Learning spectral descriptors for deformable shape correspondence.

Informative and discriminative feature descriptors play a fundamental role in deformable shape analysis. For example, they have been successfully employed in correspondence, registration, and retrieval tasks. In recent years, significant attention has been devoted to descriptors obtained from the spectral decomposition of the Laplace-Beltrami operator associated with the shape. Notable examples in this family are the heat kernel signature (HKS) and the recently introduced wave kernel signature (WKS). The Laplacian-based descriptors achieve state-of-the-art performance in numerous shape analysis tasks; they are computationally efficient, isometry-invariant by construction, and can gracefully cope with a variety of transformations. In this paper, we formulate a generic family of parametric spectral descriptors. We argue that to be optimized for a specific task, the descriptor should take into account the statistics of the corpus of shapes to which it is applied (the "signal") and those of the class of transformations to which it is made insensitive (the "noise"). While such statistics are hard to model axiomatically, they can be learned from examples. Following the spirit of the Wiener filter in signal processing, we show a learning scheme for the construction of optimized spectral descriptors and relate it to Mahalanobis metric learning. The superiority of the proposed approach in generating correspondences is demonstrated on synthetic and scanned human figures. We also show that the learned descriptors are robust enough to be learned on synthetic data and transferred successfully to scanned shapes.

Targeting the FANCJ-BRCA1 interaction promotes a switch from recombination to poleta-dependent bypass.

BRCA1 and the DNA helicase FANCJ (also known as BACH1 or BRIP1) have common functions in breast cancer suppression and DNA repair. However, the functional significance of the direct interaction between BRCA1 and FANCJ remains unclear. Here, we have discovered that BRCA1 binding to FANCJ regulates DNA damage repair choice. Thus, when FANCJ binding to BRCA1 is ablated, the molecular mechanism chosen for the repair of damaged DNA is dramatically altered. Specifically, a FANCJ protein that cannot be phosphorylated at serine 990 or bind BRCA1 inhibits DNA repair via homologous recombination and promotes poleta-dependent bypass. Furthermore, the poleta-dependent bypass promoted by FANCJ requires the direct binding to the mismatch repair (MMR) protein, MLH1. Together, our findings implicate that in human cells BRCA1 binding to FANCJ is critical to regulate DNA repair choice and promote genomic stability. Moreover, unregulated FANCJ function could be associated with cancer and/or chemoresistance.

BACH1 is a DNA repair protein supporting BRCA1 damage response.

The link between defects in BRCA1 and breast cancer development may be best understood by deciphering the role of associated proteins. BRCA1 associated C-terminal helicase (BACH1) interacts directly with the BRCA1 C-terminal BRCT repeats, which are important for BRCA1 DNA repair and are mutated in the majority of BRCA1 familial cancers. Thus, BACH1 is a likely candidate for mediating BRCA1 DNA repair and tumor suppression functions. Although previous evidence using overexpression of a dominant negative BACH1 has suggested that BACH1 is involved in BRCA1-DNA repair function, our results using BACH1 deficient cells provide direct evidence for involvement of BACH1 in DNA repair as well as for localizing BRCA1. Following DNA damage BACH1 is modified by phosphorylation, displays a BRCA1-like nuclear foci pattern and colocalizes with gamma-H2AX. Given that the BACH1/BRCA1 complex is unaltered by DNA damage and the intensity of BRCA1 foci is diminished in BACH1 deficient cells, BACH1 may serve to not only facilitate DNA repair, but also maintain BRCA1 in DNA damage foci.

Generalized tonic-clonic activity after remifentanil administration.

IMPLICATIONS: This is the first report of seizure-like activity in an adult who received remifentanil. This report confirms that opioid administration can be associated with generalized tonic-clonic seizure-like activity. It is suggested that this reaction could be referred to as the "opioid-seizure syndrome."

Extraordinary variation in a diversified family of immune-type receptor genes.

