Mucopolysaccharidosis type I (MPS I) is a rare lysosomal storage disorder treated with bone marrow transplantation or enzyme replacement therapy with laronidase, a high-cost orphan drug. Laronidase was approved by the US Food and Drug Administration and the European Medicines Agency in 2003 and by the Brazilian National Health Surveillance Agency in 2005. Many Brazilian MPS I patients have been receiving laronidase despite the absence of a governmental policy regulating access to the drug. Epidemiological and treatment data concerning MPS I (...) are scarce. This study aims to present a demographic profile of Brazilian patients with MPS I, describe the routes of access to laronidase in Brazil, and discuss associated ethical issues relating to public funding of orphan drugs. (shrink)

A total of 1918 loci, detected by the hybridization of 938 expressed sequence tag unigenes from 26 Triticeae cDNA libraries, were mapped to wheat homoeologous group 4 chromosomes using a set of deletion, ditelosomic, and nulli-tetrasomic lines. The 1918 EST loci were not distributed uniformly among the three group 4 chromosomes; 41, 28, and 31% mapped to chromosomes 4A, 4B, and 4D, respectively. This pattern is in contrast to the cumulative results of EST mapping in all homoeologous groups, as reported (...) elsewhere, that found the highest proportion of loci mapped to the B genome. Sixty-five percent of these 1918 loci mapped to the long arms of homoeologous group 4 chromosomes, while 35% mapped to the short arms. The distal regions of chromosome arms showed higher numbers of loci than the proximal regions, with the exception of 4DL. This study confirmed the complex structure of chromosome 4A that contains two reciprocal translocations and two inversions, previously identified. An additional inversion in the centromeric region of 4A was revealed. A consensus map for homoeologous group 4 was developed from 119 ESTs unique to group 4. Forty-nine percent of these ESTs were found to be homoologous to sequences on rice chromosome 3, 12% had matches with sequences on other rice chromosomes, and 39% had no matches with rice sequences at all. Limited homology was found between wheat ESTs on homoeologous group 4 and the Arabidopsis genome. Forty-two percent of the homoeologous group 4 ESTs could be classified into functional categories on the basis of blastX searches against all protein databases. (shrink)

The complex hexaploid wheat genome offers many challenges for genomics research. Expressed sequence tags facilitate the analysis of gene-coding regions and provide a rich source of molecular markers for mapping and comparison with model organisms. The objectives of this study were to construct a high-density EST chromosome bin map of wheat homoeologous group 2 chromosomes to determine the distribution of ESTs, construct a consensus map of group 2 ESTs, investigate synteny, examine patterns of duplication, and assess the colinearity with rice (...) of ESTs assigned to the group 2 consensus bin map. A total of 2600 loci generated from 1110 ESTs were mapped to group 2 chromosomes by Southern hybridization onto wheat aneuploid chromosome and deletion stocks. A consensus map was constructed of 552 ESTs mapping to more than one group 2 chromosome. Regions of high gene density in distal bins and low gene density in proximal bins were found. Two interstitial gene-rich islands flanked by relatively gene-poor regions on both the short and long arms and having good synteny with rice were discovered. The map locations of two ESTs indicated the possible presence of a small pericentric inversion on chromosome 2B. Wheat chromosome group 2 was shown to share syntenous blocks with rice chromosomes 4 and 7. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

This report describes the rationale, approaches, organization, and resource development leading to a large-scale deletion bin map of the hexaploid wheat genome. Accompanying reports in this issue detail results from chromosome bin-mapping of expressed sequence tags representing genes onto the seven homoeologous chromosome groups and a global analysis of the entire mapped wheat EST data set. Among the resources developed were the first extensive public wheat EST collection. Described are protocols for sequencing, sequence processing, EST nomenclature, and the assembly of (...) ESTs into contigs. These contigs plus singletons were used for selection of distinct sequence motif unigenes. Selected ESTs were rearrayed, validated by 5′ and 3′ sequencing, and amplified for probing a series of wheat aneuploid and deletion stocks. Images and data for all Southern hybridizations were deposited in databases and were used by the coordinators for each of the seven homoeologous chromosome groups to validate the mapping results. Results from this project have established the foundation for future developments in wheat genomics. (shrink)

