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Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software.

Tryptophan-2,3-dioxygenase (TDO2) and indoleamine-2,3-dioxygenase (IDO1) are structurally distinct heme enzymes that catalyze the conversion of L-tryptophan to N-formyl-kynurenine, and play important roles in metabolism, inflammation, and tumor immune surveillance. The enzymes can adopt an inactive, heme-free (apo) state or an active, heme-containing (holo) state, with the balance between them varying dynamically according to biological conditions. Inhibitors of holo-TDO2 are known but, despite several advantages of the heme-free state as a drug target, no inhibitors of apo-TDO2 have been reported. We describe the discovery of the first apo-TDO2 binding inhibitors, to our knowledge, and their inhibition of cellular TDO2 activity at low nanomolar concentrations. The crystal structure of a potent, small molecule inhibitor bound to apo-TDO2 reveals its detailed binding interactions within the large, hydrophobic heme binding pocket of the active site., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Halogenated closo -dodecaborates are very robust and versatile weakly coordinating anions for numerous applications. The introduction of additional substituents, e.g., pseudohalides, allows the tuning of their chemical and physical properties. In this report, the synthesis of the isocyanate-substituted closo -dodecaborates [B 12 X 11 (NCO)] 2- (X = H, F-I) was investigated. In an attempt to synthesize the undecahalogenated derivatives, a selective and halogen-dependent reaction yielding boron clusters carrying the functional groups amidinium (-NHCHNMe 2 ) and formamide (-NHC(O)H) was discovered. The halogenated anions were fully characterized by vibrational and NMR spectroscopy, mass spectrometry, and X-ray diffraction. Salts of the formamide-substituted anion [B 12 X 11 (NHC(O)H)] 2- are surprisingly thermally stable in the condensed phase. In contrast, collision-induced dissociation in the gas phase reveals that the isolated dianion [B 12 X 11 (NHC(O)H)] 2- in the gas phase preferentially loses water, while the protonated form, which was generated from decomposition of the tetraalkylammonium counterion [B 12 X 11 (NHC(O)H)H] - , tends to lose carbon monoxide. Possible reaction mechanisms are discussed.

Gaseous fragment ions generated in mass spectrometers may be employed as "building blocks" for the synthesis of novel molecules on surfaces using ion soft-landing. A fundamental understanding of the reactivity of the fragment ions is required to control bond formation of deposited fragments in surface layers. The fragment ion [B 12 X 11 ] - (X = halogen) is formed by collision-induced dissociation (CID) from the precursor [B 12 X 12 ] 2- dianion. [B 12 X 11 ] - is highly reactive and ion soft-landing experiments have shown that this ion binds to the alkyl chains of organic molecules on surfaces. In this work we investigate whether specific modifications of the precursor ion affect the chemical properties of the fragment ions to such an extent that attachment to functional groups of organic molecules on surfaces occurs and binding of alkyl chains is prevented. Therefore, a halogen substituent was replaced by a thiocyanate substituent. CID of the precursor [B 12 I 11 (SCN)] 2- ion preferentially yields the fragment ion [B 12 I 8 S(CN)] - , which shows significantly altered reactivity compared to the fragment ions of [B 12 I 12 ] 2- . [B 12 I 8 S(CN)] - has a previously unknown structural element, wherein a sulfur atom bridges three boron atoms. Gas-phase reactions with different neutral reactants (cyclohexane, dimethyl sulfide, and dimethyl amine) accompanied by theoretical studies indicate that [B 12 I 8 S(CN)] - binds with higher selectivity to functional groups of organic molecules than fragment ions of [B 12 I 12 ] 2- ( e.g. , [B 12 I 11 ] - and [B 12 I 9 ] - ). These findings were further confirmed by ion soft-landing experiments, which showed that [B 12 I 8 S(CN)] - ions attacked ester groups of adipates and phthalates, whereas [B 12 I 11 ] - ions only bound to alkyl chains of the same reagents.

