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Genes and Cells
The Fundamental Biological Unit of All Living Organisms Is the Cell
To a surprising degree, all cells are similar in design and function, whether in
human beings, in plants, or as simple single-celled organisms such as bacteria.
One major difference, however, is the presence or absence of a distinct compart-
ment, the nucleus, for the genome. Cells with a nucleus, called eukaryotes, are
found in advanced single-celled organisms and multicellular organisms. Those
without nuclei, called proka~yotes are the simplest single~elled organisms, the
The importance of the cell as a biological unit is made clear when we
consider the life cycle of advanced multicellular organisms such as human beings.
The cycle begins with the fusion of egg and sperm, themselves single cells of spe-
cialized types, to form the one-celled embryo. At the earliest stage of our life
cycle, therefore, we exist as a single cell. This cell divides into two cells, each of
those into two more, and so on, to give rise to the adult organism, which may
contain as many as 1 million billion cells (see Chapter 5~. Every one of these cells
is autonomous in some functions and dependent or interdependent in others.
The entire developmental process is regulated by the myriad interactions
within and among individual cells. These interactions regulate the capacity of
cells to multiply, to differentiate into the hundreds of different cell types that
make up our bodies, and to organize themselves into tissues, organs, and finally
the human body itself, according to a specific, well-defined architectural plan.
This cycle of activity characterizes normal healthy individuals, but the pro-
cess can go awry, leading to abno~n~al states characterized by disease in humans,
animals, and plants. Since both normal and abnormal progression of the life cycle
is governed in a fundamental way by cells, it is logical that to understand and
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exert control over these phenomena and, in a real sense, over our own lives and
biological environment, it is necessary to learn all we can about the cell and how it
conducts its activities.
Since all organisms are related through evolution, we can use information
from simple organisms to determine protein and gene functions in higher and
more complicated organisms. Furthermore, new technologies allow us to test
these inferences by expressing the genes of more complicated species, such as
humans, in the cells of simple organisms such as yeast or bacteria.
The identification of the genes and the proteins involved in various cellular
functions is only part of the story. A deep understanding of the roles played by
individual proteins requires detailed characterization of their mechanisms of
action. Ultimately this requires knowledge of the three-dimensional structure of
each protein and of the rates of its reaction with other molecules. This characteri-
zation requires the development of test-tube (in vitro) assays of function. Genet-
ics can contribute to this effort by providing components from mutant cells that
can be used to identify essential components and to test the molecular roles
inferred from the physiology of live cells. Likewise, components identified as
part of in vitro mechanisms can be used to isolate the corresponding genes and
produce defective mutants to test in the live cell the functions inferred in vitro.
Many Cellular Functions Are Carried Out by Macromolecular Assemblies That
Can Be Isolated and Reconstitutedirom Their Constituent Molecules
Some biological functions such as the fermentation of sugar to alcohol are
carried out by individual proteins, alone or in a series of catalytic reactions, but
many others including photosynthesis and the beating of sperm tails require
complex assemblies consisting of many different types of proteins and other
molecules such as lipids and carbohydrates. These subcellular molecular ma-
chines include the organelles that can be seen by light microscopy as well as many
smaller structures.
Perhaps the most successful research strategy in cell biology for the past 30
years has been to purify these molecular machines so that their functions can be
studied outside the living cell. Fortunately, the organelles and many smaller
macromolecular complexes are so well constructed that they emerge from the
trauma of separation still able to perform complex, highly integrated functions
such as contraction, transport of molecules across membranes, photosynthesis,
the production of adenosine triphosphate (ATP), protein synthesis, and gene tran-
scription. This strategy has yielded a biochemical inventory and, in addition, a
rather detailed functional characterization of each organelle showing that func
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tional specialization and division of biochemical and biophysical labor prevail at
the subcellular level.
At the same time, studies of reconstituted cell fractions have demonstrated
that most macromolecular machines are formed by the self-assembly of their
component molecules. More recently, this approach has been used to demon-
strate that cell organelles can interact in vitro to reconstitute a specific intracellu-
lar process. Whole organelles such as the nucleus can now be reversibly disas-
sembled and reassembled in the test tube. A striking feature of the current state of
research in molecular and cell biology is the remarkable degree to which the
effectiveness of the reductionist strategy has been confused by experiments.
In Each Field of Cell Biology, Particularly Favorable Cells Have Been
Identif edfor Experimental Work
To a great extent, progress in molecular and cellular biology depends on
finding cell types that are suitable for experiments. Fortunately, because of the
parsimony of nature, mechanisms for determining the most important cellular
processes are shared by cells all along the phylogenetic tree. For example, the
force-producing protein myosin from muscle can bind functionally to actin fila-
ments from all eukaryotic organisms. Similarly, protein synthesis can be recon-
stituted in vitro from different components from plant and animal cells.
Fruit flies, sea urchins, and chickens have all been excellent sources of model
systems for analyzing cell behavior during embryonic development. Amphibian
eggs, because of their large size, are ideal for the production of foreign proteins by
microinjection of messenger RNAs (mRNAs). Highly motile amoebas that can
be grown in large quantities have yielded much of the basic information about
cytoplasmic contractile proteins. Chlamydomonas, an alga with two flagella and
well-characterized genetics, has provided much of what we know about the
molecular biology of flagella and cilia.
The occurrence in yeast of three specific cell types, each of which plays a
distinctive role in the cell's life cycle, makes the organism suitable for investiga-
tions in several important areas of cell biology, including genetic programming
for cell differentiation. Yeasts are also especially valuable for combined bio-
chemical and genetic studies of control of the cell cycle, exocytosis (secretion),
endocytosis (uptake), and biogenesis of such cell organelles as mitochondria.
The Nucleus Is Both the Warehouse and the Factoryfor Most of the Cell's
Genetic Material and Activity
The nucleus has three main functions: the storage, replication, and expres-
sion of the genes. The nucleus in most human cells is a sphere roughly 10
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micrometers in diameter that contains the almost 2 meters of DNA that makes up
the human genome.
The DNA contains the code for all cellular proteins and RNAs, as illustrated
in the pathway represented by the "central dogma":
DNA ~ RNA ~ protein.
This information is processed with exquisite precision. In most cells only a tiny
fraction of the total number of genes are actually expressed at any given time (or
ever). Furthermore, the patterns of gene expression change in precisely pro-
grammed ways during development. Thus, cells in kidney and brain express
independent repertoires of genes even though they originate from a single fertil-
ized ovum and have identical copies of the genetic material. The cells of a
developing embryo act like tiny computers that accumulate and remember infor-
mation concerning their past and present locations relative to other cells and
express genes appropriate to this information. The study of the control of gene
expression is an important focus of modern cell biology research. How do the
cells of complex multicellular organisms turn on and off their genes? And how is
the position of a cell "read out" by the cell to control specific genes? These are
difficult but central questions to cell biology that are being actively pursued in
many laboratories.
DNA is complexed with proteins to form chromosomes. All human body
cells (somatic cells) contain 46 chromosomes. The germ cells (sperm in the male
and eggs in the female) that contribute to the embryos of the next generation
contain only half that number 23. In addition, the nucleus contains an abun-
dance of proteins and RNAs, representing various structural elements and the
enzymes and products of replication, transcription, and RNA processing. How all
of these components are organized within the nucleus is unknown, and research
on the three~imensional structure of chromosomes and other nuclear components
is needed to better understand how genes function and are controlled.
Nuclear Envelope
All Molecular Traffic Between the Nucleus and Cytoplasm Is by Way of the
Nuclear Envelope
Replication of chromosomes and synthesis of most mRNA molecules is
restricted to the nucleus, whereas translation of messenger RNA into protein
occurs only in the cytoplasm. Separation of chromosomes from the cytoplasmic
space is thought to ensure proper regulation of nucleic acid and protein synthesis
in the cell. Except at the time of mitosis, when the nuclear envelope breaks down,
all molecular traffic between the nucleus and cytoplasm is by way of this enve-
lope, which consists of two parallel membranes joined at regions called nuclear
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Nuclear pores consist of a precise geometrical arrangement of structural
elements. The transport of large molecules across the pores and the direction in
which individual molecules are transported (cytoplasm to nucleus or vice versa)
seems to be selective. Selective proteins are actively moved from their site of
synthesis in the cytoplasm into the nucleus by means of an active transport system
in the nuclear pores. Selective RNAs are pumped out of the nucleus through the
same pores. For the transported proteins, the specificity is known to reside in a
short sequence of their amino acids that seems to be recognized by a component
of the nuclear pore. A number of pork complex proteins have been identified.
However, the organization of these proteins in the pore complex and their role in
regulating traffic in and out of the nucleus are largely unknown. Future analyses
of the structure, molecular composition of the pore complex, and the genes
encoding its proteins will undoubtedly reveal how this gatekeeper of the nucleus
Attached to the inner surface of the nuclear envelope with its pores and pore
complexes is a fibrous network known as the nuclear lamina. The major proteins
of the lamina, called lamins, have been identified and shown to be related to the
intermediate filaments found in the cytoplasm. (See the section on cytoskeleton
in this chapter.) The nuclear envelope seems to be a major site for anchoring
chromosomes and may also facilitate the packing of DNA in the nucleus. The
reversible assembly of the lamina may help control the breakdown and reforma-
tion of the nuclear envelope during mitosis.
Chromosomes Are the Structural Units That Contain the DNA
Each chromosome consists of one extraordinarily long DNA molecule com-
plexed with a multitude of proteins. An orderly condensation of long DNA
molecules into much smaller chromosomes is mediated by nuclear proteins. The
first level of folding involves a set of five proteins called histones. DNA interacts
with histories to form a regular beadlike structure, the nucleosome. Approxi-
mately 160 nucleotide pairs of DNA are wrapped around a core formed from two
copies each of four histone molecules (the histone octamer3. This basic structure
is repeated over and over to give a beads-on-a-string appearance when chromo-
some fibers are viewed in the electron microscope.
