Quantum gate algorithm for reference-guided DNA sequence alignment.

Reference-guided DNA sequencing and alignment is an important process in computational molecular biology. The amount of DNA data grows very fast, and many new genomes are waiting to be sequenced while millions of private genomes need to be re-sequenced. Each human genome has 3.2B base pairs, and each one could be stored with 2 bits of information, so one human genome would take 6.4B bits or ∼760MB of storage (National Institute of General Medical Sciences, n.d.). Today's most powerful tensor processing units cannot handle the volume of DNA data necessitating a major leap in computing power. It is, therefore, important to investigate the usefulness of quantum computers in genomic data analysis, especially in DNA sequence alignment. Quantum computers are expected to be involved in DNA sequencing, initially as parts of classical systems, acting as quantum accelerators. The number of available qubits is increasing annually, and future quantum computers could conduct DNA sequencing, taking the place of classical computing systems. We present a novel quantum algorithm for reference-guided DNA sequence alignment modeled with gate-based quantum computing. The algorithm is scalable, can be integrated into existing classical DNA sequencing systems and is intentionally structured to limit computational errors. The quantum algorithm has been tested using the quantum processing units and simulators provided by IBM Quantum, and its correctness has been confirmed.

Quantum algorithm for de novo DNA sequence assembly based on quantum walks on graphs.

De novo DNA sequence assembly is based on finding paths in overlap graphs, which is a NP-hard problem. We developed a quantum algorithm for de novo assembly based on quantum walks in graphs. The overlap graph is partitioned repeatedly to smaller graphs that form a hierarchical structure. We use quantum walks to find paths in low rank graphs and a quantum algorithm that finds Hamiltonian paths in high hierarchical rank. We tested the partitioning quantum algorithm, as well as the quantum algorithm that finds Hamiltonian paths in high hierarchical rank and confirmed its correct operation using Qiskit. We developed a custom simulation for quantum walks to search for paths in low rank graphs. The approach described in this paper may serve as a basis for the development of efficient quantum algorithms that solve the de novo DNA assembly problem.

Sumisión química con escopolamina, a propósito de un brote de tres casos / Drug-facilitated crime with scopolamine, a presentation of three cases

En los últimos años, la Sumisión Química con escopolamina, conocida popularmente como Burundanga, ha recibido una importante atención de los medios de comunicación de masas en nuestro país sin una clara correlación con el número de casos notificados en la literatura científica. Esta ausencia de casos notificados puede ser debida en parte a la dificultad de obtener un diagnóstico analítico que permita confirmar la presencia de la misma en los sujetos que la padecen. Presentamos tres casos de varones con Sumisión Química confirmada con escopolamina atendidos en nuestro centro

In recent years, Drug-facilitated crime with Scopolamine, popularly known as Burundanga, has received significant attention from the mass media in our country without a clear correlation with the number of cases reported in the scientific literature. The absence of reported cases may be due in part to the difficulty of obtaining an analytical diagnosis that allows confirming its presence. We present three cases of confirmed Drug-facilitated crime with Scopolamine in our center

The in-vivo oxyhaemoglobin dissociation curve at sea level and high altitude.

Animals native to hypoxic environments have adapted by increasing their haemoglobin oxygen affinity, but in-vitro studies of the oxyhaemoglobin dissociation curve (ODC) in humans show no changes in affinity under physiological conditions at altitudes up to 4000m. We conducted the first in-vivo measurement of the ODC; inducing progressive isocapnic hypoxia in lowlanders at sea level, acutely acclimatized lowlanders at 3600m, and native Andeans at that altitude. ODC curves were determined by administering isocapnic steps of increasing hypoxia, and measuring blood oxygen partial pressure and saturation. The ODC data were fitted using the Hill equation and extrapolated to predict the oxygen partial pressure at which haemoglobin was 50% saturated (P50). In contrast to findings from in-vitro studies, we found a pH-related reduction in P50 in subjects at altitude, compared to sea-level subjects. We conclude that a pH-mediated increase in haemoglobin oxygen affinity in-vivo may be part of the acclimatization process in humans at altitude.

Medicina regenerativa corneal: aplicaciones en oftalmología / Regenerative corneal medicine: Ophthalmology applications

No disponible

[An unrecognized oesophageal rupture]. / Une rupture méconnue de l'oesophage abdominal.

