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I love reproduction prints, especially the fun you can have fussy cutting.
I was also using a Milliners No 11 needle, recommended to place less stress on the hands while sewing. I have reverted back to a small sharp. I suppose at the end of the day, it relies on what you feel comfortable using and how it will impact on the way you piece.
I like the fabric in these flowers.
The last of the flowers glued ready to be sewn. Now to the fun part.
Love your hexagon flowers and am about to start to make some of my own. Thanks so much for your tutorials.
I love your hexagon flowers. Thanks for your tutorial and I cant wait to start making some of my own little hexie flowers.


text:
You are here: Home / Review of "The Death of Expertise: The Campaign against Established Knowledge and Why it Matters" by Tom Nichols
The following review was published in Integrated Environmental Assessment and Management, August 2017
Tom Nichols' recent book on the increasing disconnect between experts and laypeople is quite popular, judging from its current (June 2017) No. 1 ranking in the "Philosophy/Epistemology" section of amazon.com. Not entirely surprising – the current political climate makes the topic resonate with intellectuals (aka "experts") across the board. The book is very accessible and it is a highly entertaining read. It explores why "people have had enough of experts", to quote Michael Gove, the former British Secretary of State for Education, and why it matters. This is of course not a new topic, but it has gained such incredible momentum that it now poisons the public debate on basically every relevant issue.
Central to the book is the thesis that experts in the US are more and more denigrated by willfully ignorant and intellectually lazy laypeople, who claim that 20 minutes of googling are easily on par with 20 years of experience on the job because they confuse google-induced gut feeling with actual knowledge. The book is often polemic and sarcastic, sometimes bitter – and it is fortified with a plethora of anecdotes and examples that are sometimes almost too stupefying to believe. For example, half the US population seems to have had a defined view in 2015 on whether or not to bomb the country of Agrabah – which is actually a fictitious land from Walt Disney's film Alladin. Another striking example is Nichols' examination why gourmands blatantly ignore the 2012 report of the Centre for Disease Control (CDC) that drinking raw milk is the equivalent of playing food-driven Russian roulette with children's health. He argues that this might be due to earlier diet recommendations that were retracted in the end – and then drives home the point that experts certainly get it wrong on occasion, but that they still "have a better track record than the average overweight American at keeping people alive with healthy diets". Although all these anecdotes are convincing and certainly entertaining, every now and then I wish that Nichols had dived in a bit deeper and explored the underlying principal causes and societal mechanisms in more depth.
The book examines definitions of expertise, its role in society, the consequences of experts being wrong, their role in political decision-making and the interactions between laypeople, politicians, and experts. Nichols also analyzes the impact of having access to a virtually unlimited amount of largely unvalidated and often conflicting information via the internet and the bubbles of social media. Finally, he discusses the inability of established media outlets to fact-check on a broader scale and their failure to focus on news actually worth reporting, instead of relentlessly click-baiting our lowest instincts. In particular, Nichols enjoys grinding his ax with the American education system, concluding that "'Going to college' is, for many students, just one more exercise in personal self affirmation." Not only the notorious Halloween incident at Yale University in 2015, but also very recent events at Evergreen College in Washington State seem to support the author's conclusions.
Nichols finally concludes that "The abysmal literacy, both political and general, of the American public is the foundation for all of these problems." and that, consequently "Americans have increasingly unrealistic expectations of what their political and economic system can provide. Unable to comprehend all of the complexity around them, they choose instead to comprehend almost none of it and then sullenly blame experts, politicians, and bureaucrats for seizing control of their lives." I often found myself enthusiastically nodding while reading, accompanied by a sinking feeling of despair.
The book analyzes the issue from a US perspective, which made me wonder whether we Europeans entertain a more fact-oriented, intellectually more honest public discourse. I have not yet made up my mind completely, but following the British Brexit debate certainly does not spark optimism. Perhaps we should simply use the current appalling state of affairs in the US, the UK and elsewhere as a compass pointing south, in order to work towards a more fact-based political debate, advised by experts.
Unfortunately, the book's concluding chapters are too often mere repetitions of what was already presented in earlier chapters. Every now and then they provide additional insights on why things are as bad as they are, but they offer no convincing suggestions on how we could drag ourselves out of the swamp.
In the end, Nichols' book calls for lifelong learning, asks us to respect other people's expertise and requests that we acknowledge that our society is crucially dependent on expert knowledge and action. One can only hope that the book helps to spread these crucial messages. Although, given that the book is written by an obvious expert, it might be largely ignored by those who would gain most from reading it.
Finally, two recommendations for further reading, which I came across while trying to find some way out of this mess: "More professionalism, less populism: How voting makes us stupid, and what to do about it" by Jonathan Rauch and Benjamin Wittes from the Center for Effective Public Management at Brookings (2017, free download at https://www.brookings.edu/wp-content/uploads/2017/05/more-professionalism-less-populism.pdf) and "Post-Truth – the new war on truth and how to fight back" by Matthew d'Ancona (Ebury Press, 2017).

