Security framework for smart cyber infrastructure

Cluster Computing - The rapid deployment of the Internet of Things (IoT) devices have led to the development of innovative information services, unavailable a few years ago. To provide these...     

In vitro modulation of natural killer cell activity in non-Hodgkin's lymphoma patients after therapy

Summary The depressed natural killer (NK) activity, antibody-dependent cellular cytotoxicity (ADCC) and NK cytotoxic factor cytotoxicity in untreated non-Hodgkin's lymphoma patients were found to be elevated after chemotherapy. In vitro treatment of the effector NK cells with interferon could augment the NK activity in normal subjects and treated patients to a comparable degree. Chemotherapy mainly affected the post-binding events in the NK cytotoxic process by causing an increase in the active killing potential of the NK cells. This study provides a better understanding of changes in the NK cytotoxic mechanism in non-Hodgkin's lymphoma patients and the role of interferon in this process.B. A. Mehta is a recipient of the Lady Tata Memorial Trust, India, Senior Scholarship     

An explainable and efficient deep learning framework for video anomaly detection

Cluster Computing - Deep learning-based video anomaly detection methods have drawn significant attention in the past few years due to their superior performance. However, almost all the leading...     

Hx-amides: DNA sequence recognition by the fluorescent Hx (p-anisylbenzimidazole)•pyrrole and Hx•imidazole pairings

Hx-amides are fluorescent hybrids of imidazole (I)- and pyrrole (P)-containing polyamides and Hoechst 33258, and they bind in the minor groove of specific DNA sequences. Synthesis and DNA binding studies of HxII (5) complete our studies on the first set of Hx-amides: Hx–I/P–I/P. HxPP (2), HxIP (3) and HxPI (4) were reported earlier. Results from DNase I footprinting, biosensor-SPR, CD and ΔT_M studies showed that Hx-amides interacted with DNA via the anti-parallel and stacked, side-by-side motif. Hx was found to mimic the DNA recognition properties of two consecutive pyrrole units (PP) in polyamides. Accordingly, the stacked Hx/PP pairing binds preferentially to two consecutive AT base pairs, A/T–A/T; Hx/IP prefers C–A/T; Hx/PI prefers A/T–C; and Hx/II prefers C–C. The results also showed that Hx-amides bound their cognate sequence at a higher affinity than their formamido-triamide counterparts.     

Synthesis and DNA binding properties of 1-(3-aminopropyl)-imidazole-containing triamide f-Im(∗)PyIm: A novel diamino polyamide designed to target 5'-ACGCGT-3'

A novel diamino/dicationic polyamide f-Im(?)PyIm (5) that contains an orthogonally positioned aminopropyl chain on an imidazole (Im(?)) moiety was designed to target 5'-ACGCGT-3'. The DNA binding properties of the diamino polyamide 5, determined by CD, ΔT(M), DNase I footprinting, SPR, and ITC studies, were compared with those of its monoamino/monocationic counterpart f-ImPyIm (1) and its diamino/dicationic isomer f-ImPy(?)Im (2), which has the aminopropyl group attached to the central pyrrole unit (Py(?)). The results gave evidence for the minor groove binding and selectivity of polyamide 5 for the cognate sequence 5'-ACGCGT-3', and with strong affinity (K(eq)=2.3×10(7)M(-1)). However, the binding affinities varied according to the order: f-ImPy(?)Im (2)>f-ImPyIm (1)?f-Im(?)PyIm (5) confirming that the second amino group can improve affinity, but its position within the polyamide can affect affinity.     

Design and synthesis of novel enhanced water soluble hydroxyethyl analogs of combretastatin A-4

Thirteen hydroxyethyl- analogs of combretastatin A-4 (CA-4) that contain the 1-(1′-hydroxyethyl)-1-(3″,4″,5″-trimethoxyphenyl)-2-(substituted phenyl)ethene framework were synthesized. Molecular modeling studies at the DFT level showed that compound 3j adopts a ‘twisted’ conformation mimicking CA-4. The cytotoxicity of the novel compounds against the growth of murine B16 melanoma and L1210 lymphoma cells in culture was measured using an MTT assay. Three analogs 3f, 3h, and 3j were active. Of these, 3j, which has the same substituents as CA-4 and IC₅₀ values of 16.1 and 4.1 μM against B16 and L1210 cells, respectively, was selected for further biological evaluation. The activity of 3j was verified by the NCI 60 cell line screen. Compound 3j causes microtubule depolymerization in A-10 cells with an EC₅₀ of 21.2 μM. Analog 3j, which has excellent water solubility of 479 μM, had antitumor activity in a syngeneic L1210 murine model.     

Natural killer and antibody-dependent cellular cytotoxicity in cervical carcinoma patients

Summary Natural killer (NK) cell activity and antibody dependent cell-mediated cytotoxicity (ADCC) was measured in 62 untreated cervical carcinoma patients and 25 normal healthy women, using a short-term chromium release assay. A significant reduction in NK and ADCC activity was observed in disseminated disease than in localized disease, when compared with normal donors. The majority of the patients received radiotherapy and both NK and ADCC activity recovered after therapy. Furthermore, interferon- was demonstrated to augment NK activity of peripheral blood mononuclear cells from healthy donors as well as patients. Also large granular lymphocytes separated on Percoll density gradient were the same in number in both the populations studied, although in cervical cancer there seemed to be a defect in killing activity.     

Novel diamino imidazole and pyrrole-containing polyamides: Synthesis and DNA binding studies of mono- and diamino-phenyl-ImPy*Im polyamides designed to target 5'-ACGCGT-3'

Pyrrole- and imidazole-containing polyamides are widely investigated as DNA sequence selective binding agents that have potential use as gene control agents. The key challenges that must be overcome to realize this goal is the development of polyamides with low molar mass so the molecules can readily diffuse into cells and concentrate in the nucleus. In addition, the molecules must have appreciable water solubility, bind DNA sequence specifically, and with high affinity. It is on this basis that the orthogonally positioned diamino/dicationic polyamide Ph-ImPy*Im 5 was designed to target the sequence 5'-ACGCGT-3'. Py* denotes the pyrrole unit that contains a N-substituted aminopropyl pendant group. The DNA binding properties of diamino polyamide 5 were determined using a number of techniques including CD, ΔT(M), DNase I footprinting, SPR and ITC studies. The effects of the second amino moiety in Py* on DNA binding affinity over its monoamino counterpart Ph-ImPyIm 3 were assessed by conducting DNA binding studies of 3 in parallel with 5. The results confirmed the minor groove binding and selectivity of both polyamides for the cognate sequence 5'-ACGCGT-3'. The diamino/dicationic polyamide 5 showed enhanced binding affinity and higher solubility in aqueous media over its monoamino/monocationic counterpart Ph-ImPyIm 3. The binding constant of 5, determined from SPR studies, was found to be 1.5 × 10(7)M(-1), which is ～3 times higher than that for its monoamino analog 3 (4.8 × 10(6)M(-1)). The affinity of 5 is now approaching that of the parent compound f-ImPyIm 1 and its diamino equivalent 4. The advantages of the design of diamino polyamide 5 over 1 and 4 are its sequence specificity and the ease of synthesis compared to the N-terminus pyrrole analog 2.