It is shown that (a) both the dispersion relations between the mean frequency θ0 and the mean wave number k 0 are invariant under the Lorentz transformation; and (b) the relativistic Doppler effects on θ 0 and k 0 differ. In the suboptic packet there is anomalous red shift in the mean wave number k' 0 received from a source receding with speed v: k′ 0 changes sign through zero as v goes through the value vg, the mean group velocity (...) in the packet. In the superoptic packet the anomalous red shift is in the mean frequency θ′ 0 which reverses sign through zero as v goes through the value vp, the mean phase velocity in the packet. This last finding indicates a blackout of the superoptic signal when propagated toward a receiver moving away from the source at a speed greater than vp. There is no violation of causality involved, and the final conclusion of the paper is that it is not a fundamental axiom of “special relativity,” as usually believed, to deny that information can be transmitted at speeds greater than c. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:VIOLENCE AND NONVIOLENCE IN HINDU RELIGIOUS TRADITIONS Francis X. Clooney, SJ. Boston College Outline I.Violence, Sacrifice and Ritual 1. Some basic attitudes toward the killing of animals 2.Resolving the problem of sacrificial violence by internalization 3.Substitutions 4.Renunciation and nonviolence: an elite pathway 5.Violence andnonviolenceinrelation to vegetarianism: Hans Schmidt's theses?. Traditional Hindu Theorizations of Violence in Mimamsa Ritual Theory and Vedanta Theology 1. The ritual analysis (at Mimamsa Sutra 1.1.2) (...) of the Shyena rite which is performed in order to harm enemies 2.The Vedanta analysis (at Uttara Mimamsa Sutra 3.1.25) of ritual violence in relation to the prohibition of violence??. Violence in the Life of the State HOFrancis X. Clooney, S.J. 1. The royal power to punish (danda) 2.The synthesis of the ideals of brahmin and king a..The distribution and management of violence in the Laws ofManu (1st century CE) b. Policy toward warfare in the Arthashastra of Kautilya 3.The collapse of the brahmanical synthesis—and the emergence of a (seemingly) more nonviolent Hinduism 4.A comment on Gandhi (1 869-1948) and the contemporary emergence of post-Gandhian Hindu perspectives IV.Alternate Views from Outside the Sanskritic Tradition 1. Tamil Wisdom on Violence and Nonviolence: a.Tirukkural (c. 2nd century CE) b.Cilappatikaram (5th century CE) 2.Blood and Goddesses 3.From a Village Perspective a. Some Trouble with Cows b.Mahasweta Devi and the Literary Exposure of Violence V.The Question of a Christian Perspective on the Hindu Treatment of Violence and Religion: Are Victims Necessary? Some Presuppositions: • The following reflections, complex as they are, are governed by a reluctance to simplify Hindu teaching. I seek to avoid the view that the Hindu traditions had only one view of violence and nonviolence. • I use the term "Hindu" loosely and as a shorthand, without claiming that there is a single Hindu tradition, or a single creed shared by all Hindus, or a single attitude toward violence. But neither do I claim that there are simply many traditions without any common elements which justify the appellation "Hindu." • I am reluctant to idealize the Hindu traditions as if nonviolence must necessarily be taken as the epitome ofHindu thought. India's traditions are complex, and require complex treatment. • A serious artificiality of this paper is that I treat Hinduism without simultaneously lookinginto Buddhist andJain materials, though both were traditions with important and enduring commitments to nonviolence. Particularly with respect to the renunciant, marginal components of traditions, one ought not to make overly neat or decisive distinctions Violence and Nonviolence in Hindu Religious Traditions 1 1 1 between the Hindu, Buddhist, and Jain theories and practices related to violence and nonviolence. • I attempt to give preference to indigenous discussions ofissues related to violence and nonviolence; the context and mode of thinking are important, notjust the conclusions drawn. I therefore avoid simply mining Hindu texts for an answer to a contemporary question, "What is the Hindu attitude toward violence and nonviolence?" • In most ofwhat follows we must distinguish contexts where "violence" indicates "physical action which causes pain to some living being," from contexts where "violence" indicates "an intention, rooted in anger or malice, to hurt someone." I use the word "violence" for both in order to highlight the complex issues of distinction involved. In considering the Sanskrit formulations, one likewise has to distinguish himsa as "causing pain" from himsa as "intending to harm." • It is often difficult to date ancient texts, and even when one narrows down a date—within 200-300 years—its significance still depends on other, often equally broadly stated dates. Nevertheless, I do offer dates throughout, as summarized here: •ancient Vedic sacrificial practices, from before 1200 BCE •Vedic ritual analyses and reformulations of sacrifices as ritualized acts, in the Brahmanas, from after 1000 BCE •the Upanishadic exploration of the deeper meanings of ritual and interiorized alternatives to ritual, from after 900 BCE •the Buddha, c. 500 BCE •key texts in the theorization of royal power, The Laws of Manu (beginning of Common Era) and Arthashastra (c. 150 CE) •the Tamil wisdom text Tirukkural (100 CE) •Goddess texts as evidenced in Sanskrit formulations, from after 500 CE... (shrink)

