29 research outputs found
A Serine Protease Activity Is Induced by G-CSF and Degrades Stat5 Proteins in Myeloid Cells.
Cybersecurity For Digital Manufacturing
Digital manufacturing aims to create highly customizable products with higher quality and lower costs by integrating Industrial Internet of Things, big data analytics, cloud computing, and advanced robots into manufacturing plants. As manufacturing machines are increasingly retrofitted with sensors as well as connected via wireless networks or wired Ethernet, digital manufacturing systems are becoming more accessible than ever. While advancement in sensing, artificial intelligence, and wireless technologies enables a paradigm shift in manufacturing, cyber-attacks pose significant threats to the manufacturing sector. This paper presents a review of cybersecurity in digital manufacturing systems from system characterization, threat and vulnerability identification, control, and risk determination aspects as well as identifies challenges and future work
Fracture pore evaluation of the Upper Ordovician Wufeng to Lower Silurian Longmaxi Formations in southern Sichuan Basin, SW China
Synthesis and Physicochemical Properties of Metallobacteriochlorins
Access to metallobacteriochlorins is essential for investigation
of a wide variety of fundamental photochemical processes, yet relatively
few synthetic metallobacteriochlorins have been prepared. Members
of a set of synthetic bacteriochlorins bearing 0–4 carbonyl
groups (1, 2, or 4 carboethoxy substituents, or an annulated imide
moiety) were examined under two conditions: (i) standard conditions
for zincation of porphyrins [Zn(OAc)<sub>2</sub>·2H<sub>2</sub>O in <i>N</i>,<i>N</i>-dimethylformamide (DMF) at 60–80 °C], and (ii) treatment
in tetrahydrofuran (THF) with a strong base [e.g., NaH or lithium diisopropylamide (LDA)] followed
by a metal reagent MX<sub><i>n</i></sub>. Zincation of bacteriochlorins
that bear 2–4 carbonyl groups proceeded under the former method
whereas those with 0–2 carbonyl groups proceeded with NaH or
LDA/THF followed by Zn(OTf)<sub>2</sub>. The scope of metalation (via
NaH or LDA in THF) is as follows: (a) for bacteriochlorins that bear
two electron-releasing aryl groups, M = Cu, Zn, Pd, and InCl (but
not Mg, Al, Ni, Sn, or Au); (b) for bacteriochlorins that bear two
carboethoxy groups, M = Ni, Cu, Zn, Pd, Cd, InCl, and Sn (but not
Mg, Al, or Au); and (c) a bacteriochlorin with four carboethoxy groups
was metalated with Mg (other metals were not examined). Altogether,
15 metallobacteriochlorins were isolated and characterized. Single-crystal
X-ray analysis of 8,8,18,18-tetramethylbacteriochlorin reveals the
core geometry provided by the four nitrogen atoms is rectangular;
the difference in length of the two sides is ∼0.08 Å.
Electronic characteristics of (metal-free) bacteriochlorins were probed
through electrochemical measurements along with density functional
theory calculation of the energies of the frontier molecular orbitals.
The photophysical properties (fluorescence yields, triplet yields,
singlet and triplet excited-state lifetimes) of the zinc bacteriochlorins
are generally similar to those of the metal-free analogues, and to
those of the native chromophores bacteriochlorophyll <i>a</i> and bacteriopheophytin <i>a</i>. The availability of diverse
metallobacteriochlorins should prove useful in a variety of fundamental
photochemical studies and applications
In vitro photodynamic therapy and quantitative structure-activity relationship studies with stable synthetic near-infrared-absorbing bacteriochlorin photosensitizers.
Photodynamic therapy (PDT) is a rapidly developing approach to treating cancer that combines harmless visible and near-infrared light with a nontoxic photoactivatable dye, which upon encounter with molecular oxygen generates the reactive oxygen species that are toxic to cancer cells. Bacteriochlorins are tetrapyrrole compounds with two reduced pyrrole rings in the macrocycle. These molecules are characterized by strong absorption features from 700 to >800 nm, which enable deep penetration into tissue. This report describes testing of 12 new stable synthetic bacteriochlorins for PDT activity. The 12 compounds possess a variety of peripheral substituents and are very potent in killing cancer cells in vitro after illumination. Quantitative structure-activity relationships were derived, and subcellular localization was determined. The most active compounds have both low dark toxicity and high phototoxicity. This combination together with near-infrared absorption gives these bacteriochlorins great potential as photosensitizers for treatment of cancer.Journal ArticleResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.info:eu-repo/semantics/publishe
Stable synthetic bacteriochlorins overcome the resistance of melanoma to photodynamic therapy.
Cutaneous malignant melanoma remains a therapeutic challenge, and patients with advanced disease have limited survival. Photodynamic therapy (PDT) has been successfully used to treat many malignancies, and it may show promise as an antimelanoma modality. However, high melanin levels in melanomas can adversely affect PDT effectiveness. Herein the extent of melanin contribution to melanoma resistance to PDT was investigated in a set of melanoma cell lines that markedly differ in the levels of pigmentation; 3 new bacteriochlorins successfully overcame the resistance. Cell killing studies determined that bacteriochlorins are superior at (LD(50) approximately 0.1 microM) when compared with controls such as the FDA-approved Photofrin (LD(50) approximately 10 microM) and clinically tested LuTex (LD(50) approximately 1 microM). The melanin content affects PDT effectiveness, but the degree of reduction is significantly lower for bacteriochlorins than for Photofrin. Microscopy reveals that the least effective bacteriochlorin localizes predominantly in lysosomes, while the most effective one preferentially accumulates in mitochondria. Interestingly all bacteriochlorins accumulate in melanosomes, and subsequent illumination leads to melanosomal damage shown by electron microscopy. Fluorescent probes show that the most effective bacteriochlorin produces significantly higher levels of hydroxyl radicals, and this is consistent with the redox properties suggested by molecular-orbital calculations. The best in vitro performing bacteriochlorin was tested in vivo in a mouse melanoma model using spectrally resolved fluorescence imaging and provided significant survival advantage with 20% of cures (P<0.01).Journal ArticleResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe
In Vitro Photodynamic Therapy and Quantitative Structure−Activity Relationship Studies with Stable Synthetic Near-Infrared-Absorbing Bacteriochlorin Photosensitizers
Resource-use maximisation through legume intercropping with maize in the eastern Himalayan region of India
A Maltose-Binding Protein Fusion Construct Yields a Robust Crystallography Platform for MCL1
<div><p>Crystallization of a maltose-binding protein MCL1 fusion has yielded a robust crystallography platform that generated the first apo MCL1 crystal structure, as well as five ligand-bound structures. The ability to obtain fragment-bound structures advances structure-based drug design efforts that, despite considerable effort, had previously been intractable by crystallography. In the ligand-independent crystal form we identify inhibitor binding modes not observed in earlier crystallographic systems. This MBP-MCL1 construct dramatically improves the structural understanding of well-validated MCL1 ligands, and will likely catalyze the structure-based optimization of high affinity MCL1 inhibitors.</p></div