Combinatorial solar cell libraries for the investigation of different metal back contacts for TiO2-Cu2O hetero-junction solar cells.

Here we present a comprehensive investigation of TiO2-Cu2O hetero-junction solar cells with different back contacts (Au, ITO, Cu or Ag). Combinatorial hetero-junction libraries consisting of a linear TiO2 thickness gradient produced by spray pyrolysis and a bell shaped Cu2O profile synthesized by pulsed laser deposition were chosen to investigate the impact of the two metal oxide layer thicknesses. The back contacts were deposited as round patches onto a grid of 13 × 13 points, 169 contacts for each contact material, forming a library containing 4 × 13 × 13 = 676 back contacts. Each back contact represented a solar cell with an individual TiO2 and Cu2O thickness. I-V measurements show that all four materials provide an ohmic contact and that the open circuit voltage of ∼300 mV is rather independent of both layer thicknesses and contact material. The size of the Cu2O crystals drastically decreases with distance from the center of deposition, which leads to a drastic increase of series resistance when the crystal size is <50 nm.

Suprathreshold processing of complex visual stimuli: evidence for linearity in contrast perception.

Magnitude estimation experiments show that perceived contrast for both sine and square waves is a linear function of stimulus contrast. The suprathreshold sine:square ratio required for equal perceived contrast derived from these data was verified by contrast matching experiments. These findings imply a high degree of linearity in suprathreshold visual processing of contrast.

Thermal unfolding of dodecameric glutamine synthetase: inhibition of aggregation by urea.

Thermal unfolding of dodecameric manganese glutamine synthetase (622,000 M(r)) at pH 7 and approximately 0.02 ionic strength occurs in two observable steps: a small reversible transition (Tm approximately 42 degrees C; delta H approximately equal to 0.9 J/g) followed by a large irreversible transition (Tm approximately 81 degrees C; delta H approximately equal to 23.4 J/g) in which secondary structure is lost and soluble aggregates form. Secondary structure, hydrophobicity, and oligomeric structure of the equilibrium intermediate are the same as for the native protein, whereas some aromatic residues are more exposed. Urea (3 M) destabilizes the dodecamer (with a tertiary structure similar to that without urea at 55 degrees C) and inhibits aggregation accompanying unfolding at < or = 0.2 mg protein/mL. With increasing temperature (30-70 degrees C) or incubation times at 25 degrees C (5-35 h) in 3 M urea, only dodecamer and unfolded monomer are detected. In addition, the loss in enzyme secondary structure is pseudo-first-order (t1/2 = 1,030 s at 20.0 degrees C in 4.5 M urea). Differential scanning calorimetry of the enzyme in 3 M urea shows one endotherm (Tmax approximately 64 degrees C; delta H = 17 +/- 2 J/g). The enthalpy change for dissociation and unfolding agrees with that determined by urea titrations by isothermal calorimetry (delta H = 57 +/- 15 J/g; Zolkiewski M, Nosworthy NJ, Ginsburg A, 1995, Protein Sci 4: 1544-1552), after correcting for the binding of urea to protein sites exposed during unfolding (-42 J/g). Refolding and assembly to active enzyme occurs upon dilution of urea after thermal unfolding.

Urea-induced dissociation and unfolding of dodecameric glutamine synthetase from Escherichia coli: calorimetric and spectral studies.

Urea-induced dissociation and unfolding of manganese.glutamine synthetase (Mn.GS) have been studied at 37 degrees C (pH 7) by spectroscopic and calorimetric methods. In 0 to approximately 2 M urea, Mn.GS retains its dodecameric structure and full catalytic activity. Mn.GS is dissociated into subunits in 6 M urea, as evidenced by a 12-fold decrease in 90 degrees light scattering and a monomer molecular weight of 51,800 in sedimentation equilibrium studies. The light scattering decrease in 4 M urea parallels the time course of Trp exposure but occurs more rapidly than changes in secondary structure and Tyr exposure. Early and late kinetic steps appear to involve predominantly disruption of intra-ring and inter-ring subunit contacts, respectively, in the layered hexagonal structure of Mn.GS. The enthalpies for transferring Mn.GS into urea solutions have been measured by titration calorimetry. After correcting for the enthalpy of binding urea to the protein, the enthalpy of dissociation and unfolding of Mn.GS is 14 +/- 4 cal/g. A net proton uptake of approximately 50 H+/dodecamer accompanies unfolding reactions. The calorimetric data are consistent with urea binding to multiple, independent sites in Mn.GS and the number of binding sites increasing approximately 9-fold during the protein unfolding.

