Search

The exploration of the universe has recently entered a new era thanks to the multimessenger paradigm, characterized by a continuous increase in the quantity and quality of experimental data that is obtained by the detection of the various cosmic messengers (photons, neutrinos, cosmic rays and gravitational waves) from numerous origins. They give us information about their sources in the universe and the properties of the intergalactic medium. Moreover, multi-messenger astronomy opens up the possibility to search for phenomenological signatures of quantum gravity. On the one hand, the most energetic events allow us to test our physical theories at energy regimes which are not directly accessible in accelerators; on the other hand, tiny effects in the propagation of very high energy particles could be amplified by cosmological distances. After decades of merely theoretical investigations, the possibility of obtaining phenomenological indications of Planck-scale effects is a revolutionary step in the quest for a quantum theory of gravity, but it requires cooperation between different communities of physicists (both theoretical and experimental). This review, prepared within the COST Action CA18108 ‘‘Quantum gravity phenomenology in the multi-messenger approach", is aimed at promoting this cooperation by giving a state-of-the art account of the interdisciplinary expertise that is needed in the effective search of quantum gravity footprints in the production, propagation and detection of cosmic messengers., Talent Scientific Research Program of College of Physics, Sichuan University 1082204112427, Fostering Program in Disciplines Possessing Novel Features for Natural Science of Sichuan University 2020SCUNL209, 1000 Talent program of Sichuan province 2021, Xunta de Galicia, European Commission European Union ERDF, "Maria de Maeztu'' Units of Excellence program MDM-2016-0692, Red Tematica Nacional de Astroparticulas RED2018-102661-T, La Caixa Foundation 100010434, European Commission 847648 LCF/BQ/PI21/11830030 754510, Ministry of Education, Science & Technological Development, Serbia 451-03-9/2021-14/200124, FSR Incoming Postdoctoral Fellowship Ministry of Education, Science and Technological Development, Serbia 451-03-9/2021-14/200124, University of Rijeka grant uniri-prirod-18-48, Croatian Science Foundation (HRZZ) IP-2016-06-9782, Villum Fonden 29405 DGA-FSE 2020-E2117R, European Regional Development Fund through the Center of Excellence (TK133) "The Dark Side of the Universe'' European Regional Development Fund (ESIF/ERDF), Ministry of Education, Youth & Sports - Czech Republic CoGraDS-CZ.02.1.01/0.0/0.0/15 003/0000437, Blavatnik grant, Basque Government IT-97916 Basque Foundation for Science (IKERBASQUE), European Space Agency C4000120711 4000132310, FNRS (Belgian Fund for Research), Programa de Apoyo a Proyectos de Investigacion e Innovacion Tecnologica (PAPIIT), Universidad Nacional Autonoma de Mexico TA100122, National University of La Plata X909 DICYT 042131GR, National Research, Development & Innovation Office (NRDIO) - Hungary 123996, FQXi, Swiss National Science Foundation (SNSF), European Commission 181461 199307, Netherlands Organization for Scientific Research (NWO) 680-91-119 15MV71, Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research (KAKENHI) 20H01899 20H05853 JP21F21789, Estonian Research Council PRG356, Julian Schwinger Foundation, Generalitat Valenciana Excellence PROMETEO-II/2017/033 PROMETEO/2018/165, Istituto Nazionale di Fisica Nucleare (INFN), European ITN project HIDDeN