Experimental and Numerical Validation of Whispering Gallery Resonators as Optical Temperature Sensors.

This study experimentally and numerically validates the commonly employed technique of laser-induced heating of a material in optical temperature sensing studies. Furthermore, the Er3+-doped glass microspheres studied in this work can be employed as remote optical temperature sensors. Laser-induced self-heating is a useful technique commonly employed in optical temperature sensing research when two temperature-dependent parameters can be correlated, such as in fluorescence intensity ratio vs. interferometric calibration, allowing straightforward sensor characterization. A frequent assumption in such experiments is that thermal homogeneity within the sensor volume, that is, a sound hypothesis when dealing with small volume to surface area ratio devices such as microresonators, but has never been validated. In order to address this issue, we performed a series of experiments and simulations on a microsphere supporting whispering gallery mode resonances, laser heating it at ambient pressure and medium vacuum while tracking the resonance wavelength shift and comparing it to the shift rate observed in a thermal bath. The simulations were done starting only from the material properties of the bulk glass to simulate the physical phenomena of laser heating and resonance of the microsphere glass. Despite the simplicity of the model, both measurements and simulations are in good agreement with a highly homogeneous temperature within the resonator, thus validating the laser heating technique.

Depression and anxiety in patients with multiple sclerosis treated with interferon-beta or fingolimod: Role of indoleamine 2,3-dioxygenase and pro-inflammatory cytokines.

Depression/anxiety (D/A) occurs in up to 50% of multiple sclerosis (MS) patients. Proinflammatory cytokines induce classical symptoms of depression. Activation of the inflammatory response also triggers production of indoleamine 2,3-dioxygenase (IDO), which catabolizes tryptophan, the amino acid precursor of serotonin and melatonin. It has been suggested that IDO is the link between the immune and serotonergic systems. This study aimed to quantify the levels of IDO and pro-inflammatory and anti-inflammatory cytokines in patients with MS and depression, according to treatment with interferon-beta (IFN-ß) or fingolimod. The study inclusion criteria were age 18-60 years and a clinical and radiological diagnosis of MS. One hundred and thirty-two patients diagnosed by McDonald's criteria and followed up at Brasília District Hospital, Brazil, with relapsing-remitting MS were identified as potential study participants. Thirty-five of these patients were identified to be receiving treatment with fingolimod or IFN-ß and to have a diagnosis of D/A. IDO and pro-inflammatory and anti-inflammatory cytokine levels were compared between these 35 patients and 18 healthy controls. The level of IL-10 (an anti-inflammatory cytokine) was lower in both the fingolimod-treated (P â€‹< â€‹0.001) and IFN-ß-treated (P â€‹< â€‹0.01) patient groups than in the control group. IFN-ß-treated patients showed increased IDO expression and decreased inflammatory cytokine levels. In contrast, fingolimod-treated patients showed significantly decreased expression of IDO and significantly increased levels of proinflammatory cytokines produced by innate immune cells, including tumor necrosis factor-alpha and interleukin-6. The agents used to treat MS maintain symptoms of D/A in patients with MS via different mechanisms.

From Charcot's descriptions to the current understanding of neuropsychiatric symptoms in multiple sclerosis.

Neuropsychiatric disorders in multiple sclerosis have been known since the original clinicopathological description by Charcot in the late nineteenth century. Charcot, in the last decades of his life, became involved in the field of neuropsychiatry. This produced a battle between rival schools in the era that still echoes to this day. Charcot's intuition, including the line of thought of Babinski, one of his most famous disciples, was that there was a connection between mood disorders and many of the diseases of the nervous system. Medicine's concern with establishing a relationship between mood disorders and disease stems from the ancient and middle ages with references found in the Hippocratic doctrine. However, it was only in the second half of the nineteenth and early twentieth century, with Charcot's discoveries, that this discussion was established in a structured way, laying the foundations of neuropsychiatry.

