Taxonomic Practice and Middle Missouri Prehistory: A Perspective on Donald J. Lehmer’s Contributions

Abstract

This paper is an attempt to explicate Donald J. Lehmer’s taxonomic practices. It begins with an examination of his 1954 response to the limitations of the Midwestern Taxonomic System, continues with a discussion of Lehmer and Caldwell’s attempt to introduce the Willey and Phillips Phase-Tradition-Horizon System and ends with an interpretation of the taxonomic modifications Lehmer introduced in his final synthesis of Middle Missouri prehistory. The logical properties of the M.T.S. and the Willey and Phillips System are used throughout as a background against which Lehmer’s accomplishments and mistakes can be brought into sharp focus.     

Temporal and Spatial Order in the Central Plains

Abstract

The major archeological complexes of the Central Plains can be arranged according to the Willey and Phillips system, thus recognizing not only content but time and space diemnsions.     

A revision of genus Atalophlebioides (Ephemeroptera: Leptophlebiidae)

Abstract

Atalophlebioides Phillips is redescribed as a monotypic genus endemic to New Zealand. All life stages of A. cromwelli (Phillips) are described, and a lectotype is designated. The relationships of the genus and the ecology of A. cromwelli are discussed.     

Management of externally manufactured cell therapy products: the Mayo Clinic approach

BackgroundThe rise of investigative and commercially available cell therapy products adds a new dynamic to academic medical centers; that is, the management of patient-specific cell products. The scope of cell therapy has rapidly expanded beyond in-house collection and infusion of cell products such as bone marrow and peripheral blood transplant. The complexities and volumes of cell therapies are likely to continue to become more demanding. As patient-specific “living drugs,” cell therapy products typically require material collection, product provenance, transportation and maintenance of critical quality attributes, including temperature and expiration dates. These requirements are complicated by variations in product-specific attributes, reporting requirements and interactions with industry not required of typical pharmaceuticals.MethodsTo manage these requirements, the authors set out to establish a framework within the Immune, Progenitor and Cell Therapeutics Lab, the Current Good Manufacturing Practice facility responsible for cell manufacturing at Mayo Clinic Rochester housed within the Division of Transfusion Medicine. The authors created a work unit (biopharmaceutical unit) dedicated to addressing the specialized procedures required to properly handle these living drugs from collection to delivery and housing the necessary processes to more easily integrate externally manufactured cell therapies into clinical practice.ResultsThe result is a clear set of expectations defined for each step of the process, with logical documentation of critical steps that are concise and easy to follow.ConclusionsThe authors believe this system is scalable for addressing the promised growth of cell therapy products well into the future. Here the authors describe this system and provide a framework that could be used by other centers to manage these important new therapies.     

The Stumble—From Pipe Cleaner to Bone Builder

ObjectiveTo review the history of the transition of bisphosphonate use from bench chemistry to clinical applications.MethodsPertinent medical literature, including limited-distribution as well as peer-reviewed publications, was reviewed.ResultsBisphosphonates were originally developed to interfere with calcium deposition. An expanded understanding of bone physiology, as well as a growing appreciation of bisphosphonate chemistry, allowed a broadening range of clinical applications.ConclusionThe use of bisphosphonates in clinical medicine depended on a series of fortuitous events that, at the time, were “stumbles,” not unlike the discoveries of Fleming and Newton. The logical sequence is more apparent in retrospect. (Endocr Pract. 2007;13:194-197)     

Concepts of perception,visual practice,and pattern art among the Cashinahua Indians (Peruvian Amazon area)

This paper attempts to demonstrate that consistent regard for culturally specific concepts of perception and analysis of native visual practice open new possibilities for the interpretation of Amazon Indian pattern art. For the ornamentalistics theory a new paradigm results from this, with emphasis on the processuality and performativity of the construction of meaning instead of the previous focus on structure and system, the basis for the search for iconographic traces of semantic content.     

Mourning response and intervention in stillbirth: An alternative genetic counseling approach

Abstract

Stillbirth is a frequently occurring tragedy that causes intense problems for parents experiencing it. A review of the literature suggests that the grief response of parents to stillbirth or neonatal death may present more problems than do other types of bereavement. An assessment of these problems suggests that a successful plan for management requires intervention as soon as possible after the death occurs. A protocol for such intervention is presented. It is suggested that such intervention is the proper domain of genetic counselors and represents an expanded approach to genetic counseling, particularly in the light of the recent movement toward a more psychologically oriented paradigm of genetic counseling.     

