on 28-Feb-2018 (Wed)

Do not learn if you do not understand

Learn before you memorize

Before you proceed with memorizing individual facts and rules, you need to build an overall picture of the learned knowledge. Only when individual pieces fit to build a single coherent structure will you be able to dramatically reduce the learning time. This is closely related to the problem of comprehension mentioned in Rule 1: Do not learn if you do not understand. A single separated piece of your big picture is like a single German word in the textbook of history.

Do not start from memorizing loosely related facts! First read a chapter in your book that puts them together (e.g. the principles of the internal combustion engine). Only then proceed with learning using individual questions and answers (e.g. What moves the pistons in the internal combustion engine?), etc.

Graphic deletion is as good as cloze deletion

Before you proceed with memorizing individual facts and rules, you need to build an overall picture of the learned knowledge.

Basics are usually easy to retain and only take a tiny proportion of your time.

simplicity makes is easy for the brain to always process it the same way.

splitting complex items into sub-items saves time because each item can be repeated at its own pace

We want answer to be as short as imaginably possible!

the longer the time you need to remember knowledge, the more you benefit from simplifying your items!

Cloze deletion makes the core of incremental reading.

The power of imagery explains why the concept of mind maps is so popular.

In mind maps, connections between items reflect logical connections between concepts.

Mnemonic techniques are various techniques that make remembering easier.

the true bottleneck towards long-lasting and useful memories is not in quick memorization, but in long-term retention.

Graphic deletion works great in learning geography!

enumerations are ordered and thus force the brain to always list them in the same order.

you should always try to make sure your brain works in the exactly same way at each repetition.

Learning poems is an example of learning enumerations

If knowledge of one item makes it harder to remember another item, we have a case of memory interference.

Interference is probably the single greatest cause of forgetting

the only hermetic procedure against interference is to detect and eliminate.

wording must be optimized to make sure that the brain can recall it with minimum effort.

trailing information is not supposed to be memorised as a side effect.

Cross-reference to other items can place your item in a better context, simplify wording, and reduce interference.

One of the most effective ways of enhancing recollection is to provide them with personal links.

Use objects that evoke very specific and strong emotions: love, sex, war, your late relative, object of your infatuation, Linda Tripp, Nelson Mandela, etc. It is well known that emotional states can facilitate recall

Memorizing different representations of the same fact or rule is recommended in cases where a given memory is of high value.

if there are multiple valid responses to the same question all right answer should be euqally rewarded.

Sources should accompany your items but should not be part of the learned knowledge

time stamps should be included in items to indicate the degree of obsolescence.

You will always face far more knowledge that you will be able to master. That is why prioritizing is critical for building quality knowledge in the long-term.

make sure that explanatory or optional components of the answer are placed separately so that your attention is focused on the most important part.

Context cues can be used to simplify wording of items

Avoid enumerations wherever you can. If you cannot avoid them, deal with them using cloze deletions (overlapping cloze deletions if possible).

Sets should always be avoid due to the high cost of retaining such items.

It is well known that emotional states can facilitate recall

Redundancy does not contradict minimum information principle

prioritisation is critical for building quality knowledge in the long-term.

一年返现40%，被吓到的我

• 梁萧 发布于 7小时前
• 分类：文摘

[imagelink]

一位读者留言：

XX银行推销我一个理财产品，看起来特别诱人。

年存2万，每年返4000元一辈子

年存5万，每年返10000元一辈子

......

年存100万，每年返20万一辈子

只需存五年，就返一辈子

年金可取走，不取自动进入分红账户，3.5%年复利滚存，还有分红拿。

小伙伴一下被吸引了：

——我一年存5万，存五年就行，每年返一万元，返一辈子。

这么好的事，小姐姐，你怎么看？

我怎么看，点一首《套路》送他们。

一.

