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The methods of quickly achieving the adiabatic effect through a non-adiabatic process has recently drawn widely attention both in quantum and classical regime. In this work ,we study the classical adiabatic shortcut for two- and three-Level atoms by transforming the quantum version into classical one via quantum-classical corresponding theory. The results shows that, the additional couplings between the oscillators can be used to speed up the adiabatic evolution of coupled oscillators. Furthermore, we find that the quantum-classical correspondence theory still holds for the couter-adiabatic driving Hamiltonian for the TQD. This means that, we can obtain the counter-adiabatic driving Hamiltonian for a classical system by averaging over its quantum correspondence in a quantum system. This provides a feasible way to study the classical adiabatic shortcut and the simulation for the quantum adiabatic shortcut in a classical system.

Protein therapy, wherein therapeutic proteins are delivered to treat disorders, is considered the safest and most direct approach for treating diseases. However, its applications are highly limited by the paucity of efficient strategies for delivering proteins and the rapid clearance of therapeutic proteins in vivo after their administration. Here, we demonstrate a novel strategy that can significantly prolong the circulation time of therapeutic proteins as well as minimize their immunogenicity. This is achieved by encapsulating individual protein molecules with a thin layer of crosslinked phosphorylcholine polymer that resists protein adsorption. Through extensive cellular studies, we demonstrate that the crosslinked phosphorylcholine polymer shell effectively prevents the encapsulated protein from being phagocytosed by macrophages, which play an essential role in the clearance of nanoparticles in vivo. Moreover, the polymer shell prevents the encapsulated protein from being identified by immune cells. As a result, immune responses against the therapeutic protein are effectively suppressed. This work describes a feasible method to prolong the circulation time and reduce the immunogenicity of therapeutic proteins, which may promote the development and application of novel protein therapies in the treatment of diverse diseases.

Parkinson's disease (PD) is a neurodegenerative disease of the central nervous system that results from the degeneration of dopaminergic neurons in the substantia nigra. Abnormal gait begins in the early stage and becomes severe as the disease progresses; therefore, the assessment of gait becomes an important issue in evaluating the progression of PD and the effectiveness of treatment. To provide a clinically useful gait assessment in environments with budget and space limitations, such as a small clinic or home, we propose and develop a portable method utilizing the monocular image sequences of walking to track and analyze a Parkinsonian gait pattern. In addition, a centroid tracking algorithm is developed and used here to enhance the method of quantifying kinematic gait parameters of PD in different states. Twelve healthy subjects and twelve mild patients with PD participate in this study. This method requires one digital video camera and subjects with two joint markers attached on the fibula head and the lateral malleolus of the leg. All subjects walk with a natural pace in front of a video camera during the trials. Results of our study demonstrate the stride length and walking velocity significantly decrease in PD without drug compared to PD with drug in both proposed method and simultaneous gait assessment performed by GAITRite(®) system. In gait initiation, step length and swing velocity also decrease in PD without drug compared to both PD with drug and controls. Our results showed high correlation in gait parameters between the two methods and prove the reliability of the proposed method. With the proposed method, quantitative measurement and analysis of Parkinsonian gait could be inexpensive to implement, portable within a small clinic or home, easy to administer, and simple to interpret. Although this study is assessed Parkinsonian gait, the proposed method has the potential to help clinicians and researchers assess the gait of patients with other neuromuscular diseases, such as traumatic brain injury and stroke patients.

