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Abstract: Between 1990 and 1996, we treated nine HIV-positive patients with a clinical diagnosis of thrombotic thrombocytopenic purpura (TTP) with therapeutic plasma exchange (TPE). Response to TPE was seen in [...]

Tourette Disorder (TD) is a childhood-onset neuropsychiatric and neurodevelopmental disorder characterized by the presence of both motor and vocal tics. The genetic architecture of TD is believed to be complex and heterogeneous. Nevertheless, DNA sequence variants co-segregating with TD phenotypes within multiplex families have been identified. This report examines whole exomes of affected and unaffected individuals in a multiplex TD family to discover genes involved in the TD etiology. We performed whole exome sequencing on six out of nine members in a three-generation TD multiplex family. Putative deleterious sequence variants co-segregating with TD patients were identified by our in-house bioinformatics pipeline. Induced pluripotent stem cells (iPSCs) were generated from one unaffected and two TD affected individuals. Neurons were derived from the iPSCs and biochemical assays were conducted to evaluate possible molecular differences between affected and unaffected. A rare heterozygous nonsense mutation in PNKD was co-segregated with TD in this multiplex family. Transcript and protein levels of the PNKD long isoform were reduced in neurons derived from the individuals with TD due to the nonsense mutation, indicating nonsense-mediated mRNA decay. We demonstrated that the PNKD long isoform monomer oligomerizes with itself as well as interacts with the synaptic active zone protein RIMS1α. We concluded that reduced PNKD long isoform levels are detected in all affected individuals and we provide evidence for a mechanism whereby this might contribute to the TD phenotype.

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To summarise evidence about the effectiveness of home blood pressure telemonitoring (HBPT) and identify the key components of intervention. We comprehensively searched PubMed, EMBASE and the Cochrane Library for relevant studies. The authors were contacted for additional information. Two authors independently extracted the data and assessed the risk of bias. 46 randomised controlled trials including a total of 13 875 cases were identified. Compared with usual care, HBPT improved office systolic blood pressure (BP) and diastolic BP by 3.99 mm Hg (95% confidence interval (CI): 5.06–2.93; P<0.001) and 1.99 mm Hg (95% CI: −2.60 to −1.39; P<0.001), respectively. A larger proportion of patients achieved BP normalisation in the intervention group (relative risk (RR): 1.16; 95% CI: 1.08–1.25; P<0.001). For HBPT plus additional support (including counselling, education, behavioural management, medication management with decision, adherence contracts and so on) versus HBPT alone (or plus less intense additional support), the mean changes in systolic and diastolic BP were 2.44 mm Hg (95% Cl, 4.88 to 0.00 mm Hg; P=0.05) and 1.12 mm Hg (95% CI, −2.34 to 0.1 mm Hg; P=0.07), respectively. For those surrogate outcomes, low-strength evidence failed to show difference. In subgroup analysis, high strength evidence supported a lower BP with HBPT that lasted for 6 or 12 months and was accompanied with counselling support from study personnel. HBPT can improve BP control in the hypertensive patients. It may be more efficacious when a proactive additional support is provided during the intervention process.

Highly pure Ti2SC was synthesised by microwave hybrid heating. The effects of composition and processing parameters, such as microwave output power, sintering temperature and dwell time on the formation process and morphology of Ti2SC were studied. The purity of Ti2SC is sensitive to the content of sulphur and sintering temperature. The results indicated that the optimum condition for synthesising Ti2SC was using a mixture of 1.15TiS2/2.85Ti/2C powders irradiated under a 100% microwave output power sintering at 1100°C for 3 min at Ar atmosphere. In addition, the reaction evolution of Ti2SC was discussed in details.

Prevalence estimates and treatment decisions for trachoma are based entirely on ocular clinical examination. The aim of the current study is to demonstrate that ophthalmic assistants can be trained and certified to provide trachoma grading within a single day.

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder and the most common cause of dementia. Today, only palliative therapies are available. The pathological hallmarks of AD are the presence of neurofibrillary tangles and amyloid plaques, mainly composed of the amyloid-β peptide (Aβ), in the brains of the patients. Several lines of evidence suggest that the increased production and/or decreased cleavage of Aβ and subsequent accumulation of Aβ oligomers and aggregates play a fundamental role in the disease progress. Therefore, substances which bind to Aβ and influence aggregation thereof are of great interest. A wide range of Aβ binding peptides were investigated to date for therapeutic purposes. Only very few were shown to be effective in rodent AD models or in clinical studies. Here, we review those peptides and discuss their possible mechanisms of action.

