Long-Lived Charge Separation in Single Crystals of an Electron Donor Covalently Linked to Four Acceptor Molecules.

Crystalline donor-acceptor (D-A) systems serve as an excellent platform for studying CT exciton creation, migration, and dissociation into free charge carriers for solar energy conversion. Donor-acceptor cocrystals have been utilized to develop an understanding of CT exciton formation in ordered organic solids; however, the strong electronic coupling of the D and A units can sometimes limit charge separation lifetimes due to their close proximity. Covalent D-A systems that preorganize specific donor-acceptor structures can assist in engineering crystal morphologies that promote long-lived charge separation to overcome this limitation. Here we investigate photogenerated CT exciton formation in a single crystal of a 2,5,8,11-tetraphenylperylene (PerPh4) donor to which four identical naphthalene-(1,4:5,8)-bis(dicarboximide) (NDI) electron acceptors are covalently attached at the para positions of the PerPh4 phenyl groups to yield PerPh4-NDI4. X-ray crystallography shows that the four NDIs pack pairwise into two distinct motifs. Two NDI acceptors of one PerPh4-NDI4 are positioned over the PerPh4 donors of adjacent PerPh4-NDI4 molecules with the donor and acceptor π-systems having a large dihedral angle between them, while the other two NDIs of PerPh4-NDI4 form xylene-NDI van der Waals π-stacks with the corresponding NDIs in adjacent PerPh4-NDI4 molecules. Upon selective photoexcitation of PerPh4 in the single crystal, CT exciton formation occurs in <300 fs yielding electron-hole pairs that live for more than ∼16 µs. This demonstrates the effectiveness of covalently linked D-A systems for engineering single crystal structures that promote efficient and long-lived charge separation for solar energy conversion.

Oriented Triplet Excitons as Long-Lived Electron Spin Qutrits in a Molecular Donor-Acceptor Single Cocrystal.

The photogeneration of multiple unpaired electron spins within molecules is a promising route to applications in quantum information science because they can be initialized into well-defined, multilevel quantum states (S > 1/2) and reproducibly fabricated by chemical synthesis. However, coherent manipulation of these spin states is difficult to realize in typical molecular systems due to the lack of selective addressability and short coherence times of the spin transitions. Here, these challenges are addressed by using donor-acceptor single cocrystals composed of pyrene and naphthalene dianhydride to host spatially oriented triplet excitons, which exhibit promising photogenerated qutrit properties. Time-resolved electron paramagnetic resonance (TREPR) spectroscopy demonstrates that spatially orienting triplet excitons in a single crystal platform imparts narrow, well-resolved, tunable resonances in the triplet EPR spectrum, allowing selective addressability of the spin sublevel transitions. Pulse-EPR spectroscopy reveals that at temperatures above 30 K, spin decoherence of these triplet excitons is driven by exciton diffusion. However, coherence is limited by electronic spin dipolar coupling below 30 K, where T2 varies nonlinearly with the optical excitation density due to exciton annihilation. Overall, an optimized coherence time of T2 = 7.1 µs at 20 K is achieved. These results provide important insights into designing solid-state molecular excitonic materials with improved spin qutrit properties.

Mechanism of Ultrafast Triplet Exciton Formation in Single Cocrystals of π-Stacked Electron Donors and Acceptors.