Perforation of the abdominal oesophagus from blunt trauma is an extremely rare injury. We report a case of an initially unrecognized oesophageal injury. The patient underwent an immediate laparotomy for haemorrhagic shock. The diagnosis was made by tomodensitometry and was delayed by modified radiological interpretation secondary to laparotomy. Finally, the outcome was favourable.

Altitude adaptation through hematocrit changes.

Adaptation takes place not only when going to high altitude, as generally accepted, but also when going down to sea level. Immediately upon ascent to high altitude, the carotid body senses the lowering of the arterial oxygen partial pressure due to a diminished barometric pressure. High altitude adaptation is defined as having three stages: 1) acute, first 72 hours, where acute mountain sickness (CMS or polyerythrocythemia) can occur; 2) subacute, from 72 hours until the slope of the hematocrit increase with time is zero; here high altitude subacute heart disease can occur; and 3) chronic, where the hematocrit level is constant and the healthy high altitude residents achieve their optimal hematocrit. In the chronic stage, patients with CMS increase their hematocrit values to levels above that of normal individuals at the same altitude. CMS is due to a spectrum of medical disorders focused on cardiopulmonary deficiencies, often overlooked at sea level. In this study we measured hematocrit changes in one high altitude resident traveling several times between La Paz (3510 m) and Copenhagen (35 m above sea level) for the past 3 years. We have also studied the fall in hematocrit values in 2 low-landers traveling once from La Paz to Copenhagen. High altitude adaptation is altitude and time dependent, following the simplified equation: Adaptation=Time/Altitude where High altitude adaptation factor=Time at altitude (days)/Altitude in kilometers (km). A complete and optimal hematocrit adaptation is only achieved at around 40 days for a subject going from sea level to 3510 m in La Paz. The time in days required to achieve full adaptation to any altitude, ascending from sea level, can be calculated by multiplying the adaptation factor of 11.4 times the altitude in km. Descending from high altitude in La Paz to sea level in Copenhagen, the hematocrit response is a linear fall over 18 to 23 days.

Hypoventilation in chronic mountain sickness: a mechanism to preserve energy.

Chronic Mountain Sickness (CMS) patients have repeatedly been found to hypoventilate. Low saturation in CMS is attributed to hypoventilation. Although this observation seems logical, a further understanding of the exact mechanism of hypoxia is mandatory. An exercise study using the Bruce Protocol in CMS (n = 13) compared to normals N (n = 17), measuring ventilation (VE), pulse (P), and saturation by pulse oximetry (SaO(2)) was performed. Ventilation at rest while standing, prior to exercise in a treadmill was indeed lower in CMS (8.37 l/min compared with 9.54 l/min in N). However, during exercise, stage one through four, ventilation and cardiac frequency both remained higher than in N. In spite of this, SaO(2) gradually decreased. Although CMS subjects increased ventilation and heart rate more than N, saturation was not sustained, suggesting respiratory insufficiency. The degree of veno-arterial shunting of blood is obviously higher in the CMS patients both at rest and during exercise as judged from the SaO(2) values. The higher shunt fraction is due probably to a larger degree of trapped air in the lungs with uneven ventilation of the CMS patients. One can infer that hypoventilation at rest is an energy saving mechanism of the pneumo-dynamic and hemo-dynamic pumps. Increased ventilation would achieve an unnecessary high SaO(2) at rest (low metabolism). This is particularly true during sleep.

Chronic mountain sickness: the reaction of physical disorders to chronic hypoxia.

Chronic mountain sickness (CMS) is a condition in which hematocrit is increased above the normal level in residents at high altitude. In this article we take issue with the "Consensus Statement On Chronic And Subacute High Altitude Diseases" of 2005 on two essential points: using a questionnaire to evaluate the symptoms of CMS to use the term "loss of adaptation" as opposed to "adaptation to disease in the hypoxic environment". We opine that CMS is rather an adaptive reaction to an underlying malfunction of some organs and no specific symptoms could be quantified. To substantiate our line of reasoning we reviewed 240 CMS cases seen at the High Altitude Pathology Institute in La Paz. Patients who had a high hematocrit (<58%) underwent pulmonary function studies in search for the cause of hypoxia: hypoventilation, diffusion alteration, shunts, and uneven ventilation-perfusion. The tests included arterial blood gas tests, chest x-rays, spirometry, hyperoxic tests, flow-volume curves, ventilation studies at rest and during exercise, ECG, exercise testing and doppler color echocardiography to assess heart structure and function. When correlated with clinical history these results revealed that CMS is practically always secondary to some type of anomaly in cardio-respiratory or renal function. Therefore, a questionnaire that tries to catalog symptoms common to many types of diseases that lead to hypoxia is flawed because it leads to incomplete diagnosis and inappropriate treatment. CMS, once again, was shown to be an adaptation of the blood transport system to a deficient organs' function due to diverse disease processes; the adaptation aimed at sustaining normoxia at the cellular level in the hypoxic environment at high altitude.