In this study, the influence of welding parameters, including tool rotational speed, plunge rate and dwell time, on the overlap tensile shear properties of AZ31 friction stir spot welds was investigated. The microstructures in stir zones and fracture surfaces were observed using optical microscope and scanning electron microscope respectively. The bonded width and hvalue (the distance from the tip of the partially bonded region to the top of the weld surface) were measured. The results indicated that larger bonded width and higher hvalue of the AZ31 weld result in better mechanical property. It is proposed that high tensile shear loads are produced when the tool rotational speed range of 1500–2250 rev min−1and 1 s dwell time are applied during the friction stir spot welding of AZ31. The plunge rate range from 2·5 to 10 mm s−1has insignificant influence on the tensile shear load of AZ31 joints under the present conditions. The failure mode changes from interfacial to pullout when the tool rotational speed is >2250 rev min−1. The fracture feature of AZ31 welds is brittle fracture.

In trachoma control programmes, azithromycin is distributed to treat the strains of chlamydia that cause ocular disease. We aimed to compare the effect of annual versus twice-yearly distribution of azithromycin on infection with these strains.

Outer membrane vesicles (OMVs) are released from many Gram-negative bacteria. OMVs interact with and are taken up by human cells. We and others have now showed that OMVs contain peptidoglycan, which is sensed mainly by the pattern-recognition receptor NOD1 in the cytoplasm of host cells. Vibrio choleraeis clinically important as one of the causative agents of severe dehydrating diarrhea in humans. We showed that non-O1 non-O139 V. cholerae(NOVC) strains of V. choleraproduce OMVs. Of note, we revealed that NOVC can evade NOD1-mediated immune surveillance by the quorum sensing machinery. Here we review these recent findings and discuss the relevance for our understanding of bacterial infections and innate immune responses.

To understand the effects of thermal gradient field with phase change on the crystal morphologies of high density polyethylene (HDPE) during gas assisted injection moulding (GAIM) process, the combination of the simulation of the temperature field via an enthalpy transformation method and the hierarchical structures and the crystalline morphology of HDPE were investigated in this work. The GAIM parts of HDPE 6098 can be grouped into four layers in the direction of thickness: skin layer, subskin layer, intermediate layer and core layer. Besides, the cooling logarithmic curves were adopted in this experiment, and it is found that they can clearly display the phase change plateaus even at the skin layer zone.

Slide level has a lot of influence on computer numerical control (CNC) machine tool performance. The deterioration of slide level will result in torsional vibration of the feed-axis control system and lower CNC machine tool control precision. Hence, it is necessary to investigate evaluation technology for the slide level of CNC machine tools. In this article, a novel kind of sensorless evaluation method for machine tool slide level based on linear scale or motor encoder and AC servo motor current/output torque is proposed. To improve evaluation precision, a kind of filtering method based on empirical mode decomposition (EMD) technology is employed. The analysis results of the experiments show that it is simple, rapid, feasible, and reliable to use sensorless information for evaluating slide level based on the EMD method.

To compare the effects of losartan and atenolol on plasma fibrinolytic parameters and von Willebrand factor (vWF), Chinese subjects with mild-to-moderate hypertension were randomized to receive losartan (50 mg/day; n= 30) or atenolol (50 mg/day; n= 30) for 8 weeks. If target blood pressure (< 140/90 mmHg) was not achieved at week 4, hydrochlorothiazide (12.5 mg/day) was also administered. Plasma levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and vWF were determined at baseline and after treatment. Between-group baseline characteristics and blood pressure decrease were comparable. Losartan significantly reduced plasma PAI-1 and vWF and PAI-1/tPA ratio. Atenolol significantly increased plasma tPA, but PAI-1, vWF and PAI-1/tPA ratio were unchanged. In conclusion, losartan, but not atenolol improved the fibrinolytic system and reduced plasma vWF levels in Chinese hypertensives.