Immune inhibitory receptor genes that encode a variable (V) region, a unique V-like C2 (V/C2) domain, a transmembrane region, and a cytoplasmic tail containing immunoreceptor tyrosine-based inhibition motifs (ITIMs) have been described previously in two lineages of bony fish. In the present study, eleven related genes encoding distinct structural forms have been identified in Ictalurus punctatus (channel catfish), a well characterized immunological model system that represents a third independent bony fish lineage. Each of the different genes encodes an N-terminal V region but differs in the number of extracellular Ig domains, number and location of joining (J) region-like motifs, presence of transmembrane regions, presence of charged residues in transmembrane regions, presence of cytoplasmic tails, and/or distribution of ITIM(s) within the cytoplasmic tails. Variation in the numbers of genomic copies of the different gene types, their patterns of expression, and relative levels of expression in mixed leukocyte cultures (MLC) is reported. V region-containing immune-type genes constitute a far more complex family than recognized originally and include individual members that might function in inhibitory or, potentially activatory manners.

Immune-type receptor genes in zebrafish share genetic and functional properties with genes encoded by the mammalian leukocyte receptor cluster.

An extensive, highly diversified multigene family of novel immune-type receptor (nitr) genes has been defined in Danio rerio (zebrafish). The genes are predicted to encode type I transmembrane glycoproteins consisting of extracellular variable (V) and V-like C2 (V/C2) domains, a transmembrane region and a cytoplasmic tail. All of the genes examined encode immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic tail. Radiation hybrid panel mapping and analysis of a deletion mutant line (b240) indicate that a minimum of approximately 40 nitr genes are contiguous in the genome and span approximately 0.6 Mb near the top of zebrafish linkage group 7. One flanking region of the nitr gene complex shares conserved synteny with a region of mouse chromosome 7, which shares conserved synteny with human 19q13.3-q13.4 that encodes the leukocyte receptor cluster. Antibody-induced crosslinking of Nitrs that have been introduced into a human natural killer cell line inhibits the phosphorylation of mitogen-activated protein kinase that is triggered by natural killer-sensitive tumor target cells. Nitrs likely represent intermediates in the evolution of the leukocyte receptor cluster.

Complex expression patterns of lymphocyte-specific genes during the development of cartilaginous fish implicate unique lymphoid tissues in generating an immune repertoire.

Cartilaginous fish express canonical B and T cell recognition genes, but their lymphoid organs and lymphocyte development have been poorly defined. Here, the expression of Ig, TCR, recombination-activating gene (Rag)-1 and terminal deoxynucleosidase (TdT) genes has been used to identify roles of various lymphoid tissues throughout development in the cartilaginous fish, Raja eglanteria (clearnose skate). In embryogenesis, Ig and TCR genes are sharply up-regulated at 8 weeks of development. At this stage TCR and TdT expression is limited to the thymus; later, TCR gene expression appears in peripheral sites in hatchlings and adults, suggesting that the thymus is a source of T cells as in mammals. B cell gene expression indicates more complex roles for the spleen and two special organs of cartilaginous fish-the Leydig and epigonal (gonad-associated) organs. In the adult, the Leydig organ is the site of the highest IgM and IgX expression. However, the spleen is the first site of IgM expression, while IgX is expressed first in gonad, liver, Leydig and even thymus. Distinctive spatiotemporal patterns of Ig light chain gene expression also are seen. A subset of Ig genes is pre-rearranged in the germline of the cartilaginous fish, making expression possible without rearrangement. To assess whether this allows differential developmental regulation, IgM and IgX heavy chain cDNA sequences from specific tissues and developmental stages have been compared with known germline-joined genomic sequences. Both non-productively rearranged genes and germline-joined genes are transcribed in the embryo and hatchling, but not in the adult.

Anesthesia and analgesia for newborn circumcision.

Newborn circumcision is likely the most common elective surgical procedure performed in children, yet a sizable portion of these procedures is performed without anesthesia or analgesia. This review discusses methods and techniques of analgesia and anesthesia for newborn circumcision. Behavioral, pharmacological, and regional block techniques are described. Ideally, the use of a combination of local anesthesia and behavioral techniques are most beneficial to newborns that undergo this painful procedure.

