Multiply Folded Graphene

The folding of paper, hide, and woven fabric has been used for millennia to achieve enhanced articulation, curvature, and visual appeal for intrinsically flat, two-dimensional materials. For graphene, an ideal two-dimensional material, folding may transform it to complex shapes with new and distinct properties. Here, we present experimental results that folded structures in graphene, termed grafold, exist, and their formations can be controlled by introducing anisotropic surface curvature during graphene synthesis or transfer processes. Using pseudopotential-density functional theory calculations, we also show that double folding modifies the electronic band structure of graphene. Furthermore, we demonstrate the intercalation of C60 into the grafolds. Intercalation or functionalization of the chemically reactive folds further expands grafold's mechanical, chemical, optical, and electronic diversity.Comment: 29 pages, 10 figures (accepted in Phys. Rev. B

Aduhelm, a novel anti-amyloid monoclonal antibody, for the treatment of Alzheimer\u27s Disease: A comprehensive review.

Alzheimer\u27s disease (AD) is the most common form of dementia affecting millions of individuals, including family members who often take on the role of caregivers. This debilitating disease reportedly consumes 8% of the total United States healthcare expenditure, with medical and nursing outlays accounting for an estimated $290 billion. Cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists have historically been the most widely used pharmacologic therapies for patients with AD; however, these drugs are not curative. The present investigation describes the epidemiology, pathophysiology, risk factors, presentation, and current treatment of AD followed by the role of the novel monoclonal antibody, Adulhelm, in the treatment of AD. Currently, Adulhelm is the only Food and Drug Administration (FDA) approved drug that acts to slow the progression of this disease. Adulhelm is an anti-amyloid drug that functions by selectively binding amyloid aggregates in both the oligomeric and fibrillar states. Studies show Adulhelm may help to restore neurological function in patients with AD by reducing beta-amyloid plaques and reestablishing neuronal calcium permeability. At present, there is concern the magnitude of this drug\u27s benefit may only be statistically significant, although not clinically significant. Despite skepticism, Adulhelm has proven to significantly decrease amyloid in all cortical brain regions examined. With such high stakes and potential, further research into Adulhelm\u27s clinical efficacy is warranted in the treatment of AD

Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms

<p>Abstract</p> <p>Background</p> <p>Suicidal behaviour is known to aggregate in families. Patients with psychiatric disorders are at higher risk for suicide attempts (SA), however protective and risk genetic variants for suicide appear to be independent of underlying psychiatric disorders. Here we investigate genetic variants in genes important for neurobiological pathways linked to suicidal behaviour and/or associated endophenotypes, for association with SA among patients with co-existing psychiatric illness. Selected gene-gene and gene-environment interactions were also tested.</p> <p>Methods</p> <p>DNA was obtained from bloods of 159 patients (76 suicide attempters and 83 non-attempters), who were profiled for DSM-IV Axis I psychiatric diagnosis. Twenty-eight single nucleotide polymorphisms (SNPs) from 18 candidate genes (<it>COMT, 5-HT2A, 5-HT1A, 5-HTR1B, TPH1, MAO-A, TPH2, DBH, CNR1, BDNF, ABCG1, GABRA5, GABRG2, GABRB2, SLC1A2, SLC1A3, NTRK2, CRHR1</it>) were genotyped. Genotyping was performed by KBioscience. Tests of association between genetic variants and SA were conducted using Chi squared and Armitage Trend tests. Binary logistical regression analyses were performed to evaluate the contribution of individual genetic variants to the prediction of SA, and to examine SNPs for potential gene-gene and gene-environment interactions.</p> <p>Results</p> <p>Our analysis identified 4 SNPs (rs4755404, rs2269272, rs6296 and rs1659400), which showed evidence of association with SA compared to a non-attempter control group. We provide evidence of a 3-locus gene-gene interaction, and a putative gene-environment interaction, whereby genetic variation at the <it>NTRK2 </it>locus may moderate the risk associated with history of childhood abuse.</p> <p>Conclusion</p> <p>Preliminary findings suggest that allelic variability in <it>SLC1A2/3, 5-HTR1B </it>and <it>NTRK2 </it>may be relevant to the underlying diathesis for suicidal acts.</p