Augmentation of the mechanical properties of connective tissue using ultraviolet (UV) radiation-by targeting collagen cross-linking in the tissue at predetermined UV exposure time [Formula: see text] and wavelength [Formula: see text]-has been proposed as a therapeutic method for supporting the treatment for structural-related injuries and pathologies. However, the effects of [Formula: see text] and [Formula: see text] on the tissue elasticity, namely elastic modulus [Formula: see text] and modulus of resilience [Formula: see text], are not entirely clear. We present a thermomechanical framework to reconcile the [Formula: see text]- and [Formula: see text]-related effects on [Formula: see text] and [Formula: see text]. The framework addresses (1) an energy transfer model to describe the dependence of the absorbed UV photon energy, [Formula: see text], per unit mass of the tissue on [Formula: see text] and [Formula: see text], (2) an intervening thermodynamic shear-related parameter, [Formula: see text], to quantify the extent of UV-induced cross-linking in the tissue, (3) a threshold model for the [Formula: see text] versus [Formula: see text] relationship, characterized by [Formula: see text]-the critical [Formula: see text] underpinning the association of [Formula: see text] with [Formula: see text]-and (4) the role of [Formula: see text] in the tissue elasticity. We hypothesized that [Formula: see text] regulates [Formula: see text] (UV-stiffening hypothesis) and [Formula: see text] (UV-resilience hypothesis). The framework was evaluated with the support from data derived from tensile testing on isolated ligament fascicles, treated with two levels of [Formula: see text] (365 and 254 nm) and three levels of [Formula: see text] (15, 30 and 60 min). Predictions from the energy transfer model corroborated the findings from a two-factor analysis of variance of the effects of [Formula: see text] and [Formula: see text] treatments. Student's t test revealed positive change in [Formula: see text] and [Formula: see text] with increases in [Formula: see text]-the findings lend support to the hypotheses, implicating the implicit dependence of UV-induced cross-links on [Formula: see text] and [Formula: see text] for directing tissue stiffness and resilience. From a practical perspective, the study is a step in the direction to establish a UV irradiation treatment protocol for effective control of exogenous cross-linking in connective tissues.

Recent study on optical-field-ionization collisional-excitation extreme-ultraviolet lasing of Ni-like krypton at 32.8 nm pumped by a 100-TW laser system with an optically preformed plasma waveguide is reported. By using a 9-mm-long pure krypton plasma waveguide fabricated with the axicon-ignitor-heater scheme, the 32.8-nm extreme-ultraviolet laser provided an average output of 1012 photons/pulse at pump energy of 1 J, more than one order of magnitude enhancement relative to the previous results with the same scheme at pump energy of 235 mJ. It is also found the far-field pattern of laser beams varies from a single peak profile at low pump energy to an annular profile at high pump energy due to over-ionization of krypton ions at the center of the plasma channel.

Well-dispersed gold nanoparticles (NP) coated with tiopronin were synthesized by X-ray irradiation without reducing agents. High-resolution transmission electron microscopy shows that the average core diameters of the NPs can be systematically controlled by adjusting the tiopronin to Au mole ratio in the reaction. Three methods were used to study the NP uptake by cells: quantitative measurements by inductively coupled plasma mass spectrometry, direct imaging with high lateral resolution transmission electron microscopy and transmission X-ray microscopy. The results confirmed that the NP internalization mostly occurred via endocytosis and concerned the cytoplasm. The particles, in spite of their small sizes, were not found to arrive inside the cell nuclei. The synthesis without reducing agents and solvents increased the biocompatibility as required for potential applications in analysis and biomedicine in general Refereed/Peer-reviewed

Targeting HER-2 over-expressing breast cancer cells with trastuzumab has resulted in significant improvements in both disease-free and overall survival rates. However, despite a favorable initial response, some cancer cells become resistant and develop into fatal metastatic disease. Here we report that we can specifically target HER-2 over-expressing and trastuzumab-resistant breast cancer cells by using an engineered lentivirus which has trastuzumab bound to its envelope. In vitro, this lentiviral construct mediated both the expression of reporter genes, such as enhanced green fluorescent protein (EGFP) and firefly luciferase, as well as the therapeutic gene, herpes thymidine kinase (hTK), in HER-2 over-expressing cells. Subsequent application of the pro-drug ganciclovir selectively killed breast cancer cells in which lentivirus mediated expression of hTK. In vivo, we successfully targeted the expression of firefly luciferase to trastuzumab-resistant breast cancer tumors established in nude mice. Furthermore, we found that systemic administration of trastuzumab-bound lentivirus led to expression of EGFP in circulating trastuzumab-resistant breast cancer cells. In conclusion, HER-2 over-expressing breast cancer cells resistant to trastuzumab can be targeted for selective gene expression and destruction by viruses with envelope-proteins engineered to bind to this antibody.

