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Reliable methods for detecting and analyzing gene expression are necessary tools for understanding development and investigating biological responses to genetic and environmental perturbation. With its fully sequenced genome, invariant cell lineage, transparent body, wiring diagram, detailed anatomy, and wide array of genetic tools, Caenorhabditis elegansis an exceptionally useful model organism for linking gene expression to cellular phenotypes. The development of new techniques in recent years has greatly expanded our ability to detect gene expression at high resolution. Here, we provide an overview of gene expression methods for C. elegans, including techniques for detecting transcripts and proteins in situ, bulk RNA sequencing of whole worms and specific tissues and cells, single-cell RNA sequencing, and high-throughput proteomics. We discuss important considerations for choosing among these techniques and provide an overview of publicly available online resources for gene expression data.

IMPORTANCE: In clinical trials, preoperative immune checkpoint inhibitors (ICIs) have shown clinical activity in advanced cutaneous squamous cell carcinoma (cSCC). However, these studies excluded patients with relevant comorbidities. OBJECTIVE: To evaluate radiologic and pathologic response rates to neoadjuvant-intent programed cell death protein 1 (PD-1) ICIs in a clinical population. DESIGN, SETTING, AND PARTICIPANTS: This cohort study of patients who were treated with neoadjuvant cemiplimab or pembrolizumab for advanced cSCC from January 2018 to January 2023 was conducted at 2 academic institutions in Boston, Massachusetts. Median follow-up was 9.5 months (range, 1.2-40.5). EXPOSURES: Cemiplimab or pembrolizumab. MAIN OUTCOMES AND MEASURES: Primary outcomes were radiologic and pathologic response rates. Secondary outcomes were 1-year recurrence-free survival, progression-free survival, disease-specific survival, and overall survival. RESULTS: This cohort study included 27 patients (including 9 patients [33.3%] with a history of lymphoma). Most patients were male (18 of 27 [66.7%]), with a median age of 72 years (range, 53-87 years). Most primary tumors were located on the head/neck (21 of 27 [77.8%]). There were no unexpected delays in surgery. The median number of doses before surgery was 3.5 (range, 1.0-10.0). Five patients (18.5%) ultimately declined to undergo planned surgery due to clinical responses or stability, and 1 (3.7%) did not undergo surgery due to progressive disease. The overall pathologic response rate (pathological complete response [pCR] or major pathological response) was 47.4% (9 of 19), and the overall radiologic response rate (radiologic complete response or partial response) was 50.0% (8 of 16). The pCR rate (7 of 19 [36.8%]) was higher than the radiologic complete response rate (2 of 16 [12.5%]). The pCR rate among patients with cSCC and concomitant lymphoma was 25.0%. The 1-year recurrence-free survival rate was 90.9% (95% CI, 50.8%-98.7%), progression-free survival was 83.3% (95% CI, 27.3%-97.5%), disease-specific survival was 91.7% (95% CI, 53.9%-98.8%), and overall survival was 84.6% (95% CI, 51.2%-95.9%). CONCLUSIONS AND RELEVANCE: The results of this cohort study support the reproducibility of neoadjuvant-intent immunotherapy for cSCC in the clinical setting, including for patients with a history of lymphoma. Outside of clinical trials, it is not infrequent for patients to opt out of surgery for regressing tumors. The inclusion of higher-risk patients and preference for nonsurgical treatment are 2 factors that might explain the numerically lower pathologic response rate in this institutional experience.

Despite the success of PD-1 blockade in melanoma and other cancers, effective treatment strategies to overcome resistance to cancer immunotherapy are lacking1,2. Here we identify the innate immune kinase TANK-binding kinase 1 (TBK1)3as a candidate immune-evasion gene in a pooled genetic screen4. Using a suite of genetic and pharmacological tools across multiple experimental model systems, we confirm a role for TBK1as an immune-evasion gene. Targeting TBK1 enhances responses to PD-1 blockade by decreasing the cytotoxicity threshold to effector cytokines (TNF and IFNγ). TBK1 inhibition in combination with PD-1 blockade also demonstrated efficacy using patient-derived tumour models, with concordant findings in matched patient-derived organotypic tumour spheroids and matched patient-derived organoids. Tumour cells lacking TBK1 are primed to undergo RIPK- and caspase-dependent cell death in response to TNF and IFNγ in a JAK–STAT-dependent manner. Taken together, our results demonstrate that targeting TBK1 is an effective strategy to overcome resistance to cancer immunotherapy.

Oncolytic viruses (OVs) are an emerging class of cancer therapeutics that offer the benefits of selective replication in tumour cells, delivery of multiple eukaryotic transgene payloads, induction of immunogenic cell death and promotion of antitumour immunity, and a tolerable safety profile that largely does not overlap with that of other cancer therapeutics. To date, four OVs and one non-oncolytic virus have been approved for the treatment of cancer globally although talimogene laherparepvec (T-VEC) remains the only widely approved therapy. T-VEC is indicated for the treatment of patients with recurrent melanoma after initial surgery and was initially approved in 2015. An expanding body of data on the clinical experience of patients receiving T-VEC is now becoming available as are data from clinical trials of various other OVs in a range of other cancers. Despite increasing research interest, a better understanding of the underlying biology and pharmacology of OVs is needed to enable the full therapeutic potential of these agents in patients with cancer. In this Review, we summarize the available data and provide guidance on optimizing the use of OVs in clinical practice, with a focus on the clinical experience with T-VEC. We describe data on selected novel OVs that are currently in clinical development, either as monotherapies or as part of combination regimens. We also discuss some of the preclinical, clinical and regulatory hurdles that have thus far limited the development of OVs.