DNA complexed with histories is generally referred to as chromatin. Chro-
matin fibers consisting of nucleosome beads are folded into still more complex
structures known as superbeads or supercoils, depending upon one's view of their
organization. For technical reasons this higher-order folding of chromatin has
been hard to study, and we are only beginning to understand how chromatin
folding may be related to important processes such as the turning on and off of
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Beyond superbeads or supercoils, one major level of chromosome folding
can be recognized, the so-called loops. Loops have been studied in the lampbrush
chromosomes of oocytes for more than 100 years; the giant lampbrush chromo-
somes consist of several hundred individually recognizable loops of chromatin
extending laterally from the main axis. These lampbrush loops are regions of
unusually intense RNA synthesis that provide a unique opportunity to visualize
active gene transcription. When RNA synthesis is completed, the loops contract
back into the main axis of the chromosomes. The loops are thought to retain their
individuality even during mitosis, the time of maximal chromosome condensa-
tion. Loops of chromatin similar to those of the lampbrush chromosomes can be
seen when normal mitotic chromosomes are chemically treated to loosen their
We know very little about the composition (or intranuclear location) of the
macromolecular complexes that anchor the DNA into loop-domains inside nuclei.
Fortunately, however, the genome does not remain in the dispersed state charac-
teristic of physiological activity during the entire cell cycle. At cell division
(mitosis), the nuclear envelope disassembles and the genome condenses into
discrete chromosomes. These mitotic chromosomes provide an opportunity to
study the organization of the DNA loop-domains in the absence of the many
soluble components that participate in transcription and replication. Methods are
currently being developed to identify proteins that regulate mitotic chromosome
architecture. Recently one putative component of the loop-domain anchor com-
plex was identified as the enzyme DNA topoisomerase II, which had previously
been identified as able to knot and unknot DNA molecules in vitro. Genetic
analysis shows that this activity is required at mitosis if the two sets of intertwined
DNA molecules are to be successfully partitioned to daughter cells. Future
studies should identify other components of the anchor complex and eventually
enable us to determine what role they may play in the regulation of a gene's
The domain idea has matured sufficiently during the past decade that the
genome can now be conceived of as being constrained into loops whose average
size is roughly 100,000 base pairs. In theory, the loop-domain model permits the
coordinate control of complex arrays of genes, since regions that may be very
distant in the DNA sequence may actually be physically adjacent (at the base of a
loop) in the nucleus. The nucleolus is an example of the clustering of dispersed
DNA regions into a single-functional domain where the genes (often found on
different chromosomes) encoding ribosomal RNAs associate physically and are
expressed together.
It is a striking coincidence that DNA replicates in multiple independent
blocks, which again are about 100,000 base pairs long. Thus, loop-domains (or
clusters of loop-domains) may constitute the control units for both transcription
and replication. This model predicts the existence of a new set of nuclear
components that control DNA function the structural components that anchor
the loop-domains; at present, however, these ideas have yet to be demonstrated.
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Centromeres and Kinetochores Play a Key Role in the Migration of
Chromosomes During Mitosis
During the separation of chromosomes at mitosis, microtubules of the mitotic
spindle attach to a specific site on each chromosome known as the centromere or
kinetochore. (As now used, centromere refers to the DNA sequences at this site
and kinetochore to a rather complex structure of unknown composition visible by
electron microscopy.) The centromere is fundamentally important because move-
ment of the chromosome at mitosis and meiosis into daughter cells depends on
this region; chromosomes without a centromere fail to move normally and are
eventually lost from one of the daughter cells. Centromeric DNA has been cloned
and sequenced from the yeast Saccharomyces. Remarkably, the DNA region nec-
essary for accurate segregation of a chromosome is no more than a few hundred
base pairs long in this organism. The centromeres of higher e~caryotes are larger
and their characterization will be difficult, but should prove of great interest for
comparison with the presumably simpler condition in yeast. The use of antibod-
ies produced by patients with an autoimmune disease has made it possible to
identify and clone the DNA sequence for a centromeric protein. Characterization
of this human protein and others that mediate association of the centromere with
the spindle microtubules should give insight into critical questions of chromo-
some movement during mitosis and meiosis.
Telomeres Maintain the Structural Integrity of Chromosomes
The ends of eukaryotic chromosomes, the telomeres, are special in several
ways. Telomeres stabilize chromosomes and prevent their fusion with other
broken or natural ends. In addition, their structure allows replication without loss
of DNA. The ends represent a vanishingly small amount of the total DNA in a
typical chromosome. For this reason telomeric sequences were first recognized in
certain ciliates, which have thousands of extremely small chromosomes and
hence thousands of telomeres. Telomeres have subsequently been identified in
yeast and several other organisms, including humans. In all cases they consist of
hundreds of nucleotides of simple repeated DNA (such as CCCCAA and
CCCCAAAA repeats) associated with unique proteins. Telomere sequences are
added to the ends of chromosomes at the time of chromosome replication by a
special enzyme or enzymes without the need for a DNA template, and in this way
they form a protective cap at each end of a chromosome.
Artificial Chromosomes Are Valuable Research Tools
The identification of centromeres and telomeres as well as sequences that
initiate DNA replication now permits the synthesis of artificial "minichromo-
somes" by genetic engineering techniques. Such minichromosomes have already
been introduced into yeast cells, where they function normally during both mito
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sis and meiosis. Work on artificial chromosomes in yeast will undoubtedly lead
to increased knowledge about chromosome structure and mechanics; eventually
similar studies will be possible in higher eukaryotes, simplifying the introduction
of specific genes or gene combinations into experimental organisms. One impor-
tant use for the artificial yeast chromosomes is in the cloning of very large
fragments of DNA (as many as a million nucleotide pairs).
The Nucleolus
The Nucleolus Is the Site in the Nucleus for the Transcription of Ribosomal RNA
The nucleolus is the major structural differentiation seen in nondividing
nuclei. It is formed from a specific chromosomal locus, the nucleolar organizer,
which contains the genes coding for ribosomal RNA (rRNA). When rRNA is
synthesized, it first accumulates in the nucleolus in association with a large
number of ribosomal proteins. Eventually the rRNA and proteins are transported
to the cytoplasm, where they constitute the mature ribosomes. Although the
major features of rRNA synthesis and its relation to the nucleolus were worked
out more Can 15 years ago, the nucleolus continues to tee of interest es a model for
RNA transcription and processing. In particular, we are just beginning to learn
about the nbosomal proteins and the ways they interact with rRNA to form the
ribosomes. Ribosomes themselves are crucially unportant to cell function, since
they are the machines Hat catalyze all protein synthesis.
The Primary Questions That Have Been Askedfor the Past 100 Years by
Geneticists Are Still Inspiring Research Innovation
Geneticists have always wanted to know how traits are passed from one
generation to the next. We now seek to answer these questions at higher levels of
resolution. For example, we can ask, What is the structure of genes? How do
they replicate? How are they organized on chromosomes? How do they mutate,
recombine, and repair themselves? What controls the timing of gene expression
and repression? What mechanisms control tissue-specific and cell type-specific
gene expression? The answers that we anticipate are at the level of nucleotide
sequences, the three-dimensional structure of chromatin, the mechanism of action
of enzyme complexes and specific DNA binding proteins. As answers to these
questions emerge, we can use the resulting picture of how genes act to ask even
more sophisticated questions about their products and functions.
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Genetic Analysis
The Combination of Classical Genetics and Biochemustry [las Resulted in an
Explosion of Genetic Understanding
The field of genetics has made dramatic advances within the past 25 years
largely because biologists learned that genes are made out of DNA. In classical
genetics, the arrangement of genes on the chromosomes was inferred by analysis
of crosses between organisms. In modern genetics the order of genes can in
principle be determined directly by sequencing the DNA molecules. The rapidity
and certainty with which genes can be sequenced by biochemical procedures,
even in organisms having no convenient sexual cycle or, as in humans, having a
long cycle, have come to give the illusion that classical genetics has been sub-
sumed by biochemistry. The most elegant insights, however, have emerged in the
collaboration between classical genetics and biochemistry, which has created the
field of molecular genetics. In this collaboration, the goals of genetic research
have not changed. Geneticists still seek to learn the set of instructions that specify
the architectural plans encoded in the DNA for building a functional organism.
Mutations in Essential Metabolic Pathways [rave Contributed to Our
Understanding of Both Genetics and Biochemistry
Classically, genetic analysis starts with mutations. These are alterations in a
single gene that result in changes in an organism's appearance or biochemistry
(phenotype). For example, normal yeast cells can grow on a simple medium with
no amino acid supplements. Mutations can be found that lead to the requirement
that an amino acid, say histidine, which the cells would normally produce itself,
be supplied in the growth medium. Mutations of this type are extremely useful
because the cells can be maintained and genetic crosses can be made on complete
medium, yet the mutation can be detected at any time by plating a sample of cells
onto medium that lacks the required nutrient. Such conditional and selectable
mutants have been the basis for learning the fundamentals of molecular genetics,
the physical nature of the gene, and the structure of chromosomes. These
mutations have also been important to our current understanding of biochemistry,
The analysis of many mutants, each blocked in the same biochemical pathway,
but at different steps, can lead to an understanding of how complex molecules
could be formed by sequential chemical reactions.
When coupled with genetic crosses, mutant analysis becomes a valuable tool
for dissecting some of the most complex biological functions by correlating
genotype (the nucleotide sequence) with phenotype (how the organism looks). A
decade of intensive research correlated gene structure and function with bio-
chemical activities of simple organisms. In some cases a single base-pair change
in the DNA can be correlated with the loss of the catalytic function of an enzyme
in a biochemical pathway. The metabolite required in the diet of the mutant
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organism reveals the identity of the defective biochemical pathway. The loss of
enzyme function easily explains the phenotype of the mutant organism~he
failure to grow without a metabolite in the medium since the mutant cannot
carry out one of the steps in the biosynthesis of the metabolize. Thus, classical
genetic analysis allowed the elucidation of biochemical pathways because the
essential steps in the pathways were easy to eliminate: The genes were discov-
ered through mutations with a metabolite-requiring phenotype, the functions were
inferred by inspection of the phenotype, and the proteins were identified by
application of chemical and biochemical analysis of the mutants in comparison
with the normal.
