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"content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it",
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"content": "Abstract The liver is the most common site of metastatic disease 1 . Although this metastatic tropism may reflect the mechanical trapping of circulating tumour cells, liver metastasis is also dependent, at least in part, on the formation of a ‘pro-metastatic’ niche that supports the spread of tumour cells to the liver 2 , 3 . The mechanisms that direct the formation of this niche are poorly understood. Here we show that hepatocytes coordinate myeloid cell accumulation and fibrosis within the liver and, in doing so, increase the susceptibility of the liver to metastatic seeding and outgrowth. During early pancreatic tumorigenesis in mice, hepatocytes show activation of signal transducer and activator of transcription 3 (STAT3) signalling and increased production of serum amyloid A1 and A2 (referred to collectively as SAA). Overexpression of SAA by hepatocytes also occurs in patients with pancreatic and colorectal cancers that have metastasized to the liver, and many patients with locally advanced and metastatic disease show increases in circulating SAA. Activation of STAT3 in hepatocytes and the subsequent production of SAA depend on the release of interleukin 6 (IL-6) into the circulation by non-malignant cells. Genetic ablation or blockade of components of IL-6–STAT3–SAA signalling prevents the establishment of a pro-metastatic niche and inhibits liver metastasis. Our data identify an intercellular network underpinned by hepatocytes that forms the basis of a pro-metastatic niche in the liver, and identify new therapeutic targets. Main To understand the mechanisms that underlie the formation of a pro-metastatic niche in the liver, we used the LSL-Kras G12D /+ ;LSL-Trp53 R127H /+ ;Pdx1-cre (KPC) mouse model of pancreatic ductal adenocarcinoma (PDAC) 4 , 5 . We looked for features of a pro-metastatic niche in the livers of over-16-week-old tumour-bearing KPC mice and 8- to 10-week-old non-tumour-bearing (NTB) KPC control mice, which lack PDAC but harbour pancreatic intraepithelial neoplasia (PanIN) 6 . Compared to control mice, the livers of KPC mice contained increased numbers of myeloid cells, accompanied by an increase in the deposition and expression of fibronectin and type I collagen (COL1) (Fig. 1a , Extended Data Fig. 1a–d ). Orthotopic implantation of KPC-derived PDAC cells into wild-type mice recapitulated these changes (Extended Data Fig. 1e–i ). As shown previously 7 , 8 , matrix deposition did not require myeloid cells (Extended Data Fig. 1j–l ). These results are consistent with evidence that myeloid cell accumulation and extracellular matrix deposition are key components of a pro-metastatic niche 7 , 8 , 9 , 10 . Fig. 1: Primary PDAC development induces a pro-metastatic niche in the liver. a , Images and quantification of myeloid cells, fibronectin (FN), and COL1 in the liver. Arrows indicate Ly6G + cells. Numbers in parentheses on plots indicate the number ( n ) of mice. Data pooled from two experiments. TB, tumour-bearing; NTB, non-tumour-bearing. b , Images of the liver and quantification of PDAC–YFP cells. Control mice ( n = 14) and NTB KPC mice ( n = 10) were intrasplenically injected with PDAC–YFP cells, and the liver was analysed after 10 days. Data representative of two independent experiments. c , Scatter plot of transcriptome data. FPKM, fragments per kilobase of exon per million mapped fragments ( n = 5 for both groups). Scale bars, 50 μm ( a ) and 1 cm ( b ). Statistical significance calculated using one-way analysis of variance (ANOVA) with Dunnett’s test ( a ) and two-tailed Mann–Whitney test ( b ). Data represented as mean ± s.d. Source data Full size image We next evaluated the susceptibility of the liver to metastatic colonization. Yellow fluorescent protein (YFP)-labelled KPC-derived PDAC cells (PDAC–YFP) 6 were injected into control mice and KPC mice. The metastatic burden was threefold higher in KPC mice, and metastatic lesions were detected in the livers of KPC mice at increased frequency and size with enhanced proliferation (shown using Ki-67) (Fig. 1b , Extended Data Fig. 2a, b ). Similar findings were observed using a YFP-negative KPC-derived cell line (Extended Data Fig. 2c, d ). Orthotopic implantation of PDAC cells also increased the susceptibility of the liver to metastatic colonization, and this finding was independent of the presence of CD4 + and CD8 + T cells (Extended Data Fig. 2e–s ). We next performed mRNA sequencing on RNA isolated from the livers of control and KPC mice. We identified 275 differentially expressed genes (Extended Data Fig. 3a, b , Supplementary Data 1 ) and found that genes upregulated in KPC mice were associated with immune-related processes (Extended Data Fig. 3c ). Notably, genes encoding myeloid chemoattractants, including SAA and members of the S100 family, were upregulated in KPC mice 11 , 12 , 13 (Fig. 1c , Extended Data Fig. 3d, e ). We also found enrichment of immune-related pathways, particularly the IL-6–JAK–STAT3 signalling pathway (Extended Data Fig. 3f , Supplementary Table 1 ). We validated our results by examining the livers of KPC mice for the presence of phosphorylated STAT3 (pSTAT3). STAT3 was activated in 80–90% of hepatocytes from KPC mice, compared to less than 2% of hepatocytes in control mice (Extended Data Fig. 3g, h ). By contrast, we did not detect activation of STAT1 signalling (Extended Data Fig. 3i ). Orthotopic implantation of PDAC cells also induced phosphorylation of STAT3 in hepatocytes (Extended Data Fig. 3j, k ). As IL-6 is fundamental to STAT3 signalling in hepatocytes 14 , we examined the livers of control mice ( Il6 +/+ ) and IL-6 knockout mice ( Il6 −/− ) orthotopically injected with PBS or PDAC cells. Tumour-implanted Il6 −/− mice displayed a decrease in STAT3 activation, particularly in hepatocytes (Fig. 2a , Extended Data Fig. 4a ). This loss in STAT3 activation was accompanied by reductions in myeloid cell accumulation and extracellular matrix deposition without alterations in the morphology and density of liver sinusoids (Fig. 2a and Extended Data Fig. 4a-d ). We also observed reduced expression of SAA, other chemoattractants, and extracellular matrix proteins (Fig. 2b , Extended Data Fig. 4e ). Genetic ablation of Il6 ,",
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"content": "When cancer spreads to another organ, it most commonly moves to the liver, and now researchers at the Abramson Cancer Center of the University of Pennsylvania say they know why. A new study, published today in Nature, shows hepatocytes—the chief functional cells of the liver—are at the center of a chain reaction that makes it particularly susceptible to cancer cells. These hepatocytes respond to inflammation by activating a protein called STAT3, which in turn increases their production of other proteins called SAA, which then remodel the liver and create the \"soil\" needed for cancer cells to \"seed.\" The researchers show that stopping this process by using antibodies that block IL-6—the inflammatory signal that drives this chain reaction—can limit the potential of cancer to spread to the liver. \"The seed-and-soil hypothesis is well-recognized, but our research now shows that hepatocytes are the major orchestrators of this process,\" said senior author Gregory L. Beatty, MD, Ph.D., an assistant professor of Hematology-Oncology at Penn's Perelman School of Medicine. Jae W. Lee, an MD/Ph.D. candidate in Beatty's laboratory, is the lead author. For this study, the team first used mouse models of pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer and currently the third leading cause of cancer death in the United States. They found that nearly all hepatocytes showed STAT3 activation in mice with cancer, compared to less than two percent of hepatocytes in mice without tumors. They then partnered with investigators at the Mayo Clinic Arizona and other Penn colleagues to show that this same biology could be seen in patients with pancreatic cancer as well colon and lung cancer. Genetically deleting STAT3 only in hepatocytes effectively blocked the increased susceptibility of the liver to cancer seeding in mice. The team collaborated further with investigators at the University of Kentucky to show that IL-6 controls STAT3 signaling in these cells and instructs hepatocytes to make SAA, which acts as an alarm to attract inflammatory cells and initiate a fibrotic reaction that together establish the \"soil.\" \"The liver is an important sensor in the body,\" Lee said. \"We show that hepatocytes sense inflammation and respond in a structured way that cancer uses to help it spread.\" The study also found that IL-6 drives changes in the liver whether there's a tumor present or not, implying that any condition associated with increased IL-6 levels—such as obesity or cardiovascular disease, among others—could affect the liver's receptiveness to cancer. Researchers say this provides evidence that therapies which target hepatocytes may be able to prevent cancer from spreading to the liver, a major cause of cancer mortality. ",
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] | <|im_start|>system
You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|>
<|im_start|>user
Abstract The liver is the most common site of metastatic disease 1 . Although this metastatic tropism may reflect the mechanical trapping of circulating tumour cells, liver metastasis is also dependent, at least in part, on the formation of a ‘pro-metastatic’ niche that supports the spread of tumour cells to the liver 2 , 3 . The mechanisms that direct the formation of this niche are poorly understood. Here we show that hepatocytes coordinate myeloid cell accumulation and fibrosis within the liver and, in doing so, increase the susceptibility of the liver to metastatic seeding and outgrowth. During early pancreatic tumorigenesis in mice, hepatocytes show activation of signal transducer and activator of transcription 3 (STAT3) signalling and increased production of serum amyloid A1 and A2 (referred to collectively as SAA). Overexpression of SAA by hepatocytes also occurs in patients with pancreatic and colorectal cancers that have metastasized to the liver, and many patients with locally advanced and metastatic disease show increases in circulating SAA. Activation of STAT3 in hepatocytes and the subsequent production of SAA depend on the release of interleukin 6 (IL-6) into the circulation by non-malignant cells. Genetic ablation or blockade of components of IL-6–STAT3–SAA signalling prevents the establishment of a pro-metastatic niche and inhibits liver metastasis. Our data identify an intercellular network underpinned by hepatocytes that forms the basis of a pro-metastatic niche in the liver, and identify new therapeutic targets. Main To understand the mechanisms that underlie the formation of a pro-metastatic niche in the liver, we used the LSL-Kras G12D /+ ;LSL-Trp53 R127H /+ ;Pdx1-cre (KPC) mouse model of pancreatic ductal adenocarcinoma (PDAC) 4 , 5 . We looked for features of a pro-metastatic niche in the livers of over-16-week-old tumour-bearing KPC mice and 8- to 10-week-old non-tumour-bearing (NTB) KPC control mice, which lack PDAC but harbour pancreatic intraepithelial neoplasia (PanIN) 6 . Compared to control mice, the livers of KPC mice contained increased numbers of myeloid cells, accompanied by an increase in the deposition and expression of fibronectin and type I collagen (COL1) (Fig. 1a , Extended Data Fig. 1a–d ). Orthotopic implantation of KPC-derived PDAC cells into wild-type mice recapitulated these changes (Extended Data Fig. 1e–i ). As shown previously 7 , 8 , matrix deposition did not require myeloid cells (Extended Data Fig. 1j–l ). These results are consistent with evidence that myeloid cell accumulation and extracellular matrix deposition are key components of a pro-metastatic niche 7 , 8 , 9 , 10 . Fig. 1: Primary PDAC development induces a pro-metastatic niche in the liver. a , Images and quantification of myeloid cells, fibronectin (FN), and COL1 in the liver. Arrows indicate Ly6G + cells. Numbers in parentheses on plots indicate the number ( n ) of mice. Data pooled from two experiments. TB, tumour-bearing; NTB, non-tumour-bearing. b , Images of the liver and quantification of PDAC–YFP cells. Control mice ( n = 14) and NTB KPC mice ( n = 10) were intrasplenically injected with PDAC–YFP cells, and the liver was analysed after 10 days. Data representative of two independent experiments. c , Scatter plot of transcriptome data. FPKM, fragments per kilobase of exon per million mapped fragments ( n = 5 for both groups). Scale bars, 50 μm ( a ) and 1 cm ( b ). Statistical significance calculated using one-way analysis of variance (ANOVA) with Dunnett’s test ( a ) and two-tailed Mann–Whitney test ( b ). Data represented as mean ± s.d. Source data Full size image We next evaluated the susceptibility of the liver to metastatic colonization. Yellow fluorescent protein (YFP)-labelled KPC-derived PDAC cells (PDAC–YFP) 6 were injected into control mice and KPC mice. The metastatic burden was threefold higher in KPC mice, and metastatic lesions were detected in the livers of KPC mice at increased frequency and size with enhanced proliferation (shown using Ki-67) (Fig. 1b , Extended Data Fig. 2a, b ). Similar findings were observed using a YFP-negative KPC-derived cell line (Extended Data Fig. 2c, d ). Orthotopic implantation of PDAC cells also increased the susceptibility of the liver to metastatic colonization, and this finding was independent of the presence of CD4 + and CD8 + T cells (Extended Data Fig. 2e–s ). We next performed mRNA sequencing on RNA isolated from the livers of control and KPC mice. We identified 275 differentially expressed genes (Extended Data Fig. 3a, b , Supplementary Data 1 ) and found that genes upregulated in KPC mice were associated with immune-related processes (Extended Data Fig. 3c ). Notably, genes encoding myeloid chemoattractants, including SAA and members of the S100 family, were upregulated in KPC mice 11 , 12 , 13 (Fig. 1c , Extended Data Fig. 3d, e ). We also found enrichment of immune-related pathways, particularly the IL-6–JAK–STAT3 signalling pathway (Extended Data Fig. 3f , Supplementary Table 1 ). We validated our results by examining the livers of KPC mice for the presence of phosphorylated STAT3 (pSTAT3). STAT3 was activated in 80–90% of hepatocytes from KPC mice, compared to less than 2% of hepatocytes in control mice (Extended Data Fig. 3g, h ). By contrast, we did not detect activation of STAT1 signalling (Extended Data Fig. 3i ). Orthotopic implantation of PDAC cells also induced phosphorylation of STAT3 in hepatocytes (Extended Data Fig. 3j, k ). As IL-6 is fundamental to STAT3 signalling in hepatocytes 14 , we examined the livers of control mice ( Il6 +/+ ) and IL-6 knockout mice ( Il6 −/− ) orthotopically injected with PBS or PDAC cells. Tumour-implanted Il6 −/− mice displayed a decrease in STAT3 activation, particularly in hepatocytes (Fig. 2a , Extended Data Fig. 4a ). This loss in STAT3 activation was accompanied by reductions in myeloid cell accumulation and extracellular matrix deposition without alterations in the morphology and density of liver sinusoids (Fig. 2a and Extended Data Fig. 4a-d ). We also observed reduced expression of SAA, other chemoattractants, and extracellular matrix proteins (Fig. 2b , Extended Data Fig. 4e ). Genetic ablation of Il6 ,<|im_end|>
<|im_start|>assistant
