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Semiconducting nanowire Josephson junctions represent an attractive platform to investigate the anomalous Josephson effect and detect topological superconductivity. However, an external magnetic field generally suppresses the supercurrent through hybrid nanowire junctions and significantly limits the field range in which the supercurrent phenomena can be studied. In this work, we investigate the impact of the length of InSb-Al nanowire Josephson junctions on the supercurrent resilience against magnetic fields. We find that the critical parallel field of the supercurrent can be considerably enhanced by reducing the junction length. Particularly, in 30 nm long junctions supercurrent can persist up to 1.3 T parallel field─approaching the critical field of the superconducting film. Furthermore, we embed such short junctions into a superconducting loop and obtain the supercurrent interference at a parallel field of 1 T. Our findings are highly relevant for multiple experiments on hybrid nanowires requiring a magnetic-field-resilient supercurrent.

Majorana bound states constitute one of the simplest examples of emergent non-Abelian excitations in condensed matter physics. A toy model proposed by Kitaev shows that such states can arise at the ends of a spinless p-wave superconducting chain1. Practical proposals for its realization2,3require coupling neighbouring quantum dots (QDs) in a chain through both electron tunnelling and crossed Andreev reflection4. Although both processes have been observed in semiconducting nanowires and carbon nanotubes5–8, crossed-Andreev interaction was neither easily tunable nor strong enough to induce coherent hybridization of dot states. Here we demonstrate the simultaneous presence of all necessary ingredients for an artificial Kitaev chain: two spin-polarized QDs in an InSb nanowire strongly coupled by both elastic co-tunnelling (ECT) and crossed Andreev reflection (CAR). We fine-tune this system to a sweet spot where a pair of poor man’s Majorana states is predicted to appear. At this sweet spot, the transport characteristics satisfy the theoretical predictions for such a system, including pairwise correlation, zero charge and stability against local perturbations. Although the simple system presented here can be scaled to simulate a full Kitaev chain with an emergent topological order, it can also be used imminently to explore relevant physics related to non-Abelian anyons.

There is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genome-wide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but have low individual penetrance. Combining the SNPs in a polygenic risk score (PRS) is a possible approach to improve their usefulness. Using 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR = 3.44, 95% CI 2.53–4.69, p= 3.55 × 10−15for the highest vs. lowest quintile of the weighted score, and OR = 3.18, 95% CI 2.1 = 34–4.33, p= 1.62 × 10−13for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM. Our work provides additional validation of previously discovered MM risk variants and of their combination into a PRS, which is a first step towards the use of genetics for risk stratification in the general population.

ABSTRACTObjective: To evaluate the correlation between the Bruxism Episodes Index (BEI) that determines the number of bruxism episodes per hour of sleep and sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI).Methods: Seventy-seven participants (56 women and 21 men) in which probable sleep bruxism was diagnosed using guidelines of the American Academy of Sleep Medicine underwent video-polysomnography. Sleep quality was measured using PSQI.Results: The analysis showed the lack of a statistically significant correlation between the BEI and PSQI scores (p= 0.55). Analysis also showed that the study group (bruxers) and control group (non-bruxers) did not differ significantly in terms of PSQI scores (p= 0.88).Conclusion: The intensity of bruxism seems not to affect the quality of sleep. However, the topic of the relationship between sleep quality and the occurrence of sleep bruxism requires further research, taking into account co-occurring sleep disorders and sleep architecture.

In most naturally occurring superconductors, electrons with opposite spins form Cooper pairs. This includes both conventional s-wave superconductors such as aluminium, as well as high-transition-temperature, d-wave superconductors. Materials with intrinsic p-wave superconductivity, hosting Cooper pairs made of equal-spin electrons, have not been conclusively identified, nor synthesized, despite promising progress1–3. Instead, engineered platforms where s-wave superconductors are brought into contact with magnetic materials have shown convincing signatures of equal-spin pairing4–6. Here we directly measure equal-spin pairing between spin-polarized quantum dots. This pairing is proximity-induced from an s-wave superconductor into a semiconducting nanowire with strong spin–orbit interaction. We demonstrate such pairing by showing that breaking a Cooper pair can result in two electrons with equal spin polarization. Our results demonstrate controllable detection of singlet and triplet pairing between the quantum dots. Achieving such triplet pairing in a sequence of quantum dots will be required for realizing an artificial Kitaev chain7–9.

Persevering research efforts that seek to harness the potential of singlet fission to increase the efficiency of photovoltaic devices have recently focused on vibronic mechanisms that presumably underlie this process. The fundamental theoretical input needed for treating the transitions between the electronic states involved are the Franck–Condon parameters that govern the generation of the coherent vibrational wave packets emerging in the fission phenomenon and in the experiments performed for its investigation. Their calculation for triplet states is not commonly practiced, so they are usually simulated by their singlet counterparts. On the basis of the analysis of coherence flow descriptors, here we find the validity of this approximation questionable for subtle interpretative issues of femtosecond pump–probe vibrational spectroscopy where a slight difference in a mode’s coherence power may have a pivotal role in assessing the mechanism of fission dynamics. In less sensitive instances, the approach is acceptably reliable at qualitative level, apart from a tendency to predict sporadic spurious coherences. Our methodology may lead to a potential tool for detecting those artifacts.

It has been hypothesized in the literature that a comparison of femtosecond pump–probe spectra of vibrational coherences generated in the triplet-pair electronic state via singlet fission with those in which coherences were shaped independently by direct Raman scattering may shed light on the role of individual vibrational modes in the fission process. It has been tacitly assumed that the two spectra would coincide if the fission process itself leaves the coherences unaffected. We demonstrate that there are no theoretical arguments for these spectra to coincide since vibrational wavepackets generated in the two types of experiments are formed by different mechanisms. Formulas describing the respective coherence intensities are different, containing different powers and different values of the descriptors of the electronic transitions involved. These descriptors are Franck–Condon parameters, here obtained from quantum chemistry calculations. The problem is illustrated in the example of 13,13′-bis(mesityl)-6,6′-dipentacenyl (DPMes) for which experimental spectra of both kinds were published. We show here that among the main factors governing the form of the vibrational wavepackets generated in the two kinds of experiments are the energy profiles of the coherent light pulses emitted by the pumping lasers. When the factors mentioned above are not taken into account, the comparison of the resulting coherences may lead to confusing interpretational artifacts. The same is expected to be valid also for a plethora of other applications of broadband impulsive vibrational spectroscopy.

A multicenter, prospective, observational, non-interventional study evaluated the response to treatment in patients with chronic lymphocytic leukemia (CLL) depending on the rituximab-chemotherapy (R-chemo) regimen used in routine clinical practice in Poland. The primary endpoint was the overall response rate (ORR) regarding the R-chemo regimen. The secondary endpoints were complete remission (CR), partial remission (PR), progressive disease (PD) and stable disease (SD) rates. A total of 400 CLL patients were enrolled in 20 sites in Poland. Data were collected on-line using eCRF during 6-months rituximab treatment. There were 150 treatment-naive patients (37.5%) and 250 patients with recurrent disease (62.5%) enrolled to the study. The overall ORR in R-FC-treated patients was 87.28%, 78.57% for the R-COP regimen, and for other regimens – 51.72%. Complete remission was achieved in 141 patients (36.25%), including 16.40% in patients receiving first-line treatment and 11.76% in relapsed disease. Partial remission was achieved in 166 patients (42.67%), including 38.4% in patients on first-line treatment and 38.56% in patients treated for recurrence. Complete or partial responses were achieved in 78.92% in total. No new safety signals were detected in comparison to safety profile described in Summary of Product Characteristics.

We present a novel density-functional tight-binding (DFTB) parametrization toolkit developed to optimize the parameters of various DFTB models in a fully automatized fashion. The main features of the algorithm, based on the particle swarm optimization technique, are discussed, and a number of initial pilot applications of the developed methodology to molecular and solid systems are presented.

We present an efficient numerical integration scheme (TWOCENT) to be used in the context of automatized parameterization of the density‐functional tight‐binding (DFTB) method. The accuracy of the integration process is assessed and its range of applicability is discussed. The functionality of the developed code is tested by reproducing the electronic portion of the existing mioparameter sets and by reproducing a series of reference DFT band structures of elemental solids. We present an efficient numerical integration scheme to be used in the context of automatized parameterization of the DFTB method. The functionality of the developed code is tested by reproducing the electronic portion of the existing parameter sets and a series of reference DFT band structures of elemental solids.

According to recent ab initio calculations, the energy gap between the two oppositely polarized charge-transfer (CT) states of a model pentacene dimer is anomalously large, attaining 0.8 eV. Here we introduce the self-consistent charge field approach to evaluate the electrostatic stabilization energies of the pertinent states in the pentacene crystal represented by a dedicated multiscale model system containing the model dimer as its core. We demonstrate that, contrary to common wisdom, the lower of the two CT states is barely affected by the crystalline environment whereas the upper one undergoes a large red shift. Effectively, embedding of the dimer in the crystal bulk reduces the pertinent splitting by an order of magnitude, because most of the intradimer charge–quadrupole interactions are compensated by similar interactions with surrounding molecules. This resolves the apparent contradiction between the ab initio result obtained for the dimer and the splitting of about 0.04 eV resulting from microelectrostatic calculations for the crystal.

