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Marketplaces bring together products from multiple providers and automatically manage orders that involve several suppliers. We document the use of Answer Set Programming to automatically choose products from various warehouses within a marketplace network to fulfill a specified order. The proposed solution seamlessly adapts to various objective functions utilized at different stages of order management, leading to cost savings for customers and simplifying logistics for both the marketplace and its suppliers.

AbstractThis article argues for international legal change in human rights as a consequence of a states-as-bystander effect: When states do neither actively drive nor block change processes, and alternative state-empowered authorities exist in a legal field, states’ position at the sidelines opens a path for non-state actors to enact substantive change. In human rights law, this is a process they route through General Comments, a powerful instrument of the human rights treaty bodies to set, expand, and redefine standards for global human rights. This article bears its core argument of a states-as-bystander effect by taking a single norm, the necessity of water for human life, and tracing its change process from non-existent in human rights law, to a non-right, to a condition for other rights, and, finally, to the recognition of water and sanitation as independent rights at the international level. Ultimately, the analysis shows that non-actors can enact change to law, and do so, on the heels of states’ relegation to the periphery of the human rights system. This opened the door for certain actors – transnational coalitions of expert body members, human rights advocates and issue professionals – to use General Comments in a way that not only impacts international legal change but can also withstand state opposition.

Moritz Lazarus, the first professor for psychology, is known for his Völkerpsychologie (psychology of peoples). However, his archive at the National Library of Israel contains surprisingly many texts on individual psychology, a part of his oeuvre which is still mostly unknown. In this study, digital analysis methods (image embedding and topic modeling) are used to gain a first insight into his archive and his psychology. The findings show Lazarus in a different light: A psychologist aware of the research of his time who is nevertheless rooted in social and cultural psychology. [ABSTRACT FROM AUTHOR]

ABSTRACTMoritz Lazarus, the first professor for psychology, is known for his Völkerpsychologie (psychology of peoples). However, his archive at the National Library of Israel contains surprisingly many texts on individual psychology, a part of his oeuvre which is still mostly unknown. In this study, digital analysis methods (image embedding and topic modeling) are used to gain a first insight into his archive and his psychology. The findings show Lazarus in a different light: A psychologist aware of the research of his time who is nevertheless rooted in social and cultural psychology.

Living systems carry out the reduction of N2to ammonia (NH3) through a series of protonation and electron transfer steps under ambient conditions using the enzyme nitrogenase. In the chemical industry, the Haber–Bosch process hydrogenates N2but requires high temperatures and pressures. Both processes rely on iron-based catalysts, but molecular iron complexes that promote the formation of NH3on addition of H2to N2have remained difficult to devise. Here, we isolate the tri(iron)bis(nitrido) complex [(Cp′Fe)3(μ3-N)2] (in which Cp′ = η5-1,2,4-(Me3C)3C5H2), which is prepared by reduction of [Cp′Fe(μ-I)]2under an N2atmosphere and comprises three iron centres bridged by two μ3-nitrido ligands. In solution, this complex reacts with H2at ambient temperature (22 °C) and low pressure (1 or 4 bar) to form NH3. In the solid state, it is converted into the tri(iron)bis(imido) species, [(Cp′Fe)3(μ3-NH)2], by addition of H2(10 bar) through an unusual solid–gas, single-crystal-to-single-crystal transformation. In solution, [(Cp′Fe)3(μ3-NH)2] further reacts with H2or H+to form NH3.

An accurate energy yield estimation for building-integrated photovoltaic (PV) applications with colored glass under field conditions is a key factor for architects, building planners, and potential investors. The power output of these installations depends not only on the angle of incidence but also on the incident solar spectrum. The aim of this work is to simulate the short-circuit current of PV single-cell laminates with colored solar glass under field conditions. Therefore, we use angular-dependent spectral responsivity measurement data from a physical setup. Test samples with gold-, blue-, blue-green-, and gray-colored solar glass and a reference with standard solar glass, oriented on a tilted surface, are simulated. The results for one month of field validation indicate a good agreement with a relative root mean square error between 1.9% and 2.5% for the test samples. A model comparison reveals larger errors for the blue, blue-green, and gold test samples when the spectral responsivity at normal incidence and the incident angle modifier for broadband direct irradiation are used instead. It is concluded that short-circuit current simulation using indoor characterization from spectrally resolved measurement setups provides improved accuracy that is particularly suitable for bankable energy yield estimates of colored building-integrated PV modules.