redpajama_set_name: RedPajamaCommonCrawl


text:
Q: Is there an efficient way to iterate through an avro schema? I would like to be able to iterate through and access the 'name' field values of an avro schema but have not been able to find an efficient way of doing so without getting extra values due to the particular way avro expects its schema data.
I can recursively iterate through it as though it were a js object; however, I end up with certain fields I did not want being included in my results.
For example, in the below code the only value I want to get back is 'foobar' however I also get 'Foo' which I do not want as that is the name of an array of objects rather than a single value.
{
          "type": "record",
          "name": "Foo",
          "fields": [
            {
              "name": "foobar",
              "type": "string"
            }
          ]
}

The current function I am using looks like this:
  iterateAvro = (target) => {
    let result = [];
    Object.entries(target).forEach(([key, val]) => {
        if (val === null){
          return null
        }
        if (typeof val === 'object'){
          result = result.concat(this.iterateAvro(val));
        } else {
          if(key === 'name'){
            result.push(val)
          }
        }
    })
    return result
  }

I am new to avro (and coding in general) and do not know if there is an avro specific way of doing this. Any help would be appreciated.

A: What you are doing in your function is:

*

*Convert a JavaScript object into an array of key/value pairs.

*Iterating through the pairs and:
a. If the value is null do nothing.
b. If the value is an object, apply this logic to it using recursion.
c. If the key is name push the value to an array called result accessed through a Clojure.

Your function is grabbing any value whose key is name. That is why both foobar and Foo are returned.
Looking at Apache Avro's documentation I see that inside the fields key, there is a list with multiple field objects, each of which must have a name key.
So, assuming that you would like to get the values of all the field names you could do something like this:
// JSON object gotten directly from Apache Avro's documentation.
var avroRecord = {
  "type": "record",
  "name": "LongList",
  "aliases": ["LinkedLongs"],                      // old name for this
  "fields" : [
    {"name": "value", "type": "long"},             // each element has a long
    {"name": "next", "type": ["null", "LongList"]} // optional next element
  ]
}

function getFieldsNames(record) {
  return avroRecord.fields.map((field) => {
    return field.name;
  });
}

console.log(getFieldsNames(avroRecord))
// [ 'value', 'next' ]

I hope this helps.