When cancer spreads to another organ, it most commonly moves to the liver, and now researchers at the Abramson Cancer Center of the University of Pennsylvania say they know why. A new study, published today in Nature, shows hepatocytes—the chief functional cells of the liver—are at the center of a chain reaction that makes it particularly susceptible to cancer cells. These hepatocytes respond to inflammation by activating a protein called STAT3, which in turn increases their production of other proteins called SAA, which then remodel the liver and create the "soil" needed for cancer cells to "seed." The researchers show that stopping this process by using antibodies that block IL-6—the inflammatory signal that drives this chain reaction—can limit the potential of cancer to spread to the liver. "The seed-and-soil hypothesis is well-recognized, but our research now shows that hepatocytes are the major orchestrators of this process," said senior author Gregory L. Beatty, MD, Ph.D., an assistant professor of Hematology-Oncology at Penn's Perelman School of Medicine. Jae W. Lee, an MD/Ph.D. candidate in Beatty's laboratory, is the lead author. For this study, the team first used mouse models of pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer and currently the third leading cause of cancer death in the United States. They found that nearly all hepatocytes showed STAT3 activation in mice with cancer, compared to less than two percent of hepatocytes in mice without tumors. They then partnered with investigators at the Mayo Clinic Arizona and other Penn colleagues to show that this same biology could be seen in patients with pancreatic cancer as well colon and lung cancer. Genetically deleting STAT3 only in hepatocytes effectively blocked the increased susceptibility of the liver to cancer seeding in mice. The team collaborated further with investigators at the University of Kentucky to show that IL-6 controls STAT3 signaling in these cells and instructs hepatocytes to make SAA, which acts as an alarm to attract inflammatory cells and initiate a fibrotic reaction that together establish the "soil." "The liver is an important sensor in the body," Lee said. "We show that hepatocytes sense inflammation and respond in a structured way that cancer uses to help it spread." The study also found that IL-6 drives changes in the liver whether there's a tumor present or not, implying that any condition associated with increased IL-6 levels—such as obesity or cardiovascular disease, among others—could affect the liver's receptiveness to cancer. Researchers say this provides evidence that therapies which target hepatocytes may be able to prevent cancer from spreading to the liver, a major cause of cancer mortality. <|im_end|>
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[
{
"content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it",
"role": "system"
},
{
"content": "Abstract Magnetic resonance imaging and spectroscopy are versatile methods for probing brain physiology, but their intrinsically low sensitivity limits the achievable spatial and temporal resolution. Here, we introduce a monolithically integrated NMR-on-a-chip needle that combines an ultra-sensitive 300 µm NMR coil with a complete NMR transceiver, enabling in vivo measurements of blood oxygenation and flow in nanoliter volumes at a sampling rate of 200 Hz. Main Methods based on nuclear magnetic resonance (NMR) are powerful analytical techniques in the life sciences, using nuclear spins as specific nanoscopic probes. Despite substantial advances in magnetic resonance (MR) hardware and methodology, NMR is still limited by its poor sensitivity (compared, for example, with optical methods), hindering in particular its use in the study of brain physiology and pathology. Recently, integrated circuit (IC)-based NMR systems have been introduced 1 , 2 , 3 , 4 , 5 to simplify the hardware complexity of MR experiments and to boost sensitivity. Integration of the MR detection coil with the transceiver on a single IC 4 , 5 laid the foundation for millimeter-size, sensitive MR systems for in situ and in vivo applications such as palm-size NMR spectrometry 1 and NMR spectroscopy of single cells 5 . Here, we present a monolithic needle-shaped NMR-on-a-chip transceiver (Fig. 1a,b ) that makes the advantages of IC-based NMR available for various applications in neuroscience. With its miniaturized on-chip coil, low-noise performance and compact, 450 µm-wide needle design, our NMR-on-a-chip transceiver simultaneously improves sensitivity as well as spatial and temporal resolution. In contrast to conventional microcoils 6 , 7 , the micrometer-scale interconnecting wires between the on-chip coil and the electronics combined with the fully differential design reduce the pickup of parasitic MR signals and electromagnetic interference. This enables interference-free in vivo experiments in a defined region of interest. Compared to conventional functional MR imaging (fMRI), the on-chip microcoil removes the need for time-consuming spatial encoding and allows for a continuous recording of MR signals in a nanoliter volume with millisecond resolution. Fig. 1: Schematic overview of the target application of the needle-shaped NMR-on-a-chip transceiver, the ASIC design and the experimental setup. a , The NMR needle is inserted into the target brain area, for example the somatosensory cortex, to perform localized and fast functional MR experiments. b , Fully integrated NMR-on-a-chip spectrometer with an on-chip planar broadband detection coil. The transceiver electronics include a low-noise receiver with quadrature demodulation, an H-bridge-based PA and a frequency synthesizer (containing a phase-frequency detector (PFD), a charge pump (CP) and a quadrature signal generator (IQ)). c , Experimental setup around the NMR needle: the ASIC is glued and bonded on a small carrier PCB and connected via a ribbon cable to the signal conditioning PCB. This setup can be mounted either on a carrier with a sample container and a conventional 8 mm surface coil as reference for system characterization, such as linewidth, sensitivity and SNR, and MR imaging (in vitro setup) or on an animal bed for neuronal experiments to measure changes in blood oxygenation and flow in rats (in vivo setup). The bed or carrier is placed inside a 14.1 T small-animal scanner and the system is completed by a commercial data-acquisition card and a LabVIEW-based console located in the control room. Full size image To achieve the required detection sensitivity in a form factor that is suitable for localized in vivo experiments in brain tissue, we realized a complete NMR spectrometer as a complementary metal-oxide-semiconductor (CMOS) application-specific integrated circuit (ASIC) (Fig. 1b ). This low-power (20 mW) NMR-on-a-chip transceiver features an on-chip, 24-turn, 300 µm outer diameter, transmit/receive (TX/RX) NMR coil. The RX path contains a complete quadrature receiver with an overall noise figure of 0.7 dB including a phase-locked loop (PLL)-based frequency synthesizer and protection switches for the low-noise amplifier (LNA). The TX path features an H-bridge power amplifier (PA) operating from a 3.3 V supply and driven by the on-chip PLL that produces a maximum coil current of 15 mA at 600 MHz. Owing to its amplitude and phase modulation capabilities, the on-chip electronics allow for the use of standard imaging sequences and spectroscopy techniques. In mechanical postprocessing, we first ground the manufactured chips down to a thickness of 100 µm and then shaped them as a needle with a wafer dicer. We used two different setups for in vitro characterization and for in vivo neuronal rat experiments in a 14.1 T small-animal scanner (Fig. 1c ). After first-order manual shimming, the NMR needle achieves a spectral linewidth of 12 Hz in a water phantom (Supplementary Fig. 1 ) and 53 Hz for in vivo experiments (Supplementary Fig. 2 ). We determined the sensitivity of the NMR needle using a three-dimensional gradient echo (3DGRE) sequence, resulting in a sensitive volume of 9.8 nl (Fig. 2a and Supplementary Fig. 3 ) and a time-domain spin sensitivity of \\(2.0 \\times 10^{13}{\\,\\mathrm{spins}}\\,\\mathrm{per}\\,\\sqrt {{\\mathrm{Hz}}}\\) . Compared to a conventional 8 mm surface coil, the NMR needle’s signal-to-noise ratio (SNR) per spin is 40 times higher ( Methods ). We obtained 3DGRE images of a polyimide phantom with an isotropic resolution of 13 µm in less than 15 min, demonstrating the excellent MR imaging capabilities of the NMR needle (Supplementary Fig. 4 ). Fig. 2: In vitro measurement of the sensitive volume and representative experimental results from in vivo rat forepaw stimulation experiments. a , Single-shot (that is, no averaging) 3DGRE image of the sensitive volume V sens of the NMR needle immersed in 10 mM Gd-doped water ( N = 1). b , Coronal anatomical MR image recorded with a conventional surface coil, showing the precise needle location (no averaging, N = 1). The inset shows an overlay from EPI fMRI with a contralateral activation from the stimulation of the left paw in the implantation region of the needle (average of N = 20 stimulation blocks). c , Axial anatomical MR image showing the precise needle location and implantation depth ( N = 1). The inset shows an overlay from EPI fMRI (",
"role": "user"
},
{
"content": "A team of neuroscientists and electrical engineers from Germany and Switzerland developed a highly sensitive implant that enables to probe brain physiology with unparalleled spatial and temporal resolution. They introduce an ultra-fine needle with an integrated chip that is capable of detecting and transmitting nuclear magnetic resonance (NMR) data from nanoliter volumes of brain oxygen metabolism. The breakthrough design will allow entirely new applications in the life sciences. The group of researchers led by Klaus Scheffler from the Max Planck Institute for Biological Cybernetics and the University of Tübingen as well as by Jens Anders from the University of Stuttgart identified a technical bypass that bridges the electrophysical limits of contemporary brain scan methods. Their development of a capillary monolithic nuclear magnetic resonance (NMR) needle combines the versatility of brain imaging with the accuracy of a very localized and fast technique to analyze the specific neuronal activity of the brain. \"The integrated design of a nuclear magnetic resonance detector on a single chip supremely reduces the typical electromagnetic interference of magnetic resonance signals. This enables neuroscientists to gather precise data from minuscule areas of the brain and to combine them with information from spatial and temporal data of the brain´s physiology,\" explains principal investigator Klaus Scheffler. \"With this method, we can now better understand specific activity and functionalities in the brain.\" According to Scheffler and his group, their invention may unveil the possibility of discovering novel effects or typical fingerprints of neuronal activation, up to specific neuronal events in brain tissue. \"Our design setup will allow scalable solutions, meaning the possibility of expanding the collection of data from more than from a single area—but on the same device. The scalability of our approach will allow us to extend our platform by additional sensing modalities such as electrophysiological and optogenetic measurements,\" adds the second principal investigator Jens Anders. The teams of Scheffler and Anders are very confident that their technical approach may help demerge the complex physiologic processes within the neural networks of the brain and that it may uncover additional benefits that can provide even deeper insights into the functionality of the brain. With their primary goal to develop new techniques that are able to specifically probe the structural and biochemical composition of living brain tissue, their latest innovation paves the way for future highly specific and quantitative mapping techniques of neuronal activity and bioenergetic processes in the brain cells. ",
"role": "assistant"
}
] | <|im_start|>system
You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|>
<|im_start|>user
Abstract Magnetic resonance imaging and spectroscopy are versatile methods for probing brain physiology, but their intrinsically low sensitivity limits the achievable spatial and temporal resolution. Here, we introduce a monolithically integrated NMR-on-a-chip needle that combines an ultra-sensitive 300 µm NMR coil with a complete NMR transceiver, enabling in vivo measurements of blood oxygenation and flow in nanoliter volumes at a sampling rate of 200 Hz. Main Methods based on nuclear magnetic resonance (NMR) are powerful analytical techniques in the life sciences, using nuclear spins as specific nanoscopic probes. Despite substantial advances in magnetic resonance (MR) hardware and methodology, NMR is still limited by its poor sensitivity (compared, for example, with optical methods), hindering in particular its use in the study of brain physiology and pathology. Recently, integrated circuit (IC)-based NMR systems have been introduced 1 , 2 , 3 , 4 , 5 to simplify the hardware complexity of MR experiments and to boost sensitivity. Integration of the MR detection coil with the transceiver on a single IC 4 , 5 laid the foundation for millimeter-size, sensitive MR systems for in situ and in vivo applications such as palm-size NMR spectrometry 1 and NMR spectroscopy of single cells 5 . Here, we present a monolithic needle-shaped NMR-on-a-chip transceiver (Fig. 1a,b ) that makes the advantages of IC-based NMR available for various applications in neuroscience. With its miniaturized on-chip coil, low-noise performance and compact, 450 µm-wide needle design, our NMR-on-a-chip transceiver simultaneously improves sensitivity as well as spatial and temporal resolution. In contrast to conventional microcoils 6 , 7 , the micrometer-scale interconnecting wires between the on-chip coil and the electronics combined with the fully differential design reduce the pickup of parasitic MR signals and electromagnetic interference. This enables interference-free in vivo experiments in a defined region of interest. Compared to conventional functional MR imaging (fMRI), the on-chip microcoil removes the need for time-consuming spatial encoding and allows for a continuous recording of MR signals in a nanoliter volume with millisecond resolution. Fig. 1: Schematic overview of the target application of the needle-shaped NMR-on-a-chip transceiver, the ASIC design and the experimental setup. a , The NMR needle is inserted into the target brain area, for example the somatosensory cortex, to perform localized and fast functional MR experiments. b , Fully integrated NMR-on-a-chip spectrometer with an on-chip planar broadband detection coil. The transceiver electronics include a low-noise receiver with quadrature demodulation, an H-bridge-based PA and a frequency synthesizer (containing a phase-frequency detector (PFD), a charge pump (CP) and a quadrature signal generator (IQ)). c , Experimental setup around the NMR needle: the ASIC is glued and bonded on a small carrier PCB and connected via a ribbon cable to the signal conditioning PCB. This setup can be mounted either on a carrier with a sample container and a conventional 8 mm surface coil as reference for system characterization, such as linewidth, sensitivity and SNR, and MR imaging (in vitro setup) or on an animal bed for neuronal experiments to measure changes in blood oxygenation and flow in rats (in vivo setup). The bed or carrier is placed inside a 14.1 T small-animal scanner and the system is completed by a commercial data-acquisition card and a LabVIEW-based console located in the control room. Full size image To achieve the required detection sensitivity in a form factor that is suitable for localized in vivo experiments in brain tissue, we realized a complete NMR spectrometer as a complementary metal-oxide-semiconductor (CMOS) application-specific integrated circuit (ASIC) (Fig. 1b ). This low-power (20 mW) NMR-on-a-chip transceiver features an on-chip, 24-turn, 300 µm outer diameter, transmit/receive (TX/RX) NMR coil. The RX path contains a complete quadrature receiver with an overall noise figure of 0.7 dB including a phase-locked loop (PLL)-based frequency synthesizer and protection switches for the low-noise amplifier (LNA). The TX path features an H-bridge power amplifier (PA) operating from a 3.3 V supply and driven by the on-chip PLL that produces a maximum coil current of 15 mA at 600 MHz. Owing to its amplitude and phase modulation capabilities, the on-chip electronics allow for the use of standard imaging sequences and spectroscopy techniques. In mechanical postprocessing, we first ground the manufactured chips down to a thickness of 100 µm and then shaped them as a needle with a wafer dicer. We used two different setups for in vitro characterization and for in vivo neuronal rat experiments in a 14.1 T small-animal scanner (Fig. 1c ). After first-order manual shimming, the NMR needle achieves a spectral linewidth of 12 Hz in a water phantom (Supplementary Fig. 1 ) and 53 Hz for in vivo experiments (Supplementary Fig. 2 ). We determined the sensitivity of the NMR needle using a three-dimensional gradient echo (3DGRE) sequence, resulting in a sensitive volume of 9.8 nl (Fig. 2a and Supplementary Fig. 3 ) and a time-domain spin sensitivity of \(2.0 \times 10^{13}{\,\mathrm{spins}}\,\mathrm{per}\,\sqrt {{\mathrm{Hz}}}\) . Compared to a conventional 8 mm surface coil, the NMR needle’s signal-to-noise ratio (SNR) per spin is 40 times higher ( Methods ). We obtained 3DGRE images of a polyimide phantom with an isotropic resolution of 13 µm in less than 15 min, demonstrating the excellent MR imaging capabilities of the NMR needle (Supplementary Fig. 4 ). Fig. 2: In vitro measurement of the sensitive volume and representative experimental results from in vivo rat forepaw stimulation experiments. a , Single-shot (that is, no averaging) 3DGRE image of the sensitive volume V sens of the NMR needle immersed in 10 mM Gd-doped water ( N = 1). b , Coronal anatomical MR image recorded with a conventional surface coil, showing the precise needle location (no averaging, N = 1). The inset shows an overlay from EPI fMRI with a contralateral activation from the stimulation of the left paw in the implantation region of the needle (average of N = 20 stimulation blocks). c , Axial anatomical MR image showing the precise needle location and implantation depth ( N = 1). The inset shows an overlay from EPI fMRI (<|im_end|>
