Temporal fluctuations in coherence of brain waves.

As a measure of dynamical structure, short-term fluctuations of coherence between 0.3 and 100 Hz in the electroencephalogram (EEG) of humans were studied from recordings made by chronic subdural macroelectrodes 5-10 mm apart, on temporal, frontal, and parietal lobes, and from intracranial probes deep in the temporal lobe, including the hippocampus, during sleep, alert, and seizure states. The time series of coherence between adjacent sites calculated every second or less often varies widely in stability over time; sometimes it is stable for half a minute or more. Within 2-min samples, coherence commonly fluctuates by a factor up to 2-3, in all bands, within the time scale of seconds to tens of seconds. The power spectrum of the time series of these fluctuations is broad, extending to 0.02 Hz or slower, and is weighted toward the slower frequencies; little power is faster than 0.5 Hz. Some records show conspicuous swings with a preferred duration of 5-15s, either irregularly or quasirhythmically with a broad peak around 0.1 Hz. Periodicity is not statistically significant in most records. In our sampling, we have not found a consistent difference between lobes of the brain, subdural and depth electrodes, or sleeping and waking states. Seizures generally raise the mean coherence in all frequencies and may reduce the fluctuations by a ceiling effect. The coherence time series of different bands is positively correlated (0.45 overall); significant nonindependence extends for at least two octaves. Coherence fluctuations are quite local; the time series of adjacent electrodes is correlated with that of the nearest neighbor pairs (10 mm) to a coefficient averaging approximately 0.4, falling to approximately 0.2 for neighbors-but-one (20 mm) and to < 0.1 for neighbors-but-two (30 mm). The evidence indicates fine structure in time and space, a dynamic and local determination of this measure of cooperativity. Widely separated frequencies tending to fluctuate together exclude independent oscillators as the general or usual basis of the EEG, although a few rhythms are well known under special conditions. Broad-band events may be the more usual generators. Loci only a few millimeters apart can fluctuate widely in seconds, either in parallel or independently. Scalp EEG coherence cannot be predicted from subdural or deep recordings, or vice versa, and intracortical microelectrodes show still greater coherence fluctuation in space and time. Widely used computations of chaos and dimensionality made upon data from scalp or even subdural or depth electrodes, even when reproducible in successive samples, cannot be considered representative of the brain or the given structure or brain state but only of the scale or view (receptive field) of the electrodes used. Relevant to the evolution of more complex brains, which is an outstanding fact of animal evolution, we believe that measures of cooperativity are likely to be among the dynamic features by which major evolutionary grades of brains differ.

A general strategy for producing conditional alleles of Src-like tyrosine kinases.

The Src-like tyrosine kinases require membrane localization for transformation and probably for their normal role in signal transduction. We utilized this characteristic to prepare Src-like tyrosine kinases that can be readily activated with the rationally designed chemical inducer of dimerization FK1012. Dimerization of cytoplasmic Src-like tyrosine kinases was not sufficient for signaling, but their recruitment to the plasma membrane led to the rapid activation of transcription factors identical to those regulated by crosslinking the antigen receptor. Moreover, recruitment of activated Src-like kinases to the membrane replaced signaling by the T-lymphocyte antigen receptor complex, leading to the activation of both the Ras/protein kinase C and Ca2+/calcineurin pathways normally activated by antigen receptor signaling. Since these chemical inducers of dimerization are cell permeable, this approach permits the production of conditional alleles of any of the Src-like tyrosine kinases, thereby allowing a delineation of their developmental roles.

Signal transduction in T lymphocytes using a conditional allele of Sos.

While Ras activation has been shown to play an important role in signal transduction by the T-lymphocyte antigen receptor, the mechanism of its activation in T cells is unclear. Membrane localization of the guanine nucleotide exchange factor Sos, but not Vav or Dbl, was sufficient for Ras-mediated signaling in T lymphocytes. Activation of Sos appears to involve membrane recruitment and not allosteric changes, because interaction of Sos with the linking molecule Grb-2 was not required for Ras activation. To extend this analysis, we constructed a modified Sos that could be localized to the membrane inducibly by using a rationally designed chemical inducer of dimerization, FK1012. The role of Grb-2 in signaling was mimicked with this technique, which induced the association of a modified Sos with the membrane, resulting in rapid activation of Ras-induced signaling. In contrast, inducible localization of Grb-2 to the membrane did not activate signaling and suggests that the interaction of Grb-2 with Sos in T cells is subject to regulation. This conditional allele of Sos demonstrates that membrane localization of Sos is sufficient for Ras activation in T cells and indicates that the role of Grb-2 is to realize the biologic advantages of linker-mediated dimerization: enhanced specificity and favorable kinetics for signaling. This method of generating conditional alleles may also be useful in dissecting other signal transduction pathways regulated by protein localization or protein-protein interactions.

Cloning and expression of a second photoreceptor-specific membrane retina guanylyl cyclase (RetGC), RetGC-2.