Nucleotide-dependent oligomerization of ClpB from Escherichia coli.

Self-association of ClpB (a mixture of 95- and 80-kDa subunits) has been studied with gel filtration chromatography, analytical ultracentrifugation, and electron microscopy. Monomeric ClpB predominates at low protein concentration (0.07 mg/mL), while an oligomeric form is highly populated at >4 mg/mL. The oligomer formation is enhanced in the presence of 2 mM ATP or adenosine 5'-O-thiotriphosphate (ATPgammaS). In contrast, 2 mM ADP inhibits full oligomerization of ClpB. The apparent size of the ATP- or ATPgammaS-induced oligomer, as determined by gel filtration, sedimentation velocity and electron microscopy image averaging, and the molecular weight, as determined by sedimentation equilibrium, are consistent with those of a ClpB hexamer. These results indicate that the oligomerization reactions of ClpB are similar to those of other Hsp100 proteins.

Conformational stability changes of the amino terminal domain of enzyme I of the Escherichia coli phosphoenolpyruvate: sugar phosphotransferase system produced by substituting alanine or glutamate for the active-site histidine 189: implications for phosphorylation effects.

The amino terminal domain of enzyme I (residues 1-258 + Arg; EIN) and full length enzyme I (575 residues; EI) harboring active-site mutations (H189E, expected to have properties of phosphorylated forms, and H189A) have been produced by protein bioengineering. Differential scanning calorimetry (DSC) and temperature-induced changes in ellipticity at 222 nm for monomeric wild-type and mutant EIN proteins indicate two-state unfolding. For EIN proteins in 10 mM K-phosphate (and 100 mM KCl) at pH 7.5, deltaH approximately 140 +/- 10 (160) kcal mol(-1) and deltaCp approximately 2.7 (3.3) kcal K(-1) mol(-1). Transition temperatures (Tm) are 57 (59), 55 (58), and 53 (56) degrees C for wild-type, H189A, and H189E forms of EIN, respectively. The order of conformational stability for dephospho-His189, phospho-His189, and H189 substitutions of EIN at pH 7.5 is: His > Ala > Glu > His-PO3(2-) due to differences in conformational entropy. Although H189E mutants have decreased Tm values for overall unfolding the amino terminal domain, a small segment of structure (3 to 12%) is stabilized (Tm approximately 66-68 degrees C). This possibly arises from an ion pair interaction between the gamma-carboxyl of Glu189 and the epsilon-amino group of Lys69 in the docking region for the histidine-containing phosphocarrier protein HPr. However, the binding of HPr to wild-type and active-site mutants of EIN and EI is temperature-independent (entropically controlled) with about the same affinity constant at pH 7.5: K(A)' = 3 +/- 1 x 10(5) M(-1) for EIN and approximately 1.2 x 10(5) M(-1) for EI.

Comparison of three methods for rapid determination of threshold contrast sensitivity.

Threshold contrast sensitivity functions for 13 subjects were determined on 5 consecutive days using three psychophysical methods. Each method was implemented on a microprocessor controlled display system and considered as a possible candidate for a rapid visual screening test. The methods used were Bekesy tracking, method of adjustment, and method of increasing contrast. The method of increasing contrast proved superior to the other methods in repeatability, speed, and the preservation of individual differences in contrast sensitivity over the testing period.

Do doctors know when their patients don't? A survey of doctor-patient communication in lung cancer.

OBJECTIVES: a) To determine how much patients with recently diagnosed lung cancer know about their illness and its treatment, and b) to find out if doctors know what their patients know and what they don't. PATIENTS AND METHODS: One hundred patients with recently diagnosed lung cancer, who were undergoing radiotherapy or chemotherapy, were interviewed to determine their view of their diagnosis, the extent of the cancer, the intent of treatment, and the risks and benefits of treatment. Their attending physicians' view were elicited contemporaneously, using a self-administered questionnaire. The principle outcome measure of the study was the level of agreement between the views of the patients and the doctors about the disease, the treatment, and the prognosis. Concordance between doctors' and patients' views was expressed in terms of percentage agreement, and Kappa (kappa). RESULTS: Ninety-nine percent of the patients knew that they had lung cancer. Sixty-four percent (64%) agreed with their doctor about the extent of the disease (kappa = 0.48). Most of those who disagreed underestimated the extent of their cancer. Seventy-two percent (72%) agreed with their doctor about the intent of treatment (kappa = 0.49). Thirty-six percent (36%) agreed with their doctors about their probability of cure, (kappa = 0.17): most of those who disagreed systematically overestimated it. Sixty-eight patients were receiving palliative treatment. Of these, 56% agreed with their doctor about the probability of symptomatic benefit (kappa = 0.42), but only 14% agreed with their doctor about the probability that the treatment would prolong life (kappa = 0.06). Doctors frequently failed to recognize their patients' misconceptions about the intent of treatment and the prognosis. CONCLUSION: Many patients did not understand their situation well enough to make a truly autonomous treatment decision, and their doctors often failed to recognize this.