Hintergrund: Dermatochirurgische (DC) Lehre basiert auf einer Kombination aus dem Lesen/Verstehen von Lehrbüchern und der Anwendung von operativen Eingriffen (± Supervision). Die meisten Lehrbücher sind primär textzentriert. Der Text (T) wird visuell unterstützt durch Fotos/Skizzen (S), ggf. auch Videos (V). Ein Lernziel dieser Lehre sollte es sein, dass der Lernende sich am Ende zutraut, einen Eingriff selbstständig durchzuführen. Methoden: Wir haben eine online-basierte Plattform, den FlapFinder (FF) (www.skin-surgery.org) entwickelt, die dem Anwender die DC im Gesichtsbereich primär in Form von S + V lehrt. Diese werden durch einen Kurztext (KT) und Bonusmaterial (B) unterstützt. B enthält persönliche Empfehlungen der FF-Autoren. Eine SurveyMonkey®-Analyse (Survey Monkey, San Mateo, CA, USA) sollte klären, wie dies durch den Anwender beurteilt wird. Ergebnisse: Es füllten 62 Teilnehmer den Fragebogen komplett aus. Dies war eine heterogene Gruppe (27 Dermatologen vs. 35 Nicht-Dermatologen; 32-mal Klinik vs. 30-mal Nicht-Klinik) mit unterschiedlicher Vorerfahrung. Der Großteil der Nutzer fand, dass die Kombination aus T + S + V geholfen hat, die Eingriffe zu verstehen (55/62; 88,7 %), zu erinnern (53/62, 85,5 %) und selbstständig durchzuführen (43/62; 69,3 %). Während S + V am häufigsten angewendet wurden (22/62; 35,5 % und 27/62; 43,6 %) und die Anwender angaben, hiervon am meisten profitiert zu haben (20/62; 32,3 % und 24/62; 38,7 %), wurden KT + B weniger angewendet (0/62, 0,0 % und 2/62; 3,2 %). Trotzdem würde der Großteil weder auf S, V, KT oder B verzichten wollen (49/62; 79 %) Schlussfolgerung: Die Kombination aus S + V + KT + B wird von den Lernenden der DC positiv beurteilt. S + V werden als besonders hilfreich bewertet. Zukünftige Studien müssen klären, ob das Lernziel der Anwendung der DC durch E‑Medien verändert wird. Graphic abstract:

Heat shock proteins 90 (Hsp90) are promising therapeutic targets due to their involvement in stabilizing several aberrantly expressed oncoproteins. In cancerous cells, Hsp90 expression is elevated, thereby exerting antiapoptotic effects, which is essential for the malignant transformation and tumor progression. Most of the Hsp90 inhibitors (Hsp90i) under investigation target the ATP binding site in the N-terminal domain of Hsp90. However, adverse effects, including induction of the prosurvival resistance mechanism (heat shock response or HSR) and associated dose-limiting toxicity, have so far precluded their clinical approval. In contrast, modulators that interfere with the C-terminal domain (CTD) of Hsp90 do not inflict HSR. Since the CTD dimerization of Hsp90 is essential for its chaperone activity, interfering with the dimerization process by small-molecule protein–protein interaction inhibitors is a promising strategy for anticancer drug research. We have developed a first-in-class small-molecule inhibitor (5b) targeting the Hsp90 CTD dimerization interface, based on a tripyrimidonamide scaffold through structure-based molecular design, chemical synthesis, binding mode model prediction, assessment of the biochemical affinity, and efficacy against therapy-resistant leukemia cells. 5breduces xenotransplantation of leukemia cells in zebrafish models and induces apoptosis in BCR-ABL1+(T315I) tyrosine kinase inhibitor-resistant leukemia cells, without inducing HSR.

