Enhanced human activity recognition in medical emergencies using a hybrid deep CNN and bi-directional LSTM model with wearable sensors.

Human activity recognition (HAR) is one of the most important segments of technology advancement in applications of smart devices, healthcare systems & fitness. HAR uses details from wearable sensors that capture the way human beings move or engage with their surrounding. Several researchers have thus presented different ways of modeling human motion, and some have been as follows: Many researchers have presented different methods of modeling human movements.

Winning the Fight Against Cancer.

Advances in cytotoxic chemotherapy, surgical oncology, genomic medicine, targeted small molecule treatment, cancer immunotherapy and biology-driven precision radiation oncology have resulted in significant improvements in outcomes of cancer treatment, with an increasing number of patients achieving long-term disease control or even being potentially cured. Concurrent advances in palliative care and geriatric oncology have also helped to ensure that patients are managed holistically by considering their physical, social, psychological and emotional needs in a personalised manner.

Allosteric Recognition of Homomeric and Heteromeric Pairs of Monosaccharides by a Foldamer Capsule.

The recognition of either homomeric or heteromeric pairs of pentoses in an aromatic oligoamide double helical foldamer capsule was evidenced by circular dichroism (CD), NMR spectroscopy, and X-ray crystallography. The cavity of the host was predicted to be large enough to accommodate simultaneously two xylose molecules and to form a 1:2 complex (one container, two saccharides). Solution and solid-state data revealed the selective recognition of the α- C -d-xylopyranose tautomer, which is bound at two identical sites in the foldamer cavity.

Citric acid encapsulation by a double helical foldamer in competitive solvents.

A new double helical aromatic oligoamide capsule able to bind to citric acid in polar and protic solvents was prepared. Aromatic amino acids in the sequence encode both structural (strand curvature and double helix formation) and functional features (recognition pattern) of the assembled capsule.

Polar solvent effects on tartaric acid binding by aromatic oligoamide foldamer capsules.

Aromatic oligoamide sequences able to fold into single helical capsules were functionalized with two types of side chains to make them soluble in various solvents such as chloroform, methanol or water and their propensity to recognize tartaric acid was evaluated. The binding affinities to tartaric acid and binding thermodynamics in different media were investigated by variable temperature (1)H NMR and ITC experiments, the two methods giving consistent results. We show that tartaric acid binding mainly rests on enthalpically favourable polar interactions that were found to be sufficiently strong to be effective in the presence of a polar aprotic solvent (DMSO) and even in pure methanol.

Thiostrepton interacts covalently with Rpt subunits of the 19S proteasome and proteasome substrates.

Here, we report a novel mechanism of proteasome inhibition mediated by Thiostrepton (Thsp), which interacts covalently with Rpt subunits of the 19S proteasome and proteasome substrates. We identified Thsp in a cell-based high-throughput screen using a fluorescent reporter sensitive to degradation by the ubiquitin-proteasome pathway. Thiostrepton behaves as a proteasome inhibitor in several paradigms, including cell-based reporters, detection of global ubiquitination status, and proteasome-mediated labile protein degradation.

Iterative design of a helically folded aromatic oligoamide sequence for the selective encapsulation of fructose.

The ab initio design of synthetic molecular receptors for a specific biomolecular guest remains an elusive objective, particularly for targets such as monosaccharides, which have very close structural analogues. Here we report a powerful approach to produce receptors with very high selectivity for specific monosaccharides and, as a demonstration, we develop a foldamer that selectively encapsulates fructose. The approach uses an iterative design process that exploits the modular structure of folded synthetic oligomer sequences in conjunction with molecular modelling and structural characterization to inform subsequent refinements.

Structure elucidation of host-guest complexes of tartaric and malic acids by quasi-racemic crystallography.

Racemic on the outside, but not inside: Aromatic-foldamer hosts are enantiomers and as such prefer to co-crystallize even though the guests (e.g. L-tartaric acid, see picture) in each host are not present as enantiomers.

Improved native isolation of endogenous Protein A-tagged protein complexes.

