Origin of complex crystal structures of elements at pressure

We present a unifying theory for the observed complex structures of the sp-bonded elements under pressure based on nearly free electron picture (NFE). In the intermediate pressure regime the dominant contribution to crystal structure arises from Fermi-surface Brillouin zone (FSBZ) interactions - structures which allow this are favoured. This simple theory explains the observed crystal structures, transport properties, the evolution of internal and unit cell parameters with pressure. We illustrate it with experimental data for these elements and ab initio calculation for Li.Comment: 4 pages 5 figure

Aggravated stuttering following subthalamic deep brain stimulation in Parkinson's disease - two cases

Stuttering is a speech disorder with disruption of verbal fluency which is occasionally present in patients with Parkinson's disease (PD). Long-term medical management of PD is frequently complicated by fluctuating motor functions and dyskinesias. High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment of motor fluctuations and is the most common surgical procedure in PD. Here we report the re-occurrence and aggravation of stuttering following STN-DBS in two male patients treated for advanced PD. In both patients the speech fluency improved considerably when the neurostimulator was turned off, indicating that stuttering aggravation was related to neurostimulation of the STN itself, its afferent or efferent projections and/or to structures localized in the immediate proximity. This report supports previous studies demonstrating that lesions of the basal ganglia-thalamocortical motor circuit, including the STN, is involved in the development of stuttering. In advanced PD STN-DBS is generally an effective and safe treatment. However, patients with PD and stuttering should be informed about the risk of aggravated symptoms following surgical therapy

An Ancient Relation between Units of Length and Volume Based on a Sphere

The modern metric system defines units of volume based on the cube. We propose that the ancient Egyptian system of measuring capacity employed a similar concept, but used the sphere instead. When considered in ancient Egyptian units, the volume of a sphere, whose circumference is one royal cubit, equals half a hekat. Using the measurements of large sets of ancient containers as a database, the article demonstrates that this formula was characteristic of Egyptian and Egyptian-related pottery vessels but not of the ceramics of Mesopotamia, which had a different system of measuring length and volume units

A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis : First-in-human trial of ChAd63-KH

BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. METHODS: We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFNγ ELISPOT and intracellular flow cytometry. FINDINGS: ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. CONCLUSION: The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. TRIAL REGISTRATION: This clinical trial (LEISH1) was registered at EudraCT (2012-005596-14) and ISRCTN (07766359)

Full lifetime perspectives on the costs and benefits of lay date variation in tree swallows

Animals must balance various costs and benefits when deciding when to breed. The costs and benefits of breeding at different times have received much attention, but most studies have been limited to investigating short-term season-to-season fitness effects. However, breeding early, versus late, in a season may influence lifetime fitness over many years, trading off in complex ways across the breeder?s lifepan. In this study, we examined the complete life histories of 867 female tree swallows (Tachycineta bicolor) breeding in Ithaca, New York, between 2002 and 2016. Earlier breeders outperformed later breeders in short-term measures of reproductive output and offspring quality. Though there were weak indications that females paid long-term future survival costs for breeding early, lifetime fledgling output was markedly higher overall in early-breeding birds. Importantly, older females breeding later in the season did not experience compensating life-history advantages that suggested an alternative equal-fitness breeding strategy. Rather, most or all of the swallows appear to be breeding as early as they can, and differences in lay dates appear to be determined primarily by differences in individual quality or condition. Lay date had a significant repeatability across breeding attempts by the same female, and the first lay date of females fledged in our population was strongly influenced by the first lay date of their mothers, indicating the potential for ongoing selection on lay date. By examining performance over the entire lifespan of a large number of individuals, we were able to clarify the relationship between timing of breeding and fitness and gain new insight into the sources of variability in this important life history trait.Fil: Winkler, David Ward. Cornell University; Estados UnidosFil: Hallinger, Kelly K.. Cornell University; Estados UnidosFil: Pegan, Teresa M.. University of Michigan; Estados UnidosFil: Taff, Conor C.. Cornell University; Estados UnidosFil: Verhoeven, Mo A.. University of Groningen; Países BajosFil: Van Oordt, David Chang. Cornell University; Estados UnidosFil: Stager, Maria. University of Montana; Estados UnidosFil: Uehling, Jennifer J.. Cornell University; Estados UnidosFil: Vitousek, Maren N.. Cornell University; Estados UnidosFil: Andersen, Michael J.. University of New Mexico; Estados UnidosFil: Ardia, Daniel R.. Franklin & Marshall College; Estados UnidosFil: Belmaker, Amos. Tel Aviv University; IsraelFil: Ferretti, Valentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Forsman, Anna M.. University Of Central Florida; Estados UnidosFil: Gaul, Jennifer R.. International High School at La Guardia Community College; Estados UnidosFil: Llambias, Paulo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; ArgentinaFil: Orzechowski, Sophia C.. Harvard University; Estados UnidosFil: Shipley, Ryan. Max Planck Institute For Animal Behavior; AlemaniaFil: Wilson, Maya. Virginia Polytechnic Institute. Department Of Geological Sciences; Estados UnidosFil: Yoon, Hyun Seok. University of Tennessee; Estados Unido

Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7

Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells