Important Unresolved Problems Research Articles

Neoproterozoic timescales and stratigraphy

Abstract The Infracambrian is a term for mostly Neoproterozoic successions in North Africa and areas to the east. Its base lies within the middle Neoproterozoic period, or Cryogenian, includes the youngest Neoproterozoic period, or Ediacaran, and continues into the early Cambrian to the level at which trilobites first appear. The Cryogenian lacks any biostratigraphic zonation; and no global biostratigraphic schemes exist for the Ediacaran. The formal classification of the Neoproterozoic is currently under review. The Cryogenian–Ediacaran (CE) interval includes at least three prominent diamictite horizons that are clearly linked to penecontemporaneous glaciations. The oldest is ‘Sturtian’, next oldest is ‘Marinoan’ (probably the most extensive), both names are Australian in origin but are used internationally. The Gaskiers glaciation is the youngest and probably the least extensive. There are important unresolved problems of the precise number, age, extent and nomenclature of the Neoproterozic glaciations in Australia. Several palaeomagnetic poles in the age range 600–550 Ma place glacial deposits of that age range in Australia in tropical latitudes. These data, together with older poles from Laurentia, gave rise to the notion of the Snowball Earth, in which the Earth froze over completely, but the profound refrigeration required appears to have had very little effect on biological evolution. Biostratigraphic zonation with the precision attainable throughout the Phanerozoic does not appear possible for the CE interval. Thus, most correlations are based on about 40 U–Pb and Re–Os dates. These confirm the existence of at least three glacial sequences (sequence is used here as an informal term), but it is possible that the Sturtian and Marinoan were essentially one glacial unit. Deglaciation was accompanied by the unique ‘cap carbonates’. The glacial sequences all show a characteristic δ 13 C pattern, but present knowledge is inadequate to use these patterns for detailed global correlation. The most reliable chemostratigraphic correlations are likely to be based on strontium isotope variations. Black shale horizons commonly follow deglaciation. A few basins produce Neoproterozoic hydrocarbons; others are potential producers. As a whole, the Neoproterozoic represents both a scientific and an exploration frontier.

A Defect in the Ionotropic Glutamate Receptor 6 Gene ( GRIK2) Is Associated with Autosomal Recessive Mental Retardation

Nonsyndromic mental retardation is one of the most important unresolved problems in genetic health care. Autosomal forms are far more common than X-linked forms, but, in contrast to the latter, they are still largely unexplored. Here, we report a complex mutation in the ionotropic glutamate receptor 6 gene (GRIK2, also called "GLUR6") that cosegregates with moderate-to-severe nonsyndromic autosomal recessive mental retardation in a large, consanguineous Iranian family. The predicted gene product lacks the first ligand-binding domain, the adjacent transmembrane domain, and the putative pore loop, suggesting a complete loss of function of the GLU(K6) protein, which is supported by electrophysiological data. This finding provides the first proof that GLU(K6) is indispensable for higher brain functions in humans, and future studies of this and other ionotropic kainate receptors will shed more light on the pathophysiology of mental retardation.

Electrotransfer as a Non Viral Method of Gene Delivery

Over the last few decades, various vectors have been developed in the field of gene therapy. There still exist a number of important unresolved problems associated with the use of viral as well as non viral vectors. These techniques can suffer from secondary toxicity or low gene transfer efficiency. Therefore an efficient and safe method of DNA delivery still needs to be found for medical applications. DNA electrotransfer is a physical method that consists of the local application of electric pulses after the introduction of DNA into the extra cellular medium. As electrotransfer has proven to be one of the most efficient and simple non viral methods of delivery, it may provide an important alternative technique in the field of gene therapy. The present review focuses on questions related to the mechanism of DNA electrotransfer, i.e. the basic physical processes responsible for the electropermeabilisation of lipid membranes. It also addresses the current limitations of the method as applied to DNA transfer, in particular its efficiency in achieving in vitro gene expression in cells and also its potential use for in vivo gene delivery.

