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Consultation and therapy in the boarding high school setting.

The tasks of a psychiatric consultant in the boarding high school setting are complex and require a particular set of tools. A thorough familiarity and comfort with the psychology and psychopathology of adolescence are necessities. In my view a psychodynamic point of view is most helpful. I have emphasized that students attending boarding schools are different from all other high school students in that they are experiencing a radical and more or less permanent separation from their homes a full developmental epoch earlier than their nonboarding peers. Whether this separation is helpful and growth promoting or traumatic and disruptive needs to be evaluated for each individual whose family seeks psychiatric opinion about such matters. Broad generalization is not possible. What is required is a careful evaluation of the developmental state of the particular teenager and an assessment of the psychologic meaning of the experience in terms of that child's psychic reality. To this formulation I add that a knowledge of the particular boarding schools under consideration, their cultures, mores, personnel, and administrative and academic styles can be of great additional help in making a decision. In addition to their radical and early separation from home, boarding students find themselves integrated into tightly knit school communities, each with its own unique group and institutional dynamics. The best consultation work will include an understanding of what is occurring at the interface between individual and school community. These interactions can be as critical in determining the fate of a boarding student as can be the interactions between a student living at home and interacting with his or her family. Separated from home and emotionally hungry for new objects to replace the ones left behind, the boarding student may have passionate and intense interactions with the institutions and members of the school community. In this article I have provided a recent example (Ted) of such an intense interaction, albeit one with a terrible and tragic outcome. Such anatomies of suicides as the one I have tried to reconstruct in this case can provide a realistic basis for optimism that a future recurrence can be prevented. Another case (Bob, discussed first) illustrated the potential for profound and far-reaching positive results of the consultation and treatment processes.

Adolescent↗

Task decomposition of laparoscopic surgery for objective evaluation of surgical residents' learning curve using hidden Markov model.

OBJECTIVE: Evaluation of the laparoscopic surgical skills of surgical residents is usually a subjective process carried out in the operating room by senior surgeons. The two hypotheses of the current study were: (1) haptic information and tool/tissue interactions (types and transitions) performed in laparoscopic surgery are skill-dependent, and (2) statistical models (Hidden Markov Models--HMMs) incorporating these data are capable of objectively evaluating laparoscopic surgical skills. MATERIALS AND METHODS: Eight subjects (six residents--two first-year (R1), two third-year (R3), and two fifth-year (R5)--and two expert laparoscopic surgeons) performed laparoscopic cholecystectomy on pigs using an instrumented grasper equipped with force/torque (F/T) sensors at the hand/tool interface, and F/T data was synchronized with video of the operative maneuvers. Fourteen types of tool/tissue (T/T) interactions, each associated with unique F/T signatures, were defined from frame-by-frame video analysis. HMMs for each subject and step of the operation were compared to evaluate the statistical distance between expert surgeons and residents with different skill levels. RESULTS: The statistical distances between HMMs representing expert surgeons and residents were significantly different (alpha < 0.05). Major differences occurred in: (1) F/T magnitudes; (2) type of T/T interactions and transitions between them; and (3) time intervals for each T/T interaction and overall completion time. The greatest difference in performance was between R1 (junior trainee) and R3 (midlevel trainee). Smaller changes were seen as expertise increased beyond the R3 level. CONCLUSION: HMMs incorporating haptic and visual information provide an objective tool for evaluating surgical skills. Objective evidence for a "learning curve" suggests that surgical residents acquire a major portion of their laparoscopic skill between year 1 and year 3 of training.

Animals↗

Sequencing of real-world samples using a microfabricated hybrid device having unconstrained straight separation channels.