Recently, electro-switchable optical materials have attracted much attention for their promising applications in optoelectronic devices and biological analysis. The structures of active optical moieties are dominant for the resulting performance, which raises the requirement of studying their structure-property relationship. In this study, two p-phenylenediamine–based polyamides (α-HPA and β-HPA) containing α-/β-substituted pendant naphthalene were designed and synthesized to investigate the effect of two substitution sites of naphthalene on their thermal, optical, electrochemical, electrochromic, and electrofluorochromic behaviors. Quantum chemical calculations were carried out to help the analysis of the experimental results. The as-prepared polyamides both exhibited excellent solubility, thermal stabilities (no weight loss before 300 °C in air), and optical switching stability (500 cycles). Because of the more twisted conformation and stronger charge transfer effect between diphenylamine and α-substituted naphthalene, the α-HPA exhibited higher glass transition temperature, higher coloration efficiency, weaker fluorescence quantum efficiency, red-shifted emission wavelength, and rapider switching speed than the β-HPA. This study not only presents a deep understanding of substitution sites of fluorophores on the electro-switchable optical behaviors but also demonstrates the tailorability of the electrochromic/electrofluorochromic characteristics through fine structure adjustment, paving a pathway for further development of high-performance electrochromic/electrofluorochromic materials.

Pd-catalyzed asymmetric allylic alkylation of dienyl acetates 1 and amination of allyl acetates 2 provides the corresponding chiral products in high regio- and enantioselectivities using 1,1‘-P,N-ferrocenes L1a and L2d as ligands, respectively.

Nanoscale aggregation of a new methanofullerene derivative with peripheral hydrophilic moieties was achieved within the confined space of a Nafion membrane. Transmission electron microscopic examination revealed an average size of 5.0 nm for the aggregates, while optical, fluorescence, and X-ray photoelectron spectroscopic measurements indicated excimer formation within the well-defined aggregated structure. These nanocomposites based on fullerene derivatives exhibit a significant optical-limiting capability attractive for many potential applications.

In this paper, the electrochemical and photophysical properties of two well-solubilized monofunctionalized methanofullerene derivatives (TDC60 and TC60) were investigated by cyclic voltammetry, UV−visible absorption, and fluorescence spectroscopic methods. These two methanofullerenes show almost the same electron acceptor properties. The MEH-PPV/methanofullerene blends were made, and it was found that the photoluminescence of MEH-PPV could be quenched more efficiently by TDC60. The two methanofullerenes were used to fabricate organic photovoltaic devices by taking MEH-PPV as the electron donor. Although the photovoltaic properties of the MEH-PPV/methanofullerene devices are better than those of the pristine MEH-PPV, the MEH-PPV/TDC60 device system shows even better performances. Considering the similarities of the structures as well as the electron acceptor abilities, the better performance of the MEH-PPV/TDC60 photovoltaic device should be due to the better compatibility of TDC60 with MEH-PPV, which was confirmed by AFM investigation.

STAT5A is a molecular regulator of proliferation, differentiation, and apoptosis in lymphohematopoietic cells. Here we show that STAT5A can serve as a functional substrate of Bruton's tyrosine kinase (BTK). Purified recombinant BTK was capable of directly binding purified recombinant STAT5A with high affinity (K(d) = 44 nm), as determined by surface plasmon resonance using a BIAcore biosensor system. BTK was also capable of tyrosine-phosphorylating ectopically expressed recombinant STAT5A on Tyr(694) both in vitro and in vivo in a Janus kinase 3-independent fashion. BTK phosphorylated the Y665F, Y668F, and Y682F,Y683F mutants but not the Y694F mutant of STAT5A. STAT5A mutations in the Src homology 2 (SH2) and SH3 domains did not alter the BTK-mediated tyrosine phosphorylation. Recombinant BTK proteins with mutant pleckstrin homology, SH2, or SH3 domains were capable of phosphorylating STAT5A, whereas recombinant BTK proteins with SH1/kinase domain mutations were not. In pull-down experiments, only full-length BTK and its SH1/kinase domain (but not the pleckstrin homology, SH2, or SH3 domains) were capable of binding STAT5A. Ectopically expressed BTK kinase domain was capable of tyrosine-phosphorylating STAT5A both in vitro and in vivo. BTK-mediated tyrosine phosphorylation of ectopically expressed wild type (but not Tyr(694) mutant) STAT5A enhanced its DNA binding activity. In BTK-competent chicken B cells, anti-IgM-stimulated tyrosine phosphorylation of STAT5 protein was prevented by pretreatment with the BTK inhibitor LFM-A13 but not by pretreatment with the JAK3 inhibitor HI-P131. B cell antigen receptor ligation resulted in enhanced tyrosine phosphorylation of STAT5 in BTK-deficient chicken B cells reconstituted with wild type human BTK but not in BTK-deficient chicken B cells reconstituted with kinase-inactive mutant BTK. Similarly, anti-IgM stimulation resulted in enhanced tyrosine phosphorylation of STAT5A in BTK-competent B cells from wild type mice but not in BTK-deficient B cells from XID mice. In contrast to B cells from XID mice, B cells from JAK3 knockout mice showed a normal STAT5A phosphorylation response to anti-IgM stimulation. These findings provide unprecedented experimental evidence that BTK plays a nonredundant and pivotal role in B cell antigen receptor-mediated STAT5A activation in B cells.