When Did Plate Tectonics Begin on the North China Craton? Insights from Metamorphism

Understanding when and why plate tectonics began on Earth is one of the most important unresolved problems in earth sciences. As a final result of plate tectonics, continental collisional orogens are formed, and the identification of such orogens is regarded as a milestone in recognizing the operation of plate tectonics in Earth's history. Metamorphism of continental collisional belts is generally characterized by clockwise p-T paths, especially for those involving isothermal decompression following the peak metamorphism. Therefore, clockwise p-T paths involving isothermal decompression are considered one of the important indicators for recognition of plate tectonics, especially in the early history of the earth. As one of the oldest continental blocks in the world, the North China Craton is considered a promising area for applying the large-scale synthesis approach of metamorphic p-T paths in understanding tectonic settings or processes since extensive investigations have been undertaken on the p-T-t evolution of the basement rocks over the craton. Tectonically, the North China Craton is composed of three small continental blocks (Eastern Block, Yinshan Block, and Ordos Block) and three Paleoproterozoic mobile belts (Trans-North China Orogen, Khondalite Belt, and Jiao-Liao-Ji Belt). Metamorphism of late Archean basement rocks in the Eastern and Yinshan Blocks is characterized by anticlockwise p-T paths, mostly involving isobaric cooling, suggesting that the heating source of the metamorphism was related to the underplating or intrusion of large volumes of mantle-derived magmas. Although theoretically such mantle-derived magmas form under continental magmatic arc, mantle plume or continental rift environments, only a mantle plume model can reasonably explain spatial and temporal distribution, lithological association, and structural features of the late Archean basement rocks in the Eastern and Yinshan Blocks. Therefore, mantle plumes may be the major tectonic mechanism that governed the formation and evolution of the late Archean crust in the Eastern and Yinshan Blocks, and plate tectonics may not have operated in the two blocks during late Archean period. Metamorphism of the basement rocks in the Paleoproterozoic Khondalite Belt and the Trans-North China Orogen is both characterized by clockwise p-T paths involving isothermal decompression following peak metamorphism, which suggests that the two orogens underwent initial crustal thickening followed by rapid exhumation/uplift tectonic processes. Such tectonic processes are typical indicators of collisional orogens that accommodate plate tectonics. The Paleoproterozoic Jiao-Liao-Ji Belt can be divided into the southern and northern zones, of which the former is characterized by anticlockwise p-T paths, whereas the latter is characterized by clockwise p-T paths, also indicating a regime of plate tectonics. The time of the initiation of plate tectonics in the North China Craton can be approximated by the age of the earliest juvenile crustal components in the three Paleoproterozoic tectonic belts. So far, the convincing oldest, subduction-related, juvenile crustal component in the North China Craton is the 2.56 Ga Wutai granitoids in the Trans-North China Orogen, which can be used to approximate the timing of the onset of plate tectonics in the North China Craton.

Axonal terminals of sensory neurons and their morphological diversity.

The application of electron microscopy to defining the fine structural characteristics of axon terminals and synapses was followed by a half century of intensive exploration of the molecular concomitants of synaptic activity. The summer of 2003 marks the 50th anniversary of the earliest accounts of synapses by Palay and Palade. Prompted by recent findings of specialization in the fine structure of nociceptor terminals that lack contacts remotely resembling a synapse, we present a survey of arrangements, contacts and axoplasmic contents of peripheral sensory axon terminals. The morphological principles underlying the variety of small, clear, spherical vesicles, mitochondrial aggregation, the membrane thickenings associated with sensory terminals and the organelles or inclusions associated with the site of transduction apparently do not conform to a simple parsimonious rule. It is also evident that the terminal of the central branch of bifurcated sensory axons differs structurally from its distal counterparts. This brief illustrated account addresses some important unresolved problems in the functional interpretation of the diverse morphological features exhibited in both synaptic and non-synaptic sensory axon terminals with the aim of identifying and emphasizing some key questions amenable to resolution with contemporary morphological and physiological techniques.

Research Commentary: Introducing a Third Dimension in Information Systems Design—The Case for Incentive Alignment

Prior research has generated considerable knowledge on information systems design from software engineering and user-acceptance perspectives. As organizational processes are increasingly embedded within information systems, one of the key considerations of many business processes—organizational incentives—should become an important dimension of any information systems design and evaluation, which we categorize as the third dimension: incentive alignment. Incentive issues have become important in many IS areas, including distributed decision support systems (DSS), knowledge management, and e-business supply chain coordination. In this paper we outline why incentives are important in each of these areas and specify requirements for designing incentive-aligned information systems. We identify and define important unresolved problems along the incentive-alignment dimension of information systems and present a research agenda to address them.

Introducing a Third Dimension in Information Systems Design: The Case for Incentive Alignment

Prior research has generated considerable knowledge on information systems design from software engineering and user-acceptance perspectives. As organizational processes are increasingly embedded within information systems, one of the key considerations of many business processes — organizational incentives — should become an important dimension of any information systems design and evaluation, which we categorize as the third dimension: incentive alignment. Incentive issues have become important in many IS areas, including distributed decision support systems (DSS), knowledge management, and e-business supply chain coordination. In this paper we outline why incentives are important in each of these areas and specify requirements for designing incentive-aligned information systems. We identify and define important unresolved problems along the incentive-alignment dimension of information systems and present a research agenda to address them.

