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In this paper we prove that, except for at most one, all the ranks of a right infinite word which is recurrent and not ultimately periodic are the starting point of anω-division. Using this we give a very simple proof of Shirshov's theorem. We also extend it to not necessarily finite alphabets.

A long-standing question in porphyrin chemistry is why pyrrole monomers selectively form tetrapyrrolic macrocycles, whereas the corresponding tripyrrolic macrocycles are never observed. Calix[3]pyrrole, a tripyrrolic porphyrinogen-like macrocycle bearing three sp3-carbon linkages, is a missing link molecule that might hold the key to this enigma; however, it has remained elusive. Here we report the synthesis and strain-induced transformations of calix[3]pyrrole and its furan analogue, calix[3]furan. These macrocycles are readily accessed from cyclic oligoketones. Crystallographic and theoretical analyses reveal that these three-subunit systems possess the largest strain energy among known calix[n]-type macrocycles. The ring-strain triggers transformation of calix[3]pyrrole into first calix[6]pyrrole and then calix[4]pyrrole under porphyrin cyclization conditions. The present results help explain the absence of naturally occurring three-pyrrole macrocycles and the fact that they are not observed as products or intermediate during classic porphyrin syntheses.

The layered structures of graphite and related nanographene molecules play key roles in their physical and electronic functions. However, the stacking modes of negatively curved nanographenes remain unclear, owing to the lack of suitable nanographene molecules. Herein, we report the synthesis and one-dimensional supramolecular self-assembly of negatively curved nanographenes without any assembly-assisting substituents. This curved nanographene self-assembles in various organic solvents and acts as an efficient gelator. The formation of nanofibers was confirmed by microscopic measurements, and an unprecedented double-helix assembly by continuous π–π stacking was uncovered by three-dimensional electron crystallography. This work not only reports the discovery of an all-sp2-carbon supramolecular π-organogelator with negative curvature but also demonstrates the power of three-dimensional electron crystallography for the structural determination of submicrometer-sized molecular alignment.

The excretion rate of amitriptyline N- oxide was measured in healthy human subjects after the administration of a single oral dose of amitriptyline. The total amount of this metabolite excreted accounted for about 1% of the dose. It appears in the urine soon after administration of the parent compound but has practically disappeared by the 9th hr after treatment. The role of this metabolite in amitriptyline degradation in humans is discussed.

No relevant conflicts of interest to declare.

Bone marrow vascular niches sustain hematopoietic stem cells (HSCs) and are drastically remodeled in leukemia to support pathological functions. Acute myeloid leukemia (AML) cells produce angiogenic factors, which likely contribute to this remodeling, but anti-angiogenic therapies do not improve AML patient outcomes. Using intravital microscopy, we found that AML progression leads to differential remodeling of vasculature in central and endosteal bone marrow regions. Endosteal AML cells produce pro-inflammatory and anti-angiogenic cytokines and gradually degrade endosteal endothelium, stromal cells, and osteoblastic cells, whereas central marrow remains vascularized and splenic vascular niches expand. Remodeled endosteal regions have reduced capacity to support non-leukemic HSCs, correlating with loss of normal hematopoiesis. Preserving endosteal endothelium with the small molecule deferoxamine or a genetic approach rescues HSCs loss, promotes chemotherapeutic efficacy, and enhances survival. These findings suggest that preventing degradation of the endosteal vasculature may improve current paradigms for treating AML.

The article offers news briefs related to the real estate business in San Diego, California. The Associated Students of San Diego State University (SDSU) and Sullivan Solar Power hosted a ceremony for the installation of photovoltaic panels at the Aztec AquaPlex. The construction work for the Library/Learning Resource Centre at Miramar College started on November 16, 2009. The San Diego chapter of the Associated General Contractors of America Inc. presented awards for construction projects.

Abstract 4446

The article reports that on the construction of the Phase I residences at the home neighborhoods at the Foothills, a master-planned community in Carlsbad, California.

The article reports on the introduction of another phase of homes for sale at Carriage Run in Carmel Country Highlands by Pardee Homes in San Diego, California.

The article announces several appointments in California including Ric Mangum as regional managing principal in northern California of HMC Architects, Jim Chung as senior vice president as LJL Funding LLC, and Paul McCormick as vice president and general manager of La Costa Resort and Spa.

The article offers news briefs related to real estate in San Diego, California. CB Richard Ellis Inc. was named as the premier global brand in commercial estate in the Lipsey Co. survey. Construction manager Barnhart Balfour Beatty and Redondo Beach Unified School District announced the completion of its 4.8 million dollars renovations on the elementary district schools. Richard & Richard Construction Co. Inc. was awarded with a design/build construction contract of high-end portraint studio.

The article announces appointments of several executives in San Diego, California including Jim Lawson as president of Nationwide Direct Mortgage, Gangaram Singh as new associate dean of academic affairs of the College of Business Administration in San Diego State University and Blair King as city manager of Coronado.

The article offers new briefs in the U.S. related to sale and leases of properties. El Cajon Estates LLC has purchased a 4,438 square-foot of mixed-use property which consists of three commercial buildings and two houses. James Burnett purchased 6,000 square feet of office space in Solana Beach amounting to 2.7 million dollars. Lococo Sports Inc. leased 9,931 square feet of industrial space with a contract of five years and three months at 9177 Aero Drive in the amount of 502,825 dollars.