上面这个例子，特别常见——每年存N万，年年能领钱、一直领到死。

很多人都遇到过。

银行的人会说，你可以拿这钱去当教育金、养老金、婚嫁金，留给孩子，那也是一大笔财富啊。

是不是有买买买的冲动，以为自己摇身一变千万富翁？

其实没那么神奇，它就是一款年金险。0保障功能，纯投资用的，年年返现，有的还带分红。

它的收益其实不高，为什么交几年，就能返现一辈子呢？

因为复利的魔力啊。

二.

之前我跟大家说过七十二法则——

用72除以本金翻倍的时间，可以估算理财的年化收益。

假如20岁开始买这个产品，每年交2万，共交五年，也就是总共交10万元。

然后一年返4000元，那就是要返25年，才能回本。

它的收益率大概是多少呢？72/25=2.88%。

妈诶，还不如买余额宝呢。

这是钱每年都取出来的情况下，如果一直只存不取呢？

这个产品附加了分红功能，钱一直不取，年化收益是3.5%。

72/3.5=20年。

也就是说，一分不取的情况下，一共要存20年的时间，才能赚回本钱。

用IRR公式计算，结果也差不多。

这么一看，是不是吸引力一下子就大打折扣了？

三.

大家留心的话，这几年银行电话销售的产品，许多都是“一年交N万，年年返现、返一辈子”的年金险。

有的设计的特别花哨，什么生存金啦、养老金啦、身故金啦、这个账户、那个分红的。

眼花缭乱。

但无论多么复杂，用IRR公式一算便知，收益大多只有3-4%，而且还是存几十年的情况下。

5%以上的极罕见。

这类产品，不可能像话术忽悠的那样，收益特高，能当婚嫁金、教育金、养老金用。

你要真报着这样的目的买，钱早就被通胀吞噬了...

我对年金险没意见，它有存在的价值，主要是它的营销话术特别泛滥，适合扒一扒。

四.

还有一点，银行在推这种产品时，绝对不会提到中途退保风险的。

甚至可能连这是保险，都不会说。

保险是没有保本概念的。想拿回本金，要么是持有达到一定期限、要么是达到赔付标准。

提前退保的话，损失超大的。

年金险也一样。

不是我黑银行啊...只是有时候在营销上，真的挺不靠谱。

我之前也接过类似电话，小伙子上来一通吹——我们这产品限量版，特别好，折算下来，一年给你40%...

我天，庞氏都不敢这么吹吧？

一追问才知道，一年存一万，返现4000，可不就是40%嘛...谁也没说是收益40%啊。

你自己误以为的，怪我咯？

这就是典型的营销话术了，模糊信息、似是而非，让你自己进圈套。

聊理财，就突出利润，回避风险；

聊保险，就突出回报，回避期限；

聊贷款，就突出金额，回避成本；

死缠烂打跟你磨一个小时，一点儿错都挑不出来，脑子稍一晕，就被带坑里了。

就欺负你不懂，怎么破？

the rate of a pathway may be influenced by the availability of substrates, product inhibi- tion, or alterations in the levels of allosteric activators or inhibitors. These intracellular signals typically elicit rapid responses, and are important for the moment-to-moment regulation of metabolism.

Signaling between cells provides for long-range integration of metabolism, and usually results in a response that is slower than is seen with signals that originate within the cell. Communication between cells can be mediated, for example, by surface-to-surface contact and, in some tissues, by for- mation of gap junctions, allowing direct communication between the cytoplasms of adjacent cells. However, for energy metabolism, the most important route of communication is chemical signaling between cells by bloodborne hormones or by neurotransmitters.

tissues that respond to more than one chemical signal must have several different receptors, each of which can be linked to adenylyl cyclase . These receptors, known as G protein-coupled receptors (GPCR), are characterized by an extracellular ligand-bind- ing region, seven transmembrane helices, and an intracellular domain that interacts with G proteins

The effect of the activated, occupied GPCR on second messenger formation is not direct but, rather, is mediated by specialized trimeric proteins (α, β, γ sub- units) of the cell membrane. These proteins, referred to as G pro- teins because they bind guanosine nucleotides (GTP and GDP), form a link in the chain of communication between the receptor and adenylyl cyclase .