From Charcot's descriptions to the current understanding of neuropsychiatric symptoms in multiple sclerosis / Das descrições de Charcot à compreensão atual dos sintomas neuropsiquiátricos na esclerose múltipla

ABSTRACT Neuropsychiatric disorders in multiple sclerosis have been known since the original clinicopathological description by Charcot in the late nineteenth century. Charcot, in the last decades of his life, became involved in the field of neuropsychiatry. This produced a battle between rival schools in the era that still echoes to this day. Charcot's intuition, including the line of thought of Babinski, one of his most famous disciples, was that there was a connection between mood disorders and many of the diseases of the nervous system. Medicine's concern with establishing a relationship between mood disorders and disease stems from the ancient and middle ages with references found in the Hippocratic doctrine. However, it was only in the second half of the nineteenth and early twentieth century, with Charcot's discoveries, that this discussion was established in a structured way, laying the foundations of neuropsychiatry.

RESUMO Os distúrbios neuropsiquiátricos na esclerose múltipla são conhecidos desde a descrição clínico-patológica original de Charcot no final do século XIX. Charcot nas últimas décadas de sua vida se envolveu no campo da neuropsiquiatria. Isso produziu uma batalha de escolas rivais na época que ainda ecoa até hoje. A intuição de Charcot, incluindo a linha de pensamento de Babinski, um de seus discípulos mais famosos, foi a teoria correta da conexão entre os transtornos do humor e muitas das doenças do sistema nervoso. A preocupação da Medicina em estabelecer uma relação entre transtornos do humor e doenças vem das idades antiga e média, com referências encontradas na doutrina hipocrática. No entanto, foi apenas na segunda metade do século XIX e início do século XX que, com as descobertas de Charcot essa discussão foi realizada de maneira estruturada, estabelecendo os fundamentos da neuropsiquiatria.

Design and Fabrication of an Optical Fiber Made of Water.

In this report, an optical fiber of which the core is made solely of water, while the cladding is air, is designed and manufactured. In contrast with solid-cladding devices, capillary oscillations are not restricted, allowing the fiber walls to move and vibrate. The fiber is constructed by a high direct current (DC) voltage of several thousand volts (kV) between two water reservoirs that creates a floating water thread, known as a water bridge. Through the choice of micropipettes, it is possible to control the maximal diameter and length of the fiber. Optical fiber couplers, at both sides of the bridge, activate it as an optical waveguide, allowing researchers to monitor the water fiber capillary body waves through transmission modulation and, therefore, deducing changes in surface tension. Co-confining two important wave types, capillary and electromagnetic, opens a new path of research in the interactions between light and liquid-wall devices. Water-walled microdevices are a million times softer than their solid counterparts, accordingly improving the response to minute forces.

Cavity optofluidics: a µdroplet's whispering-gallery mode makes a µvortex.

We experimentally demonstrate light-flow interaction, in which the angular momentum of circulating light excites micro-vortices. In contrast with the solid-phase of matter, where one has to overcome static friction in order to start motion, liquids have no "static drag." Relevant to almost all optofluidic micro-systems hence, µWatt optical power is sufficient to start flows, even in liquids 50 times more viscous than water. We map the flows to be three-dimensional (3D) by using a technique based on fluorescent nano-emitters; to reveal, as expected, flow speeds proportional to power divided by viscosity.

Light and Capillary Waves Propagation in Water Fibers.

The confinement of light and sound, while they are traveling in fibers, enables a variety of light-matter interactions. Therefore, it is natural to ask if fibers can also host capillary waves. Capillary waves are similar to those we see when throwing a stone into a puddle. Such capillary waves are prohibited in microfluidic devices where the liquid is bounded by solid walls. In contrast, we have fabricated fibers, which are made entirely from water and are suspended in air. The water fiber can therefore move, e.g. in a resonant mode that reassembles the motion of a guitar string. In our experiment, light guided through the water fiber allows optical interrogation of is capillary oscillations. Co-confining two important oscillations in nature: capillary and electromagnetic, might allow a new type of devices called Micro-Electro-Capillary-Systems [MECS]. The softness of MECS is a million times higher when compared to what the current solid-based technology permits, which accordingly improves MECS response to minute forces such as small changes in acceleration. Additionally, MECS might allow new ways to optically interrogate viscosity and surface tension, as well as their changes caused by introducing an analyte into the system.