High‐relief glacial valleys shape the modern topography of the Southern Patagonian Andes, but their formation remains poorly understood. Two Miocene plutonic complexes in the Andean retroarc, the Fitz Roy (49°S) and Torres del Paine (51°S) massifs, were emplaced between 16.9–16.4 Ma and 12.6–12.4 Ma, respectively. Subduction of oceanic ridge segments initiated ca. 16 Ma at 54°S, leading to northward opening of a slab window with associated mantle upwelling. The onset of major glaciations caused drastic topographic changes since ca. 7 Ma. To constrain the respective contributions of tectonic‐mantle dynamics and fluvio‐glacial erosion to rock exhumation and landscape evolution, we perform inverse thermal modeling of a new data set of zircon and apatite (U‐Th)/He from the two massifs, complemented by apatite 4He/3He data for Torres del Paine. Our results show rapid rock exhumation recorded only in the Fitz Roy massif between 10 and 8 Ma, which we ascribe to local mantle upwelling forcing surface uplift and intensified erosion around 49°S. Both massifs record a pulse of rock exhumation between 7 and 4 Ma, which we interpret as enhanced erosion during the beginning of Patagonian glaciations. After a period of erosional and tectonic quiescence in the Pliocene, increased rock exhumation since 3–2 Ma is interpreted as the result of alpine glacial valley carving promoted by reinforced glacial‐interglacial cycles. This study highlights that glacial erosion was the main driver to rock exhumation in the Patagonian retroarc since 7 Ma, but that mantle upwelling might be a driving force to rock exhumation as well. The isotopic system (U‐Th)/He in apatite and zircon record the ages in which a rock experiences relatively low temperatures (200–60°C) at shallow crustal depths (6–1 km). We present a new data set of low‐temperature thermochronometers for rocks of the Fitz Roy and Torres del Paine mountains in the Southern Patagonian Andes. Fast rock cooling can be forced by intensified surface erosion, and/or tectonic and mantle activity. An episode of fast cooling between 10 and 8 Ma was identified in the Fitz Roy mountains, and mantle upwelling forcing surface uplift, combined with high fluvial erosion may have caused fast rock exhumation. A regional episode of fast rock cooling between 7 and 4 Ma causing 1–3 km of exhumation in the Fitz Roy and Torres del Paine is coincident with the onset of Patagonian glaciations, which would have enhanced erosion and, thus, rock exhumation. An episode of fast rock cooling in the Quaternary is recorded in Torres del Paine rocks, interpreted as enhanced fluvio‐glacial erosion during the Plio‐Pleistocene climate transition toward faster glacial/interglacial cycles. Therefore, we were able to quantify separately the effects of tectonics and climate changes on rock exhumation, what is usually difficult due to simultaneously occurring processes. Mantle upwelling in Southern Patagonia is the most likely mechanism forcing rock exhumation between 10 and 8 Ma in the Fitz Roy massifApatite (U‐Th)/He data reveal glacial erosion as the main driver to the exhumation of the Fitz Roy and Torres del Paine between 7 and 4 MaApatite 4He/3He data reveal intensified fluvio‐glacial erosion in Torres del Paine as a result of the Plio‐Pleistocene climate transition Mantle upwelling in Southern Patagonia is the most likely mechanism forcing rock exhumation between 10 and 8 Ma in the Fitz Roy massif Apatite (U‐Th)/He data reveal glacial erosion as the main driver to the exhumation of the Fitz Roy and Torres del Paine between 7 and 4 Ma Apatite 4He/3He data reveal intensified fluvio‐glacial erosion in Torres del Paine as a result of the Plio‐Pleistocene climate transition