Here we report a modified peptide reagent useful for the rapid, native elution of protein complexes containing a Protein-A-tagged component. We tested this reagent for the elution of tagged endogenous protein complexes from yeast (Nup53p/Nup170p dimer; Nup1p/Kap95p/Kap60p trimer; pentameric GINS complex) and bacteria (RNAP holoenzyme). The majority of the affinity-isolated material is released within 15 minutes under mild conditions, and the elution reagent itself is readily depleted from the elution mixture by simple spin column gel filtration.

Identification of a foldaxane kinetic byproduct during guest-induced single to double helix conversion.

An aromatic oligoamide sequence was designed and synthesized to fold in a single helix having a large cavity and to behave as a host for a dumbbell-shaped guest derived from tartaric acid. NMR, molecular modeling, and circular dichroism (CD) evidence demonstrated the rapid formation of this 1:1 host-guest complex and induction of the helix handedness of the host by the guest. This complex was found to be a long-lived kinetic supramolecular byproduct, as it slowly transformed into a 2:2 host-guest complex with two guest molecules bound at the extremities of a double helix formed by the host, as shown by NMR and CD spectroscopy and a solid-state structure.

Long-range effects on the capture and release of a chiral guest by a helical molecular capsule.

Helically folded molecular capsules based on oligoamide sequences of aromatic amino acids which are capable of binding tartaric acid in organic solvents with high affinity and diastereoselectivity have been synthesized, and their structures and binding properties investigated by (1)H NMR, X-ray crystallography, circular dichroism, and molecular modeling. We found that elongating the helices at their extremities by adding monomers remote from the tartaric binding site results in a strong increase of the overall helix stability, but it does not influence the host-guest complex stability. The effect of this elongation on the binding and release rates of the guest molecules follows an unexpected non-monotonous trend.

In vitro anti-plasmodial activity of some traditionally used medicinal plants against Plasmodium falciparum.

The anti-plasmodial activity of different solvent extracts of Adhatoda vasica (root), Caesalpinia pulcherrima (leaf), Carica papaya (pulp), Erythroxylum monogynum (leaf), Lantana camara (whole plant), Ocimum sanctum (root) and Phyllanthus niruri (whole plant) were studied against Plasmodium falciparum. Of the 35 extracts tested, seven extracts showed good anti-plasmodial activity. Methanol extract of C.

Free radical 5-exo-dig cyclization as the key step in the synthesis of bis-butyrolactone natural products: experimental and theoretical studies.

Radical cyclization reactions were performed by 5-exo-dig mode to yield cis-fused bicyclic systems, leading to the synthesis of bis-butyrolactone class of natural products. The study was aimed at understanding the impact of alkyl side chains of furanoside ring systems in L-ara configuration on the radical cyclization. It was amply demonstrated by experimental studies that the increase in the length of the alkyl side chain has an effect on the cyclization: while efficient cyclization reactions could be realized with methyl and ethyl side chains, the yields were significantly reduced in the case of n-pentyl side chain.

The design of α/β-peptides: study on three-residue turn motifs and the influence of achiral glycine on helix and turn.

Novel three-residue helix-turn secondary structures, nucleated by a helix at the N terminus, were generated in peptides that have 'β-Caa-L-Ala-L-Ala,' 'β-Caa-L-Ala-γ-Caa,' and 'β-Caa-L-Ala-δ-Caa' (in which β-Caa is C-linked carbo-β-amino acid, γ-Caa is C-linked carbo-γ-amino acid, and δ-Caa is C-linked carbo-δ-amino acid) at the C terminus. These turn structures are stabilized by 12-, 14-, and 15-membered (mr) hydrogen bonding between NH(i)/CO(i+2) (i+2 is the last residue in the peptide) along with a 7-mr hydrogen bond between CO(i)/NH(i+2). In addition, a series of α/β-peptides were designed and synthesized with alternating glycine (Gly) and (S)-β-Caa to study the influence of an achiral α-residue on the helix and helix-turn structures.

Hybrid helices: motifs for secondary structure scaffolds in foldamers.

The concept of "hybrid helices" as a new motif for foldamers is presented. Hybrid helices can be realized by a combination of two or more different types of homologous and hybrid peptides, for example, beta-peptides and alpha/beta- and alpha/gamma-hybrid peptides, within the same oligomer. The different helix types of the various peptide foldamer classes are maintained and form a regular helix along the sequence of the oligomer.

