Beyond metals: theoretical discovery of semiconducting MAX phases and their potential application in thermoelectrics.

MAX phase is a family of ceramic compounds, typically known for their metallic properties. However, we show here that some of them may be narrow bandgap semiconductors. Using a series of first-principles calculations, we have investigated the electronic structures of 861 dynamically stable MAX phases. Notably, Sc2SC, Y2SC, Y2SeC, Sc3AuC2, and Y3AuC2 have been identified as semiconductors with band gaps ranging from 0.2 to 0.5 eV. Furthermore, we have assessed the thermodynamic stability of these systems by generating ternary phase diagrams utilizing evolutionary algorithm techniques. Their dynamic stabilities are confirmed by phonon calculations. Additionally, we have explored the potential thermoelectric efficiencies of these materials by combining Boltzmann transport theory with first-principles calculations. The relaxation times are estimated using scattering theory. The zT coefficients for the aforementioned systems fall within the range of 0.5 to 2.5 at temperatures spanning from 300 to 700 K, indicating their suitability for high-temperature thermoelectric applications.

Nuclear quantum effects on the vibrational dynamics of the water-air interface.

We have applied path-integral molecular dynamics simulations to investigate the impact of nuclear quantum effects on the vibrational dynamics of water molecules at the water-air interface. The instantaneous fluctuations in the frequencies of the O-H stretch modes are calculated using the wavelet method of time series analysis, while the time scales of vibrational spectral diffusion are determined from frequency-time correlation functions and joint probability distributions. We find that the inclusion of nuclear quantum effects leads not only to a redshift in the vibrational frequency distribution by about 120 cm-1 for both the bulk and interfacial water molecules but also to an acceleration of the vibrational dynamics at the water-air interface by as much as 35%. In addition, a blueshift of about 45 cm-1 is seen in the vibrational frequency distribution of interfacial water molecules compared to that of the bulk. Furthermore, the dynamics of water molecules beyond the topmost molecular layer was found to be rather similar to that of bulk water.

Simulations of disordered matter in 3D with the morphological autoregressive protocol (MAP) and convolutional neural networks.

Disordered molecular systems, such as amorphous catalysts, organic thin films, electrolyte solutions, and water, are at the cutting edge of computational exploration at present. Traditional simulations of such systems at length scales relevant to experiments in practice require a compromise between model accuracy and quality of sampling. To address this problem, we have developed an approach based on generative machine learning called the Morphological Autoregressive Protocol (MAP), which provides computational access to mesoscale disordered molecular configurations at linear cost at generation for materials in which structural correlations decay sufficiently rapidly. The algorithm is implemented using an augmented PixelCNN deep learning architecture that, as we previously demonstrated, produces excellent results in 2 dimensions (2D) for mono-elemental molecular systems. Here, we extend our implementation to multi-elemental 3D and demonstrate performance using water as our test system in two scenarios: (1) liquid water and (2) samples conditioned on the presence of pre-selected motifs. We trained the model on small-scale samples of liquid water produced using path-integral molecular dynamics simulations, including nuclear quantum effects under ambient conditions. MAP-generated water configurations are shown to accurately reproduce the properties of the training set and to produce stable trajectories when used as initial conditions in quantum dynamics simulations. We expect our approach to perform equally well on other disordered molecular systems in which structural correlations decay sufficiently fast while offering unique advantages in situations when the disorder is quenched rather than equilibrated.

Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency.

