A fluorescent molecular imaging probe with selectivity for soluble tau aggregated protein

Soluble forms of aggregated tau misfolded protein, generally termed oligomers, are considered to be the most toxic species of the different assembly states that are the pathological components of neurodegenerative disorders. Therefore, a critical biomedical need exists for imaging probes that can identify and quantify them. We have designed and synthesized a novel fluorescent probe, pTP-TFE for which binding and selectivity profiles towards aggregated tau and Aβ proteins were assessed. Our results have shown pTP-TFE to be selective for early forms of soluble tau aggregates, with high affinity of dissociation constants (K_d) = 66 nM, and tenfold selectivity over mature tau fibrils. Furthermore, we found that pTP-TFE is selective for tau over Aβ aggregates and had good cell permeability. This selectivity of pTP-TFE towards early forms of aggregated tau protein ex vivo was also supported with studies on human brain tissue containing tau and Aβ pathology. To the best of our knowledge, this is the first fluorescent molecule to be reported to have this form of selectivity profile, which suggests that pTP-TFE is a unique probe candidate for imaging-based detection of early stages of Alzheimer''s disease and other tauopathies.

pTP-TFE imaging probe can distinguish soluble tau aggregated proteins from other aggregated proteins enabling earlier detection of neurodegenerative diseases.     

Spin squeezing and quantum correlations

We discuss the notion of spin squeezing considering two mutually exclusive classes of spin-s states, namely, oriented and non-oriented states. Our analysis shows that the oriented states are not squeezed while non-oriented states exhibit squeezing. We also present a new scheme for construction of spin-s states using 2s spinors oriented along different axes. Taking the case of s=1, we show that the ‘non-oriented’ nature and hence squeezing arise from the intrinsic quantum correlations that exist among the spinors in the coupled state.     

Theory of sheath in a collisional multi-component plasma

The aim of this brief report is to study the behaviour of sheath structure in a multi-component plasma with dust-neutral collisions. The plasma consists of electrons, ions, micron size negatively charged dust particles and neutrals. The sheath-edge potential and sheath width are calculated for collisionally dominated sheath. Comparison of collisionless and collisionally dominated sheath are made.     

A new regioselective Heck vinylation with enamides. Synthesis and investigation of fluorous-tagged bidentate ligands for fast separation

Internal ligand-controlled Heck vinylations of enamides were performed with high regioselectivity and delivered moderate to good yields of dienamides. Controlled heating by microwave irradiation accelerated the palladium-catalyzed reactions, and full conversions were achieved after reaction times of only 15-30 min. New bidentate fluorous-tagged 1,3-bis(diphenylphosphino)propane ligands (F-dppp's) were synthesized and examined. The cationic vinylations of the enamides with F-dppp ligands rendered essentially the same alpha-selectivity and catalytic activity as in those vinylations where nonfluorous ligands were employed. After reaction, the fluorous-tagged ligand material was easily removed by convenient solid fluorous phase separation. The high selectivity, simplicity, and generality of the experimental procedure should make this approach to 2-acylamino-1,3-butadienes attractive.     

Analysis of a shielded TE011 mode composite dielectric resonator for stable frequency reference

Analysis of a TE₀₁₁ mode composite sapphire-rutile dielectric resonator has been carried out to study the temperature variation of resonance frequency, close to the Cs atomic clock hyperfine frequency of 9.192 GHz. The complementary behavior of dielectric permittivity with temperature of the composite has been exploited to obtain the desired turning point in the resonant frequency. The frequency of the composite structure is found to be independent of the shield diameter beyond four times the puck diameter.     

Indirect measurements of the Jahn-Teller quenched spin-orbit splitting in the 5T2g-state of KMgF3:Fe2+

The energy separation of the first excited spin-orbit States Γ_3g, Γ_4g from the Γ_5g ground state, in the orbital ⁵T_2g triplet state of Fe²⁺ in KMgF₃, has been estimated from temperature dependence measurements on the 7860 cm^-1 zero-phonon-line (ZPL) transition from Γ_5g to the orbital ⁵E_g doublet state. Using a simplified crystal field energy level model, we find the Γ_5g Γ_3g, Γ_4g separation to be ～30 cm^-1, indicating that the vibronic Jahn-Teller coupling is considerably stronger in KMgF₃:Fe²⁺ than in MgO:Fe²⁺. Far infrared absorption data on KMgF₃:Fe²⁺ in magnetic fields up to 6T, are found to be consistent with this interpretation.     

An optimized procedure for detection of proteins on carrier ampholyte isoelectric focusing and immobilized pH gradient gels with imidazole and zinc salts: its application to the identification of isoelectric focusing separated isoforms by in-gel proteolysis and mass spectrometry analysis.

A method for the characterization of proteins separated by isoelectric focusing in carrier ampholytes (CA-IEF) or immobilized pH gradient (IPG) gels by in-gel digestion and mass spectrometry is described. Proteins are detected by an improved imidazole-Sodium dodecyl sulfate (SDS)-zinc staining adapted for IEF and IPG gels. Sensitivity is close to that of mass spectrometry-compatible silver staining, but simpler and faster. Proteins were digested in imidazole-SDS-zinc stained CA-IEF and IPG gels in the presence of a zinc-chelating agent. Mass spectra were clearly interpretable as carrier ampholytes which were efficiently removed before digestion; high-sequence coverage that allowed isoform characterization was obtained by analyzing both the aqueous and the organic phase extracts.     

Far-infrared absorption of MgO: Fe2+ in magnetic fields

We have measured the far-infrared absorption of iron-doped MgO in the wavenumber region 10–200 cm^?1 and in magnetic fields up to 6 T. Absorption peaks found at 107.0 and 110.5 cm^?1 are assigned to magnetic dipole transitions between the spin-orbit Г_5g groundstate (J = 1) and the Г_3g, Г_4g excited states (J = 2) of the Fe²⁺ -ion at a cubic site. The observed magnetic field dependence shows that Г_4g is the higher excited level, so that the crystal field order of the levels is not changed by the reduction of the spin-orbit splitting attributed to a dynamic Jahn-Teller effect. An additional absorption peak at 33.4 cm^?1 is found to split in magnetic field.In iron-doped KMgF₃ absorption peaks at 52 and 87 cm^?1 that have previously been attributed to the same transitions of Fe²⁺ are found to remain unshifted and unsplit in magnetic fields up to 6 T.     

Aqueous DMF-potassium carbonate as a substitute for thallium and silver additives in the palladium-catalyzed conversion of aryl bromides to acetyl arenes

Highly selective palladium-catalyzed internal alpha-arylations of alkyl vinyl ethers with aryl and heteroaryl bromides were conveniently conducted in aqueous DMF with potassium carbonate as base and with DPPP as bidentate ligand. The corresponding acetyl arene products were, after hydrolysis, isolated in good to excellent yields. This Heck reaction procedure does not require toxic thallium or expensive silver salt additives, is promoted by water, and is suggested to proceed via charged organopalladium intermediates. Single-mode microwave irradiation was utilized in one example to shorten the reaction time.