Insulin-like growth factors and related proteins in plasma and cerebrospinal fluids of HIV-positive individuals.

BackgroundClinically significant dysregulation of the insulin-like growth factor (IGF) family proteins occurs in HIV-infected individuals, but the details including whether the deficiencies in IGFs contribute to CNS dysfunction are unknown.MethodsWe measured the levels of IGF1, IGF2, IGFBP1, IGFBP2, and IGF2 receptor (IGF2R) in matching plasma and cerebrospinal fluid (CSF) samples of 107 HIV+ individuals from CNS HIV Antiretroviral Therapy Effects Research (CHARTER) and analyzed their associations with demographic and disease characteristics, as well as levels of several soluble inflammatory mediators (TNFα, IL-6, IL-10, IL-17, IP-10, MCP-1, and progranulin). We also determined whether IGF1 or IGF2 deficiency is associated with HIV-associated neurocognitive disorder (HAND) and whether the levels of soluble IGF2R (an IGF scavenging receptor, which we also have found to be a cofactor for HIV infection in vitro) correlate with HIV viral load (VL).ResultsThere was a positive correlation between the levels of IGF-binding proteins (IGFBPs) and those of inflammatory mediators: between plasma IGFBP1 and IL-17 (β coefficient 0.28, P = 0.009), plasma IGFBP2 and IL-6 (β coefficient 0.209, P = 0.021), CSF IGFBP1 and TNFα (β coefficient 0.394, P < 0.001), and CSF IGFBP2 and TNF-α (β coefficient 0.14, P < 0.001). As IGFBPs limit IGF availability, these results suggest that inflammation is a significant factor that modulates IGF protein expression/availability in the setting of HIV infection. However, there was no significant association between HAND and the reduced levels of plasma IGF1, IGF2, or CSF IGF1, suggesting a limited power of our study. Interestingly, plasma IGF1 was significantly reduced in subjects on non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) compared to protease inhibitor-based therapy (174.1 ± 59.8 vs. 202.8 ± 47.3 ng/ml, P = 0.008), suggesting a scenario in which ART regimen-related toxicity can contribute to HAND. Plasma IGF2R levels were positively correlated with plasma VL (β coefficient 0.37, P = 0.021) and inversely correlated with current CD4+ T cell counts (β coefficient -0.04, P = 0.021), supporting our previous findings in vitro.ConclusionsTogether, these results strongly implicate (1) an inverse relationship between inflammation and IGF growth factor availability and the contribution of IGF deficiencies to HAND and (2) the role of IGF2R in HIV infection and as a surrogate biomarker for HIV VL

Parametric Amplification and Back-Action Noise Squeezing by a Qubit-Coupled Nanoresonator

We demonstrate the parametric amplification and noise squeezing of nanomechanical motion utilizing dispersive coupling to a Cooper-pair box qubit. By modulating the qubit bias and resulting mechanical resonance shift, we achieve gain of 30 dB and noise squeezing of 4 dB. This qubit-mediated effect is 3000 times more effective than that resulting from the weak nonlinearity of capacitance to a nearby electrode. This technique may be used to prepare nanomechanical squeezed states

Morphology and structure of the 1999 lava flows at Mount Cameroon Volcano (West Africa) and their bearings on the emplacement dynamics of volume-limited flows

The morphology and structure of the 1999 lava flows at Mount Cameroon volcano are documented and discussed in relation to local and source dynamics. Structures are analysed qualitatively and more detailed arguments are developed on the processes of levee formation and systematic links between flow dynamics and levee-channel interface geometry. The flows have clear channels bordered by four main types of levees: initial, accretionary, rubble and overflow levees. Thermally immature pahoehoe lava units with overflow drapes define the proximal zone, whereas rubble and accretionary levees are common in the distal region bordering thermally mature aa clinker or blocky aa flow channels. Pressure ridges, squeeze-ups and pahoehoe ropes are the prevalent compressive structures. Standlines displayed on clinkery breccias are interpreted to represent levee-channel interactions in response to changing flow levels. These data complement previous knowledge on lava flow morphology, thus far dominated by Etnean and Hawaiian examples

Observation and interpretation of motional sideband asymmetry in a quantum electro-mechanical device