H2020-MSCA-ITN-2019//860881-HIDDeN, Swedish Research Council, European Commission 2016-05996 European Research Council (ERC) European Commission 668679, Advanced ERC grant TReX, Ministry of Education, Universities and Research (MIUR) 2017X7X85K, Fonds de la Recherche Scientifique - FNRS 4.4501.18, Ministry of Research, Innovation and Digitization - Romania PN19-030102-INCDFM PN-III-P4ID-PCE-2020-2374, United States Department of Energy (DOE) DE-SC0020262, Ministry of Science, ICT & Future Planning, Republic of Korea 075-15-2020-778, German Academic Scholarship Foundation German Research Foundation (DFG) 408049454 420243324 425333893 445990517 Germany's Excellence Strategy (EXC 2121 "Quantum Universe'') 390833306 390837967 Federal Ministry of Education & Research (BMBF) 05 A20GU2 05 A20PX1, Centro de Excelencia "Severo Ochoa'' SEV-2016-0588, CERCA program of the Generalitat de Catalunya, Agencia de Gestio D'Ajuts Universitaris de Recerca Agaur (AGAUR) Generalitat de Catalunya 2017-SGR-1469 2017-SGR-929 ICCUB CEX2019-000918-M, National Science Centre, Poland 2019/33/B/ST2/00050 2017/27/B/ST2/01902, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) 306414/2020-1, Dicyt-USACH 041931MF, National Science Fund of Bulgaria KP-06-N 38/11 RCN ROMFORSK 302640, Comunidad de Madrid 2018-T1/TIC-10431 2019-T1/TIC-13177 S2018/NMT-4291, UK Research & Innovation (UKRI), Science & Technology Facilities Council (STFC) ST/T000759/1 ST/P000258/1 ST/T000732/1 ST/V005596/1, Portuguese Foundation for Science and Technology UIDB/00618/2020 UIDB/00777/2020 UIDP/00777/2020 CERN/FIS-PAR/0004/2019 PTDC/FIS-PAR/29436/2017 PTDC/FISPAR/31938/2017 PTDC/FIS-OUT/29048/2017 SFRH/BD/137127/2018, Centre National de la Recherche Scientifique (CNRS), LabEx UnivEarthS ANR-10-LABX-0023 ANR18-IDEX-0001, Junta de Andalucia European Commission A-FQM-053-UGR18, Natural Sciences and Engineering Research Council of Canada (NSERC) RGPIN-2021-03644, National Science Centre Poland Sonata Bis 2019/33/B/ST2/00050 DEC-2017/26/E/ST2/00763, Natural Sciences and Engineering Research Council of Canada (NSERC) DGIID-DGA 2015-E24/2, Spanish Research State Agency and Ministerio de Ciencia e Innovacion MCIN/AEI PID2019-104114RB-C32 PID2019-105544GB-I00 PID2019-105614GB-C21 PID2019106515GB-I00 PID2019-106802GB-I00 PID2019-107394GB-I00 PID2019-107844GB-C21 PID2019-107847RB-C41 MCIN/AEI PGC2018-095328-B-I00 PGC2018-094856-B-I00 PGC2018-096663-B-C41 PGC2018-096663-B-C44 PGC2018-094626-BC21 PGC2018-101858-B-I00 FPA2017-84543-P FPA2016-76005-C2-1-P, Spanish 'Ministerio de Universidades' BG20/00228 Spanish Government PID2020-115845GBI00 Generalitat de Catalunya Comunidad de Madrid S2018/NMT-4291 Spanish Government PID2019-105544GB-I00, Perimeter Institute for Theoretical Physics, Government of Canada through the Department of Innovation, Science and Economic Development, Province of Ontario through the Ministry of Colleges and Universities, Centre National de la Recherche Scientifique (CNRS), Netherlands Organization for Scientific Research (NWO), Fundamental Questions Institute (FQXi), European Cooperation in Science and Technology (COST) CA18108, Research Council of University of Guilan, Iniziativa Specifica TEONGRAV Iniziativa Specifica QGSKY Iniziativa Specifica QUAGRAP Iniziativa Specifica GeoSymQFT, the Spanish Research State Agency and Ministerio de Ciencia e Innovacion MCIN/AEI PID2020-115845GBI00 PID2019-108485GB-I00 PID2020-113334GB-I00 PID2020-113701GB-I00 PID2020-113775GB-I00 PID2020-118159GB-C41 PID2020-118159GA-C42 PRE2019-089024, Rothchild grant UID/MAT/00212/2020 FPU18/04571