We describe a microfabricated hybrid device that consists of a microfabricated chip containing multiple twin-T injectors attached to an array of capillaries that serve as the separation channels. A new fabrication process was employed to create two differently sized round channels in a chip. Twin-T injectors were formed by the smaller round channels that match the bore of the separation capillaries and separation capillaries were incorporated to the injectors through the larger round channels that match the outer diameter of the capillaries. This allows for a minimum dead volume and provides a robust chip/capillary interface. This hybrid design takes full advantage, such as sample stacking and purification and uniform signal intensity profile, of the unique chip injection scheme for DNA sequencing while employing long straight capillaries for the separations. In essence, the separation channel length is optimized for both speed and resolution since it is unconstrained by chip size. To demonstrate the reliability and practicality of this hybrid device, we sequenced over 1000 real-world samples from Human Chromosome 5 and Ciona intestinalis, prepared at Joint Genome Institute. We achieved average Phred20 read of 675 bases in about 70 min with a success rate of 91%. For the similar type of samples on MegaBACE 1000, the average Phred20 read is about 550-600 bases in 120 min separation time with a success rate of about 80-90%.

Animals↗

The combination of flow injection with electrophoresis using capillaries and chips.

The combined flow injection capillary electrophoresis (FI-CE) system that integrates the essential favorable merits of FI and CE, can significantly expand the application scope of CE by exploring the various on-line sample pretreatments and preconcentration of FI. The principle behind this technique, some innovative designs of the split-flow interface, as well as novel applications to a variety of analytical problems, are reviewed and discussed. Some salient features and unique advantages of this technique are outlined.

Calibration↗

Interface of Women's Mental and Reproductive Health.

The interface of women's reproductive and mental health is an evolving area of psychiatric practice, necessitating familiarity with psychobiological factors unique to women. The role of estrogen in particular has profound implications for the etiology and treatment of women's psychiatric illness, and has been reviewed along with the role of other hormones. Additionally, the stress of specific life events such as miscarriage, abortion, and menopause affects female mental health from a biological and psychosocial standpoint with the potential for secondary mood and anxiety disorders. Psychiatric issues during pregnancy and the postpartum period present special diagnostic and treatment challenges to the clinician. Biological and psychosocial treatments of these conditions have been reviewed. Management of psychiatric conditions during pregnancy and the postpartum period should include the obstetrician, pediatrician, and involved family members. Treatment decisions should involve careful assessment of the risks and benefits of any intervention including the risk of no treatment.

Abortion, Induced↗

Crystal structure of the superantigen enterotoxin C2 from Staphylococcus aureus reveals a zinc-binding site.

BACKGROUND: Staphylococcus aureus enterotoxin C2 (SEC2) belongs to a family of proteins, termed 'superantigens', that form complexes with class II MHC molecules enabling them to activate a substantial number of T cells. Although superantigens seem to act by a common mechanism, they vary in many of their specific interactions and biological properties. Comparison of the structure of SEC2 with those of two other superantigens--staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin-1 (TSST-1)--may provide insight into their mode of action. RESULTS: The crystal structure of SEC2 has been determined at 2.0 A resolution. The overall topology of the molecule resembles that of SEB and TSST-1, and the regions corresponding to the MHC class II and T-cell receptor binding sites on SEB are quite similar in SEC2. A unique feature of SEC2 is the presence of a zinc ion located in a solvent-exposed region at the interface between the two domains of the molecule. The zinc ion is coordinated to Asp83, His118, His122 and Asp9* (from the neighbouring molecule in the crystal lattice). Atomic absorption spectrometry demonstrates that zinc is also bound to SEC2 in solution. CONCLUSIONS: SEC2 appears to be capable of binding to MHC class II molecules in much the same manner as SEB. However, structure-function studies have suggested an alternative binding mode that involves a different site on the toxin. The zinc ion of SEC2 lies within this region and thus may be important for complex formation, for example by acting as a bridge between the two molecules. Other possible roles for the metal cation, including a catalytic one, are also considered.

Amino Acid Sequence↗

A web-based platform for virtual screening.

A fully integrated, web-based, virtual screening platform has been developed to allow rapid virtual screening of large numbers of compounds. ORACLE is used to store information at all stages of the process. The system includes a large database of historical compounds from high throughput screenings (HTS) chemical suppliers, ATLAS, containing over 3.1 million unique compounds with their associated physiochemical properties (ClogP, MW, etc.). The database can be screened using a web-based interface to produce compound subsets for virtual screening or virtual library (VL) enumeration. In order to carry out the latter task within ORACLE a reaction data cartridge has been developed. Virtual libraries can be enumerated rapidly using the web-based interface to the cartridge. The compound subsets can be seamlessly submitted for virtual screening experiments, and the results can be viewed via another web-based interface allowing ad hoc querying of the virtual screening data stored in ORACLE.