Research Commentary: An Agenda for Information Technology Research in Heterogeneous and Distributed Environments

Application-driven, technology-intensive research is critically needed to meet the challenges of globalization, interactivity, high productivity, and rapid adaptation faced by business organizations. Information systems researchers are uniquely positioned to conduct such research, combining computer science, mathematical modeling, systems thinking, management science, cognitive science, and knowledge of organizations and their functions. We present an agenda for addressing these challenges as they affect organizations in heterogeneous and distributed environments. We focus on three major capabilities enabled by such environments: Mobile Computing, Intelligent Agents, and Net-Centric Computing. We identify and define important unresolved problems in each of these areas and propose research strategies to address them.

Developmental regulation of benzylisoquinoline alkaloid biosynthesis in opium poppy plants and tissue cultures

Opium poppy (Papaver somniferum L.) contains a number of pharmaceutically important alkaloids of the benzylisoquinoline type including morphine, codeine, papaverine, and sanguinarine. Although these alkaloids accumulate to high concentrations in various organs of the intact plant, only the phytoalexin sanguinarine has been found at significant levels in opium poppy cell cultures. Moreover, even sanguinarine biosynthesis is not constitutive in poppy cell suspension cultures, but is typically induced only after treatment with a funga-derived elicitor. The absence of appreciable quantities of alkaloids in dedifferentiated opium poppy cell cultures suggests that benzylisoquinoline alkaloid biosynthesis is developmentally regulated and requires the differentiation of specific tissues. In the 40 yr since opium poppy tissues were first culturedin vitro, a number of reports on the redifferentiation of roots and buds from callus have appeared. A requirement for the presence of specialized laticifer cells has been suggested before certain alkaloids, such as morphine and codeine, can accumulate. Laticifers represent a complex internal secretory system in about 15 plant families and appear to have multiple evolutionary origins. Opium poppy laticifers differentiate from procambial cells and undergo articulation and anastomosis to form a continuous network of elements associated with the phloem throughout much of the intact plant. Latex is the combined cytoplasm of fused laticifer vessels, and contains numerous large alkaloid vesicles in which latex-associated poppy alkaloids are sequestered. The formation of alkaloid vesicles, the subcellular compartmentation of alkaloid biosynthesis, and the tissue-specific localization and control of these processes are important unresolved problems in plant cell biology. Alkaloid biosynthesis in opium poppy is an excellent model system to investigate the developmental regulation and cell biology of complex metabolic pathways, and the relationship between metabolic regulation and cell-type specific differentiation. In this review, we summarize the literature on the roles of cellular differentiation and plant development in alkaloid biosynthesis in opium poppy plants and tissue cultures.

Forest management challenges for operational researchers

This is an overview of operational research work that has been carried out to support strategic forest management planning, short term forest planning, forest operations, and forest fire management. It identifies important unresolved problems and new challenges that could serve as a rich source of problems for both practitioners and researchers.

Current Issues in Clinical and Experimental Cardiac Transplantation

Cardiac transplantation is now an accepted therapy for end-stage heart failure not amenable to usual medical or surgical therapy. Despite excellent survival, important unresolved problems remain. This review focuses on current issues in cardiac transplantation. These controversial areas of active interest include the relationship between histocompatibility matching and the results of transplantation, the causes and treatment of graft coronary arteriopathy, and the mechanism of reversible heart failure that is caused by reversible transplant rejection. These fascinating unresolved issues remain significant challenges to those involved in the care of heart transplant recipients. Their resolution will improve significantly the results of this form of therapy.