Combination GITR targeting/PD-1 blockade with vaccination drives robust antigen-specific antitumor immunity.

Tumor progression is facilitated immunologically by mechanisms that include low antigen expression, an absence of coimmunostimulatory signals, and the presence of regulatory T cells (Tregs), all of which act to suppress and restrict effector T cells in the tumor. It may be possible to overcome these conditions by a combination of modulatory immunotherapy agents and tumor-antigen targeting to activate and drive effective antitumor T cell responses. Here, we demonstrated that co-administration of aGITR and aPD-1 monoclonal antibodies (mAb) in combination with a peptide vaccine (Vax) in mice bearing established tumors significantly delayed tumor growth and induced complete regression in 50% of the mice. This response was associated with increased expansion and functionality of potent Ag-specific polyfunctional CD8+ T cells, reduced Tregs, and the generation of memory T cells. Tumor regression correlated with the expansion of tumor-infiltrating antigen-specific CD8+ effector memory T cells, as depletion of this cell population significantly reduced the effectiveness of the triple combination Vax/aGITR/aPD-1 therapy. These findings support the concept that dual aGITR/aPD-1 combination with cancer vaccines may be a novel strategy against poorly immunogenic tumors.

Liquid whispering-gallery-mode resonator as a humidity sensor.

We experimentally demonstrate the high sensitivity of a novel liquid state, whispering-gallery-mode optical resonator to humidity changes. The optical resonator used consists of a droplet made of glycerol, a transparent liquid that enables high optical quality factor, doped with fluorescent material. As glycerol is highly hygroscopic, the refractive index and radius of the droplet change with ambient humidity. This produces a shift on the whispering gallery mode's wavelengths, which modulates the emission of the fluorescent material. This device shows an unpreceded sensitivity of 10-3 per relative humidity percent.

Targeting of CD122 enhances antitumor immunity by altering the tumor immune environment.

Mounting evidence demonstrates that CD8+CD122+ T cells have suppressive properties with the capacity to inhibit T cell responses. Therefore, these cells are rational targets for cancer immunotherapy. Here, we demonstrate that CD122 monoclonal antibody (mAb; aCD122) therapy significantly suppressed tumor growth and improved long-term survival in tumor-bearing mice. This therapeutic effect correlated with enhanced polyfunctional, cytolytic intratumoral CD8+ T cells and a decrease in granulocytic myeloid-derived suppressor cells (G-MDSCs). In addition, aCD122 treatment synergized with a vaccine to augment vaccine-induced antigen (Ag)-specific CD8+ T cell responses, reject established tumors and generate memory T cells. Furthermore, aCD122 mAb synergized with an anti-GITR (aGITR) mAb to confer significant control of tumor growth. These results suggest CD122 might be a promising target for cancer immunotherapy, either as a single agent or in combination with other forms of immunotherapy.

Level-crossing and modal structure in microdroplet resonators.

We fabricate a liquid-core liquid-clad microcavity that is coupled to a standard tapered fiber, and then experimentally map the whispering-gallery modes of this droplet resonator. The shape of our resonator is similar to a thin prolate spheroid, which makes space for many high-order transverse modes, suggesting that some of them will share the same resonance frequency. Indeed, we experimentally observe that more than half of the droplet's modes have a sibling having the same frequency (to within linewidth) and therefore exhibiting a standing interference-pattern.

Regular oscillations and random motion of glass microspheres levitated by a single optical beam in air.

We experimentally report on optical binding of many glass particles in air that levitate in a single optical beam. A diversity of particle sizes and shapes interact at long range in a single Gaussian beam. Our system dynamics span from oscillatory to random and dimensionality ranges from 1 to 3D. The low loss for the center of mass motion of the beads could allow this system to serve as a standard many body testbed, similar to what is done today with atoms, but at the mesoscopic scale.

Regular oscillations and random motion of glass microspheres levitated by a single optical beam in air: publisher's note.

This publisher's note amends a recent publication [Opt. Express24(3), 2850-2857 (2016)] to include Acknowledgments.

Water-walled microfluidics for high-optical finesse cavities.

