Validation of a novel HPLC-based serum thymidine kinase assay for breast cancer detection

Thymidine kinase (TK) has been validated as a serum-derived, tumour-associated marker for a number of malignancies and estimation of TK activity in serum has proved useful for clinical diagnosis and monitoring of therapy. However, the use of this biomarker in the clinical practice is constrained by the lack of an automatable easy-to-perform assay. We have developed and validated a novel HPLC-based assay for measuring TK activity in biological samples. This assay is cheaper, easy to perform and does not depend on the use of expensive antibodies or isotopes. In addition, it has comparable sensitivity with the radioenzymatic assay used in the clinical practice. The assay has been evaluated with samples from breast cancer patients.<br/

Anti-lensing: the bright side of voids

More than half of the volume of our Universe is occupied by cosmic voids. The lensing magni ca- tion e ect from those under-dense regions is generally thought to give a small dimming contribution: objects on the far side of a void are supposed to be observed as slightly smaller than if the void were not there, which together with conservation of surface brightness implies net reduction in photons received. This is predicted by the usual weak lensing integral of the density contrast along the line of sight. We show that this standard e ect is swamped at low redshifts by a relativistic Doppler term that is typically neglected. Contrary to the usual expectation, objects on the far side of a void are brighter than they would be otherwise. Thus the local dynamics of matter in and near the void is crucial and is only captured by the full relativistic lensing convergence. There are also signi cant nonlinear corrections to the relativistic linear theory, which we show actually under-predicts the e ect. We use exact solutions to estimate that these can be more than 20% for deep voids. This remains an important source of systematic errors for weak lensing density reconstruction in galaxy surveys and for supernovae observations, and may be the cause of the reported extra scatter of eld supernovae located on the edge of voids compared to those in clusters.Web of Scienc

Testing a MultiTEP-based combination vaccine to reduce Aβ and tau pathology in Tau22/5xFAD bigenic mice.

BackgroundAlzheimer disease (AD) is characterized by the accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau, which together lead to neurodegeneration and cognitive decline. Current therapeutic approaches have primarily aimed to reduce pathological aggregates of either Aβ or tau, yet phase 3 clinical trials of these approaches have thus far failed to delay disease progression in humans. Strong preclinical evidence indicates that these two abnormally aggregated proteins interact synergistically to drive downstream neurodegeneration. Therefore, combinatorial therapies that concurrently target both Aβ and tau might be needed for effective disease modification.MethodsA combinatorial vaccination approach was designed to concurrently target both Aβ and tau pathologies. Tau22/5xFAD (T5x) bigenic mice that develop both pathological Aβ and tau aggregates were injected intramuscularly with a mixture of two MultiTEP epitope vaccines: AV-1959R and AV-1980R, targeting Aβ and tau, respectively, and formulated in AdvaxCpG, a potent polysaccharide adjuvant. Antibody responses of vaccinated animals were measured by ELISA, and neuropathological changes were determined in brain homogenates of vaccinated and control mice using ELISA and Meso Scale Discovery (MSD) multiplex assays.ResultsT5x mice immunized with a mixture of Aβ- and tau-targeting vaccines generated high Aβ- and tau-specific antibody titers that recognized senile plaques and neurofibrillary tangles/neuropil threads in human AD brain sections. Production of these antibodies in turn led to significant reductions in the levels of soluble and insoluble total tau, and hyperphosphorylated tau as well as insoluble Aβ42, within the brains of bigenic T5x mice.ConclusionsAV-1959R and AV-1980R formulated with AdvaxCpG adjuvant are immunogenic and therapeutically potent vaccines that in combination can effectively reduce both of the hallmark pathologies of AD in bigenic mice. Taken together, these findings warrant further development of this vaccine technology for ultimate testing in human AD

Teleportation Systems Toward a Quantum Internet

Quantum teleportation is essential for many quantum information technologies, including long-distance quantum networks. Using fiber-coupled devices, including state-of-the-art low-noise superconducting nanowire single-photon detectors and off-the-shelf optics, we achieve conditional quantum teleportation of time-bin qubits at the telecommunication wavelength of 1536.5 nm. We measure teleportation fidelities of ≥90% that are consistent with an analytical model of our system, which includes realistic imperfections. To demonstrate the compatibility of our setup with deployed quantum networks, we teleport qubits over 22 km of single-mode fiber while transmitting qubits over an additional 22 km of fiber. Our systems, which are compatible with emerging solid-state quantum devices, provide a realistic foundation for a high-fidelity quantum Internet with practical devices

