Drift of Schottky Barrier Height in Phase Change Materials.

Phase-change memory (PCM) devices have great potential as multilevel memory cells and artificial synapses for neuromorphic computing hardware. However, their practical use is hampered by resistance drift, a phenomenon commonly attributed to structural relaxation or electronic mechanisms primarily in the context of bulk effects. In this study, we reevaluate the electrical manifestation of resistance drift in sub-100 nm GeSbTe (GST) PCM devices, focusing on the contributions of bulk vs interface effects.

Spontaneous Raman scattering from vibrational polaritons is obscured by reservoir states.

Vibrational strong coupling results from the interaction between optically allowed molecular vibrational excitations and the resonant mode of an infrared cavity. Strong coupling leads to the formation of hybrid states, known as vibrational polaritons, which are readily observed in transmission measurements and a manifold of the reservoir states. In contrast, Raman spectroscopy of vibrational polaritons is elusive and has recently been the focus of both theoretical and experimental investigations.

Improved Current Density and Contact Resistance in Bilayer MoSe Field Effect Transistors by AlO Capping.

Atomically thin semiconductors are of interest for future electronics applications, and much attention has been given to monolayer (1L) sulfides, such as MoS, grown by chemical vapor deposition (CVD). However, reports on the electrical properties of CVD-grown selenides, and MoSe in particular, are scarce. Here, we compare the electrical properties of 1L and bilayer (2L) MoSe grown by CVD and capped by sub-stoichiometric AlO.

Author Correction: High-resolution record reveals climate-driven environmental and sedimentary changes in an active rift.

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High-resolution record reveals climate-driven environmental and sedimentary changes in an active rift.

Young rifts are shaped by combined tectonic and surface processes and climate, yet few records exist to evaluate the interplay of these processes over an extended period of early rift-basin development. Here, we present the longest and highest resolution record of sediment flux and paleoenvironmental changes when a young rift connects to the global oceans. New results from International Ocean Discovery Program (IODP) Expedition 381 in the Corinth Rift show 10s-100s of kyr cyclic variations in basin paleoenvironment as eustatic sea level fluctuated with respect to sills bounding this semi-isolated basin, and reveal substantial corresponding changes in the volume and character of sediment delivered into the rift.

The formation of peak rings in large impact craters.

Large impacts provide a mechanism for resurfacing planets through mixing near-surface rocks with deeper material. Central peaks are formed from the dynamic uplift of rocks during crater formation. As crater size increases, central peaks transition to peak rings.

Multifunctional tumor-targeted polymer-peptide-drug delivery system for treatment of primary and metastatic cancers.

Purpose: In order to improve drug delivery to drug-resistant ovarian tumors, we constructed a multifunctional polymer-peptide-drug conjugate (PPDC) system for effective treatment of primary and metastatic ovarian cancers.

Methods: The PPDC consists of the poly(Ethylene Glycol) (PEG) polymeric carrier conjugated via citric acid spacers to anticancer drug (Camptothecin, CPT), tumor targeting moiety (LRHR, a synthetic analog of luteinizing hormone-releasing hormone) and a suppressor of cellular antiapoptotic defense (BH3 peptide). To test the conjugates in vitro and in vivo, cancer cells were isolated from tissue samples obtained from patients with ovarian primary tumor and metastatic malignant ascites.

Receptor targeted polymers, dendrimers, liposomes: which nanocarrier is the most efficient for tumor-specific treatment and imaging?

To compare the influence of different characteristics of nanocarriers on the efficacy of chemotherapy and imaging, we designed, characterized, and evaluated three widely used nanocarriers: linear polymer, dendrimer and liposome in vitro and in vivo. These nanocarriers delivered the same anticancer drug (paclitaxel) and/or imaging agent (Cy5.5).

Targeted proapoptotic anticancer drug delivery system.

A novel targeted proapoptotic anticancer drug delivery system (DDS) was developed and evaluated both in vitro and in vivo. The system contains poly(ethylene glycol) polymer (PEG) as a carrier, camptothecin (CPT) as an anticancer drug/cell death inducer, a synthetic analogue of luteinizing hormone-releasing hormone (LHRH) peptide as a targeting moiety/penetration enhancer, and a synthetic analogue of BCL2 homology 3 domain (BH3) peptide as a suppressor of cellular antiapoptotic defense. The design of the multicomponent DDS allowed for a conjugation of one or two copies of each active ingredient (CPT, LHRH, and BH3) to one molecule of PEG carrier.

