text:
/**
 * ManagedCustomer.java
 *
 * This file was auto-generated from WSDL
 * by the Apache Axis 1.4 Mar 02, 2009 (07:08:06 PST) WSDL2Java emitter.
 */

package com.google.api.ads.adwords.axis.v201402.mcm;

/**
 * Data object that represents a managed customer.  Member of {@link
 * ManagedCustomerPage}.
 */
public class ManagedCustomer  implements java.io.Serializable {
    /* The name used by the manager to refer to the client.
     *                 This field can
     * be selected using the value "Name".This field can be filtered on.
     *                 This field is required
     * and should not be {@code null} when it is contained within {@link
     * Operator}s : ADD. */
    private java.lang.String name;

    /* The email address of the account's first login user, if any.
     * This field can be selected using
     * the value "Login".This
     * field can be filtered on.
     *                 This field is read
     * only and will be ignored when sent to the API. */
    private java.lang.String login;

    /* The company name of the account, if any.
     *                 This field can
     * be selected using the value "CompanyName".This field can be filtered on.
     *                 This field is read
     * only and will be ignored when sent to the API. */
    private java.lang.String companyName;

    /* The 10-digit ID that uniquely identifies the AdWords account.
     * This field can be selected using
     * the value "CustomerId".This
     * field can be filtered on.
     *                 This field is read
     * only and will be ignored when sent to the API. */
    private java.lang.Long customerId;

    /* Whether this account can manage clients.
     *                 This field is read only for external clients and will
     * be ignored when sent to the API.
     *                 This field can
     * be selected using the value "CanManageClients".This field can be filtered on. */
    private java.lang.Boolean canManageClients;

    /* The currency in which this account operates.
     *                 We support a subset of the currency codes derived
     * from the ISO 4217 standard.
     *                 See Currency Codes for the currently supported currencies.
     *                 This field can
     * be selected using the value "CurrencyCode".This field can be filtered on.
     *                 This field is required
     * and should not be {@code null} when it is contained within {@link
     * Operator}s : ADD.
     *                 The length of
     * this string should be between 3 and 3, inclusive. */
    private java.lang.String currencyCode;

    /* The local timezone ID for this customer.
     *                 See Time Zone Codes for the currently supported list.
     *                 This field can
     * be selected using the value "DateTimeZone".This field can be filtered on.
     *                 This field is required
     * and should not be {@code null} when it is contained within {@link
     * Operator}s : ADD. */
    private java.lang.String dateTimeZone;

    /* Whether this managed customer's account is a test account.
     *                 This field can
     * be selected using the value "TestAccount".
     *                 This field is read
     * only and will be ignored when sent to the API. */
    private java.lang.Boolean testAccount;

    public ManagedCustomer() {
    }

    public ManagedCustomer(
           java.lang.String name,
           java.lang.String login,
           java.lang.String companyName,
           java.lang.Long customerId,
           java.lang.Boolean canManageClients,
           java.lang.String currencyCode,
           java.lang.String dateTimeZone,
           java.lang.Boolean testAccount) {
           this.name = name;
           this.login = login;
           this.companyName = companyName;
           this.customerId = customerId;
           this.canManageClients = canManageClients;
           this.currencyCode = currencyCode;
           this.dateTimeZone = dateTimeZone;
           this.testAccount = testAccount;
    }

    /**
     * Gets the name value for this ManagedCustomer.
     *
     * @return name   * The name used by the manager to refer to the client.
     *                 This field can
     * be selected using the value "Name".This field can be filtered on.
     *                 This field is required
     * and should not be {@code null} when it is contained within {@link
     * Operator}s : ADD.
     */
    public java.lang.String getName() {
        return name;
    }

    /**
     * Sets the name value for this ManagedCustomer.
     *
     * @param name   * The name used by the manager to refer to the client.
     *                 This field can
     * be selected using the value "Name".This field can be filtered on.
     *                 This field is required
     * and should not be {@code null} when it is contained within {@link
     * Operator}s : ADD.
     */
    public void setName(java.lang.String name) {
        this.name = name;
    }

    /**
     * Gets the login value for this ManagedCustomer.
     *
     * @return login   * The email address of the account's first login user, if any.
     * This field can be selected using
     * the value "Login".This
     * field can be filtered on.
     *                 This field is read
     * only and will be ignored when sent to the API.
     */
    public java.lang.String getLogin() {
        return login;
    }

    /**
     * Sets the login value for this ManagedCustomer.
     *
     * @param login   * The email address of the account's first login user, if any.
     * This field can be selected using
     * the value "Login".This
     * field can be filtered on.
     *                 This field is read
     * only and will be ignored when sent to the API.
     */
    public void setLogin(java.lang.String login) {
        this.login = login;
    }

    /**
     * Gets the companyName value for this ManagedCustomer.
     *
     * @return companyName   * The company name of the account, if any.
     *                 This field can
     * be selected using the value "CompanyName".This field can be filtered on.
     *                 This field is read
     * only and will be ignored when sent to the API.
     */
    public java.lang.String getCompanyName() {
        return companyName;
    }

    /**
     * Sets the companyName value for this ManagedCustomer.
     *
     * @param companyName   * The company name of the account, if any.
     *                 This field can
     * be selected using the value "CompanyName".This field can be filtered on.
     *                 This field is read
     * only and will be ignored when sent to the API.
     */
    public void setCompanyName(java.lang.String companyName) {
        this.companyName = companyName;
    }

    /**
     * Gets the customerId value for this ManagedCustomer.
     *
     * @return customerId   * The 10-digit ID that uniquely identifies the AdWords account.
     * This field can be selected using
     * the value "CustomerId".This
     * field can be filtered on.
     *                 This field is read
     * only and will be ignored when sent to the API.
     */
    public java.lang.Long getCustomerId() {
        return customerId;
    }

    /**
     * Sets the customerId value for this ManagedCustomer.
     *
     * @param customerId   * The 10-digit ID that uniquely identifies the AdWords account.
     * This field can be selected using
     * the value "CustomerId".This
     * field can be filtered on.
     *                 This field is read
     * only and will be ignored when sent to the API.
     */
    public void setCustomerId(java.lang.Long customerId) {
        this.customerId = customerId;
    }

    /**
     * Gets the canManageClients value for this ManagedCustomer.
     *
     * @return canManageClients   * Whether this account can manage clients.
     *                 This field is read only for external clients and will
     * be ignored when sent to the API.
     *                 This field can
     * be selected using the value "CanManageClients".This field can be filtered on.
     */
    public java.lang.Boolean getCanManageClients() {
        return canManageClients;
    }

    /**
     * Sets the canManageClients value for this ManagedCustomer.
     *
     * @param canManageClients   * Whether this account can manage clients.
     *                 This field is read only for external clients and will
     * be ignored when sent to the API.
     *                 This field can
     * be selected using the value "CanManageClients".This field can be filtered on.
     */
    public void setCanManageClients(java.lang.Boolean canManageClients) {
        this.canManageClients = canManageClients;
    }

    /**
     * Gets the currencyCode value for this ManagedCustomer.
     *
     * @return currencyCode   * The currency in which this account operates.
     *                 We support a subset of the currency codes derived
     * from the ISO 4217 standard.
     *                 See Currency Codes for the currently supported currencies.
     *                 This field can
     * be selected using the value "CurrencyCode".This field can be filtered on.
     *                 This field is required
     * and should not be {@code null} when it is contained within {@link
     * Operator}s : ADD.
     *                 The length of
     * this string should be between 3 and 3, inclusive.
     */
    public java.lang.String getCurrencyCode() {
        return currencyCode;
    }

    /**
     * Sets the currencyCode value for this ManagedCustomer.
     *
     * @param currencyCode   * The currency in which this account operates.
     *                 We support a subset of the currency codes derived
     * from the ISO 4217 standard.
     *                 See Currency Codes for the currently supported currencies.
     *                 This field can
     * be selected using the value "CurrencyCode".This field can be filtered on.
     *                 This field is required
     * and should not be {@code null} when it is contained within {@link
     * Operator}s : ADD.
     *                 The length of
     * this string should be between 3 and 3, inclusive.
     */
    public void setCurrencyCode(java.lang.String currencyCode) {
        this.currencyCode = currencyCode;
    }

    /**
     * Gets the dateTimeZone value for this ManagedCustomer.
     *
     * @return dateTimeZone   * The local timezone ID for this customer.
     *                 See Time Zone Codes for the currently supported list.
     *                 This field can
     * be selected using the value "DateTimeZone".This field can be filtered on.
     *                 This field is required
     * and should not be {@code null} when it is contained within {@link
     * Operator}s : ADD.
     */
    public java.lang.String getDateTimeZone() {
        return dateTimeZone;
    }

    /**
     * Sets the dateTimeZone value for this ManagedCustomer.
     *
     * @param dateTimeZone   * The local timezone ID for this customer.
     *                 See Time Zone Codes for the currently supported list.
     *                 This field can
     * be selected using the value "DateTimeZone".This field can be filtered on.
     *                 This field is required
     * and should not be {@code null} when it is contained within {@link
     * Operator}s : ADD.
     */
    public void setDateTimeZone(java.lang.String dateTimeZone) {
        this.dateTimeZone = dateTimeZone;
    }

    /**
     * Gets the testAccount value for this ManagedCustomer.
     *
     * @return testAccount   * Whether this managed customer's account is a test account.
     *                 This field can
     * be selected using the value "TestAccount".
     *                 This field is read
     * only and will be ignored when sent to the API.
     */
    public java.lang.Boolean getTestAccount() {
        return testAccount;
    }