Algorithms↗

Solvent isotope effects on interfacial protein electron transfer in crystals and electrode films.

D(2)O-grown crystals of yeast zinc porphyrin substituted cytochrome c peroxidase (ZnCcP) in complex with yeast iso-1-cytochrome c (yCc) diffract to higher resolution (1.7 A) and pack differently than H(2)O-grown crystals (2.4-3.0 A). Two ZnCcP's bind the same yCc (porphyrin-to-porphyrin separations of 19 and 29 A), with one ZnCcP interacting through the same interface found in the H(2)O crystals. The triplet excited-state of at least one of the two unique ZnCcP's is quenched by electron transfer (ET) to Fe(III)yCc (k(e) = 220 s(-1)). Measurement of thermal recombination ET between Fe(II)yCc and ZnCcP+ in the D(2)O-treated crystals has both slow and fast components that differ by 2 orders of magnitude (k(eb)(1) = 2200 s(-1), k(eb)(2) = 30 s(-1)). Back ET in H(2)O-grown crystals is too fast for observation, but soaking H(2)O-grown crystals in D(2)O for hours generates slower back ET, with kinetics similar to those of the D(2)O-grown crystals (k(eb)(1) = 7000 s(-1), k(eb)(2) = 100 s(-1)). Protein-film voltammetry of yCc adsorbed to mixed alkanethiol monolayers on gold electrodes shows slower ET for D(2)O-grown yCc films than for H(2)O-grown films (k(H) = 800 s(-1); k(D) = 540 s(-1) at 20 degrees C). Soaking H(2)O- or D(2)O-grown films in the counter solvent produces an immediate inverse isotope effect that diminishes over hours until the ET rate reaches that found in the counter solvent. Thus, D(2)O substitution perturbs interactions and ET between yCc and either CcP or electrode films. The effects derive from slow exchanging protons or solvent molecules that in the crystal produce only small structural changes.

Crystallization↗

Infrared imaging of the nanometer-thick accumulation layer in organic field-effect transistors.

We report on infrared (IR) spectromicroscopy of the electronic excitations in nanometer-thick accumulation layers in field-effect transistor (FET) devices based on poly(3-hexylthiophene). IR data allows us to explore the charge injection landscape and uncovers the critical role of the gate insulator in defining relevant length scales. This work demonstrates the unique potential of IR spectroscopy for the investigation of physical phenomena at the nanoscale occurring at the semiconductor-insulator interface in FET devices.

Chemical Phenomena↗

Characterization of a carbohydrate transporter from symbiotic glomeromycotan fungi.

The symbiotic relationships between mycorrhizal fungi and plants have an enormous impact on terrestrial ecosystems. Most common are the arbuscular mycorrhizas, formed by fungi belonging to the phylum Glomeromycota. Arbuscular mycorrhizal fungi facilitate the uptake of soil nutrients by plants and in exchange obtain carbohydrates, thus representing a large sink for atmospheric plant-fixed CO(2). However, how carbohydrates are transported through the symbiotic interface is still unknown. Here we report the characterization of the first known glomeromycotan monosaccharide transporter, GpMST1, by exploiting the unique symbiosis of a glomeromycotan fungus (Geosiphon pyriformis) with cyanobacteria. The GpMST1 gene has a very low GC content and contains six introns with unusual boundaries. GpMST1 possesses twelve predicted transmembrane domains and functions as a proton co-transporter with highest affinity for glucose, then mannose, galactose and fructose. It belongs to an as yet uncharacterized phylogenetic monosaccharide transporter clade. This initial characterization of a new transporter family involved in fungal symbiosis will lead to a better understanding of carbon flows in terrestrial environments.

Biological Transport↗

On the mechanism of sensing unfolded protein in the endoplasmic reticulum.