The C. elegansnervous system is compact and well described, ideal for identifying genetic programs that drive neuron-specific development, function, and connectivity. Here, we present a protocol for isolating specific neuron types for gene expression profiling by bulk or single-cell RNA sequencing. We describe steps for worm synchronization, dissociation, and fluorescence-activated cell sorting (FACS) isolation. We then detail procedures for RNA extraction and preparing cells for single-cell sequencing. This protocol is applicable to the isolation of individual cell types from larval and adult animals.

Merkel cell carcinoma (MCC) is a very rare but highly aggressive cutaneous neuroendocrine carcinoma and is associated with chronic exposure to ultraviolet light and the Merkel cell polyoma virus. The incidence rate of MCC is increasing and MCC is associated with high rates of recurrence and mortality. Immune checkpoint inhibitors (ICIs) offer durable responses and significant clinical benefit with 2 agents-avelumab (anti-PD-L1) and pembrolizumab (anti-PD-1)—currently approved by the U.S. Food and Drug Administration for the treatment of advanced MCC. Despite the advances in systemic therapy options for MCC, ~50% of patients with advanced MCC treated with ICI progress on therapy. There is a paucity of studies assessing second-line systemic therapy following primary/acquired resistance to ICIs. Current management in this setting remains a clinical challenge especially in trial ineligible patients. We evaluated objective response to ipilimumab plus nivolumab in metastatic MCC refractory to anti-PD-(L)1 therapy. Thirty-one percent of patients experienced a grade III or grade IV immune-related adverse event (irAE) due to ipilimumab plus nivolumab. No patients (0/13) achieved a complete or partial response via RECISTv1.1/irRECIST. Twenty-three percent (3/13) of patients achieved stable disease as the best overall response but progressed shortly thereafter. The median progression-free survival was 1.3 months (90% CI 1.1–1.5) from the initiation of ipi-nivo. The median overall survival was 4.7 months (95% CI 3–17). This study suggests limited, if any, clinical benefit of ipi-nivo in patients with advanced anti-PD-L1/anti-PD-1 refractory MCC.

High demand for soil organic carbon data to support soil health and climate change mitigation efforts must be met with rapid, accurate, and inexpensive measurement methods. Mid-infrared spectroscopy shows promise as an alternative to conventional soil carbon analysis; however, its practicality depends on the construction and efficient use of soil spectral libraries. Subsetting, a calibration optimization technique, has potential to reduce model prediction errors. Nevertheless, the effectiveness of different subsetting criteria has yet to be well explored. This study assessed whether several subsetting criteria would result in calibration models with reduced error in the prediction of soil organic carbon content compared to models constructed from a full spectral dataset. A mid-infrared spectral library composed of Nebraska and Kansas soil samples was subset by (i) a nested wetland criterion, (ii) soilscapes, (iii) presence or absence of carbonates, and (iv) a combination of soilscape and carbonates. Partial least squares regression was used to construct all calibration models. Predictive performance of the subset models was compared to that of their corresponding full set model using several statistical metrics. Subsetting by wetlands reduced model error by 22 and 56 %. Subsetting by soilscape yielded a 13 to 55 % reduction in model error, while presence or absence of carbonates reduced model error by 21 and 46 %. Five of the eight combination soilscape and carbonate subset models reduced model error by 14 to 51 %. Overall, subsetting by soilscape or carbonate presence proved effective in improving model performance, with combination subsets proving beneficial under specific calibration set conditions.

Resource‐efficient techniques for accurate soil property estimation are necessary to satisfy the increasing demand for soil data to support environmental monitoring, precision agriculture, and spatial modeling. Over the last 30 yr, infrared soil spectroscopy has developed into a rapid, robust, and cost‐effective technique for soil carbon analysis. Ongoing global efforts to make soil spectroscopy operational require the development of soil spectral libraries, which are the main source of data for the construction of calibration models. Understanding calibration optimization is important to ensure the efficient use of soil spectral libraries for the accurate estimation of soil carbon. Moreover, spectral library transfer can benefit new data collection, soil monitoring, and modeling efforts. This review presents techniques for optimization of calibration models and library transfer. Selection of calibration set size and subsetting are presented as current calibration optimization techniques. Moreover, spiking is discussed as an effective technique for spectral library transfer. Overall, studies have suggested that an increase in calibration size improves model performance and this continues until an optimal size is reached. Additionally, subsetting can improve model performance if the resulting subsets reduce the variability of spectrally active components. Studies have also suggested that spiking is effective when used in conjunction with subsetting techniques. These findings denote the current applicability and potential of optimization and library transfer techniques for the accurate estimation of soil carbon with soil spectroscopy. Future efforts should focus on refining optimization techniques to further expand the operability of soil spectroscopy for soil carbon estimation. Effective optimization routines increase representativeness of a calibration set to unknowns.Subsetting by spectral similarity and local calibrations improve model accuracy.Spiking with subsetting for library transfer can improve model accuracy.

Motor neurons (MNs) constitute an ancient cell type targeted by multiple adult-onset diseases. It is therefore important to define the molecular makeup of adult MNs in animal models and extract organizing principles. Here, we generate a comprehensive molecular atlas of adult Caenorhabditis elegansMNs and a searchable database. Single-cell RNA sequencing of 13,200 cells reveals that ventral nerve cord MNs cluster into 29 molecularly distinct subclasses. Extending C. elegansNeuronal Gene Expression Map and Network (CeNGEN) findings, all MN subclasses are delineated by distinct expression codes of either neuropeptide or transcription factor gene families. Strikingly, combinatorial codes of homeodomain transcription factor genes succinctly delineate adult MN diversity in both C. elegansand mice. Further, molecularly defined MN subclasses in C. elegansdisplay distinct patterns of connectivity. Hence, our study couples the connectivity map of the C. elegansmotor circuit with a molecular atlas of its constituent MNs and uncovers organizing principles and conserved molecular codes of adult MN diversity.

The article examines the use of potential expert systems for productivity management at different stages of analysis. Findings show that expert systems applications can be helpful in evaluation and interpretation.