Myeloproliferative disorders: a paradox of in-vivo and in-vitro platelet function.

A patient with features of a myeloproliferative disorder developed an acute multisystems illness and died. In-vitro platelet aggregation was imparied, but necropsy revealed widespread platelet-rich thromboemboli and multiple organ infarctions. It is suggested that platelets are damaged during disseminated intravascular platelet aggregation (DIPA) and that disaggregation of platelet thrombi and recirculation of platelets give rise to their subsequent hypofunction when tested in vitro.

Two apparent Philadelphia chromosomes arising from translocations with different chromosomes in a patient with CML: 46,XY,t(7;22)(p22;q11),t(9;22)(q34;q11).

Chromosome studies on bone marrow cells and unstimulated peripheral lymphocytes from a patient with chronic myelogenous leukemia revealed the presence in all cells of two apparent Philadelphia chromosomes: one resulting from the classical translocation with a chromosome #9, and the other arising from a translocation between chromosomes #22 and #7. There was no normal chromosome #22. Some of the cells also had an i(17q), indicative of blast crisis. Repeated chromosome studies at different times during the course of the disease revealed the evolution of additional karyotypic changes. All cells from later samples had an extra #8; some of these cells had a third Philadelphia chromosome, whereas, others had a second Y chromosome. Although a few normal cells were seen in PHA-stimulated lymphocyte cultures, indicating that the patient has a normal constitutional karyotype, most of the cells had a karyotype identical to that found in unstimulated cultures. This unusual karyotype, 46,XY,t(7;22)(p22;q11),t(9;22)(q34;q11), represents the first case in which two apparent Philadelphia chromosomes are present in the leukemic cells from a patient in the absence of a normal #22 chromosome.

Photostudies of urethral varices "hemorrhoids": a forgotten lesion.

The clinical features, endoscopic findings, and management of urethral varices "hemorrhoids" are described. We also offer a preliminary pathophysiologic discussion of their genesis and their oversight.

Thermal unfolding of Acanthamoeba myosin II and skeletal muscle myosin.

Studies on the thermal unfolding of monomeric Acanthamoeba myosin II and other myosins, in particular skeletal muscle myosin, using differential scanning calorimetry (DSC) are reviewed. The unfolding transitions for intact myosin or its head fragment are irreversible, whereas those of the rod part and its fragments are completely reversible. Acanthamoeba myosin II unfolds with a high degree of cooperativity from ca. 40-45 degrees C at pH 7.5 in 0.6 M KCl, producing a single, sharp endotherm in DSC. In contrast, thermal transitions of rabbit skeletal muscle myosin occur over a broader temperature range (ca. 40-60 degrees C) under the same conditions. The DSC studies on the unfolding of the myosin rod and its fragments allow identification of cooperative domains, each of which unfolds according to a two-state mechanism. Also, DSC data show the effect of the nucleotide-induced conformational changes in the myosin head on the protein stability.

Photoaversion in retinitis pigmentosa.

Photoaversion, or light-induced interference with visual comfort and performance, has been a recognised but poorly documented symptom in retinitis pigmentosa (RP). We found that a majority of our RP patients complained of photoaversion even in the absence of significant cataract. RP patients had reduced contrast sensitivity relative to normal people, but the decrement in their visual performance as a result of glare or photostress was only slight. RP patients had raised short-term adaptation and increment threshold levels, but their rate of short-term or photopic adaptation was normal. Photoaversion in RP may result because a small interference with contrast sensitivity or adaptation can place patients in a range of functional disability, or it may derive from a combination of minor aberrations.

Effects of flurbiprofen and indomethacin on acute cystoid macular edema after cataract surgery: functional vision and contrast sensitivity.