A neural-network controlled dynamic evolutionary scheme for global molecular geometry optimizationA novel, neural network controlled, dynamic evolutionary algorithm is proposed for the purposes of molecular geometry optimization. The approach is tested for selected model molecules and some molecular systems of importance in biochemistry. The new algorithm is shown to compare favorably with the standard, statically parametrized memetic algorithm.

Abstract: The pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) has been linked with the production and activity of certain growth factors. However a significant proportion of CLL patients display immune abnormalities suggestive of aberrant cytokine secretion and/or response. In contrast to B lymphocytes, T cells of B-CLL patients characterise with the increased production of interferon-gamma (IFN-γ) and this cytokine has been indicated to prevent malignant cells from entering apoptosis including the slowly expanding population of CD5+ B cells that characterizes chronic lymphocytic leukemia. The aim of the present study was to assess whether functionally relevant interferon-gamma gene (IFNG) polymorphism (+847 A/T) contributes to the pathogenesis of B-CLL. In total 110 individuals was investigates, including 61 CLL patients and 50 healthy individuals. The presence of the IFNG AA genotype was found to be associated with susceptibility to CLL (23/61 vs. 7/50, p < 0.005, for patients and controls, respectively). This results suggest that individuals rather prone to the lower level of IFN-γ production (associated with the presence of the A allele) appear to be more susceptible to this malignant disease.

This study was performed to investigate the association between interferon (IFN)-γ single nucleotide polymorphism (SNP) and susceptibility for psoriasis vulgaris. DNA from 78 patients with psoriasis vulgaris (54 patients with type I psoriasis, 24 with type II psoriasis) and 74 healthy volunteers was investigated. IFN-γ promoter gene SNP in position 874 was evaluated by polymerase chain reaction with sequence-specific primers (PCR-SSP) and the results were compared between a group of psoriatic patients, divided into early onset of psoriasis (type I) and late onset of psoriasis (type II) subgroups, and healthy control subjects. A significant difference in the genotype frequencies between psoriasis patients and healthy controls was found (p <0.02) and no significant differences were observed analyzing subsets of psoriatic patients (gender, type of disease) also in carriage and allele frequencies. The results suggest that IFN-γ polymorphism is associated with susceptibility to psoriasis vulgaris.

Non-Hodgkin's lymphomas (nHL) are a heterogenous group of lymphoid malignancies with a different pattern of behaviour and response to treatment. In Europe and North America mainly B-cell lymphomas (86%) are observed. Indolent lymphomas are lymphoproliferative diseases with a relatively good prognosis and long natural history. They usually affect elderly people and more than 90% of cases are diagnosed in advanced stages of the disease. Forty percent all cases of nHL are indolent lymphomas. Indolent lymphomas are curable only in their early stages when radiotherapy is the treatment of choice. In advanced stages chemotherapy is used. However, up till now aggressive chemotherapy does not improve the overall survival rate and it leads to serious adverse events. This article presents current options of management of indolent nHL, especially using purine analogues and monoclonal antibodies.

Angiogenesis is a multistep process of the development of capillaries from established blood vessels. Angiogenesis probably plays a significant role in the development and progression of hematopoietic malignancies. Higher microvascular density and increased serum levels of proangiogenic factors such as vascular endothelial growth factor (VEGF) or basic fibroblasts growth factor (bFGF) have been reported in acute and chronic leukemias, myeloproliferative and myelodysplastic disorders, multiple myeloma and lymphomas. The microvessel density of bone marrow stroma in myeloproliferative disorders is increased and VEGF is considered as the most potent endothelial cell activator. The purpose of this study was to examine the expression of VEGF in bone marrow of patients with MPD. 60 paraffin-embedded bone marrow core biopsy specimens from newly diagnosed patients with MPD were evaluated. In addition 10 bone marrow core biopsy specimens from adult patients without evidence of malignancy were used as controls. Bone marrow sections were stained immunohistochemically for VEGF (PharMingen, USA). Obtained data show that MPD are associated with an increased expression of VEGF in the bone marrow. This observation support previous studies suggesting that angiogenesis may play a role in the pathophysiology of myeloproliferative disorders. Clinical significance of this phenomenon needs further investigation however thus provides rationale for use of angiogenesis inhibitors in MPD therapy.

The Merrifield model of electronic excitations in a linear molecular crystal is applied to investigate the relation between the bound electron–hole pairs (charge transfer excitons) and the corresponding continuum of unbound states. It is demonstrated that, contrary to the conventional explanation, the difference of 0.2–0.3 eV between the electric and optical band gap observed for polyacene crystals is a consequence of charge delocalization rather than lattice relaxation. The results also suggest that in some molecular crystals and polymers, moderate structural disorder may strengthen the photoconductive response instead of suppressing it, which suggests a new strategy in the search for efficient photoconductors.