Simultaneous quantification of 12 different nucleotides and nucleosides released from renal epithelium and in human urine samples using ion-pair reversed-phase HPLC

Nucleotides and nucleosides are not only involved in cellular metabolism but also act extracellularly via P1 and P2 receptors, to elicit a wide variety of physiological and pathophysiological responses through paracrine and autocrine signalling pathways. For the first time, we have used an ion-pair reversed-phase high-performance liquid chromatography ultraviolet (UV)-coupled method to rapidly and simultaneously quantify 12 different nucleotides and nucleosides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, adenosine, uridine triphosphate, uridine diphosphate, uridine monophosphate, uridine, guanosine triphosphate, guanosine diphosphate, guanosine monophosphate, guanosine): (1) released from a mouse renal cell line (M1 cortical collecting duct) and (2) in human biological samples (i.e., urine). To facilitate analysis of urine samples, a solid-phase extraction step was incorporated (overall recovery rate ? 98 %). All samples were analyzed following injection (100 ?l) into a Synergi Polar-RP 80 Å (250 × 4.6 mm) reversed-phase column with a particle size of 10 ?m, protected with a guard column. A gradient elution profile was run with a mobile phase (phosphate buffer plus ion-pairing agent tetrabutylammonium hydrogen sulfate; pH 6) in 2-30 % acetonitrile (v/v) for 35 min (including equilibration time) at 1 ml min(-1) flow rate. Eluted compounds were detected by UV absorbance at 254 nm and quantified using standard curves for nucleotide and nucleoside mixtures of known concentration. Following validation (specificity, linearity, limits of detection and quantitation, system precision, accuracy, and intermediate precision parameters), this protocol was successfully and reproducibly used to quantify picomolar to nanomolar concentrations of nucleosides and nucleotides in isotonic and hypotonic cell buffers that transiently bathed M1 cells, and urine samples from normal subjects and overactive bladder patients

Photonic Doppler velocimetry probe used to measure grain boundaries of dynamic shocked materials

Author Institution: Mission Support and Test Services, LLC; Los Alamos National LaboratorySlides presented at the 2018 Photonic Doppler Velocimetry (PDV) Users Workshop, Drury Plaza Hotel, Santa Fe, New Mexico, May 16-18, 2018

Single- and Multiple-Dose Pharmacokinetics of Darunavir Plus Ritonavir and Etravirine in Semen and Rectal Tissue of HIV-Negative Men

Antiretroviral therapy (ART) has become a central component of combination HIV prevention efforts. Defining the individual exposure of commercially available ART in genital secretions and vulnerable mucosal tissues is paramount to designing future prevention interventions

Aduhelm, a novel anti-amyloid monoclonal antibody, for the treatment of Alzheimer’s Disease: A comprehensive review

Alzheimer's disease (AD) is the most common form of dementia affecting millions of individuals, including family members who often take on the role of caregivers. This debilitating disease reportedly consumes 8% of the total United States healthcare expenditure, with medical and nursing outlays accounting for an estimated \$290 billion. Cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists have historically been the most widely used pharmacologic therapies for patients with AD; however, these drugs are not curative. The present investigation describes the epidemiology, pathophysiology, risk factors, presentation, and current treatment of AD followed by the role of the novel monoclonal antibody, Adulhelm, in the treatment of AD. Currently, Adulhelm is the only Food and Drug Administration (FDA) approved drug that acts to slow the progression of this disease. Adulhelm is an anti-amyloid drug that functions by selectively binding amyloid aggregates in both the oligomeric and fibrillar states. Studies show Adulhelm may help to restore neurological function in patients with AD by reducing beta-amyloid plaques and reestablishing neuronal calcium permeability. At present, there is concern the magnitude of this drug's benefit may only be statistically significant, although not clinically significant. Despite skepticism, Adulhelm has proven to significantly decrease amyloid in all cortical brain regions examined. With such high stakes and potential, further research into Adulhelm's clinical efficacy is warranted in the treatment of AD