    /**
     * Sets the testAccount value for this ManagedCustomer.
     *
     * @param testAccount   * Whether this managed customer's account is a test account.
     *                 This field can
     * be selected using the value "TestAccount".
     *                 This field is read
     * only and will be ignored when sent to the API.
     */
    public void setTestAccount(java.lang.Boolean testAccount) {
        this.testAccount = testAccount;
    }

    private java.lang.Object __equalsCalc = null;
    public synchronized boolean equals(java.lang.Object obj) {
        if (!(obj instanceof ManagedCustomer)) return false;
        ManagedCustomer other = (ManagedCustomer) obj;
        if (obj == null) return false;
        if (this == obj) return true;
        if (__equalsCalc != null) {
            return (__equalsCalc == obj);
        }
        __equalsCalc = obj;
        boolean _equals;
        _equals = true &&
            ((this.name==null && other.getName()==null) ||
             (this.name!=null &&
              this.name.equals(other.getName()))) &&
            ((this.login==null && other.getLogin()==null) ||
             (this.login!=null &&
              this.login.equals(other.getLogin()))) &&
            ((this.companyName==null && other.getCompanyName()==null) ||
             (this.companyName!=null &&
              this.companyName.equals(other.getCompanyName()))) &&
            ((this.customerId==null && other.getCustomerId()==null) ||
             (this.customerId!=null &&
              this.customerId.equals(other.getCustomerId()))) &&
            ((this.canManageClients==null && other.getCanManageClients()==null) ||
             (this.canManageClients!=null &&
              this.canManageClients.equals(other.getCanManageClients()))) &&
            ((this.currencyCode==null && other.getCurrencyCode()==null) ||
             (this.currencyCode!=null &&
              this.currencyCode.equals(other.getCurrencyCode()))) &&
            ((this.dateTimeZone==null && other.getDateTimeZone()==null) ||
             (this.dateTimeZone!=null &&
              this.dateTimeZone.equals(other.getDateTimeZone()))) &&
            ((this.testAccount==null && other.getTestAccount()==null) ||
             (this.testAccount!=null &&
              this.testAccount.equals(other.getTestAccount())));
        __equalsCalc = null;
        return _equals;
    }

    private boolean __hashCodeCalc = false;
    public synchronized int hashCode() {
        if (__hashCodeCalc) {
            return 0;
        }
        __hashCodeCalc = true;
        int _hashCode = 1;
        if (getName() != null) {
            _hashCode += getName().hashCode();
        }
        if (getLogin() != null) {
            _hashCode += getLogin().hashCode();
        }
        if (getCompanyName() != null) {
            _hashCode += getCompanyName().hashCode();
        }
        if (getCustomerId() != null) {
            _hashCode += getCustomerId().hashCode();
        }
        if (getCanManageClients() != null) {
            _hashCode += getCanManageClients().hashCode();
        }
        if (getCurrencyCode() != null) {
            _hashCode += getCurrencyCode().hashCode();
        }
        if (getDateTimeZone() != null) {
            _hashCode += getDateTimeZone().hashCode();
        }
        if (getTestAccount() != null) {
            _hashCode += getTestAccount().hashCode();
        }
        __hashCodeCalc = false;
        return _hashCode;
    }

    // Type metadata
    private static org.apache.axis.description.TypeDesc typeDesc =
        new org.apache.axis.description.TypeDesc(ManagedCustomer.class, true);

    static {
        typeDesc.setXmlType(new javax.xml.namespace.QName("https://adwords.google.com/api/adwords/mcm/v201402", "ManagedCustomer"));
        org.apache.axis.description.ElementDesc elemField = new org.apache.axis.description.ElementDesc();
        elemField.setFieldName("name");
        elemField.setXmlName(new javax.xml.namespace.QName("https://adwords.google.com/api/adwords/mcm/v201402", "name"));
        elemField.setXmlType(new javax.xml.namespace.QName("http://www.w3.org/2001/XMLSchema", "string"));
        elemField.setMinOccurs(0);
        elemField.setNillable(false);
        typeDesc.addFieldDesc(elemField);
        elemField = new org.apache.axis.description.ElementDesc();
        elemField.setFieldName("login");
        elemField.setXmlName(new javax.xml.namespace.QName("https://adwords.google.com/api/adwords/mcm/v201402", "login"));
        elemField.setXmlType(new javax.xml.namespace.QName("http://www.w3.org/2001/XMLSchema", "string"));
        elemField.setMinOccurs(0);
        elemField.setNillable(false);
        typeDesc.addFieldDesc(elemField);
        elemField = new org.apache.axis.description.ElementDesc();
        elemField.setFieldName("companyName");
        elemField.setXmlName(new javax.xml.namespace.QName("https://adwords.google.com/api/adwords/mcm/v201402", "companyName"));
        elemField.setXmlType(new javax.xml.namespace.QName("http://www.w3.org/2001/XMLSchema", "string"));
        elemField.setMinOccurs(0);
        elemField.setNillable(false);
        typeDesc.addFieldDesc(elemField);
        elemField = new org.apache.axis.description.ElementDesc();
        elemField.setFieldName("customerId");
        elemField.setXmlName(new javax.xml.namespace.QName("https://adwords.google.com/api/adwords/mcm/v201402", "customerId"));
        elemField.setXmlType(new javax.xml.namespace.QName("http://www.w3.org/2001/XMLSchema", "long"));
        elemField.setMinOccurs(0);
        elemField.setNillable(false);
        typeDesc.addFieldDesc(elemField);
        elemField = new org.apache.axis.description.ElementDesc();
        elemField.setFieldName("canManageClients");
        elemField.setXmlName(new javax.xml.namespace.QName("https://adwords.google.com/api/adwords/mcm/v201402", "canManageClients"));
        elemField.setXmlType(new javax.xml.namespace.QName("http://www.w3.org/2001/XMLSchema", "boolean"));
        elemField.setMinOccurs(0);
        elemField.setNillable(false);
        typeDesc.addFieldDesc(elemField);
        elemField = new org.apache.axis.description.ElementDesc();
        elemField.setFieldName("currencyCode");
        elemField.setXmlName(new javax.xml.namespace.QName("https://adwords.google.com/api/adwords/mcm/v201402", "currencyCode"));
        elemField.setXmlType(new javax.xml.namespace.QName("http://www.w3.org/2001/XMLSchema", "string"));
        elemField.setMinOccurs(0);
        elemField.setNillable(false);
        typeDesc.addFieldDesc(elemField);
        elemField = new org.apache.axis.description.ElementDesc();
        elemField.setFieldName("dateTimeZone");
        elemField.setXmlName(new javax.xml.namespace.QName("https://adwords.google.com/api/adwords/mcm/v201402", "dateTimeZone"));
        elemField.setXmlType(new javax.xml.namespace.QName("http://www.w3.org/2001/XMLSchema", "string"));
        elemField.setMinOccurs(0);
        elemField.setNillable(false);
        typeDesc.addFieldDesc(elemField);
        elemField = new org.apache.axis.description.ElementDesc();
        elemField.setFieldName("testAccount");
        elemField.setXmlName(new javax.xml.namespace.QName("https://adwords.google.com/api/adwords/mcm/v201402", "testAccount"));
        elemField.setXmlType(new javax.xml.namespace.QName("http://www.w3.org/2001/XMLSchema", "boolean"));
        elemField.setMinOccurs(0);
        elemField.setNillable(false);
        typeDesc.addFieldDesc(elemField);
    }

    /**
     * Return type metadata object
     */
    public static org.apache.axis.description.TypeDesc getTypeDesc() {
        return typeDesc;
    }

    /**
     * Get Custom Serializer
     */
    public static org.apache.axis.encoding.Serializer getSerializer(
           java.lang.String mechType,
           java.lang.Class _javaType,
           javax.xml.namespace.QName _xmlType) {
        return
          new  org.apache.axis.encoding.ser.BeanSerializer(
            _javaType, _xmlType, typeDesc);
    }

    /**
     * Get Custom Deserializer
     */
    public static org.apache.axis.encoding.Deserializer getDeserializer(
           java.lang.String mechType,
           java.lang.Class _javaType,
           javax.xml.namespace.QName _xmlType) {
        return
          new  org.apache.axis.encoding.ser.BeanDeserializer(
            _javaType, _xmlType, typeDesc);
    }

}


While colored pencils may have been a medium you encountered back in primary school, their usefulness in fine arts shouldn't be trivialized. Highly detailed and unique pieces can be made with colored pencils. Unlike other media from your schooldays, colored pencils give you extreme flexibility in color choice and precision. Through their unique blending abilities and interaction with the paper, the possibilities for what colored pencils can do will really open up if you follow these few tricks and tips below. Fair warning, however, is that these are a guide—like any craft, knowing what to do is barely half the battle. The real "trick" is focused practice. Taking the time to hone these skills through exercises will help you produce the work you're striving for.
The tooth of the paper refers to the tiny hills and valleys made from the paper's grain. Colored pencils aren't designed to be used on perfectly smooth surfaces, so it's important to find quality paper with a good tooth before you begin.
Finding paper with a good tooth shouldn't be hard, but it will take some skill to learn how to work with it. First, consider the angle that you hold your pencil. Rather than holding your pencil on its side to graze the peaks of the tooth, keep the pencil closer to the vertical, like you would when writing. This helps ensure that your sharp tip is making the most contact.
Next, aim for circular or oval-shaped strokes. When you zigzag back and forth, you create unbalanced color as you change direction against the tooth. Circles or ovals lead to smoother, more easily blended colors without leaving obvious stroke marks. Unless you're deliberately aiming to crosshatch, circles will almost always create better coverage.
How hard you press is going to affect how much of the valleys are filled in. You want to begin with a light touch. Instead of smashing down on your expensive pencils and repeatedly breaking the tips, instead work in layers. The more layers you build, the bolder your colors will be. In addition, when you get to blending, if there's more material layered on, it will blend more smoothly.
It's also important when considering pressure not to smash the tooth of the paper. Pressing too hard will flatten the tooth completely, which could ruin the blending of your work. Of course there are times when you will want to smash the tooth—or brandish—but we'll cover that below.
Understanding the colors you have and how they actually look on your paper is as important with colored pencils as it is with paint. Just looking at the color painted onto the wood or even the pigment inside will not tell you exactly how it will look on the paper.
The best way to know what you have is to create your own color swatches for your pencil sets. For each swatch, make a gradient on the paper you'll actually be using (with more color on one side than on the other). This way on each swatch you can see how the color reacts in different quantities. Once you've drawn your samples, label them with the names on the pencils and keep them handy. This way there's no guessing about whether you've chosen the right color. You can simply hold up your swatch and compare.
You can make them last longer if you organize them in groups (like "shades of green"), put them on a strip together, laminate them, and then bind them with a ring just like in a paint shop. Your colors will always be handy for comparison and you'll know what each pencil is capable of producing.
Artist-quality colored pencils are entirely different from what's sold as school supplies. Although following these other techniques will allow you to create greater works with lesser materials, you want as much flexibility as possible from your pencils.
Most professional colored pencils are softer than their cheaper counterparts. When choosing a brand, the two biggest on the market are Faber Castell Polychromos and Prismacolor. The former is an oil-based pencil, great for making many layers. However, oil-based pencils are difficult to add light colors on top of dark. Prismacolor makes wax-based pencils. While that's the same base that Crayola uses, these are much softer and better made. Wax-based pencils blend quite well, but the wax will build up at some point, making it difficult to add to. Their softness also makes them prone to breaking and difficult to keep sharp (which we'll get to in the next tip).
Colored pencils can be bought in large packs or individually. When testing what works best for you, consider buying the same color from a few different brands to figure out which blends the way you like the most. You should do this before you invest in a 72-color pack for over 100 USD. Some artists even prefer the way oil and wax mix together, and will layer them on top of each other. Regardless of which is best for you, the professional quality pencils will blend so much better than the ones for children.
How sharp should you keep your pencils? If you answered "very," you've got an edge up on this tip! A sharp tip leads to more control—both for fine lines and when filling in areas with your big circles. When the tip is dull, you need to push harder, and that pressure can ruin the tooth.
To keep them sharp you have a few options. Some artists recommend using a knife like an Xacto blade to keep the tip sharp. This allows you a lot of control, and minimal waste. These pencils aren't cheap, so you don't want to blast them all away on a mechanical sharpener. Other artists prefer mechanical sharpeners, however, because even though it eats away at your pencils faster, the softer pencils are less likely to break in the process. Remember, these are much more fragile than what's sold for school children. Simply dropping them could fracture the inside of them (though it's possible to fuse them back together with a little heat), so you want to take care with your sharpening.
The key is this: sharpen well, and sharpen often.
Blending is what it's all about with colored pencils, and there are plenty of techniques to try to get the precise smoothness you're looking for.
First, you can go with solvents. Odorless mineral spirits work best for both wax and oil-based pencils. After you've built up many layers of color, brushing them with the solvent helps the pigment seep into the valleys of the teeth, blurring their edges and creating a natural look. Some pencil companies sell markers that contain a solvent as well, but be sure to clean them after each use before they dry out. Coupled with the solvents, tissue can also help smooth your work even further. But be careful—the tissue will also pick up a lot of the color, so you may need to go back over it and repeat the process to get the desired blend.
You can also use some pencils for the blending. For both oil- and wax-based pencils, the white pencil can serve as a blender. Going over your layers with the white will smooth the color and help fill in the valleys. However, with wax-based pencils, this will also lighten the color overall. Because of this, some wax-based pencils will sell a colorless blender specifically for this purpose.
In any case, blending works best after you've built up plenty of color layers. Don't be afraid to mix different colors here too. The process is anything but fast—so be prepared to take quite a while to get the layers and the blend you're looking for.
Remember how earlier we said to avoid pushing down too hard and smashing the tooth of the paper? That can actually be used to quite a strong effect. Known as burnishing, when you apply great pressure to the pencil, the color that comes out will be much darker and bolder. If you do this atop many layers, the area will be bolder as you fill in the layers, but it also aids in pushing previous layers into the valleys. The result is a little darker and could be a bit shiny, but there are plenty of cases when that's an effect worth having.
Burnishing is always a last step. Once you've crushed the tooth, it would need to be sprayed with some kind of workable fixative to get a tooth back on. It's much easier to save it for the last step.
This final tip may seem obvious, but it's an easy beginner's mistake to make. In some media, it's very easy to change the rough design and shift big pieces. With colored pencils, the work is all about layering, so you want to make sure your drawing is perfect before you start building up, because there's very little you can change about it afterward. Focusing on precision early before picking up the color will allow you to spend more of your time getting those perfect colors right rather than fretting over proportions that are long since unchangeable.