We discuss the design, construction, and output characteristics of a versatile 10-TW Ti : sapphire laser system of high stability and spatiotemporal quality. By pumping the three amplifier stages independently and running at saturation, an energy stability of 1.3% is obtained. Controls over self-phase modulation, high-order dispersion, spatial aberration, and amplified spontaneous emission are done by robust passive methods. A time–bandwidth product of 1.2 times the Fourier-transform limit with a temporal contrast larger than 5×108 in the -10-ns scale, 2×106 in the -100-ps scale, and 104 in the -1-ps scale are achieved. The beam can be focused down to 1.2 times the diffraction limit with 80% of the energy enclosed in the Gaussian focal spot. Beam-pointing stability is

Silicon oxide (SiOx) films grown by plasma-enhanced chemical-vapor deposition (PECVD) were investigated for applications in a course wavelength-division multiplexing (CWDM) network. The SiOx films were deposited on 4-in. silicon wafers based on the reaction of N2O/SiH4 precursors. After postdeposition annealing at 1,150°C, the transmission spectra of the films prepared at different flow rates of the precursor were compared. We found that the transmission spectrum of the films deposited at the low-flow conditions can be flattened to a ripple of less than 0.5 dB ranging from visible up to 1,470 nm. In addition, the material losses at wavelengths around 1,500 nm caused by absorption of Si-H and N-H bonds were significantly reduced.

We characterize one transcription factor of DRE-binding proteins (TaDREB1) that was isolated from a drought-induced cDNA library of wheat (Triticum aestivum L.). TaDREB1 contains one conserved EREBP/AP2 domain, and shows similarity with Arabidopsis thaliana DREB family members in both overall amino-acid sequences and the secondary structure arrangement within the DNA-binding motifs. In yeast one-hybrid system, TaDREB1, can specially activate the genes fused with the promoter containing three tandemly repeated copies of the wild-type DRE sequence: TACCGACAT. In different wheat cultivars, the Ta DREB1 gene is induced by low temperature, salinity and drought; and the expression of Wcs120 that contains DRE motifs in its promoter is closely related to the expression of TaDREB1. These results suggest that TaDREB1 functions as a DRE-binding transcription factor in wheat. We also observed the dwarf phenotype in transgenic rice (T0) overexpressing TaDREB1.

A cDNA clone of a soybean gene encoding a proline-rich protein (PRP) was characterized and designated SbPRP ( Soy bean Proline- rich Protein). The SbPRP protein is a putative bimodular protein of 126 amino acids with a proline-rich domain and a hydrophobic cysteine-rich domain plus a signal peptide at the N terminal. Southern analysis indicates the presence of a single copy of the SbPRP gene in the soybean genome. The SbPRP gene expression was investigated and the results demonstrate that it accumulates in leaves and epicotyls of soybean seedlings, but not in cotyledons, hypocotyls and roots. The SbPRP mRNA was also expressed in response to salicylic acid and virus infection. In addition, the SbPRP gene transcription was regulated by circadian rhythm, salt stress, drought stress and plant hormones. These results indicate that the SbPRP gene might play a role in plant responses to multiple internal and external factors.

mRNA transcripts from salt-stressed and unstressed rice seedlings were detected by differential display to show alterations in abundance. One transcript, designated OsZFP1, was found to be significantly down-regulated by salt stress. OsZFP1 encodes a protein of 145 amino acids with three putative Cys2/Cys2-type zinc-finger domains. A homology search of GenBank databases showed that OsZFP1 is homologous to the rat and human ZIS(zinc-finger, splicing) proteins and the human nucleopore complex protein Nup358 in the zinc- finger domains. Genomic Southern analysis indicated that the OsZFP1 gene was present as a single-copy sequence in the rice genome. Restriction fragment length polymorphism mapping assigned the OsZFP1 gene to the distal position of chromosome 6. A RT-PCR assay showed that the OsZFP1 transcripts were more abundant in rice shoots than in the roots. Decreases in the level of OsZFP1 transcripts were detected in the shoots after 6 h of salt stress and in the roots after 3 h of salt stress. In addition, the expression of OsZFP1 in rice shoots was significantly repressed by exogenous application of abscisic acid. The results suggest that OsZFP1 represents a novel type of zinc-finger protein gene in plants and that it is implicated in the responses of rice plants to salt stress.

Suspension cultures of Stizolobium hassjoo cells were cultivated in a 7l bioreactor. The growth rate and intracellular L-DOPA content of the cells using two different turbine impellers were compared. There were distinct differences in growth behavior and L-DOPA productivity in the range of 100 to 500 rpm for flat-blade turbine impeller. Disk turbine retarded significantly the cell growth but not so significantly for L-DOPA production in the range of 200 to 300 rpm. The shear force intensity of the two impellers at various rotational rates was compared with shear force index (SFI), and power input per unit mass and eddy length scale. There was good consistency among the three indexes for shear force intensity. Thus with SFI the shear force intensity of bioreactor can be indirectly estimated. A critical shear stress that may cause sublytic effect in cells was identified for flat-blade turbine operated at 400 rpm. The common effect between the shear stress and the proton elicitation in the bioreactor was elucidated with a hypothesis of signal transduction by second messenger, H+. Our results suggested that H+ transduced the signal to protoplast when S. hassjoo cells were stimulated by shear stress. This resulted in an increase of H+ which triggered a similar reaction to the pH control of culture broth and enhanced the L-DOPA production.

4-Hydroxyproline di- and tri-peptides and N-cbz-hydroxypropyl- glycinamides were observed to be potent cytotoxic agents against the growth of suspended single cells, L-1210, Tmolt3, and HeLa-S3. The agents were not as potent against the growth of cultured solid tumor cells. Selected derivatives were investigated for their mode of action in Tmolt3 leukemia cells. The compounds selectively inhibited DNA synthesis at 50 and 100 microM. The target site of action of the agents appeared to be the purine de novo pathway with marked inhibition of the activities of the two regulatory enzymes of the pathway, i.e. PRPP amido-transferase and IMP dehydrogenase. d[NTP] pools were reduced by the agents consistent with their overall reduction of DNA synthesis. Other marginally inhibited targets of the agents were r-RNA polymerase and TMP-kinase activities. The DNA molecule itself did not appear to be a target of these agents.

The chemical states of iron in near-shore and deep-sea sediments were investigated by means of57Fe Mossbauer spectroscopy in combination with selective and nonselective chemical leachings. As far as a limited number of the sediments analyzed are concerned, Mossbauer spectra of near-shore sediments consist of high-spin paramgnetic ferrous (δ=1.13 mm/s, ΔEq=2.65 mm/s) and paramagnetic ferric (δ=0.35 mm/s, ΔEq=0.64 mm/s) components, while those of deep-sea sediments are composed of high-spin paramagnetic ferrous, paramagnetic ferrous, paramagnetic ferric and magnetic ferric (δ∼0.4 mm/s,H∼510 KG) components. The Fe2+/Fe3+ ratios of deepsea sediments are much smaller than those in near-shore sediments, while the total contents of iron in the former are much higher than those in the latter. This is principally due to the high contents of authigenic ferric oxides in deep-sea sediments. Further, in the aluminosilicate fraction, the Fe2+/Fe3+ ratios of deep-sea sediments are also smaller than those of near-shore sediments. This is probably attributed to high contents of clay minerals and authigenic aluminosilicates in deep-sea sediments relative to near-shore ones. The magnetic components in deepsea sediments are attributable to hematite, magnetite and/or maghemite.