The Analysis of Mutations in Other Types of Genes Requires a
Different Approach
Although these approaches permitted an understanding of metabolic path-
ways in simple organisms, they are difficult to apply to the direct analysis of
cellular structure and to questions involving the complex interactions that deter-
mine protein structure and function in higher organisms. The major difficulty lies
in our inability to connect genetics and biochemistry at higher levels of complex-
ity. Very often the function that we wish to study is part of a subcellular structure
and cannot simply be added back from the outside to correct the effect of the
mutation. Furthermore, a component of the cell's architecture may be essential
for viability, and then a mutation in this function would be lethal. Undaunted,
geneticists still made considerable progress through the mutation analysis ap-
proach by using conditional lethal mutations (for example, mutations that permit
growth at one temperature, but not at another). Despite many imaginative efforts,
it became clear that major cellular processes could not be analyzed simply by
examining phenotypes in the old ways that had elegantly sufficed for determining
basic biochemical pathways.
To associate a gene with its function in one of these complex cellular
processes required development and exploitation of new experimental strategies
that can permit the enumeration of genes controlling the synthesis and function of
the cell's architecture. The new methods enable scientists to carry out a new
chain of discovery that allows them to associate the gene with a cellular function,
with a gene product (usually a protein), and ultimately with a mechanism by
which the gene product executes the function.
Even with the latest in technologies, one still faces problems in associating
genes with products and the products with essential functions related to cellular
structure, progress of the cell division cycle, or other functions carried out by
macromolecular assemblies. The geneticists can identify candidate genes by
observing mutant properties that suggest failure in cell architecture or cell cycle.
Biochemists and cell biologists, on the other hand, can find proteins (such as actin
and tubulin) that are abundant in structures implicated in basic cell function. The
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challenge to the molecular geneticist is to find ways to bring these lines of
endeavor together so that the geneticists' genes can be associated with the bio-
chemists' proteins and the cell biologists' structure and function.
A Gene Isolation Experiment Usually Begins with the Construction
of a Gene Library
The gene library is a collection of DNA fragments carrying every gene from
the organism, each recombined with a carrier DNA molecule called a vector. The
vector contains genes that permit replication and transmission of the vector and
any DNA joined to it when the DNA is transformed into the appropriate cloning
host (usually a bacterial or yeast cell). The library is made by chopping the chro-
mosome into gene-sized pieces of DNA and then joining each piece to its vector.
The size of the library depends on the size of the organism's genome.
Isolating a Specific Gene from All the Rest of the Recombinant Molecules
Can Occur in Two General Ways
The more classical route begins with mutations, which define a gene and
whose properties (phenotype) indicate failure in a particular cellular function.
One can readily isolate the gene as a DNA fragment by using DNA transforma-
tion with gene libraries to complement a mutation. Restriction fragment length
polymorphisms (RFLPs), to be discussed later, can also be used to localize genes
or chromosomes. The isolated gene can be analyzed as a physical entity, after
which one can find the gene product and determine, in favorable cases, something
about the way in which this protein contributes to cellular function. By this route
one eventually obtains all the elements: the gene, the function, and the protein
product. This route works well with bacteria, yeast, and cultured cells of higher
organisms if the gene desired has a strongly selectable phenotype.
The second approach begins with a gene product, perhaps a protein involved
in some cellular process. Isolation of the gene for that protein depends on what is
already known about that protein and often on the ingenuity of the investigator. If
the protein sequence is known, oligonucleotide probes can be chemically synthe-
sized on the basis of information contained in the protein's amino acid sequence.
These probes can be used to screen the library by hybridization.
Other techniques involve isolating mRNA from the cell type of interest,
transcribing it into DNA, and cloning it into a vector that is designed to direct
transcription of that mRNA when it has been transformed into a bacterial host.
Colonies of bacteria producing the desired protein can be identified by antibody
binding (if an antibody is available) and then grown to yield quantities of the
desired cloned genes. These clones can be used to screen a library of genomic
DNA sequences to obtain the gene encoding the mRNA.
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GENES AND CF-~.r-s
Although it seemed unlikely that cyclic AMP would be the only intracellular
second messenger of hormones, the next system was not identified until very
recently. In this system (Figure 4-5), hormone receptors also act through a G
protein to stimulate the activity of phospholipase C (PLC), which cleaves phosphati-
dylinositol bisphosphate (PIP2) to form two distinct second-messenger molecules.
One of these is diacylglycerol (DAG), a membrane lipid that binds to and
stimulates protein kinase C. The other messenger derived from PIP2 is inositol-
trisphosphate ALPS), which acts on receptors in the endoplasmic reticulum to
release stored calcium ions and raise their cytoplasmic concentration. The two
arms of this signaling cascade, calcium ion (Cam) and protein kinase C, act on
other cellular components to produce a set of responses that includes contraction
of smooth muscle (stimulated by agents such as norepinephnne), modulation of
synaptic responses in the central nervous system, a variety of secretory responses,
and some, but not all, proliferative responses of cells to growth factors such as
_ PtdinsP~
aM AT DP
~ Pi
E CaM - E* Al
FIGURE 4-5 Calcium ion as a second messenger. [Adapted from H. R. Boume and A. L. DeFranco,
in The Oncogenes, R. Weinberg and M. Wigler, eds. (Cold Spring Harbor Press, Cold Spring Harbor,
N.Y., in press), chapter 3]
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The discovery of Gs led to the discovery of a whole family of G proteins
involved in other kinds of signal transduction. A key feature of the G protein
machine is that it allows amplification and regulation of the transduced signal by
separating excitation of the receptor from activation of the effecter in both time
and space. Thus, the encounter of a neuromodulator such as norepinephrine with
its receptor may be short-lived. When the encounter generates a GTP-bound Gs
molecule, however, the duration of activation of adenyl cyclase depends on the
length of time GTP stays bound to the G protein rather than on the tenacity with
which the receptor holds onto norepinephrine.
In addition to G. at least five other G proteins have been discovered. They
include one that mediates hormonal inhibition of adenyl cyclase, two that mediate
retinal phototransduction in rods and cones, and others that mediate hormonal
regulation of ion channels and production of second messengers derived from
phospholipids. Despite their diversity, each of the G proteins is built on the same
general plan, comprising three dissimiliar polypeptide chains, called a, if, and y.
The a chains bind and hydrolize GTP and confer on each G protein its specifici-
ties for interacting with particular receptors and effecters. The ,3 and ~ polypep-
tides anchor the protein to the membrane. In addition, the highly conserved GTP
binding sites of the a chains closely resemble similar sites in the elongation and
initiation factors of ribosomal protein synthesis and in the protein products (palm)
of the ras oncogenes and proto-oncogenes. Thus, the duplication and divergence
of genes in evolution have modified a single molecular machine and made it
useful to mediate vision, olfaction, control of cell proliferation, ribosomal protein
synthesis, and cellular regulation by many hormones and neurotransmitters.
The apparent parsimony of evolution encourages investigators to extrapolate
information obtained from one class of G proteins to another as well as to other
proteins with the conserved GTP binding site, such as p21ra&. Only a few years
ago, scientists would have scoffed at the notion that studies of bacterial protein
synthesis or retinal phototransduction could reveal anything useful about the
cause of cancer.
In addition to explaining the cellular actions of a number of important
hormones and growth factors, the cascade of events elicited by these substrates
has made two other general contributions to the understanding of signal transduc-
tion. First, the discovery of a second system of intracellular messengers encour-
ages the expectation that more such systems will soon be found. The enormous
array of chemically distinct membrane phospholipids provides an almost inex-
haustible source of potential precursor molecules for generating second messen-
Second, understanding this system has enriched our understanding of the
interplay between different second messenger systems in individual cells. For
example, epinephrine can stimulate the release of glucose from the liver via two
different pathways using different receptors and different G proteins to generate
both cyclic AMP and IP3-DAG in the same cell type. The two second-messenger
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GEAlES AND CELl~;
Growing knowledge of G proteins Chase already contributed significantly
~to~mol~ular~lunderstanding of human disease. The pathogenic~tox~ins of
vitro choJerae~ (cholera) Andes ~Bor~te//a~pertussis~:: (whooping coughs are
now known to Tact as enzymes that attach ~adenosine diphosphat~ribose
(AD~P-ribose) to~t~he~a polype~ptide chain~s~of~two specific G proteins, LOG and
G. ~respectively. The modification of G by cholera toxin stabilizes the G
l' Q
protein in its~GTP-bound form and thereby increases activation of adeny
cyclas~ei (AC);I~the resulting cyclic AMP rise in mucosal cellsl;of the intestine
causes~the profuse secretion of salt and water responsible for the often fatal
Diarrhea of cholera. In contrast,~attach~ment~by pertussis toxin of ADP-ribose~
to the a chain of G. produces a G protein that~i~is uncoupled from inte~ract~on
w~h~hormone~receptors asa~rQsuit~pertuss~isl~ioxinblocks~hormonalinhibi
, ~ ~
bisons Of AC. ~ In ~ othe~rl~cell types, pQ~4U"iS ~ toxin s ~ anions on GO or ~ a Gj-like
HI molecule block ~ligand-stimulatdd pho~spholipid~ metabolism anal elevation of
cytoplas~mk calciums (thereby inhibiting,~;for; example, release of allergic
;~ rnediators~from mast cells). ~ ~ ~ ~ ~ ~ ~ ~
~ ~ In the other direction the ability of these toxins toll introduce radioac
tively labeled ADP-ribose into the G protein cz chains has made them
valuable tools for studying G ~proteins. ~ Indeed, the G molecule was discov-
~e~red by investigators primarily interested in the mechanisms of action of
The pivotal biological roles Of the G proteins suggest that mutations in
the corresponding genes~s~houl~d produce inherited disorders of signal
transduction. One of these~possible diseases has Ben identified: inheri-
tance of a mutant allele of the gene that encodes the a chain of Produces
An inherited human disorder called pseudohypoparathyroid~ism, type ~1 (PHP-~
1~. The hypocalcomia, mental retardation, convulsions, and other clinical
manifestations of PHP-I result from partial resistance to hormones that
utilize cyclic AMP as a second messenger. Many endocrine responses
mediated by cyclic AMP are only mildly affected in PUPA resistance to
parathyroid hormone, the master hormone of calcium ion homeostasis, is a
prominent feature of PHP-I, suggesting that the amount or activity of Gs is
normally more rate-limiting for actions of this hormone than of others.
