Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibody to Langerin/CD207 localizes large numbers of CD8α+ dendritic cells to the marginal zone of mouse spleen

Dendritic cells (DCs) are strategically positioned to take up antigens and initiate adaptive immunity. One DC subset expresses CD8αα in mice and is specialized to capture dying cells and process antigens for MHC class I “cross-presentation. ” Because CD8+ DCs also express DEC205/CD205, which is localized to splenic T cell regions, it is thought that CD8+ DCs also are restricted to T zones. Here, we used a new antibody to Langerin/CD207, which colabels isolated CD8+ CD205+ DCs, to immunolabel spleen sections. The mAb labeled discrete cells with high levels of CD11c and CD8. Surprisingly most CD207+ profiles were in marginal zones surrounding splenic white pulp nodules, and only smaller numbers were in T cell areas, where CD205 colabeling was noted. Despite a marginal zone location, CD207+ DCs lacked identifying molecules for 3 different types of macrophages, localized in proximity and, in contrast to macrophages, marginal zone DCs were poor scavengers of soluble and particulate substrates. After stimulation with microbial agonists, Langerin expression disappeared from the marginal zone at 6–12 h, but was greatly expanded in the T cell areas, and by 24–48 h, Langerin expression disappeared. Therefore, anti-Langerin antibodies localize a majority of CD8+ DCs to non-T cell regions of mouse spleen, where they are distinct from adjacent macrophages.
Elastic Properties of Freely Suspended MoS2 Nanosheets

We study the elastic deformation of few layers (5 to 25) thick freely suspended MoS2 nanosheets by means of a nanoscopic version of a bending test experiment, carried out with the tip of an atomic force microscope. The Young's modulus of these nanosheets is extremely high (E = 0.33 TPa), comparable to that of graphene oxide, and the deflections are reversible up to tens of nanometers.
Evidence of cacao use in the Prehispanic American Southwest

Chemical analyses of organic residues in fragments of ceramic vessels from Pueblo Bonito in Chaco Canyon, New Mexico, reveal theobromine, a biomarker for cacao. With an estimated 800 rooms, Pueblo Bonito is the largest archaeological site in Chaco Canyon and was the center of a large number of interconnected towns and villages spread over northwestern New Mexico. The cacao residues come from pieces of vessels that are likely cylinder jars, special containers occurring almost solely at Pueblo Bonito and deposited in caches at the site. This first known use of cacao drinks north of the Mexican border indicates exchange with cacao cultivators in Mesoamerica in a time frame of about A.D. 1000–1125. The association of cylinder jars and cacao beverages suggests that the Chacoan ritual involving the drinking of cacao was tied to Mesoamerican rituals incorporating cylindrical vases and cacao. The importance of Pueblo Bonito within the Chacoan world likely lies in part with the integration of Mesoamerican ritual, including critical culinary ingredients.
Do Migrants Transfer Tacit Knowledge? The Case of Highly Skilled Bangladeshi Immigrants in the United States

Transfer of knowledge is a complex process. While codified knowledge is easy to transfer, tacit knowledge is not. "Tacit knowledge is difficult to exchange over long distance because it is heavily imbued with meaning arising from the social and institutional context in which it is produced, and this context specific nature makes it spatially sticky" (Gertler 2003). This thesis argues that there is certain tacit knowledge that migrants often transmit over long distances after customizing the knowledge to apply in different institutional settings. This thesis takes the example of Bangladesh, a country having an unfavorable socioeconomic and institutional setting for receiving new technology, and explains how, despite the unfavorable conditions, some expatriates do transfer their knowledge to Bangladesh. Based on in-depth interviews with those expatriates creating the most impact in the economy of Bangladesh, the thesis shows that highly skilled Bangladeshi immigrants in the United States transfer tacit knowledge through building partnerships with individuals and organizations in Bangladesh. The thesis also finds that these partnerships are mostly based on trust, often coming from basic commonalities: same language, common "codes" of communication, shared norms, and personal knowledge about each other.
Stability of Polymer Solar Cells