Reductive glutaraldehydation of amine groups for identification of protein N-termini.

In the present work, reductive alkylation of proteins and peptides with glutaraldehyde (reductive glutaraldehydation) is reported. The reaction is highly efficient and forms piperidine at the N-terminus as well as the side chain of lysine residues. The complete modification of protein amines was achieved by reductive glutaraldehydation in solution or in the gel in less than 15 min.

Three-residue turns in alpha/beta-peptides and their application in the design of tertiary structures.

A new three-residue turn was serendipitously discovered in alpha/beta hybrid peptides derived from alternating C-linked carbo-beta-amino acids (beta-Caa) and L-Ala residues. The three-residue beta-alpha-beta turn at the C termini, nucleated by a helix at the N termini, resulted in helix-turn (HT) supersecondary structures in these peptides. The turn in the HT motif is stabilized by two H bonds-CO(i-2)-NH(i), with a seven-membered pseudoring (gamma turn) in the backward direction, and NH(i-2)-CO(i), with a 13-membered pseudoring in the forward direction (i being the last residue)--at the C termini.

Selective growth inhibition of tumor cells by a novel histone deacetylase inhibitor, NVP-LAQ824.

We have synthesized a histone deacetylase inhibitor, NVP-LAQ824, a cinnamic hydroxamic acid, that inhibited in vitro enzymatic activities and transcriptionally activated the p21 promoter in reporter gene assays. NVP-LAQ824 selectively inhibited growth of cancer cell lines at submicromolar levels after 48-72 h of exposure, whereas higher concentrations and longer exposure times were required to retard the growth of normal dermal human fibroblasts. Flow cytometry studies revealed that both tumor and normal cells arrested in the G(2)-M phase of the cell cycle after compound treatment.

N-hydroxy-3-phenyl-2-propenamides as novel inhibitors of human histone deacetylase with in vivo antitumor activity: discovery of (2E)-N-hydroxy-3-[4-[[(2-hydroxyethyl)[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide (NVP-LAQ824).

A series of N-hydroxy-3-phenyl-2-propenamides were prepared as novel inhibitors of human histone deacetylase (HDAC). These compounds were potent enzyme inhibitors, having IC(50)s < 400 nM in a partially purified enzyme assay. However, potency in cell growth inhibition assays ranged over 2 orders of magnitude in two human carcinoma cell lines.

A novel somatostatin mimic with broad somatotropin release inhibitory factor receptor binding and superior therapeutic potential.

A rational drug design approach, capitalizing on structure-activity relationships and involving transposition of functional groups from somatotropin release inhibitory factor (SRIF) into a reduced size cyclohexapeptide template, has led to the discovery of SOM230 (25), a novel, stable cyclohexapeptide somatostatin mimic that exhibits unique high-affinity binding to human somatostatin receptors (subtypes sst1-sst5). SOM230 has potent, long-lasting inhibitory effects on growth hormone and insulin-like growth factor-1 release and is a promising development candidate currently under evaluation in phase I clinical trials.

Management of thrombosis in women with antiphospholipid syndrome.

1) Antiphospholipid antibody syndrome may be associated with unusual sites of thrombosis. 2) Laboratory evaluation involves testing for antiphospholipid antibodies: lupus anticoagulant and anticardiolipin antibodies. 3) Acute management of thrombosis involves immediate anticoagulation.

Prolonged immunoglobulin and platelet infusion for treatment of immune thrombocytopenia.

Immune thrombocytopenia (ITP) may be associated with serious hemorrhage. We describe 2 patients who received intravenous immunoglobulin given as a 24-hr continuous infusion with a concomitant continuous infusion of platelets. This regimen was rapidly effective in increasing platelet counts in both patients.

Solid-phase total synthesis of polymyxin B1.

The total solid-phase synthesis of polymyxin B1 (PMB1) has been achieved in 20% yield using the orthogonal protecting group N-1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl-(Dde). This report demonstrates that a complex peptide macrocycle can be synthesized in high yields using solid-phase synthesis. According to MS and HPLC, the synthetic peptide was identical to the naturally occurring antibiotic.