Superelectrophilic anions constitute a special class of molecular anions that show strong binding of weak nucleophiles despite their negative charge. In this study, the binding characteristics of smaller gaseous electrophilic anions of the types [B 6 X 5 ] - and [B 10 X 9 ] - (with X=Cl, Br, I) were computationally and experimentally investigated and compared to those of the larger analogues [B 12 X 11 ] - . The positive charge of vacant boron increases from [B 6 X 5 ] - via [B 10 X 9 ] - to [B 12 X 11 ] - , as evidenced by increasing attachment enthalpies towards typical σ-donor molecules (noble gases, H 2 O). However, this behavior is reversed for σ-donor-π-acceptor molecules. [B 6 Cl 5 ] - binds most strongly to N 2 and CO, even more strongly than to H 2 O. Energy decomposition analysis confirms that the orbital interaction is responsible for this opposite trend. The extended transition state natural orbitals for chemical valence method shows that the π-backdonation order is [B 6 X 5 ] - >[B 10 X 9 ] - >[B 12 X 11 ] - . This predicted order explains the experimentally observed red shifts of the CO and N 2 stretching fundamentals compared to those of the unbound molecules, as measured by infrared photodissociation spectroscopy. The strongest red shift is observed for [B 6 Cl 5 N 2 ] - : 222 cm -1 . Therefore, strong activation of unreactive σ-donor-π-acceptor molecules (commonly observed for cationic transition metal complexes) is achieved with metal-free molecular anions., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The highly reactive gaseous ion [B 12 Br 11 ] - is a metal-free closed-shell anion which spontaneously forms covalent bonds with hydrocarbon molecules, including alkanes. Herein, we systematically investigate the reaction mechanism for binding of [B 12 Br 11 ] - to the five hexane isomers yielding [B 12 Br 11 (C 6 H 14 )] - , as well as to cyclohexane and several hexene isomers (yielding [B 12 Br 11 (C 6 H 12 )] - ) using collision-induced dissociation (CID), infrared photodissociation spectroscopy (IRPD) and computational methods. CID of the different [B 12 Br 11 (C 6 H 14 )] - ions results in distinct fragmentation patterns dependent on the structure of the hexane isomer. The observed fragmentation reactions provide insights into the addition mechanism of [B 12 Br 11 ] - to hexane. Based on the observed CID patterns, we identified that either B-C bond formation through heterolytic C-C or C-H bond cleavages or B-H bond formation through heterolytic C-H cleavage occur dependent on the structure of the hexane isomer. Meanwhile, we observe identical CID spectra of adducts originating from isomers of C 6 H 12 . Spectroscopic investigations of adducts of 1-hexene and cyclohexane indicate the same product structure with an open C 6 chain. Computational investigations evidenced that low lying transition states are present, which enable a ring opening reaction of cyclohexane when binding to [B 12 Br 11 ] - .

While reactions between ions and neutral molecules in the gas phase have been studied extensively, reactions between molecular ions of same polarity remain relatively unexplored. Herein we show that reactions between fragment ions generated in the gas phase and molecular ions of the same polarity are possible by soft-landing of both reagents on surfaces. The reactive [B 12 I 11 ] 1- anion was deposited on a surface layer built up by landing the generally unreactive [B 12 I 12 ] 2- . Ex-situ analysis of the generated material shows that [B 24 I 23 ] 3- was formed. A computational study shows that the product is metastable in the gas phase, but a charge-balanced environment of a grounded surface may stabilize the triply charged product, as suggested by model calculations. This opens new opportunities for the generation of highly charged clusters using unconventional building blocks from the gas phase., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Electrophilic anions of type [B 12 X 11 ] - posses a vacant positive boron binding site within the anion. In a comparatitve experimental and theoretical study, the reactivity of [B 12 X 11 ] - with X=F, Cl, Br, I, CN is characterized towards different nucleophiles: (i) noble gases (NGs) as σ-donors and (ii) CO/N 2 as σ-donor-π-acceptors. Temperature-dependent formation of [B 12 X 11 NG] - indicates the enthalpy order (X=CN)>(X=Cl)≈(X=Br)>(X=I)≈(X=F) almost independent of the NG in good agreement with calculated trends. The observed order is explained by an interplay of the electron deficiency of the vacant boron site in [B 12 X 11 ] - and steric effects. The binding of CO and N 2 to [B 12 X 11 ] - is significantly stronger. The B3LYP 0 K attachment enthapies follow the order (X=F)>(X=CN)>(X=Cl)>(X=Br)>(X=I), in contrast to the NG series. The bonding motifs of [B 12 X 11 CO] - and [B 12 X 11 N 2 ] - were characterized using cryogenic ion trap vibrational spectroscopy by focusing on the CO and N 2 stretching frequencies ν C O and ν N 2 , respectively. Observed shifts of ν C O and ν N 2 are explained by an interplay between electrostatic effects (blue shift), due to the positive partial charge, and by π-backdonation (red shift). Energy decomposition analysis and analysis of natural orbitals for chemical valence support all conclusions based on the experimental results. This establishes a rational understanding of [B 12 X 11 ] - reactivety dependent on the substituent X and provides first systematic data on π-backdonation from delocalized σ-electron systems of closo-borate anions., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