Antitumor activity of new liposomal prodrug of mitomycin C in multidrug resistant solid tumor: insights of the mechanism of action.

The antitumor activity of a novel thiolytically cleavable lipid-based prodrug of mitomycin C (MMC) delivered by STEALTH liposomes (SL) was studied in drug resistant human ovarian carcinoma A2780/AD model and compared with free MMC and both free and SL forms of an established anticancer drug--doxorubicin (DOX). It was found that SL-prodrug (SL-pMMC) possessed enhanced antitumor activity when compared with the parent MMC, free DOX, and SL-DOX. An observance of the high antitumor efficiency of SL-pMMC was a result of its preferential accumulation in the tumor by the enhanced permeability and retention (EPR) effect, suppression of multidrug resistance (MDR) associated with P-glycoprotein and MRP drug efflux pumps, activation of caspase-dependent apoptosis signaling pathways and suppression of antiapoptotic cellular defense by increasing the BAX/BCL2 ratio.

Phosphorylated morpholine acetal human neurokinin-1 receptor antagonists as water-soluble prodrugs.

The regioselective dibenzylphosphorylation of 2 followed by catalytic reduction in the presence of N-methyl-D-glucamine afforded 2-(S)-(1-(R)-(3, 5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(5-(2- phosphoryl-3-oxo-4H,-1,2,4-triazolo)methylmorpholine, bis(N-methyl-D-glucamine) salt, 11. Incubation of 11 in rat, dog, and human plasma and in human hepatic subcellular fractions in vitro indicated that conversion to 2 would be expected to occur in vivo most readily in humans during hepatic circulation. Conversion of 11 to 2 occurred rapidly in vivo in the rat and dog with the levels of 11 being undetectable within 5 min after 1 and 8 mg/kg doses iv in the rat and within 15 min after 0.

The novel NK1 receptor antagonist MK-0869 (L-754,030) and its water soluble phosphoryl prodrug, L-758,298, inhibit acute and delayed cisplatin-induced emesis in ferrets.

The anti-emetic profile of the novel brain penetrant tachykinin NK1 receptor antagonist MK-0869 (L-754,030) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluor o)phenyl-4-(3-oxo-1,2,4-triazol-5-yl)methylmorpholine and its water soluble prodrug, L-758,298, has been examined against emesis induced by cisplatin in ferrets. In a 4 h observation period, MK-0869 and L-758,298 (3 mg/kg i.v.

Characterization of a novel, non-peptidyl antagonist of the human glucagon receptor.

We have identified a series of potent, orally bioavailable, non-peptidyl, triarylimidazole and triarylpyrrole glucagon receptor antagonists. 2-(4-Pyridyl)-5-(4-chlorophenyl)-3-(5-bromo-2-propyloxyphenyl)p yrr ole (L-168,049), a prototypical member of this series, inhibits binding of labeled glucagon to the human glucagon receptor with an IC50 = 3. 7 +/- 3.

Structural optimization affording 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-oxo-1,2,4-triazol-5-yl)methylmorpholine, a potent, orally active, long-acting morpholine acetal human NK-1 receptor antagonist.

Structural modifications requiring novel synthetic chemistry were made to the morpholine acetal human neurokinin-1 (hNK-1) receptor antagonist 4, and this resulted in the discovery of 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-ox o-1 ,2,4-triazol-5-yl)methyl morpholine (17). This modified compound is a potent, long-acting hNK-1 receptor antagonist as evidenced by its ability to displace [125I]Substance P from hNK-1 receptors stably expressed in CHO cells (IC50 = 0.09 +/- 0.

In vitro and in vivo predictors of the anti-emetic activity of tachykinin NK1 receptor antagonists.

The ability of tachykinin NK1 receptor antagonists to inhibit GR73632 (D-Ala-[L-Pro9,Me-Leu8]substance P-(7-11))-induced foot tapping in gerbils was employed as an indirect measure of brain penetration and this was compared with their ability to prevent acute emesis induced by cisplatin in ferrets. (+)-GR203040 ((2S,3S and 2R,3R)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin- 3-yl)-amine), CP-99,994 ((2S,3S)-cis-3-(2-methoxybenzylamino)-2-phenyl piperidine) dihydrochloride), and L-742,694 (2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-phenyl-4-(5-(3-oxo-1,2, 4-triazolo)methylmorpholine) potently inhibited GR73632-induced foot tapping (ID50 < or = 0.85 mg/kg), and acute retching induced by cisplatin (ID50 < or = 0.