BACKGROUND: Biallelic mutations in LIG4 encoding DNA-ligase 4 cause a rare immunodeficiency syndrome manifesting as infant-onset life-threatening and/or opportunistic infections, skeletal malformations, radiosensitivity and neoplasia. LIG4 is pivotal during DNA repair and during V(D)J recombination as it performs the final DNA-break sealing step. OBJECTIVES: This study explored whether monoallelic LIG4 missense mutations may underlie immunodeficiency and autoimmunity with autosomal dominant inheritance. METHODS: Extensive flow-cytometric immune-phenotyping was performed. Rare variants of immune system genes were analyzed by whole exome sequencing. DNA repair functionality and T-cell-intrinsic DNA damage tolerance was tested with an ensemble of in vitro and in silico tools. Antigen-receptor diversity and autoimmune features were characterized by high-throughput sequencing and autoantibody arrays. Reconstitution of wild-type versus mutant LIG4 were performed in LIG4 knockout Jurkat T cells, and DNA damage tolerance was subsequently assessed. RESULTS: A novel heterozygous LIG4 loss-of-function mutation (p.R580Q), associated with a dominantly inherited familial immune-dysregulation consisting of autoimmune cytopenias, and in the index patient with lymphoproliferation, agammaglobulinemia, and adaptive immune cell infiltration into nonlymphoid organs. Immunophenotyping revealed reduced naive CD4+ T cells and low TCR-Vα7.2+ T cells, while T-/B-cell receptor repertoires showed only mild alterations. Cohort screening identified 2 other nonrelated patients with the monoallelic LIG4 mutation p.A842D recapitulating clinical and immune-phenotypic dysregulations observed in the index family and displaying T-cell-intrinsic DNA damage intolerance. Reconstitution experiments and molecular dynamics simulations categorize both missense mutations as loss-of-function and haploinsufficient. CONCLUSIONS: This study provides evidence that certain monoallelic LIG4 mutations may cause human immune dysregulation via haploinsufficiency.

Primary osteosarcoma of the ribs: A report from the Cooperative Osteosarcoma Study Group.

PURPOSE: Primary rib osteosarcoma has not been investigated extensively, and clinical characteristics and optimal therapeutic strategies have not been defined. The authors used the database of the Cooperative Osteosarcoma Study Group (COSS) to analyze this tumor-site in depth. METHODS: The COSS database was searched for treatment-naive, high-grade osteosarcomas of the rib. Affected patients were analyzed for demographic and tumor-related factors, treatments, and outcomes. RESULTS: A total of 44 patients (23 males, 21 females; median age, 23 years [range, 6-59]) were identified. Primary metastases were detected in six of 44 (14%) patients. Surgery was performed in 40 of 44 (91%) patients and rendered 35 of 44 (80%) patients macroscopically disease-free. Chemotherapy was known to have been administered in 43 of 44 (98%) patients and radiotherapy in seven of 42 (17%) (no data for two patients). A good response to chemotherapy was only noted in five (33%) of those 15 evaluable patients who had received any preoperative chemotherapy. After a median follow-up of 2.49 (0.22-40.35) years for all patients and 6.61 (0.25-40.35) years for 26 survivors (21 of these in first complete remission), 5-year actuarial overall and event-free survival were 53.0% (8.5%) and 42.2% (8.1%), respectively. Incomplete tumor surgery was the most notable negative prognostic factor. Osteoblastic histology and a poor response to chemotherapy may have contributed. CONCLUSION: This large series provides evidence that patients with costal primaries are older than the average osteosarcoma patient, but appear to share the similar tumor biology and-if treated according to standard protocols-prognostic factors with tumors of other sites. Early, preoperative diagnosis and permanent, definitive local control remain major challenges and should contribute to improved outcomes.

Chronic refractory immune thrombocytopenia in adolescents and young adults.

Defining immune thrombocytopenia (ITP) in two age groups-children and adults-overlooks the specific clinical features and needs of adolescents and young adults (AYAS). We previously reported a high risk of chronic disease at 12 months (50%); however, data on the course of chronic ITP, the risk of refractoriness and treatment strategies in AYAS are limited. Data from patients aged 12-25 years with chronic primary ITP at 12 months were extracted from three large registries between 2004 and 2021. Clinical and laboratory data were evaluated until 48 months of follow-up (FU). Refractory ITP was defined as the administration of ≥3 different lines of therapy. A total of 427 AYAS (64% female) with chronic ITP were included. Overall, 7% and 14% were classified as 'refractory' at 12 and 48 months of FU respectively. The proportion of males was greater in the refractory group than in the non-refractory group (43% vs. 35%). AYAS with refractory disease displayed lower median platelet counts, more bleeding and a higher need for treatment at initial diagnosis and FU than non-refractory patients. This study reveals that refractory ITP is uncommon in AYAS; however, AYAS with refractory ITP display a high disease burden at all time points, including at initial diagnosis.