A fundamental understanding of cyclodextrin-closo-dodecaborate inclusion complexes is of great interest in supramolecular chemistry. Herein, we report a systematic investigation on the electronic structures and intramolecular interactions of perhalogenated closo-dodecaborate dianions B12X122- (X = F, Cl, Br and I) binding to α-, β-, and γ-cyclodextrins (CDs) in the gas phase using combined negative ion photoelectron spectroscopy (NIPES) and density functional theory (DFT) calculations. The vertical detachment energy (VDE) of each complex and electronic stabilization of each dianion due to the CD binding (ΔVDE, relative to the corresponding isolated B12X122-) are determined from the experiments along α-, β- and γ-CD in the form of VDE (ΔVDE): 4.00 (2.10), 4.33 (2.43), and 4.30 (2.40) eV in X = F; 4.09 (1.14), 4.64 (1.69), and 4.69 (1.74) eV in X = Cl; 4.11 (0.91), 4.58 (1.38), and 4.70 (1.50) eV in X = Br; and 3.54 (0.74), 3.88 (1.08), and 4.05 (1.25) eV in X = I, respectively. All complexes have significantly higher VDEs than the corresponding isolated dodecaborate dianions with ΔVDE spanning from 0.74 eV at (α, I) to 2.43 eV at (β, F), sensitive to both host CD size and guest substituent X. DFT-optimized complex structures indicate that all B12X122- prefer binding to the wide openings of CDs with the insertion depth and binding motif strongly dependent on the CD size and halogen X. Dodecaborate anions with heavy halogens, i.e., X = Cl, Br, and I, are found outside of α-CD, while B12F122- is completely wrapped by γ-CD. Partial embedment of B12X122- into CDs is observed for the other complexes via multipronged B-XH-O/C interlocking patterns. The simulated spectra based on the density of states agree well with those of the experiments and the calculated VDEs well reproduce the experimental trends. Molecular orbital analyses suggest that the spectral features at low binding energies originated from electrons detached from the dodecaborate dianion, while those at higher binding energies are derived from electron detachment from CDs. Energy decomposition analyses reveal that the electrostatic interaction plays a dominating role in contributing to the host-guest interactions for the X = F series partially due to the formation of a O/C-HX-B hydrogen bonding network, and the dispersion forces gradually become important with the increase of halogen size.

The hydride-bridged silylium cation [Et 3 Si-H-SiEt 3 ] + , stabilized by the weakly coordinating [Me 3 NB 12 Cl 11 ] - anion, undergoes, in the presence of excess silane, a series of unexpected consecutive reactions with the valence-isoelectronic molecules CS 2 and CO 2 . The final products of the reaction with CS 2 are methane and the previously unknown [(Et 3 Si) 3 S] + cation. To gain insight into the entire reaction cascade, numerous experiments with varying conditions were performed, intermediate products were intercepted, and their structures were determined by X-ray crystallography. Besides the [(Et 3 Si) 3 S] + cation as the final product, crystal structures of [(Et 3 Si) 2 SMe] + , [Et 3 SiS(H)Me] + , and [Et 3 SiOC(H)OSiEt 3 ] + were obtained. Experimental results combined with supporting quantum-chemical calculations in the gas phase and solution allow a detailed understanding of the reaction cascade., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

Opioid abuse has devastating effects on patients, their families, and society. Withdrawal symptoms are severely unpleasant, prolonged, and frequently hinder recovery or lead to relapse. The sharp increase in abuse and overdoses arising from the illicit use of potent and rapidly-acting synthetic opioids, such as fentanyl, highlights the urgency of understanding the withdrawal mechanisms related to these drugs. Progress is impeded by inconsistent reports on opioid withdrawal in different preclinical models. Here, using rats and mice of both sexes, we quantified withdrawal behaviors during spontaneous and naloxone-precipitated withdrawal, following two weeks of intermittent fentanyl exposure. We found that both mice and rats lost weight during exposure and showed increased signs of distress during spontaneous and naloxone precipitated withdrawal. However, these species differed in their expression of withdrawal associated pain, a key contributor to relapse in humans. Spontaneous or ongoing pain was preferentially expressed in rats in both withdrawal conditions, while no change was observed in mice. In contrast, withdrawal associated thermal hyperalgesia was found only in mice. These data suggest that rats and mice diverge in how they experience withdrawal and which aspects of the human condition they most accurately model. These differences highlight each species' strengths as model systems and can inform experimental design in studies of opioid withdrawal., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Nitro-functionalized undecahalogenated closo-dodecaborates [B 12 X 11 (NO 2 )] 2- were synthesized in high purities and characterized by NMR, IR, and Raman spectroscopy, single crystal X-diffraction, mass spectrometry, and gas-phase ion vibrational spectroscopy. The NO 2 substituent leads to an enhanced electronic and electrochemical stability compared to the parent perhalogenated [B 12 X 12 ] 2- (X=F-I) dianions evidenced by photoelectron spectroscopy, cyclic voltammetry, and quantum-chemical calculations. The stabilizing effect decreases from X=F to X=I. Thermogravimetric measurements of the salts indicate the loss of the nitric oxide radical (NO . ). The homolytic NO . elimination from the dianion under very soft collisional excitation in gas-phase ion experiments results in the formation of the radical [B 12 X 11 O] 2-. . Theoretical investigations suggest that the loss of NO . proceeds via the rearrangement product [B 12 X 11 (ONO)] 2- . The O-bonded nitrosooxy structure is thermodynamically more stable than the N-bonded nitro structure and its formation by radical recombination of [B 12 X 11 O] 2-. and NO . is demonstrated., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

