Towards dark current suppression in metallic photocathodes by selected-area oxidation.

Oxide-free surfaces of polycrystalline Cu are prepared using acetic acid etching after chemical-mechanical polishing. UV ozone treatment is shown to increase the work function of the cleaned Cu by up to 0.5 eV. There is also a large reduction in quantum efficiency at 265 nm. Cu sheet can be easily masked from ozone exposure by Si or glass, meaning that selected-area oxi-dation is possible. Oxygen plasma treatment has a similar effect to the UV ozone but is more difficult to mask. There is no increase in surface roughness after oxidation, meaning that the larger work function could significantly re-duce dark current in accelerator photocathodes without affecting the desired photoemission region.

The measurement of photocathode transverse energy distribution curves (TEDCs) using the transverse energy spread spectrometer (TESS) experimental system.

The minimum achievable particle beam emittance in an electron accelerator depends strongly on the intrinsic emittance of the photocathode electron source. This is measurable as the mean longitudinal and transverse energy spreads in the photoemitted electron beam (MLE and MTE respectively); consequently, MLE and MTE are notable figures of merit for photocathodes used as electron sources in particle accelerators. The overall energy spread is defined by the sum of the MTE and the MLE, and the minimization of MTE is crucial to reduce emittance and thus generate a high-brightness electron beam. Reducing the electron beam emittance in an accelerator that drives a Free-Electron Laser (FEL) delivers a significant reduction in the saturation length for an x-ray FEL, thus reducing the machine's construction footprint and operating costs while increasing the x-ray beam brightness. The ability to measure the transverse energy distribution curve of photoelectrons emitted from a photocathode is a key enabler in photocathode research and development that has prompted the Accelerator Science and Technology Centre (ASTeC) at the STFC Daresbury Laboratory to develop the Transverse Energy Spread Spectrometer to make these crucial measurements. We present details of the design for the upgraded TESS instrument with measured data for copper (100), (110), and (111) single-crystal photocathodes illuminated at UV wavelengths around 266 nm.

Measurement of the longitudinal energy distribution of electrons in low energy beams using electrostatic elements.

The Transverse Energy Spread Spectrometer (TESS) was designed primarily to study the mean transverse energy spread of electrons emitted from photocathode electron sources at both room and liquid nitrogen temperatures as a function of quantum efficiency through analysis of the photoemission footprint. By reconfiguring the potentials applied to different detector elements, TESS can also be used to measure the mean longitudinal energy spread of photoemitted electrons. Initial plans were to use electrostatic wire meshes as a retarding element which prevents the detection of electrons with insufficient energy to overcome a variable potential barrier. However, this method has proved impractical and a new method has been proposed in which the photocathode bias potential is swept (effectively from a state of no electron emission to full emission) and the emitted photocurrent is then detected by using a photoemitted charge collector. In this article, we present the TESS set-up and analyze this new method to measure the longitudinal energy distribution curve. Experimental results are presented and compared to simulated results by utilising a custom designed tracking code.

Special article: chronic granulomatous disease in the United Kingdom and Ireland: a comprehensive national patient-based registry.

There are no epidemiological studies from the British Isles of chronic granulomatous disease, characterized by recurrent, life-threatening bacterial and fungal infections and inflammatory sequelae. Patients were enrolled in a national registry and medical records were analysed. Of 94 subjects, 69 had X-linked disease, 16 had autosomal recessive disease and nine were unknown. Prevalence was 7.5/million for 1990-99 and 8.5/million for 1980-89. Suppurative adenitis, abscesses and pneumonia presented commonly. Twenty-three of 30 patients who underwent high resolution computerized tomography had chronic respiratory disease. Inflammatory sequelae included bowel stricture and urogenital tract granulomata. Growth failure was common; 75% of those measured were below the population mean. All patients received prophylactic antibiotics and 93% anti-fungal prophylaxis. Interferon gamma was used to treat infection, but rarely as prophylaxis. Despite prophylaxis, estimated survival was 88% at 10 years but 55% at age 30 years. Morbidity remains significant, severe infectious complications common. Curative treatments including stem cell transplantation should be considered for patients with frequent or serious complications.

