Wettability-based ultrasensitive detection of amphiphiles through directed concentration at disordered regions in self-assembled monolayers.

Various forms of ecological monitoring and disease diagnosis rely upon the detection of amphiphiles, including lipids, lipopolysaccharides, and lipoproteins, at ultralow concentrations in small droplets. Although assays based on droplets' wettability provide promising options in some cases, their reliance on the measurements of surface and bulk properties of whole droplets (e.g., contact angles, surface tensions) makes it difficult to monitor trace amounts of these amphiphiles within small-volume samples. Here, we report a design principle in which self-assembled monolayer-functionalized microstructured surfaces coated with silicone oil create locally disordered regions within a droplet's contact lines to effectively concentrate amphiphiles within the areas that dominate the droplet static friction. Remarkably, such surfaces enable the ultrasensitive, naked-eye detection of amphiphiles through changes in the droplets' sliding angles, even when the concentration is four to five orders of magnitude below their critical micelle concentration. We develop a thermodynamic model to explain the partitioning of amphiphiles at the contact line by their cooperative association within the disordered, loosely packed regions of the self-assembled monolayer. Based on this local analyte concentrating effect, we showcase laboratory-on-a-chip surfaces with positionally dependent pinning forces capable of both detecting industrially and biologically relevant amphiphiles (e.g., bacterial endotoxins), as well as sorting aqueous droplets into discrete groups based on their amphiphile concentrations. Furthermore, we demonstrate that the sliding behavior of amphiphile-laden aqueous droplets provides insight into the amphiphile's effective length, thereby allowing these surfaces to discriminate between analytes with highly disparate molecular sizes.

How Do Quantum Effects Influence the Capacitance and Carrier Density of Monolayer MoS2 Transistors?

When transistor gate insulators have nanometer-scale equivalent oxide thickness (EOT), the gate capacitance (CG) becomes smaller than the oxide capacitance (Cox) due to the quantum capacitance and charge centroid capacitance of the channel. Here, we study the capacitance of monolayer MoS2 as a prototypical two-dimensional (2D) channel while considering spatial variations in the potential, charge density, and density of states. At 0.5 nm EOT, the monolayer MoS2 capacitance is smaller than its quantum capacitance, limiting the single-gated CG of an n-type channel to between 63% and 78% of Cox, for gate overdrive voltages between 0.5 and 1 V. Despite these limitations, for dual-gated devices, the on-state CG of monolayer MoS2 is 50% greater than that of silicon at 0.5 nm EOT and more than three times that of InGaAs at 1 nm EOT, indicating that such 2D semiconductors are promising for improved gate control of nanoscale transistors at future technology nodes.

Polymeric Chloroquine as an Effective Antimigration Agent in the Treatment of Pancreatic Cancer.

Hydroxychloroquine (HCQ) has been the subject of multiple recent preclinical and clinical studies for its beneficial use in the combination treatments of different types of cancers. Polymeric HCQ (PCQ), a macromolecular multivalent version of HCQ, has been shown to be effective in various cancer models both in vitro and in vivo as an inhibitor of cancer cell migration and experimental lung metastasis. Here, we present detailed in vitro studies that show that low concentrations of PCQ can efficiently inhibit cancer cell migration and colony formation orders of magnitude more effectively compared to HCQ. After intraperitoneal administration of PCQ in vivo, high levels of tumor accumulation and penetration are observed, combined with strong antimetastatic activity in an orthotopic pancreatic cancer model. These studies support the idea that PCQ may be effectively used at low doses as an adjuvant in the therapy of pancreatic cancer. In conjunction with previously published literature, these studies further undergird the potential of PCQ as an anticancer agent.

Regulatory interventions improve the biosynthesis of limiting amino acids from methanol carbon to improve synthetic methylotrophy in Escherichia coli.