All other countries, including developing countries such as India and China, are still bound by the WTO's agreement on trade-related intellectual property rights (or TRIPS) with respect to drug patents.
The waiver is critical for the least developed countries. Compared with richer countries, they have a much higher disease burden, especially infectious diseases such as HIV and malaria. In 2011, about 9.7m people in these countries were living with HIV.
Many of the drugs that treat these diseases are still under patent protection. Drug patents last for 20 years and allow drugs companies time to recoup their investment into research and development and turn a profit.
Once the patent protection period ends, other drugs companies can then copy the drug and sell it as a generic medicine. These generics are much cheaper than branded drugs.
Countries such as Uganda, Cambodia and Rwanda have already taken advantage of the WTO's temporary waiver and begun to develop their own pharmaceutical industry. This has been helped by investments from drug companies in the developing world.
For example, Uganda-based Cipla Quality Chemicals was originally a joint-venture between Cipla, a large Indian generics manufacturer, and the Ugandan government. It is the only company in Africa that makes triple-combination antiretroviral drugs.
It costs pharmaceuticals companies about US$2.6 billioin to develop a new drug. If these companies were not allowed to protect their investment with patents, it is doubtful that any new drugs would be developed. So patents are an important incentive.
Although building a home grown pharmaceuticals industry is not a requirement of the WTO waiver, a strong local industry would give poor countries direct access to much needed cheap medicines.
The WTO's transitional waiver makes sense. By temporarily allowing LDCs to ignore patents on drugs, it gives them time to develop their own pharmaceuticals industries. And we are already seeing evidence of this happening. According to the UN agencies, UNDP and UNAids, the proportion of people with HIV who are not receiving antiretrovirals reduced from 90% in 2006 to 63% in 2013 thanks to the availability of drugs made by LDCs.
Despite some criticisms, the WTO's decision to extend the waiver should be praised. It seems fair and reasonable, and it doesn't excessively jeopardise companies that make branded (non-generic) drugs. They don't seem to lose much from missed royalties. Overall, the poorest countries account for less than 2% of the world's gross domestic product and about 1% of global trade in goods. Not a big business opportunity for big pharma.


text:
Q: How would I write a function for the following pattern? \begin{align}
Y(0) ={}& 1\\
Y(1) ={}& 2.5\\
Y(2) ={}& 2.5\cdot2.3\\
Y(3) ={}& 2.5\cdot 2.3\cdot 2.1\\
Y(4) ={}& 2.5\cdot 2.3\cdot 2.1\cdot 1.9\\
\vdots\,\,\,
\end{align}
How would I solve for something like $Y(1.3)$ or $Y(2.7)$? How would a function for $Y(x)$ be defined?

A: We may use the Pochhammer symbol (falling factorial ) once $Y(x)$ multiplied by $5^x$ :
\begin{align}
Y(x)\;5^x&=\left(\frac {25}2\right)_{x}=\frac{\Gamma\left(\frac {27}2\right)}{\Gamma\left(\frac {27}2-x\right)}\\
\\
\end{align}

A: Notice that
\begin{align*}
Y(x) &= \frac{25}{10} \cdot \frac{23}{10} \cdot \frac{21}{10} \cdots \frac{27 - 2x}{10} \\[5pt]
&= \frac{1}{10^x} \cdot \frac{(26)(25)(24)(23)(22)(21) \cdots (28-2x)(27-2x)}{(26)(24)(22)\cdots (28-2x)} \\
&= \frac{1}{10^x} \cdot
\frac{(26)(25)(24)(23)(22)(21) \cdots (2)(1)}{(26)(24)(22)\cdots (4)(2)}
\cdot \frac{(26-2x)(24-2x)(22-2x)\cdots (4)(2)}
{(26-2x)(25-2x)(24-2x)(23-2x)\cdots (2)(1)} \\
&= \frac{1}{10^x} \cdot
\frac{26!}{2^{13} 13!}
\cdot \frac{2^{13-x} (13-x)!}
{(26-2x)!} \\
&= \boxed{\frac{1}{20^x} \cdot \frac{26!}{13!} \cdot \frac{(13-x)!}{(26-2x)!}}.
\end{align*}
In particular, this gives you a closed form for integer $x$ when $x = 0, 1, 2, 3, \ldots, 13$.
But we'd like this to work for $x > 13$ as well (when the above formula is undefined), and for real $x$ instead of just integer $x$.
In fact, the factorial function extends to a function $\Pi(z)$ for all complex $z$ except negative integers ($z! = \Pi(z) = \Gamma(z+1)$ where $\Gamma$ is the Gamma function).
Then we get
$$
Y(x) = \frac{1}{20^x} \cdot \frac{26!}{13!} \cdot \frac{\Pi(13-x)}{\Pi(26-2x)}
$$
We still have a problem when $x > 13$ is an integer: $\Pi(13-x)$ and $\Pi(26-2x)$ are undefined but we expect $Y(x)$ to still have a formula. We can employ the duplication formula which says that
$$
\Pi(2z) = \frac{1}{\sqrt{\pi}} 4^z \Pi(z) \Pi(z - \tfrac12)
$$
with $z = 13-x$ to obtain
\begin{align*}
Y(x)
&= \frac{1}{20^x} \cdot \frac{26!}{13!} \cdot \frac{\Pi(13-x)}{(\tfrac{1}{\sqrt{\pi}})4^{13-x} \Pi(13-x)\Pi(\tfrac{25}{2} - x)} \\
&= \boxed{\left( \frac{26! \sqrt{\pi}}{13! \;4^{13}} \right) \left(\frac{1}{5^x}\right) \left(\frac{1}{\Pi(\tfrac{25}{2} - x)}\right)}.
\end{align*}
The constant term in front is of course $\Pi(\tfrac{25}{2}) = \Gamma(\tfrac{27}{2})$, so this agrees with Raymond Manzoni's answer.