Phosphorus (P) runoff from pastures can cause accelerated eutrophication of surface waters. However, few long‐term studies have been conducted on the effects of best management practices, such as rotational grazing and/or buffer strips on P losses from pastures. The objective of this study was to evaluate the long‐term effects of grazing management and buffer strips on P runoff from pastures receiving annual (5.6 Mg ha−1) poultry litter applications. A 14‐yr study was conducted on 15 small watersheds (0.14 ha) with five treatments: hayed (H), continuously grazed (CG), rotationally grazed (R), rotationally grazed with an unfertilized buffer strip (RB), and rotationally grazed with an unfertilized fenced riparian buffer (RBR). Runoff samples were collected using automatic samplers during runoff events. Average annual runoff volumes from H (40 mm yr−1) and RBR (48 mm yr−1) were lower than CG and RB, which were both 65 mm yr−1, and from R (67 mm yr−1). Rotational grazing alone did not reduce P loads compared with continuous grazing (1.88 and 1.71 kg P ha−1for R and CG, respectively). However, compared with CG, total P losses from RB pastures were reduced 36% with unfertilized buffer strips (1.21 kg P ha−1), 60% in RBR watersheds with unfertilized fenced riparian buffer strips (0.74 kg P ha−1), and 49% by converting pastures to hayfields (0.97 kg P ha−1). Hence, the use of unfertilized buffer strips, unfertilized fenced riparian buffer strips, or converting pastures to hayfields are effective best management practices for reducing P runoff in U.S. pasture systems.

"Our plant manager has just announced a 10% increase in labor productivity. Does this also mean a 10% increase in our gross profit?" "How can I know if we're gaining or losing as we try to get more total bang for the buck in our manufacturing department?" "How can I present productivity data in a way my CEO will understand?" "How can I distinguish productivity improvement contributions in the P&L statement from other factors such as price increases?" "How can I gauge the effect of my sales pricing strategies on profit growth?" The measurement procedure described in this article answers these questions through a series of easily understood mathematical formulas that have been tested and applied in a variety of corporate settings. The procedure analyzes productivity changes in terms of their contribution to profit growth. It also gives management a way to measure the effectiveness of its pricing strategies. These findings are couched in familiar financial language so that they are accessible to managers whatever their functional responsibilities. Both companies and profit centers have used this procedure to identify areas in which resources can be better employed or prices better set. Trend charts developed from the author's method have also proved to be an excellent medium for communication between executives and operations managers. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma is an aggressive tumor that accounts for most skin cancer deaths. Among the physiological barriers against therapeutic success is a strong survival program driven by genes such as MITFthat specify melanocyte identity, a phenomenon known in melanoma biology as lineage dependency. MITFoverexpression is occasionally explained by gene amplification, but here we show that super-enhancers are also important determinants of MITFoverexpression in some melanoma cell lines and tumors. Although compounds that directly inhibit MITFare unavailable, a covalent CDK7 inhibitor, THZ1, has recently been shown to potently suppress the growth of various cancers through the depletion of master transcription-regulating oncogenes and the disruption of their attendant super-enhancers. We also show that melanoma cells are highly sensitive to CDK7 inhibition both in vitro and in vivo and that THZ1 can dismantle the super-enhancer apparatus at MITFand SOX10in some cell lines, thereby extinguishing their intracellular levels. Our results show a dimension to MITFregulation in melanoma cells and point to CDK7 inhibition as a potential strategy to deprive oncogenic transcription and suppress tumor growth in melanoma.

Adding alum to poultry litter is a best management practice used to stabilize P in less soluble forms, reducing nonpoint‐source P runoff. However, little research has been conducted on how alum additions to litter affect subsequent leaching of P from soil. The objective of this study was to evaluate the effects of alum‐treated versus untreated poultry litter on P leaching from soil cores receiving long‐term poultry litter applications. Two intact soil cores were taken from each of 52 plots in a long‐term study with 13 treatments: a control, four rates each of untreated and alum‐treated litter (2.24, 4.49, 6.72, and 8.96 Mg ha−1), and four rates of ammonium nitrate (65, 130, 195, and 260 kg N ha−1). One core from each plot received the same fertilizer as for the previous 20 yr, whereas the other was unfertilized in the study year, resulting in a total of 25 treatments. Cores were exposed to natural rainfall, and P leaching was measured for 1 yr. The average soluble reactive P concentrations in the leachate varied from 0.16 to 0.44 mg P L−1in fertilized alum‐treated cores, whereas leachate from cores fertilized with untreated litter ranged from 0.40 to 2.64 mg P L−1. At the highest litter rate (8.96 Mg ha−1), alum reduced total dissolved P and total P concentrations in leachate by 83 and 80%, respectively, compared with untreated litter. These results indicate that alum additions to poultry litter significantly reduced soluble and total P fractions in leachate. This study used soil cores from a 20‐yr small plot study.Alum additions to poultry litter have a legacy effect on soil‐test P.Soils fertilized with alum had significantly lower Mehlich‐3 P values below 10 cm.Alum additions bind organic P in poultry litter and soil.Total P leachate losses were reduced by 86% with alum.

Circuit refinement involves the formation of new presynaptic boutons as others are dismantled. Nascent presynaptic sites can incorporate material from recently eliminated synapses, but the recycling mechanisms remain elusive. In early-stage C. eleganslarvae, the presynaptic boutons of GABAergic DD neurons are removed and new outputs established at alternative sites. Here, we show that developmentally regulated expression of the epithelial Na+channel (ENaC) UNC-8 in remodeling DD neurons promotes a Ca2+and actin-dependent mechanism, involving activity-dependent bulk endocytosis (ADBE), that recycles presynaptic material for reassembly at nascent DD synapses. ADBE normally functions in highly active neurons to accelerate local recycling of synaptic vesicles. In contrast, we find that an ADBE-like mechanism results in the distal recycling of synaptic material from old to new synapses. Thus, our findings suggest that a native mechanism (ADBE) can be repurposed to dismantle presynaptic terminals for reassembly at new, distant locations.