OCR for page 77
systems act in parallel to stimulate the breakdown of glycogen in the liver cell. In
contrast, the IP3-DAG and cyclic AMP work in opposite directions in platelets.
By imagining only one or Pro more second-messenger systems in addition to
cyclic AMP and IP3-DAG, we could account for almost any degree of complexity
in cellular responses to extracellular signals. Regulation of cell proliferation
involves just such a complex interplay of transduction pathways; these pathways
are just beginning to be understood.
Cytoplasrruc Free Calcium Acts as a Second Messenger
Three mechanisms for raising the free calcium ion concentration in cyto-
plasm have been found: the voltage-gated calcium channel of the plasma mem-
brane, release of calcium ions from the endoplasmic reticulum of muscle when
the surface membrane is depolarized in response to a nerve impulse, and release
of calcium ions from the endoplasmic reticulum in response to hormonal signals
acting on plasma membrane receptors. We understand how {P3 iS produced, but
not what it does to the endoplasmic reticulum to release calcium. Because of the
central role of calcium ions in signaling, the mechanisms of excitation-contrac-
tion coupling in muscle and that of calcium ion mobilization by ~3 in many cells
needs vigorous investigation.
Two processes regulated by intracellular calcium also need to be studied.
One is the release of vesicles of packaged neurotransmitters, hormones, or en-
zymes. Although we know that calcium entry is required, we do not understand
any of the subsequent steps that, for example, cause the transmitter ACh to be
released within 0.1 millisecond of the excitation of a nerve terminal. Both
botulism and tetanus are bacterial diseases whose lethal consequences are due to
toxins that interfere with this calcium-dependent secretion by nerve cells. An-
other calcium-dependent process is cell motility, including muscle contraction.
The calcium-sensitive component molecules of the contractile machinery have
been characterized in some detail, but except for muscle the physiological mecha-
nisms coordinating motility are poorly understood.
Progress is now possible in the analysis of calcium-stimulated events with the
advent of new optical methods to measure intracellular calcium ion concentra-
tions. Newly synthesized calcium-indicator dyes can be injected or allowed to
permeate into cells. The time course of changes within a single cell can now be
monitored reliably. Computer-aided spectroscopic techniques permit making
accurate maps of the changing free calcium in each pixel of a video image of the
cell observed under a high-power light microscope. The technique has already
been used to observe the fertilization of eggs and the stimulation of liver cells by
peptide hormones.
OCR for page 77
Transduction Mechanisms Use a Variery of Strategies to Alter Cellular Chemistry
in Response to Messenger Molecules
More intracellular second messengers remain to be discovered, and the
means by which they and the "established" second messenger systems integrate
control of cell function are still to be elucidated. Thus, a large number of
hormones and other chemical signals act on receptors whose transduction mecha-
nisms are unknown. These include growth hormone, many of the lymphokines,
nerve growth factor, and tumor necrosis factor. Understanding the actions of
these ligands may uncover new molecular mechanisms of signal transduction.
Moreover, each transduction system can alter its sensitivity to extracellular shm-
uli. Determining the molecular mechanisms that regulate sensitivity represents
important new opportunities in research.
A New Class of Genes Can Transform Host Cells
An oncogene (the src gene) was first identified in the transforming Rous
sarcoma retrovirus. When suitably expressed, this gene alone was capable of
transforming avian cells. Normal cellular homologues of oncogenes, or cancer
genes, were found subsequently in virtually every organism analyzed, which
suggested that transposed DNA from normal hosts had been incorporated into the
retrovirus genome, under control of viral promoters, and was capable of initiating
and maintaining transformation of infected cells. Subsequently, more than 25
oncogenes have been identified along with the normal cellular counterparts, the
cellular proto-oncogenes. Oncogenes may be resolved into families that include
elements of many of the cell-regulatory systems reviewed above: (1) the protein
products of the src gene family appear to be tyrosine-specific protein kineses (and
thus similar to growth-factor receptors) that are located at the plasma membrane
or in cytoplasm; (2) other oncogenes are related to growth factors or to their
transmembrane receptors; (3) the ras gene proteins bind and hydrolyze GTP and
seem to act as signal transducers at the plasma membrane and cytoplasm; and (4)
nuclear oncogenes probably act as transcription factors or DNA-binding proteins.
Research opportunities include the identification and functional characteriza-
tion of additional proteins encoded by oncogenes. Once defined, the pathways by
which these proteins influence cell growth and those that regulate proto-onco-
genes should provide insight into the cell cycle, cell proliferation, and control by
pharmacological means. Research into oncogenes should help us better under-
stand normal cellular proliferation, the abnormal proliferation characteristic of the
cancer cell, and pathways of significance to cellular differentiation. Other re
OCR for page 77
search using genetically engineered molecular hybrids should provide under-
standing at the molecular level of the function of each of the protein domains of
these gene products responsible for transformation.
Plant Cells Differ from Animal Cells in Many Ways
Cells of plants and animals have many features in common, such as nuclei,
endoplasmic reticula, Golgi complexes, mitochondria, plasmalemmas, coated
vesicles, microfilaments, and microtubules; but in some features and processes,
cells of these two kingdoms are distinct from one another. For example, plant, but
not animal, cells contain plastics (the generic term that includes chloroplasts and
modified chloroplasts such as amyloplasts that produce and store starch), large
vacuoles that serve as the lyric compartment (lysosome-lilce) and contain most of
the plant cell's water; they also have relatively rigid cell walls composed of
strands of cellulose embedded in amorphous carbohydrate polymers together with
a small amount of protein.
At higher levels of organization, plant cells are connected to one another by
strands of cytoplasm (plasmodesmata), rather than by junctional elements of the
type found in animal cells. The tissues and organs of plants and animals are not
organized along similar functional lines. Leaves, stems, roots, and buds have no
conspicuous counterparts in hearts, livers, skins, or lungs.
At many fundamental levels-biosynthetic pathways and structures of pro-
teins and nucleic acids-plant and animal cells are often, but not always, the
same. Thus, differences, when they occur in similar processes, often reveal much
about the basic nature of a process. It is often profitable to determine whether
newly discovered features of plants occur in animals and vice versa.
The features of plant cells and tissues that differ distinctively from those of
animals each require direct investigation. For example, in plants, mitochondria
perform the same respiratory functions (and perhaps some other, as yet undiscov-
ered functions) as they do in animals, but they generally contain much more
DNA. They also seem to use the standard genetic code, whereas the mitochondria
of animals and yeast use a nonstandard one.
In addition to photosynthesis, a number of phenomena are unique to plants,
and some are targets of active research. For example, each plant cell contains
three rather than two gene-containing compartments (the nucleus, mitochondria,
and plastics), thus greatly complicating protein targeting and the integration of
genome expression. Other research is focused on the plant's rigid cell walls,
which are constituted in different ways at different stages of development and for
various specific functions of different cell types. The composition of the cell
walls is reasonably well understood, but many questions remain unanswered.
Self-incompatibility, the inability of some plants to fertilize themselves, is an
mportant mechanism for regulating outcrossing. The expression of plant genes
OCR for page 77
can be affected by symbiotic or pathogenic microorganisms through complex
interactions. In this area, important advances have been made, especially in
studies of symbiotic nitrogen fixation, but the total effort is still very small. Some
transposable genetic elements have been characterized molecularly, but how they
are integrated into and excised from the genome remains to be understood.
Photosynthesis Is the Biological Process That Connects Life on Earth to the Sun
Through photosynthesis, light energy is converted to chemical-bond energy
stored in sugar molecules. In higher plants and algae, photosynthesis is carried
out in chloroplasts-organelles containing vesicles bounded by energy-transduc-
ing membranes in which the chlorophyll is localized. In primitive, noncompa~t-
mentalized cells-prokaryotes-these vesicles lie free in the cytoplasm.
Progress in understanding photosynthesis has been intertwined with ad-
vances in chemistry, photophysics, and biology. The path followed by carbon
during photosynthesis from carbon dioxide to sugar is now known in detail,
and most of the enzymes have been identified. The enzymes themselves are being
studied, and, surprisingly, a number of them are found to be regulated (in ways yet
to be understood) by light and by certain of the small molecules that are interme-
diates in the biosynthetic chains of photosynthetic carbohydrate production. The
regulatory mechanisms and how each enzyme interacts with other proteins and
with its substrates are questions currently being addressed.
Chloroplast Genes Are Being Mapped and Sequenced at a Rapid Rate
The chloroplast genomes of tobacco and liverwort have been fully sequenced,
and restriction maps of the chloroplast genome have been completed for at least
40 to 50 species of plants. Most gene mapping is limited to genes that were
located and initially mapped and sequenced in maize, spinach, tobacco, and the
green algae Chlamydomonas and Euglena.
As more and more chloroplast DNA is sequenced, interest will grow in
identifying the gene products of unrecognized proteins; their identification should
move us toward a better understanding of photosynthesis and plastic metabolism.
This DNA sequencing will also reveal features of plastic genes. At least one type
of promoter sequence-resembling the proka~yotic Me-has been recognized.
The existence of other kinds of control sequences remains to be established. The
identification of these and other controlling elements of plastic or nuclear-cyto-
plasmic origin that constitute the parts of the machinery for control of differential
gene expression may well be the most interesting and outstanding problem in this
research area. Its resolution is likely to illuminate the mechanisms underlying the
transcriptional control of chloroplast gene expression and to reveal research
approaches leading toward an understanding of intergenomic integration.
