Buy secnidazole 500mg cheap

A nonpolar environment thus raises the pKa of a carboxyl group (making it a weaker acid) but lowers that of an amino group (making it a stronger acid). These characteristics can be used for diagnostics of stability of tangerine to hydrothermal factors. The most important practical example of a buffered solution is human blood, which can absorb the acids and bases produced by biological reactions without changing its pH. However, it is recommended to use it with caution, as in large amounts, arginine can accumulate and result in the production of large quantities of nitric oxide, which is a potent vasodilator and thus can lead to symptomatic hypotension [86, 87]. In large breweries with up to 12 brews/day a correction of the modification procedures through an individual adjustment of temperatures and breaks is no longer planned due to time requirements of the brewhouse procedure. Only in one observed case the significant differences proved that the place of respondent residence has impact on the consumption of vegetables. And that Our experience has been that the precision problem is actually an operator problem. Oligofructoses are present in wheat, onion, garlic, artichoke tubers, endive, leek, asparagus, topinambur, and bananas. Principle of the Test When acetoacetate (diacetic acid) reacts with a ferric chloride (FeC13) solution, Bordeaux red color is formed. Also, public opinion has become more aware of contaminants in food in general, which are nowadays detectable more precisely. Due to their very high viscosity, buckwheat congress wort and mash cannot be easily filtered [252]; however, this problem is overcome by an upstream separation. Aquatic plants (hydrophytes) also have their own set of anatomical and morphological leaf adaptations. This class consists of elements that enhance or repress expression and of others that mediate the response to various signals, including hormones, heat shock, heavy metals, and chemicals. In addition, the by-products of fermentation produced by yeasts should affect the aroma and taste of the wine. Shape of the active-site cavities (pocket, cleft, and tunnel) dictates the manner of enzyme action. H3O+ O R C Y Y = H or R Aldehyde or ketone They react with alkyl halides to give internal alkynes (see Section 5. After that the contents of the kettle are pumped into a settling tank or whirlpool. In the following sections we give short overviews about the essential technological demands of the installations and refer to the leading solutions in malting plants, followed by dimensioning calculations. A pilot plant is under construction, hopefully paving the way for potential investors. Authors found 30% of respondents highlighted the quality as lower and 19% as very low. Another skeletal modification is the fusion of the clavicles, forming the furcula or wishbone. Mobilization of reserves from endosperm cells is accomplished by hydrolytic enzymes (glucanases, proteases, lipases and others) formed and secreted by the aleurone and the scutellum, and by enzymes released from starchy endosperm cells prior to grain maturation. These organisms convert solar energy into the chemical energy needed by all living things. The scb-glucans are closely packed in concentric layers in dry waxy maize granules and expand on swelling in aqueous media. A high glucose level in blood changes its osmolality, producing some clinical symptoms.