Diffuse reflectance spectroscopy (DRS) is being used in exploratory clinical applications such as cancer margin assessment on excised tissue. However, when interrogating nonplanar tissue anomalies can arise from non-uniform pressure. Herein is reported the design, fabrication, and test of flexible, thin film silicon photodetectors (PDs) bonded to a flexible substrate designed for use in conformal DRS. The PDs have dark currents and responsivities comparable to conventional Si PDs, and were characterized while flat and while flexed at multiple radii of curvature using liquid phantoms mimicking adipose and malignant breast tissue. The DRS and nearest neighbor crosstalk results were compared with Monte Carlo simulations, showing good agreement between simulation and experiment.

Several letter to the editor are presented in response to articles in previous issues including "A triple whammy on charities" in the Mar 23, 1981 issue, "Why mining looks goof to Big Oil" in the March 30, 1981 issue and "Public Broadcasting's trouble at the top" in the March 9, 1981 issue.

ABSTRACTNearly 100% of melanomas have a defect in the p16INK4A:cyclin D-CDK4/6:RB pathway, leading to abnormal cell cycle control and unregulated cellular proliferation. Here, we report that P1446A-05, a novel multi-CDK inhibitor has significant inhibitory activity against cutaneous and uveal melanoma. Mechanistic studies revealed that P1446A-05 inhibits phosphorylation targets of CDK members, and induces cell cycle arrest and apoptosis irrespective of melanoma genotype or phenotype. Additionally, we show preclinical evidence that P1446A-05 can synergize with other small molecule inhibitors previously studied in melanoma. Collectively, these data demonstrate that targeting cell cycle and transcriptional CDKs with a small molecule multi-CDK inhibitor is a viable approach for developing novel anti-melanoma therapeutics.

If the words 'UNIX' and 'security' are never in your mind at the same time, you're not alone. Until recently, the two terms were seldom mentioned in the same breath. […]

Neuromuscular dysfunction is a common feature of mitochondrial diseases and frequently presents as ataxia, spasticity and/or dystonia, all of which can severely impact individuals with mitochondrial diseases. Dystonia is one of the most common symptoms of multiple mitochondrial dysfunctions syndrome 1 (MMDS1), a disease associated with mutations in the causative gene (NFU1) that impair iron–sulfur cluster biogenesis. We have generated Caenorhabditis elegans strains that recreated patient-specific point variants in the C. elegans ortholog (nfu-1) that result in allele-specific dysfunction. Each of these mutants, Gly147Arg and Gly166Cys, have altered acetylcholine signaling at neuromuscular junctions, but opposite effects on activity and motility. We found that the Gly147Arg variant was hypersensitive to acetylcholine and that knockdown of acetylcholine release rescued nearly all neuromuscular phenotypes of this variant. In contrast, we found that the Gly166Cys variant caused predominantly postsynaptic acetylcholine hypersensitivity due to an unclear mechanism. These results are important for understanding the neuromuscular conditions of MMDS1 patients and potential avenues for therapeutic intervention.

The Ozark Highlands, particularly northwest Arkansas, is one of several regions in the United States with concentrated broiler (Gallus gallus domesticus) production. Broiler litter contains N and P; thus, litter is typically land applied to surrounding pastures as a means of recycling the litter as an organic fertilizer. However, broiler litter also contains numerous heavy metals, namely arsenic (As). Sorption reactions are a primary means of As and P retention in soil that limits As and P mobility and the potential threat of surface and groundwater contamination. However, As also competes with P for adsorption sites under some soil conditions. Therefore, it is essential to understand how broiler litter-derived As behaves in a high soil-test P environment, which characterizes many of the pastures in the Ozark Highlands. The objective of this study was to evaluate the effects of broiler-litter application rate (0 control, 5.6 low, and 11.2 high Mg litter ha−1) applied for 4 consecutive years and soil depth (0-20 and 20-50 cm) on As sorption characteristics in the presence or absence of a small concentration of P in solution. Arsenic sorption was greater to the soil of the unamended control than to the soil of the low- and high-litter treatments and was also greater in the 20- to 50-cm depth than in the 0- to 20-cm depth whether additional P was present or not. However, As sorption in the presence of added P was nearly 2-fold that when only As was present. Results demonstrate that a single isotherm does not accurately depict As sorption to soil with a variable history of broiler-litter applications. Results also suggest that there may be less of a potential to increase As mobility in the soil when broiler litter is land applied containing both As and P. Thus, the potential threat of groundwater contamination from increased As leaching may also be less than once thought.

The broiler (Gallus gallus domesticus) industry generates large quantities of nutrient- and trace metal-enriched litter. Broiler litter (BL) is typically land applied as a nutrient source for forages. Continual annual BL applications can increase nutrient and trace metal concentrations in soil over time, creating the potential for negative environmental impacts. The objective of this study was to determine the long-term effects of BL application rate on soil profile chemical properties in a Captina silt loam (fine-silty, siliceous, active, mesic, Typic Fragiudult) with a history of BL applications. Broiler litter was applied annually at 0, 5.6, and 11.2 Mg of dry weight-based litter ha−1during a 5-year period. Soil was sampled in 10-cm increments to 90 cm and characterized for pH, electrical conductivity, organic matter, dissolved organic C, P saturation, and acid-recoverable (P, K, Ca, Mg, S, Na, Fe, Mn, Zn, Cu, Al, As, Cd, Cr, and Se), Mehlich-3-extractable (P, K, Ca, Mg, Na, Fe, Mn, Zn, and Cu), and water-soluble (P, K, Ca, Mg, S, Na, Fe, Mn, Zn, Cu, Al, As, Cd, Cr, and Se) soil nutrient and trace metals. Soil nutrient and trace metal contents generally increased with continued BL application for 5 years in the Mehlich-3-extractable and water-soluble pools. Soil properties affected by litter treatment generally increased over time in the top 20 cm as litter rate increased. It seems that continued annual application of BL to soil with a history of BL application will continue to accumulate Mehlich-3-extractable and water-soluble soil nutrient and trace metals near the soil surface. A decrease in soil nutrient and trace metal contents when BL applications ceased generally did not occur. Therefore, it seems that decreases in most soil chemical property magnitudes caused by the cessation of BL applications will require more than 5 years and could continue to pose potential negative environmental consequences.