During respiration, humans breathe in more than 10,000 liters of non-sterile air daily, allowing some pathogens access to alveoli. Interestingly, alveoli outnumber alveolar macrophages (AMs), which favors alveoli devoid of AMs. If AMs, like most tissue macrophages, are sessile, then this numerical advantage would be exploited by pathogens unless neutrophils from the blood stream intervened. However, this would translate to omnipresent persistent inflammation. Developing in vivo real-time intravital imaging of alveoli revealed AMs crawling in and between alveoli using the pores of Kohn. Importantly, these macrophages sensed, chemotaxed, and, with high efficiency, phagocytosed inhaled bacterial pathogens such as P. aeruginosa and S. aureus, cloaking the bacteria from neutrophils. Impairing AM chemotaxis toward bacteria induced superfluous neutrophil recruitment, leading to inappropriate inflammation and injury. In a disease context, influenza A virus infection impaired AM crawling via the type II interferon signaling pathway, and this greatly increased secondary bacterial co-infection., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Alkanes and [B 12 X 12 ] 2- (X = Cl, Br) are both stable compounds which are difficult to functionalize. Here we demonstrate the formation of a boron-carbon bond between these substances in a two-step process. Fragmentation of [B 12 X 12 ] 2- in the gas phase generates highly reactive [B 12 X 11 ] - ions which spontaneously react with alkanes. The reaction mechanism was investigated using tandem mass spectrometry and gas-phase vibrational spectroscopy combined with electronic structure calculations. [B 12 X 11 ] - reacts by an electrophilic substitution of a proton in an alkane resulting in a B-C bond formation. The product is a dianionic [B 12 X 11 C n H 2n+1 ] 2- species, to which H + is electrostatically bound. High-flux ion soft landing was performed to codeposit [B 12 X 11 ] - and complex organic molecules (phthalates) in thin layers on surfaces. Molecular structure analysis of the product films revealed that C-H functionalization by [B 12 X 11 ] - occurred in the presence of other more reactive functional groups. This observation demonstrates the utility of highly reactive fragment ions for selective bond formation processes and may pave the way for the use of gas-phase ion chemistry for the generation of complex molecular structures in the condensed phase., Competing Interests: The authors declare no competing interest.

Objectives: This study aimed to explore cytokine alterations following pediatric sports-related concussion (SRC) and whether a specific cytokine profile could predict symptom burden and time to return to sports (RTS)., Setting: Sports Medicine Clinic., Participants: Youth ice hockey participants (aged 12-17 years) were recruited prior to the 2013-2016 hockey season., Design: Prospective exploratory cohort study., Main Measure: Following SRC, saliva samples were collected and a Sport Concussion Assessment Tool version 3 (SCAT3) was administered within 72 hours of injury and analyzed for cytokines. Additive regression of decision stumps was used to model symptom burden and length to RTS based on cytokine and clinical features. RRelieFF feature selection was used to determine the predictive value of each cytokine and clinical feature, as well as to identify the optimal cytokine profile for the symptom burden and RTS., Results: Thirty-six participants provided samples post-SRC (81% male; age 14.4 ± 1.3 years). Of these, 10 features, sex, number of previous concussions, and 8 cytokines, were identified to lead to the best prediction of symptom severity (r = 0.505, P = .002), while 12 cytokines, age, and history of previous concussions predicted the number of symptoms best (r = 0.637, P < .001). The prediction of RTS led to the worst results, requiring 21 cytokines, age, sex, and number of previous concussions as features (r = -0.320, P = .076)., Conclusions: In pediatric ice hockey participants following SRC, there is evidence of saliva cytokine profiles that are associated with increased symptom burden. However, further studies are needed.