Synthetic methylotrophy aims to engineer methane and methanol utilization pathways in platform hosts like Escherichia coli for industrial bioprocessing of natural gas and biogas. While recent attempts to engineer synthetic methylotrophs have proved successful, autonomous methylotrophy, that is, the ability to utilize methane or methanol as sole carbon and energy substrates, has not yet been realized. Here, we address an important limitation of autonomous methylotrophy in E. coli: the inability of the organism to synthesize several amino acids when grown on methanol. We targeted global and local amino acid regulatory networks. Those include removal of amino acid allosteric feedback inhibition (argAH15Y , ilvAL447F , hisGE271K , leuAG462D , proBD107N , thrAS345F , trpES40F ), knockouts of transcriptional repressors (ihfA, metJ); and overexpression of amino acid biosynthetic operons (hisGDCBHAFI, leuABCD, thrABC, trpEDCBA) and transcriptional regulators (crp, purR). Compared to the parent methylotrophic E. coli strain that was unable to synthesize these amino acids from methanol carbon, these strategies resulted in improved biosynthesis of limiting proteinogenic amino acids (histidine, leucine, lysine, methionine, phenylalanine, threonine, tyrosine) from methanol carbon. In several cases, improved amino acid biosynthesis from methanol carbon led to improvements in methylotrophic growth in methanol minimal medium supplemented with a small amount of yeast extract. This study addresses a key limitation currently preventing autonomous methylotrophy in E. coli and possibly other synthetic methylotrophs and provides insight as to how this limitation can be alleviated via global and local regulatory modifications.

Validating the revised Symptom Impact Questionnaire with a proposed fibromyalgia phenotype using experimentally-induced pain and patient self-reports.

OBJECTIVES: The Symptom Impact Questionnaire (SIQR), now used for over a decade, has strong psychometric properties based on patients' subjective questionnaire data and correlations with other general measures of severity. However, the construct validity of the SIQR in assessing the central features of fibromyalgia (FM) has not been tested specifically with more objective measures. This study examined the construct validity of the SIQR using clinical examination of prominent features of FM, as well as patient questionnaire data. METHODS: We determined if SIQR severity groups (low, moderate, high severity) in 158 chronic pain patients (50 FM, 108 Pain/No FM) predicted four central features of FM tenderness and pain: digital palpation tenderness, blood pressure cuff evoked pain, widespread pain locations, and a persistent deep ache question. RESULTS: Low, moderate, and high SIQR severity groups showed concomitant increases in tenderness in response to digital evoked palpation (F=23.5; p<0.0000; ηp2=0.23; MR=.54), blood pressure cuff evoked pain (F=17.0; p<0.0000; ηp2=0.18; MR=0.48) and number of pain location (F=38.8; p<0.0000; ηp2=0.33; MR.59). Strongest differences in SIQR severity were found in response to the question, "I have a persistent deep aching over most of my body" (F=87.5; p<0.0000; ηp2=0.53; MR=0.74). CONCLUSIONS: The SIQR strongly predicts the central features of FM tenderness and pain including its widespreadness and its multifaceted character. We propose that tenderness, both locally and over most of the body, attendant to the SIQR is the hallmark of the FM phenotype: tenderness is focal, diffuse, deep, and superficial.

Signature of Short-Range van der Waals Forces Observed in Poisson Spot Diffraction with Indium Atoms.

The phase of de Broglie matter waves is a sensitive probe for small forces. In particular, the attractive van der Waals force experienced by polarizable atoms in the close vicinity of neutral surfaces is of importance in nanoscale systems. It results in a phase shift that can be observed in matter-wave diffraction experiments. Here, we observe Poisson spot diffraction of indium atoms at submillimeter distances behind spherical submicron silicon dioxide particles to probe the dispersion forces between atoms and the particle surfaces. We compare the measured relative intensity of Poisson's spot to theoretical results derived from first principles in an earlier communication and find a clear signature of the atom-surface interaction.

Virtual Photon Approximation for Three-Body Interatomic Coulombic Decay.

Interatomic Coulombic decay (ICD) is a mechanism that allows microscopic objects to rapidly exchange energy. When the two objects are distant, the energy transfer between the donor and acceptor species takes place via the exchange of a virtual photon. On the contrary, recent ab initio calculations have revealed that the presence of a third passive species can significantly enhance the ICD rate at short distances due to the effects of electronic wave function overlap and charge transfer states [Phys. Rev. Lett. 119, 083403 (2017)PRLTAO0031-900710.1103/PhysRevLett.119.083403]. Here, we develop a virtual photon description of three-body ICD, allowing us to investigate retardation and geometrical effects which are out of reach for current ab initio techniques. We show that a passive atom can have a significant influence on the rate of the ICD process at fairly large interatomic distances, due to the scattering of virtual photons off the mediator. Moreover, we demonstrate that in the retarded regime ICD can be substantially enhanced or suppressed depending on the position of the ICD-inactive object, even if the latter is far from both donor and acceptor species.