In the early 1900s, northwest Arkansas was the leading apple (Malus sylvestrisMill.)-producing region in the United States. To maximize yields and quality, apple producers used heavy doses of lead (Pb) arsenate at the time to control agricultural pests, particularly the codling moth (CydiaLaspeyresiapomonella). Northwest Arkansas is a region underlain by karst geology, specifically fractured limestone and dolomitic bedrock, which creates the potential for rapid downward transport of surface contaminants, such as arsenic (As) from past Pb arsenate usage in the region, to the groundwater. Northwest Arkansas is also presently one of the most rapidly expanding regions in the United States in terms of urbanization and population. Thus, it is critical that high-quality surface and groundwater resources are maintained as potable water sources. The objective of this study was to evaluate the effect of land use (i.e., historic apple orchard, broiler litter-amended pasture, historic orchard-followed-by-broiler-litter-amended pasture, andnonorchard/nonlittered land use) and soil depth (i.e., 0-2, 2-4, and 4-8 cm) on acid-recoverable soil As, Pb, and phosphorus. Soil As concentrations were lowest in the 0- to 2- and/or 2- to 4-cm depth and increased with depth in all land uses, expect for the litter-only pastureland, in which soil As concentrations did not differ among soil depths. Soil Pb concentrations also increased with depth, but only in the orchard-followed-by-litter-amended pasture. Soil As and Pb concentrations were at least numerically greater in all soil depths in the orchard-followed-by-litter-amended pasture than in all other land use/soil depth combinations. Soil phosphorus concentrations were greater at all depths in the land uses that received broiler litter than in those land uses that did not and decreased with depth in all land uses. The results of this study indicate that historic Pb arsenate usage seems to be more responsible for elevated soil As concentrations than even decades of annual land application of As-containing broiler litter to pasturelands that had neverreceived Pb arsenate applications for pest control during apple production.

Poor tilth and, often, a surface crust characterize eastern Arkansas soils. Such soils have very low water infiltration and high water runoff rate leading to increase turbidity in rivers and soil erosion. Sharkey clay and Desha silt loam soils from Delta region of eastern Arkansas were used to find the effect of sodium adsorption ratio (SAR) and ionic strength (IS) on the dispersion/flocculation behaviors of the soils. Percent light transmissions at a wavelength of 530 nm were related to the concentration of clay in suspension. Each soil was equilibrated with a series of solutions having different IS and containing Na+and Ca2+in various proportions. At different IS and SAR, the two soils exhibited different behaviors. Clay dispersibility was a more sensitive function of SAR at low IS than at high IS.

Cation exchange is one of the most venerable concepts in soil science, yet it needs rethinking. This paper presents an extremely simple conceptual framework for interpreting many observed trends in cation exchange. Taking the example of Cs‐K exchange, the methods of computational molecular mechanics found that Cs‐montmorillonite is considerably higher in energy than K‐montmorillonite at constant water content, in agreement with inferences from a new thermodynamic cycle representation of cation exchange. Since montmorillonite selects Cs+over K+in real experiments, these results mean that alkali cation‐exchange selectivity is controlled by selectivity of the solution phase for the more strongly hydrated cation. Thus the clay does not “select” for Cs+over K+in any positive sense and it may be more useful to consider cation exchange as a partitioning reaction: Given two cations of equal valence, the more weakly hydrated will tend to partition into the “subaqueous” smectite interlayer phase. This concept seems not only parsimonious, but also more accurate than other hypotheses for cation exchange selectivity that impute more favorable interactions between smectite surfaces and the selected cations; such theories err by ignoring energy changes in the solution phase. This simple partitioning concept rationally explains the alkali and alkaline earth selectivity sequences as well as the selectivities of smectites for organic cations over inorganic, for larger organic cations over smaller, and for organometallic complexes over the uncomplexed metal.

Undergraduate curricula for natural resource and agronomic programs have been introduced and revised during the past several decades with a desire to stay current with emerging issues and technologies relevant to constituents. For the past decade, the Department of Crop, Soil, and Environmental Sciences (CSES) faculty at the University of Arkansas has engaged in decision making processes to revise its two undergraduate degree programs: Environmental, Soil, and Water Science (ESWS) and Crop Management (CPMG). In working separately and targeting distinct areas for improvement, CPMG and ESWS faculty have taken similar approaches to curriculum review. After reviewing other academic programs for common elements needed to revise and articulate goals for undergraduate students, faculty developed priority rankings for course topics, skill development, new course introductions, and/or revised program structures based in part on the data from curriculum matrices. Constructing and completing matrices allowed faculty to visualize strengths, weaknesses, redundancies, and gaps in the two degree programs. The CPMG faculty began meeting monthly in 1996, and within 8 years, the undergraduate curriculum in crop management had been completely revised. The ESWS faculty began meeting in 2002, and while the process is ongoing, courses have been revised and implemented, and a program structure is facilitating further improvements. Current challenges include offering new courses while simultaneously building student enrollment for a critical mass to sustain new course offerings.

