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This paper quantifies the computational complexity and parallel scalability of two algorithms for four-dimensional data assimilation (4DDA) at NASA's Global Modeling and Assimilation Office (GMAO). The first, the Goddard Earth Observing System Data Assimilation System (GEOS DAS), uses an atmospheric general circulation model (GCM) and an observation-space-based analysis system, the Physical-Space Statistical Analysis System (PSAS). GEOS DAS is very similar to global meteorological weather forecasting data assimilation systems but is used at NASA for climate research. The second, the Kalman filter, uses a more consistent algorithm to determine the forecast error covariance matrix than does GEOS DAS. For atmospheric assimilation, the gridded dynamical fields typically have more than 106 variables; therefore, the full error covariance matrix may be in excess of a teraword. For the Kalman filter this problem will require petaflop s−1 computing to achieve effective throughput for scientific research.
1. Four-dimensional data assimilation
Four-dimensional data assimilation (4DDA) is the process of combining observations with a dynamical model to generate a gridded best estimate, or analysis, of the state of the system (Daley 1991). It is thus a mapping problem, whereby scattered observations are converted into accurate maps of wind, temperature, moisture, and other variables. Figure 1.11 of Daley (1991) shows a schematic of the data assimilation cycle. The model propagates in time the estimate of the state; for example, for the global atmosphere we use a general circulation model (GCM). The analysis is a statistics-based algorithm for combining the model output, or forecast, with observations to produce the best-estimate state. This is a cycled algorithm whereby the analysis state is used to reinitialize the model, and so on. 4DDA is used in weather forecasting to initialize model forecasts, for example, at the National Centers for Environmental Prediction (NCEP; Parrish and Derber 1992; Parrish et al. 1997) and at the European Centre for Medium-Range Weather Forecasts (ECMWF; Courtier et al. 1998; Rabier et al. 1998; Andersson et al. 1998). 4DDA is also used to perform reanalyses of past datasets to obtain consistent, gridded, best estimates of the state variables of the atmosphere (e.g., wind, temperature, moisture, etc.), for example, at the National Aeronautics and Space Administration (NASA) Global Modeling and Assimilation Office (GMAO; Schubert et al. 1993, 1995), at NCEP (Kalnay et al. 1996; Kistler et al. 2001), and at ECMWF (Gibson et al. 1997). These gridded reanalysis datasets are a valuable resource for the earth science research community (GMAO 2000).
This paper quantifies the computational complexity and the scalability of distributed-memory parallel implementations of two algorithms for 4DDA at the GMAO. The first is the Goddard Earth Observing System Data Assimilation System (GEOS DAS), which uses a gridpoint-based atmospheric GCM and an observation-space-based analysis system, the Physical-Space Statistical Analysis System (PSAS). GEOS DAS is very similar to global weather forecasting algorithms, where the analysis fields are used to initialize the GCM for a model forecast. Operational global 4DDA systems such as GEOS DAS with model grids of the order 105 m have about 106 variables.1 We also present a timing profile of the baseline-resolution GEOS-2 DAS on computers with 8 or 10 processors using shared-memory parallelism. The second algorithm is the Kalman filter, which offers the promise of more accurate analyses because it evolves error statistics in a dynamically consistent manner. However, the full error covariance matrix is of dimension the square of the number of model state variables, so the algorithm will require petaflop per second computing to achieve effective throughput for scientific research. A two-dimensional (latitude–longitude) Kalman filter for the assimilation of constituent gas mixing ratio in the stratosphere was developed by our group as a prototype and research tool (Lyster et al. 1997a; Ménard et al. 2000; Menard and Chang 2000). Some of the results of this work are used to extrapolate to the complexity of a full Kalman filter with three-dimensional meteorological fields.
The results presented here are of interest to scientific software developers who make compromises between algorithmic improvements or approximations on the one hand and computer resources on the other. They also are a useful starting point for computer administrators who make strategic decisions about computer architecture, maintenance, and purchases based on many parameters, including future estimates of the problem size (e.g., the resolution of the model and the number of observations to be assimilated) and the performance and parallel scalability of the algorithms. Section 2 starts with an overview of the GEOS DAS. The discussion on complexity provides estimates of floating-point operations of the components of the data assimilation systems. Specific results are provided for the version 2, GEOS-2 DAS, which was the main production system in use at the GMAO in the late 1990s. It consists of GEOS-2 GCM with resolution 2.5° latitude, 2° longitude, and 70 vertical levels, and GEOS-2 PSAS, which assimilated about 50 000 observations per 6 h; details of these algorithms are given in section 2a,b. Section 2c provides timing profiles of the baseline production system GEOS-2 DAS that used shared-memory parallelism. Section 3 presents the algorithm for the Kalman filter and describes the two-dimensional distributed-memory parallel implementation that was used for scientific and computational research. The GCM and PSAS have tightly coupled core algorithms with computation- and communication-intensive parallel implementations: these are hydrodynamic transport (GCM) and nonsparse large matrix–vector multiplications (PSAS). Section 4 discusses technical issues and limitations in developing scalable distributed-memory parallel implementations of the GCM and PSAS, and then extends the discussion to GEOS DAS.
2. Goddard Earth Observing System Data Assimilation System (GEOS DAS)
Derivations of analysis algorithms abound (Daley 1991). We motivate briefly and derive the analysis equations for GEOS DAS based on a statistical least squares approach. Cohn (1997) places this discussion in the context of general filtering methods. The optimal estimate of the state is the value of the control variable w that minimizes the cost function J:
w is the control vector of n state variables;
wf is the forecast vector of n state variables;
wo is the vector of p observations;
𝗣f is the (n × n) given forecast error covariance matrix;
𝗥 is the (p × p) given observation error covariance matrix; and
𝗛 is the (here linearized) forward operator that models the observations by acting on the state vector (e.g., if the observations come from direct measurements of the state, then 𝗛 can be implemented by interpolation from the state grid to the observation locations).
The value of w that minimizes J is the analysis state:
where the Kalman gain is
GEOS-2 DAS uses a 6-h assimilation window [0, 6 h] for the analysis cycle that is shown schematically in Fig. 1.11 of Daley (1991). Starting from a prior analysis, the GCM generates a forecast by iterating a time-stepping algorithm:
where k is a time index and ℳk is the model operator. By convention (e.g., Daley 1991; GMAO 2000), the forecast for each data assimilation cycle ends at (0000, 0600, 1200, 1800) UTC. GEOS-2 DAS evaluates Eq. (2) for each of these 6-h forecasts using data that are accumulated ±3 h (i.e., evenly) about the forecast time. Operational algorithms at weather centers and laboratories (Daley 1991) have more constraints and attributes than the simple form of Eqs. (1), (2), and (3). Indeed, GEOS-2 DAS uses a slight modification of the cycling method just described, which involves 9 h of model iteration for each 6-h data assimilation cycle (Bloom et al. 1996). However, these caveats do not substantially modify the evaluation of computational complexity and parallel scalability in the present work.
a. The computational algorithm for GEOS DAS
We describe the complexity and timing profile for a baseline version 2, GEOS-2 DAS, which was the main production system in use at the GMAO in the late 1990s. The GEOS-2 GCM (Takacs et al. 1994) comprises a spatial fourth-order-accurate finite-difference dynamical core to model hydrodynamical processes, plus physics components for moist convection, turbulence, and shortwave and longwave radiation. The state, or prognostic, variables are horizontal winds, potential temperature, specific humidity, and surface pressure. A high-latitude spectral filter and a global Shapiro filter and polar rotation algorithm provide smoothing and numerical stability. The GEOS-2 GCM used a model resolution of 2.5° latitude, 2° longitude, and 70 vertical levels. This corresponds to three-dimensional fields with horizontal resolution 91 grid points in latitude and 144 grid points in longitude. The GEOS-2 GCM uses a multiple-time-scale computational technique (Brackbill and Cohen 1985). The dynamical core has the smallest time step of 3 min at baseline resolution. The physics components generate time tendencies at longer intervals: moist convection 10 min, turbulence 30 min, shortwave radiation 1 h, and longwave radiation 3 h. These tendencies are applied to the state variables incrementally at the shortest time scale (3 min). Fuller details are described in Takacs et al. (1994), and the next sections will discuss the complexity and timing profile of the GCM in the context of the whole data assimilation system. The number of state variables at the baseline resolution is approximately n ≈ 3 × 91 × 144 × 70 + 91 × 144 ≈ 2.6 × 106, corresponding to the 3 upper-air (i.e., three-dimensional) field arrays and 1 surface (i.e., two-dimensional) field array, although in practice up to 14 upper-air field arrays are carried by the algorithm.
Currently, the GCM is run with 1° × 1° × 48 levels, and developmental versions achieve even higher resolution. An extensive land surface model with associated prognostic variables has also been implemented in the GCM, but we will not include that in the baseline numbers. The actual resolution is not critical to this paper, which discusses scaling properties starting from the baseline resolution of the GEOS-2 DAS. Note also that this is not the same model as the finite-volume fvGCM that is used for current-generation data assimilation systems at the GMAO. Between these two GCMs some general quantities, such as asymptotic scalability, may be similar, but specific values of quantities like the model time step or wall-clock time of runs are different.
The algorithm for solving Eq. (2), that is, the analysis in Fig. 1.11 of Daley (1991), is the PSAS (Cohn et al. 1998). This solves
The time subscript k will be dropped where it is not important to the discussion. The right-hand side of Eq. (5) is sometimes called the "observed minus forecast residual" or the "innovation," and 𝗛𝗣f𝗛T + 𝗥 is called the "innovation matrix." To generate the analysis fields at the end of each 6-h cycle, GEOS-2 DAS adds the "analysis increment" wa − wf incrementally to the state variables in a similar way as the physics tendencies are applied as described above (Takacs et al. 1994; Bloom et al. 1996). The error covariance matrices 𝗣f and 𝗥 are implemented using models for variances and correlations whose parameters are obtained from prior statistics and simplifying assumptions such as stationarity (Daley 1991; GMAO 2000). Sophisticated multivariate formulations of error covariances are used to improve the quality of the analysis (Guo et al. 1998). Although this has a significant impact on the software complexity (Larson et al. 1998) it has only a secondary impact on the computational complexity and will not be considered here. The resulting matrices 𝗛𝗣f𝗛T + 𝗥 and 𝗣f𝗛T are in principle dense; however, correlation models with compact support (Gaspari and Cohn 1999) are used, which reduces the computational complexity by setting the correlation to zero beyond a fixed length. As described above, Eqs. (5) and (6) are solved for data that are aggregated over the [0, 6 h] analysis cycle. This interval will be shortened to make better use of asynoptic observations (e.g., retrievals from satellites) and accommodate shorter temporal and spatial scales of high-resolution GCMs, but the numbers in this paper refer to baseline GEOS-2 DAS with a 6-h analysis cycle. The PSAS consists of solving one p × p linear system [Eq. (5)] for the intermediate vector x using a parallel nested-preconditioned conjugate gradient solver [Cohn et al. (1998); Golub and van Loan (1989); The technical documents for the PSAS are da Silva and Guo (1996), Guo et al. (1998), and Larson et al. (1998)]. Machine-precision solutions for x are not required because the error in the analysis field wa is only required to be consistent with the error covariance 𝗣a (Cohn et al. 1998). For the baseline GEOS-2 DAS during the late 1990s there were typically p ≈ 5 × 104 observations worldwide in each 6-h period. From experience, we found that 𝒩i ≈ 10 iterations of the outer loop of the solver provides a satisfactory solution; this reduces the residual of the solver by about an order of magnitude.
The GEOS-2 DAS was run in a number of production modes (Stobie 1996). These may be generally categorized as real-time, near-real-time, and reanalysis modes. Real-time mode requires model forecast and analyses to take place sufficiently in excess of 1 day of assimilation per wall-clock day so that the results may be studied and disseminated to customers such as satellite instrument teams with real-time needs. Reanalyses are multiyear studies designed to provide long-term datasets from a frozen scientific software configuration. For example, the GMAO has completed a reanalysis for the years 1979–95 using the version GEOS-1 DAS (Schubert et al. 1993, 1995).
The data acquisition and storage system for 4DDA involves a worldwide instrumentation, telecommunication, databasing, computational, and administrative effort (Atlas 1997). We remark here only on the attributes and numbers that are relevant to the present work. In the last 60 yr about 2 billion observations that are appropriate for input to atmospheric data assimilation systems have been accumulated. The volume of these data does not present the greatest computational complexity, and operational centers are more concerned with the accuracy of these data. Considerable energy is devoted to finding and validating old observations, that is, "data rehabilitation." In the coming years, diverse new data types will be made available for data assimilation, and the volume and complexity of the data handling system will increase considerably. For example, satellite sea surface wind observations have been shown to be useful in increasing forecast accuracy of weather analyses (Atlas et al. 1996). The GMAO will also assimilate an increasing amount of nonmeteorological data, such as trace gas concentration in the atmosphere. During the late 1990s, when GEOS-2 DAS was the main operational data assimilation algorithm at the GMAO, about 105 observations were produced daily under the World Weather Watch and transmitted to worldwide weather centers and the GMAO via the Global Telecommunications System, which is under the supervision of the World Meteorological Organization (Atlas 1997). More than 70% of these were obtained from satellite measurements, mostly as temperature retrievals; the remaining were from in situ balloon-borne and land and sea surface instruments. Table 1 summarizes the baseline GEOS-2 DAS system performance and throughput. GEOS-2 DAS used shared-memory multitasking parallelism and ran on Cray J90/C90 and SGI Origin 2000 computers. At baseline resolution for the GEOS-2 GCM (2.5° × 2° × 70 levels), a day of assimilation produced in excess of 1 GB of data. Hence data assimilation at real time (1 day of assimilation per wall-clock day) did not stretch the local disk capacity or bandwidth of most modern computer systems. However, extended runs at higher throughput than real time increases the burden on storage and data processing. The most severe challenge is for reanalysis projects in which multiyear datasets are analyzed by a fixed-version DAS and the products are made available to the scientific community. The standard benchmark is a rate of 30 days of assimilation per day of wall-clock time (i.e., a 15-yr reanalysis on order half a year). At this rate the GEOS-2 DAS produced about 10 TB of data per year.
b. The computational complexity of GEOS DAS
Where appropriate, estimates of actual floating-point counts are calculated. However, where this is too difficult or vague we simply specify the scaling. The computational complexity of different algorithms cannot be compared without careful specification of the spatiotemporal problem domains. In this paper we will state when we use two or three spatial dimensions. We use the notation [0, T] to specify a fixed simulation time interval. Beyond these, the computational complexity depends on a combination of numerical and physical parameters, including the number of state variables in the model (n), the number of observations in an assimilation cycle (p), as well as numerical parameters defined in the text.
For the GEOS-2 GCM we specify separately the number of grid points in the longitude, latitude, and vertical coordinates as Nx, Ny, and Nz, respectively (i.e., n ∼ NxNyNz; we indicate here only proportionality because n includes the total number of field types—wind, height, surface pressure, and moisture—factored into the total number of gridpoints). The complexity of all four of the dynamics, moist convection, turbulence, and radiation components scale as NxNy. In any fixed interval [0, T] the complexity of the dynamics has an additional dependence on the number of time steps. Generally the number of time steps of the dynamics, that is, the temporal resolution, increases in proportion to the horizontal resolution, Nx. Also, as the update interval of the physics components is shortened there will be an additional impact on complexity (L. L. Takacs 1997, personal communication). The complexity of the dynamics, moist convection, and turbulence components scale as Nz, while the radiation scales as N2z. As the horizontal resolution is increased and the concomitant number of dynamics time steps in a fixed simulation interval is increased, the complexity of the dynamics dominates the other components. Asymptotically, for a fixed simulation interval the complexity of the dynamics scales as n4/3. Thus, if the resolution of the GCM is doubled in all three dimensions the complexity of the dynamics increases 16-fold. The memory requirement for the GCM scales as n; thus, the memory requirement in general scales less rapidly than the computational complexity. These asymptotic calculations help specify the size of computing requirements in a 10-yr or longer time frame; however, they can be misleading when applied to real developmental or production software in use today where, for example, there may be parameter regimes where the time step does not need to be reduced in proportion to the horizontal resolution. In this case, it is important to instrument and generate timing profiles of the algorithms. The next section will present the timing profile for the GEOS-2 DAS and its components.
For the GEOS-2 PSAS, the solver [Eq. (5)] has complexity f𝒩isp2, where s ≈ 0.40 is the density (fraction of nonzero elements) of the innovation matrix resulting from the use of a correlation function with compact support of 6 × 106 m. The factor f equals 2 plus the number of floating-point operations required to form each element of the matrix. The GEOS-2 PSAS calculates the matrix elements using precalculated lookup tables at each iteration of the outermost loop during the conjugate gradient iteration cycle. This reduces the overall memory requirement and allows for scalability to larger numbers of observations beyond the current values (Guo et al. 1998; Larson et al. 1998). Therefore, f may be as high as 10, but the exact value depends on the optimization of the access to the tables (Lyster et al. 2000a). The complexity of the preconditioners is neglected here because the preconditioners involve sparse matrix–vector operations compared with the full matrix solver. Equation (6) evaluates the analysis increment, and this has complexity fsnp. The analysis increment is evaluated on a 2.5° × 2° × 14 level grid, and these fields are interpolated to the model GCM grid. For the baseline GEOS-2 DAS this means that the vertical coordinate systems are interpolated from 14 to 70 levels. Note that because the GCM and PSAS use different resolution grids the values of n are context-dependent in the complexity formulas.
The baseline GEOS-2 DAS used a 6-h analysis cycle, with p ≈ 5 × 104 observations accumulated evenly about the analysis time, as described above. The analysis cycle can be made shorter, potentially leading to a more accurate algorithm. In section 3 this is discussed in the context of the Kalman filter. For now, note that as the analysis cycle time is reduced the computational complexity of the analysis equation (6) for the interval [0, 6 h] remains fixed at fsnp. However, for this fixed interval the complexity of the solver, Eq. (5), will be reduced to approximately 𝒩tf𝒩is(p/𝒩t)2 = f𝒩isp2/𝒩t, where 𝒩t is the number of analysis cycles in [0, 6 h]. Thus, if the analysis cycle time were reduced to the 3-min time step of the model dynamics for baseline GEOS-2 GCM, the complexity of the analysis solver would be reduced by a factor of 𝒩t = 120. In the following section we show that for the baseline GEOS-2 PSAS, the implementations of Eqs. (5) and (6) contribute to the computational complexity of the PSAS in the ratio 35:62. Therefore, reducing the analysis cycle time reduces the overall complexity, thus allowing the use of an increasing number of observations.
c. The timing profile of GEOS-2 DAS
The baseline GEOS-2 DAS uses shared-memory multitasking parallelism on Cray J series and SGI Origin computers. Technical issues and limitations in developing scalable distributed-memory parallel implementations of the GCM and PSAS, and by extension GEOS DAS, are discussed in section 4. In this section we discuss the timing profile of shared-memory parallel GEOS-2 DAS.
Table 2 shows the percentage of time taken by the top-level components of the baseline GEOS-2 DAS run on eight processors of an SGI Origin 2000.2 Note that the time taken for the diagnostics involves the CPU time to accumulate and process three-dimensional arrays and the time to write data to disk. The interface time accounts for the input and initial processing of the (p ≈ 5 × 104) observations, plus the quality control component, which culls a priori unreliable observations (e.g., those observations whose locations or values are in gross error). The GCM, PSAS, diagnostics, and interface software, which comprise about 150 000 lines of FORTRAN 77 and FORTRAN 90 code, make substantial use of shared-memory multitasking parallelism. Overall, 0.6% of the serial time cost of GEOS-2 DAS (i.e., as timed on a single processor) arises from code that is is not parallelized; of this, about half is in the initialization and data processing components of the PSAS and half is in the interface. As a check, we estimate the percentage of wall-clock time for the interface when GEOS-2 DAS is run on eight processors. Let u be the fraction of serial time cost of the interface; that is, u = 0.003 (henceforth u is referred to as the "serial fraction"). Then the fraction of wall-clock time of the interface on Np = 8 is approximately u/(u + (1 − u)/ Np) = 0.024. The unparallelized component of the PSAS does not significantly modify the result; however, we will later have to take this into account when dealing with the scalability of GEOS DAS for larger numbers of processors. In the present case, for eight processors the figure 0.024 (2.4%) is in line with the value shown in Table 2.
Table 3 shows the percentage of time taken by the top-level components of the baseline GEOS-2 GCM. The GCM is run in "assimilation mode" using the Matsuno time-stepping scheme. The times for the dynamics, the Shapiro filter spatial smoother, the polar rotation, and other grid transformations are bundled into a single-component designated dynamical core (Takacs et al. 1994). Although these numbers are for 10 processors of the Cray J90, they do not differ significantly from the baseline 8 processors on the SGI Origin 2000.
The percentage of time taken by the top-level components of the baseline GEOS-2 PSAS is shown in Table 4. The solver [Eq. (5)] with complexity f𝒩isp2 takes about 35% of the time while the analysis [Eq. (6)] with complexity fsnp takes 62% of the time. These expressions for complexity can be checked approximately by taking the nominal values, f = 10, p = 5 × 104, n = 106, 𝒩i = 10, and s = 0.4. Using these numbers, f𝒩isp2 = 1011 and fsnp = 2 × 1011, that is, the estimated count of floating-point operations for the PSAS is 3 × 1011 per analysis. The Cray J916 Hardware Performance Monitor reports 5 × 1011 floating-point multiplications and 4.5 × 1011 floating-point additions for the total complexity of GEOS-2 DAS (including the GCM, PSAS, diagnostics, and interface) per analysis. Therefore, Table 2 indicates that 39/100 × 9.5 × 1011 ≈ 3.7 × 1011 is more like the actual number of flops per analysis for the baseline GEOS-2 PSAS.
3. The Kalman filter
The Kalman filter (Jazwinski 1970; Cohn 1997) assimilates observations sequentially with the model, interpolated to the nearest time step (tk) when they are taken. In this regard, it is like the PSAS with a shortened analysis update cycle:
where the Kalman gain is
where sk observations are assimilated at time tk. For the Kalman filter analysis, the cycle also involves both a model forecast,
and a dynamically consistent forecast of the state error covariance matrix,
where 𝗠k is the tangent-linear model matrix, and 𝗤k is the model (or system) error covariance matrix. The analysis error covariance matrix at the new time tk+1 is
where 𝗜 is the identity matrix. The filter then proceeds sequentially in time through repeated iterations of Eqs. (7)–(11).
A two-dimensional (latitude–longitude) Kalman filter for the assimilation of stratospheric chemical constituents, developed by Lyster et al. (1997a), is being used for scientific study of stratospheric constituent gases (Ménard et al. 2000; Menard and Chang 2000). The dynamical model uses advective transport with a gridpoint-based flux-conserving algorithm (Lin and Rood 1996). The transport is driven by prescribed winds from GEOS DAS. At 2.5° × 2° resolution the number of grid points is n = 91 × 144 = 13 104 and the model time step is 15 min. This was used for the assimilation of retrieved methane from the Cryogenic Limb Array Etalon Spectrometer (CLAES) instrument aboard NASA's Upper Atmosphere Research Satellite (UARS). For CLAES, there were typically pk ≈ 15 observations, per layer, per time step. The Kalman filter achieved 150 days of assimilation per wall-clock day, or 4.1 sustained gigaflop s−1, on 128 processors of the Cray T3E-600 at NASA Goddard Space Flight Center.
For the gridpoint-based horizontal transport that is used for the two-dimensional Kalman filter, the complexity of a single time step of the model, Eq. (9), is hn, where h ≈ 10 − 100 takes into account the size of the finite-difference template. The complexity of Eq. (10) is (2h + 1)n2 per analysis cycle. The Kalman gain, Eq. (8), may be evaluated using a direct solver using 𝒪(p3k) operations. Alternatively, Eqs. (5) and (6) may be employed; their computational complexity was discussed in section 2b. However, the method described in section 2b does not generate the Kalman gain 𝗞k explicitly. The complexity of Eq. (11) is approximately (pk + 1)n2. For the GEOS-2 DAS, observations are aggregated over a 6-h analysis cycle. As described above, the value of pk for the Kalman filter is smaller than for the GEOS-2 DAS by the number of model time steps in 6 h. At baseline resolution for the GCM (2.5° × 2° × 70 layers) the time step of the dynamics is 3 min, so pk is 120 times smaller than for the PSAS. Only small experiments (e.g., pk < 103) could afford to evaluate 𝗞k directly. A Kalman filter or an approximate Kalman filter for a large-scale multivariate meteorological system would have to use an iterative solver, such as the PSAS. The matrices 𝗣f,ak are of size n2, and 𝗛k𝗣fk𝗛Tk + 𝗥k is of size p2k.
A Kalman filter based on a tangent-linear three-dimensional GCM would require considerably more resources than the two-dimensional filter described above for stratospheric analyses. The memory to store the error covariance matrices, 𝗣f,a, would be approximately n2 ≈ 6.8 × 1012 words at the baseline resolution of 2.5° × 2° × 70 levels. The floating-point operations in Eq. (10) are generated by 2n applications of the tangent-linear matrix. Assuming that the resolution and throughput is fixed at that of GEOS-2 DAS, the required operations rate for Eq. (10) would be 2n × 250 megaflop s−1 = 0.5 petaflop s−1 (the value 250 megaflop s−1 is taken from the baseline GEOS-2 DAS in Table 1). This is clearly beyond the reach of current resources. GEOS DAS, with an analysis based on PSAS, is an approximate Kalman filter. Efforts are under way worldwide and at the GMAO to develop computationally feasible improvements to 4DDA algorithms, such as reducing the analysis cycle time for GEOS DAS and developing more physically based error covariance models (Riishøjgaard 1998).
4. The scalable distributed-memory parallel GEOS DAS
The baseline GEOS-2 DAS uses shared-memory multitasking parallelism on Cray J series and SGI Origin computers. A distributed-memory parallel implementation of the GCM was designed (Lyster et al. 1997b) and prototyped (Sawyer and Wang 1999) using the Message-Passing Interface (MPI) and shmem libraries. Distributed-memory parallel PSAS was prototyped (Ding and Ferraro 1995), and an MPI PSAS kernel was developed (Guo et al. 1998; Larson et al. 1998). During the year 2001, development and validation of distributed-memory parallel GEOS DAS was completed. The GCM and PSAS have tightly coupled core algorithms with computation- and communication-intensive parallel implementations; these are hydrodynamic transport (GCM) and nonsparse large matrix–vector multiplications (PSAS; see Fig. 1). We discuss theoretical limits to the development of scalable distributed-memory parallel implementations of the GCM and PSAS. We then describe in terms of the well-known Amdahl's law (1967) how the serial component of the GEOS DAS application impacts scalability. As we developed the distributed-memory parallel application based on GEOS-2 DAS, this limit was the most important in determining the maximum number of processors that can be usefully employed to run the application.
Appendixes A and B quantify the limitations of scalable distributed-memory parallel implementations of the GCM and PSAS, respectively. We focus on the tightly coupled core hydrodynamic transport and nonsparse large matrix–vector multiply algorithms. The parallel speedup (SU), Eq. (A4), is defined as the time to run the application on one processor divided by the time to run it on Np processors. An ideal parallelization would have SU = Np. However, because of a combination of the interprocessor communication overhead and the difficulties in balancing the workload among processors, SU falls increasingly below the ideal linear scaling for an increasing number of processors. We define the maximum number of processors Npmax to be where SU is one-half the ideal value. For gridpoint-based transport algorithms Npmax is given by Eq. (A5). For parameters typical of current global transport algorithms (1° × 1° resolution, using a two-dimensional horizontal parallel domain decomposition, a single-processor speed of 100 megaflop s−1, and an interprocessor communication bandwidth of 10 MB s−1) Eq. (A5) gives Npmax = 400. The parallel matrix–vector multiply at the core of the PSAS distributes the work in matrix–vector blocks across processors and uses collective MPI library routines MPI_reduce_scatter() and MPI_all_gather() (Fig. 1). The maximum speedup is given by Eq. (B3). For typical parameters of the PSAS (p ≈ 105, s = 0.4, f = 10) Npmax is of the order of thousands of processors. Figure 2 shows that the scalability is further limited by load imbalance in the distribution of matrix–vector blocks to the processors.
We have shown that the highly coupled parallel subcomponents of distributed-memory parallel gridpoint GCM and PSAS have upper limits to their scalability in the range 400–1000 processors on SGI Origin 2000 series and similar computers. We have also shown in Tables 2, 3, and 4 that the main subcomponents of the GEOS-2 DAS (dynamical core, moist convection, turbulence, radiation, PSAS solver, PSAS analysis, diagnostics, and interfaces) have an approximately flat timing profile. This means that a large fraction of 150 000 lines of code are candidates for single-processor optimization. In addition to these issues of single-processor optimization and parallel scalability of core algorithms, we have to account for unparallelizable and unparallelized code. Similar to the discussion in section 2c, let u be the serial fraction of GEOS-2 DAS. As above, the speedup (SU) is defined as the time taken to run the application on one processor divided by the time to run it on Np processors. Then
Assuming u ≪ 1, the maximum number of processors— defined as where the speedup is one-half the ideal value—is 1/u, that is, the limit is approximately the inverse of the fraction of the serial time cost of the application; this is a statement of Amdahl's law (1967). For the baseline GEOS-2 DAS, u = 0.006 (section 2c), so the Amdahl's limit on the entire parallel GEOS-2 DAS application is 1.0/0.006 = 166 processors.
This analysis shows that, regardless of how efficiently the core computation- and communication-intensive components of the GCM and PSAS are parallelized, the parallel application based on GEOS-2 DAS will not scale beyond 166 processors. This is due to the small but ultimately significant component of unparallelized and unparallelizable code. Increasing the resolution of the transport algorithm, and using more observations, will improve scalability because there is correspondingly more work to distribute among processors. Efforts to parallelize more of GEOS DAS, as well as single-processor optimization of the serial code, should also increase the scalability of the GEOS DAS application.
5. Summary
We have discussed the computational complexity of the GEOS-2 DAS, which was the baseline production system in use at NASA's Global Modeling and Assimilation Office (GMAO) in the late 1990s. The complexity of the general circulation model (GCM) generally scales linearly with the number of gridded state variables, n, per iteration of the algorithm (with the exception of the quadratic scaling of the radiation algorithms with respect to the number of vertical levels). The need to reduce the time step of the dynamics as the spatial resolution is increased results in an asymptotic n4/3 scaling for the dynamical core for the simulation of fixed time intervals. The Physical-Space Statistical Analysis System (PSAS) has asymptotic scaling sp2 and snp. The former arises from the solver, Eq. (5), and the latter from Eq. (6), the fundamental basis of which is the error correlation between all observations and all gridpoints in an analysis cycle. The computational complexity of the PSAS is reduced by using error correlation models with compact support so that the fraction of nonzero matrix elements is s ≈ 0.4. Other modifications, such as reducing the analysis cycle time, may be used to reduce the computational complexity. We also present a timing profile of the baseline resolution GOES-2 DAS (Tables 1, 2, 3, and 4) on computers with 8 or 10 processors using shared memory parallelism. A simple application of Amdahl's law illustrates how the parallel scaling efficiency is affected by the fraction of unparallelized code. The computational complexity and the required computer memory of the Kalman filter is quadratic in n. We showed, using a simple estimate based on the performance of the GEOS-2 GCM, that a Kalman filter for atmospheric global data assimilation would require petaflop s−1 computing to achieve effective throughput for scientific research. We have developed a computationally tractable Kalman filter suitable for research on stratospheric constituent gas assimilation where the dynamics are two-dimensional. We noted that the development of a full, petaflop s−1 scale, Kalman filter would be an ambitious and scientifically significant exercise, but the main thrust for practical or operational implementations concentrate on approximate Kalman filters with reduced computational complexity.
We developed parameterized formulas that estimate the limit to distributed-memory parallel scalability of the tightly coupled transport and large matrix–vector multiplications, which are important components of the CPU time cost of the gridpoint GCM and PSAS. For SGI Origin 2000 and similar computers the scalability is limited to 400–1000 processors. In addition, the unparallelizable and unparallelized code pose significant limits on the scalability of the end-to-end algorithms. For GEOS-2 DAS the serial fraction (i.e., the fraction of CPU time cost as run on a single processor) is only 0.006. This includes I/O and represents by far the bulk of the lines of code of GEOS-2 DAS. Therefore, the Amdahl's limit of scalability of the distributed-memory parallel implementation of this application is 1/0.006 = 166 processors. This result holds regardless of how efficiently the GCM and PSAS are parallelized. Therefore, efforts to improve the throughput of GEOS DAS necessarily involve efficient parallelization of a very large number of the 150 000 lines of code (aside from the core transport and matrix–vector multiply subcomponents), and improving their serial performance.
The authors acknowledge discussions with Steven Cohn, Anthony Colyandro, Chris Ding, Gregory Gaspari, Dan Kokron, William Sawyer, Harper Pryor, Richard Rood, Meta Sienkiewicz, Lawrence Takacs, Ricardo Todling, and Philip Webster. This work was funded under the NASA High Performance Computing and Communications Initiative (HPCC) Earth and Space Science (ESS) Program Cooperative Agreement NCCS5-150, the NASA EOS Interdisciplinary Science Program, and the NASA Research and Applications Program.
Asymptotic Scalability of Distributed-Memory Parallel Gridpoint General Circulation Models
We calculate the limit on the number of processors that can be usefully employed to reduce the wall-clock time of a distributed-memory parallel-gridpoint-based transport algorithm. In the parallel decomposition, compact domains of grid points and their associated floating-point operations are distributed across processors. The limit on the number of processors is the result of the surface-to-volume effect (e.g., Foster 1995; section 2.4), whereby the impact of communication of domain surface data becomes comparable to the time to perform the floating-point operations of the algorithm. This is an approximation of the scalability in the sense that it does not account for a number of the typical complications that often occur in GCMs, namely:
We are neglecting the algorithms for parameterized physics processes, which include moist convection, turbulence, and radiation; the grid transformations; the diagnostics; and the I/O.
We are not assessing the impact of load imbalance.
We cannot simply account for indeterminacy in communications, such as in semi-Lagrangian methods.
The embarrassingly parallel parts of the GCM (e.g., some algorithms for parameterized physics processes) tend to improve the overall scaling with respect to the present calculation, while load imbalance will tend to make the scaling worse. Other components (e.g., the parallel rotation grid transformation) need a separate analysis (Lyster 2000 and articles therein). The communication of domain surface data enables algorithmic consistency across the boundary between processor domains. The present calculation is very similar to the estimate of parallel scalability of particle-in-cell methods by Lyster et al. (1995), except that case involved communication of mobile particles, which represented plasma ions and electrons, across gridpoint domain boundaries. We assume that the communication time can be approximated in terms of the number of bytes communicated per processor and the bandwidth of the communication channel (i.e., latency effects make the scalability worse, so this approximation is still good in terms of evaluating an upper bound on scalability). With this, the following calculation provides a good approximation for the scalability of the distributed-memory parallel dynamical core of the GEOS GCM.
Define the following:
Np total number of processors employed
Ng total number of grid points in the computational domain
d dimension of the physical problem
D dimension of the parallel decomposition
M single-processor speed in megaflop s−1
B interprocessor communication bandwidth in MB s−1
F number of flops/grid point/time step for the relevant transport algorithm
G the number of "layers" of guard cells in each dimension of the parallel decomposition (e.g., G = 2 for fourth-order finite difference)
P the precision of the calculation in bytes per word (i.e., P = 4 or 8)
Typically D = 1, 2, or 3, and d = 2 or 3, while d ≥ D.
Because it is difficult to parallelize global hydrodynamic algorithms in the vertical dimension, most parallel implementations use a compact horizontal, or "checkerboard," parallel decompositions (i.e., D = 2). It is therefore sufficient to quantify scalability in terms of the number of grid points in the latitude–longitude domain (i.e., horizontal transport), for which d = 2. The number of grid points around the border of each domain is then 2DN(d−1)/dg/N(D−1)/Dp ≡ 2DN1/2g/N1/2p.The communication time per time step per processor is
The CPU time per time step per processor is
Hence the ratio of communication to CPU time is
The parallel speedup (SU) is defined as the time for the application to run on one processor divided by the time to run on Np processors. With the present assumptions, we have
Therefore, we may nominally define the maximum speedup, Npmax as the number of processors for which τ in Eq. (A3) is equal to 1:
Beyond that, the floating-point operations in additional processors are effectively wasted.
The terms in τ may be characterized as follows:
2DGP/F: parameters of the computational algorithm
M/B: parameters of the computer
N1/dg: the problem resolution
N1/Dp: the surface-to-volume effect (i.e., τ gets larger in proportion to the number of processors to some geometry-dependent exponent.)
For parameters typical of current global transport algorithms, Ng = 360 × 181 (i.e., 1° × 1° resolution), d = D = 2, M = 100, B = 10, F = 50, G = 2, and P = 8, so Eq. (A5) gives Npmax = 400.
Asymptotic Scalability of Distributed-Memory Parallel Matrix–Vector Multiply for the PSAS Solver
We calculate the limit on the number of processors that can be usefully employed to reduce the wall-clock time of a distributed-memory dense matrix–vector multiply. The dominant time cost of the PSAS, Eq. (5) and (6), are large, dimension p ≈ 105, matrix–vector multiplications. For the present analysis the results do not differ significantly between the symmetric [Eq. (5)] or rectangular [Eq. (6)] cases since the structure of each dimension of the matrix is determined by a compact spatial decomposition of the multidimensional data (see Guo et al. 1998). We therefore only show the scaling analysis for the symmetric case. Parallelism is achieved by assigning subsets of the matrix–vector multiplication to each processor. The left-hand side of Fig. 1 shows schematic matrix sub-blocks that are distributed among processors (only four are illustrated). Each processor performs matrix–vector multiplies (MatVec) corresponding to its sub-block, thus yielding four partial vectors. The partial vector results are then summed using the MPI_reduce_scatter() library call. The cycle of the parallel matrix–vector multiply is then completed using the MPI_all_gather() library call (not shown in the figure).
Advanced libraries such as PLAPACK (van de Geijn et al. 1997) have custom interfaces and decompositions to support dense matrix–vector operations. We chose not to use this because the more general interface of the MPI library is both simple and compatible with the pointer-specified multidimensional vectors (Larson et al. 1998). Using a 6000-km cutoff length for correlation functions, the matrices are semidense, with density s ≈ 0.4. For the moment, we focus on the limitations on scalability due to the trade-off between communications in the MPI_reduce_scatter() and MPI_all_gather(), and the time cost of the sub-block matrix–vector multiplications. We ignore the costs of the floating-point operations in the reduction. As in appendix A, we ignore the cost of latency in the interprocessor communications.
Assuming that the collective MPI communication calls described above are implemented using an efficient method such as recursive halving (Foster 1995, section 11.2) the cost of communications is
where we have used the same definitions as in appendix A, and p ≈ 105 is the size of the vector. The CPU time per processor is
where, as in section 2b, f equals 2 plus the number of floating-point operations to form each matrix element. The parallel speedup is given by Eq. (A4), and the maximum speedup is defined in the same way as in appendix A:
For typical values for these parameters as defined in appendix A and above, Npmax = 625fs. If the matrix is precalculated, f = 2, but it may be of order 10 when elements are calculated on the fly. Memory limitations prohibit storing entire matrices, so current implementations enable a combination of prestored and on-the-fly calculation of matrix elements. The matrix density is s ≈ 0.4, so it is clear that the upper limit of scalability of semidense matrix–vector multiplications, and hence the PSAS, is of the order of thousands of processors for current generation machines and current input datasets. The value is larger than the upper limit for a GCM because transport algorithms in the dynamical cores of GCMs are sparse matrix algorithms, which have more stringent scalability limits due to the surface-to-volume effect described in appendix A.
The calculation thus far presents an upper limit on scalability. We discuss here a number of factors that reduce the scalability of the PSAS below the theoretical limit. First, on large numbers of processors the size of the vector segments are sufficiently small that message latency and synchronization dominate the communication cost of collective MPI calls. Second, the PSAS has a nested preconditioner that involves successively sparser matrix–vector multiplications (Cohn et al. 1998; Larson et al. 1998). Through Eq. (B3) (i.e., Npmax ∼ s) these will negatively effect scalability. Third, workload imbalance has a serious impact on parallel scalability. The baseline MPI PSAS kernel has an upper limit of 57 600 matrix blocks, which should be sufficient to provide a statistically uniform distribution when their work is allocated across 1000 or 2000 processors (Lyster et al. 2000). However, these blocks are of widely differing size because their dimensions depend on the nonrepeatable distribution of observations in geographical areas of the earth. Early versions of the kernel used a method for load balancing that based the costs of the block matrix–vector multiplications on the dimensions of the blocks. This was later augmented, with only incremental improvement in scalability, by dynamic scheduling and work scheduling based on statistically tuned cost estimates. The lower curve of Fig. 2 (from Lyster et al. 2000). shows the scaling of the baseline MPI PSAS kernel, including the load-balancing algorithm for 52 738 observations covering a standard 6-h analysis cycle. The poorer scaling relative to the above calculation is from a combination of load imbalance and sparse preconditioners; using s = 0.1 and f = 5 in Eq. (B3) gives Npmax = 312, which is in line with Fig. 2. The lower curve in Fig. 2 corresponds to the case of approximately 57 600s blocks. The improved scaling shown in the upper curve of the figure corresponds to the improved load balance that resulted from a refinement to 921 600s blocks. The value of the improved scaling at 256 processors was not obtained due to restricted availability of the computer at the time of the experiments. However, from the scaling up to 128 processors it is clear that the MPI PSAS kernel did not reach the theoretical limit that had been expected from the above calculation. Apart from our work on load-balancing algorithms, we have developed and continue to work on collective parallel algorithms using optimized communication procedures.
Additional affiliation: Earth System Science Interdisciplinary Center, and Department of Meteorology, University of Maryland, College Park, College Park, Maryland
Additional affiliation: Science Applications International Corporation/General Sciences Operation, Beltsville, Maryland
Additional affiliation: Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois
Corresponding author address: Dr. Peter M. Lyster, National Institutes of Health, Bethesda, MD 20892. Email: email@example.com
More recent versions of GEOS DAS have a horizontal resolution of 5 × 104 and 2.5 × 104 m.
The numbers in this paper were obtained on an Origin 2000 with 64 processors and 16 GB of memory at NASA Ames Research Laboratory. Other numbers were obtained for a Cray J916 with 16 processors and 2 GB of memory at NASA Goddard Space Flight Center.


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Data Availability StatementThe datasets used during the present research are available through the corresponding writer upon reasonable demand. expected that miR-573 interacts with SNHG1. RT-PCR verified the negative rules of miR-573 amounts by SNHG1 in breasts cancer cells as well as the Dual-luciferase reporter assay verified their complementary binding. The repression of miR-573 by SNGH1 reduced LIM domain just 4 (LMO4) mRNA and proteins expression amounts in the breasts tumor cell lines examined and induced the manifestation of cyclin D1 and cyclin E. tests indicated that LMO4 overexpression could invert siSNHG1-induced cell development arrest, cell routine inhibition and redistribution of DP2.5 cell migration in breasts tumor cells. Furthermore, the tumor xenograft model indicated that SNHG1 knockdown inhibited MDA-MB-231 development and LMO4 overexpression reversed the tumor development inhibition induced by SNHG1 knockdown. Today's research proven that SNHG1 functions as a book oncogene in breasts tumor via the SNHG/miR-573/LMO4 axis which maybe it's a promising restorative target for individuals with breast 1143532-39-1 tumor. assays. Furthermore, SNHG1 knockdown inhibited MDA-MB-231 tumor development mRNA manifestation in breast tumor tumor tissues. Today's findings exposed an oncogenic part of SNHG1 in breasts cancer and recommended that it could promote cell proliferation and cell routine development via the miR-573/LMO4 axis. Components and strategies Bioinformatic evaluation Bioinformatic evaluation of SNHG1 manifestation was performed in 1,063 breast cancer cases and 102 normal breast cases using the Human Cancer Metastasis Database (HCMDB, http://hcmdb.i-sanger.com/). The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) dataset was selected. The prediction of the potential binding site between miR-573 and SNHG1 and LMO4 was carried out by miRDB (http://www.mirdb.org/) and miRanda software (http://www.microrna.org). The PROGgeneV2 (http://genomics.jefferson.edu/proggene/index.php) was used to study the association between LMO4 expression and the overall survival of patients with breast cancer based on the "type":"entrez-geo","attrs":"text":"GSE42568″,"term_id":"42568″GSE42568 dataset (28). Human tissue samples Human breast cancer tumor tissues and matched normal breast tissues were collected from 50 patients with breast cancer at The Second Xiangya Hospital of Central South University from June 2014 to July 2017. All tissues were obtained following surgery of primary breast cancer tumors and were immediately frozen in liquid nitrogen for subsequent experiments. Prior to project initiation, written informed consent was provided by all patients enrolled in the present study and the experimental procedures were conducted under the supervision of the Ethics Committee of the Second Xiangya Hospital of the Central South University. The protocol of the experiments was approved by the Ethics Committee of the next Xiangya Hospital from the Central South College or university (authorization no. 2014S057). Cell tradition 293 cells, the human being breasts epithelial cell range MCF10A, the human being ER+ breast cancers cell lines MCF7, and T47D, as well as the human being triple-negative breast cancers (TNBC) cell lines (ER?/PR?/Her2?) MDA-MB-231 and MDA-MB-468 had been purchased through the American Type Tradition Collection (ATCC). The cell lines had been used within six months pursuing receipt. MCF10A cells had been cultured in Mammary Epithelial Cell Development Moderate (MEGM; Lonza) supplemented with 100 ng/ml cholera toxin (Sigma-Aldrich; Merck KGaA). 293, MCF7 and T47D cells had been cultured in RPMI-1640 moderate (Gibco; Thermo Fisher Scientific, Inc.) supplemented with 10% FBS (HyClone; GE Health care). MDA-MB-231 and MDA-MB-468 cells had been taken care of in DMEM (Gibco; Thermo Fisher Scientific, Inc.) containing 10% FBS (HyClone; GE Health care). All cell lines had been cultured inside a humidified incubator with 5% CO2. Plasmid building and cell transfection The entire amount of the 1143532-39-1 1143532-39-1 LMO4 open up reading framework was amplified through the cDNA of 293 cells and 1143532-39-1 ligated right into 1143532-39-1 a pcDNA3.1 plasmid. Plasmid transfection was performed using Lipofectamine 3000 (Invitrogen; Thermo Fisher Scientific, Inc.) based on the producer protocol. SNHG1 control and siRNA siRNA were purchased.
Category Archives: Autophagy
Supplementary MaterialsZBTB7A prevents clonal expansion_Supplementary Information 41388_2020_1209_MOESM1_ESM
Supplementary MaterialsZBTB7A prevents clonal expansion_Supplementary Information 41388_2020_1209_MOESM1_ESM. clonal expansion of human CD34+ cells, whereas the outgrowth of progenitors is enabled by ZBTB7A mutation. Finally, ZBTB7A expression in t(8;21) cells lead to a cell cycle arrest that could be mimicked by inhibition of glycolysis. Our findings suggest that loss of ZBTB7A may facilitate the onset of AML t(8;21), and that RUNX1-RUNX1T1-rearranged leukemia might be treated with glycolytic inhibitors. alterations with the t(8;21) subgroup of AML patients points toward a unique mechanism of leukemogenesis. While the RUNX1CRUNX1T1 fusion gene, which results from the t(8;21) translocation, has been studied extensively, it remains unclear how it may provide a fertile ground for the acquisition of genetic lesions in ZBTB7A. This oncogenic collaboration may arise from a complementary action on perturbed hematopoietic development (i.e., block of specific arms of the myeloid lineage). Expression of full length RUNX1CRUNX1T1 in a murine model does not cause leukemia [7, 8], but causes a partial block of myeloid differentiation with suppression of erythropoiesis and accumulation of immature granulocytes [9]. Interestingly, Zbtb7a has been described as a key regulator of hematopoietic differentiation with an essential role in erythropoiesis [10], lineage choice of B vs T lymphopoiesis [11] and long-term stem cell maintenance [12]. The involvement of ZBTB7A in myeloid differentiation has so far not been completely clarified, although null mouse studies showed a deficiency of mature myeloid cells in fetal liver [12]. This suggests that mutation could lead to a block of terminal myeloid purchase BSF 208075 differentiation, collaborating with purchase BSF 208075 RUNX1CRUNX1T1 to produce a complete differentiation block. Another way in which ZBTB7A mutation may collaborate with RUNX1CRUNX1T1 is related to growth regulation and metabolism. While expression of RUNX1CRUNX1T1 in stem cells causes increased proliferation [13], expression in myeloid cell lines results in growth arrest. This development arrest relates to downregulation of [14] and [15]a get better at regulator of glycolysis and an integral enzyme from the glycolytic pathway, respectively. Furthermore, AML t(8;21) continues to be described to depend on glycolytic rate of metabolism for its success [16]. Subsequently, ZBTB7A can straight repress the transcription PSTPIP1 of many genes implicated in glycolysis (and within an worth?=?0.0002) (Supplementary Fig. 1e). We also noticed that ZBTB7A WT manifestation result in a lack of transduced cells in HL60 without cell sorting (Fig. ?(Fig.1d1d). Open up in another home window Fig. 1 ZBTB7A promotes granulopoiesis while obstructing monocytic differentiation.a HL60 cells stably expressing a clear purchase BSF 208075 vector (EV), ZBTB7A mutants or WT were differentiated by ATRA treatment. Compact disc11b manifestation was evaluated by movement cytometry. b HL60 cells expressing ZBTB7A WT or mutants had been differentiated by PMA treatment stably. Compact disc14 manifestation was evaluated by movement cytometry. c HL60 ZBTB7A KO and HL60 ZBTB7A KO expressing ZBTB7A WT or mutants without induction of differentiation stably. Compact disc14 manifestation was evaluated by movement cytometry. d Competitive development of HL60 cells expressing ZBTB7A WT or mutants stably. e Traditional western blot from K562 cells, arrow shows low degrees of the ZBTB7A A175fs mutant. f K562 ZBTB7A KO without induction of differentiation. Compact disc235a manifestation was evaluated by movement cytometry. *worth? ?0.05 weighed against control cells. Since ZBTB7A was referred to to market erythroid differentiation [10] previously, we produced a K562 knockout cell range (Fig. ?(Fig.1e).1e). K562 cells could be used like a model for erythroid differentiation [20]. Needlessly to say, knockout K562 cells shown a lesser erythroid differentiation (13.89??2.8% reduction, value?=?0.0238) in comparison to control cells (Fig. ?(Fig.1f,1f, Supplementary Fig. 1f). This impaired differentiation could possibly be rescued by ectopic manifestation of ZBTB7A WT however, not from the mutants (Fig..


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嵐冴科同鞠村 廣過
巓仞 08-04
Then, when they had finished their work and the meal was ready, theyate it, and every man had his full share so that all were satisfied.As soon as they had had enough to eat and drink, they laid down torest and enjoyed the boon of sleep.
樅社凍 08-04
"We will be sure, sir," answered Telemachus, "to tell him everythingas soon as we see him. I wish I were as certain of finding Ulyssesreturned when I get back to Ithaca, that I might tell him of thevery great kindness you have shown me and of the many beautifulpresents I am taking with me."
装勸 08-04
"Menelaus," replied Telemachus, "I want to go home at once, for whenI came away I left my property without protection, and fear that whilelooking for my father I shall come to ruin myself, or find thatsomething valuable has been stolen during my absence."
濫苧橦 08-04
When it was time for them to start home, and they were folding theclothes and putting them into the waggon, Minerva began to considerhow Ulysses should wake up and see the handsome girl who was toconduct him to the city of the Phaeacians. The girl, therefore,threw a ball at one of the maids, which missed her and fell intodeep water. On this they all shouted, and the noise they made wokeUlysses, who sat up in his bed of leaves and began to wonder what itmight all be.
雨猫苧 08-03
{ "So they did as I told them; but I said nothing about the awfulmonster Scylla, for I knew the men would not on rowing if I did, butwould huddle together in the hold. In one thing only did I disobeyCirce's strict instructions- I put on my armour. Then seizing twostrong spears I took my stand on the ship Is bows, for it was therethat I expected first to see the monster of the rock, who was to do mymen so much harm; but I could not make her out anywhere, though Istrained my eyes with looking the gloomy rock all over and over
装纛歎 08-02
"Meanwhile Menelaus and I were on our way home from Troy, on goodterms with one another. When we got to Sunium, which is the point ofAthens, Apollo with his painless shafts killed Phrontis thesteersman of Menelaus' ship (and never man knew better how to handle avessel in rough weather) so that he died then and there with thehelm in his hand, and Menelaus, though very anxious to pressforward, had to wait in order to bury his comrade and give him his duefuneral rites. Presently, when he too could put to sea again, andhad sailed on as far as the Malean heads, Jove counselled evil againsthim and made it it blow hard till the waves ran mountains high. Herehe divided his fleet and took the one half towards Crete where theCydonians dwell round about the waters of the river Iardanus. There isa high headland hereabouts stretching out into the sea from a placecalled Gortyn, and all along this part of the coast as far as Phaestusthe sea runs high when there is a south wind blowing, but arterPhaestus the coast is more protected, for a small headland can makea great shelter. Here this part of the fleet was driven on to therocks and wrecked; but the crews just managed to save themselves. Asfor the other five ships, they were taken by winds and seas toEgypt, where Menelaus gathered much gold and substance among people ofan alien speech. Meanwhile Aegisthus here at home plotted his evildeed. For seven years after he had killed Agamemnon he ruled inMycene, and the people were obedient under him, but in the eighth yearOrestes came back from Athens to be his bane, and killed themurderer of his father. Then he celebrated the funeral rites of hismother and of false Aegisthus by a banquet to the people of Argos, andon that very day Menelaus came home, with as much treasure as hisships could carry.}
娉蝶吞 08-02
The immortal gods burst out laughing as they heard him, butNeptune took it all seriously, and kept on imploring Vulcan to setMars free again. "Let him go," he cried, "and I will undertake, as yourequire, that he shall pay you all the damages that are heldreasonable among the immortal gods."
潜酵俛 08-02
"Here I am, my dear sir," said he, "stay your hand therefore, andtell your father, or he will kill me in his rage against the suitorsfor having wasted his substance and been so foolishly disrespectful toyourself."
鮭伸猟 08-01
Meanwhile the suitors were throwing discs or aiming with spears at amark on the levelled ground in front of Ulysses' house, and werebehaving with all their old insolence. Antinous and Eurymachus, whowere their ringleaders and much the foremost among them all, weresitting together when Noemon son of Phronius came up and said toAntinous,
蛎囁漂 07-30
{ "'You will find the other rocks lie lower, but they are so closetogether that there is not more than a bowshot between them. [Alarge fig tree in full leaf grows upon it], and under it lies thesucking whirlpool of Charybdis. Three times in the day does shevomit forth her waters, and three times she sucks them down again; seethat you be not there when she is sucking, for if you are, Neptunehimself could not save you; you must hug the Scylla side and driveship by as fast as you can, for you had better lose six men thanyour whole crew.'
仔白 07-30
Ulysses was glad when he found he had a friend among the lookers-on,so he began to speak more pleasantly. "Young men," said he, "come upto that throw if you can, and I will throw another disc as heavy oreven heavier. If anyone wants to have a bout with me let him comeon, for I am exceedingly angry; I will box, wrestle, or run, I donot care what it is, with any man of you all except Laodamas, butnot with him because I am his guest, and one cannot compete with one'sown personal friend. At least I do not think it a prudent or asensible thing for a guest to challenge his host's family at any game,especially when he is in a foreign country. He will cut the groundfrom under his own feet if he does; but I make no exception as regardsany one else, for I want to have the matter out and know which isthe best man. I am a good hand at every kind of athletic sport knownamong mankind. I am an excellent archer. In battle I am always thefirst to bring a man down with my arrow, no matter how many more aretaking aim at him alongside of me. Philoctetes was the only man whocould shoot better than I could when we Achaeans were before Troyand in practice. I far excel every one else in the whole world, ofthose who still eat bread upon the face of the earth, but I should notlike to shoot against the mighty dead, such as Hercules, or Eurytusthe Cechalian-men who could shoot against the gods themselves. This infact was how Eurytus came prematurely by his end, for Apollo was angrywith him and killed him because he challenged him as an archer. Ican throw a dart farther than any one else can shoot an arrow. Runningis the only point in respect of which I am afraid some of thePhaecians might beat me, for I have been brought down very low at sea;my provisions ran short, and therefore I am still weak."


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Tri-State Fertilizer Recommendations for Corn, Soybeans, Wheat, and Alfalfa
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milk checks. The Coronavirus Food Assistance Program (CFAP) was developed to provide farms that have ... assistance. The intent of this program is to directly assist farms impacted by the effects of the COVID-19 ... not have participated in a program before to learn more about and apply for this program designed to ...
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EPN Virtual Event- August 11, 2020 Talking Trash: A Primer on Central Ohio's Waste Stream
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text: Becca Shern of Minimal Wellness shares her reflection on emotional nourishment. Episode 833: A Reflection on Emotional Nourishment by Becca Shern of Minimal Wellness on How To Create Sustainable Habits Becca Shern is the founder of MinimalWellness.com and is a Registered Dietitian, foodie, wellness nerd, recreational athlete, and mom. She started Minimal Wellness to help people find, navigate, and enjoy the simple path to optimal health. Eliminating the "junk" (foods, advice, stuff, excuses, distractions) helps us focus on the critical components of wellness, enabling us to be healthier, happier, and more fulfilled. Find more information about her at MinimalWellness.com. The original post is located here: http://minimalwellness.com/emotionalnourishmentreflection/ Please Rate & Review the Show! Visit Me Online at OLDPodcast.com and in The O.L.D. Facebook Group --- Support this podcast: https://anchor.fm/optimal-health-daily/support


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Best Books 2015: Outreach Resources of the Year
Outreach magazine's 12th annual celebration of the best books and media in evangelism, apologetics, leadership and more.
6 Keys to Raising Spiritually Mature Teens
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Crossing Bridges and Breaking Down Barriers
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Glenn Daman: The Forgotten Church
Why Rural Ministry Matters for Every Church in America
Advocating for Justice That Restores
We need to take another look at our prison system and our astronomical rates of incarceration.
Inspirational: 13th Annual Outreach Resources of the Year
Carlos Darby: Experience Jesus
Sharing Jesus Without Freaking Out
Evangelism the Way You Were Born to Do It
The Quiet Practice of Solitude and Secrecy
Solitude is uncomfortable and takes practice. That's OK. It's worth it to cultivate intimacy with God.
Why We Can't Ignore the Past
No matter our individual intentions, the past informs the way we relate with other ethnicities today.
Outreach Magazine Names Resources of the Year
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Filed under: Ensign, Quentin L. Cook, Quorum of the Twelve | Tagged: Apostle, article, Ensign, Latter-day Saints, lds, magazine, mormon, mormons, Quentin L. Cook, Quorum of the Twelve | 3 Comments »
Elder Quentin L. Cook—A Willing Heart and Mind
Come unto Christ
"We sometimes speak of retaining members as if we held them in. We can and we must be a friend to those who have made the choice to come unto Him. They can become discouraged when trials come, as trials always do. Yet we must remember that the best and surest friends they have are the Savior and His Father, who is also their Father. Heavenly Father and the Savior will send them the Holy Ghost to comfort them and confirm their faith if they are humbly obedient."
Filed under: doctrine, Ensign, First Presidency, Henry B. Eyring | Tagged: article, Christ, doctrine, Ensign, Henry B. Eyring, Holy Ghost, Jesus, Jesus Christ, Latter-day Saints, lds, magazine, missionary work, mormon, mormons, retention, Spirit | Leave a comment »
Ensign Promotional Video
The Church magazines have posted this promotional video on their Web site at SpecialMagazine.lds.org. It gives a good overview of the March 2008 special issue of the Ensign. The voiceover simply reads quotes from some of the articles in the issue, but it hangs together so well that it could stand on its own as a statement of our beliefs about the Savior. Check it out. You can download it in a couple of different formats and sizes.
Filed under: Ensign | Tagged: article, Christ, Ensign, Jesus, Jesus Christ, Latter-day Saints, lds, magazine, mormon, mormons | 1 Comment »
Was I Saved?
Another good article from this month's special issue of the Ensign is one that describes a situation that many Church members may find themselves in at some time or other. "Was I Saved" is one young woman's account of her visit to a friend's church meeting and her subsequent confusion about whether she really needed to publicly accept Jesus in the manner prescribed there. This article teaches us two things: (1) we should prepare people we invite to our meetings for the things that might be unfamiliar to them, and (2) we Mormons have no reason to doubt whether we've been "saved" or have done everything necessary to accept Christ. The article also refers to a good talk by Elder Oaks on this subject.
Filed under: doctrine, Ensign | Tagged: article, Christ, doctrine, Ensign, Jesus, Jesus Christ, Latter-day Saints, lds, magazine, mormon, mormons, salvation, saved | 4 Comments »
We Believe
The March 2008 Ensign, a special issue on the Lord Jesus Christ, contains an FAQ article regarding Latter-day Saint beliefs about the Savior. "We Believe," which is also available on the new Web site JesusChrist.lds.org, briefly answers questions ranging from the historical Jesus, to the Resurrection, to the role of grace in salvation, to the relative importance of Joseph Smith. Though the article cannot delve too deeply into any of these questions, the answers are straightforward and more than satisfactory explanations of Latter-day Saint doctrine on key questions of our faith.
Filed under: Ensign | Tagged: answers, article, Christ, doctrine, Ensign, Jesus, Latter-day Saints, lds, magazine, mormon, mormons, questions | 2 Comments »
New Era Cover Boy Gets TV Spotlight
We Testify of Jesus Christ
Filed under: Ensign, First Presidency, Gordon B. Hinckley | Tagged: article, Christ, Ensign, Gordon B. Hinckley, Jesus, lds, magazine, mormon, mormons, testimony | 4 Comments »
Helping Children Cope with Traumatic Situations
This month's Ensign has an article with help for families that have experienced some sort of trauma. In "Helping Children Cope with Traumatic Situations," a mother tells how a family crisis involving her newborn daughter affected her two-year-old son. She talks about the complex emotions and behaviors her son exhibited after this traumatic situation, as well as the changes she noticed in herself. This article is noteworthy because it highlights the importance of the gospel in family life and also gives solid practical advice for dealing with difficult situations. Following this story, LDS Family Services gives further information in a piece called "About Trauma," which includes symptoms and additional helps.
Filed under: Ensign, family | Tagged: article, Ensign, family, lds, magazine, mormon, mormons, trauma | Leave a comment »
Face Trials with Smiles
If you want to get to know one of the most genuinely good guys out there, read "Face Trials with Smiles" in this month's New Era. It's about Porter Ellett of Loa, Utah, a young man who lost his right arm in an accident when he was four years old but hasn't let it slow him down a bit. He is a great athlete and has a great attitude. To see pictures of him in action, read the PDF version of the article.
Filed under: New Era | Tagged: article, lds, magazine, mormon, mormons, New Era, teenagers, teens | 2 Comments »
Dating and the Eternal Perspective
No, this has nothing to do with eternal dating. "Dating and the Eternal Perspective" is the latest in a string of Ensign articles for young single adults. This one contrasts the world's ways with the Lord's ways when it comes to attitudes and behaviors related to dating, courtship, and marriage. It contains a remarkable number of quotes from General Authorities on these subjects, as well as personal stories from young adults who have had a variety of experiences in the dating arena. Here's a statement I find to be true: "Humility will help us accept the Lord's timetable when the opportunity for marriage comes sooner, as well as later, than anticipated." (For me, it was sooner.) This article has much to recommend it, and I wouldn't be surprised if it's being recommended by many singles ward bishops right now.
Filed under: Ensign, Young Single Adults | Tagged: article, dating, Ensign, lds, magazine, mormon, mormons, singles, Young Single Adults | 4 Comments »


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more than
Min CTC.
Min CTC.
Scaler Academy Review By Joydeep
Scaler Academy is the best learning experience you can have as an aspiring software engineer.
Joydeep Mukherjee
Scaler Academy is the best learning experience you can have as an aspiring software engineer.
I'm Joydeep Mukherjee (Scaler, 2020 Graduate, Google Summer of Code 2018, 2019, Former product manager at RodoIndia). I got to know about Scaler Academy from Charan (Another Scaler & former co-worker at RodoIndia, placed at Amazon). I gave the entrance test & got selected for June Batch. I believe that was the best thing in 2019. Dynamic Programming, Segment Trees, Lazy Propagation, Sorting, Searching, Two Pointers, Greedy, Advanced Object-Oriented Programming, Low-Level Design, System Design (Super Important & Super well taught), DOM, Bash, Version Control, AJAX, JSON, NoSQL, API, ECMAScript, IronMan Suit(Pretty sure people at Scaler can). You name it scaler has it. Honestly, I wasn't much into competitive coding, but after scaler, I'm not afraid. Being a backend developer I already had experience with Amazon Web Services, MongoDB, NodeJS & React. I chose the Fullstack Developer path after getting a personal call from Abhimanyu Sir himself & IMO got to learn so many more concepts though I had a pretty decent knowledge of this stuff. Even though Scaler gives you a job guarantee, I believe the result doesn't matter. What matters is the experience you will get at Scaler. From weekly 1-1 sessions with mentors, company mock interviews, daily classes & ta sessions each spanning well over several hours, will make anyone a 10x engineer.Next Story >


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get directions Kelly Apartments
133 Jpm Rd
Lewisburg, PA 17837
133 Jpm Rd
Lewisburg, PA 17837
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