Resuscitation of the critically ill patient with fluid and blood products is one of the most widespread interventions in medicine. This is especially relevant for trauma patients, as hemorrhagic shock remains the most common cause of preventable death after injury. Consequently, the study of the ideal resuscitative product for patients in shock has become an area of great scientific interest and investigation. Recently, the pendulum has swung towards increased utilization of blood products for resuscitation. However, pathogens, immune reactions and the limited availability of this resource remain a challenge for clinicians. Technologic advances in pathogen reduction and innovations in blood product processing will allow us to increase the safety profile and efficacy of blood products, ultimately to the benefit of patients. The purpose of this article is to review the current state of blood product based resuscitative strategies as well as technologic advancements that may lead to safer resuscitation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Electronic structure, collision-induced dissociation (CID) and bond properties of closo-[B 6 X 6 ] 2- (X = Cl-I) are investigated in direct comparison with their closo-[B 12 X 12 ] 2- analogues. Photoelectron spectroscopy (PES) and theoretical investigations reveal that [B 6 X 6 ] 2- dianions are electronically significantly less stable than the corresponding [B 12 X 12 ] 2- species. Although [B 6 Cl 6 ] 2- is slightly electronically unstable, [B 6 Br 6 ] 2- and [B 6 I 6 ] 2- are intrinsically stable dianions. Consistent with the trend in the electron detachment energy, loss of an electron (e - loss) is observed in CID of [B 6 X 6 ] 2- (X = Cl, Br) but not for [B 6 I 6 ] 2- . Halogenide loss (X - loss) is common for [B 6 X 6 ] 2- (X = Br, I) and [B 12 X 12 ] 2- (X = Cl, Br, I). Meanwhile, X˙ loss is only observed for [B 12 X 12 ] 2- (X = Br, I) species. The calculated reaction enthalpies of the three competing dissociation pathways (e - , X - and X˙ loss) indicated a strong influence of kinetic factors on the observed fragmentation patterns. The repulsive Coulomb barrier (RCB) determines the transition state for the e - and X - losses. A significantly lower RCB for X - loss than for e - loss was found in both experimental and theoretical investigations and can be rationalized by the recently introduced concept of electrophilic anions. The positive reaction enthalpies for X - losses are significantly lower for [B 6 X 6 ] 2- than for [B 12 X 12 ] 2- , while enthalpies for X˙ losses are higher. These observations are consistent with a difference in bond character of the B-X bonds in [B 6 X 6 ] 2- and [B 12 X 12 ] 2- . A complementary bonding analysis using QTAIM, NPA and ELI-D based methods suggests that B-X bonds in [B 12 X 12 ] 2- have a stronger covalent character than in [B 6 X 6 ] 2- , in which X has a stronger halide character.

The adaptive immune function of lymph nodes is dependent on constant recirculation of lymphocytes. In this article, we identify neutrophils present in the lymph node at steady state, exhibiting the same capacity for recirculation. In germ-free mice, neutrophils still recirculate through lymph nodes, and in mice cohoused with wild microbiome mice, the level of neutrophils in lymph nodes increases significantly. We found that at steady state, neutrophils enter the lymph node entirely via L-selectin and actively exit via efferent lymphatics via an S1P dependent mechanism. The small population of neutrophils in the lymph node can act as reconnaissance cells to recruit additional neutrophils in the event of bacterial dissemination to the lymph node. Without these reconnaissance cells, there is a delay in neutrophil recruitment to the lymph node and a reduction in swarm formation following Staphylococcus aureus infection. This ability to recruit additional neutrophils by lymph node neutrophils is initiated by LTB4. This study establishes the capacity of neutrophils to recirculate, much like lymphocytes via L-selectin and high endothelial venules in lymph nodes and demonstrates how the presence of neutrophils at steady state fortifies the lymph node in case of an infection disseminating through lymphatics., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Noble gas (Ng) containing molecular anions are much scarcer than Ng containing cations. No neon containing anion has been reported so far. Here, the experimental observation of the molecular anion [B 12 (CN) 11 Ne] - and a theoretical analysis of the boron-neon bond is reported.

The parabrachial (PB) complex mediates both ascending nociceptive signaling and descending pain modulatory information in the affective/emotional pain pathway. We have recently reported that chronic pain is associated with amplified activity of PB neurons in a rat model of neuropathic pain. Here we demonstrate that similar activity amplification occurs in mice, and that this is related to suppressed inhibition to lateral parabrachial (LPB) neurons from the CeA in animals of either sex. Animals with pain after chronic constriction injury of the infraorbital nerve (CCI-Pain) displayed higher spontaneous and evoked activity in PB neurons, and a dramatic increase in after-discharges, responses that far outlast the stimulus, compared with controls. LPB neurons in CCI-Pain animals showed a reduction in inhibitory, GABAergic inputs. We show that, in both rats and mice, LPB contains few GABAergic neurons, and that most of its GABAergic inputs arise from CeA. These CeA GABA neurons express dynorphin, somatostatin, and/or corticotropin releasing hormone. We find that the efficacy of this CeA-LPB pathway is suppressed in chronic pain. Further, optogenetically stimulating this pathway suppresses acute pain, and inhibiting it, in naive animals, evokes pain behaviors. These findings demonstrate that the CeA-LPB pathway is critically involved in pain regulation, and in the pathogenesis of chronic pain. SIGNIFICANCE STATEMENT We describe a novel pathway, consisting of inhibition by dynorphin, somatostatin, and corticotropin-releasing hormone-expressing neurons in the CeA that project to the parabrachial nucleus. We show that this pathway regulates the activity of pain-related neurons in parabrachial nucleus, and that, in chronic pain, this inhibitory pathway is suppressed, and that this suppression is causally related to pain perception. We propose that this amygdalo-parabrachial pathway is a key regulator of both chronic and acute pain, and a novel target for pain relief., (Copyright © 2020 the authors.)

