Miracle-dz/UniFAR-FTUs huggingface dataset:
AMP-Activated Protein Kinase Regulates the Cell Surface Proteome and Integrin Membrane Traffic

The cell surface proteome controls numerous cellular functions including cell migration and adhesion, intercellular communication and nutrient uptake. Cell surface proteins are controlled by acute changes in protein abundance at the plasma membrane through regulation of endocytosis and recycling (endomembrane traffic). Many cellular signals regulate endomembrane traffic, including metabolic signaling; however, the extent to which the cell surface proteome is controlled by acute regulation of endomembrane traffic under various conditions remains incompletely understood. AMP-activated protein kinase (AMPK) is a key metabolic sensor that is activated upon reduced cellular energy availability. AMPK activation alters the endomembrane traffic of a few specific proteins, as part of an adaptive response to increase energy intake and reduce energy expenditure. How increased AMPK activity during energy stress may globally regulate the cell surface proteome is not well understood. To study how AMPK may regulate the cell surface proteome, we used cell-impermeable biotinylation to selectively purify cell surface proteins under various conditions. Using ESI-MS/MS, we found that acute (90 min) treatment with the AMPK activator A-769662 elicits broad control of the cell surface abundance of diverse proteins. In particular, A-769662 treatment depleted from the cell surface proteins with functions in cell migration and adhesion. To complement our mass spectrometry results, we used other methods to show that A-769662 treatment results in impaired cell migration. Further, A-769662 treatment reduced the cell surface abundance of β1-integrin, a key cell migration protein, and AMPK gene silencing prevented this effect. While the control of the cell surface abundance of various proteins by A-769662 treatment was broad, it was also selective, as this treatment did not change the cell surface abundance of the transferrin receptor. Hence, the cell surface proteome is subject to acute regulation by treatment with A-769662, at least some of which is mediated by the metabolic sensor AMPK.
Eemian and Early Weichselian environments in southern Sweden: a multi‐proxy study of till‐covered organic deposits from the Småland peneplain

Based on their luminescence and infinite radiocarbon ages, organic deposits beneath till at two sites on the Småland peneplain, southern Sweden (Nybygget and Stora Gäddevik), are concluded to have formed before the Middle Weichselian. Applied palaeoecological methods include analyses of pollen, diatoms, charcoal fragments, macroscopic remains of vascular plants and mosses, and insect remains. Pollen‐stratigraphical correlations with previously studied interglacial/interstadial sites in southern Sweden, Denmark and northern Germany suggest that the peat at Nybygget dates from the Brørup interstadial or the final stage of the Eemian interglacial, whereas the lake sediments at Stora Gäddevik probably were emplaced during the middle Eemian. We conclude that the peat was formed in a wetland characterized by both wood swamp and open mire vegetation, and surrounded by semi‐open woodlands dominated by pine, birch and hazel. The middle Eemian sequence at the Stora Gäddevik site provides evidence of a moderately nutrient‐rich to nutrient‐rich lake environment with relatively diverse aquatic vegetation. Regional vegetation, as reconstructed using the REVEALS model, was spruce woodland mixed with pine, alder and birch, but also included more open environments with hazel, oak, grasslands and sedge‐dominated wetlands. Water shield (Brasenia schreberi), now extinct in Europe, was identified in the Eemian lake deposits, from both pollen and macroscopic remains.
High Hydrostatic Pressure for Accelerating Ripening of Goat's Milk Cheese: Proteolysis and Texture

High hydrostatic pressurization is proposed for cheese ripening acceleration. Several treatments were used for accelerating ripening of goat's milk cheese: 50 MPa / 72 h, 400 MPa / 5 min and 400 MPa / 5 min followed by 50 MPa / 72 h all at 14 °C. Moisture content and pH were higher in 400 MPa treatments compared to the others. By measuring proteolysis indexes, 400 MPa treatments were found to accelerate ripening (14 d in contrast to 28 d conventionally) due to enhanced enzyme activity from inoculated starter culture. Sensory analysis indicated bitter notes in the accelerated ripened cheese. Pressurized cheeses were less crumbly and more elastic than control.
Numerical simulations of the Netlander Ionosphere and Geodesy Experiment (NEIGE): landing site positions determination from Doppler tracking between an orbiter and landers