We examined the effect of acute cystoid macular edema (CME) on contrast sensitivity. Eyedrops were instilled into the surgically treated eye f1p4 times daily for two days preoperatively and for three months postoperatively. Angiographic and clinical CME were measured, as were contrast sensitivity and Snellen acuity. Jaeger visual acuity equivalents were calculated and digital imaging techniques used to simulate visual function. We found that angiographic CME reduces functional vision as measured by contrast sensitivity and visual acuity over a large range of sizes. In patients treated with the flurbiprofen vehicle, those without CME had higher mean contrast sensitivity scores than those with CME; this increased over time. Those treated with flurbiprofen and indomethacin had slightly higher contrast sensitivity scores than vehicle-treated patients; this also increased over time, most notably in the higher spatial frequencies. Flurbiprofen treatment improved contrast sensitivity in patients with and without CME significantly at 12 cycles per degree. Flurbiprofen-treated patients with CME in general had higher contrast sensitivity scores than vehicle-treated patients. In this population of patients having cataract surgery, treatment with flurbiprofen or indomethacin reduced the loss of functional vision associated with CME.

Erythroblast multinuclearity in bone marrow and spleen. Congenital dyserythropoietic anemia-like abnormalities without functional evidence of dyserythropoiesis.

A dyserythropoietic syndrome with coincidental immune thrombocytopenia seen during pregnancy is discussed. The morphological and serological results in this case most resemble type II congenital dyserythropoietic anemia. However, functional evidence of dyserythropoiesis was absent and the patient was not anemic. Splenectomy was performed for the resistant thrombocytopenia and microscopic examination of the spleen showed evidence of extramedullary dyserythropoiesis. The significance of these findings is discussed with regard to the spectrum of recognized dyserythropoietic disorders and the unusual discrepancy between the abnormal morphology and the absence of functional dyserythropoiesis.

New conjugate vaccines for the prevention of pneumococcal disease in developing countries.

Current pneumococcal conjugate vaccines (PCVs) are highly effective in preventing serotype-specific pneumococcal disease; however, they are relatively expensive and complicated to produce. Furthermore, PCVs do not cover all disease-causing pneumococcal serotypes. While current PCVs are available in industrialized countries and with external assistance in some low-income countries, alternative, more intrinsically affordable pneumococcal vaccines are essential for achieving more widespread use and coverage in resource-limited settings, where vaccines are often inaccessible and need is greatest. This review article describes a number of approaches to develop new PCVs designed to meet this urgent need.

Timing and uptake of ART during treatment for active tuberculosis in HIV co-infected adults in Malawi.

SETTING: Uptake of antiretroviral therapy (ART) in patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) has historically been low in Malawi. In response, the National TB Programme piloted the initiation of ART 2 weeks after initiation of TB treatment in 2008-2009, a change from the prior policy of 2 months. OBJECTIVE: To determine at programme level if earlier initiation of ART in co-infected patients receiving TB treatment will increase the uptake and continuation of ART. DESIGN: A prospective observational pilot programme evaluation using routinely collected monitoring data from the first two sites with integrated TB-HIV services in Malawi. RESULTS: There was wide variability in the ART start time before and after the policy change. Before the policy change, 16% of patients initiated ART by 3 months compared to 24% after the policy change (P < 0.001). The proportion of all co-infected patients on ART increased from 32% before the policy change to 39% after (P < 0.001). Earlier initiation of ART did not increase the occurrence of side effects and did not reduce adherence to TB treatment. CONCLUSION: Earlier initiation of ART in co-infected patients receiving TB treatment improved the uptake and continuation of ART. Malawi ART guidelines in 2011 were changed from initiating ART after 2 months to as soon as possible after starting anti-tuberculosis treatment.

Oxygen is an essential medicine: a call for international action.

Hypoxaemia is commonly associated with mortality in developing countries, yet feasible and cost-effective ways to address hypoxaemia receive little or no attention in current global health strategies. Oxygen treatment has been used in medicine for almost 100 years, but in developing countries most seriously ill newborns, children and adults do not have access to oxygen or the simple test that can detect hypoxaemia. Improving access to oxygen and pulse oximetry has demonstrated a reduction in mortality from childhood pneumonia by up to 35% in high-burden child pneumonia settings. The cost-effectiveness of an oxygen systems strategy compares favourably with other higher profile child survival interventions, such as new vaccines. In addition to its use in treating acute respiratory illness, oxygen treatment is required for the optimal management of many other conditions in adults and children, and is essential for safe surgery, anaesthesia and obstetric care. Oxygen concentrators provide the most consistent and least expensive source of oxygen in health facilities where power supplies are reliable. Oxygen concentrators are sustainable in developing country settings if a systematic approach involving nurses, doctors, technicians and administrators is adopted. Improving oxygen systems is an entry point for improving the quality of care. For these broad reasons, and for its vital importance in reducing deaths due to lung disease in 2010: Year of the Lung, oxygen deserves a higher priority on the global health agenda.