The reaction of [Se 8 ][B 12 F 11 NH 3 ] 2 with acetone and subsequent crystallization from acetone/diethyl ether yielded the selenium cation [Se(CH 2 C(O)CH 3 ) 3 ] + as a by-product, which is stabilized by the weakly coordinating undeca-fluorinated anion [B 12 F 11 NH 3 ] - . While attempting to crystallize pure [Se 8 ][B 12 F 11 NH 3 ] 2 , the structure of the isolated product, namely, tris-(2-oxoprop-yl)selenium 1-ammonio-undeca-fluoro-dodeca-borate, was surprising. The cation [Se(CH 2 C(O)CH 3 ) 3 ] + represents the first example for a cationic selenium compound with three ketone functional groups located in the β-position with respect to the selenium atom. The cation possesses almost trigonal-pyramidal C 3 symmetry and forms hydrogen bonds to the ammonio group of the anion., (© Jenne and Nierstenhöfer 2020.)

Chemically binding to argon (Ar) at room temperature has remained the privilege of the most reactive electrophiles, all of which are cationic (or even dicationic) in nature. Herein, we report a concept for the rational design of anionic superelectrophiles that are composed of a strong electrophilic center firmly embedded in a negatively charged framework of exceptional stability. To validate our concept, we synthesized the percyano-dodecoborate [B 12 (CN) 12 ] 2- , the electronically most stable dianion ever investigated experimentally. It serves as a precursor for the generation of the monoanion [B 12 (CN) 11 ] - , which indeed spontaneously binds Ar at 298 K. Our mass spectrometric and spectroscopic studies are accompanied by high-level computational investigations including a bonding analysis of the exceptional B-Ar bond. The detection and characterization of this highly reactive, structurally stable anionic superelectrophile starts another chapter in the metal-free activation of particularly inert compounds and elements., Competing Interests: The authors declare no conflict of interest.

In the title compound, Na + [Me 3 NB 12 Cl 11 ] - ·SO 2 [systematic name: sodium 1-(trimethylammonio)-undeca-chloro- closo -dodeca-borate sulfur dioxide], the SO 2 mol-ecule is η 1 - O -coordinated to the Na + cation. Surprisingly, the SO 2 mol-ecule is more weakly bound to sodium than is found in other sodium-SO 2 complexes and the SO 2 mol-ecule is essentially undistorted compared to the structure of free SO 2 . The Na + cation has a coordination number of eight in a distorted twofold-capped trigonal prism and makes contacts to three individual boron cluster anions, resulting in an overall three-dimensional network. Although the number of known η 1 - O -coordinated SO 2 complexes is growing, sodium-SO 2 complexes are still rare.

Genetic engineering of T cells with a T cell receptor (TCR) targeting tumor antigen is a promising strategy for cancer immunotherapy. Inefficient expression of the introduced TCR due to TCR mispairing may limit the efficacy and adversely affect the safety of TCR gene therapy. Here, we evaluated the safety and therapeutic efficiency of an optimized single-chain TCR (scTCR) specific for an HLA-A2.1-restricted (non-mutated) p53(264-272) peptide in adoptive T cell transfer (ACT) models using our unique transgenic mice expressing human p53 and HLA-A2.1 that closely mimic the human setting. Specifically, we showed that adoptive transfer of optimized scTCR-redirected T cells does not induce on-target and off-target autoimmunity. Furthermore, ACT resulted in full tumor protection and led to a long-lived effective, antigen-specific memory T cell response in syngeneic and xenograft models. Taken together, the study demonstrated that our scTCR specific for the broadly expressed tumor-associated antigen p53(264-272) can eradicate p53 + A2.1 + tumor cells without inducing off-target or self-directed toxicities in mouse models of ACT. These data strongly support the improved safety and therapeutic efficacy of high-affinity p53scTCR for TCR-based immunotherapy of p53-associated malignancies., (Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

The originally published version of this article contained an error in the spelling of the author Pankaj Tailor, which was incorrectly given as Pankaj Taylor. This has now been corrected in both the PDF and HTML versions of the article.

The formation of traditional ionic materials occurs principally via joint accumulation of both anions and cations. Herein, we describe a previously unreported phenomenon by which macroscopic liquid-like thin layers with tunable self-organization properties form through accumulation of stable complex ions of one polarity on surfaces. Using a series of highly stable molecular anions we demonstrate a strong influence of the internal charge distribution of the molecular ions, which is usually shielded by counterions, on the properties of the layers. Detailed characterization reveals that the intrinsically unstable layers of anions on surfaces are stabilized by simultaneous accumulation of neutral molecules from the background environment. Different phases, self-organization mechanisms and optical properties are observed depending on the molecular properties of the deposited anions, the underlying surface and the coadsorbed neutral molecules. This demonstrates rational control of the macroscopic properties (morphology and size of the formed structures) of the newly discovered anion-based layers.

