Measurement of Lepton-Jet Correlation in Deep-Inelastic Scattering with the H1 Detector Using Machine Learning for Unfolding.

The first measurement of lepton-jet momentum imbalance and azimuthal correlation in lepton-proton scattering at high momentum transfer is presented. These data, taken with the H1 detector at HERA, are corrected for detector effects using an unbinned machine learning algorithm (multifold), which considers eight observables simultaneously in this first application. The unfolded cross sections are compared with calculations performed within the context of collinear or transverse-momentum-dependent factorization in quantum chromodynamics as well as Monte Carlo event generators.

Capturing a photoexcited molecular structure through time-domain x-ray absorption fine structure.

The determination of the structure of transient molecules, such as photoexcited states, in disordered media (such as in solution) usually requires methods with high temporal resolution. The transient molecular structure of a reaction intermediate produced by photoexcitation of NiTPP-L2 (NiTPP, nickeltetraphenylporphyrin; L, piperidine) in solution was determined by x-ray absorption fine structure (XAFS) data obtained on a 14-nanosecond time scale from a third-generation synchrotron source. The XAFS measurements confirm that photoexcitation leads to the rapid removal of both axial ligands to produce a transient square-planar intermediate, NiTPP, with a lifetime of 28 nanoseconds. The transient structure of the photodissociated intermediate is nearly identical to that of the ground state NiTPP, suggesting that the intermediate adopts the same structure as the ground state in a noncoordinating solvent before it recombines with two ligands to form the more stable octahedrally coordinated NiTPP-L2.

Solar neutrinos: proposal for a new test.

The predicted flux on the earth of solar neutrinos has eluded detection, confounding current ideas of solar energy production by nuclear fusion. The dominant low-energy component of that flux can be detected by mass-spectrometric assay of the induced tiny concentration of 1.6 x 10(7) year lead-205 in old thallium minerals. Comments are solicited from those in all relevant disciplines.

Behavioural and psychological symptoms in general hospital patients with dementia, distress for nursing staff and complications in care: results of the General Hospital Study.

AIMS: Little is known about how behavioural and psychological symptoms of dementia (BPSD) manifest in the general hospital. The aim was to examine the frequency of BPSD in general hospitals and their associations with nursing staff distress and complications in care. METHODS: Cross-sectional representative study with 1469 patients aged ≥65, including 270 patients with dementia, of 33 randomly selected general hospitals in Germany. BPSD and complications were reported by nurses. RESULTS: Overall frequency of BPSD was higher in patients with dementia (76%) than without (38%). The most frequent symptoms in patients with dementia were nighttime disturbances (38%), depression (29%) and aberrant motor behaviour (28%) and the most distressing symptoms for nursing staff were delusions, aggression and nighttime disturbances. The overall frequency of BPSD increased from 67% in mild dementia, to 76% in moderate dementia and to 88% in severe dementia. The most frequent symptoms in patients without dementia were depression (19%), nighttime disturbances (13%) and irritability (13%). The most distressing symptoms were aggression and delusions, while the same symptoms were consistently rated as less distressing than in patients with dementia. Factor analysis revealed three independent groups of BPSD that explained 45% of the total variance. First, expansive symptoms (aggression, irritability, nighttime disturbances, aberrant motor behaviour and disinhibition) were frequent, distressing for nursing staff and associated with many complications. Second, psychotic symptoms (delusions and hallucinations) were infrequent, distressing and associated with some complications. Third, affective symptoms (apathy, anxiety and depression) were frequent, non-distressing and associated with few complications. The results did not change when cases with delirium were excluded from both groups. CONCLUSIONS: BPSD are common in older hospital patients with dementia and associated with considerable distress in nursing staff, as well as a wide range of special treatments needs and additional behavioural and medical complications. Management strategies are needed to improve the situation for both patients and hospital staff.

Dinaciclib is a novel cyclin-dependent kinase inhibitor with significant clinical activity in relapsed and refractory chronic lymphocytic leukemia.