“Men can never be free, because they’re weak, corrupt, worthless and restless. The people believe in authority; they’ve grown tired of waiting for miracle or mystery. Science is their religion; no greater explanation exists for them.” (Cigarette Smoking Man, "Talitha Cumi" The X-Files 3X24).

We study increasing F-sequences, where F is a dilator: an increasing F-sequence is a sequence (indexed by ordinal numbers) of ordinal numbers, starting with 0 and terminating at the first step x where F(x) is reached (at every step x + 1 we use the same process as in decreasing F-sequences, cf. [2], but with "+ 1" instead of "- 1"). By induction on dilators, we shall prove that every increasing F-sequence terminates and moreover we can determine for every dilator (...) F the point where the increasing F-sequence terminates. We apply these results to inverse Goodstein sequences, i.e. increasing (1 + Id) (ω) -sequences. We show that the theorem every inverse Goodstein sequence terminates (a combinatorial theorem about ordinal numbers) is not provable in ID 1 . For a general presentation of the results stated in this paper, see [1]. We use notions and results concerning the category ON (ordinal numbers), dilators and bilators, summarized in [2, pp. 25-31]. (shrink)

The apolipoprotein E gene plays an important role in the pathogenesis of Alzheimer's disease , and amyloid plaque comprised mostly of the amyloid-beta peptide ) is one of the major hallmarks of AD. However, the relationship between these two important molecules is poorly understood. We examined how A treatment affects APOE expression in cultured cells and tested the role of the transcription factor NF-B in APOE gene regulation. To delineate NF-B's role, we have characterized a 1098 nucleotide segment containing the (...) 5'-flanking region of the human APOE gene . Sequence analysis of this region suggests the presence of two potential NF-B elements. To demonstrate promoter activity, the region was cloned upstream of a promoterless luciferase gene. This segment was able to drive expression of luciferase in transient transfections of human fetal glial cells. Promoter activity was stimulated twofold by A treatment. Pretreatment with double-stranded DNA decoy oligonucleotides against NF-B reduced A stimulation. Deletion and mutagenetic analyses demonstrated that the distal NF-B element was functional and showed a strong DNA-protein complex band in gel shift analysis, similar to that from control NF-B consensus element. An anti-inflammatory and anti-NF-B drug, sodium salicylate, significantly blocked A-induced APOE promoter function. Our data provide evidence that upregulation of APOE by A in astroglial cells is mediated by an NF-B-element present in the 5'-flanking region of the APOE gene. (shrink)

Analysis shows that statements of ability are disguised conditionals. More exactly, the correct analysis of 'X could have done A' is 'If X h decided (chosen, willed ...) to do A, X would have done A'. Therefore having acted freely--having been able to act otherwise than one fact did--is compatible with determinism (with the causal determination of one's acts).