Discount secnidazole 1 gr overnight delivery

Late hopping refers to the addition of hop pellets to the kettle towards the end of kettle boil or directly into the whirlpool. For example, one area of great concern is the transmission of the avian flu virus to humans. This is similar to the reaction of someone who touches a hot stove and instinctually pulls his or her hand away. Foodborne pathogens in milk and the dairy farm environment: food safety and public health implications. This therapeutic strategy can preserve the natural localisation of the therapeutic protein in different organelles driven by the protein localisation signals, which also favour natural post-translational modifications. Arugula is the most widely culinary used of all determined kinds and as one of the crpops mentioned above, there were set the limits for nitrates by the European Union for this plant. These non-volatile, water-soluble, often complex substances dissolve in the wort and can reach the beer [9, 14]. In everyday practical medicine we need to know how much acid a patient is putting out in his urine on a quantitative basis. Baking experiment was conducted by the standard method used in the workplace: to flour or composite flour, weighing 500 g yeast (4%), sucrose (1%), salt (1. While the value of a sense of smell is obvious, what is the value of a sense of taste? With poor power adjustments, fractional loads may often lead to undesirable reductions in the evaporation temperature, whereby the cooling power is reduced until equilibrium is regained. Energy Flow the sun is the principal source of energy input to biological systems. During the industrial revolution, pollution prevented lichen from growing on trees. Reaction (7) can be thought of as consisting of two "partial reactions," the first corresponding to the formation (F) and the second to the subsequent decay (D) of the transition state intermediate. Babies born to mothers on a buprenorphine maintenance program showed little or no clinically measurable neonatal abstinence syndrome in contrast to findings with methadone, morphine, or heroin maintenance programs. What is the main difference, from an energy point of view, between photosynthesis and biological nitrogen fixation? Antioxidant activity in fruits and leaves of blackberry, raspberry, and strawberry varies with cultivar and developmental stage. This basic knowledge is being used in attempts to synthesize compounds that block selectin-ligand interactions and thus may inhibit the inflammatory response. The countercurrent adaption is found in many animals, including dolphins, sharks, bony fish, bees, and hummingbirds. However, enzymatically catalyzed oxidation is often observed in juice production if phenoloxidases are not deactivated. The conversion of cholesterol to pregnenolone is identical in adrenal, ovary, and testis. However, installing this tap chilling can cause the tap and font to swet, producing condensed water outside and inside of the font. Unfortunately, as a result of the clarification many valuable components are lost, which is detrimental to consumers. Dialysis and transplant patients with diabetes are more likely to report difficulty working than dialysis and transplant patients without diabetes. Umbilical artery base excess is the most direct measure of fetal metabolic acidosis. These results suggest that antimicrobial anionic peptides from whey proteins can contribute to control pathogen in reduced-salt Cheddar cheeses. In patients with new persistent left bundle branch block after transcatheter aortic valve replacement, implantation of a permanent pacemaker may be considered.

buy secnidazole 500mg cheap

1 gr secnidazole with amex

Further, the antioxidant activity represents the antioxidant power of antioxidant components. Nutrition Nutrition: taking in of nutrients which are organic substances (contain carbon) and mineral ions, containing raw materials or energy for growth and tissue repair, absorbing and assimilating them. All anelysed samples meet the requirements of Codex Alimentarius of Slovak Republic (2006). Some reptiles (alligators and crocodiles) are the most primitive animals to exhibit a four-chambered heart. Therefore, it is of interest to obtain information about the degree of degradation and the size of the proteins present. Evaluators most preferred colour and appearance of breads made from conventional wheat (90% amount of flour) and same attributes of breads made from unconventional wheat (80% amount of flour). This process is aerobic, requiring oxygen as the final oxidant of the reduced coenzymes. I regret to say that although we are not far away from the original limit, few requests find their way back within the ideal period. Tropomyosin blocks myosin binding sites on actin molecules, preventing cross-bridge formation and preventing contraction in a muscle without nervous input. These curves allow us to compare the life histories of different populations (Figure 45. Different ways of modeling ecosystems are necessary to understand how environmental disturbances will affect ecosystem structure and dynamics. Effects of genetic, preand post-harvest factors on phenolic content and antioxidant capacity of white Asparagus spears. Production involves aqueous extraction of seaweed in hot water, with the extract frozen and thawed to precipitate polysaccharides and remove water-soluble contaminants. The antioxidant capacity of milk was not measured because of low quantitation of the antioxidant enzymes. Viral hepatitis Viral hepatitis Present; transaminases and liver function normal Transaminases abnormal, liver function normal Symptomatic liver dysfunction; fibrosis by biopsy; compensated cirrhosis Decompensated liver function. Benign disorders of histidine catabolism include histidinemia and urocanic aciduria associated with impaired histidase. The differences in the sensitivity of the two methods may be the reason for the variations obtained under two methods in determining -carotene content. The peristaltic movement of the esophagus is an involuntary reflex; it takes place in response to the act of swallowing. However, permits of these foods on the market are often not possible, because the foods contain higher amount of salt which is responsible for various health problems such as the cardiovascular disease (Zachar, 2008). The soft resins are extracted from the methanol fraction by the use of hexane and then also determined gravimetrically. An anatomical shunt develops because the ventilation of the airways does not match the perfusion of the arteries surrounding those airways. There were applied doses of selenium on two concentration levels (50 g Se / ha a 100 g Se / ha) and without selenium application (in case of control), every variant in four replications. They diverge into capillaries where the heart muscle is supplied with oxygen before converging again into the coronary veins to take the deoxygenated blood back to the right atrium where the blood will be re-oxygenated through the pulmonary circuit. Developments in molecular biology and biochemistry have provided the background for sweet-taste chemistry, making it one of the most modern and attractive domains of bioorganic as well as food chemistries. The Permian period also saw a second major divergence of diapsid reptiles into archosaurs (predecessors of crocodilians and dinosaurs) and lepidosaurs (predecessors of snakes and lizards).