We established “Multitracer”, a new versatile radiotracer technique, for simultaneous tracing of a number of elements in various chemical, environmental, and biological systems. Metal foil targets (typically Au, Ag, Ge, Cu and Fe) are irradiated with C, N, or O ions accelerated up to 135 MeV/nucleon by RIKEN Ring Cyclotron. Radiochemical procedures have been developed to remove the target material leaving the nuclides as Multitracer solutions containing various radionuclides of Be, Na, Mg, K, Ca, Sc, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Se, Br, Rb, Sr, Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag, Cd, In, Sn, Te, I, Ba, Ce, Pm, Eu, Gd, Tb, Tm, Yb, Lu, Hf, W, Re, Os, Ir, Pt, and Hg. Multitracers enable efficient tracing of a number of elements, and comparison of their behavior under strictly identical experimental conditions. Such features will be demonstrated by means of an example of application to a model experiment for the study of removal mechanism of various elements from the ocean.

Using the rice salt-tolerant mutant 20 as material, a cDNA library was constructed and two salt-inducible clones, SIR5.5 and SIR8.1, were isolated by differential screening. Homology analysis revealed that the two clones together constituted a chimeric rbcL which encoded a truncated large subunit of Rubisco with 337 amino-acids, plus 64 amino-acids of unknown origin. The expressions of both the normal and the chimeric locus appeared to be developmentally regulated and salt-inducible in shoots of the salt-tolerant mutant 20 and its original variety 77-170. In roots, their expressions were salt-inducible in the salt-tolerant mutant 20 whereas no, or only premature, forms were present in the salt-treated original variety 77-170. Higher concentrations of salt reduced the expressions of both normal rbcL and the chimeric locus. ABA showed no effect on their expression.

Mysm1−/− mice have severely decreased cellularity in hematopoietic organs. We previously revealed that Mysm1 knockout impairs self-renewal and lineage reconstitution of HSCs by abolishing the recruitment of key transcriptional factors to the Gfi-1 locus, an intrinsic regulator of HSC function. The present study further defines a large LSKs in >8-week-old Mysm1−/− mice that exhibit increased proliferation and reduced cell lineage differentiation compared with those of WT LSKs. We found that IRF2 and IRF8, which are important for HSC homeostasis and commitment as transcription repressors, were expressed at lower levels in Mysm1−/− HSCs, and Mysm1 enhanced function of the IRF2 and IRF8 promoters, suggesting that Mysm1 governs the IRFs for HSC homeostasis. We further found that the lower expressions of IRF2 and IRF8 led to an enhanced transcription of p53 in Mysm1−/− HSCs, which was recently defined to have an important role in mediating Mysm1−/−-associated defects. The study also revealed that Mysm1−/− thymocytes exhibited lower IRF2 expression, but had higher Sca1 expression, which has a role in mediating thymocyte death. Furthermore, we found that the thymocytes from B16 melanoma-bearing mice, which display severe thymus atrophy at late tumor stages, exhibited reduced Mysm1 and IRF2 expression but enhanced Sca1 expression, suggesting that tumors may downregulate Mysm1 and IRF2 for thymic T-cell elimination.

The chemical states of iron in near-shore and deep-sea sediments were investigated by means of57Fe Mossbauer spectroscopy using selective and chemical leachings. The Fe2+/Fe3+ ratios of deep-sea sediments were much smaller than those of near-shore sediments, while the total contents of iron in the former were much higher than those in the latter. This is principally due to the high content of hydrogenous ferric oxyhydroxide in deep-sea sediments. Also, in the aluminosilicate fraction, the Fe2+/Fe3+ ratios of deep-sea sediments were smaller than those of near-shore sediments. This is probably attributed to the difference in the silicate mineral composition between deep-sea and near-shore sediments. X-ray reflections of clay minerals normalized to those of feldspars and quartz were more intense in deep-sea sediments than in near-shore sediments.