Oral contraceptives for functional ovarian cysts.

BACKGROUND: Functional ovarian cysts are a common gynecological problem among women of reproductive age worldwide. When large, persistent, or painful, these cysts may require operations, sometimes resulting in removal of the ovary. Since early oral contraceptives were associated with a reduced incidence of functional ovarian cysts, many clinicians inferred that birth control pills could be used to treat cysts as well. This became a common clinical practice in the early 1970s. OBJECTIVES: This review examined all randomized controlled trials that studied oral contraceptives as therapy for functional ovarian cysts. SEARCH STRATEGY: We searched the computer databases of CENTRAL, PubMed, POPLINE, and EMBASE for randomized controlled trials. We also examined the reference lists of articles and wrote to authors of all studies identified to seek articles we had missed. SELECTION CRITERIA: We included randomized controlled trials in any language that included oral contraceptives used for treatment and not prevention of functional ovarian cysts. Criteria for diagnosis of cysts were those used by authors of studies. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted data from the articles and entered them into RevMan 4.2. We used Peto odds ratios with 95% confidence intervals for dichotomous outcomes. MAIN RESULTS: We identified four randomized controlled trials from three countries; the studies included a total of 227 women. Treatment with combined oral contraceptives did not hasten resolution of functional ovarian cysts in any trial. This held true for cysts that occurred spontaneously as well as those that developed after ovulation induction. Most cysts resolved without treatment within a few cycles; persistent cysts tended to be pathological (e.g., endometrioma or para-ovarian cyst) and not physiological. AUTHORS' CONCLUSIONS: Although widely used for treating functional ovarian cysts, combined oral contraceptives appear to be of no benefit. Watchful waiting over several cycles is appropriate. Should cysts persist, surgical management is often indicated.

Effect of oxygen adsorption on the chiral Pt{531} surface.

The adsorption of oxygen on the chiral Pt{531} surface was studied by high-resolution X-ray photoelectron spectroscopy (HRXPS) and low energy electron diffraction (LEED). After the surface is annealed in oxygen (3 x 10(-7) mbar), three O 1s peaks are observed in XPS. One peak, at 529.5 eV, is assigned to chemisorbed oxygen; it disappears after annealing in vacuo to temperatures above 900 K. The other two peaks at 530.8 and 532.3 eV are stable up to at least 1250 K. They are associated with oxide clusters on the surface. These clusters readily react with coadsorbed carbon monoxide at temperatures between 315 and 620 K.

Recent cytoarchitechtonic changes in the prefrontal cortex of schizophrenics.

A variety of lines of converging evidence implicate the prefrontal cortex (PFC) in schizophrenia. In the past studies have focused on the various neurotransmitter systems that appear to be involved in schizophrenia such as dopamine, glutamate and serotonin. Recently, the focus of research has shifted away from systems and towards cellular morphology due partly to studies suggesting an increase in neural density in various regions of the PFC (1,2). A plethora of research has come out suggesting possible cytoarchitectural changes in pyramidal cells in the prefrontal cortex as well as alterations of certain GABAergic cells. This review examines the recent data that shows cytoarchitechtonic changes in cells of the prefrontal cortex.

The interstitial nuclei of the human anterior hypothalamus: an investigation of variation with sex, sexual orientation, and HIV status.

