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1.
Nature ; 434(7032): 462-9, 2005 Mar 24.
Article in English | MEDLINE | ID: mdl-15791247

ABSTRACT

A key challenge of functional genomics today is to generate well-annotated data sets that can be interpreted across different platforms and technologies. Large-scale functional genomics data often fail to connect to standard experimental approaches of gene characterization in individual laboratories. Furthermore, a lack of universal annotation standards for phenotypic data sets makes it difficult to compare different screening approaches. Here we address this problem in a screen designed to identify all genes required for the first two rounds of cell division in the Caenorhabditis elegans embryo. We used RNA-mediated interference to target 98% of all genes predicted in the C. elegans genome in combination with differential interference contrast time-lapse microscopy. Through systematic annotation of the resulting movies, we developed a phenotypic profiling system, which shows high correlation with cellular processes and biochemical pathways, thus enabling us to predict new functions for previously uncharacterized genes.


Subject(s)
Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/embryology , Caenorhabditis elegans/genetics , Embryonic Development/genetics , Genome , RNA Interference , Animals , Caenorhabditis elegans/physiology , Computational Biology , Genes, Helminth/genetics , Genomics , Phenotype , RNA, Helminth/genetics , RNA, Helminth/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism
2.
Biotechnol Bioeng ; 72(4): 501-5, 2001 Feb 20.
Article in English | MEDLINE | ID: mdl-11180071

ABSTRACT

Crystalline cross-linked xylose isomerase (CLXI, EC 5.3.1.5) and xylanase (CLX, EC 3.2.1.8) were studied in a packed-bed reactor for simultaneous catalytic reaction and separation of substrates from reaction products. Streptomyces rubiginosus xylose isomerase catalyzed a slow isomerization of L-arabinose to L-ribulose and an epimerization to L-ribose. In equilibrium the reaction mixture contained 52.5% arabinose, 22.5% ribulose, and 25% ribose. In a packed-bed column filled with CLXI, a simultaneous reaction and separation resulted in fractions where arabinose concentration varied between 100-0%, ribulose between 0-55%, and ribose between 0-100%. Trichoderma reesei xylanase II hydrolyzed and transferred xylotetraose mainly to xylotriose and xylobiose. In a packed-bed column filled with CLX, xylotetraose rapidly reacted to xylobiose and xylose by a mechanism that is not yet fully understood.


Subject(s)
Aldose-Ketose Isomerases/metabolism , Bacterial Proteins/metabolism , Disaccharides/isolation & purification , Enzymes, Immobilized/metabolism , Fungal Proteins/metabolism , Oligosaccharides/isolation & purification , Ribose/isolation & purification , Xylose/isolation & purification , Xylosidases/metabolism , Aldose-Ketose Isomerases/chemistry , Arabinose/metabolism , Bacterial Proteins/chemistry , Catalysis , Crystallization , Disaccharides/biosynthesis , Enzymes, Immobilized/chemistry , Fungal Proteins/chemistry , Oligosaccharides/biosynthesis , Pentoses/metabolism , Ribose/metabolism , Solubility , Streptomyces/enzymology , Trichoderma/enzymology , Xylan Endo-1,3-beta-Xylosidase , Xylose/biosynthesis , Xylosidases/chemistry
3.
Psychoanal Rev ; 79(3): 361-79, 1992.
Article in English | MEDLINE | ID: mdl-1438630