The objectives of a geodesy experiment performed on the basis of a network of landers, such as NEIGE (Netlander Ionosphere and Geodesy Experiment) are to measure variations of Mars’ orientation and rotation in space with a precision of a few centimeters over annual and sub-annual periods. The lander positions are not well known upon landing, depending on the technical solution chosen for the entry-descent-landing phase, and thus need to be accurately determined to achieve the scientific objectives of a geodetic experiment. We performed numerical simulations of the NEIGE experiment to evaluate our ability to recover the lander positions from Doppler shifts measurements between an orbiter around Mars and those landers, with a precision of a few centimeters.
The Connectivity of NK Landscapes' Basins - A Network Analysis

We propose a network characterization of combinatorial £t- ness landscapes by adapting the notion of inherent networks proposed for energy surfaces (Doye, 2002). We use the well- known family of landscapes as an example. In our case the inherent network is the graph where the vertices repre- sent the local maxima in the landscape, and the edges account for the transition probabilities between their corresponding basins of attraction. We exhaustively extracted such networks on representative small landscape instances, and per- formed a statistical characterization of their properties. We found that most of these network properties can be related to the search dif£culty on the underlying landscapes with varying values of . them. The resulting graph, with an indication of the £tness at each vertex, is a representation of the given problem £t- ness landscape. A useful simpli£cation of the graphs for the energy landscapes of atomic clusters was introduced in (Doye, 2002; Doye and Massen, 2005). The idea consists in taking as vertices of the graph not all the possible con£gura- tions, but only those that correspond to energy minima. For atomic clusters these are well-known, at least for relatively small assemblages. Two minima are considered connected, and thus an edge is traced between them, if the energy bar- rier separating them is suf£ciently low. In this case there is a transition state, meaning that the system can jump from one minimum to the other by thermaluctuations going through a saddle point in the energy hyper-surface. The values of these activation energies are mostly known experimentally or can be determined by simulation. In this way, a network can be built which is called the "inherent structure" or "in- herent network" in (Doye, 2002). We propose a network characterization of combinatorial £t- ness landscapes by adapting the notion of inherent networks described above. We use the well-known family of landscapes as an example because they are a useful tun- able benchmark that can provide interesting information for more realistic combinatorial landscapes. In our case the in- herent network is the graph where the vertices are all the local maxima and the edges account for transition probabil- ities between their corresponding basins of attraction. We exhaustively extract such networks on representative small landscape instances, and perform a statistical charac- terization of their properties. Our analysis was inspired, in particular, by the work of Doye (2002); Doye and Massen (2005) on energy landscapes, and in general, by the £eld of complex networks (Newman, 2003). The study of networks has exploded across the academic world since the late 90' s. Researchers from the mathematical, biological, and social sciences have made substantial progress on some previously intractable problems, bringing new techniques, reformulat- ing old ideas, and uncovering unexpected connections be- tween seemingly different problems. We aim here at bring- ing the tools of network analysis for the study of problem
High mechanical efficiency of the cross-bridge powerstroke in skeletal muscle