Paediatric anaesthesia outside the operating room.

Anaesthesiologists are regularly consulted to provide anaesthesia for children in settings other than an operating room. Current debate focuses on the appropriateness of the presence of an anaesthesiologist versus a non-anaesthesiologist. There is mounting evidence that the presence of an anaesthesiologist is safer. We will review the recent literature concerning paediatric anaesthesia outside the operating room and offer recommendations that may impact on efficacy and safety.

Anesthesia for tracheal or bronchial foreign body removal in children: an analysis of ninety-four cases.

IMPLICATIONS: This report is a description of the ventilation techniques used in 94 children undergoing general anesthesia for foreign body removal of the bronchus. No particular technique was found to be associated with a greater incidence of adverse outcomes.

Characterization of three isotypes of immunoglobulin light chains and T-cell antigen receptor alpha in zebrafish.

The zebrafish (Danio rerio) has become a significant model for understanding the developmental regulation of gene expression and holds considerable potential for characterizing the development of the immune system. Using a number of different approaches, including heterologous hybridization and short-primer PCR, cDNAs for three different classes of light-chain genes were identified and characterized. The zebrafish light chains are similar to trout type 1, trout type 2, and catfish type F, respectively. T-cell antigen receptor alpha (TCRalpha) was also identified and characterized. A high proportion of unusual transcripts including sterile transcripts, germline VJC transcripts, aberrant splice forms, and V-V transcripts were encountered in the immunoglobulin and TCR cDNAs examined. The light-chain and TCRalpha loci each consist of multiple families of V gene segments, apparent even from the small numbers of cDNAs of each isotype sequenced. The gene sequences reported provide an essential set of markers of both B- and T-cell lineages that will facilitate investigations of immune system development.

Genetic analysis of the exed region in mouse.

The extraembryonic ectoderm development (exed) mutant phenotype was described in mice homozygous for the c(6H) deletion, a radiation-induced deletion in the tyrosinase region of mouse Chromosome 7. These mutants fail to gastrulate and die around embryonic day 8.0. Several genes including, for example, embryonic ectoderm development (eed), are deleted in the c(6H) mutants; however, the portion of the chromosome responsible for the more severe exed phenotype is localized to a 20-kb region called the "exed-critical region." To understand the genetics behind the exed phenotype, we analyzed this region in two ways. First, to determine whether the 20-kb exed-critical region alone causes the mutant phenotype, we removed it from a wild-type chromosome. The resulting mice homozygous for this deletion were viable and fertile, indicating that the 20-kb exed-critical region by itself is not sufficient to cause the phenotype when deleted. We then sequenced the 20-kb exed-critical region and no expressed exons were found. Several short matches to GenBank Expressed Sequence Tag (EST) databases were identified; however, none of these ESTs mapped to the region. Taken together, these results indicate that the exed phenotype may either be a position effect on a distal gene caused by the c(6H) breakpoint or the result of composite effects of nullizygosity of multiple genes in the deletion homozygotes.

Conscious sedation with remifentanil during painful medical procedures.

Remifentanil, a recently introduced ultra-short acting opioid, was used as a component of a conscious sedation technique in 30 patients for 40 painful medical procedures. In 31 of these procedures, remifentanil provided sufficient analgesia. However, 25 of those 31 patients developed apnea that required constant verbal stimulation at doses equal to or less than the dose required for analgesia. Ten of these apneic patients developed hypoxemia (oxyhemoglobin saturation less than 90%). Nine patients required abandonment of remifentanil and addition of either ketamine or propofol to achieve an analgesic state without respiratory depression. Although discharge times with remifentanil were considerably shorter, most patients, parents, and practitioners were not satisfied with the technique because of the prolonged time to reach an analgesic state, and their fear of persistent apnea. Therefore, remifentanil is generally not a useful agent as part of a conscious sedation technique during brief painful procedures. Although discharge times are rapid, it is accompanied by a high incidence of life-threatening respiratory depression at subtherapeutic levels.