Unfolded proteins in the endoplasmic reticulum (ER) activate the ER transmembrane sensor Ire1 to trigger the unfolded protein response (UPR), a homeostatic signaling pathway that adjusts ER protein folding capacity according to need. Ire1 is a bifunctional enzyme, containing cytoplasmic kinase and RNase domains whose roles in signal transduction downstream of Ire1 are understood in some detail. By contrast, the question of how its ER-luminal domain (LD) senses unfolded proteins has remained an enigma. The 3.0-A crystal structure and consequent structure-guided functional analyses of the conserved core region of the LD (cLD) leads us to a proposal for the mechanism of response. cLD exhibits a unique protein fold and is sufficient to control Ire1 activation by unfolded proteins. Dimerization of cLD monomers across a large interface creates a shared central groove formed by alpha-helices that are situated on a beta-sheet floor. This groove is reminiscent of the peptide binding domains of major histocompatibility complexes (MHCs) in its gross architecture. Conserved amino acid side chains in Ire1 that face into the groove are shown to be important for UPR activation in that their mutation reduces the response. Mutational analyses suggest that further interaction between cLD dimers is required to form higher-order oligomers necessary for UPR activation. We propose that cLD directly binds unfolded proteins, which changes the quaternary association of the monomers in the membrane plane. The changes in the ER lumen in turn position Ire1 kinase domains in the cytoplasm optimally for autophosphorylation to initiate the UPR.

Amino Acid Sequence↗

RPBS: a web resource for structural bioinformatics.

RPBS (Ressource Parisienne en Bioinformatique Structurale) is a resource dedicated primarily to structural bioinformatics. It is the result of a joint effort by several teams to set up an interface that offers original and powerful methods in the field. As an illustration, we focus here on three such methods uniquely available at RPBS: AUTOMAT for sequence databank scanning, YAKUSA for structure databank scanning and WLOOP for homology loop modelling. The RPBS server can be accessed at http://bioserv.rpbs.jussieu.fr/ and the specific services at http://bioserv.rpbs.jussieu.fr/SpecificServices.html.

Computational Biology↗

4SALE--a tool for synchronous RNA sequence and secondary structure alignment and editing.

BACKGROUND: In sequence analysis the multiple alignment builds the fundament of all proceeding analyses. Errors in an alignment could strongly influence all succeeding analyses and therefore could lead to wrong predictions. Hand-crafted and hand-improved alignments are necessary and meanwhile good common practice. For RNA sequences often the primary sequence as well as a secondary structure consensus is well known, e.g., the cloverleaf structure of the t-RNA. Recently, some alignment editors are proposed that are able to include and model both kinds of information. However, with the advent of a large amount of reliable RNA sequences together with their solved secondary structures (available from e.g. the ITS2 Database), we are faced with the problem to handle sequences and their associated secondary structures synchronously. RESULTS: 4SALE fills this gap. The application allows a fast sequence and synchronous secondary structure alignment for large data sets and for the first time synchronous manual editing of aligned sequences and their secondary structures. This study describes an algorithm for the synchronous alignment of sequences and their associated secondary structures as well as the main features of 4SALE used for further analyses and editing. 4SALE builds an optimal and unique starting point for every RNA sequence and structure analysis. CONCLUSION: 4SALE, which provides an user-friendly and intuitive interface, is a comprehensive toolbox for RNA analysis based on sequence and secondary structure information. The program connects sequence and structure databases like the ITS2 Database to phylogeny programs as for example the CBCAnalyzer. 4SALE is written in JAVA and therefore platform independent. The software is freely available and distributed from the website at http://4sale.bioapps.biozentrum.uni-wuerzburg.de.

Algorithms↗

Client-server, distributed database strategies in a healthcare record system for a homeless population.

A computer-based healthcare record system being developed for Boston's Healthcare for the Homeless Program (BHCHP) uses client-server and distributed database technologies to enhance the delivery of healthcare to patients of this unusual population. The needs of physicians, nurses and social workers are specifically addressed in the application interface so that an integrated approach to healthcare for this population can be facilitated. These patients and their providers have unique medical information needs that are supported by both database and applications technology. To integrate the information capabilities with the actual practice of providers of care to the homeless, this computer-based record system is designed for remote and portable use over regular phone lines. An initial standalone system is being used at one major BHCHP site of care. This project describes methods for creating a secure, accessible, and scalable computer-based medical record using client-server, distributed database design.