Knowledge of the balance between nutrient inputs and removals is required for identifying regions that possess an excess or deficit of nutrients. This assessment describes the balance between the agricultural nutrient inputs and removals for nine geographical districts within Arkansas from 1997 to 2001. The total N, P, and K inputs were summed for each district and included inorganic fertilizer and collectable nutrients excreted as poultry, turkey, dairy, and hog manures. Nutrients removed by harvested crops were summed and subtracted from total nutrient inputs to calculate the net nutrient balance. The net balances for N, P, and K were distributed across the hectarage used for row crop, hay, pasture, or combinations of these land uses. Row‐crop agriculture predominates in the eastern one‐third and animal agriculture predominates in the western two‐thirds of Arkansas. Nutrients derived from poultry litter accounted for >92% of the total transportable manure N, P, and K. The three districts in the eastern one‐third of Arkansas contained 95% of the row‐crop hectarage and had net N and P balances that were near zero or negative. The six districts in the western two‐thirds of Arkansas accounted for 89 to 100% of the animal populations, had positive net balances for N and P, and excess P ranged from 1 to 9 kg P ha−1when distributed across row‐crop, hay, and pasture hectarage. Transport of excess nutrients, primarily in poultry litter, outside of the districts in western Arkansas is needed to achieve a balance between soil inputs and removals of P and N.

Locomotory activity is defined by the specification of motoneurone subtypes. In the nematode, C. elegans, DA and DB motoneurones innervate dorsal muscles and function to induce movement in the backwards or forwards direction, respectively. These two neurone classes express separate sets of genes and extend axons with oppositely directed trajectories; anterior (DA) versus posterior (DB). The DA-specific homeoprotein UNC-4 interacts with UNC-37/Groucho to repress the DB gene, acr-5 (nicotinic acetylcholine receptor subunit). We show that the C. elegans even-skipped-like homoedomain protein, VAB-7, coordinately regulates different aspects of the DB motoneurone fate, in part by repressing unc-4. Wild-type DB motoneurones express VAB-7, have posteriorly directed axons, express ACR-5 and lack expression of the homeodomain protein UNC-4. In a vab-7 mutant, ectopic UNC-4 represses acr-5 and induces an anteriorly directed DB axon trajectory. Thus, vab-7 indirectly promotes DB-specific gene expression and posteriorly directed axon outgrowth by preventing UNC-4 repression of DB differentiation. Ectopic expression of VAB-7 also induces DB traits in an unc-4-independent manner, suggesting that VAB-7 can act through a parallel pathway. This work supports a model in which a complementary pair of homeodomain transcription factors (VAB-7 and UNC-4) specifies differences between DA and DB neurones through inhibition of the alternative fates. The recent findings that Even-skipped transcriptional repressor activity specifies neurone identity and axon guidance in the mouse and Drosophila motoneurone circuit points to an ancient origin for homeoprotein-dependent mechanisms of neuronal differentiation in the metazoan nerve cord.

A small subset of neurons in the nematode Caenorhabditis elegansutilizes the catecholamine dopamine (DA) as a neurotransmitter to control or modulate movement and egg-laying. Disruption of DA-mediated behaviors represents a potentially powerful strategy to identify genes that are likely to participate in dopaminergic systems in man. In vertebrates, extracellular DA is inactivated by presynaptic DA transport proteins (DATs) that are also major targets of addictive agents, including amphetamines and cocaine. We used oligonucleotides derived from the C.elegansgenomic locusT23G5.5to isolate and characterize T23G5.5 cDNAs. Our studies predict that mRNAs from this locus encode a 615-amino-acid polypeptide with twelve stretches of hydrophobicity suitable for transmembrane domains, similar to that found in vertebrate catecholamine transporters. The inferred translation product bears highest identity (43–47%) to catecholamine (DA, norepinephrine, epinephrine) transporters within theGAT1/NETgene family and possesses conserved residues implicated in amine substrate recognition. Consistent with these findings, HeLa cells transfected with theC. eleganscDNA exhibit saturable and high affinity DA transport (Km= 1.2 μm) that is dependent on extracellular Na+and Cl−and blocked by inhibitors of mammalian catecholamine transporters, including norepinephrine transporter- and DAT-selective antagonists, tricyclic antidepressants, and the nonselective amine transporter antagonists cocaine andd-amphetamine. These studies validate theT23G5.5locus as encoding a functional catecholamine transporter, providing important comparative sequence information for catecholamine transporter structure/function studies and a path to identify regulators of dopaminergic signaling via genetic or pharmacologic manipulation of C.eleganscDNA in vivo.

This study examined the accuracy of Ward's (1990) seven-subtest short form for predicting WAIS-R IQs of 54 African Americans with brain damage. Means for age, education, and FSIQ were 47.1 years (SO= 16.6), 10.8 years (SD=2.4), and 79.3 (SD= 11.6). Short-form VIQs, PIQs, and FSIQs were within ±1 standard error of measurement of the actual WAIS-R scores 81.5%, 83.3%, and 83.3% of the time. This abbreviation may be applied to African Americans with brain damage when general estimates of intellectual functioning are required. However, the shortened scale detected reliable VIQ.PIQ discrepancies on the WAIS-R only 53% of the time. Therefore, interpretation of significant short-form-based VIQ-PIQ discrepancies should be avoided.

Ethylene is a plant growth-regulating substance that is produced by plants and soil microorganisms. Ethylene production and accumulation in soils is stimulated by the addition to the soil of compounds such as methionine, which serves as a direct precursor in ethylene biosynthesis, and by flooding, which encourages anaerobiosis. The objective of this laboratory study was to determine if the addition of either non-composted or composted broiler litter stimulated ethylene production in three ana-erobically incubated agricultural soils from eastern Arkansas. A completely randomized design was used, with non-composted and composted broiler litter as the two sources applied at three rates each. Check treatments received no litter. Both non-composted and composted poultry litter significantly increased production of ethylene in soils under flooded conditions, compared with the unamended control. At the highest rate of addition of non-composted litter (9.4 g kg-1), ethylene production in the Hilleman, Foley, and Bosket soils was 821, 678, and 327 nmol kg-1soil, respectively. At the same rate of addition of composted litter, ethylene production in these same soils was 491, 440, and 254 nmol kg-1soil. There were significant differences among soils in the quantities of ethylene produced, with the soil having the coarsest texture and lowest organic carbon content, the Bosket, producing the least ethylene. More ethylene was produced per gram of added carbon with non-composted litter than with composted litter. Differences in the abilities of the two wastes to promote ethylene production in soils may be due to differences in the bioavailability of carbon in the two materials. The compost had a lower total organic C content and a higher humic acid content than the non-composted material. The yield response of lowland rice to applications of poultry litter may be due in part to enhanced ethylene accumulation in the waste-amended soils.