Results from testing of position-sensitive capacitive Frisch-grid (PSCFG) TIBr gamma-ray detectors are presented. Due to its high atomic number, high density, and low Fano factor, TIBr offers excellent energy resolution and high detection efficiency over a wide energy range, thus providing significant advantages over other detector materials commonly used in hand-held instruments. Using high-fidelity 3-D position sensing enables the response non-uniformity caused by defects in the TIBr crystal to be corrected, thereby offering an approach to overcome one of the technical barriers limiting the use of this promising semiconductor material. By utilizing the 3-D position information, temporal and spatial variations of the charge collection efficiency are presented, which provide microscopic characterization of the PSCFG devices. Using the 3-D response correction technique, the best energy resolution measured is

Arrays of 3D position-sensitive detectors (3DPSD), operating at room temperature and using cadmium zinc telluride (CZT) and thallium bromide (TIBr) sensors, are suitable for gamma-ray spectrometry in many applications. One detector configuration, the 3D position-sensitive Virtual Frisch-Grid detector (VFG), is particularly advantageous for integrating into large area arrays. The signals generated inside each detector of the array are captured with the anode, cathode and four pads that enable the reconstruction of the position and energy of the ionizing interaction by measurements of amplitude and timing of the signals. For these applications, a low-noise front-end ASIC has been developed, capable of processing bipolar signals (needed because of AC-coupling of certain electrodes). The ASIC can be coupled to an ADC in order to form a compound “waveform digitizer” capable of post-processing the analog signals and determining amplitude and timing information. This paper describes a 32-channel front-end ASIC that is suitable for reading out a 3 × 3 or 4 × 4 element matrix in the VFG configuration. Each channel is composed of a low-noise charge amplifier with an adaptive continuous reset feedback circuit suitable for both positive and negative charge, a first order shaper and a single-to-differential converter output stage. Voltage and current references are all internally generated by 10-bit DACs and the chip is fully controllable with the I2C communication protocol. The readout channel response has been verified using the implemented injection circuit. Linear behavior up to ∼75 ke± with the gain of ∼80 mV/fC, and up to ∼200 ke± with the gain of ∼30 mV/fC was demonstrated. In conclusion, the first test result waveforms using a 137Cs radioactive source on a 5 × 5 × 12 mm3 TIBr crystal are reported.

Room-temperature operable semiconductor gamma-ray detectors offer the potential of superior energy resolution compared to scintillators, which can be valuable in the design of radionuclide identification equipment. To achieve the best energy resolution and simultaneously provide good sensitivity, multiple detection elements must be arrayed to operate in parallel. This paper describes efforts to construct such an array from multiple elements of thallium bromide (TlBr), a material that inherently offers a high interaction probability and photopeak efficiency for gamma rays. The base design of the array comprises capacitive Frisch grid (CFG) elements. A key objective is optimizing the energy resolution of each element, for which the single-carrier characteristics of the CFG design were chosen. Gains are realized through signal processing that accounts for 1-D or 3-D material inhomogeneity and charge collection variations. Fully corrected energy resolution reaches values of 1.6% FWHM at 662 keV.

The successful production of embryos by nuclear transfer (NT) employing cultured somatic donor cells depends upon a variety of factors. The objective of the present study was to investigate the effects 1) of two different activation protocols, 2) the use of quiescent or nonquiescent donor cells (G(0) or G(1) of the cell cycle), and 3) passage number of donor cells on the relative abundance (RA) of eight specific mRNAs (DNA methyltransferase, DNMT; mammalian achaete-scute homologue, Mash2; glucose transporter-1, Glut-1; heat shock protein 70.1, Hsp; desmocollin II, Dc II; E-cadherin, E-cad; interferon tau, IF; insulin-like growth factor 2 receptor, Igf2r) in single blastocysts employing a semiquantitative reverse transcription-polymerase chain reaction assay. The results were compared with those for their in vitro (IVP)- and in vivo-generated noncloned counterparts. In experiment 1, employing either FBA (fusion before activation) or AFS (fusion and activation simultaneously) to generate NT blastocysts, Hsp mRNAs were not found in NT embryos from either protocol, whereas Hsp transcripts were detectable in IVP embryos. The relative abundance (RA) of IF transcripts was significantly increased in the AFS and IVP groups compared to the FBA treatment. In experiment 2, the use of either G(0) or G(1) donor cells to produce cloned embryos both significantly reduced the relative amount of DNMT transcripts and significantly increased the RA of Mash2 compared to the IVP embryos. In addition, IF transcript levels were significantly elevated in NT blastocysts employing G(1) donor cells for NT compared to IVP embryos and those generated using G(0) cells. In experiment 3, donor cells, either from passsage 5/6 or 8, were employed for NT. DNMT transcripts were significantly decreased, whereas Mash2 transcripts were significantly increased in both NT groups compared to their IVP counterparts. The amount of IF mRNA was significantly higher in P8-derived than in P5/6 and IVP embryos. In experiment 4, the RA of DNMT transcripts was decreased in in vivo-derived blastocysts compared to those produced in vitro. Mash2 expression was increased in in vivo embryos and those IVP embryos produced in medium containing Sigma BSA. The RA of Hsp was higher in IVP embryos produced in serum containing medium than in those produced in Sigma BSA or in vivo. In vivo embryos and those produced in Life Technologies BSA had the lowest expression of IF transcripts. Expression of all other genes was not affected by variation in NT methodology or IVP culture systems throughout experiments 1-4. In conclusion, depending on steps of the cloning procedure NT-derived embryos display marked differences from their IVP- and in vivo-derived counterparts. An aberrant expression pattern in NT embryos was found with respect to genes thought to be involved in stress adaptation, trophoblastic function, and DNA methylation during preimplantation development.

Diverse studies in western North America have revealed the role of topography for dynamically shaping genetic diversity within species though vicariance, dispersal and range expansion. We examined patterns of phylogeographical diversity in the widespread but poorly studied North American vaejovid scorpion, Paruroctonus boreus Girard 1854. We used mitochondrial sequence data and parsimony, likelihood, and Bayesian inference to reconstruct phylogenetic relationships across the distributional range of P. boreus, focusing on intermontane western North America. Additionally, we developed a species distribution model to predict its present and historical distributions during the Last Glacial Maximum and the Last Interglacial Maximum. Our results documented complex phylogeographic relationships within P. boreus, with multiple, well-supported crown clades that are either geographically-circumscribed or widespread and separated by short, poorly supported internodes. We also observed subtle variation in predicted habitat suitability, especially at the northern, eastern and southern edges of the predicted distributional range under past climatic conditions. The complex phylogenetic relationships of P. boreus suggests that historical isolation and expansion of populations may have occurred. Variation in the predicted distributional range over time may implicate past climatic fluctuations in generating the patterns of genetic diversity observed in P. boreus. These findings highlight both the potential for cryptic biodiversity in widespread North American scorpion species and the importance of phylogeographical studies for understanding the factors responsible for generating the biodiversity of western North America.

The feasibility of sustained controlled delivery of pharmacologically relevant amounts of the opiate analgesic buprenorphine from a novel, mucoadhesive non-eroding oral mucosal patch was assessed in human volunteers. In a randomized, two-period crossover study, each subject received a 0.5 cm 2 patch containing 2.9 mg of buprenorphine free base at one of two oral mucosal sites (upper gum or upper lip) in period 1 of the study and at the alternate site in period 2. Patches were removed after 12 h of wear and residual drug in the patch was measured. Serum buprenorphine concentrations from time of patch application through 24 h post-application were determined. Measurements of pupillary miosis, an indicator of opiate pharmacologic activity, were made at intervals over each 24-h study period. Safety, comfort and mucoadhesion were assessed. No serious safety problems were encountered; adverse experiences were mild to moderate and were consistent with the known effects of buprenorphine. Irritation to the oral mucosa was low and acceptable. Comfort and taste were acceptable. Patches adhered satisfactorily for the entire 12-h wear period when applied to the gum, but adhesion to the lip site was less satisfactory. After an initial lag time of about 1–3 h, pharmacologically relevant serum concentrations of buprenorphine, as assessed by pupillary miosis, were attained and generally sustained for 12–24 h post-dose. Changes in pupillary diameter correlated well with serum buprenorphine levels. Serum buprenorphine AUCs after gum and lip application of the patches were 5594 ± 1419 and 3958 ±780 pg · h / ml , respectively, and indicated greater delivery of buprenorphine from the patches applied to the gum versus the lip, possibly due to the superior mucoadhesion at the gum site.

The hydrodynamic behavior of a cold experimental circulating fluidized bed (CFB) has been investigated using deterministic chaos theory. The time series of experimentally measured differential pressure fluctuations along the riser height of a CFB are analyzed. Major frequencies were identified using spectral frequency analysis. Poincare maps of the attractor were constructed and the correlation dimension measured. The hydrodynamic behavior of the CFB appears to be chaotic. The fractal correlation dimension of this chaotic attractor is found to be low, ranging from 1.5 to 1.9, for the fluidizing conditions studied.