Organic photovoltaics (OPVs) evolve in an exponential manner in the two key areas of efficiency and stability. The power conversion efficiency (PCE) has in the last decade been increased by almost a factor of ten approaching 10%. A main concern has been the stability that was previously measured in minutes, but can now, in favorable circumstances, exceed many thousands of hours. This astonishing achievement is the subject of this article, which reviews the developments in stability/degradation of OPVs in the last five years. This progress has been gained by several developments, such as inverted device structures of the bulk heterojunction geometry device, which allows for more stable metal electrodes, the choice of more photostable active materials, the introduction of interfacial layers, and roll‐to‐roll fabrication, which promises fast and cheap production methods while creating its own challenges in terms of stability.
Docking for fragment inhibitors of AmpC β-lactamase

Fragment screens for new ligands have had wide success, notwithstanding their constraint to libraries of 1,000–10,000 molecules. Larger libraries would be addressable were molecular docking reliable for fragment screens, but this has not been widely accepted. To investigate docking's ability to prioritize fragments, a library of >137,000 such molecules were docked against the structure of β-lactamase. Forty-eight fragments highly ranked by docking were acquired and tested; 23 had Ki values ranging from 0.7 to 9.2 mM. X-ray crystal structures of the enzyme-bound complexes were determined for 8 of the fragments. For 4, the correspondence between the predicted and experimental structures was high (RMSD between 1.2 and 1.4 Å), whereas for another 2, the fidelity was lower but retained most key interactions (RMSD 2.4–2.6 Å). Two of the 8 fragments adopted very different poses in the active site owing to enzyme conformational changes. The 48% hit rate of the fragment docking compares very favorably with “lead-like” docking and high-throughput screening against the same enzyme. To understand this, we investigated the occurrence of the fragment scaffolds among larger, lead-like molecules. Approximately 1% of commercially available fragments contain these inhibitors whereas only 10−7% of lead-like molecules do. This suggests that many more chemotypes and combinations of chemotypes are present among fragments than are available among lead-like molecules, contributing to the higher hit rates. The ability of docking to prioritize these fragments suggests that the technique can be used to exploit the better chemotype coverage that exists at the fragment level.
Fabrication of Graphene Nanomesh by Using an Anodic Aluminum Oxide Membrane as a Template

Graphene, a one-atom-thick two-dimensional carbon sheet, has been extensively studied owing to its broad applications in nanoelectronics, [ 1 , 2 ] nanocomposites, [ 3 , 4 ] chemical sensors and biosensors, [ 5–10 ] solar cells, [ 11–13 ] and electrical and optical devices. [ 14–16 ] However, the application of graphene in fi eldeffect transistors (FETs) is limited because of its semi-metallic behavior with zero bandgap. [ 17 , 18 ] Cutting graphene sheets into nanoribbons led to bandgap opening, with current ON/OFF ratio large enough for transistor operation. [ 19–23 ] Unfortunately, FET devices based on the individual nanoribbons exhibited low driving current and conductance. [ 22 ]
A molecular brake, not a clutch, stops the Rhodobacter sphaeroides flagellar motor

Many bacterial species swim by employing ion-driven molecular motors that power the rotation of helical filaments. Signals are transmitted to the motor from the external environment via the chemotaxis pathway. In bidirectional motors, the binding of phosphorylated CheY (CheY-P) to the motor is presumed to instigate conformational changes that result in a different rotor-stator interface, resulting in rotation in the alternative direction. Controlling when this switch occurs enables bacteria to accumulate in areas favorable for their survival. Unlike most species that swim with bidirectional motors, Rhodobacter sphaeroides employs a single stop-start flagellar motor. Here, we asked, how does the binding of CheY-P stop the motor in R. sphaeroides—using a clutch or a brake? By applying external force with viscous flow or optical tweezers, we show that the R. sphaeroides motor is stopped using a brake. The motor stops at 27–28 discrete angles, locked in place by a relatively high torque, approximately 2–3 times its stall torque.
An engineered lipocalin specific for CTLA-4 reveals a combining site with structural and conformational features similar to antibodies