Immunomodulation with romiplostim as a second-line strategy in primary immune thrombocytopenia: The iROM study.

Thrombopoietin receptor agonists (TPO-RAs) stimulate platelet production, which might restore immunological tolerance in primary immune thrombocytopenia (ITP). The iROM study investigated romiplostim's immunomodulatory effects. Thirteen patients (median age, 31 years) who previously received first-line treatment received romiplostim for 22 weeks, followed by monitoring until week 52. In addition to immunological data, secondary end-points included the sustained remission off-treatment (SROT) rate at 1 year, romiplostim dose, platelet count and bleedings. Scheduled discontinuation of romiplostim and SROT were achieved in six patients with newly diagnosed ITP, whereas the remaining seven patients relapsed. Romiplostim dose titration was lower and platelet count response was stronger in patients with SROT than in relapsed patients. In all patients, regulatory T lymphocyte (Treg) counts increased until study completion and the counts were higher in patients with SROT. Interleukin (IL)-4, IL-9 and IL-17F levels decreased significantly in all patients. FOXP3 (Treg), GATA3 (Th2) mRNA expression and transforming growth factor-ß levels increased in patients with SROT. Treatment with romiplostim modulates the immune system and possibly influences ITP prognosis. A rapid increase in platelet counts is likely important for inducing immune tolerance. Better outcomes might be achieved at an early stage of autoimmunity, but clinical studies are needed for confirmation.

Adolescents and young adults with newly diagnosed primary immune thrombocytopenia.

Current immune thrombocytopenia (ITP) guidelines target children and adults, leading to oversimplification. Adolescents and young adults (AYAS) comprise a separate group with distinct health and psychosocial issues. This study aimed to describe the clinical presentation and therapeutic strategies of ITP among AYAS. We analyzed data from two large ITP registries (PARC-ITP; CARMEN-France) and included newly diagnosed ITP patients (aged 12-25 years) with an initial platelet counts of <100×109/L. Patients with secondary ITP or non-immune thrombocytopenia (n=57) and pregnant women (n=10) were excluded. Of the 656 cases of AYAS with primary ITP registered from 2004 up to 2021, 12-month follow-up data were available for 72%. The initial median platelet count was 12×109/L. In 109 patients (17%), the diagnosis was incidental, without documented bleeding. Apart from gynecological bleeding, the clinical and therapeutical characteristics of females and males were similar. Platelet-enhancing drugs were reported in 66%, 45%, and 30% of patients at diagnosis, 1-6 months, and 6-12 months after diagnosis, respectively. Corticosteroids were the preferred treatment at all time points. At 12 months, 50% of all patients developed chronic ITP. In the subgroup of patients with initial severe thrombocytopenia (<20×109/L), those receiving frontline treatment had a higher remission rate at 1 year than those who followed an initial watch-and-wait strategy (53% and 32%; P<0.05). Our analysis indicates that the remission rate at 1 year may be associated with the initial treatment strategy. This hypothesis must be confirmed in prospective studies.

Vibrational dynamics of liquid water in an external electric field.

In our present study, we have investigated the effects of an externally applied static electric field on the vibrational dynamics of liquid water (D2O) using ab initio molecular dynamics. The rate of vibrational spectral diffusion is obtained from simulated two-dimensional infrared spectra, three-pulse photon echo intensity, and frequency correlation functions and distributions. We find that the static vibrational frequency distribution undergoes a redshift of 90 cm-1 whereas the overall vibrational dynamics get slower with the relaxation time constant to be around 4.9 ps. Thus we infer that the local hydrogen bond network tends to reorganize in the presence of an external field with an increase in local structural order as evident from the overall slower vibrational dynamics and reduced molar entropy.