<|im_start|>assistant
A team of neuroscientists and electrical engineers from Germany and Switzerland developed a highly sensitive implant that enables to probe brain physiology with unparalleled spatial and temporal resolution. They introduce an ultra-fine needle with an integrated chip that is capable of detecting and transmitting nuclear magnetic resonance (NMR) data from nanoliter volumes of brain oxygen metabolism. The breakthrough design will allow entirely new applications in the life sciences. The group of researchers led by Klaus Scheffler from the Max Planck Institute for Biological Cybernetics and the University of Tübingen as well as by Jens Anders from the University of Stuttgart identified a technical bypass that bridges the electrophysical limits of contemporary brain scan methods. Their development of a capillary monolithic nuclear magnetic resonance (NMR) needle combines the versatility of brain imaging with the accuracy of a very localized and fast technique to analyze the specific neuronal activity of the brain. "The integrated design of a nuclear magnetic resonance detector on a single chip supremely reduces the typical electromagnetic interference of magnetic resonance signals. This enables neuroscientists to gather precise data from minuscule areas of the brain and to combine them with information from spatial and temporal data of the brain´s physiology," explains principal investigator Klaus Scheffler. "With this method, we can now better understand specific activity and functionalities in the brain." According to Scheffler and his group, their invention may unveil the possibility of discovering novel effects or typical fingerprints of neuronal activation, up to specific neuronal events in brain tissue. "Our design setup will allow scalable solutions, meaning the possibility of expanding the collection of data from more than from a single area—but on the same device. The scalability of our approach will allow us to extend our platform by additional sensing modalities such as electrophysiological and optogenetic measurements," adds the second principal investigator Jens Anders. The teams of Scheffler and Anders are very confident that their technical approach may help demerge the complex physiologic processes within the neural networks of the brain and that it may uncover additional benefits that can provide even deeper insights into the functionality of the brain. With their primary goal to develop new techniques that are able to specifically probe the structural and biochemical composition of living brain tissue, their latest innovation paves the way for future highly specific and quantitative mapping techniques of neuronal activity and bioenergetic processes in the brain cells. <|im_end|>
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{
"content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it",
"role": "system"
},
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"content": "Abstract Clonal haematopoiesis involves the expansion of certain blood cell lineages and has been associated with ageing and adverse health outcomes 1 , 2 , 3 , 4 , 5 . Here we use exome sequence data on 628,388 individuals to identify 40,208 carriers of clonal haematopoiesis of indeterminate potential (CHIP). Using genome-wide and exome-wide association analyses, we identify 24 loci (21 of which are novel) where germline genetic variation influences predisposition to CHIP, including missense variants in the lymphocytic antigen coding gene LY75 , which are associated with reduced incidence of CHIP. We also identify novel rare variant associations with clonal haematopoiesis and telomere length. Analysis of 5,041 health traits from the UK Biobank (UKB) found relationships between CHIP and severe COVID-19 outcomes, cardiovascular disease, haematologic traits, malignancy, smoking, obesity, infection and all-cause mortality. Longitudinal and Mendelian randomization analyses revealed that CHIP is associated with solid cancers, including non-melanoma skin cancer and lung cancer, and that CHIP linked to DNMT3A is associated with the subsequent development of myeloid but not lymphoid leukaemias. Additionally, contrary to previous findings from the initial 50,000 UKB exomes 6 , our results in the full sample do not support a role for IL-6 inhibition in reducing the risk of cardiovascular disease among CHIP carriers. Our findings demonstrate that CHIP represents a complex set of heterogeneous phenotypes with shared and unique germline genetic causes and varied clinical implications. Main As humans age, somatic alterations accrue in the DNA of haematopoietic stem cells (HSCs) due to mitotic errors and DNA damage. Alterations that confer a selective growth advantage can lead to the expansion of particular cell lineages, a phenomenon called clonal haematopoiesis. The presence of clonal haematopoiesis has been associated with an increased risk of haematological neoplasms, cytopaenias, cardiovascular disease (CVD), infection and all-cause mortality 1 , 2 , 3 , 4 , 5 . For this reason, identifying germline causes of clonal haematopoiesis has the potential to improve our understanding of initiating events in the development of these common diseases. Large-scale studies of the germline causes of clonal haematopoiesis have used samples from the UKB and other large cohorts, but those studies have been limited mostly to clonal haematopoiesis phenotypes that can be assessed using single nucleotide polymorphism (SNP) array genotype data, such as mosaic chromosomal alternations (mCA) and mosaic loss of sex chromosomes 4 , 7 , 8 (mLOX and mLOY). Identifying individuals with CHIP, which is defined by somatic protein-altering mutations in genes that are recurrently mutated in clonal haematopoiesis, requires sequencing of blood 1 , 2 . Once a clone has expanded sufficiently, the somatic variants from this clone can be captured along with germline variants by exome sequencing. Since exome sequencing captures protein-altering variants, its large-scale application enables the detection of readily interpretable rare variant association signals, and can elucidate critical genes and pathways and potential therapeutic targeting 9 , 10 . So far, the largest genetic association study of CHIP has included 3,831 CHIP mutation carriers in a sample of 65,405 individuals and has identified four common variant loci 11 . Here, we use exome sequencing data to characterize CHIP status in 454,803 UKB 10 and 173,585 Geisinger MyCode Community Health Initiative (GHS) participants. We then conduct a common variant genome-wide association study (GWAS) and rare variant and gene burden exome-wide association study (ExWAS) of CHIP by leveraging 27,331 CHIP mutation carriers from the UKB. We perform a replication analysis using 12,877 CHIP mutation carriers from the GHS cohort. To identify germline predictors of specific clonal haematopoiesis driver mutations, we also conduct GWAS and ExWAS in carriers of CHIP mutations from individual CHIP genes. We then compare genetic association findings for CHIP to those from analyses of other clonal haematopoiesis phenotypes determined from somatic alterations in the blood, including mCA, mLOX, mLOY and telomere length. Although GWAS of these non-CHIP clonal haematopoiesis phenotypes have been conducted 4 , 7 , 12 , none have evaluated the effect of rare variation. The ExWAS we perform here represents the first systematic large-scale exploration of the effect of rare variants on the genetic susceptibility of these phenotypes. Finally, we examine the clinical consequences of somatic CHIP mutations and germline predictors of CHIP in several ways. We first conduct a PheWAS 13 of germline predictors of CHIP to understand their biological functions, and test cross-sectional phenotype associations of CHIP carrier status across 5,194 traits in the UKB. We then test the risk of incident cancer, CVD and all-cause mortality among specific CHIP gene mutation carriers and use Mendelian randomization to test for evidence of causal associations between CHIP and phenotypes of interest. Calling CHIP We used exome sequencing data from 454,803 and 173,585 individuals from the UKB and GHS cohorts, respectively, to generate large callsets of CHIP carrier status ( Methods ). In brief, we called somatic mutations using Mutect2 in a pipeline that included custom QC filtering (Extended Data Fig. 1a ), and ultimately restricted our analysis to 23 well defined and recurrent CHIP-associated genes. This focused analysis identified 29,669 variants across 27,331 individuals in the UKB (6%), and 14,766 variants across 12,877 individuals in the GHS (7.4%). DNMT3A , TET2 , ASXL1 , PPM1D and TP53 were the most commonly mutated genes in both cohorts (Extended Data Fig. 2a ). Although the GHS cohort had a wider age range, and therefore a larger number of older individuals, the prevalence by age was similar across cohorts, and reached approximately 15% by 75 years of age (Extended Data Fig. 1b,c ). Prevalence of CHIP gene-specific mutations was consistent with recurrence patterns, with mutations in the most commonly mutated CHIP genes beginning to increase in prevalence at younger ages (Extended Data Fig. 1d,e and Supplementary Note 1 ). Somatic mutations within the IDH2 and SRSF2 genes co-occurred significantly more frequently than expected in both the UKB and GHS cohorts, whereas DNMT3A mutations co-occurred less frequently with other mutations than expected (Extended Data Fig. 2b,c and Supplementary Table 1 ). Among individuals with multiple CHIP mutations",
"role": "user"
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"content": "A team of researchers at Regeneron Pharmaceuticals has identified new genomic variants associated with clonal hematopoiesis of indeterminate potential (CHIP). In their paper published in the journal Nature, the group describes how they used exome-wide and genome-wide association analyses to study differences in the blood of some people with somatic mutations. Nature has also published a Research Highlights piece in the same journal issue, discussing the work done by the New York team. Hematopoiesis is a process that results in the formation of cellular blood components. And clonal hematopoiesis is the part of the process that is involved in the development of cell lineages. The importance of the overall process is highlighted by the fact that every person produces approximately 300 billion new blood cells every single day of their life. Prior research has suggested that there are variants associated with clonal hematopoiesis of indeterminate potential in certain people—each of which can have a unique impact. In this new effort, the team at Regeneron sought to find some of them by studying information held in very large datasets, such as the UK Biobank and the Geisinger MyCode Community Health Initiative. To find the variants they were after, the researchers focused their search efforts on 23 genes that have already been associated with CHIP. By searching through data on 628,388 individuals, they were able to identify 40,208 carriers of at least one variant associated with CHIP. They then conducted exome-wide and genome-wide studies of the carriers they had identified. In so doing, they were able to identify 24 loci—21 of which had not been seen before. The researchers also found that they were able to identify some variants that could be associated with clonal hematopoiesis and the length of telomeres in certain individuals. In another part of their study, the team analyzed health traits of people listed in the UK Biobank looking for associations between people who had CHIP variants and other issues. In so doing, they found associations between people who had clonal hematopoiesis variants and diseases such as COVID-19, heart problems, obesity and problems clearing infections of various types. They also found associations between individuals with CHIP and development of cancerous tumors and myeloid leukemias. ",
"role": "assistant"
}
] | <|im_start|>system
You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|>
<|im_start|>user