Clinical-grade,large-scale,feeder-free expansion of highly active human natural killer cells for adoptive immunotherapy using an automated bioreactor

Background aimsNatural killer (NK) cell-based adoptive immunotherapy is a promising approach for the treatment of cancer. Ex vivo expansion and activation of NK cells under good manufacturing practice (GMP) conditions are crucial for facilitating large clinical trials. The goal of this study was to optimize a large-scale, feeder-free, closed system for efficient NK cell expansion.MethodsPeripheral blood mononuclear cells (PBMCs) from healthy donors and myeloma patients were cultured for 21 days using flasks, cell culture bags and bioreactors. Final products from different expansions were evaluated comparatively for phenotype and functionality.ResultsSignificant NK cell expansions were obtained in all systems. The bioreactor yielded a final product rich in NK cells (mean 38%) ensuring that a clinically relevant cell dose was reached (mean 9.8 × 10⁹ NK cells). Moreover, we observed that NK cells expanded in the bioreactor displayed significantly higher cytotoxic capacity. It was possible to attribute this partially to a higher expression level of NKp44 compared with NK cells expanded in flasks.ConclusionsThese results demonstrate that large amounts of highly active NK cells for adoptive immunotherapy can be produced in a closed, automated, large-scale bioreactor under feeder-free current GMP conditions, facilitating clinical trials for the use of these cells.     

Phillips Spring, 23HI216:

Abstract

The Phillips Spring Site is situated on a Holocene terrace of the Pomme de Terre River in northern Hickory County, Missouri. Eleven. radiocarbon dates provide a good chronologie framework for the four cultural components recognized at the site. There are three Archaic components which span the period 4280 to 1990 BP. The initial Archaic occupation coincides with the establishment of the present vegetation pattern in the area. A single Late Woodland assemblage, dating from 1410 to 1000 BP, is comparable in cultural content to components of the HighlandAspect.     

Three new genera of Leptophlebiidae (Ephemeroptera) from New Zealand

Abstract

Three new genera—Austroclima, Mauiulus, and Cryophlebia—are established for species of Leptophlebiidae from New Zealand. The following new combinations are included: Austroclima sepia (Phillips) and Cryophlebia aucklandensis (Peters). Atalophlebioides sepia is redescribed as Austroclima sepia and a neotype is designated. Two new species, Austroclima jollyae and Mauiulus luma, are described. All life stages are described, and the relationships of each genus are discussed. Keys are given to male and female imagos, subimagos, and nymphs of each species, and to all New Zealand genera with species previously placed in Atalophlebioides.     

Low rate of infusional toxicity after expanded cord blood transplantation

Background aimsUmbilical cord blood (CB) is used with increasing frequency to restore hematopoiesis in patients with bone marrow transplant who lack a suitable human leukocyte antigen–matched donor. CB transplantation is limited by low cell doses and delays in neutrophil and platelet engraftment. CB progenitors expanded ex vivo before transplantation provide more rapid hematopoietic and immune reconstitution as well as less engraftment failure compared with unmanipulated CB. However, the safety of infusing double and ex vivo–expanded CB has not been systematically examined.MethodsWe reviewed the immediate adverse events (AE) associated with the infusion of CB occurring within 24 hours in 137 patients enrolled in clinical CB transplant trials at the MD Anderson Cancer Center from February 2004 to May 2010. All patients received an unmanipulated CB unit followed by infusion of a second unmanipulated CB unit or a second CB unit expanded ex vivo with the use of cytokines in a liquid culture system or in mesenchymal stromal cell co-cultures.ResultsA total of three grade 2 and two grade 3 infusion reactions occurred within 24 hours of CB transplantation. This resulted in an AE rate of 3.7%. The majority of AEs manifested as signs of hypertension. No association with patient age, sex, disease status, premedication, ABO compatibility or total infusion volume was observed. In summary, the incidence of infusion-related toxicities in patients who receive unmanipulated and ex vivo–expanded double CB transplantation is low.ConclusionsWe conclude that the infusion of unmanipulated followed by expanded CB products is a safe procedure associated with a low probability of inducing severe reactions.     

研究报告：果蝇习得性无助影响空间位置记忆

目的 习得性无助（learned helplessness）是指动物经历了不可逃避性刺激后而产生的无助状态。它对随后实验动物的运动能力、生理状态等多方面都会产生影响,也是人类抑郁症的有效动物模型之一。目前已在多种动物模型中建立了研究习得性无助神经机制的行为实验范式,包括黑腹果蝇（Drosophila melanogaster）。之前的研究发现,经历过不可逃避高温惩罚的果蝇在活跃程度等方面有显著改变。然而,果蝇的习得性无助状态是否也影响学习认知能力,目前仍然未知。本文对果蝇空间位置学习能力是否受到习得性无助状态影响进行了研究。方法 此研究中,我们完善实验范式,分别检测果蝇在新范式中的空间位置学习行为和习得性无助行为,以及经过长时程随机刺激后果蝇空间位置学习能力的变化。结果 野生型果蝇可在此范式中展现空间位置学习能力与习得性无助状态,而经过长时程不可逃避刺激训练的果蝇,空间位置记忆有显著下降。结论 此研究完善了果蝇习得性无助行为实验范式,实验结果表明习得性无助对果蝇空间位置记忆存在影响。这将对进一步加深对动物习得性无助行为的理解,进而其发生机制研究起到推进作用。     