The liver is a key, frontline immune tissue. Ideally positioned to detect pathogens entering the body via the gut, the liver appears designed to detect, capture, and clear bacteria, viruses, and macromolecules. Containing the largest collection of phagocytic cells in the body, this organ is an important barrier between us and the outside world. Importantly, as portal blood also transports a large number of foreign but harmless molecules (e.g., food antigens), the liver's default immune status is anti-inflammatory or immunotolerant; however, under appropriate conditions, the liver is able to mount a rapid and robust immune response. This balance between immunity and tolerance is essential to liver function. Excessive inflammation in the absence of infection leads to sterile liver injury, tissue damage, and remodeling; insufficient immunity allows for chronic infection and cancer. Dynamic interactions between the numerous populations of immune cells in the liver are key to maintaining this balance and overall tissue health.

The stability and electron loss process of numerous multiply charged anions (MCAs) have been traditionally explained in terms of the classical Coulomb interaction between spatially separated charged groups. An understanding of these processes in MCAs with not well-separated excess charges is still lacking. We report the surprising properties and physical behavior of [B 12 X 12 ] 2- , X = F, Cl, Br, I, At, which are MCAs with not well-separated excess charges and cannot be described by the prevailing classical picture. In this series of MCAs, comprising a "boron core" surrounded by a "halogen shell", the sign of the total charge in these two regions changes along the halogen series from X = F-At. With the aid of experimental photoelectron spectroscopy and highly correlated ab initio electronic structure calculations, we demonstrate that the trend in the electronic stability of these MCAs is determined by the interplay between the Coulomb (de)stabilization originating from the "boron core" and "halogen shell" and the extension of the overlap between the orbitals from both regions. The second excess electron is always taken from the most positively charged region, viz., the "boron core" for X = F, Cl, and the surrounding "halogen shell" for X = I, At. This change in the physical behavior is attributed to the position of the highest occupied molecular orbital, which dwells in a region that is spatially separated from the one containing the excess negative charge. The unusual intrinsic electronic structure of the [B 12 X 12 ] 2- MCAs provides the basis for a molecular level understanding of their observed unique physical and chemical properties and a new paradigm for understanding the properties of these MCAs with not well-separated charges that departs from the prevailing model used for spatially separated charges that is based on their classical Coulomb interaction.

Second mitochondrial activator of caspase (Smac)-mimetic compounds and oncolytic viruses were developed to kill cancer cells directly. However, Smac-mimetic compound and oncolytic virus therapies also modulate host immune responses in ways we hypothesized would complement one another in promoting anticancer T-cell immunity. We show that Smac-mimetic compound and oncolytic virus therapies synergize in driving CD8 + T-cell responses toward tumors through distinct activities. Smac-mimetic compound treatment with LCL161 reinvigorates exhausted CD8 + T cells within immunosuppressed tumors by targeting tumor-associated macrophages for M1-like polarization. Oncolytic virus treatment with vesicular stomatitis virus (VSV ΔM51 ) promotes CD8 + T-cell accumulation within tumors and CD8 + T-cell activation within the tumor-draining lymph node. When combined, LCL161 and VSV ΔM51 therapy engenders CD8 + T-cell-mediated tumor control in several aggressive mouse models of cancer. Smac-mimetic compound and oncolytic virus therapies are both in clinical development and their combination therapy represents a promising approach for promoting anticancer T-cell immunity.Oncolytic viruses (OV) and second mitochondrial activator of caspase (Smac)-mimetic compounds (SMC) synergistically kill cancer cells directly. Here, the authors show that SMC and OV therapies combination also synergize in vivo by promoting anticancer immunity through an increase in CD8 + T-cell response.

The oxidation of elemental sulfur in superacidic solutions and melts is one of the oldest topics in inorganic main group chemistry. Thus far, only three homopolyatomic sulfur cations ([S 4 ] 2+ , [S 8 ] 2+ , and [S 19 ] 2+ ) have been characterized crystallographically although ESR investigations have given evidence for the presence of at least two additional homopolyatomic sulfur radical cations in solution. Herein, the crystal structure of the hitherto unknown homopolyatomic sulfur radical cation [S 8 ] .+ is presented. The radical cation [S 8 ] .+ represents the first step of the oxidation of the S 8 molecule present in elemental sulfur. It has a structure similar to the known structure of [S 8 ] 2+ , but the transannular sulfur⋅⋅⋅sulfur contact is significantly elongated. Quantum-chemical calculations help in understanding its structure and support its presence in solution as a stable compound. The existence of [S 8 ] .+ is also in accord with previous ESR investigations., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