discount secnidazole 1 gr overnight delivery

Comparative prices of Secnidazole
#RetailerAverage price
1Dillard's260
2GameStop359
3O'Reilly Automotive147
4Dell308
5Save Mart239
6CVS Caremark738
7Amazon.com805
8HSN726
9Big Lots587

1 gr secnidazole with amex

Discount secnidazole 1gr without prescription

Treatment for Wilson disease consists of a diet low in copper along with lifelong administration of penicillamine, which chelates copper, is excreted in the urine, and thus depletes the body of the excess of this mineral. With the increasing age of laying hens reduces the intensity of pigment deposition in the egg shell and increases of egg surface area, of the egg shell area, to which the pigment is stored. The Blue Light Responses Phototropism-the directional bending of a plant toward or away from a light source-is a response to blue wavelengths of light. In our view, it is difficult to assess the safety of table eggs by risk factors of chemical, biological and physical origin, as these factors capture the essence of assessment also the quality of table eggs, whether it is chemical composition of the egg contents or shell eggs indicators. The lipid particles play a role in sterol biosynthesis and serve as lipid storage for membrane synthesis. Mutations often affect somatic cells and so are passed on to successive generations of cells, but only within an organism. In addition, producers may provide new properties for foodstuff through addition of the ingredients, which are not naturally occurring in the product (Gbczyski and Jaworska, 2009). When selecting hop products, prefer those that are free from polyphenols; take into account the colloidal stability of the beer. The microorganisms included coliforms, psychrorotrophs, moulds, yeast, Escherichia coli, Brevibacterium linens, and lactic acid bacteria. Because of a growing aging population, career opportunities as a respiratory therapist are expected to remain strong. In order to adjust to the lower oxygen levels at the new altitude, the body increases the number of red blood cells circulating in the blood to ensure adequate oxygen delivery to the tissues. Gluten development is frequently supported by a homogenization step with subsequent maturation. Spongy bone is prominent in areas of bones that are not heavily stressed or where stresses arrive from many directions. The primary end point of all-cause mortality at 90 days did not differ between the two groups, nor did 28-day mortality. Today, lambic is rather rarely enjoyed in pure form in Belgium, but it is processed to gueuze, fruit lambic and other variants. Even less-related individuals, those with less genetic identity than that shared by parent and offspring, benefit from seemingly altruistic behavior. Under these saturating conditions, vi depends solely on-and thus is limited by- the rapidity with which free enzyme is released to combine with more substrate. Part of the embryo is (v) the scutellum (seed leaf), which plays an important role in dormancy and germination. The ability of an ecosystem to remain at equilibrium in spite of disturbances is called resistance. Although humans commonly distinguish taste as one sense and smell as another, they work together to create the perception of flavor. Tryptophan Following hydroxylation of tryptophan to 5-hydroxytryptophan by liver tyrosine hydroxylase, subsequent decarboxylation forms serotonin (5-hydroxytrypta- mine), a potent vasoconstrictor and stimulator of smooth muscle contraction. During plugging the hard spile should be replaced by a soft spile again, since this takes over the function of a primitive air filter. However, in recent years some studies have advocated that the measurement of protein excretion should be done on an overnight specimen. Selenium-enriched pea seeds are a potential source of dietary selenium, on account of their ability to accumulate Se, and that this Se is present mainly as SeMet, known to be favourable for human consumption. Noninvasive ventilation in acute cardiogenic pulmonary edema: a meta-analysis of randomized controlled trials. Nowadays, a number of different motifs finding algorithms are available and (Lin, biochem218. Extra-embryonic membranes are membranes present in amniotic eggs that are not a part of the body of the developing embryo.

