manu/mldr-zoomed-100char-total-queries-documents

chunk_id stringlengths 3 9	chunk stringlengths 1 100
129_182	Later in 1998, Dr. Yuan-Tsong Chen and colleagues at Duke University, using the enzyme produced in
129_183	Chinese Hamster Ovary cells demonstrated for the first time that the enzyme can clear the glycogen
129_184	and improved the muscle function in Pompe disease quail. The results of the work at Duke were
129_185	impressive with one treated bird recovering to the point of being able to fly again.
129_186	This was followed by production of clinical grade alpha-glucosidase in Chinese hamster ovary (CHO)
129_187	cells and in the milk of transgenic rabbits. This work eventually culminated in the start of
129_188	clinical trials with the first clinical trial including 4 babies receiving enzyme from rabbit milk
129_189	at Erasmus MC Sophia Children's Hospital and 3 babies receiving enzyme grown in CHO cells at Duke
129_190	University in 1999.
129_191	The currently approved Myozyme is manufactured by Genzyme Corp. in Cambridge, Massachusetts. Its
129_192	development was a complex process. Genzyme first partnered with Pharming Group NV who had managed
129_193	to produce acid alpha-glucosidase from the milk of transgenic rabbits. They also partnered with a
129_194	second group based at Duke University using Chinese hamster ovary cells. In 2001, Genzyme acquired
129_195	Novazyme which was also working on this enzyme. Genzyme also had its own product (Myozyme) grown in
129_196	CHO cells under development. In November 2001, Genzyme chief executive Henri Termeer organised a
129_197	systematic comparison of the various potential drugs in a mouse model of Pompe disease. It was
129_198	found that the Duke enzyme was the most efficacious, followed by Myozyme. However, due to easier
129_199	manufacture of Myozyme, work on the other products was discontinued.
129_200	Funding for research in this field was in part provided by the Muscular Dystrophy Association and
129_201	the Acid Maltase Deficiency Association in the US, and by the Association of Glycogen Storage
129_202	Disorders in the UK, as well as the International Pompe Association.
129_203	John Crowley became involved in the fund-raising efforts in 1998 after two of his children were
129_204	diagnosed with Pompe. He joined the company Novazyme in 1999, which was working on enzyme
129_205	replacement treatment for Pompe. Novazyme was sold to Genzyme in 2001 for over US$100 million. The
129_206	2010 film Extraordinary Measures is based on Crowley's search for a cure.
129_207	As of 2019, many biomedical companies are developing Gene therapy in hopes of helping the body
129_208	create alpha-glucosidase on its own.
129_209	References External links
129_210	GeneReview/NIH/UW entry on Glycogen Storage Disease Type II (Pompe Disease)
129_211	Understanding Pompe Disease - US National Institute of Arthritis and Musculoskeletal and Skin
129_212	Diseases
129_213	Autosomal recessive disorders Hepatology Inborn errors of carbohydrate metabolism
129_214	Lysosomal storage diseases Rare diseases
130_0	The Dumaw Creek Site is an archaeological site designated 20OA5, located along Dumaw Creek northeast
130_1	of Pentwater, Michigan, that was the location of a 17th-century village and cemetery. It is one of
130_2	the youngest pre-historic sites in Michigan, dating to the terminal Late Woodland Period just
130_3	prior to European contact. It was listed on the National Register of Historic Places in 1972.
130_4	History
130_5	The village that once stood at this location was likely inhabited in the early part of the 17th
130_6	century (about 1605–1620, according to Quimby). The people occupying the village are thought to be
130_7	the precursors of the modern Potawatomi people. It is likely that they were uprooted from this
130_8	location soon after Samuel de Champlain's 1615 visit to the region, as warring tribes spilled into
130_9	Michigan. Were they the Potawatomi people, they eventually made their way by the 1640s to the
130_10	region around Sault Ste. Marie.
130_11	Meanwhile, white pine grew up in the plain where the village stood. The pine was lumbered in
130_12	1870-1880, after which the land was gradually converted to agricultural use, and was farmed as late
130_13	as 1930. In the 1940s, oil was discovered in the area, and wells were installed.
130_14	The Dumaw Creek site was originally discovered in 1915 by a farmer, Christoph "Carl" Schrumpf