redpajama_set_name: RedPajamaStackExchange


Biofilms are communities of cells held together by a self-produced extracellular matrix typically consisting of protein, exopolysaccharide, and often DNA. A natural signal for biofilm disassembly in Bacillus subtilis is certain d-amino acids, which are incorporated into the peptidoglycan and trigger the release of the protein component of the matrix. d-Amino acids also prevent biofilm formation by the related Gram-positive bacterium Staphylococcus aureus. Here we employed fluorescence microscopy and confocal laser scanning microscopy to investigate how d-amino acids prevent biofilm formation by S. aureus. We report that biofilm formation takes place in two stages, initial attachment to surfaces, resulting in small foci, and the subsequent growth of the foci into large aggregates. d-Amino acids did not prevent the initial surface attachment of cells but blocked the subsequent growth of the foci into larger assemblies of cells. Using protein- and polysaccharide-specific stains, we have shown that d-amino acids inhibited the accumulation of the protein component of the matrix but had little effect on exopolysaccharide production and localization within the biofilm. We conclude that d-amino acids act in an analogous manner to prevent biofilm development in B. subtilis and S. aureus. Finally, to investigate the potential utility of d-amino acids in preventing device-related infections, we have shown that surfaces impregnated with d-amino acids were effective in preventing biofilm growth.
Most bacteria form matrix-enclosed communities, or biofilms, when growing on surfaces. In clinical settings, biofilms are particularly problematic since they tend to form on indwelling devices and cause persistent infections and sepsis. Biofilm-associated bacteria are much less sensitive to antibiotics, making biofilm-related infections especially difficult to cure (7, 13). Often the only solution for a biofilm-infected catheter is complete replacement, a procedure that can range from uncomfortable and inconvenient to painful, expensive, and life threatening. Consequently, the development of methods to prevent biofilm formation may be just as important for treating hospital-acquired infections as the development of new antibiotics.
Bacterial signaling molecules that trigger the dispersal of old biofilms hold promise as possible therapeutic agents. Recent work has demonstrated that d-amino acids may be an exemplary class of such compounds (10, 19). Certain d-amino acids isolated from the supernatants of disassembled Bacillus subtilis biofilms were shown to prevent biofilm formation in fresh cultures by disrupting the connection between an extracellular matrix protein and the cell. Similar inhibitory effects for Staphylococcus aureus and Pseudomonas aeruginosa biofilms suggested that d-amino acids might constitute a general strategy for inhibiting biofilm formation in opportunistic pathogens (10). Genes whose products are involved in biofilm formation are not orthologous across these species, however, and the mechanism of action of d-amino acids against biofilms formed by these dissimilar pathogens remains unknown.
Here we describe investigations of the mechanism by which d-amino acids inhibit biofilm formation by S. aureus using fluorescence and confocal scanning laser microscopy. These techniques provide a more detailed picture of biofilm development on surfaces than visual inspection and bulk staining alone. Using dyes for specific components of the biofilm, such as cells, proteins, and polysaccharides, we have found that d-amino acids inhibit biofilm formation in S. aureus in much the same way as in B. subtilis: by preventing protein localization at the cell surface. Since S. aureus employs cell surface-associated proteins to connect neighboring cells in large aggregates (9), d-amino acids could prove effective at preventing mature biofilm development.
Bacterial growth.Staphylococcus aureus wild-type (WT) strain SC01 (2) was obtained from the Kolter lab collection. Tryptic soy broth (TSB) medium and d and l isomers of proline, tyrosine, phenylalanine, tryptophan, and leucine were obtained from Sigma-Aldrich (Atlanta). Cells were cultured in a shaking LB medium overnight and diluted 1:100 in TSB medium supplemented with NaCl (3%), glucose (0.5%), and the appropriate concentrations of l- or d-amino acids (or lack thereof). Cells were grown for the specified period of time in the bottom of 6- or 12-well polystyrene plates or in 6-well plates with submerged substrates without shaking at 37°C. Planktonic cells were removed by gentle rinsing with phosphate-buffered saline (PBS) before further treatment.
Crystal violet staining.Cells were grown in 12-well plates for 24 h, and after rinsing in PBS, adhered cells were stained with crystal violet (CV) as described previously (16). Wells were stained with 500 μl of 0.1% crystal violet dye, rinsed twice with 2 ml double-distilled water, and thoroughly dried. Images were taken with an AMT 2k charge-coupled-device (CCD) camera. For the quantification of biofilm growth, 0.5 ml of ethanol (95%) was added to the CV-stained wells and incubated with shaking for 2 h. The resulting solutions of dissolved CV were diluted by a factor of 20, and their optical density was measured at 595 nm. Each data point is composed of three independent samples.
Polymer substrate fabrication.Polymer substrates used for these studies were fabricated by UV curing an epoxy (UVO-114; Epoxy Technology) or a polyurethane (Norland optical adhesive 61) in a polydimethylsiloxane mold as previously reported (1).
Assessment of d-amino acid effects on biofilms adhered to different surfaces.Cells were grown as described above for 24 h with an either d or l mixture of equal ratios of Pro, Phe, and Tyr in a final concentration of 100 μM. Cells were grown either on 6-well polystyrene plates or on 18- by 18-mm glass cover slides (VWR) or on epoxy surfaces submerged in a 6-well plate. Glass and epoxy surfaces were submerged in 6 ml of the growth medium. After rinsing, adhered cells were fixed using a 5% glutaraldehyde solution for 1 h with 0.05 M surfactin (Sigma-Aldrich). Cells were washed twice in PBS. Images were taken with an AMT 2k CCD camera against a black background.
Fluorescence microscopy.All dyes (Sytox green, fluorescein isothiocyanate [FITC], Syto 63, and Texas Red-concanavalin A [ConA]) were obtained from Invitrogen-Molecular Probes (Oregon). Fluorescence microscopy images were obtained on a Leica DMRX compound microscope fitted with a 63× water immersion lens. Cells were grown in 6-well polystyrene plates in duplicate, as described above. Cells were fixed as described above after 2, 12, and 24 h for 1 h at 50°C. Cells were then rinsed with PBS, and their membranes were made permeable by soaking the cell growth substrates in Triton X-100 (VWR), 0.1% (vol/vol) in PBS (PBST), for 15 min. The cells were labeled by replacing the PBST with Sytox green nucleic acid stain, 0.5 μM in PBST, for 15 min to an hour. The substrates were rinsed again with PBS and then imaged with the water immersion lens using a Leica FITC (K3) filter cube.
Confocal microscopy.Confocal microscopy images were obtained on a Leica TCS SP5 spectral confocal inverted microscope. S. aureus cells were grown without shaking in 37°C in TSB medium with 3% NaCl and 0.5% glucose for 24 h, applied with either a d or an l mixture of equal ratios of Pro, Phe, and Tyr in a final concentration of 100 μM. Cells were grown on a glass cover slide of 18 by 18 mm submerged in 6 ml of TSB with NaCl and glucose. Planktonic cells were removed. Adhered cells were fixed using a 5% gluteraldehyde solution for 1 h in 50°C, applied with surfactin (0.05 M). Cells were washed in 2 ml PBS. FITC (0.001%) and Syto 63 (100 μM) were added to the well, and the plate was incubated with shaking for 5 min and for an additional hour without shaking at room temperature. Cells were washed twice in PBS. Samples were then removed from the PBS rinse solution and inverted onto a cover glass (no. 1; VWR). Biofilms or adhered cells were imaged through the cover glass using the following excitation and emission wavelengths (11): 488 nm excitation and 505 to 530 nm emission detection range for FITC, 543 nm and 560 to 800 nm for Texas Red-ConA, and 633 nm and 650 to 800 nm for Syto 63.
Controlled release of d-amino acids from polymer substrates.Epoxy and polyurethane substrates were soaked overnight in 1 mM solution of either l or d isomers of Pro, Phe, and Tyr in equal molar ratios. The substrates were rinsed thoroughly with PBS, and then cells were grown on them in 6-well plates for 24 h as described above. Fluorescence microscopy images of the adhered cells were obtained as described above.
S. aureus forms biofilms on submerged surfaces (4, 17). These biofilms can be detected by staining the adhered cells with crystal violet. We screened all d-amino acids for those that were effective in inhibiting biofilm formation by strain SC01. d-Tyr, d-Pro, and d-Phe were the most effective, whereas other d-amino acids had little or no effect (Fig. 1 and data not shown; see also Fig. S1 in the supplemental material). An equimolar mixture of d-Tyr, d-Pro, and d-Phe was more effective in preventing biofilm formation than any of the individual amino acids (Fig. 1). In contrast, l-Tyr, l-Pro, l-Phe, and a mixture of the three had little or no inhibitory effect (data not shown). The d-Tyr, d-Pro, and d-Phe mixture was also more effective than the previously described mixture of d-Trp, d-Met, d-Leu, and d-Tyr that was optimal for inhibiting biofilm formation by B. subtilis (10) (see Fig. S2). It should be noted that d-amino acids did not significantly impair the growth of S. aureus cells, even at millimolar concentrations (see Fig. S3), and therefore, as observed for B. subtilis, the inhibitory effect on biofilm formation was not a result of growth inhibition. The inhibitory effect of the d-amino acid mixture was not restricted to strain SC01 and was also seen with three other S. aureus strains (see Fig. S4 and S5). Finally, the d-amino acid mixture could also disassemble an existing biofilm, but this effect required much higher concentrations (10 mM) than that needed for inhibition (<100 μM) (see Fig. S6).
d-Pro, d-Tyr, and d-Phe inhibit biofilm formation in S. aureus. Cells were cultured overnight in 12-well plates and stained with crystal violet to assess biofilm formation (a). Cells were significantly impaired in biofilm formation at concentrations of individual d-amino acids of 500 μM. Cells exposed to an equimolar mixture of all three d-amino acids were significantly impaired in biofilm formation at a concentration as low as 10 μM (b). Shown on the right is the quantification of biofilm formation as determined by crystal violet staining.
The adhesion of cells to a surface is an essential first step of biofilm formation and can occur by specific and nonspecific cell-surface interactions. To study whether d-amino acids disrupted the attachment stage of biofilm growth, we screened a representative sample of substrates. As shown in Fig. 2, d-amino acids but not l-amino acids inhibited biofilm formation equivalently on polystyrene, epoxy, and glass surfaces, suggesting that the surface properties of these different substrates were irrelevant to the mode of action of d-amino acids. This result led us to use fluorescence microscopy to investigate the effect of d-amino acids on biofilm development and morphology. As shown in Fig. 3, S. aureus cells adhered to epoxy surfaces and continued to attach and divide up to 12 h of growth. This initial attachment step (seen at 2 and 12 h), which appears as foci in the figure, was not affected by exposure to d-amino acids. Under our growth conditions, S. aureus subsequently formed large aggregates characteristic of mature biofilms on submerged surfaces within 24 h. The formation of these aggregates was blocked when cells were grown in the presence of d- but not l-amino acids (Fig. 3). We conclude that d-amino acids prevent biofilm development at a stage subsequent to the initial attachment to surfaces and continue to inhibit biofilm growth for at least 48 h.
The inhibitory effect of d-amino acids on biofilm growth is similar on different substrates. Biofilms formed equally on polystyrene, epoxy, and glass substrates after 24 h of growth and did not form in the presence of d-amino acids (+ D-aa), suggesting the mechanism of action of d-amino acids is unrelated to initial surface attachment. Biofilm attached to the surface appears white in these unstained samples. For the glass and epoxy substrates, cover glass and molded epoxy were submerged in medium in 6-well plates. For growth on polystyrene, the bottom of the well was used as the substrate.
Mature biofilm development is inhibited by d-amino acids. Biofilm growth was arrested at initial (2 h), intermediate (12 h), and advanced (24 h) developmental stages on epoxy substrates, and the cells were fixed and stained for fluorescence microscopy imaging. The dye used is a nucleic acid stain, effectively labeling the entire cytoplasm. At 12 h there is little difference between the morphology of adhered cells in untreated cultures, those treated with l-amino acids (+ Laa), and those treated with d-amino acids (+ Daa). After 24 h, however, the inhibition of biofilm growth by d-amino acids is apparent. The scale bars are 10 μm.
We hypothesized that aggregate formation during S. aureus biofilm development is blocked by d-amino acids as a result of a change in the properties of the extracellular matrix, as was shown in the case of d-amino acid inhibition of B. subtilis biofilms (10). To investigate this possibility, we characterized biofilms formed on glass coverslips with and without d-amino acids, focusing on the protein and exopolysaccharide (EPS) components of the extracellular matrix. We stained the EPS with a fluorescent concanavalin A (ConA) conjugate, and proteins were stained with the amine-reactive fluorescein isothiocyanate (FITC) (14). These dyes may also bind to proteins and carbohydrates inside the cells if the cell membrane has been compromised. Therefore, we also stained with Syto 63, a DNA-reactive dye, to distinguish binding sites in the extracellular matrix from those inside cells. Figures 4 and 5 show stacked sections of S. aureus biofilms imaged using confocal laser scanning microscopy (CLSM). Image slices were obtained at 2-μm increments moving from the top of the biofilm toward the substrate. In this way we determined the minimum thickness of the biofilm. This thickness determination was limited by the diffusion of dye into the biofilm and therefore is given as a minimum value for mature biofilms. As can be seen in Fig. 4a and 4b, cells in mature biofilms displayed large amounts of proteins at their surface. These cell surface-associated proteins were also present when biofilms were grown in the presence of l-amino acids. However, such proteins were largely absent when cells were grown in the presence of d-amino acids (Fig. 4c; see also Fig. S7A in the supplemental material). In contrast, the localization of cell wall sugars and EPS exhibited little difference between cells grown in the presence of d-amino acids and those grown with l-amino acids (Fig. 5; see also Fig. S7B and S8). It should be noted that biofilms grown in the presence of d-amino acids were significantly thinner (2 to 4 μm) than the biofilms grown in the presence of l-amino acids (10 to 24 μm). Also, the large cell aggregates found in biofilms grown with l-amino acids were absent in surface-associated cells grown in the presence of d-amino acids.