Abstract Clonal haematopoiesis involves the expansion of certain blood cell lineages and has been associated with ageing and adverse health outcomes 1 , 2 , 3 , 4 , 5 . Here we use exome sequence data on 628,388 individuals to identify 40,208 carriers of clonal haematopoiesis of indeterminate potential (CHIP). Using genome-wide and exome-wide association analyses, we identify 24 loci (21 of which are novel) where germline genetic variation influences predisposition to CHIP, including missense variants in the lymphocytic antigen coding gene LY75 , which are associated with reduced incidence of CHIP. We also identify novel rare variant associations with clonal haematopoiesis and telomere length. Analysis of 5,041 health traits from the UK Biobank (UKB) found relationships between CHIP and severe COVID-19 outcomes, cardiovascular disease, haematologic traits, malignancy, smoking, obesity, infection and all-cause mortality. Longitudinal and Mendelian randomization analyses revealed that CHIP is associated with solid cancers, including non-melanoma skin cancer and lung cancer, and that CHIP linked to DNMT3A is associated with the subsequent development of myeloid but not lymphoid leukaemias. Additionally, contrary to previous findings from the initial 50,000 UKB exomes 6 , our results in the full sample do not support a role for IL-6 inhibition in reducing the risk of cardiovascular disease among CHIP carriers. Our findings demonstrate that CHIP represents a complex set of heterogeneous phenotypes with shared and unique germline genetic causes and varied clinical implications. Main As humans age, somatic alterations accrue in the DNA of haematopoietic stem cells (HSCs) due to mitotic errors and DNA damage. Alterations that confer a selective growth advantage can lead to the expansion of particular cell lineages, a phenomenon called clonal haematopoiesis. The presence of clonal haematopoiesis has been associated with an increased risk of haematological neoplasms, cytopaenias, cardiovascular disease (CVD), infection and all-cause mortality 1 , 2 , 3 , 4 , 5 . For this reason, identifying germline causes of clonal haematopoiesis has the potential to improve our understanding of initiating events in the development of these common diseases. Large-scale studies of the germline causes of clonal haematopoiesis have used samples from the UKB and other large cohorts, but those studies have been limited mostly to clonal haematopoiesis phenotypes that can be assessed using single nucleotide polymorphism (SNP) array genotype data, such as mosaic chromosomal alternations (mCA) and mosaic loss of sex chromosomes 4 , 7 , 8 (mLOX and mLOY). Identifying individuals with CHIP, which is defined by somatic protein-altering mutations in genes that are recurrently mutated in clonal haematopoiesis, requires sequencing of blood 1 , 2 . Once a clone has expanded sufficiently, the somatic variants from this clone can be captured along with germline variants by exome sequencing. Since exome sequencing captures protein-altering variants, its large-scale application enables the detection of readily interpretable rare variant association signals, and can elucidate critical genes and pathways and potential therapeutic targeting 9 , 10 . So far, the largest genetic association study of CHIP has included 3,831 CHIP mutation carriers in a sample of 65,405 individuals and has identified four common variant loci 11 . Here, we use exome sequencing data to characterize CHIP status in 454,803 UKB 10 and 173,585 Geisinger MyCode Community Health Initiative (GHS) participants. We then conduct a common variant genome-wide association study (GWAS) and rare variant and gene burden exome-wide association study (ExWAS) of CHIP by leveraging 27,331 CHIP mutation carriers from the UKB. We perform a replication analysis using 12,877 CHIP mutation carriers from the GHS cohort. To identify germline predictors of specific clonal haematopoiesis driver mutations, we also conduct GWAS and ExWAS in carriers of CHIP mutations from individual CHIP genes. We then compare genetic association findings for CHIP to those from analyses of other clonal haematopoiesis phenotypes determined from somatic alterations in the blood, including mCA, mLOX, mLOY and telomere length. Although GWAS of these non-CHIP clonal haematopoiesis phenotypes have been conducted 4 , 7 , 12 , none have evaluated the effect of rare variation. The ExWAS we perform here represents the first systematic large-scale exploration of the effect of rare variants on the genetic susceptibility of these phenotypes. Finally, we examine the clinical consequences of somatic CHIP mutations and germline predictors of CHIP in several ways. We first conduct a PheWAS 13 of germline predictors of CHIP to understand their biological functions, and test cross-sectional phenotype associations of CHIP carrier status across 5,194 traits in the UKB. We then test the risk of incident cancer, CVD and all-cause mortality among specific CHIP gene mutation carriers and use Mendelian randomization to test for evidence of causal associations between CHIP and phenotypes of interest. Calling CHIP We used exome sequencing data from 454,803 and 173,585 individuals from the UKB and GHS cohorts, respectively, to generate large callsets of CHIP carrier status ( Methods ). In brief, we called somatic mutations using Mutect2 in a pipeline that included custom QC filtering (Extended Data Fig. 1a ), and ultimately restricted our analysis to 23 well defined and recurrent CHIP-associated genes. This focused analysis identified 29,669 variants across 27,331 individuals in the UKB (6%), and 14,766 variants across 12,877 individuals in the GHS (7.4%). DNMT3A , TET2 , ASXL1 , PPM1D and TP53 were the most commonly mutated genes in both cohorts (Extended Data Fig. 2a ). Although the GHS cohort had a wider age range, and therefore a larger number of older individuals, the prevalence by age was similar across cohorts, and reached approximately 15% by 75 years of age (Extended Data Fig. 1b,c ). Prevalence of CHIP gene-specific mutations was consistent with recurrence patterns, with mutations in the most commonly mutated CHIP genes beginning to increase in prevalence at younger ages (Extended Data Fig. 1d,e and Supplementary Note 1 ). Somatic mutations within the IDH2 and SRSF2 genes co-occurred significantly more frequently than expected in both the UKB and GHS cohorts, whereas DNMT3A mutations co-occurred less frequently with other mutations than expected (Extended Data Fig. 2b,c and Supplementary Table 1 ). Among individuals with multiple CHIP mutations<|im_end|>
<|im_start|>assistant
A team of researchers at Regeneron Pharmaceuticals has identified new genomic variants associated with clonal hematopoiesis of indeterminate potential (CHIP). In their paper published in the journal Nature, the group describes how they used exome-wide and genome-wide association analyses to study differences in the blood of some people with somatic mutations. Nature has also published a Research Highlights piece in the same journal issue, discussing the work done by the New York team. Hematopoiesis is a process that results in the formation of cellular blood components. And clonal hematopoiesis is the part of the process that is involved in the development of cell lineages. The importance of the overall process is highlighted by the fact that every person produces approximately 300 billion new blood cells every single day of their life. Prior research has suggested that there are variants associated with clonal hematopoiesis of indeterminate potential in certain people—each of which can have a unique impact. In this new effort, the team at Regeneron sought to find some of them by studying information held in very large datasets, such as the UK Biobank and the Geisinger MyCode Community Health Initiative. To find the variants they were after, the researchers focused their search efforts on 23 genes that have already been associated with CHIP. By searching through data on 628,388 individuals, they were able to identify 40,208 carriers of at least one variant associated with CHIP. They then conducted exome-wide and genome-wide studies of the carriers they had identified. In so doing, they were able to identify 24 loci—21 of which had not been seen before. The researchers also found that they were able to identify some variants that could be associated with clonal hematopoiesis and the length of telomeres in certain individuals. In another part of their study, the team analyzed health traits of people listed in the UK Biobank looking for associations between people who had CHIP variants and other issues. In so doing, they found associations between people who had clonal hematopoiesis variants and diseases such as COVID-19, heart problems, obesity and problems clearing infections of various types. They also found associations between individuals with CHIP and development of cancerous tumors and myeloid leukemias. <|im_end|>
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[
{
"content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it",
"role": "system"
},
{
"content": "Abstract The COVID-19 pandemic triggered a surge in demand for facemasks to protect against disease transmission. In response to shortages, many public health authorities have recommended homemade masks as acceptable alternatives to surgical masks and N95 respirators. Although mask wearing is intended, in part, to protect others from exhaled, virus-containing particles, few studies have examined particle emission by mask-wearers into the surrounding air. Here, we measured outward emissions of micron-scale aerosol particles by healthy humans performing various expiratory activities while wearing different types of medical-grade or homemade masks. Both surgical masks and unvented KN95 respirators, even without fit-testing, reduce the outward particle emission rates by 90% and 74% on average during speaking and coughing, respectively, compared to wearing no mask, corroborating their effectiveness at reducing outward emission. These masks similarly decreased the outward particle emission of a coughing superemitter, who for unclear reasons emitted up to two orders of magnitude more expiratory particles via coughing than average. In contrast, shedding of non-expiratory micron-scale particulates from friable cellulosic fibers in homemade cotton-fabric masks confounded explicit determination of their efficacy at reducing expiratory particle emission. Audio analysis of the speech and coughing intensity confirmed that people speak more loudly, but do not cough more loudly, when wearing a mask. Further work is needed to establish the efficacy of cloth masks at blocking expiratory particles for speech and coughing at varied intensity and to assess whether virus-contaminated fabrics can generate aerosolized fomites, but the results strongly corroborate the efficacy of medical-grade masks and highlight the importance of regular washing of homemade masks. Introduction Airborne transmission of infectious respiratory diseases involves the emission of microorganism-containing aerosols and droplets during various expiratory activities (e.g., breathing, talking, coughing, and sneezing). Transmission of viruses in emitted droplets and aerosols to susceptible individuals may occur via physical contact after deposition on surfaces, reaerosolization after deposition, direct deposition of emitted droplets on mucosal surfaces (e.g., mouth, eyes), or direct inhalation of virus-laden aerosols 1 , 2 . Uncertainty remains regarding the role and spatial scale of these different transmission modes (contact, droplet spray, or aerosol inhalation) for specific respiratory diseases, including for COVID-19 3 , 4 , 5 , 6 , 7 , in particular settings, but airborne transmission stems from the initial expiratory emission of aerosols or droplets. Consequently, the wearing of masks—in addition to vigilant hand hygiene—has been put forth as a means to mitigate disease transmission, especially in healthcare settings 8 , 9 , 10 , 11 . Much research has indicated that masks can provide significant protection to the wearer, although proper mask fitting is critical to realizing such benefits 12 , 13 , 14 , 15 . Alternatively, masks can potentially reduce outward transmission by infected individuals, providing protection to others 7 , 16 , 17 . There have been indications of asymptomatic carriers of COVID-19 infecting others 18 , 19 , 20 , leading to increasing, albeit inconsistent 21 , 22 , 23 , 24 , calls for more universal wearing of masks or face coverings by the general public to help control disease transmission during pandemics. It is therefore important to understand the efficacy of masks and face coverings of different types in reducing outward transmission of aerosols and droplets from expiratory activities. Results from epidemiological and clinical studies assessing the effectiveness of masks in reducing disease transmission suggest that mask wearing can provide some benefits 10 , 11 , especially with early interventions, but often the results lack statistical significance 25 , 26 , 27 , 28 , 29 , 30 , 31 . Laboratory studies provide another means to assess or infer mask effectiveness. Measurement of material filtration efficiencies can provide initial guidance on potential mask effectiveness for preventing outward transmission 15 , 32 , 33 , 34 , 35 , but do not directly address mask performance when worn. Early photographic evidence indicates masks can limit the spread of cough-generated particles 36 . Measurements using simulated breathing with an artificial test head showed the concentration of particles between 0.02 μm-1 μm decreases across masks of different types 37 . Also using simulated breathing, Green et al. 38 found surgical masks effectively reduced outward transmission of endospores and vegetative cells, with seemingly greater reduction of particles > 0.7 μm compared to smaller particles. Using volunteers, Davies et al. 32 found that surgical and home-made cotton masks substantially reduce emission of culturable microorganisms from coughing by healthy volunteers, with similar reduction observed over a range of particle sizes (from 0.65 μm to > 7 μm). Milton et al. 16 found that surgical masks substantially reduced viral copy numbers in exhaled “fine” aerosol (≤ 5 μm) and “coarse” droplets (> 5 μm) from volunteers having influenza, with greater reduction in the coarse fraction. This result differs somewhat from very recent measurements by Leung et al. 13 , who showed a statistically significant reduction in shedding of influenza from breathing in coarse but not fine particles with participants wearing surgical masks. They did, however, find that masks reduced shedding of seasonal coronavirus from breathing for both coarse and fine particles, although viral RNA was observed in less than half of the samples even with no mask, complicating the assessment. The above studies all indicate a strong potential for masks to help reduce transmission of respiratory illnesses. To date, however, none have investigated the effectiveness of masks across a range of expiratory activities, and limited consideration has been given to different mask types. Furthermore, no studies to date have considered the masks themselves as potential sources of aerosol particles. It is well established that fibrous cellulosic materials, like cotton and paper, can release large quantities of micron-scale particles (i.e., dust) into the air 39 , 40 , 41 , 42 . Traditionally, these particles have not been considered a potential concern for respiratory viral diseases like influenza or now COVID-19, since these diseases have been thought to be transmitted via expiratory particles emitted directly from the respiratory tract of infected individuals 43 . Early",
"role": "user"
},
{
"content": "Laboratory tests of surgical and N95 masks by researchers at the University of California, Davis, show that they do cut down the amount of aerosolized particles emitted during breathing, talking and coughing. Tests of homemade cloth face coverings, however, show that the fabric itself releases a large amount of fibers into the air, underscoring the importance of washing them. The work is published today (Sept. 24) in Scientific Reports. As the COVID-19 pandemic continues, the use of masks and other face coverings has emerged as an important tool alongside contact tracing and isolation, hand-washing and social distancing to reduce the spread of coronavirus. The Centers for Disease Control and Prevention, or CDC, and the World Health Organization endorse the use of face coverings, and masks or face coverings are required by many state and local governments, including the state of California. The goal of wearing face coverings is to prevent people who are infected with COVID-19 but asymptomatic from transmitting the virus to others. But while evidence shows that face coverings generally reduce the spread of airborne particles, there is limited information on how well they compare with each other. Sima Asadi, a graduate student working with Professor William Ristenpart in the UC Davis Department of Chemical Engineering, and colleagues at UC Davis and Icahn School of Medicine at Mount Sinai, New York, set up experiments to measure the flow of particles from volunteers wearing masks while they performed \"expiratory activities\" including breathing, talking, coughing and moving their jaw as if chewing gum. Asadi and Ristenpart have previously studied how people emit small particles, or aerosols, during speech. These particles are small enough to float through the air over a considerable distance, but large enough to carry viruses such as influenza or coronavirus. They have found that a fraction of people are \"superemitters\" who give off many more particles than average. The 10 volunteers sat in front of a funnel in a laminar flow cabinet. The funnel drew air from in front of their faces into a device that measured the size and number of particles exhaled. They wore either no mask, a medical-grade surgical mask, two types of N95 mask (vented or not), a homemade paper mask or homemade one- or two-layer cloth mask made from a cotton T-shirt according to CDC directions. Credit: UC Davis Up to 90 percent of particles blocked The tests only measured outward transmission—whether the masks could block an infected person from giving off particles that might carry viruses. Without a mask, talking (reading a passage of text) gave off about 10 times more particles than simple breathing. Forced coughing produced a variable amount of particles. One of the volunteers in the study was a superemitter who consistently produced nearly 100 times as many particles as the others when coughing. In all the test scenarios, surgical and N95 masks blocked as much as 90 percent of particles, compared to not wearing a mask. Face coverings also reduced airborne particles from the superemitter. Homemade cotton masks actually produced more particles than not wearing a mask. These appeared to be tiny fibers released from the fabric. Because the cotton masks produced particles themselves, it's difficult to tell if they also blocked exhaled particles. They did seem to at least reduce the number of larger particles. The results confirm that masks and face coverings are effective in reducing the spread of airborne particles, Ristenpart said, and also the importance of regularly washing cloth masks. ",