Dinaciclib (SCH727965) is a selective CDKi chosen for clinical development based upon a favorable therapeutic index in cancer xenograft models. We performed a phase I dose escalation study of dinaciclib in relapsed and refractory chronic lymphocytic leukemia (CLL) patients with intact organ function and WBC<200 × 10(9) /l. Five separate dose levels (5 mg/m(2), 7 mg/m(2), 10 mg/m(2), 14 mg/m(2) and 17 mg/m(2)) were explored dosing on a weekly schedule × 3 with 1 week off (4-week cycles) using a standard 3+3 design with expansion cohorts to optimize safety. Fifty-two patients were enrolled with relapsed and refractory CLL. Escalation through cohorts occurred with two dose-limiting toxicity (DLTs) at the 17 mg/m(2) dose (tumor lysis syndrome (TLS) and pneumonia). The phase II expansion occurred at 14 mg/m(2) with 16 patients receiving this dose with one DLT (TLS). Additional stepped up dosing to the maximum tolerated dose was examined in 19 patients at this dose. Adverse events included cytopenias, transient laboratory abnormalities and TLS. Responses occurred in 28 (54%) of patients independent of del(17)(p13.1) with a median progression-free survival of 481 days. Dinaciclib is clinically active in relapsed CLL including those patients with high risk del(17)(p13.1) disease and warrants future study.

Effects of sodium chloride on pregnant sheep with reduced uteroplacental perfusion pressure.

This study investigated the effects of NaCl supplementation (5 mEq/kg/day) on the arterial pressure of pregnant and nonpregnant sheep with and without reduction of uteroplacental perfusion pressure. In pregnant sheep receiving NaCl supplementation during the third trimester, reduction of aortic pressure caudal to the kidneys to 65% of the upstream pressure (occlusion) caused a progressive increase in mean arterial pressure from 89 +/- 3 to 110 +/- 3 mm Hg over 2 weeks. Occlusion was accompanied by a decrease in urine flow. Six of seven sheep died or were killed because of severe respiratory distress. No abnormalities were detected in nonpregnant sheep or pregnant sheep receiving NaCl supplementation only. Pregnant sheep that were occluded but received no supplementary NaCl did not become hypertensive but aborted about 2 weeks after occlusion. These results indicate that reduction of uteroplacental perfusion pressure causes hypertension in NaCl-supplemented pregnant sheep but not in sheep receiving a normal, low sodium diet.

LDL-induced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture.

Human aortic medial smooth muscle cells (SMC) and umbilical vein endothelial cells (EC) in culture were exposed to various concentrations of plasma low density (LDL) and high density (HDL) lipoproteins prepared from normolipemic donors in order to assess their effects on cell growth. So that the effects of each lipoprotein could be evaluated separately and in combination, lipoproteins were added to culture medium containing lipoprotein deficient serum (LPDS, d greater than 1.25 g/ml at a protein concentration of 4.5 mg/ml of medium). The addition of LDL at cholesterol concentrations of 160 microgram/ml of culture medium, resulted in significant reductions in both the number of SMC and EC cells per dish within 3 days of exposure (P less than 0.001, SMC; P less than 0.01, EC), when compared with LPDS controls and the starting cell numbers. This cytotoxic phenomenon was dose-related, and only at LDL cholesterol concentrations equal to or below 50 microgram/ml were no marked changes observed. In contrast, HDL at all concentrations tested produced no such deleterious effects. Autoradiographic assessment of DNA synthesis confirmed these findings. After 48 h of continuous exposure to tritiated thymidine, labeling indexes reached much lower plateaus in the LDL-treated groups.

Pulmonary and systemic vascular effects of exogenous prostaglandin I2 in fetal lambs.

