Chromosome studies in "preleukemia". III. Myelofibrosis

Cytogenetic studies were done on 18 patients with myelofibrosis or the closely related syndrome, undifferentiated myeloproliferative disorder (MPD). Clones of cells with chromosome abnormalities were demonstrated in the blood of eight individuals, including two with a history of radiation therapy and two with "acute myelofibrosis". Trisomy 8 was present in the latter two patients, but otherwise, there was no consistent cytogenetic pattern or correlation with specific hematologic findings. Sixteen of these patients have been followed for more than 1 year or until death; none has progressed to leukemia. The results indicate that chromosome abnormalities are relatively common in this disorder, but as with polycythemia vera, and unlike some other "preleukemic" states, the aberrant clones in myelofibrosis do not appear to indicate that clinical leukemia is imminent.     

Effects of hypothalamic temperature changes on the sweat rate in Macaca mulatta

The concept of cardiac reconditioning centers for the prevention and rehabilitation of coronary patients has been tremendously successful in Germany over the past 20 years. At least 40 such centers are located throughout the country. Physicians, nurses, and physical therapists work closely together in the various facets of the rehabilitation process. The financial backing for these facilities is primarily through governmental and regional insurance companies, whose officials are apparently convinced that in the long run supporting preventive measures is financially sound. Objective data supporting their convictions come from studies such as that of Brusis, who showed that such as that of 1,500 employees was diminished by nearly 70 percent during a two-year period after cardiac reconditioning, as compared to a similar time period before the rehabilitation experience. Subjective benefits, which are extremely difficult to quantitate in meaningful terms, were nonetheless expressed by nearly all the patients with whom I conversed. Perhaps they have experienced the same feelings that Mark Twain did when he observed that "all frets and worries and chafings sank to sleep in the presence of the benignant serenity of the Alps; the Great Spirit of the Mountains breathed his own peace upon their hurt minds and sore hearts and healed them."     

NFPA 70E

National Fire Protection Association 70E, standard for electrical safety in the workplace is a consensus standard approved as an American national standard. Whereas the NFPA 70 National Electrical Code is primarily an installation standard for premise electrical systems, focuses on electrical safety requirements to protect individuals working on or near electrical equipment. This article will discuss some of the key aspects of the 2004 Edition of NFPA 70E, with a focus on safety-related work practices. In addition, this article also presents some of the potential directions for requirements in future editions of NFPA 70E.     

A reconfigurable FACTS system for university laboratories

To fully understand the dynamic performance of the multiple flexible ac transmission systems (FACTS) devices, a hardware setup is needed to complement software simulation for university research laboratories. This paper presents the schematic and basic controls of a reconfigurable FACTS system that can be used to realize the major voltage-sourced-converter FACTS topologies: the StatCom, the static synchronous series compensator (SSSC), and the unified power-flow controller (UPFC). Furthermore, the state models and control algorithms for the FACTS devices are proposed. The digital signal processor (DSP)-based control system enables new control methods to be rapidly implemented. The comparison of the experimental and simulation results is also provided to verify the proposed controls. The paper culminates in a list of suggested experiments appropriate for an elective/graduate course in electric power systems.     

An observation system simulation experiment for the impact of landsurface heterogeneity on AMSR-E soil moisture retrieval

Using a high-resolution hydrologic model, a land surface microwave emission model (LSMEM), and an explicit simulation of the orbital and scanning characteristics for the advanced microwave sensing radiometer (AMSR-E), an observing system simulation experiment (OSSE) is carried out to assess the impact of land surface heterogeneity on large-scale retrieval and validation of soil moisture products over the U.S. Southern Great Plains using the 6.925 GHz channel on the AMSR-E sensor. Land surface heterogeneity impacts soil moisture products through the presence of nonlinearities in processes represented by the LSMEM, as well as the fundamental inconsistency in spatial scale between gridded soil moisture imagery derived from in situ point-scale sampling, numerical modeling, and microwave remote sensing sources. Results within the 575000 km² Red-Arkansas River basin show that, for surfaces with vegetation water contents below 0.75 kg/m², these two scale effects induce root mean squared errors (RMSEs) of 1.7% volumetric (0.017 cm_water³/cm_soil³ ) into daily 60 km AMSR-E soil moisture products and RMS differences of 3.0% (0.030 cm_water/3cm_soil³ ) into 60 km comparisons of AMSR-E soil moisture products and in situ field-scale measurements of soil moisture sampled on a fixed 25-km grid     

DNA vaccination against Theiler''s murine encephalomyelitis virus leads to alterations in demyelinating disease