"role": "assistant"
}
] | <|im_start|>system
You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|>
<|im_start|>user
Abstract The COVID-19 pandemic triggered a surge in demand for facemasks to protect against disease transmission. In response to shortages, many public health authorities have recommended homemade masks as acceptable alternatives to surgical masks and N95 respirators. Although mask wearing is intended, in part, to protect others from exhaled, virus-containing particles, few studies have examined particle emission by mask-wearers into the surrounding air. Here, we measured outward emissions of micron-scale aerosol particles by healthy humans performing various expiratory activities while wearing different types of medical-grade or homemade masks. Both surgical masks and unvented KN95 respirators, even without fit-testing, reduce the outward particle emission rates by 90% and 74% on average during speaking and coughing, respectively, compared to wearing no mask, corroborating their effectiveness at reducing outward emission. These masks similarly decreased the outward particle emission of a coughing superemitter, who for unclear reasons emitted up to two orders of magnitude more expiratory particles via coughing than average. In contrast, shedding of non-expiratory micron-scale particulates from friable cellulosic fibers in homemade cotton-fabric masks confounded explicit determination of their efficacy at reducing expiratory particle emission. Audio analysis of the speech and coughing intensity confirmed that people speak more loudly, but do not cough more loudly, when wearing a mask. Further work is needed to establish the efficacy of cloth masks at blocking expiratory particles for speech and coughing at varied intensity and to assess whether virus-contaminated fabrics can generate aerosolized fomites, but the results strongly corroborate the efficacy of medical-grade masks and highlight the importance of regular washing of homemade masks. Introduction Airborne transmission of infectious respiratory diseases involves the emission of microorganism-containing aerosols and droplets during various expiratory activities (e.g., breathing, talking, coughing, and sneezing). Transmission of viruses in emitted droplets and aerosols to susceptible individuals may occur via physical contact after deposition on surfaces, reaerosolization after deposition, direct deposition of emitted droplets on mucosal surfaces (e.g., mouth, eyes), or direct inhalation of virus-laden aerosols 1 , 2 . Uncertainty remains regarding the role and spatial scale of these different transmission modes (contact, droplet spray, or aerosol inhalation) for specific respiratory diseases, including for COVID-19 3 , 4 , 5 , 6 , 7 , in particular settings, but airborne transmission stems from the initial expiratory emission of aerosols or droplets. Consequently, the wearing of masks—in addition to vigilant hand hygiene—has been put forth as a means to mitigate disease transmission, especially in healthcare settings 8 , 9 , 10 , 11 . Much research has indicated that masks can provide significant protection to the wearer, although proper mask fitting is critical to realizing such benefits 12 , 13 , 14 , 15 . Alternatively, masks can potentially reduce outward transmission by infected individuals, providing protection to others 7 , 16 , 17 . There have been indications of asymptomatic carriers of COVID-19 infecting others 18 , 19 , 20 , leading to increasing, albeit inconsistent 21 , 22 , 23 , 24 , calls for more universal wearing of masks or face coverings by the general public to help control disease transmission during pandemics. It is therefore important to understand the efficacy of masks and face coverings of different types in reducing outward transmission of aerosols and droplets from expiratory activities. Results from epidemiological and clinical studies assessing the effectiveness of masks in reducing disease transmission suggest that mask wearing can provide some benefits 10 , 11 , especially with early interventions, but often the results lack statistical significance 25 , 26 , 27 , 28 , 29 , 30 , 31 . Laboratory studies provide another means to assess or infer mask effectiveness. Measurement of material filtration efficiencies can provide initial guidance on potential mask effectiveness for preventing outward transmission 15 , 32 , 33 , 34 , 35 , but do not directly address mask performance when worn. Early photographic evidence indicates masks can limit the spread of cough-generated particles 36 . Measurements using simulated breathing with an artificial test head showed the concentration of particles between 0.02 μm-1 μm decreases across masks of different types 37 . Also using simulated breathing, Green et al. 38 found surgical masks effectively reduced outward transmission of endospores and vegetative cells, with seemingly greater reduction of particles > 0.7 μm compared to smaller particles. Using volunteers, Davies et al. 32 found that surgical and home-made cotton masks substantially reduce emission of culturable microorganisms from coughing by healthy volunteers, with similar reduction observed over a range of particle sizes (from 0.65 μm to > 7 μm). Milton et al. 16 found that surgical masks substantially reduced viral copy numbers in exhaled “fine” aerosol (≤ 5 μm) and “coarse” droplets (> 5 μm) from volunteers having influenza, with greater reduction in the coarse fraction. This result differs somewhat from very recent measurements by Leung et al. 13 , who showed a statistically significant reduction in shedding of influenza from breathing in coarse but not fine particles with participants wearing surgical masks. They did, however, find that masks reduced shedding of seasonal coronavirus from breathing for both coarse and fine particles, although viral RNA was observed in less than half of the samples even with no mask, complicating the assessment. The above studies all indicate a strong potential for masks to help reduce transmission of respiratory illnesses. To date, however, none have investigated the effectiveness of masks across a range of expiratory activities, and limited consideration has been given to different mask types. Furthermore, no studies to date have considered the masks themselves as potential sources of aerosol particles. It is well established that fibrous cellulosic materials, like cotton and paper, can release large quantities of micron-scale particles (i.e., dust) into the air 39 , 40 , 41 , 42 . Traditionally, these particles have not been considered a potential concern for respiratory viral diseases like influenza or now COVID-19, since these diseases have been thought to be transmitted via expiratory particles emitted directly from the respiratory tract of infected individuals 43 . Early<|im_end|>
<|im_start|>assistant
Laboratory tests of surgical and N95 masks by researchers at the University of California, Davis, show that they do cut down the amount of aerosolized particles emitted during breathing, talking and coughing. Tests of homemade cloth face coverings, however, show that the fabric itself releases a large amount of fibers into the air, underscoring the importance of washing them. The work is published today (Sept. 24) in Scientific Reports. As the COVID-19 pandemic continues, the use of masks and other face coverings has emerged as an important tool alongside contact tracing and isolation, hand-washing and social distancing to reduce the spread of coronavirus. The Centers for Disease Control and Prevention, or CDC, and the World Health Organization endorse the use of face coverings, and masks or face coverings are required by many state and local governments, including the state of California. The goal of wearing face coverings is to prevent people who are infected with COVID-19 but asymptomatic from transmitting the virus to others. But while evidence shows that face coverings generally reduce the spread of airborne particles, there is limited information on how well they compare with each other. Sima Asadi, a graduate student working with Professor William Ristenpart in the UC Davis Department of Chemical Engineering, and colleagues at UC Davis and Icahn School of Medicine at Mount Sinai, New York, set up experiments to measure the flow of particles from volunteers wearing masks while they performed "expiratory activities" including breathing, talking, coughing and moving their jaw as if chewing gum. Asadi and Ristenpart have previously studied how people emit small particles, or aerosols, during speech. These particles are small enough to float through the air over a considerable distance, but large enough to carry viruses such as influenza or coronavirus. They have found that a fraction of people are "superemitters" who give off many more particles than average. The 10 volunteers sat in front of a funnel in a laminar flow cabinet. The funnel drew air from in front of their faces into a device that measured the size and number of particles exhaled. They wore either no mask, a medical-grade surgical mask, two types of N95 mask (vented or not), a homemade paper mask or homemade one- or two-layer cloth mask made from a cotton T-shirt according to CDC directions. Credit: UC Davis Up to 90 percent of particles blocked The tests only measured outward transmission—whether the masks could block an infected person from giving off particles that might carry viruses. Without a mask, talking (reading a passage of text) gave off about 10 times more particles than simple breathing. Forced coughing produced a variable amount of particles. One of the volunteers in the study was a superemitter who consistently produced nearly 100 times as many particles as the others when coughing. In all the test scenarios, surgical and N95 masks blocked as much as 90 percent of particles, compared to not wearing a mask. Face coverings also reduced airborne particles from the superemitter. Homemade cotton masks actually produced more particles than not wearing a mask. These appeared to be tiny fibers released from the fabric. Because the cotton masks produced particles themselves, it's difficult to tell if they also blocked exhaled particles. They did seem to at least reduce the number of larger particles. The results confirm that masks and face coverings are effective in reducing the spread of airborne particles, Ristenpart said, and also the importance of regularly washing cloth masks. <|im_end|>
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] | 2,049 |
[
{
"content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it",
"role": "system"
},
{
"content": "Abstract The inertial sliding of physisorbed submonolayer islands on crystal surfaces contains unexpected information on the exceptionally smooth sliding state associated with incommensurate superlubricity and on the mechanisms of its disappearance. Here, in a joint quartz crystal microbalance and molecular dynamics simulation case study of Xe on Cu(111), we show how superlubricity emerges in the large size limit of naturally incommensurate Xe islands. As coverage approaches a full monolayer, theory also predicts an abrupt adhesion-driven two-dimensional density compression on the order of several per cent, implying a hysteretic jump from superlubric free islands to a pressurized commensurate immobile monolayer. This scenario is fully supported by the quartz crystal microbalance data, which show remarkably large slip times with increasing submonolayer coverage, signalling superlubricity, followed by a dramatic drop to zero for the dense commensurate monolayer. Careful analysis of this variety of island sliding phenomena will be essential in future applications of friction at crystal/adsorbate interfaces. Main Systems achieving low values of dry sliding friction are of great physical and, potentially, technological interest 1 , 2 , 3 , 4 . Superlubricity—the vanishing of static friction—and the consequent ultra-low dynamic friction between crystal faces that are sufficiently hard and mutually incommensurate 5 , 6 , is experimentally rare and has been demonstrated or implied in only a relatively small number of cases, including telescopic sliding among carbon nanotubes 7 , 8 , sliding graphite flakes on a graphite substrate 9 , 10 , 11 , cluster nanomanipulation 12 , 13 and sliding colloidal layers 14 , 15 . It is essential that we increase the understanding of this phenomenon and, in view of potential nanotechnology applications, examine new and more generic systems beyond these. Submonolayer islands of rare gas atoms adsorbed on crystal surfaces offer an excellent platform to address friction at crystalline interfaces. Despite much experimental 16 , 17 , 18 , 19 , 20 , 21 , 22 and theoretical 23 , 24 , 25 , 26 , 27 work, superlubricity is a phenomenon that remains poorly explored in such systems. In the submonolayer range (0 < θ < 1, where θ is the coverage) and at low temperatures, adsorbate phase diagrams versus coverage θ are well known to display phase-separated two-dimensional (2D) solid islands, usually incommensurate with the surface lattice, coexisting with the 2D adatom vapour 28 , 29 . Using a quartz crystal microbalance (QCM), the inertial sliding friction of these islands is measured by the inverse of the slip time τ s = (1/4π)[δ( Q −1 )/δ f ], the ratio of the adsorbate-induced change in inverse quality factor over the respective change in the substrate oscillation frequency 30 . The peak of the inertial force acting on an island deposited on the QCM is expressed as F in = ρ isl SA (2π f ) 2 (where ρ isl is the 2D density at the centre of an adsorbed island of area S , and A and f are the oscillation amplitude and frequency, respectively), and equals the viscous frictional force F visc = Mv / τ s, (where M is the mass of the island and v is speed). This means that superlubricity should indirectly show up as an unusually large slip time. For over two decades, QCM work has shown that physisorbed atoms or molecules condense and generally slide above a submonolayer coverage θ sf , and τ s may typically reach values from hundreds of picoseconds to a nanosecond. These results 17 , 19 , 30 and the corresponding pioneering atomistic simulations 23 , 31 have provided much valuable initial information about the temperature and system dependence of inertial friction. So far, however, crucial aspects that specifically address the island structure of the adsorbate, the edge-originated pinning and in particular the change in commensurability and superlubricity with coverage (issues that, in our view, are important to nanofriction) have not yet come under scrutiny. Here, we present a joint experimental and theoretical study of the sliding of adsorbate islands on a crystalline substrate, and reveal surprising information about the exceptionally easy sliding suggestive of superlubricity, about its limiting factors (caused by edges and defects), and its eventual spontaneous demise at full coverage. Our chosen example is physisorbed Xe on Cu(111), a system for which the phase diagram is well studied (as is the case for other rare gas adsorbates on graphite and metal surfaces) 28 . Between ∼ 50 and 90 K, Xe monolayers condense on Cu(111) as a commensurate 2D solid. We conventionally designate this as unit coverage θ = 1, characterized by a density where is the commensurate adatom spacing. Low-energy electron diffraction at 50 K locates the Xe atoms on top of surface Cu atoms 32 , the planar distance ( a 0 ) of which is close to the Xe–Xe spacing in bulk Xe ( a Xe = 0.439 nm). At lower temperatures, the full Xe monolayer is known from surface extended X-ray measurements to shrink into an ‘overdense’ ( ρ > ρ 0 ) incommensurate structure, reaching commensurability only at 50 K following thermal expansion 33 . Conversely, the 2D atom density in Xe monatomic islands, which coexist with the adatom 2D vapour at submonolayer coverage, is not specifically known, but is often assumed to be equal to ρ 0 . Our results in fact show that the 2D crystalline Xe islands ( θ < 1) are slightly ‘underdense’ ( ρ isl < ρ 0 ) and increasingly incommensurate with thermal expansion, reaching a 2D density 4% below ρ 0 near 50 K. In this incommensurate state, the 2D lattice inside the Xe islands should slide superlubrically over the Cu(111) substrate, as expected for a ‘hard’ slider. Indeed, even though the Xe–Xe attraction V Xe−Xe ≈ 20 meV is an order of magnitude smaller than the Xe–Cu(111) adhesion energy E a ≈ 190 meV (ref. 28 ), it is an order of magnitude larger, and thus harder, than the weak Cu(111) surface corrugation, E c ≈ 1–2 meV (ref.",