Evolution of structure and information processing in the nervous system: Part IV of a general theory

Starting from fundamental principles, evolution of the nervous system is modelled as a random walk process in a multidimensional representation space (the F-space). This space is not flat, it is highly structured in terms of step probability. Fundamental considerations of evolutionary speed, efficiency of information processing, and priorities lead to specific theoretical predictions of the most probable pathways of evolution of the nervous system and its mechanisms of information processing. These processes are represented as vector paths (F-paths) in the F-space. Cognition becomes a process of correlations of the input signal to information stored in memories. Higher level brain processes involve extrapolation and interpolation along F-paths, input data reduction by clearly specifiable abstraction methods, and a unique process using abstracted analogs. These processes define and limit what the brain does and how it can do it. These considerations lead to certain inevitable conclusions (consequences of the fundamental principles) for the basis of our logical reasoning, decision-making, the process of dreaming (conscious and sleep), and explicit definitions of consciousness, unconsciousness, and personality. Detailed applications of this theory for analyzing empirical findings are suggested in the final paragraphs.     

Perspective on Mutagenesis and Repair: The Standard Model and Alternate Modes of Mutagenesis

ABSTRACT

The basic ideas of replication, mutagenesis, and repair have outlined a picture of how point mutations occur that has provided a valuable framework for theory and experiment, much as the Standard Model of particle physics has done for our concept of fundamental particles. However, alternative modes of mutagenesis are being defined that are changing our perspective of the “Standard Model” of mutagenesis, requiring an expanded model. The genome is now envisioned as being in dynamic equilibrium between a multitude of forces for mutational change and forces that counteract such change. By maintaining a delicate balance between these forces, cells avoid unwanted or excessive mutations. Yet, cells allow mutagenesis to occur under certain conditions. We can define an emerging paradigm. Namely, mechanisms exist that can direct point mutations to specific designated genes or regions of genes. In some cases, this is achieved by specific enzymes, and in other cases high mutability is programmed into the sequence of certain genes to help generate diversity. In yet additional cases, general mutability is increased under stress, and selective forces allow the recovery of favorable mutants.     

The ammonia-lyases: enzymes that use a wide range of approaches to catalyze the same type of reaction

Abstract

The paradigm that protein structure determines protein function has been clearly established. What is less clear is whether a specific protein structure is always required to carry out a specific function. Numerous cases are now known where there is no apparent connection between the biological function of a protein and the other members of its structural class, and where functionally related proteins can have quite diverse structures. A set of enzymes with these diverse properties, the ammonia-lyases, will be examined in this review. These are a class of enzymes that catalyze a relatively straightforward deamination reaction. However, the individual enzymes of this class possess a wide variety of different structures, utilize a diverse set of cofactors, and appear to catalyze this related reaction through a range of different mechanisms. This review aims to address a basic question: if there is not a specific protein structure and active site architecture that is both required and sufficient to define a catalyst for a given chemical reaction, then what factor(s) determine the structure and the mechanism that is selected to catalyze a particular reaction?     

基于支持向量机的民航飞行人员人格选拔分类器的探讨

目的:探究将统计学习方法应用于心理测验所得的大量数据进行学习分析的可行性,并基于探究结果对飞行职业的人格特征进行进一步探索,为飞行人员的选拔及评估提供新的思路。方法:从某航空公司随机抽取1020名男性被试,其中飞行人员510名,非飞行人员510名,采用卡特尔16项人格测试对其进行测验,施测后对得到的16项因子分采用支持向量机就随机划分的训练组和测试组进行学习,分析学习结果。结果:挑选出4项因子作为分类的特征因子,基于线性支持向量机构建的分类器在交叉验证下的平均正确率为64%。结论:采用SVM构建的分类器具有一定的可靠性和有效性。     

A stromal-free,serum-free system to expand ex vivo hematopoietic stem cells from mobilized peripheral blood of patients with hematologic malignancies and healthy donors

