Compact single-shot electro-optic detection system for THz pulses with femtosecond time resolution at MHz repetition rates.

Electro-optical detection has proven to be a valuable technique to study temporal profiles of THz pulses with pulse durations down to femtoseconds. As the Coulomb field around a relativistic electron bunch resembles the current profile, electro-optical detection can be exploited for non-invasive bunch length measurements at accelerators. We have developed a very compact and robust electro-optical detection system based on spectral decoding for single-shot longitudinal bunch profile monitoring at the European X-ray Free Electron Laser (XFEL) for electron bunch lengths down to 200 fs (rms). Apart from the GaP crystal and the corresponding laser optics at the electron beamline, all components are housed in 19 in. chassis for rack mount and remote operation inside the accelerator tunnel. An advanced laser synchronization scheme based on radio-frequency down-conversion has been developed for locking a custom-made Yb-fiber laser to the radio-frequency of the European XFEL accelerator. In order to cope with the high bunch repetition rate of the superconducting accelerator, a novel linear array detector has been employed for spectral measurements of the Yb-fiber laser pulses at frame rates of up to 2.26 MHz. In this paper, we describe all sub-systems of the electro-optical detection system as well as the measurement procedure in detail and discuss the first measurement results of longitudinal bunch profiles of around 400 fs (rms) with an arrival-time jitter of 35 fs (rms).

Ising-model description of long-range correlations in DNA sequences.

We model long-range correlations of nucleotides in the human DNA sequence using the long-range one-dimensional (1D) Ising model. We show that, for distances between 10(3) and 10(6) bp, the correlations show a universal behavior and may be described by the non-mean-field limit of the long-range 1D Ising model. This allows us to make some testable hypothesis on the nature of the interaction between distant portions of the DNA chain which led to the DNA structure that we observe today in higher eukaryotes.

Finite-temperature behavior of glueballs in lattice gauge theories.

We propose a new method to compute glueball masses in finite temperature lattice gauge theory which at low temperature is fully compatible with the known zero temperature results and as the temperature increases leads to a glueball spectrum which vanishes at the deconfinement transition. We show that this definition is consistent with the Isgur-Paton model and with the expected contribution of the glueball spectrum to various thermodynamic quantities at finite temperature. We test our proposal with a set of high precision numerical simulations in the 3D gauge Ising model and find a good agreement with our predictions.

Nucleation dynamics in two-dimensional cylindrical Ising models and chemotaxis.

The aim of our work is to study the effect of geometry variation on nucleation times and to address its role in the context of eukaryotic chemotaxis (i.e., the process which allows cells to identify and follow a gradient of chemical attractant). As a first step in this direction we study the nucleation dynamics of the two-dimensional Ising model defined on a cylindrical lattice whose radius changes as a function of time. Geometry variation is obtained by changing the relative value of the couplings between spins in the compactified (vertical) direction with respect to the horizontal one. This allows us to keep the lattice size unchanged and study in a single simulation the values of the compactification radius which change in time. We show both with theoretical arguments and numerical simulations that squeezing the geometry allows the system to speed up nucleation times even in presence of a very small energy gap between the stable and the metastable states. We then address the implications of our analysis for directional chemotaxis. The initial steps of chemotaxis can be modeled as a nucleation process occurring on the cell membrane as a consequence of the external chemical gradient (which plays the role of energy gap between the stable and metastable phases). In nature most of the cells modify their geometry by extending quasi-one-dimensional protrusions (filopodia) so as to enhance their sensitivity to chemoattractant. Our results show that this geometry variation has indeed the effect of greatly decreasing the time scale of the nucleation process even in presence of very small amounts of chemoattractants.

Ab initio identification of putative human transcription factor binding sites by comparative genomics.

BACKGROUND: Understanding transcriptional regulation of gene expression is one of the greatest challenges of modern molecular biology. A central role in this mechanism is played by transcription factors, which typically bind to specific, short DNA sequence motifs usually located in the upstream region of the regulated genes. We discuss here a simple and powerful approach for the ab initio identification of these cis-regulatory motifs. The method we present integrates several elements: human-mouse comparison, statistical analysis of genomic sequences and the concept of coregulation. We apply it to a complete scan of the human genome. RESULTS: By using the catalogue of conserved upstream sequences collected in the CORG database we construct sets of genes sharing the same overrepresented motif (short DNA sequence) in their upstream regions both in human and in mouse. We perform this construction for all possible motifs from 5 to 8 nucleotides in length and then filter the resulting sets looking for two types of evidence of coregulation: first, we analyze the Gene Ontology annotation of the genes in the set, searching for statistically significant common annotations; second, we analyze the expression profiles of the genes in the set as measured by microarray experiments, searching for evidence of coexpression. The sets which pass one or both filters are conjectured to contain a significant fraction of coregulated genes, and the upstream motifs characterizing the sets are thus good candidates to be the binding sites of the TF's involved in such regulation. In this way we find various known motifs and also some new candidate binding sites. CONCLUSION: We have discussed a new integrated algorithm for the "ab initio" identification of transcription factor binding sites in the human genome. The method is based on three ingredients: comparative genomics, overrepresentation, different types of coregulation. The method is applied to a full-scan of the human genome, giving satisfactory results.

Tuberculosis in a rural hospital in northern Kenya.

A 9-year survey on tuberculosis control at Sololo General Hospital (Marsabit District) is presented. 700 patients were treated and followed up from 1982 to 1990. The paper deals with the major constraints of TB control in a nomadic population on the borderland with Ethiopia; it highlights the need of the short course regimen and the TB manyatta programme to increase the percentage of cured patients.

Increased incidence of cancer in chronic pancreatitis.