130_15	1854–1949, who was pulling a stump from his field. Schrumpf discovered 18 skeletons and various
130_16	artifacts in 1915–16. These artifacts were catalogued by the Museum of Anthropology at the
130_17	University of Michigan in 1924, but the artifacts and records were not generally well known by
130_18	archaeologists. Schrumpf eventually sold the collection to a private dealer, and they eventually
130_19	made their way, sans any identifying data, to George I. Quimby at the Field Museum in 1959.
130_20	Quimby eventually tracked the source of the artifacts to the Dumaw Creek site, and in 1960-62 did
130_21	some summer surface collection there. He also located other artifacts already dug from the site.
130_22	Description
130_23	The Dumaw Creek site is located on a sandy plain near Dumaw Creek, a tributary of the Pentwater
130_24	River, at a site not easily accessible by canoe. The creek itself runs through a small valley
130_25	about beneath the level of the plain. The site, covering , was used as a village and burial
130_26	ground.
130_27	The village is thought to have been a semi-permanent settlement with dome-shaped wigwams. The
130_28	people hunted and fished, and grew corn and pumpkins.
130_29	Artifacts
130_30	Artifacts and features found at the site include burials, faunal remains, stone tools, bone tools,
130_31	red ocher/mineral paint (used for ceremonial coloring), copper artifacts, shell artifacts, tobacco
130_32	pipes, animal skins, and vegetal and textile remains.
130_33	At least nineteen, and perhaps as many as 55 skeletons were removed from burial sites in the Dumaw
130_34	Creek site. The bodies were wrapped in furs and buried with stone implements and copper beads.
130_35	The stone implements found include arrowheads, knives, and scraping tools of chipped flint and axes
130_36	of a hard, granular stone. Quimby reports that 99% of the stone tools were small triangular points
130_37	or arrowheads, aka Madison points, indicative of a Late Woodland period placement. There were also
130_38	a considerable number of copper artifacts found at the site. Many were large bead-like tubes of
130_39	copper known as hair pipes, which were worn as hair ornaments. There were also other, generally
130_40	smaller copper beads, conical decorations, and copper plaques, as well as shell beads and pendants.
130_41	Carved stone pipe bowls were also found, as well as animal skins and pottery.
130_42	The pottery is described by Quimby as grit-tempered vessels with round-bottomed, globular forms
130_43	with broad orifices and slightly flaring rims. The rim edges are often scalloped or crimped. The
130_44	vessel pictured below with a scalloped rim has been compared to the Moccasin Bluff Scalloped type
130_45	from the Moccasin Bluff site on the St. Joseph River in southwestern Michigan. This pottery type
130_46	is diagnostic of a Late Woodland period temporal placement, just before European contact. There was
130_47	also a shell pendant with a "weeping eye" design as shown below. This motif has been seen in other
130_48	Late Prehistoric sites in the Great Lakes area.
130_49	References
130_50	Buildings and structures in Oceana County, Michigan
130_51	Archaeological sites on the National Register of Historic Places in Michigan
130_52	National Register of Historic Places in Oceana County, Michigan Potawatomi Late Woodland period
131_0	Dag Ivar Wirén (15 October 1905 – 19 April 1986) was a Swedish composer.
131_1	Life
131_2	Wirén was born at Striberg near Nora. His father had a roller blind factory, and there were
131_3	various musical activities in the family home; he took piano lessons, and was a student at the
131_4	Karolinska school in Örebro, and played the bass drum and celesta in the town orchestra.
131_5	Wirén studied at the Stockholm conservatory from 1926 to 1931, which gave him much exposure to
131_6	music from all periods; hearing Arthur Honegger's oratorio King David in 1927 was an important
131_7	experience.
131_8	In 1932 he won the state stipend and used the award money to continue his studies in Paris, where
131_9	he lived from 1931 to 1934. While there, he studied composition under the Russian composer Leonid
131_10	Sabaneyev, though he admitted later that his endless attendance of concerts, and not his tutoring
131_11	with Sabaneyev, had the greater impact on his own work. In Paris he met Igor Stravinsky (as well as
131_12	his compatriot Gösta Nystroem) and was exposed to the music of Stravinsky, Sergei Prokofiev and the
131_13	French composers of Les Six.