Recent studies have examined and demonstrated the potential cancer chemopreventive activity of freeze-dried berries including strawberries and black raspberries. Although ellagic acid, an abundant component in these berries, has been shown to inhibit carcinogenesis both in vivo and in vitro, several studies have reported that other compounds in the berries may also contribute to the observed inhibitory effect. In the present study, freeze-dried strawberries (Fragara ananassa, FA) or black raspberries (Rubus ursinus, RU) were extracted, partitioned and chromatographed into several fractions (FA-F001, FA-F003, FA-F004, FA-F005, FA-DM, FA-ME from strawberries and RU-F001, RU-F003, RU-F004, RU-F005, RU-DM, RU-ME from black raspberries). These extracts, along with ellagic acid, were analyzed for anti-transformation activity in the Syrian hamster embryo (SHE) cell transformation model. None of the extracts nor ellagic acid by themselves produced an increase in morphological transformation. For assessment of chemopreventive activity, SHE cells were treated with each agent and benzo[a]pyrene (B[a]P) for 7 days. Ellagic acid, FA-ME and RU-ME fractions produced a dose-dependent decrease in transformation compared with B[a]P treatment only, while other fractions failed to induce a significant decrease. Ellagic acid, FA-ME and RU-ME were further examined using a 24 h co-treatment with B[a]P or a 6 day treatment following 24 h with B[a]P. Ellagic acid showed inhibitory ability in both protocols. FA-ME and RU-ME significantly reduced B[a]P-induced transformation only when co-treated with B[a]P for 24 h. These results suggest that a methanol extract from strawberries and black raspberries may display chemopreventive activity. The possible mechanism by which these methanol fractions (FA-ME, RU-ME) inhibited cell transformation appear to involve interference of uptake, activation, detoxification of B[a]P and/or intervention of DNA binding and DNA repair.

An ether-insoluble resin glycoside fraction was obtained from the seeds of Cuscuta australis. Identification and characterization of alkaline hydrolysis products by means of GC, FABMS, and ¹H, ¹³C, and 2D NMR revealed the material to be composed of three new glycosidic acids, cuscutic acids A1−A3 (1−3); triglycosides with (11S)-jalapinolic or (11S)-convolvulinolic acid as the aglycon; and acetic, isobutyric, (2S)-2-methylbutyric, tiglic, and (2R,3R)-nilic acids. The resin glycoside is considered to be a complex mixture of glycosidic ester-type oligomers (up to heptamers) with a core consisting of a number of the above cuscutic acids each acylated with one or two carboxylic acid moieties.

A simple method was developed whereby immunoperoxidase and immunofluorescence techniques were applied in consecutive steps to demonstrate the presence of two antigens in the same tissue section. This method was applied in three model, two antigens were shown: a) each (gastrin and pepsinogen II) inside one of two different cell types (gastrin (G) and antral peptic cells), b) each (kappa or gamma light chains) inside different cells of the same type (plasma cells); also, both (kamma and gamma light chains) inside the same cell (Reed-Sternberg cell), and c) both (pepsinogen I and II) inside the same cell (chief cell of oxyntic glands). The results could be viewed and photographed either simultaneously, when the antigens were in different cells, or sequentially, when the antigens were in the same cells.