"role": "user"
},
{
"content": "It's possible to vary (even dramatically) the sliding properties of atoms on a surface by changing the size and \"compression\" of their aggregates: an experimental and theoretical study conducted with the collaboration of SISSA, the Istituto Officina dei Materiali of the CNR (Iom-Cnr-Democritos), ICTP in Trieste, the University of Padua, the University of Modena e Reggio Emilia, and the Istituto Nanoscienze of the CNR (Nano-Cnr) in Modena, has just been published in Nature Nanotechnology. (Nano)islands that slide freely on a sea of copper, but when they become too large (and too dense) they end up getting stuck: that nicely sums up the system investigated in a study just published in Nature Nanotechnology. \"We can suddenly switch from a state of superlubricity to one of extremely high friction by varying some parameters of the system being investigated. In this study, we used atoms of the noble gas xenon bound to one another to form two-dimensional islands, deposited on a copper surface (Cu 111). At low temperatures these aggregates slide with virtually no friction,\" explains Giampaolo Mistura of the University of Padua. \"We increased the size of the islands by adding xenon atoms and until the whole available surface was covered the friction decreased gradually. Instead, when the available space ran out and the addition of atoms caused the islands to compress, then we saw an exceptional increase in friction.\" The study was divided into an experimental part (mainly carried out by the University of Padua and Nano-Cnr/University of Modena and Reggio Emilia) and a theoretical part (based on computer models and simulations) conducted by SISSA/Iom-Cnr-Democritos/ICTP. \"To understand what happens when the islands are compressed, we need to appreciate the concept of 'interface commensurability',\" explains Roberto Guerra, researcher at the International School for Advanced Studies (SISSA) in Trieste and among the authors of the study. \"We can think of the system we studied as one made up of Lego bricks. The copper substrate is like a horizontal assembly of bricks and the xenon islands like single loose bricks,\" comments Guido Paolicelli of the CNR Nanoscience Institute. \"If the substrate and the islands consist of different bricks (in terms of width and distance between the studs), the islands will never get stuck on the substrate. This situation reproduces our system at temperatures slightly above absolute zero where we observe a state of superlubricity with virtually no friction. However, the increase in surface of the islands and the resulting compression of the material causes the islands to become commensurate to the substrate – like Lego bricks having the same pitch – and when that happens they suddenly get stuck.\" sample of crystalline copper used as a ‘sliding’ substrate. Credit: Nano-Cnr, Modena The study is the first to demonstrate that it is possible to dramatically vary the sliding properties of nano-objects. \"We can imagine a number of applications for this,\" concludes Guerra. \"For example, nanobearings could be developed that, under certain conditions, are capable of blocking their motion, in a completely reversible manner.\" ",
"role": "assistant"
}
] | <|im_start|>system
You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|>
<|im_start|>user
Abstract The inertial sliding of physisorbed submonolayer islands on crystal surfaces contains unexpected information on the exceptionally smooth sliding state associated with incommensurate superlubricity and on the mechanisms of its disappearance. Here, in a joint quartz crystal microbalance and molecular dynamics simulation case study of Xe on Cu(111), we show how superlubricity emerges in the large size limit of naturally incommensurate Xe islands. As coverage approaches a full monolayer, theory also predicts an abrupt adhesion-driven two-dimensional density compression on the order of several per cent, implying a hysteretic jump from superlubric free islands to a pressurized commensurate immobile monolayer. This scenario is fully supported by the quartz crystal microbalance data, which show remarkably large slip times with increasing submonolayer coverage, signalling superlubricity, followed by a dramatic drop to zero for the dense commensurate monolayer. Careful analysis of this variety of island sliding phenomena will be essential in future applications of friction at crystal/adsorbate interfaces. Main Systems achieving low values of dry sliding friction are of great physical and, potentially, technological interest 1 , 2 , 3 , 4 . Superlubricity—the vanishing of static friction—and the consequent ultra-low dynamic friction between crystal faces that are sufficiently hard and mutually incommensurate 5 , 6 , is experimentally rare and has been demonstrated or implied in only a relatively small number of cases, including telescopic sliding among carbon nanotubes 7 , 8 , sliding graphite flakes on a graphite substrate 9 , 10 , 11 , cluster nanomanipulation 12 , 13 and sliding colloidal layers 14 , 15 . It is essential that we increase the understanding of this phenomenon and, in view of potential nanotechnology applications, examine new and more generic systems beyond these. Submonolayer islands of rare gas atoms adsorbed on crystal surfaces offer an excellent platform to address friction at crystalline interfaces. Despite much experimental 16 , 17 , 18 , 19 , 20 , 21 , 22 and theoretical 23 , 24 , 25 , 26 , 27 work, superlubricity is a phenomenon that remains poorly explored in such systems. In the submonolayer range (0 < θ < 1, where θ is the coverage) and at low temperatures, adsorbate phase diagrams versus coverage θ are well known to display phase-separated two-dimensional (2D) solid islands, usually incommensurate with the surface lattice, coexisting with the 2D adatom vapour 28 , 29 . Using a quartz crystal microbalance (QCM), the inertial sliding friction of these islands is measured by the inverse of the slip time τ s = (1/4π)[δ( Q −1 )/δ f ], the ratio of the adsorbate-induced change in inverse quality factor over the respective change in the substrate oscillation frequency 30 . The peak of the inertial force acting on an island deposited on the QCM is expressed as F in = ρ isl SA (2π f ) 2 (where ρ isl is the 2D density at the centre of an adsorbed island of area S , and A and f are the oscillation amplitude and frequency, respectively), and equals the viscous frictional force F visc = Mv / τ s, (where M is the mass of the island and v is speed). This means that superlubricity should indirectly show up as an unusually large slip time. For over two decades, QCM work has shown that physisorbed atoms or molecules condense and generally slide above a submonolayer coverage θ sf , and τ s may typically reach values from hundreds of picoseconds to a nanosecond. These results 17 , 19 , 30 and the corresponding pioneering atomistic simulations 23 , 31 have provided much valuable initial information about the temperature and system dependence of inertial friction. So far, however, crucial aspects that specifically address the island structure of the adsorbate, the edge-originated pinning and in particular the change in commensurability and superlubricity with coverage (issues that, in our view, are important to nanofriction) have not yet come under scrutiny. Here, we present a joint experimental and theoretical study of the sliding of adsorbate islands on a crystalline substrate, and reveal surprising information about the exceptionally easy sliding suggestive of superlubricity, about its limiting factors (caused by edges and defects), and its eventual spontaneous demise at full coverage. Our chosen example is physisorbed Xe on Cu(111), a system for which the phase diagram is well studied (as is the case for other rare gas adsorbates on graphite and metal surfaces) 28 . Between ∼ 50 and 90 K, Xe monolayers condense on Cu(111) as a commensurate 2D solid. We conventionally designate this as unit coverage θ = 1, characterized by a density where is the commensurate adatom spacing. Low-energy electron diffraction at 50 K locates the Xe atoms on top of surface Cu atoms 32 , the planar distance ( a 0 ) of which is close to the Xe–Xe spacing in bulk Xe ( a Xe = 0.439 nm). At lower temperatures, the full Xe monolayer is known from surface extended X-ray measurements to shrink into an ‘overdense’ ( ρ > ρ 0 ) incommensurate structure, reaching commensurability only at 50 K following thermal expansion 33 . Conversely, the 2D atom density in Xe monatomic islands, which coexist with the adatom 2D vapour at submonolayer coverage, is not specifically known, but is often assumed to be equal to ρ 0 . Our results in fact show that the 2D crystalline Xe islands ( θ < 1) are slightly ‘underdense’ ( ρ isl < ρ 0 ) and increasingly incommensurate with thermal expansion, reaching a 2D density 4% below ρ 0 near 50 K. In this incommensurate state, the 2D lattice inside the Xe islands should slide superlubrically over the Cu(111) substrate, as expected for a ‘hard’ slider. Indeed, even though the Xe–Xe attraction V Xe−Xe ≈ 20 meV is an order of magnitude smaller than the Xe–Cu(111) adhesion energy E a ≈ 190 meV (ref. 28 ), it is an order of magnitude larger, and thus harder, than the weak Cu(111) surface corrugation, E c ≈ 1–2 meV (ref.<|im_end|>
<|im_start|>assistant
It's possible to vary (even dramatically) the sliding properties of atoms on a surface by changing the size and "compression" of their aggregates: an experimental and theoretical study conducted with the collaboration of SISSA, the Istituto Officina dei Materiali of the CNR (Iom-Cnr-Democritos), ICTP in Trieste, the University of Padua, the University of Modena e Reggio Emilia, and the Istituto Nanoscienze of the CNR (Nano-Cnr) in Modena, has just been published in Nature Nanotechnology. (Nano)islands that slide freely on a sea of copper, but when they become too large (and too dense) they end up getting stuck: that nicely sums up the system investigated in a study just published in Nature Nanotechnology. "We can suddenly switch from a state of superlubricity to one of extremely high friction by varying some parameters of the system being investigated. In this study, we used atoms of the noble gas xenon bound to one another to form two-dimensional islands, deposited on a copper surface (Cu 111). At low temperatures these aggregates slide with virtually no friction," explains Giampaolo Mistura of the University of Padua. "We increased the size of the islands by adding xenon atoms and until the whole available surface was covered the friction decreased gradually. Instead, when the available space ran out and the addition of atoms caused the islands to compress, then we saw an exceptional increase in friction." The study was divided into an experimental part (mainly carried out by the University of Padua and Nano-Cnr/University of Modena and Reggio Emilia) and a theoretical part (based on computer models and simulations) conducted by SISSA/Iom-Cnr-Democritos/ICTP. "To understand what happens when the islands are compressed, we need to appreciate the concept of 'interface commensurability'," explains Roberto Guerra, researcher at the International School for Advanced Studies (SISSA) in Trieste and among the authors of the study. "We can think of the system we studied as one made up of Lego bricks. The copper substrate is like a horizontal assembly of bricks and the xenon islands like single loose bricks," comments Guido Paolicelli of the CNR Nanoscience Institute. "If the substrate and the islands consist of different bricks (in terms of width and distance between the studs), the islands will never get stuck on the substrate. This situation reproduces our system at temperatures slightly above absolute zero where we observe a state of superlubricity with virtually no friction. However, the increase in surface of the islands and the resulting compression of the material causes the islands to become commensurate to the substrate – like Lego bricks having the same pitch – and when that happens they suddenly get stuck." sample of crystalline copper used as a ‘sliding’ substrate. Credit: Nano-Cnr, Modena The study is the first to demonstrate that it is possible to dramatically vary the sliding properties of nano-objects. "We can imagine a number of applications for this," concludes Guerra. "For example, nanobearings could be developed that, under certain conditions, are capable of blocking their motion, in a completely reversible manner." <|im_end|>
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[
{
"content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it",
"role": "system"
},
{