Evidence for a Spatially Modulated Superfluid Phase of

In superfluid ^{3}He-B confined in a slab geometry, domain walls between regions of different order parameter orientation are predicted to be energetically stable. Formation of the spatially modulated superfluid stripe phase has been proposed. We confined ^{3}He in a 1.1 µm high microfluidic cavity and cooled it into the B phase at low pressure, where the stripe phase is predicted. We measured the surface-induced order parameter distortion with NMR, sensitive to the formation of domains. The results rule out the stripe phase, but are consistent with 2D modulated superfluid order.

The Psychopharmacological Thriller: Representations of Psychotropic Pills in American Popular Culture.

Psychotropic medications have increasingly become a staple of modern life, with one in five adults now taking some kind of psychiatric pill. Consequently, our voracious consumption of psychotropic pills has begun to raise significant questions about how psychopharmacology radically transforms-modifies, manipulates, molds, and manufactures-human identities one pill at a time. Moreover, this biochemical micro-engineering of the human self has begun to emerge as one of contemporary culture's major preoccupations as new narratives-in memoir, literature, television, film, and popular music-have begun to explore not only mental illnesses themselves but also the medications we take to treat those illnesses. In this newly emergent genre, which I call the psychopharmacological thriller, new narrative techniques are being developed to probe the inner neurochemistry of the human brain, how medications alter that neurochemistry, and the wide-ranging questions raised by this brave new proliferation of psychopharmacology in everyday life.

Nonadditivity of Optical and Casimir-Polder Potentials.

An atom irradiated by an off-resonant laser field near a surface is expected to experience the sum of two fundamental potentials, the optical potential of the laser field and the Casimir-Polder potential of the surface. Here, we report a new nonadditive potential, namely, the laser-induced Casimir-Polder potential, which arises from a correlated coupling of the atom with both the laser and the quantum vacuum. We apply this result to an experimentally realizable scenario of an atomic mirror with an evanescent laser beam leaking out of a surface. We show that the nonadditive term is significant for realistic experimental parameters, transforming potential barriers into potential wells, which can be used to trap atoms near surfaces.

Living with Cancer: an Educational Intervention in Cancer Patients Can Improve Patient-Reported Knowledge Deficit.

A cancer diagnosis requires significant information to facilitate health care decision making, understand management options, and health care system navigation. Patient knowledge deficit can decrease quality of life and health care compliance. Surveys were distributed to attendees of the Mayo Clinic "Living with and Surviving Cancer" patient symposium January 2015. Follow-up survey was sent to participants 3 months after the symposium. Surveys included demographic data and patient-reported disease comprehension, symptom burden, desired information, and quality-of-life assessment. Demographics: 113 patients completed the pre-intervention survey. Average age was 64.7 years. Disease types included hematologic (N = 50) and solid malignancies (N = 77). Most patients self-reported adequate baseline understanding of their disease (80 %), screening tests (74 %), and monitoring tools (72 %). Lowest knowledge topics were legal issues (13 %) and pain management (35 %). Pre- and post-analysis: 79 of the initial 113 participants completed both surveys. In the post-symposium setting, durable knowledge impact was noted in disease understanding (pre 80 % vs post 92 %), treatment options (pre 60 % vs post 76 %), nutrition (pre 68 % vs post 84 %), and legal issues (pre 15 % vs post 32 %). Most patients desired increased understanding regarding disease, screening tests, nutrition, and stress and fatigue management. The level of desired information for these topics decreased in the post-symposium setting, statistically significant decrease noted in 4 of 5 topics assessed. Knowledge needs and deficit in cancer care range from disease-specific topics, social stressors, and health care navigation. A cancer patient-centered symposium can improve patient-reported knowledge deficit, with durable responses at 3 months, but patient needs persist.

Deformation-induced transitional myofibroblasts contribute to compensatory lung growth.