Characterization of the binding and activity of a high affinity, pseudoirreversible morpholino tachykinin NK1 receptor antagonist.

2(S)-((3,5-Bis(trifluoromethyl)benzyl)-oxy)-3(S)-phenyl-4-((3-oxo-1,2,4- triazol-5-yl)methyl)morpholine (L-742,694) is a selective morpholino tachykinin NK1 receptor antagonist that inhibits the binding of 125I-substance P to the human tachykinin NK1 receptor with a Kd = 37 pM. Increasing concentrations of L-742,694 added to cells 15 min prior to agonist progressively increase the apparent EC50 of substance P for inducing the synthesis of inositol phosphate in Chinese hamster ovary (CHO) cells expressing human tachykinin NK1 receptor and decrease the maximal level of stimulation observed. In contrast, addition of substance P and L-742,694 to the cells at the same time results in an increase in the EC50 for substance P with no decrease in the maximal level of stimulation.

Tachykinin NK1 receptor antagonists act centrally to inhibit emesis induced by the chemotherapeutic agent cisplatin in ferrets.

These studies have compared the pharmacological profile of two non-peptide human type neurokinin1 (hNK1) receptor selective antagonists, L-741,671 and a quaternised compound L-743,310. In radioligand binding studies L-741,671 and L-743,310 had high affinity for ferret and cloned hNK1 receptors [Ki (nM) ferret 0.7 and 0.

Characterization of the interaction of diacylpiperazine antagonists with the human neurokinin-1 receptor: identification of a common binding site for structurally dissimilar antagonists.

We recently described a novel series of diacylpiperazine antagonists of the human neurokinin (NK)-1 receptor. The diacylpiperazine compounds are structurally dissimilar from previously described NK-1 antagonists. L-161,664 [1-(N,N-diphenylaminocarbonyl)-4-(N',N'-di-n-pentylaminocarbony l) piperazine-2-diethylaminopropylcarboxamide] inhibits 125I-substance P binding to the human NK-1 receptor with an IC50 of 43 +/- 21 nM but has 50-fold and 200-fold lower affinity for the human NK-2 and NK-3 receptors, respectively.

Identification of L-tryptophan derivatives with potent and selective antagonist activity at the NK1 receptor.

As part of a program of screening the Merck sample collection, N-ethyl-L-tryptophan benzyl ester was identified as a weak antagonist at the substance P (NK1) receptor. Structure-activity studies showed that the indole ring system could be replaced by 3,4-dichlorophenyl, alpha- or beta-naphthyl, or benzthiophene with retention or only small loss of affinity. It was found that acylation of the tryptophan nitrogen gave compounds with higher affinity than N-ethyl or other basic amines.

Characterization of the interaction of N-acyl-L-tryptophan benzyl ester neurokinin antagonists with the human neurokinin-1 receptor.

We have recently shown that a series of N-acyl-L-tryptophan benzyl esters are potent substance P antagonists (Macleod, A. M., Merchant, K.

Characterization of the binding of a potent, selective, radioiodinated antagonist to the human neurokinin-1 receptor.

We have synthesized a potent, selective, radioiodinated antagonist of the human neurokinin-1 (NK1) receptor and have characterized its binding to the cloned receptor expressed in Chinese hamster ovary cells. (cis)-2-(Diphenylmethyl)-N-[(2-iodophenyl)-methyl]-1- azabicyclo[2.2.

Determination of the amino acid residues in substance P conferring selectivity and specificity for the rat neurokinin receptors.

We have measured the affinity of various analogs and fragments of the tachykinin substance P for the cloned rat NK1, NK2, and NK3 receptors heterologously expressed in Chinese hamster ovary cells. The hydrophobic carboxyl-terminal pentapeptide sequence substance P-(7-11) binds with similar affinity (2-20 microM) to all three receptors. Our data suggest that addition of one to three amino-terminal residues to this sequence results in the optimization of its interaction within the binding pocket of the NK1 receptor.

Identification of the insulin-like growth factor I (IGF I) epitopes recognized by monoclonal and polyclonal antibodies to IGF I.

We have characterized the binding epitopes of human insulin-like growth factor I (IGF I) for a polyclonal (UB286) and a monoclonal (SM 1.2) antibody using IGF analogs obtained by site-directed mutagenesis. The polyclonal antibody, UB286, which was obtained from the National Hormone and Pituitary Program, recognizes determinants surrounding residues 15 and 16 in the B-region and residues 49-51, 55 and 56 in the A-region.