OCR for page 77
Gene Expression in C~oroplasts Is Both Developmentally and
Functionally Regulated
Like mitochondria, plastics contain genetic material, but not all of their
components are products of these genes. Many proteins of the chloroplast are
imported from the cytoplasm, and these are encoded in nuclear genes. For
example, the larger of the two subunits of ribulose bisphosphate carboxylase/
oxygenase (rubisco) is the product of a chloroplast gene, whereas the smaller
subunit is the product of a nuclear gene.
How the photosynthetic apparatus of chloroplasts is produced, that is, its
biogenesis, is a question fundamental to understanding the life of a plant or alga
cell. A number of related questions are under active investigation: What are the
special characteristics of chloroplast genes? What are the enzymes and mecha-
nisms for their replication? What are the mechanisms for controlling the expres-
sion of sets of developmentally regulated chloroplast genes? How is the expres-
sion of these genes integrated with the expression of nuclear genes for chloroplast
components? How are nuclear gene-coded, cytoplasmically synthesized proteins
targeted to plastics, and what are the mechanisms for their uptake and integration
into the life of the plastic? How does the machinery for chloroplast gene
expression interact with the machinery of the nuclear-cytoplasmic compartment?
Among the most interesting aspects of the plant eukaryotic cell is the integration
of the activities of its multiple compartmentalized genomes-of nuclei, plastics,
and mitochondria. The nature of the integrating mechanisms can now be investi-
The Origin of Plastids Is Still a Mystery
One of the great puzzles of modern biology is how euk~uyotic cells origi-
nated. A unique characteristic of eukaryotes is the presence of multiple compart-
mentalized genomes. In plants, these include the nucleus, mitochondria, and
plastics. The question of how the expression of these genomes is integrated has
already been raised. An older unanswered question is, How did the multiple
genomes come into existence? There are two obvious possibilities. One is that
membranous compartments formed in the structural equivalent of a modern
proka~yotic cell, and some genes then became sequestered in each compartment.
A second possibility, favored by most available evidence, is that the major
organelles characteristic of eukaryotic cells-mitochondria (which are found in
the cells of all but a very few eukaryotes) and chloroplast~are the descendants
of symbiotic bacteria that entered early eukaryotic cells. To account for the
genetic organization of contemporary eukalyotic cells it is necessary to assume
the movement of genes or gene functions from the symbiont to the host genome.
Many researchers have interpreted the available evidence as suggesting multiple
origins, involving different groups of bacteria, for chloroplasts and perhaps for
mitochondria also. These hypotheses require further analysis.
OCR for page 77
What evolutionary pressures led to the existence of the different information-
processing systems now found in the nuclear-cytoplasmic and organelle compart-
ments? Are the different systems relics of the independent evolution of two
progenitor cell types that subsequently joined to become the ancestral form of the
modem eukaryotic cell? Alternatively, did two or three information storage and
processing systems evolve within a single cell? What we learn about the molecu-
lar biology of the organelle and the nuclear-cytoplasmic systems may lead to a
better understanding of the origin and evolution of eukaryotic cells as well as of
the forces and mechanisms underlying the shifts of genes among genomes.
Evolutionary relations among genomes are much better understood now than
they were half a dozen years ago because of the accumulation of nucleic acid
sequence data. However, the forces that have led to the segregation of genes in
nuclei, mitochondria, and plastics are unknown. Gene-transfer methods are
beginning to be used to explore these questions from the focus of the nuclear
genome. Efficient organelle gene transfer (transformation) methods that would
greatly aid such investigations remain to be developed.
The Plant Cell Wall
Research on the Extracellular Matrix (Cell Wall) of Plants Is Crucial to
Understanding [low Plants Grow
Lacking a skeletal structure and subjected to a fluctuating osmotic environ-
ment, plant cells rely on rigid cell walls to serve as cementing substances between
cells, to provide mechanical strength, and to support high internal osmotic pres-
sures. For many years, it has been known that the ultimate shape and strength of
such walls are largely determined by the pattern and extent of deposition of
extended fibrils composed of cellulose (glucose molecules joined in p-1,4 link-
age). In recent years, the concept has evolved that a second framework, com-
posed of cross-linked extended rods of a hydroxyproline-rich glycoprotein called
extensin, also contributes to strength and shape in some plant cell ~es. Inter-
spersed within these frameworks exist a variety of ma~x polysaccharides, some
having complex structures. One example is the recently discovered, highly
branched rhamnogalacturonan II polymer that contains a number of variously
linked sugars including a novel monosaccharide called aceric acid, which was
previously unknown in nature. Progress in determining the structure of these
polysaccharides has advanced considerably in recent years, in part as a result of
vastly improved techniques for the analysis of complex carbohydrates. These
techniques require the use of expensive instrumentation such as mass and nuclear
magnetic resonance spectrometers. Increased access to such instrumentation
would hasten progress in the study of extracellular matrices of both plants and
Understanding plant cell-wall structure is crucial for the ultimate understand-
ing of how plants grow. Plants increase in size by expanding their rigid cell walls,
OCR for page 77
but our understanding of the mechanism by which this occurs is still limited. The
process is known to be under hormonal control; wall loosening is believed to
occur by processes of breakage and reformation of crucial linkages and by
turnover of some wall polymers, but the specific processes remain elusive. Re-
cent structural analyses have provided evidence for intra- and interchain linkages
between extensin molecules through isodityrosine residues, presumably formed
in the wall by a peroxidase-mediated reaction. Similar enzymes may also be
responsible for the formation of cross-links between phenolic components at-
tached in ester-linkage to matrix polysaccharides. Other recent studies have
implicated hormonally regulated degradative enzymes involved in the turnover of
some wall polysaccharides, such as xyloglucan, in the process of wall extension.
On the basis of current knowledge of wall structure, one can estimate that
there must be more than a hundred different enzymes required for wall assembly.
Not one of these enzymes has yet been purified and characterized in detail,
although a number have been detected and assayed in crude membrane prepara-
tions isolated from plants. Similarly, no gene responsible for coding for these
enzymes has been identified, mapped, or cloned. Exciting progress has been
made recently for the cell-wall protein extensin, since a gene for this protein has
recently been cloned and characterized. Coupled with previous structural infor-
mation on the protein, data from the gene sequence now give the entire amino acid
sequence of the protein so that we can identify sites of glycosylation, cross-
linking, and possible areas of interaction of this polymer with other wall compo-
We now recognize that the cell wall is a dynamic structure. Not only do
changes occur during normal growth and development, but the wall also responds
quickly to external perturbations such as mechanical damage, water, or tempera-
ture stress and upon interaction with symbionts, pathogens, or parasites. Recent
work has defined some of these "wound" responses in some detail. Specific
changes identified are a cessation of cellulose synthesis coupled with induction of
synthesis of a related beta-glucan called callose, which seals off areas of assault;
induction of lignin or suberin synthesis; and elevation of synthesis of the soluble
precursor to cell-wall extensin. This latter compound in some cases seems to
serve as an agglutinin for invading pathogens. Most exciting is the recent work
implicating fragments of wall polysaccharides as regulatory molecules. One
example is an oligogalacturonide released from the wall by invading pathogens;
this oligosaccharide serves as a specific inducer of the synthesis of phytoalex-
ins-plant-made antibiotics that are toxic to invading microorganisms. Other
examples include small phenolic compounds that may be released from the wall
and that signal interactions crucial for the establishment of plant parasites or
symbiotic associations with bacteria (see Chapter 11~.
Recent advances in our ability to analyze the structure of wall components
indicate that the time is rapidly approaching when data from structural studies can
be integrated with growth physiology studies to achieve an overall understanding
OCR for page 77
of plant growth. Recent development of specific dyes and monoclonal antibodies
that interact with specific linkages in the wall should lead to a much better under-
standing of the localization and interaction of the various polymers in the wall.
Cloning of the extensin genes will now allow a study of the regulation of various
members of this family of genes; the patterns of expression of these genes should
help clarify the various functions of this unusual polymer. The exciting discovery
that fragments of wall components serve as regulatory signals will undoubtedly
open a whole new area of study on ways plants communicate and interact with
other organisms. Finally, recent advances in the biochemistry of membrane
proteins may lead to breakthroughs in the identification and isolation of enzymes
and their corresponding genes involved in wall synthesis. Since plant cell walls
are a major sink for biomass, much of which is only poorly digestible, it is hoped
that our ultimate ability to modify wall structure by modifying the expression of
genes controlling wall assembly will lead to a greater understanding of just how
flexible such wall structure can be, and perhaps also to the development of plants
with improved agronomic or nutritional value.


text:
Package: epic5 (1.0-2) [universe]
Links for epic5
Ubuntu Resources:
Download Source Package epic5:
Please consider filing a bug or asking a question via Launchpad before contacting the maintainer directly.
Original Maintainer (usually from Debian):
- Kurt Roeckx
It should generally not be necessary for users to contact the original maintainer.
External Resources:
- Homepage [www.epicsol.org]
Similar packages:
epic irc client, version 5
epic5 is an irc client based on ircII. It is primarily suited to users who wish to write their own irc scripts or have irc scripts written by others.
Previous versions of epic were 100% compatible with ircII 2.8.2, though this is no longer the case. Instead we've taken a new direction and chosen to find places where compatibility with ircII is undesirable and fix them. No gratuitous incompatibilities have been added, though many new features have been.
Other Packages Related to epic5
- dep: libc6 (>= 2.4)
- Embedded GNU C Library: Shared libraries
also a virtual package provided by libc6-udeb
- dep: libncurses5 (>= 5.6+20071006-3)
- shared libraries for terminal handling
- dep: libperl5.10 (>= 5.10.0)
- shared Perl library
- dep: libruby1.8 (>= 22.214.171.124)
- Libraries necessary to run Ruby 1.8
- dep: libssl0.9.8 (>= 0.9.8f-5)
- SSL shared libraries
- dep: tcl8.4 (>= 8.4.16)
- Tcl (the Tool Command Language) v8.4 - run-time files
- sug: epic5-script
- Package not available
Download epic5
Architecture | Package Size | Installed Size | Files |
amd64 | 601.9 kB | 1,628.0 kB | [list of files] |
i386 | 554.5 kB | 1,528.0 kB | [list of files] |

subset: commoncrawl


text:
Ernakulam Karayogam Elder Citizens Forum: Meeting, T.D.M. Hall, 4 p.m.