In the nematode, Caenorhabditis elegans, the body wall muscles contain paramyosin and two different types of myosin heavy chain, MHC A and MHC B. In mutants that do not express MHC B or that express defective paramyosin, muscle structure is disrupted and movement is impaired. Second site mutations in the sup-3 locus partially reverse these defects and are correlated with a 2- to 3-fold increase in the accumulation of the MHC A isoform. The sup-3 mutations occur at a high frequency (10-4) after ethyl methanesulfonate (EMS) mutagenesis. This is comparable to the average EMS-induced mutation rate per gene in C. elegans. In this paper we show that the sup-3 mutation is an amplification of the structural gene for the MHC A protein, myo-3. We employed genomic Southern hybridization with MHC gene-specific probes in order to measure the copy number of the myo-3 gene relative to that of the MHC B gene, unc-54. We have identified the putative amplification junctions for these sup-3 alleles using a set of cosmid clones which encompass myo-3 region. Although it has been suggested that gene amplification plays an important role in evolution, there are few known cases of gene amplification in the germ line cells of multicellular organisms. The results shown here provide a clear example of a heritable gene amplification event that occurs at a high frequency in the germ line. Similar events may thus represent the initial event in the evolution of new function and in the formation of multigene families.

In the light of growing global competition, organizations around the world today are constantly under pressure to produce high-quality products at an economical price. The integration of design and manufacturing activities into one common engineering effort has been recognized as a key strategy for survival and growth. Design for manufacturability (DFM) is an approach to design that fosters the simultaneous involvement of product design and process design. The implementation of the DFM approach requires the collaboration of both the design and manufacturing functions within an organization. Many reasons can be cited for the inability to implement the DFM approach effectively, including: lack of interdisciplinary expertise of designers; inflexibility in organizational structure, which hinders interaction between design and manufacturing functions; lack of manufacturing cost information at the design phase; and absence of integrated engineering effort intended to maximize functional and manufacturability objectives. The purpose of this research is to show how expert systems methodology could be used to provide manufacturability expertise during the design phase of a product. An object- and rule-based expert system has been developed that has the capability: (1) to make process selection decisions based on a set of design and production parameters to achieve cost-effective manufacture; and (2) to estimate manufacturing cost based on the identified processes. The expertise for primary process selection is developed for casting and forging processes. The specialized processes considered are die casting, investment casting, sand casting, precision forging, open die forging and conventional die forging. The processes considered for secondary process selection are end milling and drilling. The cost estimation expertise is developed for the die casting process, the milling and drilling operations, and the manual assembly operations. The results obtained from the application of the expert system suggest that the use of expert systems methodology is a feasible method for implementing the DFM approach.

Groucho and Tup1 are members of a conserved family of WD repeat proteins that interact with specific transcription factors to repress target genes. Here we show that mutations in WD domains of the Groucho-like protein, UNC-37, affect a motor neuron trait that also depends on UNC-4, a homeodomain protein that controls neuronal specificity in Caenorhabditis elegans. In unc-4 mutants, VA motor neurons assume the pattern of synaptic input normally reserved for their lineal sister cells, the VB motor neurons; the loss of normal input to the VAs produces a distinctive backward movement defect. Substitution of a conserved residue (H to Y) in the fifth WD repeat in unc-37(e262) phenocopies the Unc-4 movement defect. Conversely, an amino acid change (E to K) in the sixth WD repeat of UNC-37 is a strong suppressor of unc-37(e262) and of specific unc-4 missense mutations. We have previously shown that UNC-4 expression in the VA motor neurons specifies the wild-type pattern of presynaptic input. Here we demonstrate that UNC-37 is also expressed in the VAs and that unc-37 activity in these neurons is sufficient to restore normal movement to unc-37(e262) animals. We propose that UNC-37 and UNC-4 function together to prevent expression of genes that define the VB pattern of synaptic inputs and thereby generate connections specific to the VA motor neurons. In addition, we show that the WD repeat domains of UNC-37 and of the human homolog, TLE1, are functionally interchangeable in VA motor neurons which suggests that this highly conserved protein domain may also specify motor neuron identity and synaptic choice in more complex nervous systems.

Management of N nutrition of cotton (Gossypium hirsutumL.) is one of the most critical aspects of successful cotton production, but growth and yield responses of individual cotton cultivars to N fertilization is relatively unknown. The objective of this research was to evaluate the responses of three cotton cultivars (Arkot 518, Stoneville 453, and Deltapine 90) to soil‐applied N fertilization rates. The study was conducted for 3 yr on a Hebert silt loam soil (fine‐silty, mixed, thermic Aeric Ochraqualf). Few significant (ɑ = 0.05) cultivar × N rate interaction differences were found, although main effects of the N treatments and the cultivars were evident. The most pronounced responses of the cotton were found as an effect of the N‐fertilization treatments. Nitrogen rates in excess of 112 kg N ha−1did not significantly increase seed cotton yields in any year of the study. The mean yield of the cultivars among N rates was significantly different in only one year of the study. Earliness of the cotton was reduced by increasing N rate, as indicated by significant differences in nodes above white flower (NAWF) measurements. Significant differences were also found in the NAWF measurements for the cultivars, thereby inferring maturity differences among the cultivars tested. Of the cultivars evaluated, Arkot 518 was earliest, followed by Stoneville 453, and then Deltapine 90. Significant interactions of cultivar and N rate were found only in three dates of NAWF (1991), and one date of petiole NO‐3‐N content (1990). Soil samples taken after 3 yr of continuous fertilization treatments showed a significant NO‐3‐N accumulation at the 15‐ to 45‐cm depth only in plots treated with 224 kg N ha−1.