Ultrafast triplet formation in donor-acceptor (D-A) systems typically occurs by spin-orbit charge-transfer intersystem crossing (SOCT-ISC), which requires a significant orbital angular momentum change and is thus usually observed when the adjacent π systems of D and A are orthogonal; however, the results presented here show that subnanosecond triplet formation occurs in a series of D-A cocrystals that form one-dimensional cofacial π stacks. Using ultrafast transient absorption microscopy, photoexcitation of D-A single cocrystals, where D is coronene (Cor) or pyrene (Pyr) and A is N,N-bis(3'-pentyl)-perylene-3,4:9,10-bis(dicarboximide) (C5PDI) or naphthalene-1,4:5,8-tetracarboxydianhydride (NDA), results in formation of the charge transfer (CT) excitons Cor•+-C5PDI•-, Pyr•+-C5PDI•-, Cor•+-NDA•-, and Pyr•+-NDA•- in <300 fs, while triplet exciton formation occurs in τ = 125, 106, 484, and 958 ps, respectively. TDDFT calculations show that the SOCT-ISC rates correlate with charge delocalization in the CT exciton state. In addition, time-resolved EPR spectroscopy shows that Cor•+-C5PDI•- and Pyr•+-C5PDI•- recombine to form localized 3*C5PDI excitons with zero-field splittings of |D| = 1170 and 1250 MHz, respectively. In contrast, Cor•+-NDA•- and Pyr•+-NDA•- give triplet excitons in which |D| is only 1240 and 690 MHz, respectively, compared to that of NDA (2091 MHz), which is the lowest energy localized triplet exciton, indicating that the Cor-NDA and Pyr-NDA triplet excitons have significant CT character. These results show that charge delocalization in CT excitons impacts both ultrafast triplet formation as well as the CT character of the resultant triplet states.

Using Molecular Design to Enhance the Coherence Time of Quintet Multiexcitons Generated by Singlet Fission in Single Crystals.

Multiexciton quintet states, 5(TT), photogenerated in organic semiconductors using singlet fission (SF), consist of four quantum entangled spins, promising to enable new applications in quantum information science. However, the factors that determine the spin coherence of these states remain underexplored. Here, we engineer the packing of tetracene molecules within single crystals of 5,12-bis(tricyclohexylsilylethynyl)tetracene (TCHS-tetracene) to demonstrate a 5(TT) state that exhibits promising spin qubit properties, including a coherence time, T2, = 3 µs at 10 K, a population lifetime, Tpop, = 130 µs at 5 K, and stability even at room temperature. The single-crystal platform also enables global alignment of the spins and, consequently, individual addressability of the spin-sublevel transitions. Decoherence mechanisms, including exciton diffusion, electronic dipolar coupling, and nuclear hyperfine interactions, are elucidated, providing design principles for increasing T2 and the operational temperature of 5(TT). By dynamically decoupling 5(TT) from the surrounding spin bath, T2 = 10 µs is achieved. These results demonstrate the viability of harnessing singlet fission to initiate multiple electron spins in a well-defined quantum state for next-generation molecular-based quantum technologies.

EVALUATION OF THE EFFECT OF ADEMOL ON THE DYNAMICS OF NEURON-SPECIFIC ENOLASE IN TRAUMATIC BRAIN INJURY IN RATS.

The great hopes of modern medicine for neuroprotective therapy have stimulated scientists around the world to actively search for new effective means of influencing the pathophysiological cascades of the development of neuronal damage. Aim. To evaluate the effect of the use of the adamantane derivative 1-adamantylethyloxa-3-morpholino-2-propanol hydrochloride (ademol) compared with amantadine sulfate and 0.9% NaCl solution on the activity dynamics of neuron-specific enolase in rats with acute traumatic brain injury (TBI) . The therapeutic effect of ademol in experimental traumatic brain injury was evaluated using a dose of 2 mg/kg (i/v) every 12 hours for 8 days. The pseudo-operated animals and the control group received a 0.9% NaCl solution at a dose of 2 ml/kg i/v, and the comparison group received amantadine sulfate at a dose of 5 mg/kg in the same mode. To determine the effectiveness of the studied drugs in brain injury, the level of neuron-specific enolase (NSE) was used. The course infusion in rats with TBI of solutions of ademol (2 mg/kg) and amantadine sulfate (5 mg/kg) during the 8 days of the TBI model, significantly reduced the increase in the NSE level in animals of the control pathology group by an average of 52.1 and 38.2%. Thus, the results obtained indicate that when using ademol at a dose of 2 mg/kg i/v and amantadine sulfate (5 mg/kg i/v), powerful neurocytoprotective properties appear against the background of a model head injury. Moreover, the neuroprotective effect of ademol manifested itself more clearly, since in terms of the ability to prevent the increase in NSE levels, it significantly dominated the reference drug by an average of 22.5%.

Singlet Fission in Perylene Monoimide Single Crystals and Polycrystalline Films.