Axial-Bonding-Driven Dimensionality Effect on the Charge-Density Wave in NbSe2.

2H-NbSe2 is a prototypical charge-density-wave (CDW) system, exhibiting such a symmetry-breaking quantum ground state in its bulk and down to a single-atomic-layer limit. However, how this state depends on dimensionality and what governs the dimensionality effect remain controversial. Here, we experimentally demonstrate a robust 3 × 3 CDW phase in both freestanding and substrate-supported bilayer NbSe2, far above the bulk transition temperature. We exclude environmental effects and reveal a strong temperature and thickness dependence of Raman intensity from an axially vibrating A1g phonon mode, involving Se ions. Using first-principles calculations, we show that these result from a delicate but profound competition between the intra- and interlayer bonding formed between Se-pz orbitals. Our results suggest the crucial role of Se out-of-plane displacement in driving the CDW distortion, revealing the Se-dominated dimensionality effect and establishing a new perspective on the chemical bonding and mechanical stability in layered CDW materials.

Visualizing Chiral Interactions in Carbohydrates Adsorbed on Au(111) by High-Resolution STM Imaging.

Carbohydrates are the most abundant organic material on Earth and the structural "material of choice" in many living systems. Nevertheless, design and engineering of synthetic carbohydrate materials presently lag behind that for protein and nucleic acids. Bottom-up engineering of carbohydrate materials demands an atomic-level understanding of their molecular structures and interactions in condensed phases. Here, high-resolution scanning tunneling microscopy (STM) is used to visualize at submolecular resolution the three-dimensional structure of cellulose oligomers assembled on Au(1111) and the interactions that drive their assembly. The STM imaging, supported by ab initio calculations, reveals the orientation of all glycosidic bonds and pyranose rings in the oligomers, as well as details of intermolecular interactions between the oligomers. By comparing the assembly of D- and L-oligomers, these interactions are shown to be enantioselective, capable of driving spontaneous enantioseparation of cellulose chains from its unnatural enantiomer and promoting the formation of engineered carbohydrate assemblies in the condensed phases.

Secondary malignant neoplasms after bone and soft tissue sarcomas in children, adolescents, and young adults.

BACKGROUND: Increased survival in young sarcoma patients comes along with a higher incidence of second malignant neoplasms (SMNs). The incidence, latency, histiotype, and outcome of these patients were analyzed because this information is essential to design evidence-based long-term follow-up care programs for young sarcoma survivors. METHODS: Patients entered on clinical trials or registered in registries with a primary sarcoma in 1 of the cooperative sarcoma study groups in the framework of the Society for Pediatric Oncology and Hematology (GPOH) were screened for SMNs. Descriptive analysis, the Kaplan-Meier method, the Gray model, the Fine-Gray model, and the Cox regression model were used for the statistical analyses. RESULTS: A total of 159 out of 7079 (2.2%) patients were registered with a SMN. Among them, 104 solid SMNs (65%) and 56 hematologic SMNs (35%) occurred. Median latency from first diagnosis of sarcoma to the diagnosis of SMN was 6.8 years (range, 0-26.7 years). Cumulative incidence of SMN was 8.8% after 30 years. Five-year-survival was 67.1% (95% confidence interval [CI], 66.0-68.2) for the 7079 patients and it was 45.1% (95% CI, 36.2-53.6) after the diagnosis of a SMN (subcohort of n = 159 patients). CONCLUSIONS: There is a remarkable high cumulative incidence of SMNs after bone and soft tissue sarcomas in children, adolescents, and young adults. Therefore, effective transition as well as risk adapted long-term follow-up care programs should be developed and offered to young sarcoma survivors. LAY SUMMARY: Bone sarcomas and soft tissue tumors are rare tumors in children, adolescents, and young adults. The treatment varies, but may comprise chemotherapy, surgery, and/or radiotherapy. Developing a subsequent malignant tumor is a long-term risk for the patients. To better characterize this risk, we analyzed the data of 7079 patients (up to 21 years old) with bone sarcomas or soft tissue tumors. Our findings provide a basis to counsel young sarcoma survivors on their individual risk of subsequent malignant tumors. Moreover, these data can help to establish recommendations for aftercare in young sarcoma survivors.