129_182

Later in 1998, Dr. Yuan-Tsong Chen and colleagues at Duke University, using the enzyme produced in

129_183

Chinese Hamster Ovary cells demonstrated for the first time that the enzyme can clear the glycogen

129_184

and improved the muscle function in Pompe disease quail. The results of the work at Duke were

129_185

impressive with one treated bird recovering to the point of being able to fly again.

129_186

This was followed by production of clinical grade alpha-glucosidase in Chinese hamster ovary (CHO)

129_187

cells and in the milk of transgenic rabbits. This work eventually culminated in the start of

129_188

clinical trials with the first clinical trial including 4 babies receiving enzyme from rabbit milk

129_189

at Erasmus MC Sophia Children's Hospital and 3 babies receiving enzyme grown in CHO cells at Duke

129_190

University in 1999.

129_191

The currently approved Myozyme is manufactured by Genzyme Corp. in Cambridge, Massachusetts. Its

129_192

development was a complex process. Genzyme first partnered with Pharming Group NV who had managed

129_193

to produce acid alpha-glucosidase from the milk of transgenic rabbits. They also partnered with a

129_194

second group based at Duke University using Chinese hamster ovary cells. In 2001, Genzyme acquired

129_195

Novazyme which was also working on this enzyme. Genzyme also had its own product (Myozyme) grown in

129_196

CHO cells under development. In November 2001, Genzyme chief executive Henri Termeer organised a

129_197

systematic comparison of the various potential drugs in a mouse model of Pompe disease. It was

129_198

found that the Duke enzyme was the most efficacious, followed by Myozyme. However, due to easier

129_199

manufacture of Myozyme, work on the other products was discontinued.

129_200

Funding for research in this field was in part provided by the Muscular Dystrophy Association and

129_201

the Acid Maltase Deficiency Association in the US, and by the Association of Glycogen Storage

129_202

Disorders in the UK, as well as the International Pompe Association.

129_203

John Crowley became involved in the fund-raising efforts in 1998 after two of his children were

129_204

diagnosed with Pompe. He joined the company Novazyme in 1999, which was working on enzyme

129_205

replacement treatment for Pompe. Novazyme was sold to Genzyme in 2001 for over US$100 million. The

129_206

2010 film Extraordinary Measures is based on Crowley's search for a cure.

129_207

As of 2019, many biomedical companies are developing Gene therapy in hopes of helping the body

129_208

create alpha-glucosidase on its own.

129_209

References External links

129_210

GeneReview/NIH/UW entry on Glycogen Storage Disease Type II (Pompe Disease)

129_211

Understanding Pompe Disease - US National Institute of Arthritis and Musculoskeletal and Skin

129_212

Diseases

129_213

Autosomal recessive disorders Hepatology Inborn errors of carbohydrate metabolism

129_214

Lysosomal storage diseases Rare diseases

130_0

The Dumaw Creek Site is an archaeological site designated 20OA5, located along Dumaw Creek northeast

130_1

of Pentwater, Michigan, that was the location of a 17th-century village and cemetery. It is one of

130_2

the youngest pre-historic sites in Michigan, dating to the terminal Late Woodland Period just

130_3

prior to European contact. It was listed on the National Register of Historic Places in 1972.

130_4

History

130_5

The village that once stood at this location was likely inhabited in the early part of the 17th

130_6

century (about 1605–1620, according to Quimby). The people occupying the village are thought to be

130_7

the precursors of the modern Potawatomi people. It is likely that they were uprooted from this

130_8

location soon after Samuel de Champlain's 1615 visit to the region, as warring tribes spilled into

130_9

Michigan. Were they the Potawatomi people, they eventually made their way by the 1640s to the

130_10

region around Sault Ste. Marie.

130_11

Meanwhile, white pine grew up in the plain where the village stood. The pine was lumbered in

130_12

1870-1880, after which the land was gradually converted to agricultural use, and was farmed as late

130_13

as 1930. In the 1940s, oil was discovered in the area, and wells were installed.

130_14

The Dumaw Creek site was originally discovered in 1915 by a farmer, Christoph "Carl" Schrumpf

130_15

1854–1949, who was pulling a stump from his field. Schrumpf discovered 18 skeletons and various

130_16

artifacts in 1915–16. These artifacts were catalogued by the Museum of Anthropology at the

130_17

University of Michigan in 1924, but the artifacts and records were not generally well known by

130_18

archaeologists. Schrumpf eventually sold the collection to a private dealer, and they eventually

130_19

made their way, sans any identifying data, to George I. Quimby at the Field Museum in 1959.

130_20

Quimby eventually tracked the source of the artifacts to the Dumaw Creek site, and in 1960-62 did

130_21

some summer surface collection there. He also located other artifacts already dug from the site.

130_22

Description

130_23

The Dumaw Creek site is located on a sandy plain near Dumaw Creek, a tributary of the Pentwater

130_24

River, at a site not easily accessible by canoe. The creek itself runs through a small valley

130_25

about beneath the level of the plain. The site, covering , was used as a village and burial

130_26

ground.

130_27

The village is thought to have been a semi-permanent settlement with dome-shaped wigwams. The

130_28

people hunted and fished, and grew corn and pumpkins.

130_29

Artifacts

130_30

Artifacts and features found at the site include burials, faunal remains, stone tools, bone tools,

130_31

red ocher/mineral paint (used for ceremonial coloring), copper artifacts, shell artifacts, tobacco

130_32

pipes, animal skins, and vegetal and textile remains.

130_33

At least nineteen, and perhaps as many as 55 skeletons were removed from burial sites in the Dumaw

130_34

Creek site. The bodies were wrapped in furs and buried with stone implements and copper beads.

130_35

The stone implements found include arrowheads, knives, and scraping tools of chipped flint and axes

130_36

of a hard, granular stone. Quimby reports that 99% of the stone tools were small triangular points

130_37

or arrowheads, aka Madison points, indicative of a Late Woodland period placement. There were also

130_38

a considerable number of copper artifacts found at the site. Many were large bead-like tubes of

130_39

copper known as hair pipes, which were worn as hair ornaments. There were also other, generally

130_40

smaller copper beads, conical decorations, and copper plaques, as well as shell beads and pendants.

130_41

Carved stone pipe bowls were also found, as well as animal skins and pottery.

130_42

The pottery is described by Quimby as grit-tempered vessels with round-bottomed, globular forms

130_43

with broad orifices and slightly flaring rims. The rim edges are often scalloped or crimped. The

130_44

vessel pictured below with a scalloped rim has been compared to the Moccasin Bluff Scalloped type

130_45

from the Moccasin Bluff site on the St. Joseph River in southwestern Michigan. This pottery type

130_46

is diagnostic of a Late Woodland period temporal placement, just before European contact. There was

130_47

also a shell pendant with a "weeping eye" design as shown below. This motif has been seen in other

130_48

Late Prehistoric sites in the Great Lakes area.

130_49

References

130_50

Buildings and structures in Oceana County, Michigan

130_51

Archaeological sites on the National Register of Historic Places in Michigan

130_52

National Register of Historic Places in Oceana County, Michigan Potawatomi Late Woodland period

131_0

Dag Ivar Wirén (15 October 1905 – 19 April 1986) was a Swedish composer.

131_1

Life

131_2

Wirén was born at Striberg near Nora. His father had a roller blind factory, and there were

131_3

various musical activities in the family home; he took piano lessons, and was a student at the

131_4

Karolinska school in Örebro, and played the bass drum and celesta in the town orchestra.

131_5

Wirén studied at the Stockholm conservatory from 1926 to 1931, which gave him much exposure to

131_6

music from all periods; hearing Arthur Honegger's oratorio King David in 1927 was an important

131_7

experience.

131_8

In 1932 he won the state stipend and used the award money to continue his studies in Paris, where

131_9

he lived from 1931 to 1934. While there, he studied composition under the Russian composer Leonid

131_10

Sabaneyev, though he admitted later that his endless attendance of concerts, and not his tutoring

131_11

with Sabaneyev, had the greater impact on his own work. In Paris he met Igor Stravinsky (as well as

131_12

his compatriot Gösta Nystroem) and was exposed to the music of Stravinsky, Sergei Prokofiev and the

131_13

French composers of Les Six.