Restenosis after successful percutaneous transluminal coronary angioplasty

R ESTENOSIS after initially successful percutaneous transluminal coronary angioplasty (PTCA) remains one of the most important unresolved problems associated with this procedure, occurring in approximately 25% to 35% of patients. The peculiar pattern of restenosis is such that the recurrence of signs and symptoms of ischemia appears in the vast majority of patients between 2 and 5 months after the procedure, and is rarely seen after 8 months.‘-4 Although restenosis usually can be effectively managed by repeat PTCA,596 the large number of patients so affected adds significantly to the morbidity and detracts from the potential economic advantages of this therapeutic modality. It might even be argued that PTCA is medically ineffective and financially wasteful in the occasional patient who requires multiple repeat PTCAs’ and ultimately, coronary bypass surgery. Ever mindful that restenosis is a common problem with obvious clinical implications, physicians routinely monitor post-PTCA patients with frequent stress tests, adding to its financial and emotional cost. Restenosis rates have remained constant despite improved initial results in ever more complex cases; hence, better catheter and guidewire technoIogy and increased operator experience are not the answers to this problem.3*8*g Recognition that recent clinical trials of antiplatelet agents and vasodilators have proven ineffective as preventive measures is a further sobering thought. Where do we go from here? This review of potential mechanisms of restenosis and the factors influencing its occurrence is undertaken on the premise that a compilation of such information will benefit both the clinician and the investigator.

Can mt2? mb2Arise from Small Corrections in Four-Family Models?

The origin of the observed quark and lepton spectrum is one of the important unresolved problems in theoretical physics. This spectrum is (by construction) arbitrary within the Standard Model [SM]1 and therefore it may serve as a window to new physics beyond the SM (i.e. at energy scales above a few hundred GeV).

Important unresolved problems in marine chemistry

SEVERAL research problems come to mind that would fall into the category of unresolved problems in marine chemistry. The chemistry and biochemistry of deep sea thermal vents and near-shore submarine vents are intriguing problem areas that are currently the focus of great attention at the empirical level.

The Late Weichselian glacial maximum in western Svalbard

The glacial history of Svalbard and the Barents Sea during the Late Weichselian has been much debated during the last few years; reviews are presented by Andersen (1981), Boulton et al. (1982), ElverhBi & Solheim (1983) and Vorren & Kristoffersen (1986). In our opinion (Mangerud et al. 1984) it is now demonstrated that a relatively large ice-sheet complex existed over most of Svalbard and large parts (if not all) of the Barents Sea. One of the main arguments for a large ice sheet is the pattern of uplift, including the 9,800 B.P. date on the 100 m shoreline in Kong Karls Land (Salvigsen 1981). Important unresolved problems include how large that ice sheet was, the location of the different ice domes and ice fronts, the age and duration of the glacial maximum, and the deglaciation history. We will here report on these problems bringing some results from the Van Mijenfjorden and Isfjorden area (Fig. 1); a more comprehensive paper is in preparation.

Photoradiation therapy: Current status and applications in the treatment of brain tumors

Photoradiation therapy is achieved when a photosensitizing drug is activated by light to form products that are lethal to tumor cells. The most commonly used drug is hematoporphyrin derivative, which is preferentially taken up and retained by malignant tissue. Photoactivation is usually produced by using a dye laser tuned at 630 nm (red light). The primary mechanism of neoplastic cell damage in photoradiation therapy involves the production of free radicals formed during illumination of hematoporphyrin derivative by light of this wavelength. The treatment would seem to damage first the tumor cell membrane, then the cytoplasmic inclusions, and finally the nucleus. Photoradiation therapy has been quite effective in the treatment of superficial malignancies, especially in skin, breast, eye, bladder, bronchus, and stomach. Experience with brain tumors is still limited. Important unresolved problems in the application of photoradiation therapy to gliomas include relative uptake of hematoporphyrin derivative into the tumor, limited light penetration of the tissue, local heating, and damage induced in normal brain by photoradiation therapy.

Simultaneous observations of equatorial ionospheric scintillation on four frequencies

RADIO waves emanating from stars or satellites fluctuate in intensity when received on the ground. This phenomenon, radioscintillation, arises from irregularities in the ionosphere through which the waves must pass. These scintillations have been studied in an attempt to understand the properties of the irregulatiries themselves but with the advent of satellite communications the knowledge of the ionospheric scintillations has become essential for the proper planning of the systems. One of the important unresolved problems is the variation of scintillation with frequency. This note describes our recordings of the scintillations at equatorial latitudes occurring simultaneously on 40, 140, 360 and 860 MHz.

Investment sequencing, allocation, and learning in the design of water resources systems: An empirical application

Four of the more important unresolved problems in the design of water resources systems involve a determination of methods to deal with technological progress (e.g., new desalting processes), availability of water from more than a single supply source, the rate of investment in the capital complex employed to exploit the resource along with the allocation of water once the capital complex is in place, and price sensitive demands for water. The importance of these issues is demonstrated, and a decision framework is advanced which formally incorporates each along with a new technique for solving large‐scale investment‐sequencing and water allocation problems. The robustness and convergence properties are formally demonstrated. Finally, the framework is applied to an empirical situation in California with rather encouraging results.