Many molecules of active Gα protein are formed by one activated receptor. [Note: The ability of a hor- mone or neurotransmitter to stimulate or inhibit adenylyl cyclase depends on the type of Gα protein that is linked to the receptor. One family of G proteins, designated G s , stimulates adenylyl cyclase ; another family, designated G i , inhibits the enzyme

The next key link in the cAMP second messen- ger system is the activation by cAMP of a family of enzymes called cAMP-independent protein kinases , for example, protein kinase A (Figure 8.8). Cyclic AMP activates protein kinase A by binding to its two regulatory subunits, causing the release of active catalytic subunits. The active subunits catalyze the transfer of phosphate from ATP to specific serine or threonine residues of protein substrates. The phosphorylated proteins may act directly on the cell’s ion channels, or, if enzymes, may become activated or inhibited. Protein kinase A can also phosphorylate proteins that bind to DNA, causing changes in gene expression. [Note: Several types of protein kinases are not cAMP-dependent, for example, protein kinase C

The phosphate groups added to proteins by protein kinases are removed by protein phosphatases —enzymes that hydrolytically cleave phosphate esters (see Figure 8.8). This ensures that changes in protein activity induced by phosphorylation are not permanent

cAMP is rapidly hydrolyzed to 5'-AMP by cAMP phospho diesterase , one of a family of enzymes that cleave the cyclic 3',5'-phosphodiester bond.

cAMP is rapidly hydrolyzed to 5'-AMP by cAMP phospho diesterase , one of a family of enzymes that cleave the cyclic 3',5'-phosphodiester bond. 5'-AMP is not an intracellular signaling molecule. Thus, the effects of neurotransmitter- or hormone-mediated

increases of cAMP are rapidly terminated if the extracellular signal is removed. [Note: Phosphodiesterase is inhibited by methyl xanthine derivatives, such as theophylline and caffeine. 1

Pyruvate is the end product of glycolysis in cells with mitochondria and an adequate supply of oxygen. This series of ten reactions is called aerobic glycolysis because oxygen is required to reoxidize the NADH formed during the oxidation of glyceraldehyde 3-phosphate (Figure 8.9B). Aerobic glycolysis sets the stage for the oxidative decarboxylation of pyruvate to acetyl CoA, a major fuel of the TCA (or citric acid) cycle. Alternatively, pyruvate is reduced to lactate as NADH is oxidized to NAD + (Figure 8.9C). This conversion of glucose to lactate is called anaerobic glycolysis because it can occur without the participation of oxygen. Anaerobic glycolysis allows the production of ATP in tissues that lack mitochondria (for example, red blood cells) or in cells deprived of sufficient oxygen

Glucose cannot diffuse directly into cells, but enters by one of two trans- port mechanisms: a Na + -independent, facilitated diffusion transport sys- tem or a Na + -monosaccharide cotransporter system.

The glucose trans- porters display a tissue-specific pattern of expression. For exam- ple, GLUT-3 is the primary glucose transporter in neurons. GLUT-1 is abundant in erythrocytes and blood brain barrier, but is low in adult muscle, whereas GLUT-4 is abundant in adipose tis- sue and skeletal muscle. [Note: The number of GLUT-4 trans- porters active in these tissues is increased by insulin.

In facilitated diffusion, glucose movement follows a concentration gradient, that is, from a high glucose concentration to a lower one. For example, GLUT-1, GLUT -3, and GLUT-4 are primarily involved in glucose uptake from the blood. In contrast, GLUT-2, which is found in the liver and kidney, can either transport glucose into these cells when blood glucose levels are high, or transport glucose from these cells when blood glucose levels are low (for example, during fasting). [Note: GLUT-2 is also found in pancreatic β cells.] GLUT-5 is unusual in that it is the primary transporter for fructose (instead of glucose) in the small intestine and the testes.