Gujarat Emporium: Exhibition cum sale, Women's Association Hall, Dewan's Road, 10 am.
DC Books: Book festival, Bay Pride Mall, Marine Drive, 10.30 a.m.
Durbar Hall Arts Centre: Exhibition of paintings by Ajay Sekher, 10 am.
Chinmaya Mission: Bhagavad Gita and Prasnopanishad class, Nettepadam Road, 6 p.m.
Kunnathukulangara Bhagawathi Temple: Festival, 5 a.m., Kesavanpadi, Thiruvankulam.
More In: MISCELLANEOUS | Today's Paper


text:
About Lindsay Phillips
Lindsay Phillips (born December 7, 1984) is an American entrepreneur. Phillips is the creator and founder of Lindsay Phillips, a shoe and accessories company exclusively for women. Biography: Phillips was born in Clearwater, Florida on Dec 7, 1984. Her father, Paul Phillips, is a cardiologist and her mother, Liz Phillips, worked as a nurse. Phillips attended Berkeley Preparatory School in Tampa, Florida. It was during this time that Lindsay developed the concept for sandals that would eventually lead her to launch SwitchFlops - interchangeable flip-flops with removable straps to match any outfit. Encouraged by the favorable responses she received after creating ceramic flips flops - part of an art class project - she began expanding her vision by toying with the idea of creating colorful straps and buttons that could diversify the look of just one pair of flip flops. She soon realized that by using hook-and-loop fasteners, her vision of "Change Your Look, Not Your Sole" was complete. By the end of her high school career, Phillips applied for a patent. Following graduation from Berkeley Prep in 2003, she attended Rollins College in Winter Park, Florida, interning with Ralph Lauren Corporation in New York City during two of her summer breaks. She also attended Semester at Sea, a shipboard, global study abroad program, during which she simultaneously studied and toured several countries including Venezuela, Brazil, South Africa, the Republic of Maurituis, Myanmar, India, Vietnam, China, and Japan. Phillips has frequently commented that her travels abroad have greatly influenced her designs. She graduated in 2007 with a BA in Art History and a minor in communications. Career: Phillips' career began in high school with an idea she developed in an art class. In 2004, Phillips received her patent, and with the help of her mother Liz, began searching for a manufacturer. In January 2007, Phillips debuted her SwitchFlops product at the Surf Expo Trade Show in Orlando, Florida. Phillips has since expanded her company to include other footwear, as well as accessories like bags and scarves. Her shoes and accessories have been featured in several publications including Everyday with Rachel Ray, People Magazine (Style Watch Edition), Star, InStyle, Us Weekly, Woman's World, Redbook, and The New York Times. Her products have also been featured on The View,The Martha Stewart Show, and Good Morning America. Phillips has donated to the Mammogram Voucher Program at Morton Plant Hospital, the Young Survival Coalition, and a donor's choice campaign. She has also won several awards, including the Stevie Award for Best Entrepreneur(2009), the Women's Leadership Exchange 2009 Biz Wiz Award, the Ernst & Young Entrepreneur of the Year Award(2010), and a Rollins College's Young Alumni Achievement Award (2012).
Text from this biography licensed under
creative commons license


text:
MN: Switch My Trip Campaign Promotes New Commutes
This week, Metro Transit and the region's Transportation Management Organizations (TMOs) launched Switch My Trip, a campaign that encourages Twin Cities workers and residents who typically drive alone to try getting around in a new way.
Participants pledge to replace at least one drive-alone trip between now and June 30 with a trip by bus, train, bicycle, car- or vanpool, walking or by teleworking. Metro Transit and TMO staff members will promote Switch My Trip and provide commuter information at dozens of workplaces and other events throughout the spring.
"Switch My Trip is an easy way to discover the many benefits of leaving the car behind – even for just a trip or two each week," said Metro Transit General Manager Brian Lamb.
Participants become eligible to win gift cards after the initial pledge and can also enter additional prize drawings for taking trips without driving alone. Prizes include memberships to destination locations like the Science Museum of Minnesota and gift cards for local restaurants. A complete listing of prizes is available at switchmytrip.org.
Switch My Trip is sponsored by Metro Transit and the region's TMOs: Anoka County Commute Solutions, downtown Minneapolis Commuter Connection, St. Paul Smart Trips and Commuter Services, which serves the I-494 corridor and the southwest metro. TMOs work with employers and commuters to explore transportation options that reduce traffic congestion.
Throughout the campaign, Switch My Trip participants are encouraged to share their story on social media using the hashtag #SwitchMyTrip.


text:
A Picture of Subsidized Households Meaning of Codes(11)
blank or -1 = low reporting or unknown. 0 = rounds to zero. 888 = units spread in many counties, none has over 1/3 of units. 99 = 99% or more. |
Name | Start | Width | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Program | pgm | 1 | 2 |
Summary level is in the FIRST column:
Programs are in the SECOND column. Numeric values are used in the data file, while letters are used in printed reports:
* Note that programs 6-9, (S, T, F, L) are not included in housing agency summaries, since they are independently managed. Programs 2-5 (B, P, C, K) are administered by HUD's "Office of Public & Indian Housing" through local housing agencies. Programs 6-8 (S, T, F) are administered by HUD's "Office of Housing." Program 9 (L) is administered by the Internal Revenue Service. Sort sequence: All records are sorted by state abbreviation (US summaries are in " U" at the beginning). Programs run by housing agencies (2-5 or B, P, C, K) are then sorted by housing agency number ("code"). The remaining, independent, projects are sorted by county and zip code, with missing county or missing zip at the end. Summary tract records are sorted by county & tract. Each user may re-sort the data as needed. |
Address & City | name | 5 | 40 | Name of the project, agency, state, or size class. For summary level 6, projects: name is in the first 16 characters of this item, a brief address is in the next 16 characters and city is in the last 8 characters. When a project has more than one address, a central one was picked, as discussed below under "Latitude." For any project in programs 2-4 (B, P, C) whose agency does not have the same code as the beginning of the project number, we put a note in the name (e.g. RQ001001 is noted as being: @RQ005). This is in positions 1-6 of the name, or at the end of the street address (columns 27-32 of this field, which are 31-36 of the record) if that part of the street address was blank. For any project in programs 6-7 (S, T, F) the first character of the name shows the sub-program, and the name is actually in characters 2-12 of this item. The subprograms are:
For summary level 7 in program 1 (A), Census tract summaries across all programs, this item shows: population, renter households, and percent in various programs, in the format: "12345pop 2345ren 12P 12C 12H 12L". The abbreviations are as above, except H is a total of programs 6, 7 and 8 (S, T and F). |
Code | code | 48 | 11 | Project code or number: This always starts with a 2-letter state abbreviation (RQ for Puerto Rico, as used in most HUD project numbers). In summary levels 1-3, this code has a very brief label, like AL for Alabama. For summary levels 4-7, the meaning varies by program: In program 1 (A: i.e., for tract summaries that include all programs present in the tract), this code shows: state, tilde (~), HUD units as % of housing units in the tract in 1990, and number of housing units in the tract in 1990, like "AL~12% 1234 " In programs 2-5 (B, P, C, K) this code shows: state abbreviation, then blank and agency#, then blank and project# if any, like: "AK 001 001" In program 2 or B, an M after the project# (in the 11th character) means Mutual Ownership. Portability households are coded with the agencythey are billed to (whence they moved). In program 6 or S this code shows: state, 2-digit HUD office, and project number, like "AK01R123456" In programs 7-8, (T, F) this code shows: state, underline, 3-digit HUD office and project number, like "AK_11144666" For this group, if state was unknown, we generated it from the HUD field office code. There may be some errors where offices cross state lines. In program 9 or L this code shows: state, curly bracket ({), then state-defined project ID, if any, like "AK{87-123" |
Units Available | units | 61 | 7 | Number of units: Units under contract for federal subsidy, and available for occupancy. This count is as of 5/98 (same as tenant data) for Public & Indian Housing, Certificates, Vouchers and Moderate Rehabilitation. In other programs it is not as recent as the tenant data: it is as of 9/30/95, except in Tax Credits it is 12/94. If an agency overall has more Certificates+Vouchers than it reports on, we assume each tract has extra Certificates+Vouchers in the same proportion (but we assume no more than one and a half times as many in a tract as the number reported).. The number of units was missing and had to be estimated for a few projects. In Tax Credits, when we show 35 units we had no data (and used 35 since it is the national average); projects which truly had 35 or 36 units are shown as 36. In Ofc. of Housing (programs 6-8 or S-F), 66 units mean we had no data (and used 66, the national average); 67 means actually 66 or 67. In Public & Indian Housing, zero units are shown for 95 projects. It is believed most are not active project numbers. |
%Occupied | occ | 69 | 2 | Occupied units as % of available. This count is available in program 3 (P: Public Housing) from a source independent of the reports that describe individual households, so we can show household reports as a percent of occupied units (next item). Elsewhere no data are actually available, and numbers are assumed, purely for calculating reporting rates: In program 6 (S) occupancy rates are stipulated at 98%, and in programs 7-8 (T, F) at 96% (Wallace 1993, page 2-27, though his figures are based on rent revenue, and occupancy is less). In other programs we stipulate 99%, since almost all units are assumed occupied. |
%Reported | rep | 72 | 2 | Households for which reports were received, as % of occupied units. We use household reports received through 5/98 or 7/98. Only the most recent report on each household is counted. We go far enough back in the files to have the same number of household reports as occupied units, in each Public & Indian project or Certificate+Voucher or Moderate Rehabilitation program, but no farther back than 30 months before 5/98. Households reported to have moved out are not counted, of course. In Office of Housing programs we always use the most recent 30 months, and reduce weights in any projects with over-reporting. Over-reporting happens when agencies do not report move-outs, so more than one household is in the HUD file, for the same unit. In Tax Credits no reporting is required. Some summary data are in the report, but not the data file, from Opportunities to Improve Oversight of the Low-Income Housing Program, 1997. When households take certificates or vouchers to a new area (portability), they are reported by the local agency there, but are still billed to and in this file are counted against the original agency that issued them a certificate or voucher. The 1996 file wrongly counted them against the agency that reported them. Some of the units available in Section 236 projects are occupied by households with incomes high enough to pay full rent, without subsidy. These households are not always reported to HUD and, if not, their characteristics are not included in this report. |