It is common and chemically intuitive to assign cations electrophilic and anions nucleophilic reactivity, respectively. Herein, we demonstrate a striking violation of this concept: The anion [B 12 Cl 11 ] - spontaneously binds to the noble gases (Ngs) xenon and krypton at room temperature in a reaction that is typical of "superelectrophilic" dications. [B 12 Cl 11 Ng] - adducts, with Ng binding energies of 80 to 100 kJ mol -1 , contain B-Ng bonds with a substantial degree of covalent interaction. The electrophilic nature of the [B 12 Cl 11 ] - anion is confirmed spectroscopically by the observation of a blue shift of the CO stretching mode in the IR spectrum of [B 12 Cl 11 CO] - and theoretically by investigation of its electronic structure. The orientation of the electric field at the reactive site of [B 12 Cl 11 ] - results in an energy barrier for the approach of polar molecules and facilitates the formation of Ng adducts that are not detected with reactive cations such as [C 6 H 5 ] + . This introduces the new chemical concept of "dipole-discriminating electrophilic anions.", (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The very reactive [B(CN) 3 ] 2- dianion has a strongly nucleophilic boron atom and can be used for the synthesis of tricyanoborates, which otherwise are difficult to access. Herein the reaction of this anion with HgCl 2 is reported. The main product is the anionic mercury complex [Hg(B(CN) 3 ) 2 ] 2- . Heteronuclear NMR spectroscopic experiments shows that the reaction proceeds via the intermediate [ClHgB(CN) 3 ] 2- . Even though [Hg(B(CN) 3 ) 2 ] 2- is the main product, it is difficult to obtain it in pure form, because it slowly decomposes in the presence of water and air to [(NC)HgB(CN) 3 ] - . All three anions were fully characterized by hetereonuclear NMR spectroscopy ( 11 B, 13 C, and 199 Hg). Single-crystal X-ray diffraction studies of the salts K[ClHgB(CN) 3 ], [Ph 4 P] 2 [Hg(B(CN) 3 ) 2 ], K[(NC)HgB(CN) 3 ], and [Ph 4 P][(NC)HgB(CN) 3 ] revealed linear coordination environments around mercury for all anions. The Hg-B bonds range from 2.219(5) Å in [Hg(B(CN) 3 ) 2 ] 2- to 2.148(11) Å in [ClHgB(CN) 3 ] - , are in accord with the sum of the covalent radii of mercury and boron, and can be described as covalent single bonds. A comparison with related complexes indicates that the [B(CN) 3 ] 2- dianion is a stronger ligand than chloride, cyanide, or carbenes. [Hg(B(CN) 3 ) 2 ] 2- hydrolyses in solution only in the presence of oxygen. It is suggested that cis-[Hg(OH) 2 (B(CN) 3 ) 2 ] 2- is formed as a very unstable intermediate, which decomposes very fast to [(NC)HgB(CN) 3 ] - and other products. The anion cis-[Hg(OH) 2 (B(CN) 3 ) 2 ] 2- would contain mercury in the unusual oxidation state +IV. Quantum-chemical calculations were performed to support this assumption.

The partly halogenated and N-alkylated closo-dodecaborates [B 12 Cl 6 H 5 N(propyl) 3 ] - and [B 12 Br 6 H 5 NR 3 ] - (R = ethyl-pentyl) were prepared by alkylation of [B 12 H 11 NH 3 ] - and subsequent halogenation with elemental chlorine or N-bromosuccinimide. Simple metathesis reactions yielded the [HNMe 3 ] + , [C 6 mim] + , [NBu 4 ] + , and Na + salts, which were characterized by heteronuclear NMR and IR spectroscopy as well as electrospray ionization mass spectrometry. The crystal structures of the salts [HNMe 3 ][B 12 Br 6 H 5 N(ethyl) 3 ]·CH 3 CN, [HNMe 3 ][B 12 Br 6 H 5 N(propyl) 3 ], Na[B 12 Br 6 H 5 N(butyl) 3 ], and [HNMe 3 ][B 12 Cl 7 H 4 N(propyl) 3 ]·CH 3 CN were determined by single-crystal X-ray diffraction. The [C 6 mim] + salts are thermally stable to temperatures higher than 300 °C. The melting points are between 57 and 80 °C, which classify the [C 6 mim] + salts of [B 12 Cl 6 H 5 N(propyl) 3 ] - and [B 12 Br 6 H 5 NR 3 ] - (R = propyl-pentyl) as ionic liquids. The anions are oxidized only at potentials higher than 2 V versus Fc 0/+ as determined by cyclic voltammetry. The solubility of the sodium salts in CH 2 Cl 2 solution was determined by NMR spectroscopy. With the increasing length of the alkyl chain attached to the ammonio group the solubility is significantly enhanced. A solubility up to 125 mmol/L for Na[B 12 Br 6 H 5 N(pentyl) 3 ] in dichloromethane was determined. In addition, the trialkylation of the perchlorinated anion [B 12 Cl 11 NH 3 ] - was investigated in detail. A Hofmann elimination was observed to occur at higher temperatures, when alkyl groups with β-hydrogen atoms were introduced. Organic substituents without β-hydrogen atoms gave more stable compounds; however, trialkylation proved to be difficult presumably due to steric hindrance. The crystal structure of the byproduct [PPh 4 ] 2 [B 12 Cl 11 N(propargyl) 2 ] was determined.