This is an energy-requiring process that transports glucose “against” a concentration gradient—that is, from low glucose concentrations outside the cell to higher concentrations within the cell. This system is a carrier-mediated process in which the movement of glucose is coupled to the concentration gradient of Na + , which is transported into the cell at the same time. The carrier is a sodium-depen- dent–glucose transporter or SGLT. This type of transport occurs in the epithelial cells of the intestine (see p. 87), renal tubules, and choroid plexus. [Note: The choroid plexus, part of the blood brain barrier, also contains GLUT-1.]

The conversion of glucose to pyruvate occurs in two stages (Figure 8.11). The first five reactions of glycolysis correspond to an energy investment phase in which the phosphorylated forms of intermediates are synthesized at the expense of ATP. The subsequent reactions of glycolysis constitute an energy generation phase in which a net of two mole cules of ATP are formed by substrate-level phosphorylation (see p. 102) per glucose molecule metabolized.

Phosphorylated sugar molecules do not readily penetrate cell mem- branes, because there are no specific transmembrane carriers for these compounds, and because they are too polar to diffuse through the lipid core of membranes. The irreversible phosphorylation of glu- cose (Figure 8.12), therefore, effectively traps the sugar as cytosolic glucose 6-phosphate, thus committing it to further metabolism in the cell. Mammals have several isozymes of the enzyme hexokinase that catalyze the phosphorylation of glucose to glucose 6-phosphate

In most tissues, the phosphorylation of glucose is catalyzed by hexokinase , one of three regulatory enzymes of glycolysis (see also phosphofructokinase and pyruvate kinase ). Hexokinase has broad substrate specificity and is able to phos- phorylate several hexoses in addition to glucose. Hexokinase is inhibited by the reaction product, glucose 6-phosphate, which accumulates when further metabolism of this hexose phosphate is reduced. Hexokinase has a low K m (and, therefore, a high affin- ity, see p. 59) for glucose. This permits the efficient phosphoryla- tion and subsequent metabolism of glucose even when tissue concentrations of glucose are low (Figure 8.13). Hexokinase , however, has a low V max for glucose and, therefore, cannot sequester (trap) cellular phosphate in the form of phosphorylated hexoses, or phosphorylate more sugars than the cell can use.

In liver parenchymal cells and β cells of the pan- creas, glucokinase (also called hexokinase D , or type IV ) is the predominant enzyme responsible for the phosphorylation of glu- cose. In β cells, glucokinase functions as the glucose sensor, determining the threshold for insulin secretion (see p. 310). In the liver, the enzyme facilitates glucose phosphorylation during hyper- glycemia. [Note: Hexokinase also serves as a glucose sensor in neurons of the hypothalamus, playing a key role in the adrenergic response to hypoglycemia

Glucokinase differs from hexokinase in several impor- tant properties. For example, it has a much higher K m , requiring a higher glucose concentration for half-saturation (see Figure 8.13). Thus, glucokinase functions only when the intracellular concentration of glucose in the hepatocyte is elevated, such as during the brief period following consumption of a carbohy- drate-rich meal, when high levels of glucose are delivered to the liver via the portal vein. Glucokinase has a high V max , allow- ing the liver to effectively remove the flood of glucose delivered by the portal blood. This prevents large amounts of glucose from entering the systemic circulation following a carbohydrate- rich meal, and thus minimizes hyperglycemia during the absorptive period. [Note: GLUT-2 insures that blood glucose equilibrates rapidly across the membrane of the hepatocyte.]

