Dihydropteroate synthase gene mutations in Pneumocystis and sulfa resistance

Pneumocystis pneumonia (PCP) remains a major cause of illness and death in HIV-infected persons. Sulfa drugs, trimethoprim-sulfamethoxazole (TMP-SMX) and dapsone are mainstays of PCP treatment and prophylaxis. While prophylaxis has reduced the incidence of PCP, its use has raised concerns about development of resistant organisms. The inability to culture human Pneumocystis, Pneumocystis jirovecii, in a standardized culture system prevents routine susceptibility testing and detection of drug resistance. In other microorganisms, sulfa drug resistance has resulted from specific point mutations in the dihydropteroate synthase (DHPS) gene. Similar mutations have been observed in P. jirovecii. Studies have consistently demonstrated a significant association between the use of sulfa drugs for PCP prophylaxis and DHPS gene mutations. Whether these mutations confer resistance to TMP-SMX or dapsone plus trimethoprim for PCP treatment remains unclear. We review studies of DHPS mutations in P. jirovecii and summarize the evidence for resistance to sulfamethoxazole and dapsone

ACR: Attention Collaboration-based Regressor for Arbitrary Two-Hand Reconstruction

Reconstructing two hands from monocular RGB images is challenging due to frequent occlusion and mutual confusion. Existing methods mainly learn an entangled representation to encode two interacting hands, which are incredibly fragile to impaired interaction, such as truncated hands, separate hands, or external occlusion. This paper presents ACR (Attention Collaboration-based Regressor), which makes the first attempt to reconstruct hands in arbitrary scenarios. To achieve this, ACR explicitly mitigates interdependencies between hands and between parts by leveraging center and part-based attention for feature extraction. However, reducing interdependence helps release the input constraint while weakening the mutual reasoning about reconstructing the interacting hands. Thus, based on center attention, ACR also learns cross-hand prior that handle the interacting hands better. We evaluate our method on various types of hand reconstruction datasets. Our method significantly outperforms the best interacting-hand approaches on the InterHand2.6M dataset while yielding comparable performance with the state-ofthe-art single-hand methods on the FreiHand dataset. More qualitative results on in-the-wild and hand-object interaction datasets and web images/videos further demonstrate the effectiveness of our approach for arbitrary hand reconstruction

Stamp transferred suspended graphene mechanical resonators for radio-frequency electrical readout

We present a simple micromanipulation technique to transfer suspended graphene flakes onto any substrate and to assemble them with small localized gates into mechanical resonators. The mechanical motion of the graphene is detected using an electrical, radio-frequency (RF) reflection readout scheme where the time-varying graphene capacitor reflects a RF carrier at f=5-6 GHz producing modulation sidebands at f +/- fm. A mechanical resonance frequency up to fm=178 MHz is demonstrated. We find both hardening/softening Duffing effects on different samples, and obtain a critical amplitude of ~40 pm for the onset of nonlinearity in graphene mechanical resonators. Measurements of the quality factor of the mechanical resonance as a function of DC bias voltage Vdc indicate that dissipation due to motion-induced displacement currents in graphene electrode is important at high frequencies and large Vdc

Aerosol Microdroplets Exhibit a Stable pH Gradient

Suspended aqueous aerosol droplets (\u3c50 μm) are microreactors for many important atmospheric reactions. In droplets and other aquatic environments, pH is arguably the key parameter dictating chemical and biological processes. The nature of the droplet air/ water interface has the potential to significantly alter droplet pH relative to bulk water. Historically, it has been challenging to measure the pH of individual droplets because of their inaccessibility to conventional pH probes. In this study, we scanned droplets containing 4-mercaptobenzoic acid–functionalized gold nanoparticle pH nanoprobes by 2D and 3D laser confocal Raman microscopy. Using surface-enhanced Raman scattering, we acquired the pH distribution inside approximately 20-μm-diameter phosphate-buffered aerosol droplets and found that the pH in the core of a droplet is higher than that of bulk solution by up to 3.6 pH units. This finding suggests the accumulation of protons at the air/water interface and is consistent with recent thermodynamic model results. The existence of this pH shift was corroborated by the observation that a catalytic reaction that occurs only under basic conditions (i.e., dimerization of 4-aminothiophenol to produce dimercaptoazobenzene) occurs within the high pH core of a droplet, but not in bulk solution. Our nanoparticle probe enables pH quantification through the cross-section of an aerosol droplet, revealing a spatial gradient that has implications for acid-base–catalyzed atmospheric chemistry

Results from the fly’s eye experiment

We report recently analyzed results on the energy spectrum, and composition of cosmic rays above 0.3 EeV. We observe a break in the spectrum at 3 EeV and a changing composition. The results can be explained by a simple two component model: galactic cosmic rays dominated by heavy primaries and an extragalactic component dominated by light primaries. The observed isotropic arrival direction distribution is consistent with the predictions of this model. A 320 EeV event was also recorded. © 1995 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87516/2/839_1.pd

Evidence for Changing of Cosmic Ray Composition between 10\u3csup\u3e17\u3c/sup\u3e and 10\u3csup\u3e18\u3c/sup\u3e eV from Multicomponent Measurements

The average mass composition of cosmic rays with primary energies between 1017 and 1018eV has been studied using a hybrid detector consisting of the High Resolution Fly\u27s Eye (HiRes) prototype and the MIA muon array. Measurements have been made of the change in the depth of shower maximum and the muon density as a function of energy. The results show that the composition is changing from a heavy to lighter mix as the energy increases. © 2000 The American Physical Society

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing.

Neurodegenerative disorders of ageing (NDAs) such as Alzheimer disease, Parkinson disease, frontotemporal dementia, Huntington disease and amyotrophic lateral sclerosis represent a major socio-economic challenge in view of their high prevalence yet poor treatment. They are often called 'proteinopathies' owing to the presence of misfolded and aggregated proteins that lose their physiological roles and acquire neurotoxic properties. One reason underlying the accumulation and spread of oligomeric forms of neurotoxic proteins is insufficient clearance by the autophagic-lysosomal network. Several other clearance pathways are also compromised in NDAs: chaperone-mediated autophagy, the ubiquitin-proteasome system, extracellular clearance by proteases and extrusion into the circulation via the blood-brain barrier and glymphatic system. This article focuses on emerging mechanisms for promoting the clearance of neurotoxic proteins, a strategy that may curtail the onset and slow the progression of NDAs