Biomolecular reagents that enable the specific molecular recognition of proteins play a crucial role in basic research as well as medicine. Up to now, antibodies (immunoglobulins) have been widely used for this purpose. Their predominant feature is the vast repertoire of antigen-binding sites that arise from a set of 6 hypervariable loops. However, antibodies suffer from practical disadvantages because of their complicated architecture, large size, and multiple functions. The lipocalins, on the other hand, have evolved as a protein family that primarily serves for the binding of small molecules. Here, we show that an engineered lipocalin, derived from human Lcn2, can specifically bind the T cell coreceptor CTLA-4 as a prescribed protein target with subnanomolar affinity. Crystallographic analysis reveals that its reshaped cup-like binding site, which is formed by 4 variable loops, provides perfect structural complementarity with this “antigen. ” Furthermore, comparison with the crystal structure of the uncomplexed engineered lipocalin indicates a pronounced induced-fit mechanism, a phenomenon so far considered typical for antibodies. By recognizing the same epitope on CTLA-4 that interacts with the counterreceptors B7.1/B7.2 on antigen-presenting cells the engineered Lcn2 exhibits strong, cross-species antagonistic activity, as evidenced by biological effects comparable with a CTLA-4-specific antibody. With its proven stimulatory activity on T cells in vivo, the CTLA-4 blocking lipocalin offers potential for immunotherapy of cancer and infectious disease. Beyond that, lipocalins with engineered antigen-binding sites, so-called Anticalins, provide a class of small (≈180 residues), structurally simple, and robust binding proteins with applications in the life sciences in general.
Mass spectrometry-based metabolomics application to identify quantitative resistance-related metabolites in barley against Fusarium head blight.

Quantitative resistance is generally controlled by several genes. More than 100 resistance quantitative trait loci (QTLs) have been identified in wheat and barley against Fusarium head blight (FHB), caused by Gibberella zeae (anamorph: Fusarium graminearum), implying the possible occurrence of several resistance mechanisms. The objective of this study was to apply metabolomics to identify the metabolites in barley that are related to resistance against FHB. Barley genotypes, Chevron and Stander, were inoculated with mock or pathogen during the anthesis stage. The disease severity was assessed as the proportion of spikelets diseased. The genotype Chevron (0.33) was found to have a higher level of quantitative resistance than Stander (0.88). Spikelet samples were harvested at 48 h post-inoculation; metabolites were extracted and analysed using an LC-ESI-LTQ-Orbitrap (Thermo Fisher, Waltham, MA, USA). The output was imported to an XCMS 1.12. 1 platform, the peaks were deconvoluted and the adducts were sieved. Of the 1826 peaks retained, a t-test identified 496 metabolites with significant treatment effects. Among these, 194 were resistance-related (RR) constitutive metabolites, whose abundance was higher in resistant mock-inoculated than in susceptible mock-inoculated genotypes. Fifty metabolites were assigned putative names on the basis of accurate mass, fragmentation pattern and number of carbons in the formula. The RR metabolites mainly belonged to phenylpropanoid, flavonoid, fatty acid and terpenoid metabolic pathways. Selected RR metabolites were assayed in vitro for antifungal activity on the basis of fungal biomass production. The application of these RR metabolites as potential biomarkers for screening and the potential of mass spectrometry-based metabolomics for the identification of gene functions are discussed.
Essential global role of CDC14 in DNA synthesis revealed by chromosome underreplication unrecognized by checkpoints in cdc14 mutants