In many mammals, including humans, removal of one lung (pneumonectomy) results in the compensatory growth of the remaining lung. Compensatory growth involves not only an increase in lung size, but also an increase in the number of alveoli in the peripheral lung; however, the process of compensatory neoalveolarization remains poorly understood. Here, we show that the expression of α-smooth muscle actin (SMA)-a cytoplasmic protein characteristic of myofibroblasts-is induced in the pleura following pneumonectomy. SMA induction appears to be dependent on pleural deformation (stretch) as induction is prevented by plombage or phrenic nerve transection (P < 0.001). Within 3 days of pneumonectomy, the frequency of SMA+ cells in subpleural alveolar ducts was significantly increased (P < 0.01). To determine the functional activity of these SMA+ cells, we isolated regenerating alveolar ducts by laser microdissection and analyzed individual cells using microfluidic single-cell quantitative PCR. Single cells expressing the SMA (Acta2) gene demonstrated significantly greater transcriptional activity than endothelial cells or other discrete cell populations in the alveolar duct (P < 0.05). The transcriptional activity of the Acta2+ cells, including expression of TGF signaling as well as repair-related genes, suggests that these myofibroblast-like cells contribute to compensatory lung growth.

Strong van der Waals Adhesion of a Polymer Film on Rough Substrates.

We propose that chemically inert polymeric films can enhance van der Waals (vdW) forces in the same way as nanofabrication of biomimetic adhesive materials. For the vdW adhesion of an ethylene-chlorotrifluoroethylene (ECTFE) film on rough metal and dielectric substrates, we present a model that combines microscopic quantum-chemistry simulations of the polymer response functions and the equilibrium monomer-substrate distance with a macroscopic quantum-electrodynamics calculation of the Casimir force between the polymer film and the substrate. We predict adhesive forces up to 2.22 kN/mm2, where the effect is reduced by substrate roughness and for dielectric surfaces.

Relaxin activates peroxisome proliferator-activated receptor γ (PPARγ) through a pathway involving PPARγ coactivator 1α (PGC1α).

Relaxin activation of its receptor RXFP1 triggers multiple signaling pathways. Previously, we have shown that relaxin activates PPARγ transcriptional activity in a ligand-independent manner, but the mechanism for this effect was unknown. In this study, we examined the signaling pathways of downstream of RXFP1 leading to PPARγ activation. Using cells stably expressing RXFP1, we found that relaxin regulation of PPARγ activity requires accumulation of cAMP and subsequent activation of cAMP-dependent protein kinase (PKA). The activated PKA subsequently phosphorylated cAMP response element-binding protein (CREB) at Ser-133 to activate it directly, as well as indirectly through mitogen activated protein kinase p38 MAPK. Activated CREB was required for relaxin stimulation of PPARγ activity, while there was no evidence for a role of the nitric oxide or ERK MAPK pathways. Relaxin increased the mRNA and protein levels of the coactivator protein PGC1α, and this effect was dependent on PKA, and was completely abrogated by a dominant-negative form of CREB. This mechanism was confirmed in a hepatic stellate cell line stably that endogenously expresses RXFP1. Reduction of PGC1α levels using siRNA diminished the regulation of PPARγ by relaxin. These results suggest that relaxin activates the cAMP/PKA and p38 MAPK pathways to phosphorylate CREB, resulting in increased PGC1α levels. This provides a mechanism for the ligand-independent activation of PPARγ in response to relaxin.

Genome-wide expression profiling in the peripheral blood of patients with fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is a common pain disorder characterized by nociceptive dysregulation. The basic biology of FM is poorly understood. Herein we have used agnostic gene expression as a potential probe for informing its underlying biology and the development of a proof-of-concept diagnostic gene expression signature. METHODS: We analyzed RNA expression in 70 FM patients and 70 healthy controls. The isolated RNA was amplified and hybridized to Affymetrix® Human Gene 1.1 ST Peg arrays. The data was analyzed using Partek Genomics Suite version 6.6. RESULTS: Fibromyalgia patients exhibited a differential expression of 421 genes (p<0.001), several relevant to pathways for pain processing, such as glutamine/glutamate signaling and axonal development. There was also an upregulation of several inflammatory pathways and downregulation of pathways related to hypersensitivity and allergy. Using rigorous diagnostic modeling strategies, we show "locked" gene signatures discovered on Training and Test cohorts, that have a mean Area Under the Curve (AUC) of 0.81 on randomized, independent external data cohorts. Lastly, we identified a subset of 10 probesets that provided a diagnostic sensitivity for FM of 95% and a specificity of 96%. We also show that the signatures for FM were very specific to FM rather than common FM comorbidities. CONCLUSIONS: These findings provide new insights relevant to the pathogenesis of FM, and provide several testable hypotheses that warrant further exploration and also establish the foundation for a first blood-based molecular signature in FM that needs to be validated in larger cohorts of patients.

Remodeling of alveolar septa after murine pneumonectomy.