One of the membrane guanylyl cyclases (GCs), RetGC, is expressed predominantly in photoreceptors. No extracellular ligand has been described for RetGC, but it is sensitive to activation by a soluble 24-kDa protein (p24) and is inhibited by Ca2+. This enzyme is, therefore, thought to play a role in resynthesizing cGMP for photoreceptor recovery or adaptation. By screening a human retinal cDNA library at low stringency with the cytoplasmic domains from four cyclases, we cloned cDNAs encoding a membrane CG that is most closely related to RetGC. We have named this GC RetGC-2, and now term the initially described RetGC RetGC-1. By in situ hybridization, mRNA encoding RetGC-2 is found only in the outer nuclear layer and inner segments of photoreceptor cells. By using synthetic peptide antiserum specific for each RetGC subtype, RetGC-2 can be distinguished from RetGC-1 as a slightly smaller protein in immunoblots of bovine rod outer segments. Membrane GC activity of recombinant RetGC-2 expressed in human embryonic kidney 293 cells is stimulated by the activator p24 and is inhibited by Ca2+ with an EC50 value of 50-100 nM. Our data reveal a previously unappreciated diversity of photoreceptor GCs.

Catharine Waugh McCullouch papers in the Mary Earhart Dillon collection, 1869-1945

Collection primarily documents McCulloch's research on women's legal status, and her work with the Illinois Equal Suffrage Association, the National American Woman Suffrage Association, and the League of Women Voters. There is also documentation of women in the legal profession, of McCulloch's friendships with the other women suffragists and lawyers, and some biographical material. The papers contain little information about her family or social life.

Letter from David Phips to Colonel Jonathan Snelling regarding escort of Governor Hutchinson to Harvard Commencement, 1773 July 12

David Phips wrote this letter to Colonel Jonathan Snelling from Cambridge on July 12, 1773, to inform him that Massachusetts Governor Thomas Hutchinson had requested the accompaniment of guards during his travels from Milton to Cambridge on July 21, 1773, to attend the Harvard College Commencement exercises. In the letter, Phips informs Snelling that he has issued warrants to the guards, instructing them to congregate at the Sign of the Grey Hound in Roxbury, Massachusetts at eight o'clock on the morning of the 21st. He explains that twelve other men will march, under the command of Sub-Brigadier Sumner, to the Governor's home in Milton to escort him to Roxbury, where the larger party will assemble. These heightened security measures were certainly prompted by political unrest, although this is not stated explicitly in the letter. Phips concludes by saying: "I shall order a dinner for us at Bradish's, where I hope to have the pleasure to dine with you."

Notes on cases in Barnstable County, 1791

Pamphlet containing notes on various cases, including a case "for not delivering goods put on board the defendant's vessel" and another "for concealing a pregnancy."

Inquiry of land rights, c. 1795

Handwritten list of five directives for completing the title search on a property purchased by a Mr. Harris from Andrew Bordman IV. The property was inherited from Bordman's mother Sarah, who in turn received the property from the estate of her brother Spencer Phips.

Warrant, 1752 April 7

Photostat of a royal warrant for Andrew Bordman III's appointment as "Justice of our Inferior Court of Common Pleas" in Middlesex county, witnessed by Spencer Phips, Massachusetts Lieutenant Governor. A note added May 19, 1752 confirms Bordman's test of declaration and oath of office before Francis Foxcroft and Samuel Danforth.

John Oldham counterbond to James Clarke & Richard Moores, 1722 May 14

This legal document, a counterbond, was created on May 14, 1722 and involved John Oldham, James Clark, and Richard Moores. All three men were residents of Cambridge at the time of its creation. The document specifies Oldham's financial obligations to Clark, a cordwainer, and Moores, a tailor and was "Sign[ed], sealed & [delivered] in the presence of Nathaniel Sparhawk and Noah Sparkhawk." The document also refers to the "trustees for the town of Cambridge" Spencer Shipps, Nathaniel Sparhawk and John Dickson.

Barre, Massachusetts 15 Minute Digital Raster Graphic

This layer is a digital raster graphic of the historic 15-minute USGS topographic quadrangle map of Barre, Massachusetts. The suvery (ground condition) date is 1887, the edition date is March, 1894 and the map was reprinted in 1942. A digital raster graphic (DRG) is a scanned image of a U.S. Geological Survey (USGS) standard series topographic map, including all map collar information. The image inside the map neatline is geo-referenced to the surface of the earth and fit to the Universal Transverse Mercator projection. The horizontal positional accuracy and datum of the DRG matches the accuracy and datum of the source map. The names of quadrangles which border this one appear on the map collar in their respective positions (N,S,E,W) in relation to this map.

Brookfield, Massachusetts 15 Minute Digital Raster Graphic

This layer is a digital raster graphic of the historic 15-minute USGS topographic map of the Brookfield, Massachusetts quadrangle. The survey date (ground condition) of this map is 1886-1887, the edition date is April, 1893 and the map was reprinted in 1942. A digital raster graphic (DRG) is a scanned image of a U.S. Geological Survey (USGS) standard series topographic map, including all map collar information. The image inside the map neatline is geo-referenced to the surface of the earth and fit to the Universal Transverse Mercator projection. The horizontal positional accuracy and datum of the DRG matches the accuracy and datum of the source map. The names of quadrangles which border this one appear on the map collar in their respective positions (N,S,E,W) in relation to this map.