%<1Yr | mover | 75 | 2 | % in program less than a year. If it is 100% or 0%, the project has reported only admissions, or no admissions, either of which is usually a data quality problem. This item and all remaining items are expressed as a percent of occupied units, not available units. The items were calculated from units for which household reports were received, and these are believed to be generally representative of all occupied units. |
H.Hold.Siz | size | 78 | 3.1 | Average size of household, with decimal point & decimal place (for example 2.5). To find the number of people served by the agency, multiply this size by units available and % occupied. |
Av.Rent | rent | 82 | 3 | Average gross household rent per month. This includes rent the household pays to the agency or landlord, and an estimate of any separately metered utilities they pay (and also ownership costs in Indian ownership programs). Based on households with rent in the range $1-$2,498; other rents are considered errors. Virtually all zero rents are missing data, since the minimum rent (10% of income) applied to positive income (see note on missing data in income) gives positive gross rent. However if gross rent is lower than estimated utilities, rent to the agency or landlord may be zero. This is item 14 on form HUD-50058 (highest of: 10% of gross income, 30% of adjusted income, or welfare rent), except in vouchers, where it is item 22k (total family contribution), and Indian Mutual, where it is item 17h (family cost). |
Spending | spend | 86 | 3 | Average Federal spending per unit per month. Not fully comparable across programs. For Public & Indian housing, this only includes 1996 operating and modernization spending, since the construction costs have already been paid for, and opportunity cost is not available. It omits Drug Elimination Grants, which are the only other major source of current spending. Operating subsidy to all agencies, and modernization funding to large agencies (generally over 250 units), is distributed every year by formula so we use the actual funding. For smaller agencies modernization funding is competitive, and they do not all receive it each year, so the actual funding in any one year would not reflect average long term costs. As an approximation we found the average modernization per unit, and multiplied this average by the units in each agency to estimate the long term expected value of modernization spending. A higher fraction of Indian agencies receive modernization than of other agencies, so we did the average separately for Indian and non-Indian agencies. At each agency, for purposes of this summary, total spending is averaged per occupied unit per month, without differentiating among projects. In fact some projects receive more or less than average each year. For other programs, total spending is calculated for each unit (from the rent calculation form) and averaged, so averages should vary correctly in each tract and agency. In Certificates+Vouchers and Moderate Rehabilitation our estimate also includes the 8% administrative fee. |
Av.Income | incom | 90 | 3.2 | Average total household income. This is shown in thousands of dollars per year, with decimal point. This is basically total income before adjustments, expected for the next 12 months, but it does exclude some types of income which HUD regulations do not count at all, such as earnings of minors, and scholarships. Averages below $1,000 are shown as .00-.99 thousand dollars. Averages below $10,000 are shown as 1.0-9.9 thousand dollars. Higher averages are shown as 10. to 99. thousand dollars. (All software that we are familiar with can handle this floating decimal point; normally declare the maximum width: 3 and maximum decimal positions: 2.) Based on households with income in the range $1-99000. Virtually all zero incomes are missing data, since even homeless households moving in would expect some income assistance in the year to come. |
%<$5000 | i5 | 94 | 2 | % Below $5,000 | ||||||||||||||||||||||||||||||||||||||||||||||||||
%$20000+ | i20 | 97 | 2 | % $20,000 or more (you can get the category $5-19,999 by subtraction) | ||||||||||||||||||||||||||||||||||||||||||||||||||
%Wages | wage | 100 | 2 | % Majority of household's income comes from wages and/or business | ||||||||||||||||||||||||||||||||||||||||||||||||||
%Welf | welf | 103 | 2 | % Majority of household's income comes from welfare (AFDC, TANF, or General Assistance, not Supplemental Security Income) Note that remaining households have majority of income from another source, such as pensions, Social Security, SSI, unemployment benefits or child support, or have a mixture, with no type giving a majority of income. Welfare income may not all be identified in this file, because of changes in the welfare programs. In private projects (Office of Housing programs) the data collection form 50059 identifies "Public Assistance," and the instructions say this does not include Supplemental Security Income (SSI). In other programs, the form 50058 (6/93 version, used for most data in this report) has categories including SSI, AFDC (Aid to Families with Dependent Children), General Assistance, and "Other nonwage." The 1997-98 versions of form 50058 have changed AFDC to the current national name TANF (Temporary Assistance for Needy Families; many states have unique local names). "Welfare" in this report includes Public Assistance from form 50059 and AFDC, TANF, and General Assistance from form 50058. Before the new form 50058 came into use (and it is still not in use in some agencies), some TANF income may have been placed under Other nonwage, or other categories which are not counted as welfare here, or the source of income may have been left blank. It will always be hard to measure a national program with 20-30 local names. Data on source of income (both wages & welfare) had to be suppressed in the New York City Housing Authority (NY 005), since only 1% were reported to be on welfare, which indicated some error in processing the data on source of income. |
Incm.Mix | mix | 106 | 2 | Income mix as percent of average income. The larger the number, the more income mix. This is the coefficient of variation, which is the standard deviation of income, as a percent of the average income. The standard deviation measures how far each household's income is from the average income. Incomes that are far above or below average have large effects, since the differences are squared before being averaged. A correction in the calculations results in 11% larger income mix estimates in programs 6-7 (S, T, F), and 4% larger nationally. |
%ofMed | med | 109 | 2 | Average of: household's income as percent of local median income, adjusted for household size. Local median incomes are estimated regularly by HUD, because they are used in setting income limits for housing subsidies. The most common income limit is L50, 50% of local median income, adjusted for household size. There are some state and national floors and ceilings, which restrict the amount of variation from area to area. Here we compare the income of each subsidized household to the local adjusted median income (i.e. twice the L50 limit), so for example if local median income is $30,000 (and the L50 limit is $15,000), then a subsidized household with $10,000 income has 33% of local median income. Every year, HUD estimates the median income of families in each metropolitan area and each non-metropolitan county, in order to establish income limits. That estimate is based on both subsidized and unsubsidized families. "Families," used in establishing median incomes, include only people living together who are related by blood, marriage or adoption; people living alone are not used for establishing median incomes, but of course they are eligible for subsidy, and are included in all the statistics on subsidized housing. When we say "adjusted for household size" we mean the following: We make no adjustment in households with 4 people. We reduce the denominator (the estimate of local median income) by 10% for each person under 4 in a household (3 people: 90% of the 4-person denominator; 2 people: 80%; 1 person: 70%). We increase the denominator 8% for each person over 4 in the household (5 people: 108% of the 4-person denominator; 6 people: 116%; etc.). The terms family and household here have specific meanings. The area median income is based on both subsidized and unsubsidized families. Families include only people living together who are related by blood, marriage or adoption; people living alone are not used for establishing median incomes. They all are included in the broader term household and all are of course eligible for subsidy, so when writing about people living in subsidized units, we use the broad term households. There is also another sense of family, as opposed to elderly households, which was once a common distinction in HUD programs. We avoid that usage, since we now have many non-elderly single people in HUD programs. When we want to indicate households where the head and spouse are under age 62, we use the term non-elderly. |
%Age<25 | a24 | 112 | 2 | % Under age 25: age of head or spouse, whichever is older | ||||||||||||||||||||||||||||||||||||||||||||||||||
%Age62+ | a62 | 115 | 2 | % Age 62+ | ||||||||||||||||||||||||||||||||||||||||||||||||||
%Age85+ | a85 | 118 | 2 | % Age 85+ (part of line above) | ||||||||||||||||||||||||||||||||||||||||||||||||||
%Disab<62 | d61 | 121 | 2 | % With disability, as % of households below age 62 (includes households where either head or spouse has handicap or disability) | ||||||||||||||||||||||||||||||||||||||||||||||||||
%Disab62+ | d62 | 124 | 2 | % With disability, as % of households age 62 or more | ||||||||||||||||||||||||||||||||||||||||||||||||||
%Minority | min | 127 | 2 | % Minority | ||||||||||||||||||||||||||||||||||||||||||||||||||
%Black | blac | 130 | 2 | % Black, not Hispanic | ||||||||||||||||||||||||||||||||||||||||||||||||||
%Hispanic | hisp | 133 | 2 | % Hispanic (of any race) | ||||||||||||||||||||||||||||||||||||||||||||||||||
%Nat.Amer | indn | 136 | 2 | % Native American | ||||||||||||||||||||||||||||||||||||||||||||||||||
%Asin-Pac | asia | 139 | 2 | % Asian or Pacific Islander | ||||||||||||||||||||||||||||||||||||||||||||||||||
Dif PR-HA | dif | 142 | 2 | Difference between project & agency in % Minority: measures extent to which subsidized minorities live in different places from subsidized whites. Scale is 0-50 for agencies (individual small projects can exceed 50). The larger the number, the more separately whites & minorities live. For Public Housing projects, this is the difference between: % minority for the project, and overall % minority for Public Housing at the agency. Difference is shown for each project (in absolute value). Average of these differences is shown for each agency. For Certificates+Vouchers (which do not have projects), difference is based on Census tracts with more than 10 households reported: average difference between: % minority among Certificates+Vouchers in the tract, and overall % minority among Certificates+Vouchers at the agency. Summaries of this item exclude agencies that are under 5% or over 95% minority, and agencies with only one project or tract, since there cannot be much difference there. |