The interstitial nuclei of the human anterior hypothalamus (INAH1-4) have been considered candidates for homology with the sexually dimorphic nucleus of the preoptic area of the rat. Volumetric sexual dimorphism has been described for three of these nuclei (INAH1-3), and INAH3 has been reported to be smaller in homosexual than heterosexual men. The current study measured the INAH in Nissl-stained coronal sections in autopsy material from 34 presumed heterosexual men (24 HIV- and 10 HIV+), 34 presumed heterosexual women (25 HIV- and 9 HIV+), and 14 HIV+ homosexual men. HIV status significantly influenced the volume of INAH1 (8% larger in HIV+ heterosexual men and women relative to HIV- individuals), but no other INAH. INAH3 contained significantly more neurons and occupied a greater volume in presumed heterosexual males than females. No sex difference in volume was detected for any other INAH. No sexual variation in neuronal size or density was observed in any INAH. Although there was a trend for INAH3 to occupy a smaller volume in homosexual men than in heterosexual men, there was no difference in the number of neurons within the nucleus based on sexual orientation.

Survey of transcripts in the adult Drosophila brain.

BACKGROUND: Classic methods of identifying genes involved in neural function include the laborious process of behavioral screening of mutagenized flies and then rescreening candidate lines for pleiotropic effects due to developmental defects. To accelerate the molecular analysis of brain function in Drosophila we constructed a cDNA library exclusively from adult brains. Our goal was to begin to develop a catalog of transcripts expressed in the brain. These transcripts are expected to contain a higher proportion of clones that are involved in neuronal function. RESULTS: The library contains approximately 6.75 million independent clones. From our initial characterization of 271 randomly chosen clones, we expect that approximately 11% of the clones in this library will identify transcribed sequences not found in expressed sequence tag databases. Furthermore, 15% of these 271 clones are not among the 13,601 predicted Drosophila genes. CONCLUSIONS: Our analysis of this unique Drosophila brain library suggests that the number of genes may be underestimated in this organism. This work complements the Drosophila genome project by providing information that facilitates more complete annotation of the genomic sequence. This library should be a useful resource that will help in determining how basic brain functions operate at the molecular level.

In utero cocaine-induced dysfunction of dopamine D1 receptor signaling and abnormal differentiation of cerebral cortical neurons.

Monoamines modulate neuronal differentiation, and alteration of monoamine neurotransmission during development produces specific changes in neuronal structure, function, and pattern formation. We have previously observed that prenatal exposure to cocaine in a clinically relevant animal model produces increased length of pyramidal neuron dendrites in the anterior cingulate cortex (ACC) postnatally. We now report that cocaine administered intravenously to pregnant rabbits at gestational stages preceding and during cortical histogenesis results in the early onset of hypertrophic dendritic outgrowth in the embryonic ACC. Confocal microscopy of DiI-labeled neurons revealed that the atypical, tortuous dendritic profiles seen postnatally in ACC-cocaine neurons already are apparent in utero. No defects in neuronal growth were observed in visual cortex (VC), a region lacking prominent dopamine innervation. In striking correlation with our in vivo results, in vitro experiments revealed a significant enhancement of spontaneous process outgrowth of ACC neurons isolated from cocaine-exposed fetuses but no changes in neurons derived from visual cortex. The onset of modified growth in vivo is paralleled by reduced D(1A) receptor coupling to its G-protein. These data suggest that the dynamic growth of neurons can be regulated by early neurotransmitter signaling in a selective fashion. Prenatal onset of defects in dopamine receptor signaling contributes to abnormal circuit formation and may underlie specific cognitive and behavioral dysfunction.

The interstitial nuclei of the human anterior hypothalamus: an investigation of sexual variation in volume and cell size, number and density.

The four interstitial nuclei of the anterior hypothalamus (INAH) have been considered as candidate human nuclei for homology with the much studied sexually dimorphic nucleus of the preoptic area of the rat. Assessment of the INAH for sexual dimorphism has produced discrepant results. This study reports the first systematic examination of all four INAH in the human for sexual variation in volume, neuronal number and neuronal size. Serial Nissl-stained coronal sections through the medial preoptic area and anterior hypothalamus were examined from 18 males and 20 females who died between the ages of 17 and 65 without evidence of hypothalamic pathology or infection with the human immunodeficiency virus. A computer-assisted image-analysis system and commercial stereology software package were employed to assess total volume, neuronal number and mean neuronal size for each INAH. INAH3 occupied a significantly greater volume and contained significantly more neurons in males than in females. No sex differences in volume were detected for any of the other INAH. No sexual variation in neuronal size or packing density was observed in any nucleus. The present data corroborate two previous reports of sexual dimorphism of INAH3 but provide no support for previous reports of sexual variation in other INAH.