Glucokinase activity is not directly inhibited by glucose 6-phos- phate as are the other hexokinases , but rather is indirectly inhibited by fructose 6-phosphate (which is in equilibrium with

glucose 6-phosphate, a product of glucokinase ), and is indi- rectly stimulated by glucose (a substrate of glucokinase ) via the following mechanism. Glucokinase regulatory protein (GKRP) in the liver regulates the activity of glucokinase through reversible binding. In the presence of fructose 6- phosphate, glucokinase is translocated into the nucleus and binds tightly to the regulatory protein, thus rendering the enzyme inactive (Figure 8.14). When glucose levels in the blood (and also in the hepatocyte, as a result of GLUT-2) increase, glucokinase is released from the regulatory protein, and the enzyme re-enters the cytosol where it phosphorylates glucose to glucose 6-phosphate. [Note: Fructose 1-phosphate inhibits formation of the glucokinase -GKRP complex.] Glucokinase functions as a glucose sensor in the maintenance of blood glucose homeosta- sis. Mutations that decrease the activity of glu- cokinase are the cause of a rare form of dia- betes, maturity onset diabetes of the young type 2 (MODY 2).

The irreversible phosphorylation reaction catalyzed by phospho - fructokinase-1 ( PFK-1 ) is the most important control point and the rate-limiting and committed step of glyco l ysis (Figure 8.16). PFK-1 is controlled by the available concentrations of the substrates ATP and fructose 6- phosphate, and by regulatory substances described below. 1. Regulation by energy levels within the cell: PFK-1 is inhibited allosterically by elevated levels of ATP, which act as an “energy- rich” signal indicating an abundance of high-energy compounds. Elevated levels of citrate, an intermediate in the TCA cycle (see p. 109), also inhibit PFK-1 . Conversely, PFK-1 is activated alloster- ically by high concentrations of AMP, which signal that the cell’s energy stores are depleted. [Note: Citrate inhibition favors the use of glucose for glycogen synthesis, see p.125.] 2. Regulation by fructose 2,6-bisphosphate: Fructose 2,6-bisphos- phate is the most potent activator of PFK-1 (see Figure 8.16), and is able to activate the enzyme even when ATP levels are high. Fructose 2,6-bisphosphate is formed by phosphofructokinase-2 ( PFK-2 ), an enzyme different than PFK-1 . PFK-2 is a bifunctional protein that has both the kinase activity that produces fructose 2,6-bisphosphate and a phosphatase activity that dephosphory- lates fructose 2,6-bisphosphate back to fructose 6-phosphate. In liver, the kinase domain is active if dephosphorylated and is inac- tive if phosphorylated (Figure 8.17). [Note: Fructose 2,6-bisphos

phate is an inhibitor of fructose 1,6-bisphosphatase , an enzyme of gluconeogenesis (see p. 120 for a discussion of the regulation of gluconeogenesis). The reciprocal actions of fructose 2,6-bisphos- phate on glycolysis (activation) and gluconeogenesis (inhibition) ensure that both pathways are not fully active at the same time, preventing a futile cycle in which glucose would be converted to pyruvate followed by resynthesis of glucose from pyruvate.]

During the well-fed state: Decreased levels of glucagon and elevated levels of insulin, such as occur following a carbohydrate- rich meal, cause an increase in fructose 2,6-bis- phosphate and, thus, in the rate of glycolysis in the liver (see Figure 8.17). Fructose 2,6-bisphosphate, therefore, acts as an intracellular signal, indicating that glucose is abundant.

During starvation: Elevated levels of glucagon and low levels of insulin, such as occur during fasting (see p. 327), decrease the intracellular concentration of hepatic fructose 2,6-bisphos- phate. This results in a decrease in the overall rate of glycolysis and an increase in gluconeogenesis.