Teleportation Systems Toward a Quantum Internet

Quantum teleportation is essential for many quantum information technologies, including long-distance quantum networks. Using fiber-coupled devices, including state-of-the-art low-noise superconducting nanowire single-photon detectors and off-the-shelf optics, we achieve conditional quantum teleportation of time-bin qubits at the telecommunication wavelength of 1536.5 nm. We measure teleportation fidelities of ≥90% that are consistent with an analytical model of our system, which includes realistic imperfections. To demonstrate the compatibility of our setup with deployed quantum networks, we teleport qubits over 22 km of single-mode fiber while transmitting qubits over an additional 22 km of fiber. Our systems, which are compatible with emerging solid-state quantum devices, provide a realistic foundation for a high-fidelity quantum Internet with practical devices

Picosecond Synchronization of Photon Pairs through a Fiber Link between Fermilab and Argonne National Laboratories

We demonstrate a three-node quantum network for C-band photon pairs using 2 pairs of 59 km of deployed fiber between Fermi and Argonne National Laboratories. The C-band pairs are directed to nodes using a standard telecommunication switch and synchronized to picosecond-scale timing resolution using a coexisting O- or L-band optical clock distribution system. We measure a reduction of coincidence-to-accidental ratio (CAR) of the C-band pairs from 51 $\pm$ 2 to 5.3 $\pm$ 0.4 due to Raman scattering of the O-band clock pulses. Despite this reduction, the CAR is nevertheless suitable for quantum networks

The recovery of European freshwater biodiversity has come to a halt

Owing to a long history of anthropogenic pressures, freshwater ecosystems are among the most vulnerable to biodiversity loss1. Mitigation measures, including wastewater treatment and hydromorphological restoration, have aimed to improve environmental quality and foster the recovery of freshwater biodiversity2. Here, using 1,816 time series of freshwater invertebrate communities collected across 22 European countries between 1968 and 2020, we quantified temporal trends in taxonomic and functional diversity and their responses to environmental pressures and gradients. We observed overall increases in taxon richness (0.73% per year), functional richness (2.4% per year) and abundance (1.17% per year). However, these increases primarily occurred before the 2010s, and have since plateaued. Freshwater communities downstream of dams, urban areas and cropland were less likely to experience recovery. Communities at sites with faster rates of warming had fewer gains in taxon richness, functional richness and abundance. Although biodiversity gains in the 1990s and 2000s probably reflect the effectiveness of water-quality improvements and restoration projects, the decelerating trajectory in the 2010s suggests that the current measures offer diminishing returns. Given new and persistent pressures on freshwater ecosystems, including emerging pollutants, climate change and the spread of invasive species, we call for additional mitigation to revive the recovery of freshwater biodiversity.publishedVersio

Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.

Discovery of most autosomal recessive disease-associated genes has involved analysis of large, often consanguineous multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of new dominant causes of rare, genetically heterogeneous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios. Here we analyzed 4,125 families with diverse, rare and genetically heterogeneous developmental disorders and identified four new autosomal recessive disorders. These four disorders were identified by integrating Mendelian filtering (selecting probands with rare, biallelic and putatively damaging variants in the same gene) with statistical assessments of (i) the likelihood of sampling the observed genotypes from the general population and (ii) the phenotypic similarity of patients with recessive variants in the same candidate gene. This new paradigm promises to catalyze the discovery of novel recessive disorders, especially those with less consistent or nonspecific clinical presentations and those caused predominantly by compound heterozygous genotypes

The origins and spread of domestic horses from the Western Eurasian steppes

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: All collapsed and paired-end sequence data for samples sequenced in this study are available in compressed fastq format through the European Nucleotide Archive under accession number PRJEB44430, together with rescaled and trimmed bam sequence alignments against both the nuclear and mitochondrial horse reference genomes. Previously published ancient data used in this study are available under accession numbers PRJEB7537, PRJEB10098, PRJEB10854, PRJEB22390 and PRJEB31613, and detailed in Supplementary Table 1. The genomes of ten modern horses, publicly available, were also accessed as indicated in their corresponding original publications57,61,85-87.NOTE: see the published version available via the DOI in this record for the full list of authorsDomestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 BC. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture