Expression cloning of a cDNA for human ceramide glucosyltransferase that catalyzes the first glycosylation step of glycosphingolipid synthesis.

We have isolated a cDNA encoding human ceramide glucosyltransferase (glucosylceramide synthase, UDP-glucose:N-acylsphingosine D-glucosyltransferase, EC 2.4.1.80) by expression cloning using as a recipient GM-95 cells lacking the enzyme. The enzyme catalyzes the first glycosylation step of glycosphingolipid synthesis and the product, glucosylceramide, serves as the core of more than 300 glycosphingolipids. The cDNA has a G+C-rich 5' untranslated region of 290 nucleotides and the open reading frame encodes 394 amino acids (44.9 kDa). A hydrophobic segment was found near the N terminus that is the potential signal-anchor sequence. In addition, considerable hydrophobicity was detected in the regions close to the C terminus, which may interact with the membrane. A catalytically active enzyme was produced from Escherichia coli transfected with the cDNA. Northern blot analysis revealed a single transcript of 3.5 kb, and the mRNA was widely expressed in organs. The amino acid sequence of ceramide glucosyltransferase shows no significant homology to ceramide galactosyltransferase, which indicates different evolutionary origins of these enzymes.

How the first biopolymers could have evolved.

In this work, we discuss a possible origin of the first biopolymers with stable unique structures. We suggest that at the prebiotic stage of evolution, long organic polymers had to be compact to avoid hydrolysis and had to be soluble and thus must not be exceedingly hydrophobic. We present an algorithm that generates such sequences for model proteins. The evolved sequences turn out to have a stable unique structure, into which they quickly fold. This result illustrates the idea that the unique three-dimensional native structures of first biopolymers could have evolved as a side effect of nonspecific physicochemical factors acting at the prebiotic stage of evolution.

Adherence to the first-AUG rule when a second AUG codon follows closely upon the first.

The rule that eukaryotic ribosomes initiate translation exclusively at the 5' proximal AUG codon is abrogated under rare conditions. One circumstance that has been suggested to allow dual initiation is close apposition of a second AUG codon. A possible mechanism might be that the scanning 40S ribosomal subunit flutters back and forth instead of stopping cleanly at the first AUG. This hypothesis seems to be ruled out by evidence presented herein that in certain mRNAs, the first of two close AUG codons is recognized uniquely. To achieve this, the 5' proximal AUG has to be provided with the full consensus sequence; even small departures allow a second nearby AUG codon to be reached by leaky scanning. This context-dependent leaky scanning unexpectedly fails when the second AUG codon is moved some distance from the first. A likely explanation, based on analyzing the accessibility of a far-downstream AUG codon under conditions of initiation versus elongation, is that 80S elongating ribosomes advancing from the 5' proximal start site can mask potential downstream start sites.

The first extrasolar planet discovered with a new-generation high-throughput Doppler instrument

We report the detection of the first extrasolar planet, ET-1 (HD 102195b), using the Exoplanet Tracker (ET), a new-generation Doppler instrument. The planet orbits HD 102195, a young star with solar metallicity that may be part of the local association. The planet imparts radial velocity variability to the star with a semiamplitude of 63.4 ± 2.0 m s^-1 and a period of 4.11 days. The planetary minimum mass (m sin i) is 0.488MJ ± 0.015M_J. The planet was initially detected in the spring of 2005 with the Kitt Peak National Observatory (KPNO) 0.9 m coudé feed telescope. The detection was confirmed by radial velocity observations with the ET at the KPNO 2.1 m telescope and also at the 9 m Hobby-Eberly Telescope (HET) with its High Resolution Spectrograph. This planetary discovery with a 0.9 m telescope around a V = 8.05 magnitude star was made possible by the high throughput of the instrument: 49% measured from the fiber output to the detector. The ET's interferometer-based approach is an effective method for planet detection. In addition, the ET concept is adaptable to multiple-object Doppler observations or very high precision observations with a cross-dispersed echelle spectrograph to separate stellar fringes over a broad wavelength band. In addition to spectroscopic observations of HD 102195, we obtained brightness measurements with one of the automated photometric telescopes at Fairborn Observatory. Those observations reveal that HD 102195 is a spotted variable star with an amplitude of ~0.015 mag and a 12.3 ± 0.3 day period. This is consistent with spectroscopically observed Ca II H and K emission levels and line-broadening measurements but inconsistent with rotational modulation of surface activity as the cause of the radial velocity variability. Our photometric observations rule out transits of the planetary companion.

The First Child In A Chinese Family Who Could Read Prior To Entry Into Elementary School: A Qualitative Intrinsic Case Study

ABSTRACT This study is an account of the literacy-related human environment a Chinese girl experienced as the first person in the history of her family who was able to read prior to entry into elementary school. Temporally speaking, the study spanned more than a decade from the initial, tentative research question to the formal, primary research question. Spatially speaking, it crossed three cultures: the Chinese, Korean, and American cultures. The study was inspired by the Zero Project in China, known as the "Project of Quality Education and Implementation for Children Aged Zero (fetus) to Six." The significance of the content issue in a child's literacy curriculum was explored in an interdisciplinary way. Case study served as a holistic research approach and provided the researcher with free temporal and spatial distance to pursue the indefinably multi-dimensional intricacies of a child's early literacy acquisition among generations in the family. Interpretation of the case was based on the relevant concepts within the scope of the researcher's knowledge of Chinese culture. Major findings revealed that the child's literacy acquisition was inseparably related to her parents' background as well as their awareness of and attitudes towards literacy, and that the foundation of all this was the harmony of the family. Through the lens of generational attitudes towards literacy and especially the lens of the researcher's multicultural life experiences, this study contributes to the field of curriculum studies in general and early literacy curriculum in particular by stimulating people to reconsider what to read to children, besides how to read to them. It calls attention once again to the classic curriculum question, "What knowledge is of most worth?" as well as what is the most essential spiritual food human beings need besides physical needs. This study suggests that Chinese philosophy should be included in a child's early literacy curriculum in China and calls for dialogues on the content issue of curriculum to gain a deeper understanding of human nature so that humans might co-live peacefully with all beings in the universe.

The Importance of the First Psychotherapy Case in the Development of the Therapist's Professional Self as Viewed Through the Lens of Self Psychology

This paper explores the gap in the literature between what is herein referred to as the "first psychotherapy case" and its impact on the development of the trainee psychotherapist's professional self. The self psychology concepts of identity development, selfobject needs and fulfillment, narcissism, shame, countertransference, and structuralization are incorporated into the theoretical framework from which this developmental milestone is viewed. The theory's emphasis on early experiences and the development of self highlight the distinctiveness of the first case for the therapist. The beginning psychotherapy case poses a unique context for selfobject experiences and the developing self, involving both the therapist's presumably mature needs (assuming an existing cohesive nuclear self) and more infantile needs as the professional, peripheral self develops. As a result, the potential and important implications for the psychotherapist, the patient, training implications for the supervisor, and the ensuing treatment through termination are identified. The intent is to shed light on an area that is understudied thus far, and to begin a conversation as to why and how the impact of the first case on the psychotherapist should be examined. Implications, limitations, and ideas for future exploratory and qualitative research are also discussed.

The First Century of Right to Arms Litigation

This Article examines state court cases involving the right to arms, during the first century following ratification of the Amendment in 1791. This is not the first article to survey some of those cases. This Article includes additional cases, and details the procedural postures and facts, not only the holdings. The Article closely examines how the Supreme Court integrated the nineteenth century arms cases into Heller and McDonald to shape modern Second Amendment law. Part I briefly explains two English cases which greatly influenced American legal understandings. Semayne’s Case is the foundation of “castle doctrine” — the right to home security which includes the right of armed self-defense in the home. Sir John Knight’s Case fortified the tradition of the right to bear arms, providing that the person must bear arms in a non-terrifying manner. Part II examines American antebellum cases; these are the cases to which Heller looked for guidance on the meaning of the Second Amendment. Part III looks at cases from Reconstruction and the early years of Jim Crow, through 1891. As with the antebellum cases, the large majority of post-war cases are from the Southeast, which during the nineteenth century was the region most ardent for gun control. The heart of gun control country was Tennessee and Arkansas; courts there resisted some infringements of the right to arms, but eventually gave up. Heller and McDonald did not look to the Jim Crow cases as constructive precedents on the Second Amendment.

Disquieting Discretion: Race, Geography & the Colorado Death Penalty in the First Decade of the Twenty-First Century

This Article demonstrates through original statistical research that prosecutors in Colorado were more likely to seek the death penalty against minority defendants than against white defendants. Moreover, defendants in Colorado’s Eighteenth Judicial District were more likely to face a death prosecution than defendants elsewhere in the state. Our empirical analysis demonstrates that even when one controls for the differential rates at which different groups commit statutorily death-eligible murders, non-white defendants and defendants in the Eighteenth Judicial District were still more likely than others to face a death penalty prosecution. Even when the heinousness of the crime is accounted for, the race of the accused and the place of the crime are statistically significant predictors of whether prosecutors will seek the death penalty. We discuss the implications of this disparate impact on the constitutionality of Colorado’s death penalty regime, concluding that the Colorado statute does not meet the dictates of the Eighth Amendment to the Constitution.