discount secnidazole 1gr without prescription

Discount secnidazole 500 mg free shipping

This classification could then be transformed to an ``evidence model' for future development of additional practice guidelines regarding specific diagnostic evaluations and therapeutic interventions (Executive Summary). This is very consistent with another fifty determinations, using randomly selected patient blood (fig. Congress Extends Funding for the Bipartisan-Supported Federal Home Visiting Program. It is important when recruiting a panel to choose people who have a desire to be involved and are committed to giving the time it takes. Fluid accumulation, survival, and recovery of kidney function in critically ill patients with acute kidney injury. None appears to be ready at this time for widespread application in clinical practice. Insect pollinated flowers might also have stripes which act as guide-lines for insects. Therefore, a large number of studies have been conducted to estimate the prevalence of proteinuria in children. Generally, these control algorithms can be classified into (i) classic or standard algorithms and (ii) advanced algorithms. The greater the difference in electronegativity between the bonded atoms, the greater is the polarity of the bond. On the other hand, rapid methods of yeast identification allow to eliminate harmful or pathogenic microflora. The body cannot sustain the bursts of energy mediated by epinephrine and norepinephrine for long times. The detection of nitrite in the urine can be used to indicate the presence of bacteria such as Escherchi coli, proteius, klebsiella, enterobacter, citrobacter, and salmonella will reduce urinary nitrate to nitrite. These optical sensors consist essentially of an oxygen-sensitive membrane and an optical system. The red coloring of blood comes from the iron-containing protein hemoglobin, illustrated in Figure 40. The highest cadmium content of herbal teas was found in 2009 (white willow - bark). Scientists look at patterns in data and try to explain differences or deviations from these patterns. The main chain of xylan is attacked by xylanases that catalyze hydrolysis of the internal -1,4-glycosidic bonds, thus decreasing the degree of polymerization and facilitating further digestion to xylose by exo-acting -xylosidases. The classic poisons H2S, carbon monoxide, and cyanide inhibit cytochrome oxidase and can therefore totally arrest respiration. Sucrose content: generally, not more than 5 g / 100g; not more than 10 g / 100 g for acacia honey (Robinia pseudoacacia), alfalfa honey (Medicago sativa), banksia honey (Banksia menziesii), sulla honey (Hedysarum), eucalyptus honey (Eucalyptus camadulensis) leatherwood honey (Eucryphia lucida, Eucryphia milliganii) and citrus honey (Citrus spp. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. These individuals are advised to eat fish low in mercury: salmon, tilapia, shrimp, pollock, and catfish. Electrical stimulation of nerve leads to a fall in membrane thiamin triphosphate and release of free thiamin. Now the rest of the world does not like this word "standard", Standard Reference Material. Yeast management consists of the propagation plant, the yeast crop and the waste yeast treatment. The uncoupler that has been used most frequently is 2,4-dinitrophenol, but other compounds act in a similar manner. An excess of Ca2+, concentration of which depends on the enzyme origin, inhibits the activity of -amylases because of the carboxyl groups in their active sites. In phageinfected E coli, the phage protein P binds to dnaB and the P/dnaB complex binds to ori by interacting with the O protein. The enzyme occurs in all major aerobic tissues in the mitochondria and the cytosol.