SUMMARY We were interested to estimate the maximum mechanical efficiency with which chemical energy derived from ATP hydrolysis is converted into mechanical work by individual cross-bridges when they perform their powerstroke synchronously. Glycerinated rabbit psoas muscle fibres, containing ATP molecules almost equal in number to the cross-bridges within the fibre, were activated to shorten under various afterloads by laser-flash photolysis of caged Ca2+. In these conditions, almost all the cross-bridges are in the state where the ATP is hydrolyzed but the products have not yet been released from the cross-bridge (M-ADP-Pi) immediately before activation, and can hydrolyze only one ATP molecule during the flash-induced mechanical response. Power output records of the fibres following activation indicated that the cross-bridges actually started their powerstroke almost synchronously. The amount of ATP utilized at 1 s after activation was estimated from the amount of isometric force developed after interruption of fibre shortening, while the amount of work done was calculated by multiplying the amount of afterload by the distance of fibre shortening. A conservative estimation of the maximum mechanical efficiency at a load of 0.5–0.6 Po was 0.7, suggesting that the actual maximum mechanical efficiency of cross-bridge powerstrokes may be close to unity.
Determining Causal Exposure-Response Relationships With Randomized Concentration-Controlled Trials

Determining causal effects in exposure-response relationships is an important but also a challenging task since confounding factors that affect both drug exposure and response often exist and lead to confounding biases in causal effect estimation. Randomized concentration control (RCC) trials are designed to eliminate or to reduce the confounding bias. However, statistical issues in the design and analysis of these trials have not been examined closely in the literature. Analysis of dose-exposure relationship may also be affected by confounding factors if they affect dose adjustments. We examined these issues and suggest methodological and practical solutions. In particular, we proposed using instrumental variables (IV) for the estimation of causal effects in both exposure-response and dose-exposure relationships. We also examined the impacts of confounded treatment heterogeneity on the IV estimate for RCC trials. We illustrated these approaches with a trial design scenario showing the importance of considering multiple practical factors that may alter the performance of the IV estimate. The performance of the IV estimates was examined by simulations for a wide range of scenarios. The results showed clear advantages for the IV estimates over routine estimates. Some situations in which the IV estimates may fail were also identified.
The water masses between Mindanao and New Guinea

Water masses between Mindanao and New Guinea are investigated, using hydrographic data, during two R/V Kaiyo World Ocean Circulation Experiment cruises conducted in October 1992 and February 1994. The analysis of this data indicates that the South Pacific Tropical Water (SPTW), which is formed in the southern hemisphere, reached the area of Morotai Island in 1992 and farther north in 1994. The Antarctic Intermediate Water (AAIW) exists in the southwestern area of the southernmost Philippine Sea. There is northeastward flow between Talaud Islands and Morotai Island, which is probably a part of the retroflection of the Mindanao Current. The remnant of the North Pacific Intermediate Water, advected by the flow from the Celebes Sea, was found in 1992. The New Guinea Coastal Undercurrent, transporting SPTW and AAIW from the southern hemisphere, is divided into at least two parts because the retroflection of the Mindanao Current prevents its shallow part from reaching farther north; the shallow part of SPTW turns eastward as a source water of North Equatorial Countercurrent and retroflects toward the southeast. AAIW and the lower part of SPTW flow northward and seem to be linked with the Mindanao Undercurrent.
A trial of methadone tapering schedules in pediatric intensive care unit patients exposed to prolonged sedative infusions*

Objectives: To compare the efficacy of a low-dose methadone tapering schedule to a high-dose methadone tapering schedule in pediatric intensive care unit patients exposed to infusions of fentanyl, with or without infusions of midazolam, for ≥5 days. Design: Prospective, double-blind, randomized trial. Setting: Pediatric intensive care unit in a tertiary care children's hospital. Patients: Seventy-eight patients, 74 of whom had been receiving infusions of both fentanyl and midazolam, were randomized. Forty-one patients were randomized to the low-dose methadone group and 37 were randomized to the high-dose methadone group. Sixty patients successfully completed the trial, 34 were in the low-dose methadone group, and 26 were in the high-dose methadone group. Interventions: Patients were randomized to receive methadone either at a starting dose of 0.1 mg/kg/dose (low-dose methadone group) or at a starting dose based on both the patient's weight and the most recent fentanyl infusion rate (high-dose methadone group). In each group, methadone was administered every 6 hrs for the first 24 hrs and then every 12 hrs for the second 24 hrs. The methadone was then decreased to once daily and tapered off over the next 10 days. Patients were monitored for withdrawal symptoms using the Modified Narcotic Withdrawal Score. Measurements and Main Results: The percentage of patients who successfully completed the 10-day methadone taper was the same in the low-dose methadone group as in the high-dose methadone group (56% vs. 62%; p = .79). Patients that failed to complete the assigned methadone taper had a greater total fentanyl dose and longer pediatric intensive care unit length of stay compared to patients who completed the assigned methadone taper. Conclusions: Patients who received infusions of fentanyl for at least 5 days were just as likely to complete a low-dose methadone taper as a high-dose methadone taper. Because of the risks of both withdrawal and oversedation with any fixed methadone schedule, the methadone dose must be adjusted according to each patient's response.
Bone morphogenetic proteins in the early development of zebrafish