In this study the lytic cycle of a filamentous phage is reported. Under normal laboratory cultivation conditions a virulent form could spontaneously and easily arise from a temperate phage. The virulent one could superinfect cells containing Cf1t lysogen. Therefore, we have named it Cf1tv. In a colony formation assay using cells from an infected culture, two types of colonies were observed, small and large. It could be proven that the formation of small colonies is the result of killing during Cf1tv infection. The number of small colony forming units (cfu) increased with infection time and reached a maximum at 16 h after infection, then dropped to the initial cell concentration at 28 h after infection; 28 h were required to kill all infected cells. Large colonies contained uninfected or phage-resistant cells, but no lysogenic cells. Bacterial death was further confirmed by a microculture assay. At 2 h after infection, normal-dividing cells (cfu giving large colonies) contained about 40% of Cf1tv-infected cells, then the percentage decreased with infection time. Slow-dividing cells (infected cfu giving small colonies) initially contained 55% of cells; this percentage increased slightly at 4 h after infection, then decreased at 8 h after infection. Non-dividing cells initially contained 5% of infected cells, then their numbers rapidly increased with time after infection. The cell division was seriously affected and finally stopped. During one-step growth, the latent period was 30 min and there was no burst; phages were released at 30 min after infection and the rate of release increased gradually with time after infection. Phage DNA integration into host chromosome could not be observed.

1-Acetyl-4-phenyl-1,2,4-triazolidine-3,5-dione (APTD) has hypolipidaemic, anti-inflammatory, analgesic, antineoplastic, and aldose reductase inhibitory activities in animals. Disposition studies using pooled plasma and urine samples showed that [1-14C-acetyl]-1-acetyl-4-phenyl-1,2,4-triazolidine-3,5-dione (14C-APTD) had a maximum half-life of 20 hours. Urinary excretion accounted for less than 3% of the radioactivity elimination, while faecal excretion may account for up to 45% of the total elimination. In a 96-hour tissue distribution study, there was no sequestering of 14C-APTD in any of the organs. 14C-APTD demonstrated significant aqueous partitioning, and almost no binding to bovine serum albumin. In L1210 tumour cells, 14C-APTD was bound to DNA and RNA, and there was no binding to intracellular protein. 14C-APTD underwent significant metabolism in mice. One metabolite excreted in urine was identified; two other possible metabolites were proposed.

Iron foil was irradiated with an 80 MeV/nucleon16O-ion beam. The foil was dissolved in hydrochloric acid, and Fe2+ in the solution was oxidized to Fe3+ with hydrogen peroxide. The solution was diluted to 6M in HCl and was passed through an anion exchange column. Washing with 6M HCl yielded a carrier- and salt-free multitracer solution covering radioactive nuclides of elements from sodium to manganese.

A sand sample collected at the foot of Flaming Mountain was studied further. On the basis of the change in the relative intensity after heat treatment, one of the sextets observed in its Mossbauer spectrum at liquid nitrogen temperature was ascribed to goethite. This result provides a useful information on the geological history of the region where the mountain is located.

The chemical states of iron in a deep-sea sediment, a manganese nodule and a nearshore sediment are studied before and after chemical leaching. The Mossbauer spectra of the manganese nodule after chemical leaching clearly revealed the presence of a ferrous component not identified in previons studies. The ferrous component in the deep-sea sediment and the manganese nodule are shown to originate in terrigenous materials transported from lands through the atmosphere.