Confocal microscopy images of S. aureus biofilms grown with or without d-amino acids reveal a difference in the presence of extracellular protein. Biofilms were stained with protein-specific (green) and DNA-specific (red) dyes to image the localization of the peptide component of the biofilm matrix. (a) CLSM imaging of wild-type biofilms shows a clear localization of extracellular proteins to the cell wall in an image slice taken from the interior of a large cell aggregate. The higher-magnification image on the bottom shows this localization clearly, with even the septa between dividing cells stained. (b) Images were taken as lateral cross sections of the biofilm, with the height of each section indicated from the top of the biofilm. The presence of protein at the cell surface is clearly seen throughout the aggregates. (c) In d-amino acid-treated cultures, there was no biofilm present on the substrate surface and there was a distinct lack of protein localization on the cell surfaces, in contrast to the images in panel b. The dispersed cells and clusters seen in panel c were adhered to the substrate surface, and the two images shown are typical of the morphology and staining across the entire substrate as seen in multiple additional images. The scale bars are 5 μm except for that in the lower frame of panel a, which is 1 μm.
Confocal laser scanning microscopy images show no difference in the localization of EPS in S. aureus aggregates from cultures grown with d- or l-amino acids. These cells were stained with EPS-specific (blue) and DNA-specific (red) dyes, and the imaging sections were obtained in the same manner as those in Fig. 4. (a) Cultures treated with l-amino acids exhibited robust biofilms with localization of EPS around the cells in the aggregates. (b) Those treated with d-amino acids retained the EPS surrounding the cells but adhered as a submonolayer film, lacking the thickness and structure of a mature biofilm. As in Fig. 4c, the cells shown in panel b were attached only at the surface of the substrate. The scale bars are 5 μm.
The ability of d-amino acids to disrupt biofilm formation makes them potentially useful for addressing the problems associated with device-related infections. To investigate this possibility, we asked whether the slow release of d-amino acids from the substrate, rather than supplying them in the growth medium, would be sufficient to impede biofilm formation. Accordingly, we soaked substrates, including epoxy- and polyurethane-based polymers, in medium containing d-amino acids or l-amino acids. The substrates were washed and placed in fresh growth medium lacking supplemented d-amino acids or l-amino acids. The results shown in Fig. 6 demonstrate that S. aureus formed robust biofilms when cultured on immersed surfaces impregnated with l-amino acids. In contrast, biofilm formation was inhibited on surfaces impregnated with d-amino acids. As a negative control, glass surfaces, which do not absorb the d-amino acid mixture, were used (see Fig. S9 in the supplemental material). On these surfaces, S. aureus biofilm growth was unaffected. Therefore, diffusion of d-amino acids was as effective as d-amino acids in the medium for inhibiting biofilm formation.
The diffusive release of d-amino acids from polymer surfaces inhibits biofilm growth. (A) Polymer substrates were soaked in l- or d-amino acids overnight and rinsed before use as growth substrates in medium lacking supplemented amino acids of either kind. (B) Both epoxy- and polyurethane-based growth substrates resisted biofilm accumulation when soaked with d-amino acids but not l-amino acids, recapitulating the results of cultures grown in the presence of amino acids of either chirality. The images were obtained by fluorescence microscopy using Sytox green to label the cytoplasm. The scale bars are 10 μm.
Many bacteria, including S. aureus, produce d-amino acids upon entry into the stationary phase of growth (11). d-Amino acids incorporate into the peptide cross bridge of the peptidoglycan component of the cell wall (5, 6, 11). It was previously shown that d-tyrosine, d-leucine, d-tryptophan, and d-methionine were active in inhibiting biofilm formation by B. subtilis, whereas d isomers of other amino acids, such as d-phenylalanine, were inert in inhibiting biofilm formation (10). In contrast, in S. aureus the d isomers that were found to be active in inhibiting biofilm formation were d-phenylalanine, d-proline, and d-tyrosine (Fig. 1). Under the conditions described here, a mixture of d-Tyr, d-Pro, and d-Phe was more effective in preventing biofilm formation than the previously described mixture of d-Trp, d-Met, d-Leu, and d-Tyr (see Fig. S2 in the supplemental material). These differences suggest S. aureus and B. subtilis differ either in the mechanism by which d-amino acids are integrated in the cell wall or, alternatively, in the way they sense and respond to the incorporation of unusual d-amino acids.
Exposure to d-amino acids did not inhibit the growth of S. aureus in shaking cultures (see Fig. S3 in the supplemental material). Rather, the effect of d-amino acids appeared to be specific to biofilm formation. The first step of biofilm formation is the attachment of bacteria to a surface. The fact that S. aureus adhered to and formed biofilms equally well on various substrates and that d-amino acids prevented biofilm growth in an identical manner across all of the substrates tested (Fig. 2) suggested that the inhibition step was unrelated to the mechanism of initial attachment of bacteria to surfaces. Indeed, fluorescence microscopy (Fig. 3) revealed that initial surface attachment was unaffected by treatment with d-amino acids. Instead, these images showed that bacteria adhered to the submerged surface but did not proceed to form fully developed biofilms. The initial surface attachment of bacteria was similar irrespective of treatment with l- or d-amino acids. By 24 h of growth, however, the untreated and l-amino acid-treated cultures had developed mature biofilms with large cell aggregates. In contrast, biofilm development in cultures exposed to d-amino acids was arrested at the attachment stage. It is likely, therefore, that the effects of d-amino acids are restricted to the accumulation step in biofilm development.
Confocal microscopy gave a more detailed picture of biofilm development during exposure to d-amino acids. Using FITC and Syto 63 as a cell body counterstain, protein could be seen to localize at or around the cell wall of the constituent cells of S. aureus biofilms (Fig. 4a). Whereas cells in biofilm aggregates that had formed in l-amino acid-treated cultures were clearly decorated with protein (Fig. 4b), the lack of these large supracellular structures and of protein surrounding the cells in the d-amino acid cultures (Fig. 4c; see also Fig. S7A in the supplemental material) suggests a functional relationship between the effect of d-amino acids and a protein component of the matrix. Several surface proteins play an important role in biofilm aggregates for S. aureus (8, 9, 15, 20). Thus, an appealing hypothesis is that d-amino acids prevent the localization of cell-cell adhesion proteins, thereby inhibiting the aggregate formation necessary for biofilm development. If so, then the role of d-amino acids in S. aureus would be analogous to that observed in B. subtilis, for which d-amino acid treatments have been shown to trigger the release from cells of the matrix protein TasA (3, 18). In B. subtilis, a recently characterized accessory protein, TapA (TasA anchoring/assembly protein), serves to anchor the TasA amyloid fibers to the cell wall and is mislocalized in response to d-amino acids (10, 19). Interestingly, however, TapA has no apparent ortholog in S. aureus. The fact that d-amino acids are effective at blocking these different and unrelated adhesion proteins from localizing at the cell wall suggests that they may comprise a general biofilm dispersal strategy.
The polysaccharide component of the S. aureus biofilms, on the other hand, was present in attached cells irrespective of amino acid exposure. These polysaccharides were seen to be concentrated in the large aggregates along with protein. Whereas biofilms did not form in d-amino acid-treated cultures, polysaccharides were still seen associated with the cell surface, confirming that the principal effect of the d-amino acids is to disrupt cell surface protein localization. These results suggest that the mechanism of action of d-amino acids may be similar across dissimilar bacterial species.
S. aureus is a leading cause of hospital-acquired infections (12, 17). Many of the problems associated with this pathogen stem from its capacity to form biofilms. The apparently ubiquitous nature of the effects of d-amino acid exposure is promising for applications in preventing biofilms in medical and industrial settings. Specifically, the ability to control the release of d-amino acids from device surfaces, such as implant coatings or catheter walls, to inhibit the formation of biofilms would significantly reduce the difficulty and cost associated with keeping these devices in place. The experimental procedure to evaluate the effectiveness of surfaces impregnated with d-amino acids is illustrated in Fig. 6A. The effects of d-amino acids on biofilm growth from impregnated substrates were identical to those on biofilms grown from cultures exposed to d-amino acids in the growth medium. Biofilms formed normally on glass surfaces, which should not absorb d-amino acids (see Fig. S9 in the supplemental material), demonstrating that the effect of the d-amino acids was a result of controlled release from the polymer substrate. Lacking the protective properties of a mature biofilm, these adhered cells are likely more susceptible to antimicrobial agents such as antibiotics, which can be used to treat bacterial infection more easily.
We thank D. A. Weitz and the Harvard Materials Research and Engineering Center (DMR-0213805) for the use of their confocal imaging facilities and M. Gilmore for strains MN8, NCTC 10833, and RN4220.
I.K.-G. is a postdoctoral fellow of the Human Frontier Science Program. This work was supported by NIH grants to R.K. (GM58213) and R.L. (GM18546), as well as grants from the BASF Advanced Research Initiative at Harvard University to J.A., R.K., and R.L.
↵† Supplemental material for this article may be found at http://dx.doi.org/10.1128/JB.05534-11.
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text:
Blackbird Song
by Randy Lundy
Published by University of Regina Press
Review by Shelley A. Leedahl
$19.95 ISBN 9-780889-775572
It's been a fair while since the poetry-reading public's heard from writer and University of Regina (Campion College) professor Randy Lundy, but the outstanding blurbs on his third poetry collection, Blackbird Song, will definitely whet the appetites of his fans, and they should draw several new readers to these spare, contemplative poems scored with birds, prairie memories, and the moon in many different incarnations. Top Canadian poets like Lorna Crozier ("Wow, I say again and again"), Patrick Lane (he includes Lundy among "the masters"), and Don McKay ("visionary") sing sweet praises, and Linda Hogan writes that these poems "are grounded constellations created of fire and ice". When senior poets' blurbs are poetry in and of themselves, you know you're doing something right.
And Lundy is certainly doing something right. Firstly, he's turning inward, and asking questions both of himself and the universe that may be unanswerable, ie: "are you waiting for the appearance of that something whose appearance/would be its own vanishing?". He's creating unique images and juxtaposing words in fresh ways. Some of these poems are brief and reminiscent of haiku. Many are odes: to lovers; to "bread fresh from the oven" and the hands that prepared it; to trees across the seasons, and to ancestors. The poet recalls the strong women in his family, including grandmothers "who skinned trapped animals, tanned hides; and cut the/throats of sheep to let them bleed out".
The book's divided into three sections, and as the title and elegant line art cover- image of a blackbird suggest, birds predominate. In the opening piece, "January," we read that the author's mother, "exists for me/the way the owl/perches/on black spruce". We find birds in similes ("Night comes swiftly like the wing of a blackbird") and metaphors, ie: a great grey owl is a "low-winter-snowcloud" – this is the kind of writing that's earned Lundy such brilliant kudos. I love his north-returning geese, "dragging their shadows".
These are also poems of place: the Cypress Hills, Buffalo Pound Lake, and the moon – yes, the moon, or "night sun," is perhaps Lundy's best-described domain. He treats us to a "hand-drum-full-moon," and the "Birchbark-silver peel of a waning/almost-gone-now moon".
Reading these quiet (and sometimes self-deprecating) mediations is akin to hearing the poet think out loud – indeed, the words think or thinking appear in several of these poems; even the mountains are "thinking themselves into being./Thinking magma-flow, thinking/the liquid fire at the core of/everything," and a winter elm tree's engaged in "Deep thinking at the core". Readers should also engage in the thinking these poems inspire: read the pieces slowly, perhaps sit with them individually. Savour the images. Like the red-winged blackbird on the cover, these poems are most effective when given adequate space.
But take the poet's sage advice, too: "Try not to think. Try the meditation of heart-mind. If you listen/closely, you will hear the oxidized hinges on the doors of perception/squeak, opening and closing, swinging an inch or two, in the just-now rise of wind".
THIS BOOK IS AVAILABLE AT YOUR LOCAL BOOKSTORE OR FROM THE SASKATCHEWAN PUBLISHERS GROUP WWW.SKBOOKS.COM
Tags: Poetry, Randy Lundy, Shelley A. Leedahl
← I Tumble Through the Diamond Dust breathing at dusk →