Essentials in the diagnosis of acid-base disorders and their high altitude application.

This report describes the historical development in the clinical application of chemical variables for the interpretation of acid-base disturbances. The pH concept was already introduced in 1909. Following World War II, disagreements concerning the definition of acids and bases occurred, and since then two strategies have been competing. Danish scientists in 1923 defined an acid as a substance able to give off a proton at a given pH, and a base as a substance that could bind a proton, whereas the North American Singer-Hasting school in 1948 defined acids as strong non-buffer anions and bases as non-buffer cations. As a consequence of this last definition, electrolyte disturbances were mixed up with real acid-base disorders and the variable, strong ion difference (SID), was introduced as a measure of non-respiratory acid-base disturbances. However, the SID concept is only an empirical approximation. In contrast, the Astrup/Siggaard-Andersen school of scientists, using computer strategies and the Acid-base Chart, has made diagnosis of acid-base disorders possible at a glance on the Chart, when the data are considered in context with the clinical development. Siggaard-Andersen introduced Base Excess (BE) or Standard Base Excess (SBE) in the extracellular fluid volume (ECF), extended to include the red cell volume (eECF), as a measure of metabolic acid-base disturbances and recently replaced it by the term Concentration of Titratable Hydrogen Ion (ctH). These two concepts (SBE and ctH) represent the same concentration difference, but with opposite signs. Three charts modified from the Siggaard-Andersen Acid-Base Chart are presented for use at low, medium and high altitudes of 2500 m, 3500 m, and 4000 m, respectively. In this context, the authors suggest the use of Titratable Hydrogen Ion concentration Difference (THID) in the extended extracellular fluid volume, finding it efficient and better than any other determination of the metabolic component in acid-base disturbances. The essential variable is the hydrogen ion.

Non-invasive measurement of circulation time using pulse oximetry during breath holding in chronic hypoxia.

Pulse oximetry during breath-holding (BH) in normal residents at high altitude (3510 m) shows a typical graph pattern. Following a deep inspiration to total lung capacity (TLC) and subsequent breath-holding, a fall in oxyhemoglobin saturation (SaO(2) is observed after 16 s. The down-pointed peak in SaO(2) corresponds to the blood circulation time from the alveoli to the finger where the pulse oximeter probe is placed. This simple maneuver corroborates the measurement of circulation time by other methods. This phenomenon is even observed when the subject breathes 88% oxygen (PIO(2) = 403 mmHg for a barometric pressure of 495 mmHg). BH time is, as expected, prolonged under these circumstances. Thus the time delay of blood circulation from pulmonary alveoli to a finger is measured non-invasively. In the present study we used this method to compare the circulation time in 20 healthy male high altitude residents (Group N with a mean hematocrit of 50%) and 17 chronic mountain sickness patients (Group CMS with a mean hematocrit of 69%). In the two study groups, the mean circulation time amounted to 15.94 +/-2.57 s (SD) and to 15.66 +/-2.74 s, respectively. The minimal difference was not significant. We conclude that the CMS patients adapted their oxygen transport rate to the rise in hematocrit and blood viscosity.

Activity and resistance of iron-containing amorphous, zeolitic and mesostructured materials for wet peroxide oxidation of phenol.

Iron-containing materials have been prepared following several strategies of synthesis and using different silica supports (amorphous, zeolitic and mesostructured materials). Activity and stability of these materials was evaluated on the wet peroxide oxidation of phenol under mild reaction conditions (100 degrees C, air pressure of 1MPa and stoichiometric amount of hydrogen peroxide for the complete mineralisation of phenol). Their catalytic performance was monitored in terms of phenol and total organic carbon (TOC) conversions, by-products distribution (aromatics compounds and carboxylic acids) and degree of metal leached into the aqueous solution. The nature and local environment of iron species is strongly dependent on the synthetic route, which dramatically influences their catalytic performance. Crystalline iron oxide species supported over mesostructured SBA-15 materials have demonstrated to be the most interesting catalysts for phenol degradation according to its high organic mineralisation, low sensitivity to leaching out and good oxidant efficiency.