Prolonged swing phase rectus femoris (RF) activity has been implicated as a cause of stiff-knee gait (SKG) in children with cerebral palsy (CP) and continues to be cited as an indicator for RF intervention. The purpose of this study was to determine what, if any, association exists between abnormal RF activity during preswing, initial swing and/or midswing and SKG in children with CP. This retrospective analysis involved three examiners independently reviewing sagittal plane knee kinematic and RF surface electromyographic (EMG) data from 407 affected limbs of 234 pediatric patients with CP. Five kinematic parameters were rated by each examiner as normal or pathologic: peak knee flexion, knee range of motion during initial swing, total knee range of motion, peak knee flexion timing, and rate of knee flexion. These ratings were used to classify each limb into one of three groups: SKG, Borderline SKG, or Non-SKG. From a representative EMG tracing, RF activity was examined during: the first half of preswing, the latter 2/3 of initial swing, and midswing. Chi-squared tests were used to determine if significant associations existed between SKG and RF activation during these three subphases. There was no association between SKG and prolonged RF activity during the latter 2/3 of initial swing or during midswing. However, a significant relationship between SKG and RF activity during the first half of preswing was found (p

The knee joint is the one of the most common locations for congenital and developmental musculoskeletal abnormalities. Initial imaging of the knee joint should always begin with conventional radiographs. However, evaluation of the bone marrow, cartilaginous, ligamentous, and other soft-tissue components of the knee joint are better characterized with magnetic resonance imaging (MRI). We present the MRI findings of prevalent congenital and developmental abnormalities in the paediatric knee with particular emphasis on the components of the growing skeleton.

A 40-year-old man presented with a 25-year history of cramps affecting the abdomen, neck, and limbs. Examination revealed fasciculation in the forearms, abdomen, and chin (video on the Neurology ® Web site at [Neurology.org][1]). There was shoulder girdle wasting with bilateral mastectomy scars (figure, B and C). Creatine kinase (CK) was 1,650 U/L (normal < 310 U/L). Electrodiagnostic studies revealed sensory neuronopathy with neurogenic changes on EMG. Genetic testing demonstrated excess CAG repeats in the androgen receptor gene, confirming Kennedy disease.1 This X-linked disorder is the most common adult-onset spinal muscular atrophy. CK can be markedly raised.2 Gynecomastia results from androgen insufficiency and can precede the development of neurologic symptoms. [1]: http://www.neurology.org/

As the demand for cloned embryos and offspring increases, the need arises for the development of nuclear transfer procedures that are improved in both efficiency and ease of operation. Here, we describe a novel zona-free cloning method that doubles the throughput in cloned bovine embryo production over current procedures and generates viable offspring with the same efficiency. Elements of the procedure include zona-free enucleation without a holding pipette, automated fusion of 5-10 oocyte-donor cell pairs and microdrop in vitro culture. Using this system, zona-free embryos were reconstructed from five independent primary cell lines and cultured either singularly (single-IVC) or as aggregates of three (triple-IVC). Blastocysts of transferable quality were obtained at similar rates from zona-free single-IVC, triple-IVC, and control zona-intact embryos (33%, 25%, and 29%, respectively). In a direct comparison, there was no significant difference in development to live calves at term between single-IVC, triple-IVC, and zona-intact embryos derived from the same adult fibroblast line (10%, 13%, and 15%, respectively). This zona-free cloning method could be straightforward for users of conventional cloning procedures to adopt and may prove a simple, fast, and efficient alternative for nuclear cloning of other species as well.

Several studies have shown that both quiescent and proliferating somatic donor cells can be fully reprogrammed after nuclear transfer (NT) and result in viable offspring. So far, however, no comparative study has conclusively demonstrated the relative importance of donor cell cycle stage on nuclear cloning efficiency. Here, we compare two different types of bovine fetal fibroblasts (BFFs) that were synchronized in G 0 , G 1 , and different phases within G 1 . We show that for non-transgenic (non-TG) fibroblasts, serum starvation into G 0 results in a significantly higher percentage of viable calves at term than synchronization in early G 1 or late G 1 . For transgenic fibroblasts, however, cells selected in G 1 show significantly higher development to calves at term and higher post-natal survival to weaning than cells in G 0 . This suggests that it may be necessary to coordinate donor cell type and cell cycle stage to maximize overall cloning efficiency.