%0-1 Bedroom | bed0 | 145 | 2 | % 0-1 Bedrooms (efficiency apartments & 1 bedroom units) We treat units with no bedrooms reported and more than 2 people as missing data, and omit them from numerator & denominator of bedroom percents. |
%3+Bedrms | bed3 | 148 | 2 | % 3 Bedrooms or more Note that 2-bedroom units can be obtained by subtraction. |
%2Sp+Chil | sp2 | 151 | 2 | % Both spouses: married couple with 1 or more children under 18 | ||||||||||||||||||||||||||||||||||||||||||||||||||
%1Sp+Chil | sp1 | 154 | 2 | % Spouse not present; but 1 or more children under 18 are present | ||||||||||||||||||||||||||||||||||||||||||||||||||
%Female | fem | 157 | 2 | % Female head. This is bigger than single parents, since many elderly women are female heads, but have no children present. | ||||||||||||||||||||||||||||||||||||||||||||||||||
%Br>Peopl | bedx | 160 | 2 | % Overhoused, with more bedrooms than people | ||||||||||||||||||||||||||||||||||||||||||||||||||
%w/Utility | utav | 163 | 2 | % With valid utility allowance ($1-$1,000 are considered valid) This is an estimate of the utilities the household needs to pay to the utility company. It is zero if all utilities are included in rent | ||||||||||||||||||||||||||||||||||||||||||||||||||
Av.Utility | atav | 166 | 3 | Average utility allowance, among households with it, in $ per month | ||||||||||||||||||||||||||||||||||||||||||||||||||
Mos.Stay | stay | 170 | 2 | Average months since moved in. Excludes programs 4-5(C,K), since move in dates before 1993 are not known | ||||||||||||||||||||||||||||||||||||||||||||||||||
Mos.Wait | wait | 173 | 2 | Average months on waiting list, among admissions. Excludes programs 6-9 (S, T, F, L), which do not report waiting list dates | ||||||||||||||||||||||||||||||||||||||||||||||||||
Mos.Rept | rept | 176 | 2 | Average number of months since manager reported on household. Households are reported annually, on a flow basis, so for good recent data the average should be about 6 months. Larger averages mean recent data have not been received, or have not been accepted, because of errors. |
Latitude | lat | 179 | 6.3 | Average latitude. Data file includes decimal point and 3 decimal places For all summaries except projects this is an arithmetic mean, weighted by number of subsidized units. (If there is only one certificate or voucher in a tract, we round latitude and longitude to 2 decimal places instead of 3, to preserve confidentiality.) For projects with only one address, we give its latitude and longitude. For projects with more than one address, we pick the address that is closest to the median latitude and median longitude of the whole project, and use this address' latitude, longitude, zip code, county, tract, etc. (see Subsidized Housing Projects' Geographic Codes, 1996) |
Longitude | long | 186 | 8.3 | Average longitude. Data file includes decimal point and 3 decimal places. Negative means West longitude, which covers most of the United States. Zero is on a line through Ghana, Spain & Britain; negative numbers go to -180 in the Aleutians; positive numbers go to +180, also in the Aleutians. Distances in miles between points a and b can be calculated (where f=.0174532925 and converts from degrees to radians): |
Zip | zip | 195 | 5 | Zip code, assigned by the postal service, unique within United States. 88888 means no Zip code has 1/3 of units | ||||||||||||||||||||||||||||||||||||||||||||||||||
County | tract | 202 | 12.2 | Numeric codes for state, county & census tract State in first 2 positions: 2-digit code, from 01 for Alabama to 78 for Virgin Islands. Consistent with the 2-letter abbreviation in the earlier item, "Code" except for portability, where "Code" shows the state that issued the Certificates+Vouchers, and this field shows the state where they are used. These 2 columns are only in the data file, not in the printed report. County in next 3 positions: 3-digit code, unique within state. 888 means no county has 1/3 of units Census tract in last 7 positions: 7-digit code, for the tract surrounding the project, code unique within county, including decimal point and 2 decimal places. 8888.00 means no tract has 1/3 of units. These 7 columns are only in the data file, not in the printed report. These are FIPS (Federal Information Processing Standards) codes, consistent with the 1990 Census codes & maps. For example 060710022.01 is in California (06), in San Bernardino County (071), tract 22.01. |
T%Poverty | tpov | 216 | 2 | Tract % Poor: Poor as % of population, in Census tract that surrounds project, data as of 1990 This, like other items, is averaged for all projects, weighted by number of units in each project |
T%Minrty | tmin | 219 | 2 | Tract % Minority: Minorities as % of population, in Census tract that surrounds project, data as of 1990 | ||||||||||||||||||||||||||||||||||||||||||||||||||
T%OwnSFD | tow1 | 222 | 2 | Tract Single Family Owners: Households that are owner-occupants of single family detached homes, as % of households in Census tract that surrounds project, data as of 1990. This counts owner-occupants in buildings with 1 unit, not townhouses, condominiums, or mobile homes | ||||||||||||||||||||||||||||||||||||||||||||||||||
MSA | msa | 225 | 4 | Metropolitan Statistical Area (MSA or PMSA). Code is unique within the United States. 0 means not in any metropolitan area (blank or -1 means status unknown) 8888 means no metro area has 1/3 of units. MSA and PMSA (Primary Metropolitan Statistical Area) codes form one consistent series; the distinction is minor: PMSAs are pieces of even larger "Consolidated" areas (CMSAs), while MSAs are free-standing. These are statistical areas established by the Office of Management and Budget. HUD has subdivided some for setting Fair Market Rents and Income Limits, and HUD's areas are not reflected here |
Place | place | 230 | 4 | Census Bureau Code for the city, town, or Census-defined place (such as a well-known locality that is not legally incorporated). Unique within state. 8888 means that no code has 1/3 of units. These codes are not the same as FIPS place codes or minor civil division (MCD) codes, each of which has 5 digits, nor the same as Census MCD codes (3 digits). All codes are compared at http://www.census.gov/population/www/estimates/mcdplace.html | ||||||||||||||||||||||||||||||||||||||||||||||||||
Cong.Dist | cd | 237 | 2 | Congressional District, for the Congress elected in 1994. 88 means no district has 1/3 of units. Unique within state. | ||||||||||||||||||||||||||||||||||||||||||||||||||
HA.Size | cl | 238 | 1 | Size class of housing agency, total units in all programs
Download the WordPerfect documentation for A Picture of Subsidized Households - 1998.


text:
G.Skill releases DDR3 2300MHz 8GB memory for the Intel P67 platform
Published on 20th April 2011 by
Press Release
This press release is written by a third party and the content does not reflect the opinion of bit-tech's editorial team
G.Skill releases DDR3 2300MHz 8GB memory for the Intel P67 platform.
The world's fastest 8GB (4GBx2) desktop memory for overclocking enthusiasts.
Taipei, Taiwanー19th April 2011
ー G.Skill International Co. Ltd., manufacturer of extreme performance memory and solid-state storage with solid quality, today announces the world's fastest 8GB (4GBx2) DDR3 memory, rated at 2300MHz CL9 with only 1.65V voltage. This ultimate memory kit will join G.Skill award winning Ripjaws-X family and will be available soon via G.Skill global authorized distribution partner.
Since the demand of big capacity memory has grown dramatically, G.Skill R&D team has been dedicated to develop the fastest and best performing products based on 4GB memory sticks continuously. Following the marvelous achievement of DDR3 1900MHz 48GB and DDR3 2200MHz 16GB kits, G.Skill once again pushed the memory speed further and developed the industry leading memory kit. The DDR3 2300MHz CL9 kit has passed a series of rigorous tests and guarantees the best stability and performance.
"The 2300MHz RipjawsX 8GB gives you extreme speed and you can also enjoy the big capacity simutanously. It not only delivers record breaking overclocking performance, but also broaden your choices for building up an extreme performance workstation and a gaming machine" said Michael Chao, senior R&D manager at G.Skill.
All G.Skill memory products come with lifetime warranty and the G.Skill technical team is always ready to provide consumers with complete technical support via online forums, facebook, telephone and email.
About G.Skill
Established in 1989 by enthusiasts, G.Skill is a leading memory & Solid State Drive manufacturer based in Taipei, Taiwan. The company's top priority is Quality. All of our products undergo a series of the most rigorous tests and strict quality control processes. In addition to a committed, qualified IC testing house to examine our products, all G.Skill products are 100% tested to ensure the highest yield, reliability and quality.
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National Public Radio's Linda Wertheimer has talked to American Democrats throughout the country, and one overriding message has come through for the future, still undecided, Democratic candidate.
"American people are saying we don't care what you do, just do what works," Wertheimer said.
Wertheimer, NPR's senior national correspondent, spoke Monday night at a packed Cornell Auditorium on MU's campus as a part of the Lloyd B. Thomas lecture and performance series kicking off MU's Arts and Science week. Her lecture was titled, "Here it Comes: Another Presidential Election."
Wertheimer has covered elections for the past three decades with NPR, reporting on four presidential elections, eight congressional elections, 10 presidential nomination conventions and 12 election nights. She is probably best known for her 13 years hosting NPR's "All Things Considered," one of the top five shows on U.S. radio. In 1998, Vanity Fair named her one of America's 200 most influential women.
"She's very engaging," said MU journalism professor Michael Grinfeld, who attended the lecture. Her book, "Listening to America: Twenty-Five Years in the Life of a Nation as Heard on National Public Radio" celebrates NPR's history and is in tune with what she does on an everyday basis: She listens to America.
On the campaign trail
Wertheimer spoke of her recent experiences in various states talking with Democratic voters about their possible candidates for president. While many had differing opinions on certain issues, almost all were united on the front to oust Bush from the White House.
Wertheimer gave various examples of Democrats around the nation hoping for a candidate with some clout.
She spoke to an airline pilot in New Hampshire who really loved Howard Dean's politics but, after the Iowa Caucuses, switched to support Sen. John Kerry.
"I am still fascinated about the Dean phenomena," Wertheimer said. "He really ran two campaigns. One in person and one on the Internet. The two didn't really meld, though."
As for the other candidates, it just wasn't their year. Wertheimer did say that Sen. John Edwards may have a chance in the future.
"Right now, Edwards is really No. 1 on the B-list," Wertheimer said.
Kerry is predicted to win the Wisconsin primary today unless voters there come out with a surprise.
"Kerry is the default candidate and the best bet to beat Bush," Wertheimer said. "This thing is about to be over, and the final say will come from the Cheeseheads."