The article offers news briefs related to sales of real estate property in San Diego, California including the acquisition of 12,760 square-feet of office space at 10803 Thornmint Road by Douglas E. Barnhart worth 3.5 million, the buying of research and development facility by Bixby Land Co. worth 9.2 million dollars, and purchase of two-unit apartment by Benamel Development Inc. DBPP.

The article reports that financial consulting firm RoseRyan Inc. has restructured the company into two independent business enterprises, RoseRyan and Q5, to better serve its patrons in Southern California.

The article announces the appointments of several people from San Diego, California including Ian E. Bowman, who joined MTM Constructions Inc. as quality control manager, John W. Coates, who has been named parks and recreation director of the city of Carlsbad, California, and Nancy Lee, who has joined Sharp Coronado Hospital as the chief nursing officer.

Dasatinib (BMS-354825) is a multi-targeted kinase inhibitor of BCR-ABL and SRC with significant activity in patients with CML resistant or intolerant to front-line Imatinib (IM). However, the information so far available are to great extent limited to controlled clinical trials, which usually recruited patients with acceptable performance status, and no major organ dysfunction. Noteworthy, this fact, although essential for ethical reasons in clinical trials, may somehow determine an overestimation of the clinical benefit of new compounds. Thus, further studies based on non selected populations are indeed opportune.A total of 124 patients (61 male and 63 females) with CML resistant or intolerant to IM received Dasatinib as second line therapy outside from clinical trials. 91 patients had a resistant disease, 19 were intolerant to IM and 14 patients were both resistant and intolerant to IM. Median age at switching to Dasatinib was 56.5 years (range 21-82). 62/124 patients escalated IM before switching from 400 to 600 mg/day and 26/62 patients received an additional dose escalation from 600 to 800 mg/day. Median time on IM prior to the switch to Dasatinib was 36 months (range 2-99), whereas median time on IM after dose escalation was 9 months (range: 1-43).Dasatinib was given at 100 mg once daily in 54/124 patients (43%), at 70 mg twice daily in 43/124 patients (35%) and at 50 mg once daily in the remaining patients (22%).Response (hematologic, cytogenetic and molecular), toxicities according to NCI-CTC, discontinuation/dose reduction of Dasatinib, event-free survival (EFS) and overall survival (OS) were evaluated.With a median follow-up of 12 months, 94% of patients attained a complete hematological response (CHR), whereas 69% and 51% achieved a major (MCyR) or a complete cytogenetic response and 32% attained a major molecular response (MMR). Cumulative EFS and OS at 12 months were 91 and 93% respectively. These data are in line with those of clinical trials, but the population of the present study was not selected.The commonest grade III/IV adverse events were thrombocytopenia and neutropenia, occurring in around half of patients. Only 3% of the patients suffered from a grade III-IV pleural effusion or dyspnea.The achievement of CHR, MCyR, CCyR and MMR significantly influenced EFS (p=0.006; 0.04; 0.008 and 0.003 respectively) and OS (p=0.002; 0.02; 0.004 and 0.001 respectively) both in univariate and in multivariate analysis.Intriguingly, neither the dose nor the duration of prior IM affected the response to Dasatinib, neither before switching to Dasatinib (p= 0.9 and p=0.4) nor after it (p=0.4 and 0.7). Moreover, dose escalation to IM 600 or 800 mg/day did not influence negatively the subsequent response to Dasatinib (p=0.8). In addition, we did not observe any difference in the response rate (CHR, MCyR, CCyR, MMR) between patients who received prior IM for more than 3 years with respect to those patients who received it for less than 3 years (p=0.9).Regarding Dasatinib therapy, we observed a statistically significant better outcome in term of both DFS and OS for those patients receiving lower doses continuously without interruption (p=0.05 and p=0.04) with respect to patients who received higher doses but were forced to stop the treatment due to grade III-IV toxicity. This observation clearly indicate the necessity of administer dasatinib continuously to patients in order to override possible mechanisms of resistance due to the reduction of the plasma level of the drug.We confirm the safety and efficacy of Dasatinib as second line therapy for unselected patients with CML either resistant or refractory to IM even outside from clinical trials. Neither the dose nor the duration of Imatinib affects the response to Dasatinib. As well, patients receiving continuously Dasatinib, even at low doses, perform better. In conclusion, these findings show an increase possibility of cure for unselected patients resistant or intolerant to Imatinib submitted to second line therapy with Dasatinib in everyday clinical practice.No relevant conflicts of interest to declare.

The C6 synthon (X) for the production of leukotriene B4 (XI) is prepared according to the reaction scheme, starting with the chiral lactone (I).

Cellular immune responses to human immunodeficiency virus type 1 (HIV-1) antigens, microbial recall antigens, and CD3 monoclonal antibody were studied in HIV-1-infected asymptomatic patients in a phase II, double-blind trial of immunization with recombinant HIV-1 gp160 in or not in association with zidovudine. A vigorous and persistent lymphoproliferative response (LPR) to HIV-1 Env antigens was observed in vaccinated patients. Neither Env-specific lymphocyte cytotoxicity nor LPR to recall antigens was significantly influenced by gp160 administration. The induction of LPRs to HIV-1 envelope proteins did not show positive effects on the course of HIV-1 infection. Patients treated with zidovudine alone or in combination with the immunogen showed improvement of T lymphocyte responses and transient reduction of viremia. These results suggest that antiretroviral therapy is more beneficial than immunization with gp160 and should always be considered in association with future vaccination and immunotherapeutic interventions in HIV-1-infected subjects.