Discount 1gr secnidazole visa

Energy sources, temperature, water, inorganic nutrients, and soil are factors limiting the distribution of living things in terrestrial systems. Some well-defined processes, however, differ in requirements of water consumption and, in particular, the techniques used to recover proteins solved in fruit water. Since these covalent changes are relatively stable, an enzyme that has been "poisoned" by an irreversible inhibitor remains inhibited even after removal of the remaining inhibitor from the surrounding medium. They are present in some storage or secretory granules, such as the chromaffin granules of the adrenal medulla. The League traded its famous hopped beer from Hamburg mainly to the Netherlands, where the little village of Amsterdam had been named as one of two exclusive custom places for beer from Hamburg in 1323. Heavy Metals in Food Crops and the Associated Potential for Combined Health Risk due to Interactions between Metals. Urobiline: Pigmented derivative of urobilinogen Urobilinogen: Derivative of bilirubine, which is made in the intestine by the gut bacteria. Discontinuation of vasopressin before norepinephrine in the recovery phase of septic shock. The term cholestatic jaundice is used to include all cases of extrahepatic obstructive jaundice. The corresponding author had final responsibility for the decision to submit for publication. Fluorescence is very strongly improved when fluorescing molecules are transferred from the aqueous milieu into a nonpolar environment. Dietary fats and health: dietary recommendations in the context of scientific evidence. Thus, the residual sugars do not contribute greatly to the perceived sweetness of beer. The high number of cracked eggs have a negative impact on the efficiency of production of table eggs and breeding economy of the laying hens on the farm. S S + E+ + -S releases electron Transition state is stabilized + + + + S E H E H Reaction is faster Arenium ion is stabilized S + E+ -S withdraws electron Transition state is destabilized + + S + + + S E H E H Reaction is slower Arenium ion is destabilized Orientation Similarly, groups already present on the benzene ring direct the orientation of the new substituent to ortho, para or meta positions. In adults, the hip bones, or coxal bones, are formed by the fusion of three pairs of bones: the ilium, ischium, and pubis. Honey with fewer crystal nuclei crystallizes more slowly, forming larger crystals that tend to fall to the bottom of the container (buckwheat and honeydew honeys), resulting in a stratified structure. Newer mass spectrometry methods allow one to identify hundreds to thousands of proteins in proteins extracted from very small numbers of cells (< 1 g). However, all three enzymes have been found in other sites, and the neuronal enzyme is also inducible. Numerous epidemiological studies and clinical trials have shown a relationship between the level of blood pressure and faster progression of diabetic kidney disease. Tuchman M et al: the biochemical and molecular spectrum of ornithine transcarbamoylase deficiency. Pseudo-ruminants have similar digestive processes as ruminants but do not have the four-compartment stomach. Acrylamide content in prunes Similarly to plum stew also prunes are typically processed by heat treatment, therefore in this type of plum products a significant acrylamide content was determined in concentrations comparable to plum stew. Cortisone or similar synthetic derivatives such as prednisolone, the active metabolite of prednisone, are used to treat inflammatory diseases, rheumatoid arthritis and bronchial asthma. In tropical countries, the major starch source is cassava and most starch in the Far East is from rice. For example, a rise in blood glucose levels triggers the pancreatic release of insulin. Paired measurements of 30 percent glycerol correction factor and whole blood correction factor (from Hulands et al. Of all cultivated grain varieties, barley exhibits the best adaptability and also grows well in cold, rainy climate zones with long daylight periods as at the edge of hot, dry steppes. Concentration of cholesterol increased in experimental groups in comparison with the control group, but differences were insignificant (p >0.

Buy secnidazole 1gr with amex

Soil scientists need to have a strong background in physical and life sciences, plus a foundation in mathematics. Indeed, appropriate regulation of some genes (eg, the Trp operon) relies upon this coupling of transcription and translation. Control filtration velocity by means of a continuous turbidity measurement (turbidimeter) of the wort. Interest in the expanding sector of manufactured foods has already led to the exploitation of new sources, many of nonplant origin, and provided new attributes to support new product development. People with lesions in the vestibular area of the somatosensory cortex see vertical objects in the world as being tilted. This mechanism provides for rapid control of the synthesis of a protein that sequesters Fe2+, a potentially toxic molecule. Once germination has proceeded for the desired time, the grain is gently dried to produce malt. The other major source of long-chain fatty acid is synthesis (lipogenesis) from carbohydrate, mainly in adipose tissue and the liver. Some orchids, like the Australian hammer orchid, use scent as well as visual trickery in yet another sexual deception strategy to attract wasps. Greek letters (. etc) are used to distinguish different subunits of a heterooligomeric protein, and subscripts indicate the number of each subunit type. Carbohydrates have two main active nuclei, 13C and 1H, whereas less frequently used nuclei are 2H, 3H, 11B, 15N, 17O, 19F, and 31P. However, most useful drugs bind through the use of multiple weak bonds (ionic and weaker). Prion diseases may manifest themselves as infectious, genetic, or sporadic disorders. In addition, patulin application induced evident changes in femoral bone microstructure of these animals. Genetic diversity is therefore required so that in changing environmental or stress conditions, some of the progeny can survive. Complicated multistep reactions; the expensive, toxic, and environment-polluting reagents required; and chromatographic purification of the products limit relevant studies to the laboratory scale. Thus, there are numerous variations possible and the formulation concept is very versatile. Based on the fundamentals established in antiquity, the cities generated the technology and organization for professional brewing. Determination of total polyphenols Total polyphenols were determined by the method of Lachman et al. Modern pharmaceutical science also recognizes the importance of these plant compounds. For example, a lager may have a characteristic estery aroma, but the intensity may vary. Electrons do not move freely in the space around the nucleus but are confined to regions of space called shells. Almost all solutes, except for proteins, are filtered out into the glomerulus by a process called glomerular filtration. An additional two or more years is spent specifically studying kidney disorders and their accompanying effects on the body. In general, the timing of the Pleistocene extinctions correlated with the arrival of humans and not with climate-change events, which is the main competing hypothesis for these extinctions. This led to the realization that receptors of the steroid or thyroid type are members of a large superfamily of nuclear receptors. Unlike the mizuna and Chinese mustard, this vegetable is sensitive to low temperatures and thus at temperatures around zero its above-ground parts get frosted and lose their palatability (Kopec, 2010). The values for radioactivity are plotted against time, and the half-life of the protein (the time for the radioactivity to decline from its peak value to one-half of its peak value) can be calculated from the resulting graph, discounting the times for the injected protein to equilibrate (mix) in the blood and in the extravascular spaces. The highest antimicrobial effect was observed in the variants with grapevine seeds.