"content": "Abstract Objective To evaluate if induction of labour at 41 weeks improves perinatal and maternal outcomes in women with a low risk pregnancy compared with expectant management and induction of labour at 42 weeks. Design Multicentre, open label, randomised controlled superiority trial. Setting 14 hospitals in Sweden, 2016-18. Participants 2760 women with a low risk uncomplicated singleton pregnancy randomised (1:1) by the Swedish Pregnancy Register. 1381 women were assigned to the induction group and 1379 were assigned to the expectant management group. Interventions Induction of labour at 41 weeks and expectant management and induction of labour at 42 weeks. Main outcome measures The primary outcome was a composite perinatal outcome including one or more of stillbirth, neonatal mortality, Apgar score less than 7 at five minutes, pH less than 7.00 or metabolic acidosis (pH <7.05 and base deficit >12 mmol/L) in the umbilical artery, hypoxic ischaemic encephalopathy, intracranial haemorrhage, convulsions, meconium aspiration syndrome, mechanical ventilation within 72 hours, or obstetric brachial plexus injury. Primary analysis was by intention to treat. Results The study was stopped early owing to a significantly higher rate of perinatal mortality in the expectant management group. The composite primary perinatal outcome did not differ between the groups: 2.4% (33/1381) in the induction group and 2.2% (31/1379) in the expectant management group (relative risk 1.06, 95% confidence interval 0.65 to 1.73; P=0.90). No perinatal deaths occurred in the induction group but six (five stillbirths and one early neonatal death) occurred in the expectant management group (P=0.03). The proportion of caesarean delivery, instrumental vaginal delivery, or any major maternal morbidity did not differ between the groups. Conclusions This study comparing induction of labour at 41 weeks with expectant management and induction at 42 weeks does not show any significant difference in the primary composite adverse perinatal outcome. However, a reduction of the secondary outcome perinatal mortality is observed without increasing adverse maternal outcomes. Although these results should be interpreted cautiously, induction of labour ought to be offered to women no later than at 41 weeks and could be one (of few) interventions that reduces the rate of stillbirths. Trial registration Current Controlled Trials ISRCTN26113652 . Introduction Adverse perinatal outcomes gradually increase after 40 gestational weeks and are substantially increased post-term (≥42 weeks (≥294 days)). 1 2 The risk of stillbirth has been shown to increase after term, 1 2 3 4 5 and worldwide as much as 14% of stillbirths are associated with prolonged pregnancy. 2 Furthermore, maternal complications also increase with duration of pregnancy after 40 weeks. 1 To date, no agreement exists on how to manage late term (41 weeks+0 days to 42 weeks+0 days) pregnancies. The World Health Organization recommends induction of labour at 41 weeks, 6 and many countries offer induction of labour between 41 and 42 weeks to avoid prolonged pregnancy. 7 8 Randomised controlled trials have compared induction of labour with expectant management in prolonged pregnancies, most with inconclusive results for perinatal mortality and major morbidity. 9 The results from the latest Cochrane review (2018) showed lower rates of caesarean delivery and perinatal death but a higher rate of operative vaginal delivery in the induction group compared with the expectant management group. 9 After the latest Cochrane review and after the initiation of the present study, 10 two large randomised controlled trials examining low risk pregnancies have been published. A large trial from the United States, ARRIVE (A Randomized Trial of Induction Versus Expectant Management), compared induction of labour in nulliparous women at 39 weeks+0 days to 39 weeks+4 days with expectant management until 41 weeks+0 days. 11 No significant difference was found in perinatal outcome between groups, whereas the frequency of caesarean delivery was significantly lower in the early induction group. Another large recent trial from the Netherlands, INDEX (INDuction of labour at 41 weeks with a policy of EXpectant management until 42 weeks), compared induction of labour at 41 weeks+0 days to 41 weeks+1 day with expectant management until 42 weeks+0 days. 12 The results could not confirm non-inferiority for adverse perinatal outcome of expectant management, instead a significantly higher risk of adverse perinatal outcome was found in the expectant management group. No significant difference in the rate of caesarean delivery was found. The current practice in many centres in the United Kingdom and Scandinavia is to induce delivery no later than 42 weeks, but several studies suggest that the risk of perinatal mortality and morbidity has actually already increased significantly at 41 weeks. 3 4 5 The risk of stillbirth increases gradually from 39 weeks of gestation 13 and increases exponentially as the pregnancy approaches 42 weeks, 3-5 13 whereas the risk of neonatal mortality is not increased until 42 weeks according to most studies. 3-5 13 We therefore found it clinically justified to compare induction of labour at 41 weeks with expectant management and induction at 42 weeks for maternal and perinatal outcomes. At the start of the present trial, only two studies (one was an abstract) out of 30 included in the Cochrane review specifically compared induction of labour at 41 weeks with expectant management until 42 weeks. 14 15 We evaluated if induction of labour at 41 weeks+0-2 days compared with expectant management and induction of labour at 42 weeks+0-1 days was superior in terms of perinatal outcome in healthy women with a low risk pregnancy. Methods Study design SWEPIS (SWEdish Post-term Induction Study) was a multicentre, open label, randomised controlled superiority trial conducted in Sweden from May 2016 to October 2018. The trial was register based, with randomisation and most data collection done by using the Swedish Pregnancy Register. 16 Fourteen hospitals with antenatal clinics linked to the register were involved in the trial. Five of the hospitals were university clinics and nine were county hospitals comprising about 60 000 deliveries per year of the around 115 000 to 120 000 annual deliveries in Sweden. The trial was conducted according to the CONSORT guidelines. The protocol is available online ( ) and as a publication.",
"role": "user"
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{
"content": "Inducing labour at 41 weeks in low risk pregnancies is associated with a lower risk of newborn death compared with expectant management (a \"wait and see\" approach) until 42 weeks, suggests a trial published by The BMJ. Although the overall risk of death at 42 weeks is low, the researchers say induction of labour should be offered to women no later than 41 full weeks. It is generally accepted that there is an increased risk of problems (\"adverse perinatal outcomes\") for both mother and baby at or beyond 42 weeks of pregnancy. Some studies have suggested that inducing labour from 41 weeks onwards improves these outcomes, but there is no international consensus on how to manage healthy pregnancies lasting more than 41 weeks. Current practice in the UK and Scandinavia is to induce delivery for all women who have not gone into labour by 42 weeks. So researchers in Sweden set out to compare induction of labour at 41 weeks with expectant management until 42 weeks in low risk pregnancies. The trial involved 2,760 women (average age 31 years) with an uncomplicated, single pregnancy recruited from 14 Swedish hospitals between 2016 and 2018. Women were randomly assigned to induction of labour at 41 weeks (1,381) or expectant management (1,379) until induction at 42 weeks if necessary. The main outcome was a combined measure of babies' health, including stillbirth or death in the first few days of life (known as perinatal death), Apgar score less than 7 at five minutes, low oxygen levels, and breathing problems. Other outcomes included admission to an intensive care baby unit, Apgar score less than 4 at five minutes, birth weight, pneumonia, or sepsis. Type of delivery and mothers' health just after giving birth were also assessed. For the main outcome measure, the researchers found no difference between the groups (2.4% of women in the induction group had an adverse perinatal outcome compared with 2.2% in the expectant management group). Other outcomes, such as caesarean sections and mothers' health after giving birth, also did not differ between the groups. However, six babies in the expectant management group died compared with none in the induction group, and the trial was stopped early. The researchers estimate that, for every 230 women induced at 41 weeks, one perinatal death would be prevented. They point to some limitations, such as differences in hospital policies and practices, that could have affected the results. But they say women with low risk pregnancies \"should be informed of the risk profile of induction of labour versus expectant management and offered induction of labour no later than at 41 full weeks. This could be one (of few) interventions that reduces stillbirth,\" they conclude. This view is supported in a linked editorial by Professor Sara Kenyon and colleagues, who say induction at 41 weeks \"looks like the safer option for women and their babies.\" They stress that choice is important within maternity care, and say \"clear information about available options should be accessible to all pregnant women, enabling them to make fully informed and timely decisions.\" ",
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}
] | <|im_start|>system
You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|>
<|im_start|>user
Abstract Objective To evaluate if induction of labour at 41 weeks improves perinatal and maternal outcomes in women with a low risk pregnancy compared with expectant management and induction of labour at 42 weeks. Design Multicentre, open label, randomised controlled superiority trial. Setting 14 hospitals in Sweden, 2016-18. Participants 2760 women with a low risk uncomplicated singleton pregnancy randomised (1:1) by the Swedish Pregnancy Register. 1381 women were assigned to the induction group and 1379 were assigned to the expectant management group. Interventions Induction of labour at 41 weeks and expectant management and induction of labour at 42 weeks. Main outcome measures The primary outcome was a composite perinatal outcome including one or more of stillbirth, neonatal mortality, Apgar score less than 7 at five minutes, pH less than 7.00 or metabolic acidosis (pH <7.05 and base deficit >12 mmol/L) in the umbilical artery, hypoxic ischaemic encephalopathy, intracranial haemorrhage, convulsions, meconium aspiration syndrome, mechanical ventilation within 72 hours, or obstetric brachial plexus injury. Primary analysis was by intention to treat. Results The study was stopped early owing to a significantly higher rate of perinatal mortality in the expectant management group. The composite primary perinatal outcome did not differ between the groups: 2.4% (33/1381) in the induction group and 2.2% (31/1379) in the expectant management group (relative risk 1.06, 95% confidence interval 0.65 to 1.73; P=0.90). No perinatal deaths occurred in the induction group but six (five stillbirths and one early neonatal death) occurred in the expectant management group (P=0.03). The proportion of caesarean delivery, instrumental vaginal delivery, or any major maternal morbidity did not differ between the groups. Conclusions This study comparing induction of labour at 41 weeks with expectant management and induction at 42 weeks does not show any significant difference in the primary composite adverse perinatal outcome. However, a reduction of the secondary outcome perinatal mortality is observed without increasing adverse maternal outcomes. Although these results should be interpreted cautiously, induction of labour ought to be offered to women no later than at 41 weeks and could be one (of few) interventions that reduces the rate of stillbirths. Trial registration Current Controlled Trials ISRCTN26113652 . Introduction Adverse perinatal outcomes gradually increase after 40 gestational weeks and are substantially increased post-term (≥42 weeks (≥294 days)). 1 2 The risk of stillbirth has been shown to increase after term, 1 2 3 4 5 and worldwide as much as 14% of stillbirths are associated with prolonged pregnancy. 2 Furthermore, maternal complications also increase with duration of pregnancy after 40 weeks. 1 To date, no agreement exists on how to manage late term (41 weeks+0 days to 42 weeks+0 days) pregnancies. The World Health Organization recommends induction of labour at 41 weeks, 6 and many countries offer induction of labour between 41 and 42 weeks to avoid prolonged pregnancy. 7 8 Randomised controlled trials have compared induction of labour with expectant management in prolonged pregnancies, most with inconclusive results for perinatal mortality and major morbidity. 9 The results from the latest Cochrane review (2018) showed lower rates of caesarean delivery and perinatal death but a higher rate of operative vaginal delivery in the induction group compared with the expectant management group. 9 After the latest Cochrane review and after the initiation of the present study, 10 two large randomised controlled trials examining low risk pregnancies have been published. A large trial from the United States, ARRIVE (A Randomized Trial of Induction Versus Expectant Management), compared induction of labour in nulliparous women at 39 weeks+0 days to 39 weeks+4 days with expectant management until 41 weeks+0 days. 11 No significant difference was found in perinatal outcome between groups, whereas the frequency of caesarean delivery was significantly lower in the early induction group. Another large recent trial from the Netherlands, INDEX (INDuction of labour at 41 weeks with a policy of EXpectant management until 42 weeks), compared induction of labour at 41 weeks+0 days to 41 weeks+1 day with expectant management until 42 weeks+0 days. 12 The results could not confirm non-inferiority for adverse perinatal outcome of expectant management, instead a significantly higher risk of adverse perinatal outcome was found in the expectant management group. No significant difference in the rate of caesarean delivery was found. The current practice in many centres in the United Kingdom and Scandinavia is to induce delivery no later than 42 weeks, but several studies suggest that the risk of perinatal mortality and morbidity has actually already increased significantly at 41 weeks. 3 4 5 The risk of stillbirth increases gradually from 39 weeks of gestation 13 and increases exponentially as the pregnancy approaches 42 weeks, 3-5 13 whereas the risk of neonatal mortality is not increased until 42 weeks according to most studies. 3-5 13 We therefore found it clinically justified to compare induction of labour at 41 weeks with expectant management and induction at 42 weeks for maternal and perinatal outcomes. At the start of the present trial, only two studies (one was an abstract) out of 30 included in the Cochrane review specifically compared induction of labour at 41 weeks with expectant management until 42 weeks. 14 15 We evaluated if induction of labour at 41 weeks+0-2 days compared with expectant management and induction of labour at 42 weeks+0-1 days was superior in terms of perinatal outcome in healthy women with a low risk pregnancy. Methods Study design SWEPIS (SWEdish Post-term Induction Study) was a multicentre, open label, randomised controlled superiority trial conducted in Sweden from May 2016 to October 2018. The trial was register based, with randomisation and most data collection done by using the Swedish Pregnancy Register. 16 Fourteen hospitals with antenatal clinics linked to the register were involved in the trial. Five of the hospitals were university clinics and nine were county hospitals comprising about 60 000 deliveries per year of the around 115 000 to 120 000 annual deliveries in Sweden. The trial was conducted according to the CONSORT guidelines. The protocol is available online ( ) and as a publication.<|im_end|>
<|im_start|>assistant