redpajama_set_name: RedPajamaCommonCrawl


Alexis Manigo, like most 16 year olds, desired to have her own money. She applied for a job. When the hiring manager asked for documentation, that's when her life began to unravel. Everything she thought and knew about herself was a lie.
Would you sacrifice economic equality for social justice?
What shall be done with the colored people?
This man was the best inland pilot on the coast. He defied the traditions and stereotypes of the time and dispelled the rumors of the Civil War that exist to this very day.


Even though spring seems to be finally here I love my once a week comfort food dessert and Crumble a classic School Dinner Dessert is my favourite. There are so many different ways to make it but the one that we seem to make through the year is this Delicious Bramley Apple and Sultana Crumble. I love just plain apple crumble but the cinnamon and the sultana's really make this version a little extra treat than just plain apples. I like to use either our classic Crumble Topping or our Oaty Crumble which I will be sharing soon.
We have included affiliate links to some of the ingredients and resources we have used to make this recipe. If you purchase via the links we may earn a small commission.
Make the Basic Crumble Topping according to our instructions.
Peel, core and cut into cubes 2 large Bramley apple.
Place in the bottom of the pie dish.
Sprinkle with the ground cinnamon and Sugar.
Pour the Crumble Topping over the top.
Place in the oven for around 30 minutes until the top is golden.
Scroll down for a printable version of this recipe to add to your recipe folder.
Best served with vanilla ice-cream or natural bio yoghurt.
When an item can be used for multiple purposes in my kitchen I'm always happy. I have a set of different sized Oval Pyrex dishes that pretty much get used for most things like our Shepherd's Pie, Lasagne, Chocolate Bread and Butter Pudding and any time I make a Crumble.
A peeler and corer are the other essentials it makes it easier for my kids to join in preparing the dessert as well. This apple and avocado set is an updated version of the one that I have and probably the best item in it is the apple slicer – so many snack times made easier using one of these!
I love a pop of colour at the table and these colourful bowls are perfect for cereal in the morning, dessert throughout the day and look good enough for when we entertain as well. I love the unusual shape of them too!
Classic family dessert with a twist this Bramley apple crumble is easy to make and best served with some vanilla ice-cream or to compliment the sweetness of the apples some natural yoghurt.
Peel, core and cut into cubes 1 large bramley apple.
Find the ingredients and recipe for your basic crumble topping here.
Such a delicious crumble recipe with easy to follow directions! Thank you for the awesome recipe.
Crumbles are my favorite because they are so ridiculously easy to make! No messing around with pie crusts or anything tricky! So delicious!
What a yummy crumble recipe! I brought it to a family gathering and everyone enjoyed it. Thanks so much for sharing this fabulous homemade goodness!


I have been super busy since I posted 2 days ago!!
I finally finished a cuff that I've been working on for around 2 weeks while we were moving. I was super stumped for a name so asked my Lovely FaceBook friends for their input and was given the name "Emerald Empress" which I thought was an awesome name for it.
I was in a bit of an emotional turmoil at the time and couldn't figure out whether I was coming or going and this was the result. The sides of the cuff are ALMOST identical but opposite, and it's like looking in a warped mirror.
I also finished a hair barrette today, which was nice and easy for a change.
The Barrette is called "Deep Purple" and I am quite please with the end result of my "quick" project.
My car died on me the other day….literally, blew the engine, it was covered by warranty BUT my warranty company decided it was too expensive to replace the engine on the car and said they would give me another car to replace it…….NOW that's excellent……except……the dealership is a 2 hour drive away, I have no money, and I have no car to get there…..One of Hubby's friends has kindly offered us his car BUT we still need money to put petrol in his car to get there and money to put petrol in the new car to get home…….
After you have ranted about my sale, come back to my blog, pop a link on the page to where you did it, and go in the draw which will be drawn this Saturday the 1st of September.
The Coupon Code for the sale is BLOGSALE and the discount amount is 25% off….and remember, the more you share and talk about this, the more likely I am to do another giveaway LOL!!!
Ok due to being on an iPad and using the Facebook app, I can't post links, but I WILL tell you where I posted: on my personal profile, on the EBEG public page, and on my ABeadedWorld page :) we're friends, we're both part of EBEG and I'm pretty sure you've liked my beading page :) So hopefully you can find the links.
I came to follow your blog!!It's lovely.I just find it!!
I will spread the word!
Hi All, The winner of the lovely ring is number 1….ABeadedWorld.
Meg I already have your address so I'll forward it off to you on Monday.


text:
Sneakers give art a run for its money at first-of-a-kind Sotheby's auction
NEW YORK (Reuters) – Move over Monet. Nike is hot on your heels.
Sotheby's in New York announced on Thursday its first-ever auction dedicated to sneakers, underlining their fast-growing status as collectibles able to command tens of thousands of dollars.
Sotheby's is teaming up with streetwear marketplace Stadium Goods to auction 100 pairs of the rarest sneakers ever produced, including a sample of one of the first Nike Inc running shoes with a pre-sale high estimate of $160,000.
The Nike "Moon Shoe" is one of only 12 pairs created. It was designed by Nike co-founder and track coach Bill Bowerman for runners at the 1972 Olympics trials and the pair up for auction is handmade, Stadium Goods said.
Other sneakers include 2011 and 2016 versions of the "Back to the Future Part II" limited-edition shoes by Nike that were inspired by the 1989 film starring Michael J. Fox.
The 2016 version of the futuristic shoe, complete with self-lacing technology, is expected to sell for between $50,000 and $70,000.
"We've long talked about how sneakers are this generation's luxury fashion, and being able to collaborate with a brand with the history and esteem of Sotheby's is further proof of that," John McPheters, co-founder of New York-based Stadium Goods, said in a statement.
Other shoes in the online sale, beginning on Thursday and ending on July 23, include sought-after and limited-edition sneakers produced by Adidas, Air Jordan and rapper Kanye West's Yeezy collection.
Noah Wunsch, global head of eCommerce at Sotheby's, said the sneaker sale was bringing together "art, culture and fashion" and marked another step in the auction house's expansion of offerings of highly coveted luxury goods.
The shoes are on public exhibit at Sotheby's in New York through July 23.
The highest price fetched at public auction for sneakers is thought to be $190,373 in 2017 for a pair of signed Converse shoes said to have been worn by Michael Jordan in the 1984 Olympic basketball final. The shoes were auctioned through California sports memorabilia company SCP.
(Reporting by Jill Serjeant in Los Angeles; Editing by Peter Cooney)
Self-Taught Artist Creates Hybrid Photo-Drawings To Mess With Your Brain (New Pics)
This Remote Resort Offers You The Chance To Sleep On A Net Over The Ocean For $400 A Night
People Are Sharing Pics Of Their Sweet Dogs Turned Into Werewolves With This Muzzle From Amazon


The Washington Post reported last week that "for the first time in at least 50 years, a majority of U.S. public school students" in pre-kindergarten through 12th grade live in poverty. In Maryland, 43 percent of students live in poverty. In Virginia, 39 percent. In the District of Columbia, the poverty-rate for school-aged children is an alarming 61%. Read more about why this matters and what Junior Achievement of Greater Washington is doing to address this critical issue.