Ambulatory Care Information Systems↗

Remote processing server for ECG-based clinical diagnosis support.

In this paper, we present the development of a remote server that provides a user-friendly access to advanced electrocardiographic (ECG) signal processing techniques. The prototype supplies telemedicine facilities to doctors for clinical indexes remote computation to support diagnosis through the Internet. The user-friendly interface is based on the selection of the desired ECG signal processing tools on a Web browser window. The centralized structure of the system permits unique and user-independent update and management of the software and, therefore, is especially suitable for remote or rural regions to have access to the new ECG information techniques.

Algorithms↗

Unique regulation of the matrix metalloproteinase, gelatinase B.

PURPOSE: The matrix metalloproteinase (MMP), gelatinase B, is expressed by both corneal cell types found at the epithelial-stromal tissue interface, the site of basement membrane repair in the healing cornea. This study investigates the relative regulation of gelatinase B compared to other MMPs in response to agents related to those found in the corneal repair environment or in corneal ulcers. METHODS: A culture model of corneal cells isolated from rabbit was used. RESULTS: Gelatinase B is the major MMP expressed by corneal epithelial cells, whereas stromal fibroblasts produce gelatinase B along with three other MMPs: collagenase, stromelysin, and gelatinase A. Phorbol-12-myristate 13-acetate (PMA) stimulates gelatinase B mRNA and protein synthesis by corneal cells, which is similar to its effect on the other MMPs. Stimulation occurs, at least partially, at the transcriptional level. PMA-stimulated MMP expression follows biphasic kinetics, with the major effect on collagenase, stromelysin, and gelatinase A occurring during the late component. In contrast, the major gelatinase B response occurs during the early component. Transforming growth factor-beta (TGF-beta) has no effect on constitutive expression of gelatinase B by fibroblasts; however, expression stimulated by PMA is enhanced. In contrast, constitutive expression of collagenase and stromelysin is inhibited by TGF-beta. However, in the presence of PMA, the initial inhibitory effect of TGF-beta is reversed after treatment. CONCLUSION: Gelatinase B expression is regulated differently from other corneal MMPs. This provides a mechanism for control of basement membrane repair independent of repair processes in the stroma.

Animals↗

Protein-protein interaction domains and the heterodimerization of thyroid hormone receptor variant alpha2 with retinoid X receptors.

Heterodimerization between thyroid hormone receptors (TRs) and retinoid X receptors (RXRs) is mediated by a weak dimerization interface within the DNA- binding domains (DBDs) and a strong interface within the C-terminal ligand- binding domains of the receptors. Previous studies have shown that the conserved ninth heptad in the TR ligand-binding domain appears to play a critical role in heterodimerization with RXR. However, despite lacking the full ninth heptad, TR variant alpha2 (TRv alpha2) can heterodimerize with RXR on specific direct repeat response elements, but not on palindromic elements or in solution. Two possibilities may account for TRv alpha2-RXR heterodimerization on direct repeats. First, the DBD of TRv alpha2 may play a critical role in heterodimerization with RXR. Second, a specific sequence within the unique C terminus of TRv alpha2 may promote the formation of TRv alpha2-RXR heterodimers. In this study, we used receptor chimeras in which the DBD of RXR was replaced by either the TR DBD or an unrelated DBD from the metalloregulatory transcription factor AMT1 to address the role of the DBD dimerization interface in TRv alpha2-RXR heterodimerization. Gel mobility shift analyses showed that whereas TR alpha1 formed heterodimers with these chimeras, TRv alpha2 failed to do so. Deletion of the unique C terminus of TRv alpha2 had only a marginal effect on heterodimerization with RXR. Mutations within the DBD dimerization interface abolished heterodimerization of full-length TRv alpha2 with RXR but only marginally affected heterodimerization of full-length TR alpha1 with RXR. These data support the hypothesis that the TR-RXR DBD dimerization interface plays a critical role in TRv alpha2-RXR heterodimerization. Additional data show that the amino acid residues that make direct TR-RXR contacts within the DBDs also may play a role in receptor monomer binding to DNA, since mutations within these residues severely impair this interaction.

Amino Acid Sequence↗