharmaceuticals, Inc: Employment. Bearss:Tolero Pharmaceuticals, Inc: Employment. Warner:Tolero Pharmaceuticals: Employment.

Peterson: Tolero Pharmaceuticals, Inc.: Employment. K: Tolero Pharmaceuticals, Inc.: Employment. Whatcott: Tolero Pharmaceuticals, Inc.: Employment. Siddiqui-Jain: Tolero Pharmaceuticals, Inc.: Employment. Weitman: Tolero Pharmaceuticals, Inc.: Employment. Bearss: Tolero Pharmaceuticals, Inc.: Employment. Warner: Tolero Pharmaceuticals, Inc.: Employment.

Abnormal expression of receptor tyrosine kinase Axl has been associated with poor prognosis in different cancers including acute myeloid leukemia (AML) and has been linked to drug resistance against chemotherapy as well as targeted therapies including FLT3 inhibitors (Park et al. Leukemia2015). With its role in tumorigenesis, Axl has been actively pursued as a potential therapeutic target with small molecule inhibitors. TP-0903, a type I inhibitor, was designed in silico on an Axl scaffold that does not clash with the Axl gatekeeper residue, Leu620 (Mollard et al. ACS Med Chem Lett2011). Since Axl inhibitors are known to also interact with FLT3 (Myers et al. J Med Chem2016), we evaluated the hypothesis that TP-0903 demonstrates preclinical activity against FLT3-ITD+AML through a mechanism that potentially involves both Axl and FLT3 inhibition.

Parikh: Pharmacyclics: Honoraria, Research Funding. Shanafelt:Pharmacyclics: Research Funding; Janssen: Research Funding; Genentech: Research Funding; GlaxoSmithKline: Research Funding; Celgene: Research Funding; Cephalon: Research Funding; Hospira: Research Funding. Warner:Tolero Pharmaceuticals: Employment, Equity Ownership, Patents & Royalties. Bearss:Tolero Pharmaceuticals: Employment, Equity Ownership, Patents & Royalties. Kay:Pharmacyclics: Research Funding; Tolero Pharmaceuticals: Research Funding; Acerta: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Morpho-Sys: Membership on an entity's Board of Directors or advisory committees; Infinity Pharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.