ABSTRACT

The narcissist and borderline personality types complement one another's defensive style providing needed defensive externalization of disavowed and split-off feelings. One is exploitative, grandiose, and dominant, forever seeking admiration and exhibiting an aggrandized self; the other experiences humiliation, neediness, helplessness, and terror of aloneness. They form a powerful complementary dyad wherein each identifies with disavowed emotional experiences displayed in the other. They can coexist for lengths of time, defensively discharging unwanted feelings. In the first case presented above, the transference was split initially, with the masoborderline patient being victimized and humiliated by her sadonarcissistic lover. In the second case, a male sadonarcissist enacted disavowed feelings through relationships with masoborderline women. In both cases, defensive enactment was fed by a complementary, intense, and symbiotic relationship. Complementary dynamics can be subtle and difficult to analyze. They involve defensive identification that draws on projection, enactment, and externalization--all difficult defenses to analyze. Enactment rather than remembering is inimical to the development of insight into transference and genetic connections and must be worked through for the analysis to progress. More than the usual analytic patience and resolve is needed to work through the difficult entrapments caused by these dynamics.


Subject(s)
Borderline Personality Disorder/psychology , Masochism , Narcissism , Psychoanalytic Theory , Sadism , Adult , Defense Mechanisms , Humans , Male , Object Attachment , Psychoanalytic Therapy , Transference, Psychology
4.
Psychoanal Rev ; 74(4): 487-515, 1987.
Article in English | MEDLINE | ID: mdl-3124150

ABSTRACT

In this paper, I have summarized the large body of literature on the N.T.R. and noted that the term has been broadened from Freud's original definition of deterioration following improvement or correct analytic work to include a negativistic, ongoing narcissistic reaction with failure to recover. Like Freud, Klein became very pessimistic about reversing this phenomenon. The N.T.R. is a multidetermined but not unitary clinical phenomenon that has generated much controversy. Its dynamics involve interpersonal and intrapsychic elements. Aggression, revenge, and oppositional reactions interfere with analytic progress and may range from temporary to a characteristic way of responding in the analysis. Aggression, the reaction to early frustration and deprivation, plays a large part in the narcissistic organization. Patients who experience N.T.Rs. are shown to have strong narcissistic features. Interpersonally, conflict between longings for fusion and the wish for separateness is central. The transference-countertransference is made difficult by projective identification. Envy and narcissism are critical in the N.T.R. patient's intrapsychic dynamics. Clinical material illustrated the difficult interpersonal and intrapsychic factors that prevailed in a severe N.T.R. patient. The N.T.R. is an insidious obstacle to analytic success and one that requires mastery of the interpersonal and intrapsychic dynamics of the patient and the treatment situation.


Subject(s)
Defense Mechanisms , Negativism , Psychoanalytic Therapy , Aggression/psychology , Countertransference , Guilt , Humans , Identification, Psychological , Jealousy , Male , Narcissism , Object Attachment , Projection , Psychoanalytic Theory , Transference, Psychology
5.
Psychoanal Rev ; 73(2): 103-28, 1986.
Article in English | MEDLINE | ID: mdl-3092259

ABSTRACT

This paper reviewed the merits of and problems with the concept of projective identification. On the negative side, lack of universal meaning of the term was cited. Personal countertransference receives little regard, while an isomorphic reading of patient feelings may be used to gratify omnipotent symbiotic analyst and patient fantasies. On the positive side, the concept offers a framework that can lead to deeper understanding of difficult therapeutic situations. It helps the analyst process and contain distressing feelings and eschews interpretation that can be destructive to the analytic process. Proper use of projective identification should engage the patient's ego rather than foster passivity and merger wishes. Case material was presented which illustrated problems with and merits of the concept. Personal countertransference, especially therapeutic omnipotence, was shown to receive insufficient attention. The important role of complementarity in projective identification was illustrated in the treatment of depression, a disorder which can offer difficult treatment resistances. In conclusion, the concept should not be used as a justification for analyst omnipotence and avoidance of countertransference responsibility. The concept, however, can lead to a deepening of the analytic situation if it is used with caution and respect for the patient's separateness.


Subject(s)
Identification, Psychological , Projection , Countertransference , Depressive Disorder/therapy , Empathy , Female , Humans , Male , Psychoanalytic Interpretation , Psychoanalytic Therapy , Suicide, Attempted/psychology , Symbiosis
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