In most mammals, removing one lung (pneumonectomy) results in the compensatory growth of the remaining lung. In mice, stereological observations have demonstrated an increase in the number of mature alveoli; however, anatomic evidence of the early phases of alveolar growth has remained elusive. To identify changes in the lung microstructure associated with neoalveolarization, we used tissue histology, electron microscopy, and synchrotron imaging to examine the configuration of the alveolar duct after murine pneumonectomy. Systematic histological examination of the cardiac lobe demonstrated no change in the relative frequency of dihedral angle components (Ends, Bends, and Junctions) (P > 0.05), but a significant decrease in the length of a subset of septal ends ("E"). Septal retraction, observed in 20-30% of the alveolar ducts, was maximal on day 3 after pneumonectomy (P < 0.01) and returned to baseline levels within 3 wk. Consistent with septal retraction, the postpneumonectomy alveolar duct diameter ratio (Dout:Din) was significantly lower 3 days after pneumonectomy compared to all controls except for the detergent-treated lung (P < 0.001). To identify clumped capillaries predicted by septal retraction, vascular casting, analyzed by both scanning electron microscopy and synchrotron imaging, demonstrated matted capillaries that were most prominent 3 days after pneumonectomy. Numerical simulations suggested that septal retraction could reflect increased surface tension within the alveolar duct, resulting in a new equilibrium at a higher total energy and lower surface area. The spatial and temporal association of these microstructural changes with postpneumonectomy lung growth suggests that these changes represent an early phase of alveolar duct remodeling.

Robotic-Assisted Esophageal Surgery.

BACKGROUND: The adoption of minimally invasive approaches to the management of esophageal disease has been slow, except for the laparoscopic management of gastroesophageal reflux disease. However, the advent of new surgical technologies - in particular, robotic-assisted surgical systems - has revolutionized esophageal surgery. METHODS: The literature was systematically reviewed using the keywords "robotic," "esophageal surgery," "esophagectomy," "fundoplication," and "esophageal myotomy." The reference lists from these articles were then also analyzed. RESULTS: Forty-nine studies were included in our comprehensive review of robotic-assisted esophageal surgery, and they consisted of literature reviews, case reports, retrospective and prospective case series, and randomized controlled trials. CONCLUSIONS: Robotic-assisted esophageal surgery is a safe and effective way of treating esophageal disorders, including gastroesophageal reflux disease, achalasia, leiomyomas, and cancer. The use of robotic surgical systems has many benefits for managing disorders of the esophagus, but more studies, including randomized controlled trials, are necessary.

Role of 4-hydroxybutyrate-CoA synthetase in the CO2 fixation cycle in thermoacidophilic archaea.

Metallosphaera sedula is an extremely thermoacidophilic archaeon that grows heterotrophically on peptides and chemolithoautotrophically on hydrogen, sulfur, or reduced metals as energy sources. During autotrophic growth, carbon dioxide is incorporated into cellular carbon via the 3-hydroxypropionate/4-hydroxybutyrate cycle (3HP/4HB). To date, all of the steps in the pathway have been connected to enzymes encoded in specific genes, except for the one responsible for ligation of coenzyme A (CoA) to 4HB. Although several candidates for this step have been identified through bioinformatic analysis of the M. sedula genome, none have been shown to catalyze this biotransformation. In this report, transcriptomic analysis of cells grown under strict H(2)-CO(2) autotrophy was consistent with the involvement of Msed_0406 and Msed_0394. Recombinant versions of these enzymes catalyzed the ligation of CoA to 4HB, with similar affinities for 4HB (K(m) values of 1.9 and 1.5 mm for Msed_0406 and Msed_0394, respectively) but with different rates (1.69 and 0.22 µmol × min(-1) × mg(-1) for Msed_0406 and Msed_0394, respectively). Neither Msed_0406 nor Msed_0394 have close homologs in other Sulfolobales, although low sequence similarity is not unusual for acyl-adenylate-forming enzymes. The capacity of these two enzymes to use 4HB as a substrate may have arisen from simple modifications to acyl-adenylate-forming enzymes. For example, a single amino acid substitution (W424G) in the active site of the acetate/propionate synthetase (Msed_1353), an enzyme that is highly conserved among the Sulfolobales, changed its substrate specificity to include 4HB. The identification of the 4-HB CoA synthetase now completes the set of enzymes comprising the 3HP/4HB cycle.