A novel multigene family encodes diversified variable regions.

Antigen recognition in the adaptive immune response by Ig and T-cell antigen receptors (TCRs) is effected through patterned differences in the peptide sequence in the V regions. V-region specificity forms through genetically programmed rearrangement of individual, diversified segmental elements in single somatic cells. Other Ig superfamily members, including natural killer receptors that mediate cell-surface recognition, do not undergo segmental reorganization, and contain type-2 C (C2) domains, which are structurally distinct from the C1 domains found in Ig and TCR. Immunoreceptor tyrosine-based inhibitory motifs that transduce negative regulatory signals through the cell membrane are found in certain natural killer and other cell surface inhibitory receptors, but not in Ig and TCR. In this study, we employ a genomic approach by using the pufferfish (Spheroides nephelus) to characterize a nonrearranging novel immune-type receptor gene family. Twenty-six different nonrearranging genes, which each encode highly diversified V as well as a V-like C2 extracellular domain, a transmembrane region, and in most instances, an immunoreceptor tyrosine-based inhibitory motif-containing cytoplasmic tail, are identified in an approximately 113 kb P1 artificial chromosome insert. The presence in novel immune-type receptor genes of V regions that are related closely to those found in Ig and TCR as well as regulatory motifs that are characteristic of inhibitory receptors implies a heretofore unrecognized link between known receptors that mediate adaptive and innate immune functions.

Conscious sedation with remifentanil and midazolam during brief painful procedures in children.

OBJECTIVE: To test the hypothesis that remifentanil, because of its favorable pharmacokinetic properties, would be advantageous to use in combination with midazolam to provide analgesia and sedation during brief painful procedures. DESIGN: Prospective observation and data collection. SETTING: University hospital. PATIENTS: Seventeen children aged 2 to 12 years, who underwent 20 brief, painful procedures. INTERVENTIONS: Administration of intravenous midazolam hydrochloride, 0.05 mg/kg, and remifentanil hydrochloride, 1 microg/kg, followed by a remifentanil infusion at 0.1 microg x kg(-1) x min(-1). The dose was titrated at 5-minute intervals to levels of sedation and analgesia. MAIN OUTCOME MEASURES: Successful remifentanil doses, times to discharge readiness, side effects, complications, and requirement for additional medications. RESULTS: The technique was successful in 17 of 20 procedures. The mean +/- SD successful dose was 0.4 +/- 0.2 microg x kg(-1) x min(-1). Four children developed hypoxemia that abated with mild stimulation; 1 child became unresponsive and required positive-pressure ventilation. The mean +/- SD time to reach discharge criteria was 9.5 +/- 4.3 minutes. Hypoxemia was avoided in 10 of 13 patients by continuous stimulation throughout the procedure. CONCLUSION: The use of remifentanil and midazolam during brief, painful procedures results in rapid times to discharge but is complicated by a high incidence of life-threatening respiratory depression at subtherapeutic levels.

Psychogenic stridor: a cause of acute upper airway obstruction.

A 17-year-old boy was seen in the emergency department with signs and symptoms of acute upper airway obstruction, closely resembling epiglottitis. Immediate management consisted of induction of general anesthesia with spontaneous ventilation. Because no organic pathologic process was found, and in combination with subsequently known psychosocial stressors, a diagnosis of psychogenic stridor, a conversion disorder, was made. Conversion disorders may be seen by the busy family practitioner or pediatrician and are frequently underdiagnosed.

Sedation and anesthesia outside the operating room: answers to common questions.

In recent years, practitioners have recognized the importance of providing comfort to children and have increased their use of analgesics and anxiolytics during painful medical procedures. In this article, the author reviews commonly asked questions regarding administering sedation to children for painful procedures outside the operating room. Current safety guidelines are reviewed, as well as qualifications of personnel performing sedations, contraindications to sedation, fasting guidelines before sedation, and common sedation techniques.