The end of the nineteenth century and the whole of the twentieth may justifiably be called a time of great discoveries in the micro-, macro-, and megaworlds. All bearing witness to the dynamic life of the universe, these discoveries have resulted primarily from progress in the instruments of research, leading to the discovery of many new elementary particles, new forms of interaction, fields, and astrophysical objects — quasars, pulsars, sources of X-ray emissions, and others. An understanding of the essence of (...) the processes involved in these objects and phenomena, however, comes up against certain difficulties , the overcoming of which is to be sought primarily along the lines of further improvement of the tools of research and processing of the information acquired, the application of existing theories and the development of new ones in physics and astrophysics, and the utilization of the achievements of the science of the most general laws of the motion and development of nature, society, and thought, i.e., dialectical materialism, as the general methodology of acquisition of scientific knowledge. (shrink)

We prove that in IST, Nelson's internal set theory, the Uniqueness and Collection principles, hold for all (including external) formulas. A corollary of the Collection theorem shows that in IST there are no definable mappings of a set X onto a set Y of greater (not equal) cardinality unless both sets are finite and #(Y) ≤ n #(X) for some standard n. Proofs are based on a rather general technique which may be applied to other nonstandard structures. In particular we (...) prove that in a nonstandard model of PA, Peano arithmetic, every hyperinteger uniquely definable by a formula of the PA language extended by the predicate of standardness, can be defined also by a pure PA formula. (shrink)

Let X be a separable Banach space and Q be a coanalytic subset of . We prove that the set of sequences in X which are weakly convergent to some eX and is a coanalytic subset of . The proof applies methods of effective descriptive set theory to Banach space theory. Using Silver’s Theorem [J. Silver, Every analytic set is Ramsey, J. Symbolic Logic 35 60–64], this result leads to the following dichotomy theorem: if X is a Banach space, is (...) a regular method of summability and is a bounded sequence in X, then there exists a subsequence iL such that either there exists eX such that every subsequence iH of iL is weakly summable w.r.t. to e and QiH,e); or for every subsequence iH of iL and every eX with QiH,e)the sequence iH is not weakly summable to e w.r.t. . This is a version for weak convergence of an Erdös–Magidor result, see [P. Erdös, M. Magidor, A note on Regular Methods of Summability, Proc. Amer. Math. Soc. 59 232–234]. Both theorems obtain some considerable generalizations. (shrink)

This article presents a novel full-reference image quality assessment algorithm by depicting the sub-band characteristics in the wavelet domain. The proposed image quality assessment method is based on energy estimation in the wavelet-transformed image. Image QA is achieved by applying a multilevel wavelet decomposition on both the original and the enhanced image. Next, the wavelet energy and vector are computed to obtain the percentage of the energy that corresponds to the approximation and the details, respectively. Further, the approximate and (...) detailed energy levels of both the original and the enhanced images are compared to formulate an image quality assessment. Numerous experiments are conducted on a dozen of image enhancement algorithms. The results presented show that the image with poor contrast in the foreground than the background has continuous regular coefficient values. The probability density function for such an image has a relatively lower WE and skewness compared with the background. The proposed scheme not only evaluates the global information of an image but also estimates the fine, detailed changes in an enhanced image. Thus, the proposed metric serves as an objective and effective FR criterion for color image QA. The experimental results presented confirm that the proposed WE metric is an efficient and useful metric for evaluating the quality of the color image enhancement. (shrink)