Effects of PGI2 upon pulmonary vascular resistance and systemic arterial pressure of near term fetuses were evaluated in anesthetized, exteriorized, unventilated fetal lambs by means of an open-chest, pump-perfused lung preparation. These effects were compared to those of PGE1 and PGE2 in the same animals. Intrapulmonary arterial infusions of PGI2 produced dose-dependent decreases in pulmonary vascular resistance and systemic arterial pressure. Effects of PGI2 upon pulmonary vascular resistance are intermediate with respect to those of PGE1 (greater) and PGE2 (less). PGI2 is a potent hypotensive compound when administered to fetal lambs, producing dose-dependent decreases in systemic arterial pressure. When the three prostaglandins are infused into the pulmonary artery, effects on systemic arterial pressure of PGE1 and PGI2 are nearly identical. Effects of PGE2 are considerably less. PGI2 is a potent dilator of fetal lamb vessels and could play a role in circulatory control during perinatal transition.

Influence of videofilm-induced emotional stress on the flow properties of blood.

The hemorheologic effects of emotional stress induced by a videofilm were investigated in 10 healthy volunteers. Blood samples were obtained from the antecubital vein before, during, and after the end of the videofilm. Blood pressure and heart rate were simultaneously measured. There was a statistically significant increase in blood and plasma viscosity during and immediately after the end of the videofilm, which correlated with an increase in plasma catecholamine concentrations. This hemorheologic behavior can be explained as a result of an endogenous hemoconcentration that takes place if the Starling equilibrium of intravascular vs extravascular fluid is changed. These observations could lead to new aspects of the pathophysiology of acute myocardial infarction initiated by severe emotional stress.

Porcine atrophic rhinitis: a model for studying nasal physiology and pathophysiology.

Porcine infectious atrophic rhinitis is a disease of swine which ought to be of considerable interest to rhinologists. We have reviewed some aspects of human atrophic rhinitis, and some aspects of etiology incidence, pathology and physiology of porcine infectious atrophic rhinitis. Swine with this nasal problem fail rather dramatically, to gain as much weight as unaffected animals. We have speculated on several reasons for this including altered nasal physiology and trigeminal reflexes and reduced olfaction. Photographs of infected pigs are included.

Frequency shift and asymmetric line shape of the fourth anti-Stokes component from a hydrogen Raman shifter.

We have measured the spectral properties of the fourth anti-Stokes component of the output of a pressurized, molecular hydrogen, Raman shifter pumped by the intense output of a frequency-doubled narrowband pulsed dye laser. All the observed line shapes are asymmetric, with full widths at half-maximum ranging from 0.3 to 0.8 cm(-1). The spectral peak of the Raman-shifted light varies linearly with the intensity of the pump light and is given by sigma(rho,I) = sigma(rho) + AI. The previously measured density-dependent Stokes shift is sigma(rho), the intensity of the laser is I, and A is 1.5 +/- 0.2 cm(-1)/(TW/cm(2)). The electric field-induced shift and asymmetric line shape limit the accuracy and resolution of spectroscopic measurements made with light from a hydrogen Raman shifter. We propose that these observations may be explained by the ac Stark effect in the Raman shifting medium.

Positive end expiratory pressure (PEEP) and right to left shunting in immature goats.

Immature fetal goats were exteriorized by caesarean section and catheters were placed in a pulmonary vein (PV), carotid artery (CA), femoral artery (FA), and the main pulmonary artery (PA). The goats were ventilated at 7.5 and 15 cm H20 positive end expiratory pressure (PEEP) between control periods at 0 PEEP. Right to left shunting (Qs/Qt) was calculated for three anatomic sites: lung, foramen ovale, and ductus arteriosus, and for two summation shunts: preductal and total. Total Qs/Qt increased in 8 of 14 animals at 7.5 cm H2O PEEP and in 7 of 12 animals at 15 cm H2O PEEP. Intrapulmonary shunting increased in only one experiment. The increase in total Qs/Qt resulted from elevated extrapulmonary shunting, always including the ductus arteriosus. The variation in response to PEEP was from animal to animal and not from one level to another within one animal. Changes in total Qs/Qt on PEEP did not correlate with the size of control Qs/Qt at any site.

Perinatal pulmonary prostaglandin production.

Products of reactions catalyzed by prostaglandin cyclo-oxygenase [prostaglandins (PG), thromboxanes] were analyzed by gas chromatography with electron-capture detection in the venous effluents of in situ Krebs-perfused lungs of exteriorized fetal goats and sheep before and after ventilation with air. The major products were 6-keto-PGF1 alpha and 6,15-diketo[13,14-dihydro] PGI2 without blood components. After ventilation, which decreased pulmonary vascular resistance to 63% of the before-ventilation value, lung production of 6-keto-PGF1 alpha and metabolite increased 50 and 230%, respectively. These data, in addition to earlier findings of inhibition of ventilation-induced pulmonary vasodilation by indomethacin and increased net production of PG-like material after ventilation of blood-perfused fetal lungs, support the hypothesis that ventilation of fetal lungs with air at birth increases synthesis of PGI2 by or near pulmonary resistance vessels, resulting in high local concentrations of PGI2 near its site of production. PGI2 appears to be important in the pulmonary vascular resistance decrease that is necessary for successful perinatal transition.

Effects of increased intracranial pressure on pulmonary vascular resistance of fetal and neonatal goats.

The effects of increased intracranial pressure on the pulmonary circulation were investigated in fetal and neonatal goats. Pulmonary vascular resistance and systemic arterial pressure increased with elevation of intracranial pressure in neonatal animals. Alpha-adrenergic blockade completely eliminated both of these responses. The response of the fetal pulmonary circulation was unlike that seen in the postnatal animal. Although there was a slight elevation of pulmonary vascular resistance initially, the predominant response was a decrease in resistance. The decrease in fetal pulmonary vascular resistance was unaffected by phenoxybenzamine, but reversed by propranolol. After the beta-adrenergic blockade, increased intracranial pressure produced an increase in pulmonary vascular resistance. Similarly, ventilation of fetal lungs resulted in an increase in pulmonary vascular resistance after increased intracranial pressure. These results demonstrate for the first time that pulmonary vascular resistance may be altered in fetal and neonatal animals by increasing intracranial pressure. The elevation of pulmonary vascular resistance after elevated intracranial pressure must be due to an active pulmonary vascular constriction.

An early step in Pseudomonas exotoxin action is removal of the terminal lysine residue, which allows binding to the KDEL receptor.

During the intoxication process, Pseudomonas exotoxin (PE) and immunotoxins containing PE internalize into the target cell and become processed into two fragments, and the carboxyl fragment translocates into the cytosol where it inactivates elongation factor 2. We have proposed that after internalization into cells the carboxyl-terminal fragment of PE (amino acids 280-613), which ends in REDLK, binds to the KDEL receptor (ERD2) which carries it to the endoplasmic reticulum, from which the PE fragment translocates to the cytosol. Earlier experiments showing that REDL but not REDLK binds to the KDEL receptor suggested that the terminal lysine is removed sometime during the intoxication process. To determine if and where this occurs, we exposed a peptide ending in REDLK to malignant cells in culture and found that binding to the KDEL receptor was restored. Restoration of receptor binding also occurred if a peptide or toxin ending in REDLK at its carboxyl terminus was incubated with plasma, indicating that the terminal lysine is removed prior to entry of the toxin into the cell. We conclude that plasma carboxypeptidase(s) cleave(s) the lysine residue from the carboxyl terminus of PE and PE-containing immunotoxins as an early and essential step in their cellular intoxication pathway.

Efficient monochromator to isolate VUV light generated by four-wave mixing techniques.

The lateral chromatic aberration from a LiF lens, which is positioned off-axis with respect to the incident light beams, is used to isolate the VUV light generated by the four-wave mixing technique from the intense pump light. The transmittance of the monochromator at the VUV wavelength is limited by the transmittance of a single lens. The ratio of transmitted-to-incident pump energy is 3.3 x 10(-6). A single monochromator with two interchangeable lenses can be used for either tightly focused or collimated pump beams.