Quantum electro-mechanical systems offer a unique opportunity to probe quantum noise properties in macroscopic devices, properties which ultimately stem from the Heisenberg Uncertainty Principle. A simple example of this is expected to occur in a microwave parametric transducer, where mechanical motion generates motional sidebands corresponding to the up and down frequency-conversion of microwave photons. Due to quantum vacuum noise, the rates of these processes are expected to be unequal. We measure this fundamental imbalance in a microwave transducer coupled to a radio-frequency mechanical mode, cooled near the ground state of motion. We also discuss the subtle origin of this imbalance: depending on the measurement scheme, the imbalance is most naturally attributed to the quantum fluctuations of either the mechanical mode or of the electromagnetic field

Correlation between fracture surface morphology and toughness in Zr-based bulk metallic glasses

Fracture surfaces of Zr-based bulk metallic glasses of various compositions tested in the as-cast and annealed conditions were analyzed using scanning electron microscopy. The tougher samples have shown highly jagged patterns at the beginning stage of crack propagation, and the length and roughness of this jagged pattern correlate well with the measured fracture toughness values. These jagged patterns, the main source of energy dissipation in the sample, are attributed to the formation of shear bands inside the sample. This observation provides strong evidence of significant “plastic zone” screening at the crack tip

Complete response of skull base inverted papilloma to chemotherapy: Case report.

BackgroundInverted papilloma (IP) is the most common benign sinonasal neoplasm. Endoscopic techniques, improved understanding of pathophysiology, and novel surgical approaches have allowed rhinologists to treat IPs more effectively, with surgery being the mainstay of therapy. Frontal sinus IP poses a challenge for surgical therapy due to complex anatomy and potentially difficult surgical access.ObjectivesWe reported a unique case of a massive frontal sinus IP that presented with intracranial and orbital extension, with near resolution after chemotherapy.MethodsA retrospective case review of a patient with a frontal sinus IP treated at a tertiary academic medical center.ResultsA 75-year-old male patient presented with nasal obstruction, purulent nasal discharge, and a growing left supraorbital mass. Endoscopy demonstrated a mass that filled both frontal and ethmoid sinuses, with orbital invasion. There also was substantial erosion of the posterior table, which measured 1.73 × 1.40 cm. A biopsy specimen demonstrated IP with carcinoma in situ. The patient was deemed unresectable on initial evaluation and, subsequently, underwent chemotherapy (carboplatin and paclitaxel). The tumor had a dramatic response to chemotherapy, and the patient elected for definitive surgery to remove any residual disease. During surgery, only a small focus of IP was found along the superior wall of the frontal sinus. No tumor was found elsewhere, including at the site of skull base erosion. The final pathology was IP without carcinoma in situ or dysplasia.ConclusionThis was the first reported case of chemotherapeutic "debulking" of IP, which facilitated surgical resection, despite substantial intracranial and orbital involvement. Although nearly all IPs can be treated surgically, rare cases, such as unresectable tumors, may benefit from systemic chemotherapy

Quantum squeezing of motion in a mechanical resonator

As a result of the quantum, wave-like nature of the physical world, a harmonic oscillator can never be completely at rest. Even in the quantum ground state, its position will always have fluctuations, called the zero-point motion. Although the zero-point fluctuations are unavoidable, they can be manipulated. In this work, using microwave frequency radiation pressure, we both prepare a micron-scale mechanical system in a state near the quantum ground state and then manipulate its thermal fluctuations to produce a stationary, quadrature-squeezed state. We deduce that the variance of one motional quadrature is 0.80 times the zero-point level, or 1 dB of sub-zero-point squeezing. This work is relevant to the quantum engineering of states of matter at large length scales, the study of decoherence of large quantum systems, and for the realization of ultra-sensitive sensing of force and motion

A Comparative Analysis of the Bootstrap versus Traditional Statistical Procedures Applied to Digital Analysis Based on Benford\u27s Law

This study develops a bootstrap procedure applied to digital analysis based on Benford’s Law. It shows that the developed procedure provides accurate diagnoses of fraud as opposed to traditional statistical procedures. The traditional procedures such as the chi-square goodness-of-fit test exhibit the problem of excessive power as the volume of transactions becomes large. This problem may lead auditors to expend unnecessary fraud investigation costs. In contrast, applications of the proposed bootstrap procedure to reported annual earnings of S&P 1500 companies, Federal Election Commission data, and extremely fraudulent data demonstrate the robustness of the proposed procedure over different periods of time and across small or large financial data sets