Romiplostim in children with newly diagnosed or persistent primary immune thrombocytopenia.

Immune thrombocytopenia (ITP) is a disease of heterogenous origin characterized by low platelet counts and an increased bleeding tendency. Three disease phases have been described: newly diagnosed (≤ 3 months after diagnosis), persistent (> 3-12 months after diagnosis), and chronic (> 12 months after diagnosis). The majority of children with ITP have short-lived disease and will not need treatment. For children with newly diagnosed ITP, who have increased bleeding symptoms, short courses of steroids are recommended. In children who do not respond to first-line treatment or who become steroid dependent, thrombopoietin receptor agonists (TPO-RAs) are recommended because of their efficacy and safety profiles. In this narrative review, we evaluate the available evidence on the use of the TPO-RA romiplostim to treat children with newly diagnosed or persistent ITP and identify data from five clinical trials, five real-world studies, and a case report. While the data are more limited for children with newly diagnosed ITP than for persistent ITP, the collective body of evidence suggests that romiplostim is efficacious in increasing platelet counts in children with newly diagnosed or persistent ITP and may result in long-lasting treatment-free responses in some patients. Furthermore, romiplostim was found to be well tolerated in the identified studies. Collectively, the data suggest that earlier treatment with romiplostim may help children to avoid the side effects associated with corticosteroid use and reduce the need for subsequent treatment.

Thermodynamically stable polymorphs of nitrogen-rich carbon nitrides: a C3N5 study.

We have carried out an extensive search for stable polymorphs of carbon nitride with C3N5 stoichiometry using the minima hopping method. Contrary to the widely held opinion that stacked, planar, graphite-like structures are energetically the most stable carbon nitride polymorphs for various nitrogen contents, we find that this does not apply for nitrogen-rich materials owing to the high abundance of N-N bonds. In fact, our results disclose novel morphologies with moieties not previously considered for C3N5. We demonstrate that nitrogen-rich compounds crystallize in a large variety of different structures due to particular characteristics of their energy landscapes. The newly found low-energy structures of C3N5 have band gaps within good agreement with the values measured in experimental studies.

Organic Mixed-Valence Compounds and the Overhauser Effect in Insulating Solids.

Recent experiments have shown that the organic free radical 1,3-bisdiphenylene-2-phenylallyl (BDPA) can induce an Overhauser effect dynamic nuclear polarization in insulating solids, a feat previously considered not to be possible. Here, we establish that this peculiar ability of the BDPA radical stems from its mixed-valence nature and the ensuing intramolecular charge transfer. Using state-of-the-art DMRGSCF calculations, we confirm the class II mixed-valence nature of BDPA with the characteristic double-well potential energy surface, and we investigate the mechanism of the consequent electron hopping. A two-component vibronic Hamiltonian is then employed to compute the rate of electron hopping from a quantum dynamical time-propagation of the density matrix. The predicted hyperfine coupling oscillations indeed fall within the frequency range required for an Overhauser effect. The paradigm of mixed-valence compounds as a mining source opens many possibilities for the development and fine tuning of novel polarizing agents.

Artificial neural networks for the kinetic energy functional of non-interacting fermions.

A novel approach to find the fermionic non-interacting kinetic energy functional with chemical accuracy using machine learning techniques is presented. To that extent, we apply machine learning to an intermediate quantity rather than targeting the kinetic energy directly. We demonstrate the performance of the method for three model systems containing three and four electrons. The resulting kinetic energy functional remarkably accurately reproduces self-consistently the ground state electron density and total energy of reference Kohn-Sham calculations with an error of less than 5 mHa. This development opens a new avenue to advance orbital-free density functional theory by means of machine learning.