text:
Draft Info
Eagles History
Practice Squad
Eagles Dominate the Titans
Posted: December 4th, 2022 | Author: Tommy Lawlor | Filed under: Philadelphia Eagles | 3 Comments »
The Eagles closed out the month of October with a 35-13 win over the Steelers. That was a dominant performance. Over the ensuing four games, the Eagles were erratic. They would play good on offense or defense, but not both. Special teams went from bad to mediocre. The team went 3-1 in that stretch, but some started to question how good the Eagles were.
On Sunday, they answered emphatically. The Eagles beat the Titans 35-10. The game wasn't even that close. The Eagles outgained Tennessee 453 to 209. When you factor in sacks, the Titans didn't gain a yard in the third quarter. The difference in the two teams was obvious.
Going into the game, the big worry was how the Eagles would stop Derrick Henry. That turned out to be a non-issue. Henry had no room to run and finished 11-30. The DL did a good job of clogging the running lanes. The secondary flew up aggressively in run support.
No run game meant the pressure was on Ryan Tannehill and the passing game. Spoiler alert…that didn't go well. Tannehill made some plays with his legs and that might have stayed an issue, but Brandon Graham sacked him and fell on Tannehill's ankles. Tannehill wasn't the same after that. The Eagles DL flew off the ball and ended up sacking him six times.
https://twitter.com/Eaglesfans9/status/1599500070579159040
This was the best defensive performance since the beginning of the year. Amazingly, they did this without taking the ball away. One of the real keys was good tackling. Eagles DBs have been erratic at times this year. James Bradberry thinks run defense is optional. I knew the defense would play well when he came in aggressively on an early run and made a physical tackle. Marcus Epps and Reed Blankenship were strong, physical tacklers.
Last week the Eagles ran for 363 yards and scored 40 points. On Sunday the Eagles only ran for 67 yards. They scored 35 points and played backups for much of the fourth quarter. How? Jalen Hurts led a dynamic passing attack, throwing for 380 yards and 3 TDs. AJ Brown and DeVonta Smith each went for over 100 yards on the day. Why run when you can throw like that?
The @Eagles are the first @NFL team to throw for 350+ yards after rushing for 350+ yards the previous week since the 1987 Los Angeles Raiders (356 rushing on 11/30/87; 360 passing on 12/6/87). #FlyEaglesFly
— John Gonoude (@john_gonoude) December 4, 2022
That is a crazy stat. It shows you how versatile and dynamic the offense is.
Hurts was a little sloppy early on, but then he settled in and shredded the Titans secondary. Smith ran great routes and got open consistently. Brown made some impressive contested catches. This play was wild.
https://twitter.com/NFL/status/1599495473194147840
I'm not sure what was better, the throw or the catch. Brown had no separation. He just put his hands up at the last second and secured the ball. Hurts dropped that one in the bucket, as the saying goes. He gave AJ a chance to make a play and that's just what happened.
Hurts sliced and diced the Titans in part because he had great protection. The gamebook only shows three QB hits. Hurts did run for a TD, but did very little running. He got the ball to his receivers and let them make plays.
Maybe the most surprising part of the game was the Eagles STs units. They were…good. Britain Covey had punt returns of 20, 16, 27 and 25 yards. He put the offense in good field position a couple of times. Covey got good blocking and that gave him room to run.
LB Christian Elliss played his first game of the year and made an instant impact on STs. He had two tackles, both big hits. That seemed to bring some juice to a unit that desperately needed it. Nakobe Dean also had a big hit on STs. Dean then had to come in the game on defense when Kyzir White got banged up. I thought Dean looked good. He finished with 5 tackles and a TFL.
There weren't any major injuries. Quez Watkins did hurt his shoulder.
Eagles WR Quez Watkins said "I should be fine" when asked about his shoulder injury.
— Jeff McLane (@Jeff_McLane) December 4, 2022
That is great to hear.
The one negative in this game was penalties. The Eagles were flagged 12 times for 80 yards. A couple of those were questionable, but most were legit. There were a lot of false starts on the OL. I have no idea what was going on, but it was highly frustrating. Luckily the Eagles overcame the festival of flags. In a different game, that might have really hurt them.
Tennessee came into the game at 7-4. Their defense was 7th in points allowed. No team had scored more than 20 points on them since September. The Chiefs scored 20 against them a few weeks back and that game went to overtime.
Seeing the Eagles score 35 and make it look easy at times was crazy. This offense can be special.
The Eagles are now 11-1.
They just keep winning.
3 Comments on "Eagles Dominate the Titans"
1 The Linc - A.J. Brown dominates in his revenge recreation - Philadelphia News Station said at 10:07 AM on December 5th, 2022:
[…] Eagles Dominate the Titans – Iggles BlitzThis was the very best defensive efficiency because the starting of the yr. Amazingly, they did this with out taking the ball away. One of many actual keys was good tackling. Eagles DBs have been erratic at occasions this yr. James Bradberry thinks run protection is non-obligatory. I knew the protection would play properly when he got here in aggressively on an early run and made a bodily sort out. Marcus Epps and Reed Blankenship had been robust, bodily tacklers. Final week the Eagles ran for 363 yards and scored 40 factors. On Sunday the Eagles solely ran for 67 yards. They scored 35 factors and performed backups for a lot of the fourth quarter. How? Jalen Hurts led a dynamic passing assault, throwing for 380 yards and three TDs. AJ Brown and DeVonta Smith every went for over 100 yards on the day. Why run when you'll be able to throw like that? […]
2 Eagles News: AJ Brown dominates in his revenge game - Tnspills said at 12:20 PM on December 5th, 2022:
[…] Eagles Dominate the Titans – Iggles BlitzThis was the best defensive performance since the beginning of the year. Amazingly, they did this without taking the ball away. One of the real keys was good tackling. Eagles DBs have been erratic at times this year. James Bradberry thinks run defense is optional. I knew the defense would play well when he came in aggressively on an early run and made a physical tackle. Marcus Epps and Reed Blankenship were strong, physical tacklers. Last week the Eagles ran for 363 yards and scored 40 points. On Sunday the Eagles only ran for 67 yards. They scored 35 points and played backups for much of the fourth quarter. How? Jalen Hurts led a dynamic passing attack, throwing for 380 yards and 3 TDs. AJ Brown and DeVonta Smith each went for over 100 yards on the day. Why run when you can throw like that? […]
3 Eagles News: A.J. Brown dominates in his revenge game said at 2:27 PM on December 5th, 2022:
Game Preview – SF at PHI
Scouting the Niners
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Opposite Directions
Over the past five weeks, the Eagles are 2-2-1. The losses came in close games against the Steelers and Ravens, two of the best teams in the league. The Cowboys are 1-4 in that same span. Two of the losses … Continue reading →
Yeah, But…
The Eagles are in first place. Carson Wentz is heating up. Travis Fulgham is legit. The defense just came up with three takeaways and sealed the win over the Giants on Thursday night with a huge play. Yeah, but… The … Continue reading →
More Roster Additions
Roster Move: #Eagles have signed free agents: WR Rashard Davis, G Darrell Greene, CB D.J. Killings, S Tre Sullivan, WR Bryce Treggs, WR Greg Ward — Philadelphia Eagles (@Eagles) February 7, 2018 Davis was a dynamic PR in college. It … Continue reading →
Harold Carmichael Gets Honored
Former Eagles WR Harold Carmichael was recently honored. Congratulations to #Eagles legend Harold Carmichael on his induction into the @BCFHOF! pic.twitter.com/GHEIvvyRjv — Philadelphia Eagles (@Eagles) February 11, 2018 Carmichael was a star player for Southern University before being drafted in … Continue reading →
Early Additions
The Eagles added some young players to challenge for 2018 roster spots. P Cameron Johnston TE Adam Zaruba CB Elie Bouka WR Marquess Wilson S Harold Jones-Quartey C Jon Toth TE Joshua Perkins Zaruba could be a player to watch. … Continue reading →
DeSean Update
DeSean Jackson signed a big deal with Tampa in the offseason. Expectations were sky high for him and the Bucs. Jameis Winston has a strong arm and Mike Evans draws plenty of double teams. Jackson is off to a slow … Continue reading →
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Choose one or multiple applications for your workflows.
The procure-to-pay app for finance and purchasing departments.
Employee expense management made easy.
Set up layered checklists for recurring tasks.
Customized solutions to automate your unique workflows.
Validation & recognition for invoices.
Looking for a platform to build your own workflows?


eChannelling PLC, the pioneer and largest doctor channelling network in Sri Lanka, announces its partnership with Lanka Hospitals PLC, the most accredited hospital in Sri Lanka, to offer a new and unique Self-Help Kiosk Machine, which was inaugurated by Dr. Sarath Paranvithana, Chairman – Lanka Hospitals, along with Mr. P. G. Kumarasinghe Sirisena, Chairman – Sri Lanka Telecom and Mobitel in the presence of staff and patients recently.
For the first time in Sri Lanka, customers can now channel doctors via the Self-Help Kiosk Machine with ease. The easy-to-use Self-Help Kiosk Machines are available at Lanka Hospitals, and can be operated by patients/customers without any hassle to make appointments. This new service will not only enhance convenience, but will also serve to increase productivity of both eChannelling and Lanka Hospitals.
This is especially an ideal option for walk-in patients or customers who presently channel doctors through channelling counters at Lanka hospitals. The Self-Help Kiosk Machines will do away with the need to stand in long queues at no extra cost.
Patients can also make appointments via eChannelling by dialing 225 from any mobile network and 1225 from an SLT phone. Appointments can also be made through the eChannelling Mobile App or through www.echannelling.com.
(From Left) Mobitel Chairman Mr. P. G. Kumarasinghe Sirisena and Lanka Hospitals Chairman Dr. Sarath Paranavithana unveiling the Self-Help Kiosk Machines at Lanka Hospitals.


