PAN AIR: A computer program for predicting subsonic or supersonic linear potential flows about arbitrary configurations using a higher order panel method. Volume 4: Maintenance document (version 1.1)

The Maintenance Document is a guide to the PAN AIR software system, a system which computes the subsonic or supersonic linear potential flow about a body of nearly arbitrary shape, using a higher order panel method. The document describes the over-all system and each program module of the system. Sufficient detail is given for program maintenance, updating and modification. It is assumed that the reader is familiar with programming and CDC (Control Data Corporation) computer systems. The PAN AIR system was written in FORTRAN 4 language except for a few COMPASS language subroutines which exist in the PAN AIR library. Structured programming techniques were used to provide code documentation and maintainability. The operating systems accommodated are NOS 1.2, NOS/BE and SCOPE 2.1.3 on the CDC 6600, 7600 and Cyber 175 computing systems. The system is comprised of a data management system, a program library, an execution control module and nine separate FORTRAN technical modules. Each module calculates part of the posed PAN AIR problem. The data base manager is used to communicate between modules and within modules. The technical modules must be run in a prescribed fashion for each PAN AIR problem. In order to ease the problem of supplying the many JCL cards required to execute the modules, a separate module called MEC (Module Execution Control) was created to automatically supply most of the JCL cards. In addition to the MEC generated JCL, there is an additional set of user supplied JCL cards to initiate the JCL sequence stored on the system

Antibodies to hnRNP core proteins inhibit in vitro splicing of human β-globin pre-mRNA

In vitro splicing of human beta-globin pre-mRNA can be fully inhibited by treatment of the splicing extract with polyclonal antibodies against hnRNP core proteins prior to the addition of pre-mRNA. Inhibition of the first step in the splicing pathway, cleavage at the 5' splice site and lariat formation, requires more antibodies than inhibition of the second step, cleavage at the 3' splice site and exon ligation. The anti-hnRNP antibodies can also inhibit the splicing reaction after the formation of the active nucleoprotein splicing complex which is known to occur during the initial lag period. Thus, hnRNP core proteins appear to be present in the complex that performs pre-mRNA splicing

Nuclease resistant methylphosphonate-DNA/LNA chimeric oligonucleotides

Synthesis of chimeric 9-mer oligonucleotides containing methylphosphonate-linkages and locked nucleic acid (LNA) monomers, their binding affinity towards complementary DNA and RNA, and their 3′-exonucleolytic stability are described. The obtained methylphosphonate-DNA/LNA chimeric oligonucleotides display similarly high RNA affinity and RNA selectivity as a corresponding 9-mer DNA/LNA chimeric oligonucleotide, but much higher resistance towards 3′-exonucleolytic degradation

Effect of Antisense TGF-β1 Oligodeoxynucleotides in Streptozotocin-Induced Diabetic Rat Kidney

Transforming growth factor (TGF)-β1 is an important fibrogenic factor that is involved in the pathogenesis of diabetic nephropathy. We evaluated the effect of circular antisense TGF-β1 oligodeoxynucleotides (ODNs) on the TGF-β1 expression in the rat mesangial cell culture and in streptozotocin (STZ)-induced diabetic rats. Circular antisense TGF-β1 ODNs were found to be stable in rat serum, significantly decreasing TGF-β1 mRNA expression compared with linear antisense ODNs in the rat mesangial cell culture. Circular antisense TGF-β1 ODNs were introduced into the tail vein of normal rats using hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer method and were confirmed to be delivered effectively into the kidney, liver, lungs, and spleen. To inhibit the overexpression of TGF-β1 in diabetic kidneys, we introduced circular antisense TGF-β1 ODNs into the STZ-induced diabetic rats. On day 13 after circular antisense TGF-β1 ODNs injection, TGF-β1 mRNA and protein expression markedly decreased and urinary TGF-β1 excretion rate also dropped in the circular antisense TGF-β1 ODNs-treated diabetic rats. These results suggest that circular antisense TGF-β1 ODNs may be a useful tool for developing new therapeutic application for progressive diabetic nephropathy

Theories of schizophrenia: a genetic-inflammatory-vascular synthesis

BACKGROUND: Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. DISCUSSION: A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular and immune/inflammatory systems. SUMMARY: A vascular-inflammatory theory of schizophrenia brings together environmental and genetic factors in a way that can explain the diversity of symptoms and outcomes observed. If these ideas are confirmed, they would lead in new directions for treatments or preventions by avoiding inducers of inflammation or by way of inflammatory modulating agents, thus preventing exaggerated inflammation and consequent triggering of a psychotic episode in genetically predisposed persons

The length of the downstream exon and the substitution of specific sequences affect pre-mRNA splicing in vitro.

We have shown previously that truncation of the human beta-globin pre-mRNA in the second exon, 14 nucleotides downstream from the 3' splice site, leads to inhibition of splicing but not cleavage at the 5' splice site. We now show that several nonglobin sequences substituted at this site can restore splicing and that the efficiency of splicing depends on the length of the second (downstream) exon and not a specific sequence. Deletions in the first exon have no effect on the efficiency of in vitro splicing. Surprisingly, an intron fragment from the 5' region of the human or rabbit beta-globin intron 2, when placed 14 nucleotides downstream from the 3' splice site, inhibited all the steps in splicing beginning with cleavage at the 5' splice site. This result suggests that the intron 2 fragment carries a "poison" sequence that can inhibit the splicing of an upstream intron