Using glycerinated spasmoneme of giant Zoothamnium sp., the physical properties of spasmoneme before and after Ca2+-induced contraction (pCa 4.5) were investigated. The volume change of spasmoneme contraction was measured under zero tension. The length and diameter decreased by about 50% of their initial value as a result of contraction, which means that contraction is nearly isotropic. Thus the volume of spasmoneme decreased drastically by 86% of its original value. The swollen ratio of extended and contracted spasmoneme were 0.07 and 0.37, respectively. Tension-extension relationships of extended and contracted spasmonemes were measured. By applying the theory of rubber elasticity, the number of segments of a chain in originally extended spasmoneme was only 3.3, i.e., the chain was almost a straight one. On the other hand, the number of segments of a chain in contracted spasmoneme was more than 100, i.e., the chain was essentially a random one. Furthermore, the total number of chains in single spasmoneme was the same in extended and contracted spasmoneme. This means that the interchain cross-links of chains were not influenced by addition or removal of Ca2+. Moreover, the molecular weight of a chain is estimated to be at most about 50 kd. By considering all these results, it is concluded that the contractile mechanism of spasmoneme originates in the intramolecular folding and unfolding induced by Ca2+ binding and detaching.     

Impacts of global environmental change on future health and health care in tropical countries

The most common strategy in the development of HIV-1 protease inhibitors has been the design of high affinity transition state analogs that effectively compete with natural substrates for the active site. A second approach has been the development of compounds that inactivate the protease by destabilizing its quaternary or tertiary structure. A successful optimization of these strategies requires an accurate knowledge of the energetics of structural stabilization and binding, and the identification of those regions in the protease molecule that are critical to stability and function. Here the energetics of stabilization of the HIV-1 protease has been measured for the first time by high sensitivity differential scanning calorimetry. These studies have permitted the evaluation of the different components of the Gibbs energy of stabilization (the enthalpy, entropy and heat capacity changes). The stability of the protease is pH-dependent and due to its dimeric nature is also concentration-dependent. At pH 3.4 the Gibbs energy of stabilization is close to 10 kcal/mol at 25 degreesC, consistent with a dissociation constant of 5x10(-8) M. The stability of the protease increases at higher pH values. At pH 5, the Gibbs energy of stabilization is 14.5 kcal/mol at 25 degreesC, consistent with a dissociation constant of 2.3x10(-11) M. The pH dependence of the Gibbs energy of stabilization indicates that between pH 3.4 and pH 5 an average of 3-4 ionizable groups per dimer become protonated upon unfolding. A structure-based thermodynamic analysis of the protease molecule indicates that most of the Gibbs energy of stabilization is provided by the dimerization interface and that the isolated subunits are intrinsically unstable. The Gibbs energy, however, is not uniformly distributed along the dimerization interface. The dimer interface is characterized by the presence of clusters of residues (hot spots) that contribute significantly and other regions that contribute very little to subunit association. At the dimerization interface, residues located at the carboxy and amino termini contribute close to 75% of the total Gibbs energy (Cys95, Thr96, Leu97, Asn98 and Phe99 and Pro1, Ile3, Leu5). Residues Thr26, Gly27 and Asp29 located at the base of the active site are also important, and to a lesser extent Gly49, Ile50, Gly51 located at the tip of the flap region. The structure-based thermodynamic analysis also predicts the existence of regions of the protease with only marginal stability and a high propensity to undergo independent local unfolding. In particular, the flap region occupies a very shallow energy minimum and its conformation can easily be affected by relatively small perturbations. This property of the protease can be related to the ability of some mutations to elicit resistance towards certain inhibitors.     

Downregulation of the pro-apoptotic protein Bak is required for the ras-induced transformation of intestinal epithelial cells

Anoikis is a form of programmed cell death induced in normal epithelial cells by detachment from the extracellular matrix [1] [2] [3]. In epithelial cells of the intestine and other organs, activated rasinduces resistance to anoikis [3] [4], but the actual molecular effectors directly involved in the apoptotic machinery that execute or block anoikis have not yet been identified. Bak, a pro-apoptotic member of the Bcl-2 family, is downregulated in a high proportion of colorectal tumours [5]. In addition, Bak is an important regulator of apoptosis in normal intestinal epithelial cells [6] [7]. Here, we show that activated rasinduces the downregulation of Bak in rat and human intestinal epithelial cells. This ras-induced downregulation of Bak expression could be suppressed by an inhibitor of phosphatidylinositol (PI) 3-kinase, an enzyme already implicated in ras-induced resistance to anoikis [8]. Ectopic expression of Bak in ras-transformed rat intestinal epithelial IEC-18 cells inhibited ras-induced resistance to anoikis and significantly reduced their tumorigenicity. We conclude, therefore, that the ability of rasto downregulate Bak, and the consequent resistance to anoikis, are essential components of the transforming capacity of this oncogene in intestinal epithelial cells.     

Outcome of long-term enteral feeding

In the past two decades, many technical advances have made tube enteral feeding much more comfortable and acceptable to patients and their families. This has greatly expanded the use of this therapy, both in clinical conditions where it was traditionally prescribed and in many other diagnoses. This expanded use raises important questions about how much enteral nutrition is being used, the medical outcome in different clinical conditions, and the quality of life experienced by long-term therapy users. This article addresses these outcome issues for patients in the nonhospital setting.