Background aimsThe number of hematopoietic stem cells (HSCs) is critical for transplantation. The ex vivo expansion of mobilized peripheral blood (MPB) HSCs is of clinical value for reconstitution to meet clinical need.MethodsThis study proposed a simple, defined, stromal-free and serum-free culture system (SF-HSC medium) for clinical use, which is composed of Iscove's modified Dulbecco's medium, cytokine cocktails and serum substitutes. This study also characterized the cellular properties of expanded MPB CD133⁺ HSCs from patients with hematologic malignancies and healthy donors by surface antigen, colony-forming cell, long-term culture-initiating cell, gene expression and in vivo engraftment assays.ResultsThe expanded fold values of CD45⁺ white blood cells and CD34⁺, CD133⁺, CD34⁺CD38^?, CD133⁺CD38^?, CD34⁺CD133⁺, colony-forming and long-term culture-initiating cells at the end of 7-day culture from CD133⁺ MPB of hematologic malignancies were 9.4-fold, 5.9-fold, 4.0-fold, 35.8-fold, 21.9-fold, 3.8-fold, 11.8-fold and 6.7-fold, and values from healthy donor CD133⁺ MPB were 20.7-fold, 14.5-fold, 8.5-fold, 83.8-fold, 37.3-fold, 6.2-fold, 19.1-fold and 14.6-fold. The high enrichment of CD38^? cells, which were either CD34⁺ or CD133⁺, sustained the proliferation of early uncommitted HSCs. The expanded cells showed high levels of messenger RNA expression of HOBX4, ABCG2 and HTERT and had the in vivo ability to re-populate NOD/SCID mice.ConclusionsOur results demonstrated that an initial, limited number of MPB CD133⁺ HSCs could be expanded functionally in SF-HSC medium. We believe that this serum-free expansion technique can be employed in both basic research and clinical transplantation.     

Some remarks on the taxonomic status of Paraschizopera Wells, 1981 (Copepods: Harpacticoida)

The monotypic genus Paraschizopera Wells, 1981 (ex Diosaccidae) is transferred to the Tetragonicipitidae on the basis of segmentation of antennary exopod and P2-P4 endopods, setation of P1 and overall similarity in mouthpart structure. Paraschizopera is the most primitive genus of the family and closely related to Diagoniceps Willey, 1930 which is redefined to encompass only the laevis-group. The menaiensis-group is allocated to Paraschizopera which includes now P. beckeri Wells (type-species), P. menaiensis (Geddes) and P. trifida (Yeatman). The new name D. brevicauda is proposed for Diagoniceps sp. sensu Bodin (1979). Keys are provided to the species of Paraschizopera and Diagoniceps, and to the genera of the Tetragonicipitidae.     

Stem-like memory T cells are generated during hollow fiber perfusion-based expansion and enriched after cryopreservation in an automated modular cell therapy manufacturing process

Background aimsModular automation is a flexible and reliable option to build the foundation of a new or evolving process or to introduce automation to a process that is already established. Herein the authors demonstrate that modular automation provides both high-quality and high-yield T-cell products.MethodsCells from three individual donors collected on an automated continuous flow centrifugation system were successfully expanded in a functionally closed, automated, perfusion-based hollow fiber bioreactor. These cells were then prepared for cryopreservation in an automated closed-system device that maintains temperature and aliquots a mixed cell product and cryoprotectant into product bags. Cell product bags were thawed and expanded in flasks. Samples taken throughout this manufacturing process were analyzed for cell phenotype, exhaustion markers and functionality. The proportion of CD4+ and CD8+ T cells was maintained through each step, from pre-expansion and post-expansion to immediately after thaw and 24 h after thaw.ResultsInterestingly, phenotypic markers such as CD45RO, CD45RA and CCR7 evolved throughout the process and stem-like memory T cells emerged as the predominant phenotype in the clinically relevant 24-h post-thaw sample.ConclusionsModular automation supported the generation of stem-like memory T cells that were not terminally exhausted and were able to produce effector cytokines upon restimulation.     

X-ray crystallography of chemical compounds

AimsAccurate knowledge of molecular structure is a prerequisite for rational drug design. This review examines the role of X-ray crystallography in providing the required structural information and advances in the field of X-ray crystallography that enhance or expand its role.Main methodsX-ray crystallography of new drugs candidates and intermediates can provide valuable information of new syntheses and parameters for quantitative structure activity relationships (QSAR).Key findingsCrystallographic studies play a vital role in many disciplines including materials science, chemistry, pharmacology, and molecular biology. X-ray crystallography is the most comprehensive technique available to determine molecular structure. A requirement for the high accuracy of crystallographic structures is that a ‘good crystal’ must be found, and this is often the rate-limiting step. In the past three decades developments in detectors, increases in computer power, and powerful graphics capabilities have contributed to a dramatic increase in the number of materials characterized by X-ray crystallography. More recently the advent of high-throughput crystallization techniques has enhanced our ability to produce that one good crystal required for crystallographic analysis.SignificanceContinuing advances in all phases of a crystallographic study have expanded the ranges of samples which can be analyzes by X-ray crystallography to include larger molecules, smaller or weakly diffracting crystals, and twinned crystals.