Background Human immunodeficiency virus (HIV) infection of CD4(-) cells has been demonstrated, and this may be an important mechanism for HIV transmission. Results We demonstrated that a membrane protein, claudin-7 (CLDN-7), is involved in HIV infection of CD4(-) cells. A significant increase in HIV susceptibility (2- to 100-fold) was demonstrated when CLDN-7 was transfected into a CD4(-) cell line, 293T. In addition, antibodies against CLDN-7 significantly decreased HIV infection of CD4(-) cells. Furthermore, HIV virions expressing CLDN-7 on their envelopes had a much higher infectivity for 293T CD4(-) cells than the parental HIV with no CLDN-7. RT-PCR results demonstrated that CLDN-7 is expressed in both macrophages and stimulated peripheral blood leukocytes, suggesting that most HIV virions generated in infected individuals have CLDN-7 on their envelopes. We also found that CLDN-7 is highly expressed in urogenital and gastrointestinal tissues. Conclusion Together these results suggest that CLDN-7 may play an important role in HIV infection of CD4(-) cells.

A simple and novel salicidation process applying pulsed laser annealing as the first annealing step was used to induce TiSi2 formation. Both Raman spectroscopy and transmission electron microscope results confirm the formation of a new phase of Ti disilicide, the pure C40 TiSi2 after laser irradiation. Direct C54 phase growth on the basis of C40 template bypassing the C49 phase is accomplished at the second annealing temperature as low as 600°C. Line width independent formation of the C54 phase was observed on patterned wafers using this salicidation process and “fine line effect” is thus eliminated.

Powder X-ray diffraction and electrical-resistivity measurement were used to study the structure and the Tc variation of Y(Ba1−xRx)2Cu3O7−δ(0≤x≤0.2; R=La, Pr, and Nd). The solubility limit was estimated as x=0.05, 0.075, and >0.2 with R=Nd, Pr, and La, respectively, which depends on the ionic radius of dopants. All three series undergo an orthorhombic-to-tetragonal transition at x≈0.15-0.2. Meanwhile, the Tc increases slightly through a maximum at x≈0.025; then decreases rapidly with x, indicating an overdoped system for YBa2Cu3O7−δ. Whereas, the normal-state resistivity increases with x for all temperature ranges. The similarities and differences with various dopants are discussed in conjunction with ionic size, valence change and hole-filling mechanism.

Human T-cell leukaemia viruses (HTLVs) have genomic organization distinct from that of other replication-competent retroviruses, possessing four genes, gag, pol, env and χ. The unique fourth gene, χ (also referred to as lor), is located between env and the 3′ long terminal repeat (LTR), encoding a protein of relative molecular mass 40,000 for HTLV-I and 37,000 for HTLV-II1,2, located in the nucleus of infected cells3,4. HTLV-I is the causative agent of adult T-cell leukaemia (ATL), a T-lymphocyte malignancy5,6, while HTLV-II has been found associated with a T-cell variant of hairy cell leukaemia7,8. Both viruses immortalize T cells in vitro9–11. However, the mechanism of cellular transformation induced by HTLV is not known as there seems to be no common site of provirus integration in primary ATL cells12 and the viras contains no classical oncogene sequences13,14. These observations have provoked speculation that the unique and strongly conserved χ protein (85% amino-acid homology between HTLV-I and -II) is involved in HTLV leukaemogenesis. Recent mutagenesis experiments in our laboratory have shown that the χ gene is essential for HTLV replication15. It has also been shown that the LTRs of HTLV and the related bovine leukaemia virus (BLV) are activated in trans in virus-infected cells16–19, and, although such experiments did not directly demonstrate a role for the χ protein in transcriptional activation, it has been suggested that the χ protein is responsible for the transcriptional activation of the LTR and may be involved in cellular transformation3,4,16. We have now developed a transient co-transfection assay which demonstrates that transcriptional activation of the HTLV LTR is mediated solely by the χ protein and that no other virus genes are required.

A novel human retrovirus (HTLV-II) was previously found associated with a T-cell variant of hairy-cell leukaemia. Molecular cloning demonstrates that the complete provirus genome is 8.8 kilobase pairs in size and is transmissible to uninfected cells. Two types of infectious deleted provirus were also characterized. The sequences of HTLV-II are distinct from those of HTLV-I.