Singlet fission (SF) is a spin-allowed process in which a photogenerated singlet exciton down-converts into two triplet excitons. Perylene-3,4-dicarboximide (PMI) has singlet and triplet state energies of 2.4 and 1.1 eV, respectively; thus making SF slightly exoergic and providing triplet excitons that have sufficient energy to raise the efficiency of single-junction solar cells by reducing thermalization losses from hot excitons formed when absorbed photons have energies higher than the semiconductor bandgap. However, PMI SF in the solid state has not been studied previously. Here, we show that 2,5-diphenyl-N-(2-ethylhexyl)perylene-3,4-dicarboximide (dp-PMI) crystallizes into a slip-stacked intermolecular morphology favorable for SF. Transient absorption microscopy and spectroscopy show that dp-PMI SF occurs in ≤50 ps in both single crystals and polycrystalline thin films with a triplet yield of 150 ± 20%. Ultrafast SF in the solid state, the high triplet yield, and its photostability make dp-PMI an attractive candidate for SF-enhanced solar cells.

Acoustic particle trapping driven by axial primary radiation force in shaped traps.

We study particle trapping driven by the axial primary radiation force (A-PRF) in shaped traps exposed to standing bulk acoustic waves (S-BAW) using numerical simulations and experiments. The utilization of the stronger A-PRF as the main retention force is a consequence of standing-wave formation along the flow direction, instead of the orthogonal direction as in the case of traditionally used lateral-PRF S-BAW trapping setups. The study of particle dynamics reveals that the competition between A-PRF and viscous drag force governs particle trajectory. The ratio of the acoustic energy to the viscous work (ß) provides a general criterion for particle trapping at a distinctive off-node site that is spatially controllable. Particles get trapped for ß≥ß_{cr} at some distance away from the nodal plane and the distance varies as ß^{-c} (c=0.6-1.0). The use of A-PRF as the retention force could potentially allow traditional S-BAW trapping systems to envisage high-throughput advancements surpassing the current standards in cell-handling unit operations.

Real-world impact of anti-HER2 therapy-related cardiotoxicity in patients with advanced HER2-positive breast cancer.

BACKGROUND: Anti-HER2 therapy-related cardiotoxicity is well described in the context of clinical trials, particularly in the setting of early stage disease, but there is more limited data in advanced breast cancer and in the real world setting. MATERIAL AND METHODS: A prospectively-maintained registry database with 312 consecutive patients diagnosed with HER2 positive advanced breast cancer in Australia was analysed. RESULTS: 287 patients (92%) received anti-HER2 therapy, 17 (6%) experienced anti-HER2 therapy-related cardiotoxicity. Patients who experienced cardiotoxicity were more likely to have ≥2 risk factors for cardiotoxicity (OR 3.9 95% CI 1.4-11.3 p = 0.01). A prior diagnosis of cardiovascular disease was significantly associated with cardiotoxicity (OR 7.1 95% CI 1.3-39.5). Cardiotoxicity resolved on imaging in 65% of patients; there was no association between severity and resolution. 11 patients (65%) received cardiologist input. Of the patients who developed cardiotoxicity, 12 patients (71%) received further anti-HER2 therapy in the first- or second-line setting without recurrent cardiotoxicity. DISCUSSION AND CONCLUSION: Therapy-related cardiotoxicity is an uncommon complication of anti-HER2 therapy in the real world setting. Cardiac toxicity resolved in the majority of affected patients, and further anti-HER2 therapy was administered without recurrence of cardiac issues. Our data suggests anti-HER2 therapy can be safely given in routine care, even in patients with risk factors for toxicity.

Author Correction: LSD1 activation promotes inducible EMT programs and modulates the tumour microenvironment in breast cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

LSD1 activation promotes inducible EMT programs and modulates the tumour microenvironment in breast cancer.