The observed melting temperature of embedded particles can be either lower or higher than the bulk equilibrium melting point. Explanations for the observed melting-temperature elevation are still controversial and have been attributed either to an elevation caused by a strain energy effect and/or an interfacial energy effect, or to metastable superheating. Furthermore, there seems to be some confusion regarding the relationship between equilibrium melting-point elevation and the superheating effect. We suggest that the observed increase in melting temperature for embedded particles is caused by both an equilibrium melting-point elevation and a metastable superheating effect, and the two effects tend to be concurrent. An attempt has been made to clarify the two effects in the melting process of indium particles embedded in an aluminium matrix.

A superheating of 5oC has been observed in bulk polycrystalline selenium with a mean grain size of about 10 mum. The superheating is interpreted on the basis of the unique grain boundary structure inside the Se samples, which gives rise to a free energy barrier to liquid nuclei formation in the grain boundaries.

In this letter, we report the first attempt to determine the grain-boundary enthalpy and its grain size dependence in a nanocrystalline (NC) element. Nanocrystallization of amorphous Se was achieved by isothermal annealing. Calorimetric measurements showed that the grain-boundary enthalpy decreases with a reduction in the grain size of the NC Se samples. This behaviour, which is consistent with other related measurements and computer simulation results, implies that the intrinsic nature of a grain boundary in polycrystals changes with the dimension of crystallites in the nanometre regime.

In the progeny of somatic cell hybrids formed by fusion of human lymphocytes and Chinese hamster mutant cells, a single human chromosome A2 was selectively retained when grown in appropriate medium.

An ethanol extract of Psoralea corylifolia caused strong DNA polymerase inhibition in a whole cell bioassay specific for inhibitors of DNA replication enzymes. Bioassay-directed purification of the active compounds led to the isolation of the new compound corylifolin (1) and the known compound bakuchiol (2) as DNA polymerase inhibitors. On the basis of the structures of 1 and 2, resveratrol (3) was tested and found to be active as a DNA polymerase inhibitor in this bioassay. Neobavaisoflavone (4) was isolated as a DNA polymerase inhibitor, daidzein (5) as a DNA polymerase and topoisomerase II inhibitor, and bakuchicin (6) as a topoisomerase II inhibitor.

Using ferritin as a marker of reactive microglia, we demonstrated a close association between proliferation of reactive microglia and expression of human immunodeficiency virus type 1 (HIV-1) in brain tissue from autopsied cases of acquired immunodeficiency syndrome (AIDS). An increased number of ferritin-positive reactive microglia was observed in formalin-fixed paraffin-embedded brain sections from all 13 AIDS cases examined. Similar findings were observed in brain tissue from other neurological diseases (subacute sclerosing penencephalitis, herpes simplex encephalitis and multiple sclerosis). Multinucleated giant cells were found in 7 of the AIDS cases which were also intensely labeled for ferritin. Dual-label immunohistochemistry using anti-ferritin and cell-specific markers showed that ferritin-positive cells were distinct from astrocytes, neurons and endothelia using anti-glial fibrillary acidic protein (anti-GFAP), anti-neurofilament protein and Ulex europaeus agglutinin 1, respectively. In 5 AIDS brains, only ferritin-positive cells were shown to contain HIV-1 gp41 antigen using dual-label immunohistochemistry. In addition, HIV-1 RNA was localized in territin-positive reactive microglia but not in GFAP-positive astrocytes using immunohistochemistry combined with in situ hybridization. Ferritin-positive reactive microglia and multinucleated giant cells were colabeled with the microglial marker, Ricinus communis agglutinin 1 (RCA-1). Howerver, RCA-1 also extensively stained resting microglia only a few of which were colabeled for ferritin. The density of ferritin-positive cells was correlated with the presence of HIV-1 RNA-positive cells in AIDS brain. Thus, ferritin immunoreactivity can be used as an activation marker of microglia in archival paraffin sections and reflects the extent of inflammation in HIV-1-infected brain.