Modification of polyketides with fluorine offers a promising approach to develop new pharmaceuticals. While synthetic chemical methods for site-selective incorporation of fluorine in complex molecules have improved in recent years, approaches for the biosynthetic incorporation of fluorine in natural compounds are still rare. Here, we report a strategy to introduce fluorine into complex polyketides during biosynthesis. We exchanged the native acyltransferase domain of a polyketide synthase, which acts as the gatekeeper for the selection of extender units, with an evolutionarily related but substrate tolerant domain from metazoan type I fatty acid synthase. The resulting polyketide-synthase/fatty-acid-synthase hybrid can utilize fluoromalonyl coenzyme A and fluoromethylmalonyl coenzyme A for polyketide chain extension, introducing fluorine or fluoro-methyl units in polyketide scaffolds. We demonstrate the feasibility of our approach in the chemoenzymatic synthesis of fluorinated 12- and 14-membered macrolactones and fluorinated derivatives of the macrolide antibiotics YC-17 and methymycin.

AbstractStriking a balance between the weed control capacity of living mulches and their competition with the main crop is complex. At rates that avoid severe injury to living mulch, herbicides may reduce their vigor while simultaneously contributing to weed control. In a 2-yr field study carried out in Freeville, NY, we evaluated the effects of various combinations consisting of two herbicides, applied sequentially at reduced rates, on the growth of a sunn hemp living mulch and weeds (including common lambsquarters, common purslane, hairy galinsoga, and Powell amaranth). When a herbicide with primarily POST activity (Type 1; e.g., rimsulfuron, 0.005 to 0.007 kg ai ha−1) was applied first, performance of sunn hemp (1700 to 3900 kg ha−1dry biomass; 10% to 88% groundcover) was poor and weed growth (25% to 62% groundcover) was high, likely because sunn hemp was severely injured at a young growth stage and was outcompeted by weeds. A follow-up application (approximately 2 wk later) of a herbicide with primarily PRE and residual activities (Type 2; e.g., metribuzin, 0.05 to 0.15 kg ai ha−1), with a surfactant to enhance its POST activity, had little effect on established weeds. However, because sunn hemp was already 20 cm tall at weed emergence, applying a Type 2 herbicide first did not cause severe injury to sunn hemp and reduced weed pressure, thereby also enhancing sunn hemp performance (3,800 to 6,100 kg ha−1dry biomass; 85% to 94% groundcover). Moreover, the follow-up application of a Type 1 herbicide affected the smaller weeds more (4% to 21% groundcover) than the better-established sunn hemp. Our results demonstrate that an appropriate sequence of herbicides at reduced rates may be important to control weeds while maintaining a healthy living mulch stand.

ABSTRACTMacroautophagy/autophagy can play a cytoprotective role after photodynamic damage to malignant cells, depending on the site of subcellular damage initiated by reactive oxygen species. There is evidence for such protection when mitochondria are among the targets. Targeting lysosomes has been reported to be more effective for photokilling, perhaps because autophagy offers no cytoprotection. Photodynamic damage to both lysosomes and mitochondria can, however, markedly enhance the overall level of photokilling. Two mechanisms have been proposed to account for this result. Lysosomal photodamage leads to the release of calcium ions, resulting in the activation of the protease CAPN (calpain). CAPN then cleaves ATG5 to a fragment (tATG5) capable of interacting with mitochondria to enhance pro-apoptotic signals. It has also been proposed that targeting lysosomes for photodynamic damage can impair mitophagy, a process that could mitigate the pro-apoptotic effects of mitochondrial targeting. The level of lysosomal photodamage required for suppression of mitophagy is unclear. The “tATG5 route” involves the catalytic action of CAPN, activated by a degree of lysosomal photodamage barely detectible by a viability assay. ER photodamage can also initiate paraptosis, a death pathway functional even in cell types with impaired apoptosis and apparently unaffected by autophagy.Abbreviations: ALLN: N-acetyl-Leu-Leu-norleucinal (cell-permeable inhibitor of calpain); ATG: autophagy related; BPD: benzoporphyrin derivative (Visudyne); ER: endoplasmic reticulum; EtNBS: 5-ethylamino-9-diethyl-aminobenzo[a]phenothiazinium chloride; MTT: a tetrazolium dye; NPe6: mono N-aspartyl chlorin e6; PDT: photodynamic therapy; ROS: reactive oxygen species

