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The standard approach for single-sequence RNA secondary structure prediction uses a nearest-neighbor thermodynamic model with several thousand experimentally determined energy parameters. An attractive alternative is to use statistical approaches with parameters estimated from growing databases of structural RNAs. Good results have been reported for discriminative statistical methods using complex nearest-neighbor models, including CONTRAfold, Simfold, and ContextFold. Little work has been reported on generative probabilistic models (stochastic context-free grammars [SCFGs]) of comparable complexity, although probabilistic models are generally easier to train and to use. To explore a range of probabilistic models of increasing complexity, and to directly compare probabilistic, thermodynamic, and discriminative approaches, we created TORNADO, a computational tool that can parse a wide spectrum of RNA grammar architectures (including the standard nearest-neighbor model and more) using a generalized super-grammar that can be parameterized with probabilities, energies, or arbitrary scores. By using TORNADO, we find that probabilistic nearest-neighbor models perform comparably to (but not significantly better than) discriminative methods. We find that complex statistical models are prone to overfitting RNA structure and that evaluations should use structurally nonhomologous training and test data sets. Overfitting has affected at least one published method (ContextFold). The most important barrier to improving statistical approaches for RNA secondary structure prediction is the lack of diversity of well-curated single-sequence RNA secondary structures in current RNA databases.

Middle ear effusions from 100 patients (ages 6 months to 10 years) with serous otitis media were examined. The IgA, IgG, and lysozyme were demonstrated at a higher level in the effusions than the corresponding sera, indicating local production. The mucoid type contained higher level of immunoglobulins and lysozyme compared to serous type effusions.Bacteria were found in 77% of the effusions by means of a smear, and 52% yielded positive bacterial culture. The incidence of positive culture in effusions of the patients less than 6 years of age was 60%, while the group older than 6 years old was 32%, and the group over 8 was only 22%. Bacterial recovery rate was inversely related to the dramatic increase with age of IgA and IgG and Iysozyme levels in effusions.

A tumor cell-associated protein, previously shown to be present in the circulation of carcinogen-treated and tumor-bearing animals and cancer patients, has now been identified in the cytosol of embryonic tissue. This oncofetal protein, which is absent from the plasma of normal animals, has been purified from the plasma of tumor-bearing rats by a series of steps including ammonium sulfate fractionation and chromatography on Sepharose CL-6B and on CM Affi-Gel Blue. The tumor and fetal-associated 60-kd rat factors appear to be identical based on their reactivity to polyclonal antibody produced against the tumor factor. The factor, assayed by its ability to induce the transport of RNA from isolated nuclei, is a phosphoprotein with a minimum molecular weight of 60,000, as determined by polyacrylamide gel electrophoresis. In its purified form it is phosphorylated in the presence of the catalytic subunit of heart muscle protein kinase and ATP but does not exhibit auto-phosphorylating activity. 32P-orthophosphate is also incorporated into the phosphoprotein in vivo.

A total of 175 effusions obtained from 172 patients suffering from chronic otitis media with effusions was examined for bacterial smear and culture. Eighty percent showed positive bacterial smear, but only 49% yielded positive bacterial culture. The mucoid effusions had positive cultures in only 37%, whereas the bacterial culture rate was higher in serous (59%) and leukocytic (64%) types. The isolation of common pathogens accounted for about 50% of the isolates, and nonpathogens accounted for the remaining 50%. The high incidence of microorganisms in the middle ear effusions in the present series raises the possibility of bacterial contribution in many cases of OME.

Analyses of effusions and sera from patients with otitis media with effusion demonstrated local production in the middle ear of lysozyme, IgA and IgG. The effusion IgM was markedly elevated in some patients, also indicating local production. Complement C3with rare exception was significantly lower in effusions than sera, suggesting utilization of complement in the middle ear, perhaps in conjunction with antibodies. The presence of high levels of lysozyme and immunoglobulins in effusions correlates with the low isolation rate of microorganisms in culture and may influence survival of organisms in the middle ear.

Aspects of both the humoral and cell-mediated immune responses of mice to rat skin xenografts were studied sequentially and quantitated. Antirat lymphocytotoxic and hemagglutinating antibodies were first detectable at 7 and 6 days, respectively, after primary grafting and their appearance in serum corresponded to the time of graft rejection. Lymphocytotoxic titers were low after primary grafting but increased greater than 4-fold after secondary grafting. Cytotoxicity of mouse spleen and axillary lymph node cells for 51Cr-labeled rat lymphocyte target cells was first detectable 5 days after primary grafting but was quite low showing a peak of only 7 specific 51Cr release 6 days after grafting. In contrast, the cytotoxicity of mouse spleen and lymph node cells for allogeneic target cells after primary skin allografting was significantly greater. It is suggested that the magnitude of the cell-mediated immune response to skin xenografts is less than the response to allografts and that the quicker and more vigorous rejection of skin xenografts is due to a larger participation of humoral antibody in the rejection process.

THERE are numerous reports of the presence of abnormal levels of various serum proteins in psychotic patients.1-4 Serum globulins have been examined for antibody to brain tissue and to other antigens.5-7 Presumably, these antibodies appear in the serum as a result of autoimmunization or from stimulation by foreign antigens. Elevated γglobulin levels may result also from an increase in antibodies that are normally present in human sera. Elevated titers of various hemagglutinins occur in certain diseases and have been an aid in diagnosis.8 About 98% of normal individuals have low levels of sheep hemagglutinins in their sera. As a result of serum sickness, Hodgkin's disease, leukemia, infectious mononucleosis, and a number of other illnesses, hemagglutinin levels may increase considerably. Cold hemagglutinins have been found in 95% of normal sera in low titer, and high titers are occasionally associated with primary atypical

Prostatic acid phosphatase can be detected in individual human prostatic fluids by means of gel diffusion antigen-antibody precipitation with specific staining procedures. The fluids can be diluted to various degrees before the reaction fails. This titre, or limiting dilution, ranged from 1 : 64 to 1 : 16,000. It paralleled the results obtained by the King-Armstrong assay of enzyme activity. Gel diffusion analysis revealed the presence of twoantigens with acid phosphatase activity.