Inducing labour at 41 weeks in low risk pregnancies is associated with a lower risk of newborn death compared with expectant management (a "wait and see" approach) until 42 weeks, suggests a trial published by The BMJ. Although the overall risk of death at 42 weeks is low, the researchers say induction of labour should be offered to women no later than 41 full weeks. It is generally accepted that there is an increased risk of problems ("adverse perinatal outcomes") for both mother and baby at or beyond 42 weeks of pregnancy. Some studies have suggested that inducing labour from 41 weeks onwards improves these outcomes, but there is no international consensus on how to manage healthy pregnancies lasting more than 41 weeks. Current practice in the UK and Scandinavia is to induce delivery for all women who have not gone into labour by 42 weeks. So researchers in Sweden set out to compare induction of labour at 41 weeks with expectant management until 42 weeks in low risk pregnancies. The trial involved 2,760 women (average age 31 years) with an uncomplicated, single pregnancy recruited from 14 Swedish hospitals between 2016 and 2018. Women were randomly assigned to induction of labour at 41 weeks (1,381) or expectant management (1,379) until induction at 42 weeks if necessary. The main outcome was a combined measure of babies' health, including stillbirth or death in the first few days of life (known as perinatal death), Apgar score less than 7 at five minutes, low oxygen levels, and breathing problems. Other outcomes included admission to an intensive care baby unit, Apgar score less than 4 at five minutes, birth weight, pneumonia, or sepsis. Type of delivery and mothers' health just after giving birth were also assessed. For the main outcome measure, the researchers found no difference between the groups (2.4% of women in the induction group had an adverse perinatal outcome compared with 2.2% in the expectant management group). Other outcomes, such as caesarean sections and mothers' health after giving birth, also did not differ between the groups. However, six babies in the expectant management group died compared with none in the induction group, and the trial was stopped early. The researchers estimate that, for every 230 women induced at 41 weeks, one perinatal death would be prevented. They point to some limitations, such as differences in hospital policies and practices, that could have affected the results. But they say women with low risk pregnancies "should be informed of the risk profile of induction of labour versus expectant management and offered induction of labour no later than at 41 full weeks. This could be one (of few) interventions that reduces stillbirth," they conclude. This view is supported in a linked editorial by Professor Sara Kenyon and colleagues, who say induction at 41 weeks "looks like the safer option for women and their babies." They stress that choice is important within maternity care, and say "clear information about available options should be accessible to all pregnant women, enabling them to make fully informed and timely decisions." <|im_end|>
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315,
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539,
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28814,
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13,
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3135,
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387,
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92485,
11,
38156,
315,
23791,
22525,
311,
387,
9076,
311,
3278,
912,
3010,
1109,
520,
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3174,
5672,
323,
1436,
387,
832,
320,
1073,
2478,
8,
39455,
430,
26338,
279,
4478,
315,
2103,
28813,
82,
13,
41574,
12506,
9303,
82445,
70544,
3507,
75936,
45,
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9795,
4103,
662,
29438,
2467,
4550,
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258,
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20124,
27115,
5376,
1306,
220,
1272,
13033,
1697,
5672,
323,
527,
32302,
7319,
1772,
9860,
320,
120156,
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320,
120156,
17168,
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4682,
220,
16,
220,
17,
578,
5326,
315,
2103,
28813,
706,
1027,
6982,
311,
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11,
220,
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18,
220,
19,
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20,
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220,
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82,
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449,
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13,
220,
17,
24296,
11,
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1101,
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449,
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315,
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220,
1272,
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13,
220,
16,
2057,
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11,
912,
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6866,
389,
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311,
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320,
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10,
15,
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311,
220,
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10,
15,
2919,
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82308,
13,
578,
4435,
6401,
21021,
40912,
38156,
315,
23791,
520,
220,
3174,
5672,
11,
220,
21,
323,
1690,
5961,
3085,
38156,
315,
23791,
1990,
220,
3174,
323,
220,
2983,
5672,
311,
5766,
44387,
20209,
13,
220,
22,
220,
23,
10836,
4147,
14400,
19622,
617,
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38156,
315,
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449,
1755,
519,
6373,
304,
44387,
82308,
11,
1455,
449,
28093,
8500,
3135,
369,
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258,
4306,
29528,
323,
3682,
93144,
19025,
13,
220,
24,
578,
3135,
505,
279,
5652,
3623,
17207,
2194,
3477,
320,
679,
23,
8,
8710,
4827,
7969,
315,
2211,
288,
548,
276,
9889,
323,
824,
258,
4306,
4648,
719,
264,
5190,
4478,
315,
64885,
58159,
9889,
304,
279,
38156,
1912,
7863,
449,
279,
1755,
519,
6373,
1912,
13,
220,
24,
4740,
279,
5652,
3623,
17207,
2194,
3477,
323,
1306,
279,
61568,
315,
279,
3118,
4007,
11,
220,
605,
1403,
3544,
4288,
4147,
14400,
19622,
38936,
3428,
5326,
82308,
617,
1027,
4756,
13,
362,
3544,
9269,
505,
279,
3723,
4273,
11,
83179,
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320,
32,
10836,
1534,
41574,
315,
2314,
2720,
25187,
355,
33185,
519,
9744,
705,
7863,
38156,
315,
23791,
304,
854,
121481,
788,
3278,
520,
220,
2137,
5672,
10,
15,
2919,
311,
220,
2137,
5672,
10,
19,
2919,
449,
1755,
519,
6373,
3156,
220,
3174,
5672,
10,
15,
2919,
13,
220,
806,
2360,
5199,
6811,
574,
1766,
304,
824,
258,
4306,
15632,
1990,
5315,
11,
20444,
279,
11900,
315,
2211,
288,
548,
276,
9889,
574,
12207,
4827,
304,
279,
4216,
38156,
1912,
13,
13596,
3544,
3293,
9269,
505,
279,
26746,
11,
40400,
320,
5358,
2720,
315,
23791,
520,
220,
3174,
5672,
449,
264,
4947,
315,
4154,
1002,
519,
6373,
3156,
220,
2983,
5672,
705,
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38156,
315,
23791,
520,
220,
3174,
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10,
15,
2919,
311,
220,
3174,
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10,
16,
1938,
449,
1755,
519,
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3156,
220,
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10,
15,
2919,
13,
220,
717,
578,
3135,
1436,
539,
7838,
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809,
2521,
488,
369,
31959,
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258,
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15632,
315,
1755,
519,
6373,
11,
4619,
264,
12207,
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5326,
315,
31959,
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258,
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15632,
574,
1766,
304,
279,
1755,
519,
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13,
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304,
279,
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315,
2211,
288,
548,
276,
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574,
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13,
578,
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6725,
304,
1690,
36282,
304,
279,
3723,
15422,
323,
60280,
35102,
374,
311,
49853,
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912,
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1109,
220,
2983,
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11,
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430,
279,
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315,
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258,
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323,
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220,
3174,
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220,
18,
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2103,
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220,
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220,
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519,
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220,
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279,
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13,
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198,
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198,
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220,
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304,
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374,
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264,
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64,
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323,
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578,
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41,
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279,
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315,
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220,
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374,
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11,
279,
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2019,
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315,
23791,
1288,
387,
9076,
311,
3278,
912,
3010,
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220,
3174,
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13,
1102,
374,
8965,
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430,
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374,
459,
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315,
5435,
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329,
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909,
369,
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323,
8945,
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220,
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315,
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13,
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617,
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220,
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60525,
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11,
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374,
912,
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389,
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311,
10299,
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220,
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13,
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279,
6560,
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220,
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13,
2100,
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24067,
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9616,
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315,
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220,
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519,
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13,
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66637,
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11,
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31209,
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1990,
220,
679,
21,
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220,
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11215,
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311,
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315,
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320,
16,
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519,
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16,
11,
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220,
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13,
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279,
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19,
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6,
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13,
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279,
1925,
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11,
279,
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912,
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1990,
279,
5315,
320,
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19,
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315,
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304,
279,
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17,
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276,
14491,
323,
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6,
2890,
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11,
1101,
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539,
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1990,
279,
5315,
13,
4452,
11,
4848,
24869,
304,
279,
1755,
519,
6373,
1912,
8636,
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279,
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11,
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13,
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11,
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220,
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11,
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13,
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11,
430,
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279,
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13,
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2019,
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449,
3428,
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82308,
330,
5562,
387,
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315,
279,
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315,
38156,
315,
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19579,
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519,
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323,
9076,
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315,
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912,
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387,
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264,
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555,
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26039,
323,
18105,
11,
889,
2019,
38156,
520,
220,
3174,
5672,
330,
95373,
1093,
279,
30549,
3072,
369,
3278,
323,
872,
24869,
1210,
2435,
8631,
430,
5873,
374,
3062,
2949,
71271,
2512,
11,
323,
2019,
330,
7574,
2038,
922,
2561,
2671,
1288,
387,
15987,
311,
682,
20895,
3278,
11,
28462,
1124,
311,
1304,
7373,
16369,
323,
32100,
11429,
1210,
220,
128257,
198
] | 2,107 |
[{"content":"You are a great journalist. Users will give you a scientific paper paper and ask you to(...TRUNCATED) | "<|im_start|>system\nYou are a great journalist. Users will give you a scientific paper paper and as(...TRUNCATED) | [128256,9125,198,2675,527,264,2294,23672,13,14969,690,3041,499,264,12624,5684,5684,323,2610,499,311,(...TRUNCATED) | 2,229 |
[{"content":"You are a great journalist. Users will give you a scientific paper paper and ask you to(...TRUNCATED) | "<|im_start|>system\nYou are a great journalist. Users will give you a scientific paper paper and as(...TRUNCATED) | [128256,9125,198,2675,527,264,2294,23672,13,14969,690,3041,499,264,12624,5684,5684,323,2610,499,311,(...TRUNCATED) | 1,847 |
[{"content":"You are a great journalist. Users will give you a scientific paper paper and ask you to(...TRUNCATED) | "<|im_start|>system\nYou are a great journalist. Users will give you a scientific paper paper and as(...TRUNCATED) | [128256,9125,198,2675,527,264,2294,23672,13,14969,690,3041,499,264,12624,5684,5684,323,2610,499,311,(...TRUNCATED) | 1,792 |
[{"content":"You are a great journalist. Users will give you a scientific paper paper and ask you to(...TRUNCATED) | "<|im_start|>system\nYou are a great journalist. Users will give you a scientific paper paper and as(...TRUNCATED) | [128256,9125,198,2675,527,264,2294,23672,13,14969,690,3041,499,264,12624,5684,5684,323,2610,499,311,(...TRUNCATED) | 2,218 |
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