17 children between 5 and 15 years of age received mazindol for one year (2 mg daily). Their height was carefully evaluated by 2 physicians at 6 month intervals, and they were observed for the following year without any therapy. In each case, the growth rate slowed during mazindol administration (0.6 in/yr) compared to the previous year (1.5 in/yr). Assays of growth hormone during mazindol administration demonstrated reduced responses to insulin hypoglycemia and arginine (2 patients) and exercise (3 patients). It seems likely that mazindol reduces growth by increasing nor-epinephrine in the ventromedial nucleus of the hypothalamus, and it is interesting that increasing dopamine in that nucleus stimulates growth hormone release.

Concentration of zinc in hair and serum of children with short stature (familial or constitutional) was measured by atomic absorption spectrophotometry. Some of them were treated with methyltestosterone (MT), 10 mg. daily. Our Zn values were similar to those reported for normal children. Nevertheless, children receiving MT had higher Zn levels than the children without medication. Since Zn deficiency is associated with growth retardation, these results raise the question of whether increased Zn retention may be one of the mechanisms by which androgens accelerate growth. We were unable to find any significant difference between the Zn levels from children with familial short stature and those from children with constitutional growth delay.

Concentration of zinc (Zn) in hair, urine and serum were measured by atomic absorption spectrophotometry in one 14-month old girl with typical features of Fetal Alcohol Syndrome (FAS) (peculiar facies, congenital malformations, pre and post natal growth deficiency). She was born to an alcoholic woman who continued drinking heavily throughout her pregnancy. Zinc level was low in hair (66 μg/g) and urine (266.8 μg/g of creatinine) but normal in serum(95 μg%), reflecting probable chronic depletion of Zn. (Normal values are: hair 193 ± 18 μg/g, serum 75-160 μg%, urine 400-600 μg/g.) It has been shown that the offspring of Zn-deficient rats have marked growth retardation and high incidence of congenital malformation, some of which are similar to those seen in FAS. Alcoholic patients have been found to lose increased amounts of zinc in urine. Therefore, it is tempting to speculate that congenital Zn deficiency plays an important role in the pathogenesis of this syndrome.

Since there is a relationship between prostaglandin metabolism, Se and glutathione peroxidase (GSH-PX), and diabetics are reported to have low levels of Se and prostacyclin, we have wondered whether some of the problems which occur in IDM (cardiomyopathy and persistent fetal circulation) might be related to Se deficiency. We studied Se in whole blood of IDM (within 1-2 days after birth) and their mothers. The IDM had a birth weight (mean±SD) of 3857±1075 gm, gestational age of 37.8±1.5 wks, 1 and 5 minute Apgar scores of 7.3±2.7 and 8.8±1.7 respectively. Correlation between the maternal and infants' blood Se concentration in IDM group was not significant. Comparison between IDM, normal full term newborn (NB) infants, and the mother of IDM follows: This preliminary study did not find unusually low Se in whole blood of IDM or their mothers, but because of the potential importance of Se in IDM, a larger study is still indicated.

The optimal dose for health and the toxic dose of Se are not widely separated. Very little information is available about the toxic effects of Se during perinatal period, particularly on growth. We studied 13 group (A) and 15 group (B) suckling rat pups by providing sodium selenite in the drinking water of their corresponding mothers, dam A and dam B, at the concentration of 0 and 3 ppm Se, respectively. After the first 3 weeks of exposure, 6 of the dam B pups were adopted by dam A who had no Se in drinking water (C). Experiment was carried out during the first 6 veeks post partum. Percent change in wt from the baseline values (Ao and Bo) follows: Se concentrations were higher in every tissue of B compared to A. Two of the B pups died although their dams were not intoxicated. Se obtained through breast milk may have a toxic influence on suckling rat pups including a retarding effect on growth despite the absence of an effect on the corresponding dam which nay be indicative of a relative increase of susceptibility. The effect on growth seems to be partially reversible.