Aromatase deficiency

500 mg secnidazole amex

Appearance and crumb colour of breads made from conventional wheat (100 and 90% amount of wholemeal flour) were evaluated better than these attributes of breads made from blue coloured wheat (same amount of wholemeal flour). Where pectin networks are cross-linked by interaction with Ca2+ ions, the galacturonate sequences can play a dual role. Therefore, there are two distinctive strains; one is generally cultivated for fibre (hemp) and the other for drug use (marijuana) (Mechoulam, 1970). Age of laying hens, weeks 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 x - mean Egg laying intensity, % 50. Among reasons that this enzyme is important is the fact that approximately 50% of the drugs humans ingest are metabolized by isoforms of cytochrome P450; these enzymes also act on various carcinogens and pollutants. Once the aldehyde or ketone group of the open chain form is used up in a reaction, the cyclic forms open up to produce more open chain form to maintain the equilibrium. Chlorogenic acids and other cinnamates - nature, occurrence, dietary burden, absorption and metabolism. The nature of the hydrogen bonds in proteins dictates their properties and behaviour. Bicarbonate is a truly strong universal concentrated nutritional medicine that works effectively in many clinical situations that we would not normally think of. Breathing and gas exchange are both altered by changes in the compliance and resistance of the lung. Beers that are full in body could also be described as high body, viscous, thick, satiating, creamy or chewy. Mutagenicity of the mycotoxin patulin in cultured Chinese hamster V79 cells, and its modulation by intracellular glutathione. Regular milk yield recording was performed during the evening milking in around the middle of April, May and June. Features of the immune system, such as pathogen identification, specific response, amplification, retreat, and remembrance are essential for survival against pathogens. Non-machine-related downtime: downtime of a machine caused by external reasons (not of the machine itself) [s]. A: Thrombin-induced cleavage of Arg-Gly bonds of the A and B chains of fibrinogen to produce fibrinopeptides (left-hand side) and the and chains of fibrin monomer (right-hand side). However, the former 10% is important, as the rate of increase of Ca2+ in the myoplasm is important, and entry via the Ca2+ channels contributes appreciably to this. The 1, 2 or 3 amides are obtained from esters by treatment with ammonia or 1 or 2 amines, respectively. Plants that have only one leaf per node have leaves that are said to be either alternate-meaning the leaves alternate on each side of the stem in a flat plane-or spiral, meaning the leaves are arrayed in a spiral along the stem. Deficiency-leading to rickets in children and osteomalacia in adults-continues to be a problem in northern latitudes, where sunlight exposure is poor. Evaluating the effectiveness of pasteurization for reducing human illnesses from Salmonella spp. Umbilical and uteroplacental blood flow velocity waveforms in pregnancies with fetal growth retardation. Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function. The graph can also identify panelists who are consistently giving higher (or lower) scores compared to the panel average.

References:

  • https://www.uvm.edu/sites/default/files/media/TRE_UVMLaughing_River.pdf
  • https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-015-2538-z.pdf
  • https://oncologypro.esmo.org/content/download/44473/831588/1/Testicular-Cancer-Rosti-Garolla.pdf