High Value Lies, Ugly Truths, and the First Amendment

Lying has a complicated relationship with the First Amendment. It is beyond question that some lies – such as perjury or pretending to be a police officer – are not covered by the First Amendment. But it is equally clear that some lies, even intentionally lying about military honors, are entitled to First Amendment protection. U.S. v. Alvarez, 132 S. Ct. 2537 (2012). To date, however, both Supreme Court doctrine and academic commentary has taken for granted that any constitutional protection for lies is purely prophylactic – it protects the liar to avoid chilling truthful speech. This Article is the first to argue, contrary to conventional wisdom, that certain types of lies paradoxically advance the values underlying the First Amendment. Our framework is descriptively novel and doctrinally important insofar as we provide the first comprehensive post-Alvarez look at the wide range of lies that may raise First Amendment issues. Because there was no majority opinion in Alvarez, there is uncertainty about which standard of constitutional scrutiny should apply to protected lies, an issue we examine at length. Moreover, our normative claim is straightforward: when a lie has intrinsic or instrumental value it should be treated differently from other types of lies and warrant the greatest constitutional protection. Specifically, we argue that investigative deceptions – lies used to secure truthful factual information about matters of public concern – deserve the utmost constitutional protection because they advance the underling purposes of free speech: they enhance political discourse, help reveal the truth, and promote individual autonomy. A prototypical investigative deception is the sort of misrepresentation required in order for an undercover journalist, investigator, or activist to gain access to information or images of great political significance that would not be available if the investigator disclosed her reporting or political objectives. Tactical use of such lies have a long history in American journalism and activism, from Upton Sinclair to his modern day heirs. Using the proliferation of anti-whistleblower statutes like Ag Gag laws as an illustrative example, we argue that investigative deceptions are a category of high value lies that ought to receive rigorous protection under the First Amendment. At the same time, we recognize that not all lies are alike and that in other areas, the government regulation of lies serves legitimate interests. We therefore conclude the Article by drawing some limiting principles to our theory.

Understanding the structure of the first atomic contact in gold

We have studied experimentally jump-to-contact (JC) and jump-out-of-contact (JOC) phenomena in gold electrodes. JC can be observed at first contact when two metals approach each other, while JOC occurs in the last contact before breaking. When the indentation depth between the electrodes is limited to a certain value of conductance, a highly reproducible behaviour in the evolution of the conductance can be obtained for hundreds of cycles of formation and rupture. Molecular dynamics simulations of this process show how the two metallic electrodes are shaped into tips of a well-defined crystallographic structure formed through a mechanical annealing mechanism. We report a detailed analysis of the atomic configurations obtained before contact and rupture of these stable structures and obtained their conductance using first-principles quantum transport calculations. These results help us understand the values of conductance obtained experimentally in the JC and JOC phenomena and improve our understanding of atomic-sized contacts and the evolution of their structural characteristics.

Carybdea marsupialis (Cubozoa) in the Mediterranean Sea: The first case of a sting causing cutaneous and systemic manifestations

A woman stung by the box jellyfish Carybdea marsupialis (Cnidaria, Cubozoa) at a Spanish Mediterranean beach, showed systemic manifestations over several months (pain far from the inoculation point, arthralgia, paresthesia, hyperesthesia, increase of eosinophils and IgE) in addition to the skin condition.

The X-ray outburst of the Galactic Centre magnetar SGR J1745−2900 during the first 1.5 year

In 2013 April a new magnetar, SGR 1745−2900, was discovered as it entered an outburst, at only 2.4 arcsec angular distance from the supermassive black hole at the centre of the Milky Way, Sagittarius A*. SGR 1745−2900 has a surface dipolar magnetic field of ∼2 × 1014 G, and it is the neutron star closest to a black hole ever observed. The new source was detected both in the radio and X-ray bands, with a peak X-ray luminosity LX ∼ 5 × 1035 erg s−1. Here we report on the long-term Chandra (25 observations) and XMM–Newton (eight observations) X-ray monitoring campaign of SGR 1745−2900 from the onset of the outburst in 2013 April until 2014 September. This unprecedented data set allows us to refine the timing properties of the source, as well as to study the outburst spectral evolution as a function of time and rotational phase. Our timing analysis confirms the increase in the spin period derivative by a factor of ∼2 around 2013 June, and reveals that a further increase occurred between 2013 October 30 and 2014 February 21. We find that the period derivative changed from 6.6 × 10−12 to 3.3 × 10−11 s s−1 in 1.5 yr. On the other hand, this magnetar shows a slow flux decay compared to other magnetars and a rather inefficient surface cooling. In particular, starquake-induced crustal cooling models alone have difficulty in explaining the high luminosity of the source for the first ∼200 d of its outburst, and additional heating of the star surface from currents flowing in a twisted magnetic bundle is probably playing an important role in the outburst evolution.

Steamboats and pleasure travels: success and failure of the first Spanish initiatives in the mid-nineteenth century

Steam technology revolutionised maritime transport during the nineteenth century. Together with the establishment of the first regular lines, steamers soon led to the commencement of pleasure navigation. The aim of this article is to analyse the impact and scope of this process in Spain, by means of a study of the first experiences in the mid-nineteenth century. In addition to a brief introduction and final conclusions, the paper is structured around four sections. The first contains an appraisal of the situation of passenger transport. Some information is then provided regarding the first cruise in 1854. Next, the essay highlights some of the features of short excursions that were very well received by the public, especially in the island of Majorca. Finally, attention is given to a very special type of travel, the main attraction of which lay in the opportunity to witness an event of a military nature.