Bone morphogenetic proteins (BMPs) are known to be widely involved in various biological processes. Many of the members of the BMP family, as well as related factors, receptors and molecules in the BMP signaling pathway, have been isolated, but their precise functions are still unclear. In addition to the ‘classical’ model organism Xenopus, zebrafish, Danio rerio, is now considered to be a suitable model organism to study the roles of the BMP signaling pathway during embryogenesis. Mutagenesis screens have identified a number of mutants in the pathway. Although they do not cover the entire members of the BMP signaling cascade that are currently known, they serve as a powerful tool to broaden our understanding of BMP functions, in combination with other experimental techniques.
Trends of HIV-1 and HIV-2 prevalence among pregnant women in Guinea-Bissau, West Africa: possible effect of the civil war 1998–1999

Objectives: Sentinel surveys in Bissau, the capital of Guinea-Bissau, have shown low prevalence of HIV-1 but high HIV-2 prevalence before 1998. Guinea-Bissau experienced a civil war in 1998–1999. To examine specifically the trends of HIV prevalence from antenatal surveys in Bissau, Guinea-Bissau in 1987–2004, and whether the civil war in 1998–1999 could have an effect on HIV prevalence levels after the conflict. Methods: Since 1987, anonymous HIV testing in delivering women has been performed at the maternity clinic, Simão Mendes National Hospital, Bissau, as part of the national sentinel surveillance programme. Consecutive sampling was performed for approximately 3 months between September and December each year. Serological analyses were performed at the National Public Health Laboratory in Guinea-Bissau. Results: A total of 20 422 women were tested for HIV between 1987 and 2004. The total HIV-1 prevalence increased from 0.0% in 1987 to 4.8% in 2004 and the total HIV-2 prevalence decreased from 8.3% in 1987 to 2.5% in 2004. The HIV-1 prevalence increased from 2.5% in 1997 to 5.2% in 1999, but stabilized in subsequent years. Conclusions: There was a significant increase in HIV-1 prevalence in the years 1987–2004 and a significant decline in HIV-2 prevalence over the same period. The civil war in 1998–1999 may have sparked HIV-1 transmission, as HIV-1 prevalence more than doubled between 1997 and 1999, but there is no evidence of a long-term effect on the trends of HIV-1 or HIV-2 prevalence.
Effects of Celecoxib on Prostanoid Biosynthesis and Circulating Angiogenesis Proteins in Familial Adenomatous Polyposis

Vascular cyclooxygenase (COX)-2-dependent prostacyclin (PGI2) may affect angiogenesis by preventing endothelial activation and platelet release of angiogenic factors present in platelet α-granules. Thus, a profound inhibition of COX-2-dependent PGI2 might be associated with changes in circulating markers of angiogenesis. We aimed to address this issue by performing a clinical study with celecoxib in familial adenomatous polyposis (FAP). In nine patients with FAP and healthy controls, pair-matched for gender and age, we compared systemic biosynthesis of PGI2, thromboxane (TX) A2, and prostaglandin (PG) E2, assessing their urinary enzymatic metabolites, 2,3-dinor-6-keto PGF1α (PGI-M), 11-dehydro-TXB2 (TX-M), and 11-α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), respectively. The impact of celecoxib (400 mg b.i.d. for 7 days) on prostanoid biosynthesis and 14 circulating biomarkers of angiogenesis was evaluated in FAP. Intestinal tumorigenesis was associated with enhanced urinary TX-M levels, but unaffected by celecoxib, suggesting the involvement of a COX-1-dependent pathway, presumably from platelets. This was supported by the finding that in cocultures of a human colon adenocarcinoma cell line (HT-29) and platelets enhanced TXA2 generation was almost completely inhibited by pretreatment of platelets with aspirin, a preferential inhibitor of COX-1. In FAP, celecoxib profoundly suppressed PGE2 and PGI2 biosynthesis that was associated with a significant increase in circulating levels of most proangiogenesis proteins but also the antiangiogenic tissue inhibitor of metalloproteinase 2. Urinary PGI-M, but not PGE-M, was negatively correlated with circulating levels of fibroblast growth factor 2 and angiogenin. In conclusion, inhibition of tumor COX-2-dependent PGE2 by celecoxib may reduce tumor progression. However, the coincident depression of vascular PGI2, in a context of enhanced TXA2 biosynthesis, may modulate the attendant angiogenesis, contributing to variability in the chemopreventive efficacy of COX-2 inhibitors such as celecoxib.
Thinning and expansion of the substorm plasma sheet

More than 50,000 measurements with the AMPTE IRM satellite in the magnetotail are used for a superposed epoch analysis of the occurrence frequency of the near-Earth central plasma sheet, which is directly related to its thickness, around 39 major substorm onsets. For all radial distances between 10 and 19 RE, the central plasma sheet gets thinner during the 30–45 min preceding substorm onset, but starts to expand immediately after the onset. The central plasma sheet regains its initial thickness around the beginning of the recovery phase. These observations fit into the framework of the near-Earth neutral line model, if the neutral line is assumed to form beyond the IRM apogee.
Integrated Magnetics and Multiferroics for Compact and Power-Efficient Sensing, Memory, Power, RF, and Microwave Electronics

The coexistence of electric polarization and magnetization in multiferroic materials provides great opportunities for realizing magnetoelectric (ME) coupling, including electric field control of magnetism, or vice versa, through a strain-mediated ME coupling in layered magnetic/ferroelectric multiferroic heterostructures. Strong ME coupling has been the enabling factor for different multiferroic devices, which, however, has been elusive, particularly at RF/microwave frequencies. In this paper, most recent progress on new integrated multiferroic devices for sensing RF and microwave electronics will be presented, including novel RF Nano-electro-mechanical systems ME resonators with picotesla sensitivity for dc magnetic fields and novel gigahertz magnetic and multiferroic integrated inductors with a wide operation frequency range of 0.3~3 GHz, a high quality factor close to 20, and a voltage tunable inductance of 50%~150%. At the same time, we will also demonstrate other tunable RF devices, including integrated non-reciprocal tunable bandpass filter with ultrawideband isolation more than 13 dB. These novel magnetics and multiferroic devices show great promise for applications, such as compact, lightweight, and power-efficient sensing, memory, RF, and microwave integrated electronics.
Place Annihilation: Area Bombing and the Fate of Urban Places

ABSTRACT Aerial bombardment in World War II brought devastation to innumerable settlements in the European and Pacific theaters of war. A distinctive development, however, was the area bombing of cities remote from the battle zones, particularly in Germany and Japan, where Allied bombing raids razed more than 750 km2 of central built-up areas and involved nearly every city. Some 1.5 million civilian residents of those countries were killed in this way and more than 2 million were seriously injured. To the millions uprooted from their homes by official evacuation were added more than 16 million made homeless by bomb destruction. This paper examines these events as a process of place annihilation and immolation: the combined destruction of resident civilians, residential communities, their neighborhoods, and major features of the urban environment and civil ecology. The destruction of urban support systems, the nature of civilian injuries and death, the areal differentiation of damages, and the problem of t.