A simple ray approximation is demonstrated for the backscattering of sound by a thin empty cylindrical shell in water at normal incidence. The approximation is applied to the region near the coincidence frequency and is used to interpret prominent features in that region associated with a subsonic guided wave. With increasing ka, the features exhibit a transition from resonance behavior dominated by interference with the specular reflection. Another feature is the interference of resonance contributions of the leaky s0 Lamb wave which may produce maxima or minima in the amplitude depending on the ka region. The cylinder studied is 2.5% thick stainless steel for ease of comparison with a similar spherical shell [P. L. Marston and N. H. Sun, J. Acoust. Soc. Am. 92, 3315–3319 (1992)] and the guided wave properties were computed from elasticity theory rather than shell approximations. A novel geometric derivation is given for the relative phases of the coupling coefficients of subsonic waves on cylinders and spheres and some implications for scattering by slightly eccentric spheroids are noted.

Examined here by directed mutation, circular dichroism spectroscopy, and kinetics are the relationships of five residues, Asp13, Glu14, Lys16, His41, and Arg131, to the catalytic function and structural organization of adenylosuccinate synthetase from Escherichia coli. The D13A mutant has no measurable activity. Mutants E14A and H41N exhibit 1% of the activity of the wild-type enzyme and 2-7-fold increases in the Km of substrates. The mutant K16Q has 34% of the activity of wild-type enzyme and Km values for substrates virtually unchanged from those of the wild-type system. Mutation of Arg131 to leucine caused only a 4-fold increase in the Km for aspartate relative to the wild-type enzyme. The dramatic effects of the D13A, E14A, and H41N mutations on kcat are consistent with the putative roles assigned to Asp13 (catalytic base), His41 (catalytic acid), and Glu14 (structural organization of the active site). The modest effect of the R131L mutation on the binding of aspartate is also in harmony with recent crystallographic investigations, which suggests that Arg131 stabilizes the conformation of the loop that binds the beta-carboxylate of aspartate. The modest effect of the K16Q mutation, however, contrasts with significant changes brought about by the mutation of the corresponding lysines in the P-loop of other GTP- and ATP-binding proteins. Crystallographic structures place Lys16 in a position of direct interaction with the gamma-phosphate of GTP. Furthermore, lysine is present at corresponding positions in all known sequences of adenylosuccinate synthetase. We suggest that along with a modest role in stabilizing the transition state of the phosphotransfer reaction, Lys16 may stabilize the enzyme structurally. In addition, the modest loss of catalytic activity of the K16Q mutant may confer such a selective disadvantage to E. coli that this seemingly innocuous mutation is not tolerated in nature.

To define the domains in the envelope glycoprotein important for antibody neutralization of the human immunodeficiency virus type 1 (HIV-1), monoclonal antibodies (mAbs) were generated by immunizing mice with purified glycoprotein gp120 of the IIIB isolate. One mAb, G3-4, reacted with the gp120 of homologous (IIIB) and heterologous (RF) isolates. In addition, mAb G3-4 efficiently neutralized both IIIB and RF viruses in vitro, as well as four of nine primary HIV-1 isolates. In competition immunoassays, mAb G3-4 and soluble CD4 were found to inhibit one another in binding to gp120. However, no competition was seen between mAb G3-4 and mAbs directed to the third variable region or the fourth conserved region of gp120. In particular, mAb G3-4 did not compete with our human mAb 15e, which identifies a discontinuous epitope on gp120 involved in group-specific neutralization of HIV-1 and in gp120-CD4 binding. Epitope-mapping studies on mAb G3-4 with synthetic or unglycosylated recombinant peptides were negative, suggesting that its epitope may be discontinuous. Indeed, this hypothesis was confirmed by showing the loss of mAb G3-4 serologic reactivity when gp120 was first denatured. We conclude that the site recognized by mAb G3-4 represents another discontinuous epitope on gp120 important for neutralization of HIV-1.

This paper presents a finite element algorithm for two-dimensional nonlinear inverse heat conduction analysis. The proposed method is capable of handling both unknown surface heat flux and unknown surface temperature of solids using temperature histories measured at a few discrete point. The proposed algorithms were used in the study of the thermofracture behavior of leaking pipelines with experimental verifications.