Aldolase cleaves fructose 1,6-bisphosphate to dihydroxy acetone phosphate and glyceraldehyde 3-phosphate (see Figure 8.16). The reaction is reversible and not regulated. [Note: Aldolase B , the iso- form in the liver and kidney, also cleaves fructose 1-phosphate, and functions in the metabolism of dietary fructose

Isomerization of dihydroxyacetone phosphate Triose phosphate isomerase interconverts dihydroxyacetone phos- phate and glyceraldehyde 3-phosphate (see Figure 8.16). Dihydro xy - acetone phosphate must be isomerized to glycer aldehyde 3-phosphate for further metabolism by the glycolytic pathway. This isomerization results in the net production of two molecules of glycer - aldehyde 3-phosphate from the cleavage products of fructose 1,6- bisphosphate.

Oxidation of glyceraldehyde 3-phosphate The conversion of glyceraldehyde 3-phosphate to 1,3-bisphospho- glycerate by glyceraldehyde 3-phosphate dehydrogenase is the first oxidation-reduction reaction of glycolysis (Figure 8.18). [Note: Because there is only a limited amount of NAD + in the cell, the NADH formed by this reaction must be reoxidized to NAD + for gly- colysis to continue. Two major mechanisms for oxidizing NADH are: 1) the NADH-linked conversion of pyruvate to lactate (anaerobic, see p. 96), and 2) oxidation of NADH via the respiratory chain (aero- bic, see p. 75). The latter requires substrate shuttles (see p. 79.]

Synthesis of 1,3-bisphosphoglycerate (1,3-BPG): The oxidation of the aldehyde group of glyceraldehyde 3-phosphate to a carboxyl group is coupled to the attachment of P i to the carboxyl group. The high-energy phosphate group at carbon 1 of 1,3-BPG con- serves much of the free energy produced by the oxidation of glyceraldehyde 3-phosphate. The energy of this high-energy phosphate drives the synthesis of ATP in the next reaction of glycolysis.

Mechanism of arsenic poisoning: The toxicity of arsenic is explained primarily by the inhibition of enzymes such as pyruvate dehydrogenase , which require lipoic acid as a coenzyme (see p. 110). However, pentavalent arsenic (arsenate) also can prevent net ATP and NADH production by glycolysis, without inhibiting the pathway itself. The poison does so by competing with inor- ganic phosphate as a substrate for glyceraldehyde 3-phosphate dehydrogenase , forming a complex that spontaneously hydrolyzes to form 3-phosphoglycerate (see Figure 8.18). By bypassing the synthesis of and phosphate transfer from 1,3- BPG, the cell is deprived of energy usually obtained from the gly- colytic pathway. [Note: Arsenic also replaces P i on the F 1 domain of ATP synthase (see p. 78), resulting in formation of ADP-arsen- ate that is rapidly hydrolyzed.]

Synthesis of 2,3-bisphosphoglycerate (2,3-BPG) in red blood cells: Some of the 1,3-BPG is converted to 2,3-BPG by the action of bisphosphoglycerate mutase (see Figure 8.18). 2,3-BPG, which is found in only trace amounts in most cells, is present at high con- centration in red blood cells (increases O 2 delivery, see p. 31). 2,3-BPG is hydrolyzed by a phosphatase to 3-phosphoglycerate, which is also an intermediate in glycolysis (see Figure 8.18). In the red blood cell, glycolysis is modified by inclusion of these “shunt” reactions.

Synthesis of 3-phosphoglycerate producing ATP When 1,3-BPG is converted to 3-phosphoglycerate, the high-energy phosphate group of 1,3-BPG is used to synthesize ATP from ADP (see Figure 8.18). This reaction is catalyzed by phosphoglycerate kinase , which, unlike most other kinases , is physiologically reversible. Because two molecules of 1,3-BPG are formed from each glucose molecule, this kinase reaction replaces the two ATP molecules con- sumed by the earlier formation of glucose 6-phosphate and fructose 1,6-bisphosphate. [Note: This is an example of substrate-level phos- phoryl ation, in which the energy needed for the production of a high- energy phosphate comes from a substrate rather than from the electron transport chain (see J. below and p. 113 for other examples).]