Mixed-Valence Compounds as Polarizing Agents for Overhauser Dynamic Nuclear Polarization in Solids*.

Herein, we investigate a novel set of polarizing agents-mixed-valence compounds-by theoretical and experimental methods and demonstrate their performance in high-field dynamic nuclear polarization (DNP) NMR experiments in the solid state. Mixed-valence compounds constitute a group of molecules in which molecular mobility persists even in solids. Consequently, such polarizing agents can be used to perform Overhauser-DNP experiments in the solid state, with favorable conditions for dynamic nuclear polarization formation at ultra-high magnetic fields.

A High-Rate Two-Dimensional Polyarylimide Covalent Organic Framework Anode for Aqueous Zn-Ion Energy Storage Devices.

Rechargeable aqueous Zn-ion energy storage devices are promising candidates for next-generation energy storage technologies. However, the lack of highly reversible Zn2+-storage anode materials with low potential windows remains a primary concern. Here, we report a two-dimensional polyarylimide covalent organic framework (PI-COF) anode with high-kinetics Zn2+-storage capability. The well-organized pore channels of PI-COF allow the high accessibility of the build-in redox-active carbonyl groups and efficient ion diffusion with a low energy barrier. The constructed PI-COF anode exhibits a specific capacity (332 C g-1 or 92 mAh g-1 at 0.7 A g-1), a high rate capability (79.8% at 7 A g-1), and a long cycle life (85% over 4000 cycles). In situ Raman investigation and first-principle calculations clarify the two-step Zn2+-storage mechanism, in which imide carbonyl groups reversibly form negatively charged enolates. Dendrite-free full Zn-ion devices are fabricated by coupling PI-COF anodes with MnO2 cathodes, delivering excellent energy densities (23.9 ∼ 66.5 Wh kg-1) and supercapacitor-level power densities (133 ∼ 4782 W kg-1). This study demonstrates the feasibility of covalent organic framework as Zn2+-storage anodes and shows a promising prospect for constructing reliable aqueous energy storage devices.

Tumbling with a limp: local asymmetry in water's hydrogen bond network and its consequences.

Ab initio molecular dynamics simulations of liquid water under equilibrium ambient conditions, together with a novel energy decomposition analysis, have recently shown that a substantial fraction of water molecules exhibit a significant asymmetry between the strengths of the two donor and/or the two acceptor interactions. We refer to this recently unraveled aspect as the "local asymmetry in the hydrogen bond network". We discuss how this novel aspect was first revealed, and provide metrics that can be consistently employed on simulated water trajectories to quantify this local heterogeneity in the hydrogen bond network and its dynamics. We then discuss the static aspects of the asymmetry, pertaining to the frozen geometry of liquid water at any given instant of time and the distribution of hydrogen bond strengths therein, and also its dynamic characteristics pertaining to how fast this asymmetry decays and the kinds of molecular motions responsible for this decay. Following this we discuss the spectroscopic manifestations of this asymmetry, from ultrafast X-ray absorption spectra to infrared spectroscopy and down to the much slower terahertz regime. Finally, we discuss the implications of these findings in a broad context and their relation to the current notions about the structure and dynamics of liquid water.

In silico investigation of Cu(In,Ga)Se2-based solar cells.

Photovoltaics is one of the most promising and fastest-growing renewable energy technologies. Although the price-performance ratio of solar cells has improved significantly over recent years, further systematic investigations are needed to achieve higher performance and lower cost for future solar cells. In conjunction with experiments, computer simulations are powerful tools to investigate the thermodynamics and kinetics of solar cells. Over the last few years, we have developed and employed advanced computational techniques to gain a better understanding of solar cells based on copper indium gallium selenide (Cu(In,Ga)Se2). Furthermore, we have utilized state-of-the-art data-driven science and machine learning for the development of photovoltaic materials. In this Perspective, we review our results along with a survey of the field.