Butterfly Tachyons in Vacuum String Field Theory

We use geometrical conformal field theory methods to investigate tachyon fluctuations about the butterfly projector state in Vacuum String Field Theory. We find that the on-shell condition for the tachyon field is equivalent to the requirement that the quadratic term in the string-field action vanish on shell. This further motivates the interpretation of the butterfly state as a D-brane. We begin a calculation of the tension of the butterfly, and conjecture that this will match the case of the sliver and further strengthen this interpretation.Comment: 14 pages, 6 figures, revte

Development of machine learning classifiers to predict compound activity on prostate cancer cell lines

Prostate cancer is the most common type of cancer in men. The disease presents good survival rates if treated at the early stages. However, the evolution of the disease in its most aggressive variant remains without effective therapeutic answers. Therefore, the identification of novel effective therapeutics is urgently needed. On these premises, we developed a series of machine learning models, based on compounds with reported highly homogeneous cell-based antiproliferative assay data, able to predict the activity of ligands towards the PC-3 and DU-145 prostate cancer cell lines. The data employed in the development of the computational models was finely-tuned according to a series of thresholds for the classification of active/inactive compounds, to the number of features to be implemented, and by using 10 different machine learning algorithms. Models' evaluation allowed us to identify the best combination of activity thresholds and ML algorithms for the classification of active compounds, achieving prediction performances with MCC values above 0.60 for PC-3 and DU-145 cells. Moreover, in silico models based on the combination of PC-3 and DU-145 data were also developed, demonstrating excellent precision performances. Finally, an analysis of the activity annotations reported for the ligands in the curated datasets were conducted, suggesting associations between cellular activity and biological targets that might be explored in the future for the design of more effective prostate cancer antiproliferative agents

Hydroxamic Acid Derivatives: From Synthetic Strategies to Medicinal Chemistry Applications

Since the approval of three hydroxamic acid-based HDAC inhibitors as anticancer drugs, such functional groups acquired even more notoriety in synthetic medicinal chemistry. The ability of hydroxamic acids (HAs) to chelate metal ions makes this moiety an attractive metal binding group-in particular, Fe(III) and Zn(II)-so that HA derivatives find wide applications as metalloenzymes inhibitors. In this minireview, we will discuss the most relevant features concerning hydroxamic acid derivatives. In a first instance, the physicochemical characteristics of HAs will be summarized; then, an exhaustive description of the most relevant methods for the introduction of such moiety into organic substrates and an overview of their uses in medicinal chemistry will be presented

Star Algebra Projectors

Surface states are open string field configurations which arise from Riemann surfaces with a boundary and form a subalgebra of the star algebra. We find that a general class of star algebra projectors arise from surface states where the open string midpoint reaches the boundary of the surface. The projector property of the state and the split nature of its wave-functional arise because of a nontrivial feature of conformal maps of nearly degenerate surfaces. Moreover, all such projectors are invariant under constant and opposite translations of their half-strings. We show that the half-string states associated to these projectors are themselves surface states. In addition to the sliver, we identify other interesting projectors. These include a butterfly state, which is the tensor product of half-string vacua, and a nothing state, where the Riemann surface collapses.Comment: 65 pages, 23 figures, LaTe

Vacuum String Field Theory ancestors of the GMS solitons

We define a sequence of VSFT D-branes whose low energy limit leads exactly to a corresponding sequence of GMS solitons. The D-branes are defined by acting on a fixed VSFT lump with operators defined by means of Laguerre polynomials whose argument is quadratic in the string creation operators. The states obtained in this way form an algebra under the SFT star product, which is isomorphic to a corresponding algebra of GMS solitons under the Moyal product. In order to obtain a regularized field theory limit we embed the theory in a constant background B field.Comment: 1+16 pages; v2: typos corrected; v3: two appendices added, final versio

Discovery of potent pyrrolo-pyrimidine and purine HDAC inhibitors for the treatment of advanced prostate cancer

The development of drugs for the treatment of advanced prostate cancer (PCA) remains a challenging task. In this study we have designed, synthesized and tested twenty-nine novel HDAC inhibitors based on three different zinc binding groups (trifluoromethyloxadiazole, hydroxamic acid, and 2-mercaptoacetamide). These warheads were conveniently tethered to variously substituted phenyl linkers and decorated with differently substituted pyrrolo-pyrimidine and purine cap groups. Remarkably, most of the compounds showed nanomolar inhibitory activity against HDAC6. To provide structural insights into the Structure-Activity Relationships (SAR) of the investigated compounds, docking of representative inhibitors and molecular dynamics of HDAC6-inhibitor complexes were performed. Compounds of the trifluoromethyloxadiazole and hydroxamic acid series exhibited promising anti-proliferative activities, HDAC6 targeting in PCA cells, and in vitro tumor selectivity. Representative compounds of the two series were tested for solubility, cell permeability and metabolic stability, demonstrating favorable in vitro drug-like properties. The more interesting compounds were subjected to migration assays, which revealed that compound 13 and, to a lesser extent, compound 15 inhibited the invasive behaviour of androgen-sensitive and –insensitive advanced prostate cancer cells. Compound 13 was profiled against all HDACs and found to inhibit all members of class II HDACs (except for HDAC10) and to be selective with respect to class I and class IV HDACs. Overall, compound 13 combines potent inhibitory activity and class II selectivity with favorable drug-like properties, an excellent anti-proliferative activity and marked anti-migration properties on PCA cells, making it an excellent lead candidate for further optimization

Reference Renal Artery Diameter Is a Stronger Predictor of Contrast-Induced Nephropathy than Chronic Kidney Disease in Patients with High Cardiovascular Risk

Introduction: The incidence of contrast-induced nephropathy (CIN) increases in high cardiovascular risk patients. Chronic kidney disease (CKD) is a known risk factor for CIN development. In a previous report, we demonstrated that the mean reference renal artery diameter (RVD) is an important determinant of CKD in patients undergoing coronary angiography for ischemic heart disease. However, RVD was never tested as a predictor of CIN. Aim: To look at the predictors of CIN. Methods: A total of 218 consecutive patients undergoing coronary and renal angiography were enrolled from the cohort of the RAS-CAD study (NCT 01173666). CIN was defined as a relative increase in baseline serum creatinine ≧25% within 1 week of contrast administration. Results: The incidence of CIN was 22%. In a fully adjusted model, contrast medium dose (20 ml increase, OR 1.12, 95% CI 1.06–1.19, p 2 increase, OR 0.59, 95% CI 0.41–0.86, p Conclusions: In patients undergoing coronary angiography for ischemic heart disease, RVD is a stronger predictor of CIN than CKD