Guanine-rich telomeric sequences stimulate DNA polymerase activity in vitro.

Guanine-rich oligonucleotides and short telomeric DNA sequences can self-associate into G-quartet stabilized complexes. We discovered that this self-association can occur in sequencing reactions and that higher-order structures stimulate DNA polymerase to synthesize extended DNA strands. Base analogues were used to identify Hoogsteen base pairings as stabilizing forces in these stimulatory DNA structures. Scanning force microscopy confirmed that quartet-DNA was formed from these oligomers and that these extended, four-stranded structures could be bound by DNA polymerase. Since guanine quartet-stabilized structures are proposed to exist in vivo, such structures may stimulate DNA polymerization in vivo.

Voicing judgements by chinchillas trained with a reward paradigm.

Experiments were performed to replicate and extend previous findings of similar categorization of voiced/voiceless consonant-vowel (CV) syllables by humans and chinchillas. A reward paradigm was applied to the question of how stimulus range affects the voice-onset-time (VOT) corresponding to the voiced/voiceless category boundary. Each of four adult chinchillas and four human subjects identified synthetic CV syllables as voiced (/ba/, /da/, /ga/) or voiceless (/pa/, /ta/, /ka/) using voiceless standards of either 80 or 120 ms. In both humans and animals, extending the VOT range from 80 to 120 ms shifted category boundaries to longer VOTs, but to a different extent across listeners. Control experiments suggested that listeners were attending to different phonetic cues in a manner that depended on the listener, rather than on species. The results are interpreted in terms of similar contextual effects and use of multiple phonetic cues to voicing in humans and animals.

DNA recognition properties of the N-terminal DNA binding domain within the large subunit of replication factor C.

Replication Factor C (RFC) is a five-subunit protein complex required for eukaryotic DNA replication and repair. The large subunit within this complex contains a C-terminal DNA binding domain which provides specificity for PCNA loading at a primer-template and a second, N-terminal DNA binding domain of unknown function. We isolated the N-terminal DNA binding domain from Drosophila melanogaster and defined the region within this polypeptide required for DNA binding. The DNA determinants most efficiently recognized by both the Drosophila minimal DNA binding domain and the N-terminal half of the human large subunit consist of a double-stranded DNA containing a recessed 5' phosphate. DNA containing a recessed 5' phosphate was preferred 5-fold over hairpined DNA containing a recessed 3' hydroxyl. Combined with existing data, these DNA binding properties suggest a role for the N-terminal DNA binding domain in the recognition of phosphorylated DNA ends.

Octamer-primed cycle sequencing using dye-terminator chemistry.

Octamer Sequencing Technology, OST, is a method of DNA sequencing using single octamer oligonucleotides to prime cycle sequencing reactions. This sequencing strategy is faster than a traditional primer-walking strategy, since access to this optimized octamer library eliminates delays associated with designing and synthesizing gene specific primers. In this report, OST has been optimized for fluorescent, dye-terminator cycle sequencing reactions to facilitate parallel processing of samples. The successful adaptation of OST to an automated sequencing platform and the design of and access to an octamer library are critical steps towards developing an efficient 'closed-loop' DNA sequencing system.

Octamer-primed cycle sequencing: design of an optimized primer library.

This paper describes a novel method of primer walking using octamer oligonucleotides to prime DNA sequencing reactions. Octamer sequencing is compatible with isotopic and fluorescent sequencing chemistry, reaction conditions are optimized such that the samples can be processed in parallel, and the procedure has the potential to be automated. This strategy is faster than the traditional primer walking sequencing strategy, as the existence of a primer library allows immediate access to a primer for the next sequencing reaction, eliminating delays associated with designing and synthesizing gene-specific primers. The octamer library is comprised of optimized sequencing primers, such that octamer sequencing yields results equivalent to or better than traditional primer walking. This technology is more economical because gene-specific sequencing primers, the major cost in the reaction, are replaced by an optimized subset of frequently occurring octamers that are able to prime multiple reactions.