Ruptured fission yeast walls. Structural discontinuities related to the cell cycle.

Distributions of rupture sites of fission yeast cells ruptured by glass beads have been related to a new morphometric analysis. As shown previously (Johnson et al., Cell Biophysics, 1995), ruptures were not randomly distributed nor was their distribution dictated by geometry, rather, ruptures at the extensile end were related to cell length just as the rate of extension is related to cell length. The extension patterns of early log, mid-log, late log, and stationary phase cells from suspension cultures were found to approximate the linear growth patterns of Kubitschek and Clay (1986). The median length of cells was found to decline through the log phase in an unbalanced manner.

Smashed fission yeast walls. Structural discontinuities related to wall growth.

Twenty-three samples of fission yeast cells (Schizosaccharomyces pombe) were smashed by shaking them with glass beads. The samples represented all phases of the culture cycle, with the lag and log phases emphasized. Ruptured walls of the smashed cells were observed by phase-contrast and electron microscopy. Ruptures were tabulated with respect to their magnitudes and locations. Ruptures occurred not at random, nor at sites directed by geometry, but predominated in certain definable wall regions. These discontinuities were correlated with morphogenetic activities of the cell. Thus, the extensile end was found to be most fragile through most of the culture cycle. Also fragile was the nonextensile end, its edge more than its middle. Further, the data were applied to the testing of predictions from extant models (Johnson endohydrolytic softening model and Wessels presoftened-posthardened and crosslinking model) for hyphal tip extension. The frequency of rupture at the extensile (old) end of the cell was qualitatively predicted by both models; the frequency at the nonextensile (new) end was not predictable by either. Rupture frequencies and characteristics at other regions conformed to predictions by one or the other model, but rarely by both.

Inadequate treatment of excessive erythrocytosis / Tratamiento inadecuado en la eritrocitosis excesiva

Los pacientes con el mal de montaña crónico o eritrocitosis excesiva (EE) son residentes de la altura (3600 m), con mayor o igual 6.5 x 10 a la sexta glóbulos rojos (GR) que presentan cianosis.Esto ocasiona problemas estéticos y psicológicos en su vida ya que las demás personas creen que son alcohólicos. Cuando hay aumento de los GR, ellos buscan una cura milagrosa. De acuerdo a los conceptos evolutivos de la EE, los tratamientos han incluído; sanguijuelas, radioterapia de la médula ósea mediante administración de substancias radiactivas como el fósforo, y más recientemente, flebotomías, infusiuones de té, tabletas de ajo y la más peligrosa la administración de la fenilhidrazina, agente citotóxico prohibido. Encontramos que la mayoría de los pacientes con EE tienen placas radiográficas de tórax anormales. El concepto de los tratamientos es el de disminuir los GR. Sin embargo, la fenilhidrazina es tóxica para la médula ósea, el hígado y otros tejidos, cambiando el color de la piel de cianótica a icterica. Las conjuntivas se tornan ictéricas y la harina de café oscura. Una vez iniciado el tratamiento, la sangre de los pacientes es analizada periódicamente y el recuento de GR disminuyue, con lo que quedan satisfechos. Sin embargo, este medicamento tóxico puede producir la muerte. Al reducir los GR, el contenido arterial de oxígeno (CaO2) en la sangre disminuye. Las pruebas ergométricas en estos pacientes durante el tratamiento producen gran débito de oxígeno. En el paciente descrito, en el 4to nivel del protocolo de Bruce,m el dolor intenso de ambasd pantorrillas se hizo intolerable y requirió oxígeno post ejercicio. Al interrumpirse la fenilhidrazina, el, CaO2 retorna a niveles normales en aproximadamente 60 días, con una elevación de los GR por encima de los valores iniciales, y mejoría de la capacidad de ejercicio. Este y muchos otros casos nos llevan a creer que la EE es un mecanismo de compensación de la enfermedad pulmonar en la altura y que la cantidad de GR no debe ser disminuída.

Acute pancreatitis.

Acute pancreatitis is an inflammatory disease of variable clinical severity. The pathologic conditions that correlate with clinical severity and with local systemic complications range from mild edema to pancreatic an peripancreatic necrosis. This article discusses diagnosis, etiology, laboratory evaluation, and imaging studies with respect to acute pancreatitis. Assessing the prognosis, detecting complications, and therapy are discussed also.