The CDC14 family of multifunctional evolutionarily conserved phosphatases includes major regulators of mitosis in eukaryotes and of DNA damage response in humans. The CDC14 function is also crucial for accurate chromosome segregation, which is exemplified by its absolute requirement in yeast for the anaphase segregation of nucleolar organizers; however the nature of this essential pathway is not understood. Upon investigation of the rDNA nondisjunction phenomenon, it was found that cdc14 mutants fail to complete replication of this locus. Moreover, other late-replicating genomic regions (10% of the genome) are also underreplicated in cdc14 mutants undergoing anaphase. This selective genome-wide replication defect is due to dosage insufficiency of replication factors in the nucleus, which stems from two defects, both contingent on the reduced CDC14 function in the preceding mitosis. First, a constitutive nuclear import defect results in a drastic dosage decrease for those replication proteins that are regulated by nuclear transport. Particularly, essential RPA subunits display both lower mRNA and protein levels, as well as abnormal cytoplasmic localization. Second, the reduced transcription of MBF and SBF-controlled genes in G1 leads to the reduction in protein levels of many proteins involved in DNA replication. The failure to complete replication of late replicons is the primary reason for chromosome nondisjunction upon CDC14 dysfunction. As the genome-wide slow-down of DNA replication does not trigger checkpoints [Lengronne A, Schwob E (2002) Mol Cell 9:1067–1078], CDC14 mutations pose an overwhelming challenge to genome stability, both generating chromosome damage and undermining the checkpoint control mechanisms.
Quantitative analysis by in vivo imaging of the dynamics of vascular and axonal networks in injured mouse spinal cord

Understanding the endogenous repair capacity of spinal cord is pivotal to develop strategies to improve it. Here we design a paradigm of spinal cord lesion in the dorsal column using a 2-photon microscopy technique to dynamically and chronically monitor simultaneous changes of vascular and axonal networks in living mice up to 4 months postinjury. High-resolution images showed that early explorative sprouting of surviving injured axons resulted in extensive regrowth until and past the lesion site within 2 months. Blood vessel density was transiently up-regulated and most neurovascular interactions occurred within 2 weeks. Time-lapse analysis showed that neovessels exerted a potent growth stimulating action, but no guidance effect on neighboring sprouts, possibly because of their geometry and plasticity. Nevertheless, if reconnection depends on axon sprout density, stimulation of angiogenesis would probably be beneficial to repair. More generally, this imaging approach is showing promise to aid in monitoring brain diseases and the efficacy of potential treatments.
Food Away From Home: How much does it really influence diet quality?

This study confirms that eating food away from home (FAFH) adversely affects dietary intake. By looking at changes within individuals’ dietary intake over two days, thus controlling for self-selection issues, we find that FAFH causes increased caloric intake and reduced diet quality. Our estimates on the effect of specific meals show that lunch and dinner consumed away from home have the largest effect on total daily caloric intake, but that breakfast has the largest negative effect on total diet quality. In particular, eating breakfast away from home decreases intake of fruit, whole grains and dairy and increases the percent of calories from saturated fats and solid fats, alcohol and added sugar. Eating lunch and dinner away from home also reduce diet quality, affecting similar dietary components, with dinner away from home also reducing vegetable intake. Unlike past studies based on correlation analyses, this study shows how FAFH can have a causal impact on weight gain.
PIDD mediates the association of DNA-PKcs and ATR at stalled replication forks to facilitate the ATR signaling pathway

Abstract The DNA-dependent protein kinase (DNA-PK), consisting of the DNA binding Ku70/80 heterodimer and the catalytic subunit DNA-PKcs, has been well characterized in the non-homologous end-joining mechanism for DNA double strand break (DSB) repair and radiation resistance. Besides playing a role in DSB repair, DNA-PKcs is required for the cellular response to replication stress and participates in the ATR-Chk1 signaling pathway. However, the mechanism through which DNA-PKcs is recruited to stalled replication forks is still unclear. Here, we report that the apoptosis mediator p53-induced protein with a death domain (PIDD) is required to promote DNA-PKcs activity in response to replication stress. PIDD is known to interact with PCNA upon UV-induced replication stress. Our results demonstrate that PIDD is required to recruit DNA-PKcs to stalled replication forks through direct binding to DNA-PKcs at the N’ terminal region. Disruption of the interaction between DNA-PKcs and PIDD not only compromises the ATR association and regulation of DNA-PKcs, but also the ATR signaling pathway, intra-S-phase checkpoint and cellular resistance to replication stress. Taken together, our results indicate that PIDD, but not the Ku heterodimer, mediates the DNA-PKcs activity at stalled replication forks and facilitates the ATR signaling pathway in the cellular response to replication stress.
Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation

The forebrain cholinergic system promotes higher brain function in part by signaling through the M1 muscarinic acetylcholine receptor (mAChR). During Alzheimer's disease (AD), these cholinergic neurons degenerate, therefore selectively activating M1 receptors could improve cognitive function in these patients while avoiding unwanted peripheral responses associated with non-selective muscarinic agonists. We describe here benzyl quinolone carboxylic acid (BQCA), a highly selective allosteric potentiator of the M1 mAChR. BQCA reduces the concentration of ACh required to activate M1 up to 129-fold with an inflection point value of 845 nM. No potentiation, agonism, or antagonism activity on other mAChRs is observed up to 100 μM. Furthermore studies in M1−/− mice demonstrates that BQCA requires M1 to promote inositol phosphate turnover in primary neurons and to increase c-fos and arc RNA expression and ERK phosphorylation in the brain. Radioligand-binding assays, molecular modeling, and site-directed mutagenesis experiments indicate that BQCA acts at an allosteric site involving residues Y179 and W400. BQCA reverses scopolamine-induced memory deficits in contextual fear conditioning, increases blood flow to the cerebral cortex, and increases wakefulness while reducing delta sleep. In contrast to M1 allosteric agonists, which do not improve memory in scopolamine-challenged mice in contextual fear conditioning, BQCA induces β-arrestin recruitment to M1, suggesting a role for this signal transduction mechanism in the cholinergic modulation of memory. In summary, BQCA exploits an allosteric potentiation mechanism to provide selectivity for the M1 receptor and represents a promising therapeutic strategy for cognitive disorders.
Health Technology Literacy: A Transdisciplinary Framework for Consumer-Oriented Practice

There is dramatic growth in the aging population and advances in technology innovation in the 21st century. Health technology can play a significant role in effectively helping older adults and people with chronic health conditions and disabilities to maintain function and independence. JordanMarsh’s book, Health Technology Literacy: A Transdisciplinary Framework for Consumer-Oriented Practice, highlights the importance of understanding and using health technology to engage in an empowerment cycle (data, information knowledge, wisdom, transitions, influence, and capital) within a socioecological framework. Through the lens of socioecological theory, the book offers a big-picture perspective on transdisciplinary consumer-oriented practice in the area of health technology literacy. The main objectives of the book are identified by the seven chapter titles: (1) “Telehealth as a fulcrum in health technology,” (2) “Literacy for an age of health,” (3) “Health information seeking behavior on the web,” (4) “The personal health record: Building human capital for health,” (5) “Devices as adjuncts to a being healthy at home,” (6) “Digital games: Consumer resources for health capital,” and (7) “Consumer-centric health technology: Wicked problems and delicious disruptive solutions. ” In a systematic manner, the book addresses issues related to telehealth (or e-health) in the home, work, and community environments. Jordan-Marsh has a background in nursing and psychology and is currently a professor of social work. Her transdisciplinary teaching, research, and practice background is apparent in the strong conceptual framework that is the foundation of this work. The book informs readers of useful e-health resources and of knowledge needed to understand and effectively access these resources. Furthermore, it challenges readers with the invitation to a virtual health-care culture that treats patients as partners, not just consumers or research subjects. Literature related to health technology continues to increase. Among of field of various noteworthy texts, Jordan-Marsh’s book stands out because it provides a socioecological framework, models, and resources to formulate
Sulfur‐Tolerant Redox‐Reversible Anode Material for Direct Hydrocarbon Solid Oxide Fuel Cells

A novel composite anode material consisting of K(2) NiF(4) -type structured Pr(0.8) Sr(1.2) (Co,Fe)(0.8) Nb(0.2) O(4+δ) (K-PSCFN) matrix with homogenously dispersed nano-sized Co-Fe alloy (CFA) has been obtained by annealing perovskite Pr(0.4) Sr(0.6) Co(0.2) Fe(0.7) Nb(0.1) O(3-δ) (P-PSCFN) in H(2) at 900 °C. The K-PSCFN-CFA composite anode is redox-reversible and has demonstrated similar catalytic activity to Ni-based cermet anode, excellent sulfur tolerance, remarkable coking resistance and robust redox cyclability.