Near infrared (NIR) spectroscopy using a fiber optic probe shows great promise for the nondestructive in situmonitoring of tissue engineered construct development; however, the NIR evaluation of matrix components in samples with high water content is challenging, as water absorbances overwhelm the spectra. In this study, we established approaches by which NIR spectroscopy can be used to select optimal individual engineered hydrogel constructs based on matrix content and mechanical properties. NIR spectroscopy of dry standard compounds allowed identification of several absorbances related to collagen and/or proteoglycan (PG), of which only two could be identified in spectra obtained from hydrated constructs, at ∼5940 and 5800 cm−1. In dry sample mixtures, the ratio of these peaks correlated positively to collagen and negatively to PG. In NIR spectra from engineered cartilage hydrogels, these peaks reflected higher collagen and PG content and dynamic modulus values, permitting the differentiation of constructs with poor and good matrix development. Similarly, the increasing baseline offset in raw NIR spectra also reflected matrix development in hydrated constructs. However, weekly monitoring of NIR spectra and the peaks at ∼5940 and 5800 cm−1was not adequate to differentiate individual constructs based on matrix composition. Interestingly, changes in the baseline offset of raw spectra could be used to evaluate the growth trajectory of individual constructs. These results demonstrate an optimal approach for the use of fiber optic NIR spectroscopy for in situmonitoring of the development of engineered cartilage, which will aid in identifying individual constructs for implantation.Impact statementA current demand in tissue engineering is the establishment of nondestructive approaches to evaluate construct development during growth in vitro. In this article, we demonstrate original nondestructive approaches by which fiber optic NIR spectroscopy can be used to assess matrix (PG and collagen) formation and mechanical properties in hydrogel-based constructs. Our data provide a cohesive molecular-based approach for in situlongitudinal evaluation of construct development during growth in vitro.The establishment of these approaches is a valuable step toward the real-time identification and selection of constructs with optimal properties, which may lead to successful tissue integration upon in vivoimplantation.

Knowledge of protein structures is essential to understand proteins’ functions, evolution, dynamics, stabilities, and interactions and for data-driven protein- or drug design. Yet, experimental structure determination rates are far exceeded by that of next-generation sequencing, resulting in less than 1/1000th of proteins having an experimentally known 3D structure. Computational structure prediction seeks to alleviate this problem, and the Critical Assessment of Protein Structure Prediction (CASP) has shown the value of consensus and meta-methods that utilize complementary algorithms. However, traditionally, such methods employ majority voting during template selection and model averaging during refinement, which can drive the model away from the native fold if it is underrepresented in the ensemble. Here, we present TopModel, a fully automated meta-method for protein structure prediction. In contrast to traditional consensus and meta-methods, TopModel uses top-down consensus and deep neural networks to select templates and identify and correct wrongly modeled regions. TopModel combines a broad range of state-of-the-art methods for threading, alignment, and model quality estimation and provides a versatile workflow and toolbox for template-based structure prediction. TopModel shows a superior template selection, alignment accuracy, and model quality for template-based structure prediction on the CASP10–12 datasets compared to 12 state-of-the-art stand-alone primary predictors. TopModel was validated by prospective predictions of the nisin resistance protein (NSR) protein from Streptococcus agalactiaeand LipoP from Clostridium difficile, showing far better agreement with experimental data than any of its constituent primary predictors. These results, in general, demonstrate the utility of TopModel for protein structure prediction and, in particular, show how combining computational structure prediction with sparse or low-resolution experimental data can improve the final model.