In submerged microcavities there is a tradeoff between resonant enhancement for spatial water and light overlap. Why not transform the continuously resonating optical mode to be fully contained in a water microdroplet per se? Here we demonstrate a sustainable 30-µm-pure water device, bounded almost completely by free surfaces, enabling >1,000,000 re-circulations of light. The droplets survive for >16 h using a technique that is based on a nano-water bridge from the droplet to a distant reservoir to compensate for evaporation. More than enabling a nearly-perfect optical overlap with water, atomic-level surface smoothness that minimizes scattering loss, and ∼99% coupling efficiency from a standard fibre. Surface tension in our droplet is 8,000 times stronger than gravity, suggesting a new class of devices with water-made walls, for new fields of study including opto-capillaries.

Adele Bloch-Bauer (1881-1925): Possible diagnoses for Gustav Klimt's Lady in Gold.

One of the most famous works by the Austrian symbolist painter Gustav Klimt and one of the most widely reproduced works of art worldwide, Adele Bloch-Bauer I which portrays the beautiful wife of Austrian magnate Ferdinand Bloch-Bauer. Adele was the only woman painted by Klimt on more than one occasion. Apart from the beauty and value of the painting, the daring sea of gold that surrounds Adele and the gentle intimacy with which her fragile figure is portrayed have shrouded the history of this painting in mystery. Beyond speculation as to a special bond between artist and model, observation of the painting with a keener, clinical gaze yields evidence of potential illness in the model: facial erythema which, if not produced artificially by makeup, could represent a malar rash; pallor or cyanosis of the hands; and her draped fingers, which seemingly attempt to hide a deformity. This paper seeks to provide a biographical review both of the painter, Gustav Klimt, and of the subject, Adele Bloch-Bauer; to analyse Klimt's two portrayals of her in a search for evidence of a potential intimate relationship between artist and muse and, finally, to compile clinical evidence of possible diagnoses for the Lady in Gold.

Tweezers controlled resonator.

We experimentally demonstrate trapping a microdroplet by using an optical tweezer and then activating it as a microresonator by bringing it close to a tapered-fiber coupler. Our tweezers facilitated the tuning of the coupling from the under-coupled to the critically-coupled regime while the quality-factor [Q] is 12 million and the resonator's size is at the 80 µm scale.

Optical binding in white light.

We experimentally demonstrate, for the first time, binding of aerosols of various sizes and shapes in white light. The optomechancial interaction between particles is long range and is in the underdamped regime. Incoherency allows mitigation of interference fringes to enable monotonically changing the distance between particles from 60 µm to contact, constituting a parametrically controlled testbed for transition studies at new scales.

Exercise and fatigue in rheumatoid arthritis.

Fatigue, the enduring sensation of weakness, lack of energy, tiredness or exhaustion, is described by 40%-80% of patients with rheumatoid arthritis as their most disabling symptom with wide-ranging consequences for quality of life. Little attention has been paid to its multidimensional nature or to its reliability as a measure to evaluate progression of the disease. Low impact aerobic exercise affects the level of fatigue, and this same level of fatigue influences the exercise itself. We searched Medline, Cochrane Collaboration Register of Controlled Trials (CCRCT), Lilacs, PubMed and Scopus databases for randomized controlled trials (with appropriate description of methods, materials and results) on the assessment of fatigue and exercise. Review articles, case reports, letters to the editor and editorials were excluded. Of 121 references initially identified, 4 randomized controlled trials met the inclusion criteria. Two studies used the MAF scale (Multidimensional Assessment of Fatigue), one used the MAC (Mental Adjustment to Cancer) fatigue scale, and all trials used POMS (Profile of Mood States) to assess fatigue. All four trials conducted a 12 week program of two to three times/ week and different periods of follow-up. Two studies used low impact aerobic exercise, one used dance-based exercise, and another study followed a home cardiopulmonary conditioning program using a stationary bicycle. While fatigue appears to be a reliable outcome measure in the clinical management of RA, especially when related to exercise prescription, further research is needed to evaluate the correlation between exercise, fatigue and quality of life, using fatigue scales validated to explore the different components of fatigue and its wide-ranging consequences.