In cattle, oocytes obtained from follicles smaller than 3 mm in diameter can undergo maturation in vitro, progressing to MII and undergoing fertilization, but are developmentally incompetent. Cytoplasts were prepared from in vitro matured oocytes aspirated from small (1-3 mm) or large (6-12 mm) follicles and fused to serum starved mural granulosa cells. Following activation, reconstructed embryos were cultured for 7 days and classified G1 to G4, before being processed for nuclei counting or transferred to synchronized recipients. Oocytes from small follicles had lower rates of polar body extrusion (59.6 vs. 69%; 731/1230 vs. 608/857) and fusion (71.4 vs. 78.8%; 360/497 vs. 364/465; P < 0.06). There were no differences in total rate of blastocysts development (60 vs. 59.8%; small vs. large), or any grade classification. A significant interaction was detected between follicle size and embryo grade with G3 embryos from small follicles having a greater cell number. Developmental competence of G1 and G2 embryos did not differ at day 27 (48 vs. 46%; 16/33 vs. 17/37; small vs. large). Although there were no differences in fetal size between the two groups, differences in allantois length (53 vs. 86 mm; small vs. large; P < 0.002) and allantois width (9.5 vs. 13 mm; small vs. large; P < 0.06) were seen. No differences in survival to term (2/13 in each group) were observed. These results indicate that cytoplasts from follicles of 1-3 and 6-12 mm in diameter are equally developmentally competent when used in a nuclear transfer procedure.

Summary Carcinoembryonic antigen (CEA) was measured preoperatively in 43 patients who underwent complete resection of primary lung cancer. 7 of 43 patients (17%) had CEA levels in the cancer diagnostic range ( > 40.9 μg/litre), none of whom survived longer than 10 months. At two years, it was apparent that those patients with a preoperative CEA less than 21 μg had a better survival rate than those with a CEA 21–40.9 μg/litre ( P

Radioactive glucose and 2-deoxy- d -glucose (deoxyglucose) were compared as tracers for estimating the rate of rat brain glucose utilization after an intravenous injection. The [brain] : [blood] ratio of deoxyglucose content was twice as large as that of glucose at 5 min, 3 times at 45 min, and 13 times at 240 min. While [2- 14 C]glucose accounted for about 20% of total brain 14 C (acid soluble) at 10 min, labeled deoxyglucose took 45 min to fall to comparable levels. Labeled 2-deoxy- d -glucose-6-phosphate (deoxyglucose phosphate) did not accumulate after 10 min despite the fact that deoxyglucose was available continuously for phosphorylation. This resulted from loss of deoxyglucose phosphate, which was in proportion to its concentration. The disappearance of deoxyglucose phosphate was probably catalyzed by glucose-6-phosphatase, which reacts with deoxyglucose phosphate and which is present in brain. Since the [brain]: [blood] ratio of labeled deoxyglucose increases as time passes and since deoxyglucose phosphate is lost from brain at an appreciable rate, its use for quantitative determination of the rate of rat brain glucose utilization is much more complex than previously realized. Approximately 45 min are necessary to reduce background contamination to acceeptable levels for autoradiography during which time substantial amounts of deoxyglucose phosphate may be lost. The primary reason for using deoxyglucose to measure glucose utilization by the brain is the assumption that deoxyglucose phosphate is lost very slowly from the brain. In view of the fact that loss of deoxyglucose phosphate cannot be ignored, the advantage of labeled deoxyglucose over labeled glucose is open to question.