Often denied scientific status, Völkerpsychologiewas set forth as a psychological program endeavoring to find insights into the structure and content of the ‘mind’ of social groups, especially ‘peoples’, which were regarded as the prototypical manifestation of those groups. This article examines how Moritz Lazarus and Heymann Steinthal’s nineteenth-century Völkerpsychologiecame to be regarded as having the status of a science, by analyzing its scientific program. I claim that these founders of Völkerpsychologiedeveloped a moderate methodological materialism by embracing a historical turn in psychology, which—to a degree—enabled a synthesis of the methodologies of the social and the natural sciences. This approach is correlated with their modus operandi, collaboration through the medium of a journal.

AbstractLiving mulches can provide many sustainability benefits. However, living mulch–cash crop competition and unreliable weed control are major challenges in living mulch systems. In this study, we evaluated the potential of herbicides used at reduced rates in combination with living mulch to suppress weeds, while simultaneously reducing living mulch vigor. Herbicide treatments were a combination of two POST applications, each consisting of a single, different herbicide. Field trials were conducted in Freeville, NY, USA, using: fresh market field tomato as cash crop; sesbania and sunn hemp as living mulch; and the herbicides fomesafen, halosulfuron, metribuzin, and rimsulfuron. In 2015, when water was not limiting, tomato yield and living mulch biomass were positively correlated. This relationship was negative in 2016, likely because of drought during the growing season. Compared with the untreated living mulch check, using the herbicide treatments in combination with living mulch reduced tomato yield losses by up to 71% in 2015 and 51% in 2016. In these herbicide plus living mulch plots, weed biomass was reduced by up to 97%, compared with the weedy check. Living mulch in herbicide treatments generated up to 2500 kg ha−1of dry matter during both 2015 and 2016, with an average ground cover of 63% in 2015 and 85% in 2016. A predominantly PRE herbicide with residual soil activity (metribuzin), followed by a herbicide with greater POST activity (halosulfuron/rimsulfuron) was the most effective herbicide application sequence. Results from our study indicate that well-designed herbicide applications may enhance the practicability of living mulch systems.

Non-natural azetidine-based amino acids (Aze) present interesting features in protein engineering. A simple organometallic route toward unsaturated carboxylic acid precursors is presented. Subsequent metal-catalyzed asymmetric reduction allowed for the synthesis of a new library of 2-azetidinylcarboxylic acids, which were finally employed in the formation of small peptide chains.

A series of Co(I), Co(II), and Ni(II) compounds were prepared by employing the open pentadienyl 2,4-(Me3C)2C5H5(Pdl′) and some edge-bridged variants (ePdl) such as 6,6′-dimethylcyclohexadienyl (dmch), cycloheptadienyl (chd), and cyclooctadienyl (cod). The sterically encumbered Pdl′ ligand allowed the first synthesis of an open cobaltocene derivative [(η3-Pdl′2)Co] (1), which adopts a low-spin configuration and features two η3-coordinate Pdl′ units. For Ni(II), the heteroleptic derivative [(η3-Pdl′)Ni(acac)] (2) and the open nickelocene [(η3-Pdl′2)Ni] (3) were isolated. Complex 3is isostructural to its Co analogue (1). The reactivity patterns, however, change when similar reactions are performed with the edge-bridged pentadienyl derivatives (ePdl = dmch, chd, and cod). For [Co(acac)2] the reaction with K(dmch) and K(chd) resulted in reduction of Co(II) to Co(I), concomitant with ligand coupling to form bridging Co(I) complexes 5and 6with μ2-η4:η4-(dmch)2and μ2-η4:η4-(chd)2units, respectively. In contrast, the isolation of [(η3-dmch)2Ni] (7) and [(η3-cod)2Ni] (8) proceeds in excellent yields. In addition, several Co(I) complexes of the type [(η3-cod)Co(L3)] (L = PMe3; L2= dppe/dmpe, L = PMe3/CO) were prepared, which feature low melting and sublimation/distillation points. These complexes may offer potential for ALD/CVD processes.