Patients affected by chronic pancreatitis were followed between 1970 and 1984 in a study set up to evaluate the natural history of the disease. The study population included 172 consecutive patients diagnosed as having chronic pancreatitis in the Gastroenterology Unit of the S. Giovanni Battista Hospital in Torino, Italy. Of them, 23 were found to be affected by cancer during the 14-year follow-up period. The incidence calculated using the person-year method was compared with data from the General Population Cancer Registry of Piemonte Region. The age-specific relative risks of cancer were increased manifold. Sex- and age-specific relative risks were markedly increased for liver, tongue, lip, and rectum tumors in males, and for liver, bone, and breast tumors in females. Selection bias did not seem to be an adequate explanation of this association. Survival curves were plotted by the estimation methods of Cutler-Ederer with year intervals for the complete study population and for the different type of cancer. Known risk factors and indicators for the expected tumors were evaluated by the Cox Proportional Hazard Regression Model. The incidence of cancer increases significantly with age but not with smoking, alcohol use, and diabetes. Our epidemiological study suggests an increased risk of pancreatic as well as extrapancreatic cancer in patients with chronic pancreatitis compared with the general population. Cancer seems to be a main determinant in the natural history of the disease.

Peripheral nerve function and metabolic control in diabetes mellitus.

Measurement of conduction velocity along the H reflex arc was used to study sensorimotor peripheral nerve function in diabetic patients during short- and long-term improvement of hyperglycemia. In ten type I diabetics a slight (p less than 0.05) conduction increase occurred after 6 hours of normal glycemia induced by an artificial endocrine pancreas. Similar but more prominent improvement occurred in twelve type I diabetics treated with continuous subcutaneous insulin injection for 6 months. The results suggest that nerve conduction slowing in diabetic patients stems partly from reversible, nonstructural abnormalities and partly from more slowly reversible morphological or chemical changes in peripheral nerve.

Metformin reduces insulin requirement in Type 1 (insulin-dependent) diabetes.

The effect of metformin on Type 1 (insulin-dependent) diabetes has been assessed with the artificial pancreas. Fourteen Type 1 diabetic patients of normal body weight received in addition to their usual insulin therapy 850 mg metformin or placebo three times a day for 4-6 weeks. The sequence was placebo-metformin in eight patients and metformin-placebo in the other six. On the last day of metformin or placebo treatment, an artificial pancreas was used for about 36 h to assess insulin requirement. There was a 25.8% reduction in insulin requirement during metformin management despite slightly lower blood glucose levels (5.25 +/- 0.20 versus 5.98 +/- 0.18 mmol/l, p less than 0.01). Maximum reduction (about 50%) occurred 2 h after both lunch and dinner. There was no nocturnal effect. A marked decrease in specific insulin binding before metformin was found (0.56 +/- 0.27% to 10(7) monocytes versus 2.82 +/- 0.75 of control subjects) and significant increase after metformin (1.36 +/- 0.36%, p less than 0.05). There were no significant changes in blood lactate, total and HDL-cholesterol, triglycerides and C-peptide levels. These results show that insulin receptor binding is diminished in Type 1 diabetes, perhaps as a consequence of higher peripheral blood insulin levels and that metformin can improve binding, and so reduce the amount of insulin needed to reach euglycaemia. The insulin sparing effect is greatest after meals, and interference with intestinal absorption of sugars may also be important. It follows that metformin could be usefully administered to Type 1 diabetic patients with unimpaired liver and renal function to reduce their insulin requirement.

To what extent does the artificial pancreas facilitate the surgery of preoperatively not localized insulinomas?

The patient study has been performed in order to evaluate the usefulness of the artificial pancreas in the surgical management of previously not localized insulinomas. In the 4 patients studied, blood glucose was maintained both overnight and during surgery up to a preselected individualized level in order to avoid hypoglycemia. During surgery, only one patient required dextrose infusion. The continuous intrasurgical monitoring of blood glucose in the 4 cases examined showed that: (1) anesthesia induction, surgical incision and viscera mobilization were accompanied by a rise in blood glucose (10.30 mg/dl), reaching the highest levels 30-40 min after the start of the operation; (2) adenoma manipulation was followed by a drop in blood glucose (10.40 mg/dl), reaching the lowest level after 30-40 min; (3) adenoma resection was followed by a rise in blood glucose (25-40 mg/dl), particularly evident after 30-40 min. It is concluded that the artificial pancreas is certainly useful during surgery of insulin-producing tumors, allowing continuous monitoring of glycemia and avoiding dangerous blood glucose excursions: however, when the insulinoma is not identified during surgery, the periods elapsing between the surgical phases and the blood glucose changes observed can be too prolonged to ensure successful conservative serial pancreatectomy in all cases.

Preprandial and postprandial variations of insulin sensitivity in different times of the day assessed by the artificial pancreas in type I diabetics.

The aim of this study is to see whether changes in insulin need and in sensitivity to exogenous insulin occur in insulin-dependent diabetics receiving 3 daily non-isocaloric meals (at 0630, 1200 and 1730). In 9 type I diabetics submitted to the artificial pancreas control the insulin administered/dietary carbohydrates index (I/C) after breakfast (2.4 +/- 0.5) was significantly higher than after lunch (0.8 +/- 0.1) and after supper (0.84 +/- 0.1) (p less than 0.01). A trend to the reduced insulin sensitivity in the morning was also observed in fasting periods, when it was calculated as the ratio between blood glucose and insulin administered (BG/I): differences of BG/I however were not significant. It was concluded that diurnal variations of insulin sensitivity do occur in type I diabetic subjects, with an increment of insulin requirement in the morning.