Design, construction, alignment, and calibration of a compact velocimetry experiment

A velocimetry experiment has been designed to measure shock properties for small, cylindrical, metal targets (8 mm diameter × 2 mm thick). A target is accelerated by high explosives, caught, then retrieved for later inspection. The target is expected to move at a velocity of 0.1 to 3 km/sec. The complete experiment canister is ~105 mm in diameter and 380 mm long. Optical velocimetry diagnostics include the Velocity Interferometer System for Any Reflector (VISAR) and photon Doppler velocimetry (PDV). The packaging of the velocity diagnostics is not allowed to interfere with the foam catchment or an X-ray imaging diagnostic. Using commercial lenses, a single optical relay collects Doppler-shifted light for both VISAR and PDV. The use of fiber optics allows measurement of point velocities on the target surface for accelerations lasting for 3 mm of travel. Operating at 532 nm, the VISAR has separate illumination fibers requiring alignment. The PDV diagnostic operates at 1550 nm but is aligned and calibrated at 670 nm. VISAR and PDV diagnostics are complimentary measurements that image spots in close proximity on the target surface. Because the optical relay uses commercial glass, optical fibers’ axial positions are offset to compensate for chromatic aberrations. The optomechanical design requires careful attention to fiber management, mechanical assembly and disassembly, foam catchment design, and X-ray diagnostic field of view.Calibration and alignment data are archived at each assembly sequence stage. The photon budgets for the VISAR and PDV diagnostics are separately estimated

Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria

Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency, and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (?10 wbc/?l) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure is a mediator of bladder sensation. Here, using bladder biopsy samples, we have investigated urothelial ATP signaling in OAB patients with microscopic pyuria. Basal, but not stretch-evoked, release of ATP was significantly greater from the urothelium of OAB patients with pyuria than from non-OAB patients or OAB patients without pyuria (<10 wbc/?l). Basal ATP release from the urothelium of OAB patients with pyuria was inhibited by the P2 receptor antagonist suramin and abolished by the hemichannel blocker carbenoxolone, which differed from stretch-activated ATP release. Altered P2 receptor expression was evident in the urothelium from pyuric OAB patients. Furthermore, intracellular bacteria were visualized in shed urothelial cells from ?80% of OAB patients with pyuria. These data suggest that increased ATP release from the urothelium, involving bacterial colonization, may play a role in the heightened symptoms associated with pyuric OAB patients

Integrated Carbon Budget Models for the Everglades Terrestrial-Coastal-Oceanic Gradient: Current Status and Needs for Inter-Site Comparisons

Recent studies suggest that coastal ecosystems can bury significantly more C than tropical forests, indicating that continued coastal development and exposure to sea level rise and storms will have global biogeochemical consequences. The Florida Coastal Everglades Long Term Ecological Research (FCE LTER) site provides an excellent subtropical system for examining carbon (C) balance because of its exposure to historical changes in freshwater distribution and sea level rise and its history of significant long-term carbon-cycling studies. FCE LTER scientists used net ecosystem C balance and net ecosystem exchange data to estimate C budgets for riverine mangrove, freshwater marsh, and seagrass meadows, providing insights into the magnitude of C accumulation and lateral aquatic C transport. Rates of net C production in the riverine mangrove forest exceeded those reported for many tropical systems, including terrestrial forests, but there are considerable uncertainties around those estimates due to the high potential for gain and loss of C through aquatic fluxes. C production was approximately balanced between gain and loss in Everglades marshes; however, the contribution of periphyton increases uncertainty in these estimates. Moreover, while the approaches used for these initial estimates were informative, a resolved approach for addressing areas of uncertainty is critically needed for coastal wetland ecosystems. Once resolved, these C balance estimates, in conjunction with an understanding of drivers and key ecosystem feedbacks, can inform cross-system studies of ecosystem response to long-term changes in climate, hydrologic management, and other land use along coastlines