The observed difference of 0.2–0.3 eV between the optical and electric band gap in organic solids was commonly attributed to vibrational relaxation. The recently calculated values [I.V. Brovchenko, Chem. Phys. Lett. 278 (1997) 355] of the lattice relaxation energy in the vicinity of a charge carrier or a charge-transfer state never exceed 0.02–0.03 eV, demonstrating that the conventional rationalization of the difference is no longer tenable. An alternative explanation is proposed where the difference is interpreted in terms of charge delocalization and the past controversies are attributed to inconsistencies in treating this contribution to energy.

The recently introduced quadratic(two-electron) valenceindices, ionic and covalent, derived from the Hartree–Fock finite-difference approach, are applied to selected organic and inorganic molecules to demonstrate their utility in monitoring chemical bonding patterns in molecular systems. The indices are defined in terms of differerences between simultaneous probabilities of finding two electrons on specified atoms, calculated from the molecular and separated-atom-limit(SAL) wave functions, respectively, in the UHF approximation. The total quadratic valence number represents the overall number of chemical bonds in the system under consideration; it is interpreted as the molecular expectation value of the difference operator of the molecular and SAL density operators. This interpretation leads to a new set of ionic atomic and diatomic valence components; these modified valence numbers are discussed using the two-orbital model in the UHF scheme. A new procedure is proposed for dividing the one-center contributions to the bond valences; it generates effective bond orders in qood agreement with chemical expectations. The new valence quantities are tested on selected typical molecules and prototype hydrogen-bonded dimers. A more extensive study has been carried out on small-ring propellanes, to examine changes in bond valences between bridgehead atoms in selected systems. Keywords: chemical valence: UHF difference approach; chemical bond: two-electron model; bond multiplicities; ionic/covalent bond components; propellanes: valence study.

Malignant melanoma is a neoplasm with an often unpredictable course and metastases potentially affecting all organs of the human body. Metastases into the gall bladder are rare. The role of hormonal background in the development and progression of malignant melanoma has not been established. The authors present a case of a 63-year-old man who had initially undergone long-term hormone therapy for the treatment of prostate cancer, and later presented with melanoma metastatic to the gall bladder.

Primary cutaneous T-cell lymphomas (CTCL) represent a heterogeneous group of neoplasms derived from skin-homing T cells. CTCL behave similarly to indolent B-cell lymphomas. There is increasing evidence that angiogenesis may be important in lymphoproliferative disorders. The aim of the study was to evaluate microvessel density (MVD) as a parameter of tumor angiogenesis measured by the expression of CD34 in the skin samples in CTCL patients. Formaldehyde-fixed, paraffin-embedded skin tumor biopsy specimens from 25 patients (16 men, 9 women) with CTCL (mycosis fungoides), and 8 skin samples from healthy volunteers were analysed. The preparations were stained with haematoxylin and eosin, and evaluated histopathologically. Staining for endothelial cells with monoclonal antibody against CD34 revealed a mean number of 134 dots per mm2for CTCL and 106 dots/mm2for controls; the difference was statistically significant (p=0.0388). Our study shows a higher number of microvessels in primary CTCL compared with normal skin. Microvascular endothelial cells have become an important target in cancer therapy. Increased MVD in the skin of CTCL patients indicate that angiogenesis may play a role in the growth of CTCL, and raises the possibility of using angiogenesis inhibitors in CTCL therapy.

Miklos: AOP Orphan: Honoraria; Novo nordisk: Honoraria. Strugov:Janssen: Honoraria, Other: Travel expense, Research Funding; Abbvie: Other: Travel expense. Lewerin:Abbvie: Consultancy. Grosicki:Affimed: Research Funding. Steurer:Novartis: Consultancy, Honoraria, Research Funding. Montillo:Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Research Funding. Middeke:Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Stefanelli:Novartis: Employment, Equity Ownership. Vincent:Novartis: Employment. G:Novartis: Employment. Österborg:Beigene: Research Funding; Abbvie: Research Funding; Gilead: Consultancy, Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding.

Background:In 2014, a planned interim analysis of an open-label, two-arm, randomized, phase III study of ofatumumab (OFA) vs physicians' choice (PC) treatment (most patients received rituximab-, alemtuzumab-, alkylator-, or fludarabine-based therapies) in patients with bulky fludarabine-refractory chronic lymphocytic leukemia (BFR CLL) was performed to assess the effectiveness of OFA in the time-period prior to administering small molecule kinase inhibitors. The study did not meet its primary endpoint of progression-free survival (PFS) as assessed by the independent review committee (median PFS 5.4 months vs 3.6 months; hazard ratio [HR]=0.79, 95% confidence interval [CI]: 0.50, 1.24; p=0.268). Here, we report the 5-year follow-up of the study.