text:
Pint-Sized Stories: The Christmas Party
Chloe Choi and Luka Ardon, Centerspread Editors • December 16, 2022
The Marvelous Ms. Mog
Sophie Sun, Reporter • December 16, 2022
Angela Mogilefsky, English teacher and BSU advisor nicknamed "Ms. Mog", was born in Evanston, Illinois, but Mogilefsky's father received a job offer in Washington when she was one year old. So, the...
Sophie Stoddart, Reporter • December 15, 2022
Concerts with a Camera
Student finds passion in concert photography
Luka Ardon, Centerspread Editor • December 15, 2022
Denzel Curry, Kid Cudi and Metro Boomin. What do all of these rappers have in common? They have been photographed by senior Damon Pourmohsen. "I got into photography kind of by accident. I had always...
Exchange student speaks on her experience at PVHS
Elsa Sjo is an exchange student from Sweden and is currently a junior here at PVHS. She grew up in Norrkoping, Sweden and will be staying at PVHS for one year, continuing to pursue her interests. "I...
What is the Human Rights Coalition?
Sierra Namvari, Photography Editor • December 15, 2022
The Human Rights Coalition at PVHS was formed many years ago in order to bring together various clubs, all with the objective of encouraging diversity and supporting the fight against discrimination. The...
New Club Highlights Jewish Traditions and Culture
Olivia Kao, Reporter • December 15, 2022
As a wave of new clubs arise this year, one particular club, the first of its kind, celebrates and brings awareness to Jewish culture on campus. With no apparent club surrounding Jewish culture,...
PVHS Hosts Private School Shadow Day
Lucia Ruiz, Editor-in-Chief • December 15, 2022
On Dec. 7, students from local private schools enjoyed the annual Private School Shadow Day, during which ASB provided students a glimpse into the campus culture through tours, classroom sit-ins, and activities...
From Touchdowns to Theater
Josh Munoz's journey to acting
Eva Mayrose, Opinion Editor • December 15, 2022
Having been a football star for the majority of his high school career, theater would seem to be the last place that senior Josh Munoz would fit in. Though Munoz definitely made good memories with...
Pint-Sized Stories: Friendsgiving Dinner
Chloe Choi and Luka Ardon, Centerspread Editors • November 10, 2022
Mrs. Salgado Does it All: Teaching, Training, Parenting
Kelly Donahue, Features Editor • November 10, 2022
Only her second year on campus as a teacher, Marissa Salgado does it all. Many students are familiar with her, whether they have had her as an anatomy or biology teacher, or have seen her in the...
Growing Up, What Was Your Favorite TV Show?
Zara Deen, Reporter • November 10, 2022


text:
Kaspika
Caspian Seals Conservation Agency
THE CASPIAN EXHIBITION
On determining the age of Caspian seals (Pusa caspica)
22/05/2020 29/06/2020 Kaspika 0 Comment determination of age, Kaspika, mortality, Phoca caspica, Pusa caspica, reason for mortality, the Caspian, the Caspian Sea, the Caspian seal, the Institute of Hydrobiology and Ecology
© 2019. Zh.A. Sydykova. Institution "The Institute of Hydrobiology and Ecology", Scientific and Production Center of Fisheries, LLP; e-mail: zh_sydykova@ihe.kz
The determination of age is essential for learning many aspects of animal biology and is carried out with comparative anatomical and morphological studies in the field of systematics and population variability; it allows establishing the reproduction rate, individual life span, and the age composition of the animal population. This, in turn, allows assess the relative numerical state of the population, which is important for regulating fishing and establishing a strategy for the conservation of valuable animal species (Klevezal, 1967).
The Caspian seal is the only marine mammal in the Caspian, endemic to this sea. Since 2008, the Caspian seal has been on the Red List of the International Union for Conservation of Nature with Endangered status. Caspian seals belong to pagophilic animals and during the breeding season they gather on the ice formed in the northern and northeastern parts of the sea. With the onset of spring and the disappearance of ice, part of the seals, which did not successfully molt, form large preconnubia – rookeries on islands and sand islands – underwater shoals located in the shallow zones of the north and north-eastern parts of the Caspian. There are small rookeries in the Middle and Southern Caspian also. The most complete data on the age composition of seals on rookeries date back to the 30-40s of the last century (Badamshin, 1950).
The largest casts of dead seals in the Caspian took place from the end of the 20th to the beginning of the 21st century, when the number of dead animals was tens of thousands. Mortality occurs for a number of reasons (pollution of the sea, diseases, by-catch in fishing nets, and others). In the last decade, corpses of seals found on the coast of the sea are estimated to be hundreds of individuals. Determining the age composition of dead animals is important for calculating the loss and predicting the demographic status of the Caspian seal population.
T.M. Eibatov (1986) studied in detail the macromorphology and microstructure of permanent teeth, established the tooth formula, described the area of the first annual layer and determined the age of Caspian seals. S. Wilson and coauthors (2014) analyzed the mortality of the Caspian seal for the period of 1971–2008, using data including age, body condition, pathology, and concentrations of organochlorine compounds in corpses from 1997 to 2002.
In recent years, the largest cast of dead seals on the coast in the Kazakhstan area of the Caspian Sea occurred in the spring of 2017. According to official data, the number of dead seals was about 300 individuals. To assess the age composition, fangs were taken from 67 dead animals in the Kalamkas area and the western part of the Tyub-Karagan Peninsula. For this work, a random subset of 36 fangs of different species was compiled.
Dental decalcification was carried out on the basis of an acid agent (nitric acid). The manufacture of histological preparations was carried out by generally accepted methods.
The length of dead seals from the nose to the end of the tail in the subsample was 75 to 139 cm, the sexual composition showed an excess of 2.17 times the number of females. The age composition was in the range from 0+ to 26 years, including: up to 1 year – 33.3%, 1-2.8%, 2 -2.8%, 3-11.1%, 4 – 11.1%, 5 – 13.9%, 6 – 8.3%, 7 – 5.6%, 8 -2.8%, 12 – 5.6%, 26 – 2.8%.
Scientific Adviser: M.T. Baymukanov, Ph.D. (Biology).
To download the abstract in Russian: Sydykova, 2019.
Photo by M.T. Baimukanov, the Director of the Institute of Hydrobiology and Ecology (Irgely, Kazakhstan). The Caspian seal. The Komsomolskiy Bay, spring, 2016.
← Caspian seals empathize with each other
On illegal sealing of Caspian seals →
Кратко / Briefly
Новости / News
IPEE RAS expedition has returned from Dagestan
22/12/2020 Kaspika 0
The IPEE RAS expedition has returned from the Dagestan coast of the Caspian Sea with collected materials to find out the reasons for the mass
Scientists from Moscow are finding out reasons for the death of seals
The Caspian seal, Autumn, 2020
The Caspian seal has been inscribed into the Red Book of Kazakhstan
The Kazakhstani expedition
A large batch of sturgeons was seized in Kazakhstan
Border guards rescued 43 Caspian seals
The survey on Maly Zhemchuzhny Island
The first patient
Some news of the Russian Federation Government
The Caspian seal: to be silent is impossible
Dangerous conditions for the survival of Caspian seals
Seal migration tracks are being observed with satellite tags
International Economic Forum Caspian Dialogue, 2019
The Caspian seal has disappeared from Maly Zhemchuzhny
The Caspian seal might be inscribed into the Red Book of Russia
Caspian Seal Research and Rehabilitation Centre in Kazakhstan
Мы / About us
Агентство по спасению каспийских тюленей – некоммерческий, общественный проект. Не радикалы, не агенты, не противники нефти; нам совершенно не нравится, когда природоохранную деятельность превращают в экономический или политический инструмент. Мы просто хотим спасти нашего тюленя, который вот-вот исчезнет. Сохраним его – сохраним и Каспий. Только так.
Our agency for the conservation of Caspian seals is a non-commercial public project. We are not radicals, not agents, not against oil production; we do not like it when environmental protection is turned into an economic or political tool. We just want to save our seal, which is about to be extinct. If we save the seal, we will save the Caspian Sea. This is the only way.
E-mail: kaspika@list.ru
YouTube: KASPIKA TV
ПОМОЧЬ ПРОЕКТУ ☘
Copyright © 2021 Kaspika. All rights reserved.


text:
Q: How to pass tibble of variable names and function calls to tibble I'm trying to go from a tibble of variable names and functions like this:
N <- 100
dat <-
tibble(
  variable_name = c("a", "b"),
  variable_value = c("rnorm(N)", "rnorm(N)")
)

to a tibble with two variables a and b of length N
dat2 <-
  tibble(
    a = rnorm(N),
    b = rnorm(N)
  )

is there a !!! or rlang-y way to accomplish this?

A: We can evalutate the string
library(dplyr)
library(purrr)
library(tibble)
deframe(dat) %>%
      map_dfc(~ eval(rlang::parse_expr(.x)))

-output
# A tibble: 100 x 2
         a       b
     <dbl>   <dbl>
 1  0.0750  2.55
 2 -1.65   -1.48
 3  1.77   -0.627
 4  0.766  -0.0411
 5  0.832   0.200
 6 -1.91   -0.533
 7 -0.0208 -0.266
 8 -0.409   1.08
 9 -1.38   -0.181
10  0.727   0.252
# … with 90 more rows

A: Here is a base way with a pipe and a as_tibble call.
Map(function(x) eval(str2lang(x)), setNames(dat$variable_value, dat$variable_name)) %>%
  as_tibble


text:
US should hike the gas tax to help fix crumbling roads, says ex-GM vice chair
Published Wed, Jan 31 20186:19 PM EST Updated Wed, Jan 31 20187:40 PM EST
Kellie Ell@KellieAutumnEll
Raising the federal gas tax is an investment for the economy, says Bob Lutz.
"We've got the cheapest gasoline in the civilized world," he says. "Nobody's even going to notice it," he says.
It's been more than two decades since the last federal gas tax hike.
American highways are on average more than 28 years old, Lutz says.
Any investment in infrastructure should include technology: Former Transportation Secretary
Squawk Alley
Repairing an aging infrastructure is worth the price of gas tax hikes, said Bob Lutz, CEO of VLF Automotive, an American-based automotive company.
"We've got the cheapest gasoline in the civilized world," Lutz told CNBC on "Squawk Alley." "A nickel here or a dime there, with the weekly fluctuations in gasoline prices, nobody's even going to notice it."
The statement came a day after President Donald Trump made his first State of the Union address, where he talked about his proposed $1 trillion to $1.7 trillion infrastructure program to rebuild America's roads, bridges and railroads that "this country so desperately needs."
Lutz, a former vice chairman of General Motors, said he, like the U.S. Chamber of Commerce, supports raising the federal gas tax in order to fund the investment. Earlier this month the Chamber promoted a gas-tax increase of 5 cents per year over the course of five years.
A tax increase of 5 cents would raise the current average price per gallon to about $2.64 for gasoline and about $3.03 for diesel, according to AAA.
Money raised from the tax is allotted to the Highway Trust Fund. But critics, including some GOP leaders, argue that not all of the money collected from the tax is actually put in the fund.
The last tax hike was in 1993, during the first year of the Clinton administration. It increased the gas tax by 4.3 cents, bringing the total tax to 18.4 cents per gallon for gasoline and 24.4 cents for diesel.
Rodney Slater, who served as Transportation secretary from 1997 to 2001 under President Bill Clinton, said money raised from the 1993 tax hike was first used to balance the budget.
It wasn't until 1997 that money from that increase was put into the trust fund and used for smart roadways and to make GPS available to civilians, Slater said Wednesday on "Squawk Alley."
"That's been 20 years," said Slater, who agreed investments in infrastructure are needed. Funds raised from the 1993 tax hike have largely been eroded, he said.
"We've gone a number of years where we've gone without investing in our infrastructure as we need to," Slater said.
That infrastructure, Lutz said, includes American highways that are more than 28 years old on average.
"A crumbling infrastructure like that, whether it's roads, bridges or whatever, is a drain on the economy," Lutz said. "It causes problems. It slows transportation, [and] it creates accidents."
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