Comparative studies: enalapril versus hydrochlorothiazide as first-step therapy for the treatment of primary hypertension.

Thirty-nine patients were entered into a 12-week, randomized, double-blind, parallel protocol to assess the safety and efficacy of enalapril (MK-421, 10 to 20 mg bid), hydrochlorothiazide (HCTZ, 25 to 50 mg bid), or combined drug therapy (MK-421 + HCTZ) for the treatment of primary hypertension. Specifically monitored were the effects of each drug program on BP and pulse, serum chemistries, body fluid composition and weight, renal function, and the renin-angiotensin-aldosterone axis. Results indicate that MK-421, HCTZ, and combined therapy were equally effective in lowering BP; none of the therapies significantly altered glomerular filtration rate or effective renal plasma flow. Patients on MK-421 experienced no change in volume, an increase in plasma potassium, no change in fractional sodium or potassium excretion, and a decreased urine osmolality associated with an enhanced free-water clearance. Plasma renin activity was increased, plasma angiotensin II was decreased, and plasma aldosterone was unchanged. In contrast, patients on HCTZ developed volume contraction, hypokalemia associated with an increase in fractional sodium and potassium excretion, and an increased urine osmolality associated with a decreased free-water clearance. Plasma renin activity was increased, however, plasma angiotensin II and plasma aldosterone were unchanged. Patients on combined therapy with MK-421 + HCTZ demonstrated qualitatively similar changes in serum chemistries, body fluid volumes, and renal function compared with patients receiving HCTZ alone, whereas changes in the renin-angiotensin-aldosterone system in these patients were qualitatively similar, but more marked, compared with those occurring in patients receiving MK-421 alone. We conclude that MK-421 is an effective first-step antihypertensive agent that does not produce adverse metabolic, volume, or renal effects.

Effects of prazosin therapy on BP, renal function, and body fluid composition.

To our knowledge, the long-term effects of prazosin hydrochloride, an alpha 1-adrenoceptor antagonist, on renal function and body fluid composition have not been previously reported. Fourteen hypertensive men in whom the BP was normalized with prazosin monotherapy, underwent assessment of renal function and body fluid composition following short-term (three to six weeks), long-term (five to six months), and withdrawal (two weeks) therapy. Neither short- nor long-term prazosin therapy had any adverse effect on the glomerular filtration rate or effective renal plasma flow. Renal vascular resistance was decreased 14% during short-term therapy, but not during long-term therapy. Urine flow rate, urine osmolality, free water clearance, and fractional sodium and potassium excretions were statistically unchanged throughout drug therapy. Plasma volume and extracellular fluid volume were increased following both short- and long-term therapy. Long-term prazosin monotherapy effectively lowers BP without resulting in drug tolerance, however, sodium retention probably limits its antihypertensive effectiveness.

Effects of indoramin therapy on BP, renal function, and body fluid composition.

Indoramin hydrochloride is a new alpha 1-adrenoceptor antagonist. Eleven hypertensive men in whom the BP was normalized with indoramin underwent assessment of renal function, renal hemodynamics, and body fluid composition following short-term (three to six weeks), long-term (five to six months), and withdrawal (two weeks) therapy. Short-term indoramin therapy produced a 28% increase in glomerular filtration rate, a 24% increase in effective renal plasma flow, and a 31% decrease in renal vascular resistance. Although urine flow rate and free water clearance were unchanged, fractional sodium excretion decreased 38%. Long-term indoramin therapy was associated with qualitatively similar renal effects, but the changes did not achieve statistical significance. Plasma volume was increased only during short-term therapy; however, body weight was increased following both short- and long-term therapy. Indoramin effectively lowers BP without producing deleterious renal effects.