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1)patterns of genetic variability in human mitochondria show evidence for recombination have
provoked considerable argument and much correspondence concerning the quality of the data,
the nature of the analyses and the biological realism of mitochondrial recombination. While the
majority of evidence now points towards a lack of effective recombination, at least in humans,
the debate has highlighted how difficult the detection of recombination can be in genomes with
unusual mutation processes and complex demographic histories. A major difficulty is the lack of
consensus about how to measure linkage disequilibrium. I show that measures differ in the way
they treat data that are uninformative about recombination, and that when just those pairwise
comparisons that are informative about recombination are used, there is agreement between
different statistics. In this light, the significant negative correlation between linkage
disequilibrium and distance in at least some of the data sets is a real pattern that requires
explanation
2)The analysis of mitochondrial DNA (mtDNA) has been a potent tool in our understanding of
human evolution, owing to characteristics such as high copy number, apparent lack of
recombination, high substitution rate and maternal mode of inheritance. However, almost all
studies of human evolution based on mtDNA sequencing have been confined to the control
region, which constitutes less than 7% of the mitochondrial genome. These studies are
complicated by the extreme variation in substitution rate between sites, and the consequence of
parallel mutations causing difficulties in the estimation of genetic distance and making
phylogenetic inferences questionable. Most comprehensive studies of the human mitochondrial
molecule have been carried out through restriction-fragment length polymorphism analysis,
providing data that are ill suited to estimations of mutation rate and therefore the timing of
evolutionary events. Here, to improve the information obtained from the mitochondrial molecule
for studies of human evolution, we describe the global mtDNA diversity in humans based on
analyses of the complete mtDNA sequence of 53 humans of diverse origins. Our mtDNA data, in
comparison with those of a parallel study of the Xq13.3 region in the same individuals, provide a
concurrent view on human evolution with respect to the age of modern humans.
3)Nephropathy associated with BK virus has emerged as an important cause of allograft failure
in renal transplant recipients. Here we exploited a recently developed novel monocyte based
solid phase T cell selection system, in which monocytes are immobilized on solid support, for
antigen-specifi c T cell purifi cation. The underlying hypothesis of this new method is that
antigen-specifi c T cells recognize, bind their cognate antigens faster than non-specifi c T cells
and are concentrated on the surface after removing the non-adherent cells by washing. Moreover,
activated antigen-specifi c T cells proliferate more rapidly than non-specifi c T cells, further
increasing the frequency and purity of antigen-specifi c T cells. Optimal selection times for BK
virus-specifi c T cells are studied. Our data demonstrated that T cell selection can usually
increase the frequency of antigen-specifi c T cells by 10 fold, whereas T cell expansion
following the selection boost the frequency of antigen-specifi c T cells by another ~10 fold. This
new T cell selection system is superior to traditional stimulation method (i.e. simply mixing
antigen presenting cells and lymphocytes together) in generating antigen-specifi c T cells. This
inexpensive and simple T cell selection system can produce large quantity of highly purifi ed BK
virus-specifi c T cells within 1–2 weeks after initial T cell activation.
4)Naturally occurring 222Rn (radon; t1/2 = 3.8 days) is a good natural tracer of groundwater
discharge because it is conservative and typically 2-3 orders of magnitude higher in groundwater
than surface waters. In addition, new technology has allowed rapid and inexpensive field
measurements of radon-in-water. Results from the C-25 Canal, a man-made canal in east-central
Florida thought to be dominated by groundwater inflows, display how one can quickly assess a
water body for locations of groundwater inputs. Although only the eastern portion of the canal
was surveyed, use of a few assumptions together with some continuous radon measurements
allowed reasonable estimates of the groundwater inflows to be made. Groundwater discharge
estimates of 327,000 m3/day and 331,000 m3/day were measured for two stations based on
determining the groundwater fraction of the total stream flow. This fraction in each case was
calculated by correcting radon concentrations for decay over transit times determined from
concentration differences between the apparent focal point of groundwater discharge (with a
concentration of 520±80 dpm/L) estimated to be 17.7 km upstream from the downstream sample
locations. During the same period, an average flow of 312,000±70,000 m3/day was determined
from time-series measurements of radon at a fixed downstream location. Coincident current
meter readings and a measured cross-section area allowed an independent assessment of the total
stream discharge of 336,000 m3/day. The radon-derived estimates thus indicate that 90 of the
total flow is groundwater derived, consistent with the known characteristics of this waterway.
Solution
1)patterns of genetic variability in human mitochondria show evidence for recombination have
provoked considerable argument and much correspondence concerning the quality of the data,
the nature of the analyses and the biological realism of mitochondrial recombination. While the
majority of evidence now points towards a lack of effective recombination, at least in humans,
the debate has highlighted how difficult the detection of recombination can be in genomes with
unusual mutation processes and complex demographic histories. A major difficulty is the lack of
consensus about how to measure linkage disequilibrium. I show that measures differ in the way
they treat data that are uninformative about recombination, and that when just those pairwise
comparisons that are informative about recombination are used, there is agreement between
different statistics. In this light, the significant negative correlation between linkage
disequilibrium and distance in at least some of the data sets is a real pattern that requires
explanation
2)The analysis of mitochondrial DNA (mtDNA) has been a potent tool in our understanding of
human evolution, owing to characteristics such as high copy number, apparent lack of
recombination, high substitution rate and maternal mode of inheritance. However, almost all
studies of human evolution based on mtDNA sequencing have been confined to the control
region, which constitutes less than 7% of the mitochondrial genome. These studies are
complicated by the extreme variation in substitution rate between sites, and the consequence of
parallel mutations causing difficulties in the estimation of genetic distance and making
phylogenetic inferences questionable. Most comprehensive studies of the human mitochondrial
molecule have been carried out through restriction-fragment length polymorphism analysis,
providing data that are ill suited to estimations of mutation rate and therefore the timing of
evolutionary events. Here, to improve the information obtained from the mitochondrial molecule
for studies of human evolution, we describe the global mtDNA diversity in humans based on
analyses of the complete mtDNA sequence of 53 humans of diverse origins. Our mtDNA data, in
comparison with those of a parallel study of the Xq13.3 region in the same individuals, provide a
concurrent view on human evolution with respect to the age of modern humans.
3)Nephropathy associated with BK virus has emerged as an important cause of allograft failure
in renal transplant recipients. Here we exploited a recently developed novel monocyte based
solid phase T cell selection system, in which monocytes are immobilized on solid support, for
antigen-specifi c T cell purifi cation. The underlying hypothesis of this new method is that
antigen-specifi c T cells recognize, bind their cognate antigens faster than non-specifi c T cells
and are concentrated on the surface after removing the non-adherent cells by washing. Moreover,
activated antigen-specifi c T cells proliferate more rapidly than non-specifi c T cells, further
increasing the frequency and purity of antigen-specifi c T cells. Optimal selection times for BK
virus-specifi c T cells are studied. Our data demonstrated that T cell selection can usually
increase the frequency of antigen-specifi c T cells by 10 fold, whereas T cell expansion
following the selection boost the frequency of antigen-specifi c T cells by another ~10 fold. This
new T cell selection system is superior to traditional stimulation method (i.e. simply mixing
antigen presenting cells and lymphocytes together) in generating antigen-specifi c T cells. This
inexpensive and simple T cell selection system can produce large quantity of highly purifi ed BK
virus-specifi c T cells within 1–2 weeks after initial T cell activation.
4)Naturally occurring 222Rn (radon; t1/2 = 3.8 days) is a good natural tracer of groundwater
discharge because it is conservative and typically 2-3 orders of magnitude higher in groundwater
than surface waters. In addition, new technology has allowed rapid and inexpensive field
measurements of radon-in-water. Results from the C-25 Canal, a man-made canal in east-central
Florida thought to be dominated by groundwater inflows, display how one can quickly assess a
water body for locations of groundwater inputs. Although only the eastern portion of the canal
was surveyed, use of a few assumptions together with some continuous radon measurements
allowed reasonable estimates of the groundwater inflows to be made. Groundwater discharge
estimates of 327,000 m3/day and 331,000 m3/day were measured for two stations based on
determining the groundwater fraction of the total stream flow. This fraction in each case was
calculated by correcting radon concentrations for decay over transit times determined from
concentration differences between the apparent focal point of groundwater discharge (with a
concentration of 520±80 dpm/L) estimated to be 17.7 km upstream from the downstream sample
locations. During the same period, an average flow of 312,000±70,000 m3/day was determined
from time-series measurements of radon at a fixed downstream location. Coincident current
meter readings and a measured cross-section area allowed an independent assessment of the total
stream discharge of 336,000 m3/day. The radon-derived estimates thus indicate that 90 of the
total flow is groundwater derived, consistent with the known characteristics of this waterway.

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1)patterns of genetic variability in human mitochondria show evidenc.pdf

  • 1. 1)patterns of genetic variability in human mitochondria show evidence for recombination have provoked considerable argument and much correspondence concerning the quality of the data, the nature of the analyses and the biological realism of mitochondrial recombination. While the majority of evidence now points towards a lack of effective recombination, at least in humans, the debate has highlighted how difficult the detection of recombination can be in genomes with unusual mutation processes and complex demographic histories. A major difficulty is the lack of consensus about how to measure linkage disequilibrium. I show that measures differ in the way they treat data that are uninformative about recombination, and that when just those pairwise comparisons that are informative about recombination are used, there is agreement between different statistics. In this light, the significant negative correlation between linkage disequilibrium and distance in at least some of the data sets is a real pattern that requires explanation 2)The analysis of mitochondrial DNA (mtDNA) has been a potent tool in our understanding of human evolution, owing to characteristics such as high copy number, apparent lack of recombination, high substitution rate and maternal mode of inheritance. However, almost all studies of human evolution based on mtDNA sequencing have been confined to the control region, which constitutes less than 7% of the mitochondrial genome. These studies are complicated by the extreme variation in substitution rate between sites, and the consequence of parallel mutations causing difficulties in the estimation of genetic distance and making phylogenetic inferences questionable. Most comprehensive studies of the human mitochondrial molecule have been carried out through restriction-fragment length polymorphism analysis, providing data that are ill suited to estimations of mutation rate and therefore the timing of evolutionary events. Here, to improve the information obtained from the mitochondrial molecule for studies of human evolution, we describe the global mtDNA diversity in humans based on analyses of the complete mtDNA sequence of 53 humans of diverse origins. Our mtDNA data, in comparison with those of a parallel study of the Xq13.3 region in the same individuals, provide a concurrent view on human evolution with respect to the age of modern humans. 3)Nephropathy associated with BK virus has emerged as an important cause of allograft failure in renal transplant recipients. Here we exploited a recently developed novel monocyte based solid phase T cell selection system, in which monocytes are immobilized on solid support, for antigen-specifi c T cell purifi cation. The underlying hypothesis of this new method is that antigen-specifi c T cells recognize, bind their cognate antigens faster than non-specifi c T cells and are concentrated on the surface after removing the non-adherent cells by washing. Moreover, activated antigen-specifi c T cells proliferate more rapidly than non-specifi c T cells, further increasing the frequency and purity of antigen-specifi c T cells. Optimal selection times for BK
  • 2. virus-specifi c T cells are studied. Our data demonstrated that T cell selection can usually increase the frequency of antigen-specifi c T cells by 10 fold, whereas T cell expansion following the selection boost the frequency of antigen-specifi c T cells by another ~10 fold. This new T cell selection system is superior to traditional stimulation method (i.e. simply mixing antigen presenting cells and lymphocytes together) in generating antigen-specifi c T cells. This inexpensive and simple T cell selection system can produce large quantity of highly purifi ed BK virus-specifi c T cells within 1–2 weeks after initial T cell activation. 4)Naturally occurring 222Rn (radon; t1/2 = 3.8 days) is a good natural tracer of groundwater discharge because it is conservative and typically 2-3 orders of magnitude higher in groundwater than surface waters. In addition, new technology has allowed rapid and inexpensive field measurements of radon-in-water. Results from the C-25 Canal, a man-made canal in east-central Florida thought to be dominated by groundwater inflows, display how one can quickly assess a water body for locations of groundwater inputs. Although only the eastern portion of the canal was surveyed, use of a few assumptions together with some continuous radon measurements allowed reasonable estimates of the groundwater inflows to be made. Groundwater discharge estimates of 327,000 m3/day and 331,000 m3/day were measured for two stations based on determining the groundwater fraction of the total stream flow. This fraction in each case was calculated by correcting radon concentrations for decay over transit times determined from concentration differences between the apparent focal point of groundwater discharge (with a concentration of 520±80 dpm/L) estimated to be 17.7 km upstream from the downstream sample locations. During the same period, an average flow of 312,000±70,000 m3/day was determined from time-series measurements of radon at a fixed downstream location. Coincident current meter readings and a measured cross-section area allowed an independent assessment of the total stream discharge of 336,000 m3/day. The radon-derived estimates thus indicate that 90 of the total flow is groundwater derived, consistent with the known characteristics of this waterway. Solution 1)patterns of genetic variability in human mitochondria show evidence for recombination have provoked considerable argument and much correspondence concerning the quality of the data, the nature of the analyses and the biological realism of mitochondrial recombination. While the majority of evidence now points towards a lack of effective recombination, at least in humans, the debate has highlighted how difficult the detection of recombination can be in genomes with unusual mutation processes and complex demographic histories. A major difficulty is the lack of consensus about how to measure linkage disequilibrium. I show that measures differ in the way they treat data that are uninformative about recombination, and that when just those pairwise
  • 3. comparisons that are informative about recombination are used, there is agreement between different statistics. In this light, the significant negative correlation between linkage disequilibrium and distance in at least some of the data sets is a real pattern that requires explanation 2)The analysis of mitochondrial DNA (mtDNA) has been a potent tool in our understanding of human evolution, owing to characteristics such as high copy number, apparent lack of recombination, high substitution rate and maternal mode of inheritance. However, almost all studies of human evolution based on mtDNA sequencing have been confined to the control region, which constitutes less than 7% of the mitochondrial genome. These studies are complicated by the extreme variation in substitution rate between sites, and the consequence of parallel mutations causing difficulties in the estimation of genetic distance and making phylogenetic inferences questionable. Most comprehensive studies of the human mitochondrial molecule have been carried out through restriction-fragment length polymorphism analysis, providing data that are ill suited to estimations of mutation rate and therefore the timing of evolutionary events. Here, to improve the information obtained from the mitochondrial molecule for studies of human evolution, we describe the global mtDNA diversity in humans based on analyses of the complete mtDNA sequence of 53 humans of diverse origins. Our mtDNA data, in comparison with those of a parallel study of the Xq13.3 region in the same individuals, provide a concurrent view on human evolution with respect to the age of modern humans. 3)Nephropathy associated with BK virus has emerged as an important cause of allograft failure in renal transplant recipients. Here we exploited a recently developed novel monocyte based solid phase T cell selection system, in which monocytes are immobilized on solid support, for antigen-specifi c T cell purifi cation. The underlying hypothesis of this new method is that antigen-specifi c T cells recognize, bind their cognate antigens faster than non-specifi c T cells and are concentrated on the surface after removing the non-adherent cells by washing. Moreover, activated antigen-specifi c T cells proliferate more rapidly than non-specifi c T cells, further increasing the frequency and purity of antigen-specifi c T cells. Optimal selection times for BK virus-specifi c T cells are studied. Our data demonstrated that T cell selection can usually increase the frequency of antigen-specifi c T cells by 10 fold, whereas T cell expansion following the selection boost the frequency of antigen-specifi c T cells by another ~10 fold. This new T cell selection system is superior to traditional stimulation method (i.e. simply mixing antigen presenting cells and lymphocytes together) in generating antigen-specifi c T cells. This inexpensive and simple T cell selection system can produce large quantity of highly purifi ed BK virus-specifi c T cells within 1–2 weeks after initial T cell activation. 4)Naturally occurring 222Rn (radon; t1/2 = 3.8 days) is a good natural tracer of groundwater discharge because it is conservative and typically 2-3 orders of magnitude higher in groundwater
  • 4. than surface waters. In addition, new technology has allowed rapid and inexpensive field measurements of radon-in-water. Results from the C-25 Canal, a man-made canal in east-central Florida thought to be dominated by groundwater inflows, display how one can quickly assess a water body for locations of groundwater inputs. Although only the eastern portion of the canal was surveyed, use of a few assumptions together with some continuous radon measurements allowed reasonable estimates of the groundwater inflows to be made. Groundwater discharge estimates of 327,000 m3/day and 331,000 m3/day were measured for two stations based on determining the groundwater fraction of the total stream flow. This fraction in each case was calculated by correcting radon concentrations for decay over transit times determined from concentration differences between the apparent focal point of groundwater discharge (with a concentration of 520±80 dpm/L) estimated to be 17.7 km upstream from the downstream sample locations. During the same period, an average flow of 312,000±70,000 m3/day was determined from time-series measurements of radon at a fixed downstream location. Coincident current meter readings and a measured cross-section area allowed an independent assessment of the total stream discharge of 336,000 m3/day. The radon-derived estimates thus indicate that 90 of the total flow is groundwater derived, consistent with the known characteristics of this waterway.