In the nematode, Caenorhabditis elegans, VA and VB motor neurons arise from a common precursor cell but adopt different morphologies and synapse with separate sets of interneurons in the ventral nerve cord. A mutation that inactivates the unc-4 homeodomain gene causes VA motor neurons to assume the VB pattern of synaptic input while retaining normal axonal polarity and output; the disconnection of VA motor neurons from their usual presynaptic partners blocks backward locomotion. We show that expression of a functional unc-4-β-galactosidase chimeric protein in VA motor neurons restores wild-type movement to an unc-4 mutant. We propose that unc-4 controls a differentiated characteristic of the VA motor neurons that distinguishes them from their VB sisters, thus dictating recognition by the appropriate interneurons. Our results show that synaptic choice can be controlled at the level of transcription in the post-synaptic neuron and identify a homeoprotein that defines a subset of cell-specific traits required for this choice.

The adsorption of trichloroethene, C2HCl3, on clay mineral surfaces in the presence of water has been modeled as an example describing a general program that uses molecular dynamics simulations to study the sorption of organic materials at the clay mineral/aqueous solution interface. Surfaces of the clay minerals kaolinite and pyrophyllite were hydrated at different water levels corresponding to partial and complete monolayers of water. In agreement with experimental trends, water was found to outcompete C2HCl3for clay surface sites. The simulations suggest that at least three distinct mechanisms coexist for C2HCl3on clay minerals in the environment. The most stable interaction of C2HCl3with clay surfaces is by full molecular contact, coplanar with the basal surface. This kind of interaction is suppressed by increasing water loads. A second less stable and more reversible interaction involves adsorption through single‐atom contact between one Cl atom and the surface. In a third mechanism, adsorbed C2HCl3never contacts the clay directly but sorbs onto the first water layer. To test the efficacy of existing force field parameters of organic compounds in solid state simulations, molecular dynamics simulations of several representative organic crystals were also performed and compared with the experimental crystal structures. These investigations show that, in general, in condensed‐phase studies, parameter evaluations are realistic only when thermal motion effects are included in the simulations. For chlorohydrocarbons in particular, further explorations are needed of atomic point charge assignments. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 144–153, 1998

The Stansbury shoreline, one of the conspicuous late Pleistocene shorelines of Lake Bonneville, consists of tufa-cemented gravel and barrier beaches within a vertical zone of about 45 m, the lower limit of which is 70 m above the modern average level of Great Salt Lake. Stratigraphic evidence at a number of localities, including new evidence from Crater Island on the west side of the Great Salt Lake Desert, shows that the Stansbury shoreline formed during the transgressive phase of late Pleistocene Lake bonneville (sometime between about 22,000 and 20,000 yr B.P.). Tufa-cemented gravel and barrier beaches were deposited in the Stansbury shorezone during one or more fluctuations in water level with a maximum total amplitude of 45 m. We refer to the fluctuations as the Stansbury oscillation. The Stansbury oscillation cannot have been caused by basin-hypsometric factors, such as stabilization of lake level at an external overflow threshold or by expansion into an interior subbasin, or by changes in drainage basin size. Therefore, changes in climate must have caused the lake level to reverse its general rise, to drop about 45 m in altitude (reducing its surface area by about 18%, 5000 km 2), and later to resume its rise. If the sizes of Great Basin lakes are controlled by the mean position of storm tracks and the jetstream, which as recently postulated may be controlled by the size of the continental ice sheets, the Stansbury oscillation may have been caused by a shift in the jetstream during a major interstade of the Laurentide ice sheet.

This paper is concerned with the problem of determining the optimum number of machines to have in a production process. The problem is analyzed as a resource allocation problem involving the minimum cost allocation of limited floor space, capital budget, and available overtime among various types of machines. The dynamic nature of the problem is also included in the analysis. A deterministic mixed integer programming model is described. A numerical example is presented to illustrate the approach and its utility as an alternative way to address the machine requirements problem.

The maximum adsorptions of the lower members of the mono- and di-carboxylic acids from aqueous solutions were determined for coconut charcoals of different degrees of activation. Based on these results, a method for estimating pore size was applied to the more finely porous charcoals. To corroborate the pore sizes estimated from acid adsorption, pore size – area distributions were calculated from measurements of the water vapor sorption isotherms of the charcoals. An alternation in the maximum amounts of adsorbed acids was observed with the more active charcoals. Acids with an even number of carbon atoms had larger adsorptions than acids with an odd number. The alternation was much more marked for the di- than for the mono-carboxylic acids. A remarkable correlation between the alternation of adsorptions and of melting points of both acid series was observed. An explanation for the general phenomenon of alternation based on rotational motion of molecules in the solid state is given as an alternative to the widely held one based on tilting of molecular chains.

A previously described method of combining measurements of numerous pebble cross-sections in three orthogonal planes into a single average ellipsoid was found to be in need of improvement. The method of reconciling redundancies and of distributing the errors can be left unchanged. The original measurements of principal half-axes, however, rather than being normalized as the ratios of larger half-axes divided by the smaller, should be normalized so that they produce ellipses of standard area. The coefficients of ellipses so normalized will produce distributions with a pronounced central tendency even in those cases that produce markedly skewed distributions of coefficients for ellipses normalized by the former method. Equations of the previous paper that must be amended are given in their new form.