All 5 enzymes of the urea cycle have been determined on liver samples obtained from rats during late foetal and neonatal life. Since no argininosuccinate synthetase activity could be detected before

We used the incorporation of tracer quantities of radiolabeled glucose analogues into muscle and CNS tissues to determine, first, whether unilateral dorsal root deafferentation affects hindlimb flexor and extensor muscles of that side equally. For this we compared the incorporation of [ 3 H]fluorodeoxyglucose into selected muscles in the intact and the deafferented side. The muscles were dissected out after exercise on a treadmill, and tracer incorporation was measured by scintillation counting. Second, we used the [ 14 C]2-DG radioautographic method of Sokoloff to seek confirmation of the involvement of certain CNS structures in locomotor control. We found fascinating side to side asymmetries in glucose metabolism, in the cervical spinal cord, motor cortex, and caudate nucleus. There is still debate about the manner in which “neuronal function”, regional blood flow, and glucose metabolism, may be coupled (or even on the existence of such coupling). However, these methods can be useful by their anatomical resolution, and the possibility of making multiple regional measurements from a single subject.

Publisher Summary This chapter discusses the methods that can be used to assay acetyl-CoA carboxylase. The optical methods are most convenient however are unsuitable except for enzyme of high purity because of interference from turbidity and contaminating adenosine triphosphatase (ATPase). The procedures employed in assaying the mammary enzyme are based on measuring the incorporation of H 14 CO 3 – into malonyl-CoA under carefully restricted conditions, which give highly reproducible results. The enzyme is first activated by incubating with citrate for 15 minutes, substrates are then added and incubation is continued for 10 minutes. The reaction is halted with perchloric acid and residual H 14 CO 3 – is completely removed and the [ 14 C]malonyl-CoA is determined in a liquid scintillation spectrometer. Two methods are used: (1) assay method A, which is employed throughout the purification procedure; and (2) assay method B, which provides conditions for maximum activity. The principal differences between these methods are in the concentrations of assay components, the use of Mn 2+ in assay A and Mg 2+ in assay B, and the inclusion of an ATP-generating system in assay A.

The measurement of the serum level of most of the apo-lipoproteins is a tedious operation, unsuited to routine use. But two of these proteins, namely those designated as CI and CII, are known to stimulate the activity of lipoprotein lipase, and are thus open to estimation via a sensitive enzymic reaction. The purpose of this report is to describe some results which have been obtained with an assay based on the observation by Whayne and Felts (19 70) that guinea pig post-heparin plasma does not hydrolyse Intralipid unless it is activated by the addition of human or rat serum.

A method is described which enables the ability of human serum to activate guinea pig lipoprotein lipase to be measured in terms of an arbitrary standard. Evidence is offered which strongly suggests that the substance measured is also the activator of human lipoprotein lipase and observations on the relative levels of activator in human sera are given.

A method has been devised for the complete chemical analysis of serum lipoproteins, in which the constituents are separated by thin-layer chromatography and then measured by means of a flame ionisation detector. Since the response of the detector differs for each constituent, it is necessary to use a previously prepared calibration curve for each one. A complete analysis can be obtained from a single run on about 20 μg of lipoprotein. However, from 5−10 chromatograms are needed for an adequate degree of precision. The method, which could be adapted to the measurement of tissue lipids, takes less than 2 h to complete. This speed and simplicity seem to give the method considerable potential for the investigation of patients with disorders of lipid transport.

γ-Guanidinobutyramide has been shown to reduce blood urea levels in experimental animals and humans by an extra-renal mechanism. The effect of this compound on the activity of urea cycle enzymes in rat liver has been investigated by in vitro and in vivo studies. Evidence of M in vitro inhibition ofargininosuccinate synthetase activity has been obtained. It is, however, unlikely that the reduction of blood urea observed after therapeutic exhibition of the drug is due to urea cycle enzyme inhibition.

A competitive protein-binding assay for the measurement of plasma oestriol in pregnancy is described, using a binding protein prepared from lamb uterus. The method involves an acid hydrolysis with subsequent extraction and partition of the oestriol followed by competition with labelled oestriol for binding sites on the uterine cytosol preparation. The binding protein was prepared in bulk and freeze-dried to avoid the problems involved in dealing with small, variable batches. The protein was found to be specific for oestrogens and extremely stable and showing no deterioration after storage for seven months at ambient temperature.

A comparison of a simple automated method for total urinary oestrogens (“oestriol”) in pregnancy with a reputedly specific manual technique showed that the results obtained using the automated method were significantly higher than those found using the manual method. This discrepancy was found to be largely, if not totally, due to losses occurring during the manual procedure, implying that the automated method gives the more accurate result.