Complex regulatory networks control epithelial-to-mesenchymal transition (EMT) but the underlying epigenetic control is poorly understood. Lysine-specific demethylase 1 (LSD1) is a key histone demethylase that alters the epigenetic landscape. Here we explored the role of LSD1 in global epigenetic regulation of EMT, cancer stem cells (CSCs), the tumour microenvironment, and therapeutic resistance in breast cancer. LSD1 induced pan-genomic gene expression in networks implicated in EMT and selectively elicits gene expression programs in CSCs whilst repressing non-CSC programs. LSD1 phosphorylation at serine-111 (LSD1-s111p) by chromatin anchored protein kinase C-theta (PKC-θ), is critical for its demethylase and EMT promoting activity and LSD1-s111p is enriched in chemoresistant cells in vivo. LSD1 couples to PKC-θ on the mesenchymal gene epigenetic template promotes LSD1-mediated gene induction. In vivo, chemotherapy reduced tumour volume, and when combined with an LSD1 inhibitor, abrogated the mesenchymal signature and promoted an innate, M1 macrophage-like tumouricidal immune response. Circulating tumour cells (CTCs) from metastatic breast cancer (MBC) patients were enriched with LSD1 and pharmacological blockade of LSD1 suppressed the mesenchymal and stem-like signature in these patient-derived CTCs. Overall, LSD1 inhibition may serve as a promising epigenetic adjuvant therapy to subvert its pleiotropic roles in breast cancer progression and treatment resistance.

[Hormonal islet cell tumors. Proposition of a diagnostic-therapeutic model]. / Guzy hormonalnie czynne trzustki. Propozycja modelu diagnostyczno-terapeutycznego.

Islet cell tumors make a serious therapeutic problem due to their specific clinical presentation and the necessity of applying a variety of multidisciplinary diagnostic and therapeutic methods. The authors present their own algorithm for diagnosing and treatment of islet-cell tumors worked out basing on many-year experience.

The effect of Jewish religiosity of elderly Israelis on their life satisfaction, health, function and activity.

The purpose of this study was to examine the factors that make for 'successful aging'. In particular, we examined the relationship between the degree of religious or traditional observance on overall life satisfaction, health, function, and activity of an elderly population. The subjects chosen were aged from 68 to 75 and were divided into two groups: 37 percent were traditionally observant ('traditional') and 67 percent religiously observant ('religious'). Overall the sociodemographic features of both groups were similar. The results of the study did show, however, that the most significant factors in influencing the subjects' life satisfaction were religiosity and functional adequacy. Our conclusions from these findings indicate that the religious observant elderly person, who is religiously active, retains a social status that earns him respect because of this activity. This status even provides him with a source of power in his social group, as a result of which he functions more effectively and is more satisfied with life.

A ten year study of heparin therapy for thrombophlebitis in ambulatory patients.

During the past ten years, we have observed 407 patients with thrombophlebitis using a standardized outpatient regimen including subcutaneously self-administered heparin therapy. A definite protocol for tapering and discontinuing anticoagulants was applied which allows a correlation between duration of heparin administration, decreasing heparin resistance and symptomatic improvement. In acute and subacute thrombophlebitis, this method induced symptomatic resolution within less than two months in half of the patients and within less than six months in 78%. The number of recurrences during the follow-up period was acceptable and the frequency of complications minimal. We conclude that, except in the most severe, toxic instances of thrombophlebitis or in suspected pulmonary embolism, hospitalization--complete bedrest and intravenously administered anticoagulants--is unnecessary and wasteful.

Long-term function of NCGT vascular conduits in a multicenter trial: evaluation of physical chemical parameters.

Our experience with the NCGT graft has now encompassed 12 years in experimental animals and 4.5 years clinical experience with 134 grafts in man. It has previously been suggested that vessel wall structure, interface-charge, electric potential, and polarity of the blood intimal interface appear critical in the prevention of intravascular thrombosis in all vascular prosthetic bypass grafts. This concept has now been confirmed using ferritin, colloidal iron and fluorescamine intimal labelling. These provide a quantitative special characterization of the surface charges of several grafts, including the NCGT graft. Study indicates that each step in the production of the NCGT graft results in a cumulative increase in the structured negative charge of the vascular interface. The more dense the structured negative charge of the prosthesis, the more resistant is the graft to short and long-term thrombosis in experimental animals and man. The experience has been confirmed with a comparative analysis of implantation results in 105 patients up to 4.5 years with 65 to 70% patency rate over that time interval. Statistical analysis of parameters confirm again that the polarity and structure of the vascular interface is important in the effective function and patency rate of the grafts.