A major feature of human immunodeficiency virus (HIV) infection is disordered B-cell function, which paradoxically includes both pathologic overactivity (elevated serum antibodies, lymphadenopathy, and increased risk for lymphoma) and underactivity (impaired antibody immunity, particularly to bacterial polysaccharide antigens). B-cell immune dysfunction contributes significantly to HIV-related morbidity and also represents an obstacle to eventual definitive treatment by anti-HIV immunization. Our laboratory has recently identified in normal B-cell populations certain VH gene subfamilies with a developmentally regulated pattern of utilization. In particular, B cells bearing rearranged VH3L were rare in the germinal center but uniformly abundant in the blood and lymphoid mantle zone. We used this index gene subfamily as a clonal criterion for the pattern of B-cell development in lymphocytes of HIV-positive individuals. In a series of 19 HIV- positive subjects, a striking deficit of VH3L B cells was observed; in contrast, none of the 16 normal subjects showed this abnormality. Other VH subfamilies (VH1N, VH4/6, and VH5N) were unaffected in the HIV- positive patients. This VH3L clonal deficit and other recent phenotype and histopathologic findings suggest that the general B-cell dysfunction in HIV is due to a discreet maturational arrest at the germinal center stage.

A nuclear protein that recognizes u.v.-damaged DNA was detected in extracts from murine F9 embryonic stem cells using a DNA-binding assay. The nuclear-protein-binding activity was increased in cells after treatment with retinoic acid/dibutyryl cyclic AMP (dbcAMP), with optimum induction at 6 days. In vitro treatment of nuclear extracts with agents that affect protein conformation (such as urea, Nonidet P40 and Ca2+) slightly modulated the damage-recognition activity. Furthermore, treatment of nuclear extracts with phosphatase dramatically inhibited the binding activity. In addition, damaged-DNA recognition of the nuclear extracts was effectively inhibited by damaged double- and single-stranded DNA. The expression of the nuclear protein with similar characteristics was abundant in HeLa cells and was increased in drug- or u.v.-resistant cells. The findings suggest that the recognition of a u.v.-DNA adduct is modulated, at least in part, by an activity that is induced during retinoic acid/dbcAMP-induced differentiation. These results also imply that the identified damage-recognition protein may be important for the sensitivity or resistance of mammalian cells to DNA damage.

A broad enhancement of the form function f(ka) for steady‐state backscattering by thin spherical shells in the midfrequency range has been noted by several investigators. Consequences of this enhancement on the backscattering of tone bursts are investigated with a Fourier synthesis of the temporal response from the exact f(ka). The emphasis is on incident bursts that are sufficiently short so that scattering consists primarily of distinct echoes associated with the specular reflection and different circumnavigations of a dominant surface guided wave. That wave lies on the subsonic branch of the lowest antisymmetric Lamb mode for a fluid‐loaded shell designated as a0− by some authors. A ray method, previously verified for echo amplitudes from leaky (or supersonic) Lamb waves on thick shells [S. Kargl and P. Marston, J. Acoust. Soc. Am. 85, 1014–1028 (1989)], is generalized to subsonic waves. The ray method well approximates echo amplitudes from the Fourier synthesis provided the incident burst is sufficiently long that effects of dispersion are weak. Over a broad frequency range, the amplitude of the earliest a0− echo is enhanced relative to the specular echo. For the 2.5% thick stainless steel shell in water considered, the enhancement factor peaks near ka≊46 where the amplitude ratio ≊3.1. The ray theory suggests that the peak ratio depends only weakly on shell thickness and material parameters provided certain conditions hold. The a0− wave is also found to contribute a prominent wave packet to the far‐field impulse response of the shell. The radiation damping and velocity of relevant surface waves were computed from the complete elastic equations and those results may be helpful for testing thin shell approximations near the coincidence frequency.

The ray representation of the scattering from an empty cylindrical shell is compared with the exact results of the partial‐wave series. The specific example considered is a thick stainless steel shell having the same parameters as a previous synthesis for spheres illustrated by Kargl and Marston [J. Acoust. Soc. Am. 89, 2545–2558 (1991)]. The present computation demonstrates a general agreement with the exact result for ka down to 7 and confirms the applicability of a simple approximation for the complex coupling coefficient.