redpajama_set_name: RedPajamaStackExchange


text:
Expansion of circulating TFH cells and their associated molecules: involvement in the immune landscape in patients with chronic HBV infection
Ting-Ting Hu1,
Xiao-Fei Song1,
Yu Lei1,
Huai-Dong Hu1,
Hong Ren1 &
Peng Hu1
Blood CXCR5+CD4+ T cells are defined as circulating T follicular helper (TFH) cells, which is required for effective humoral immunity. This study aimed to investigate the role of circulating TFH cells in patients with chronic hepatitis B virus (CHB) infection.
The frequency and phenotype of circulating TFH cells were monitored by flow cytometry in CHB patients and in healthy controls (HC). The expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA was analyzed using real-time PCR. Serum HBsAg, HBeAg, HBeAb, HBV DNA loads, ALT and AST were determined. The potential association of the frequency of TFH cells and their surface markers with clinical parameters was assessed.
The frequency of CXCR5+CD4+ T cells was increased in CHB patients and positively correlated with ALT and AST but not with HBV DNA loads. Moreover, an expansion of ICOS-, PD-1-, CD40L-, and IL-21R-expressing TFH cells occurred in CHB patients, but failed to correlate with ALT, AST and HBV DNA loads. Interestingly, the frequency of CXCR5+CD4+ T cells and ICOS+CXCR5+CD4+ T cells was significantly higher in HBeAg positive CHB patients than in HC. Additionally, the percentages of CXCR5+CD4+ T cells were positively correlated with AST, and ICOS-expressing CXCR5+CD4+ T cells were negatively correlated with HBV DNA loads. No significant differences in the frequency of CXCR5+CD4+ T cells were observed between inactive carrier (IC) patients and healthy controls. However, ICOS-, PD-1-, CD40L-expressing TFH cells were increased in IC patients and positively correlated with AST. Furthermore, the expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA in TFH cells was higher in CHB patients than in HC.
These data demonstrate that circulating TFH cells may participate in HBV-related immune responses. In addition to the frequency of TFH cells, the phenotype of these cells plays an important role in CHB patients.
Approximately 350 million people worldwide are carriers of hepatitis B virus (HBV), and half a million to 1 million of these carriers die from liver diseases each year [1]. Therapeutic management of chronic hepatitis B patients can stop or slow the progression of the disease and reduce complications, but it is impossible to eradicate HBV and reverse liver damage [1, 2]. The outcome of infection and the pathogenesis of liver disease are determined by dynamic interactions between the virus and the host immune system [3]. Thus, elucidating the immune mechanisms that underlie these interactions is critical. Previous studies suggested that the innate and cellular immune responses are major contributors to HBV clearance [4]. However, the role of humoral immunity in controlling HBV remains poorly characterized.
Antibody production by B cells is critical for the clearance of pathogens and for the establishment of long-term humoral immunity [5]. T follicular helper (TFH) cells are the major CD4+ T cell subset that is essential for full B cell responses, including germinal center reactions, isotype class switching, and antibody affinity maturation [6]. No unique markers of TFH cells have been reported, and TFH cells are currently defined using a combination of several markers that are directly related to the functions of these cells [6]. TFH cells express large amounts of B cell lymphoma 6 (Bcl-6) [7], which is necessary and sufficient for the development of TFH cells in vivo [8]. Chemokine (C-X-C) receptor 5 (CXCR5) is transiently expressed on CD4+ T cells during their interaction with peptide-MHC, but TFH cells can be distinguished from other T cells by their sustained expression of high levels of CXCR5 [9]. CXCR5 promotes the colocalization of T and B cells [10]. TFH cells express surface molecules that play functional roles in T cell and B cell collaboration, such as inducible costimulator (ICOS), programmed cell-death protein 1 (PD-1), and CD40 ligand (CD40L). TFH cells also secrete interleukin 4 (IL-4) and interleukin 21 (IL-21), which are cytokines that promote growth, differentiation, and class switching in B cells [11].
The unique localization of TFH cells within germinal centers is a fundamental feature of this subset of T cells [12].However, it is difficult to obtain lymphoid tissue from patients for research purposes. Therefore, a surrogate strategy is required to assess the quality of TFH cell responses in humans. CXCR5+CD4+ T cells in the blood may serve as counterparts of TFH cells for this purpose. CXCR5+CD4+ T cells are known as circulating TFH cells; these cells share functional properties with TFH cells and appear to represent the circulating memory compartment of TFH cells [13–15]. In addition, several studies demonstrated that CXCR5+CD4+ T cells derived from both the circulation and germinal centers potently induce antibody production during co-culture with B cells in vitro [14, 16, 17]. The role of blood CXCR5+CD4+T cells in patients with autoimmunity has been explored [13, 14], but little is known about the role of circulating CXCR5+CD4+ T cells in patients with chronic HBV infection. In this study, we explored the frequency and phenotype of circulating TFH cells in patients with chronic HBV infection and examined the potential association of CXCR5+CD4+ T cells with clinical parameters. This study may provide novel insights regarding the role of circulating CXCR5+CD4+ T cells in patients with chronic HBV infection.
Clinical data from subjects in the five groups
Table 1 presents the demographic and clinical characteristics of subjects from the chronic HBV infection and HC groups. A total of 38 patients with chronic HBV infection were recruited, including 17 males and 21 females with ages ranging from 7 to 60 years. The subjects were divided into the following groups according to AASLD guidelines [18]: HBeAg-positive chronic hepatitis B (HBeAg + CHB) (n = 14); immune tolerant carrier (IT) (n = 8); inactive carrier (IC) (n = 10); and HBeAg-negative chronic hepatitis B (HBeAg- CHB) (n = 6). In addition, 12males and 13 females with ages ranging from 23 to 64 years were included as controls. The patients with chronic HBV infection were comparable to the healthy controls with respect to sex and age. All patients with chronic HBV infection were positive for HBV DNA, and half of these patients had elevated levels of ALT and/or AST. Notably, the healthy controls were negative for HBV DNA and had normal ALT and AST levels.
Table 1 The demographic and clinical characteristics of subjects
Significantly increased frequency of CXCR5+CD4+ T cells in patients with chronic HBV infection compared to healthy controls
To determine the potential role of peripheral CXCR5+CD4+ T cells in patients with chronic HBV infection, the frequency of peripheral blood CXCR5+CD4+ T cells within the CD4+ T cell population was monitored by flow cytometry (Figure 1). The percentages of CXCR5+CD4+ T cells were 17.87% (2.95-88.03%) in the chronic HBV infection group and 11.13% (2.92-34.48%) in the HC group. As shown in Figure 1C, the frequency of CXCR5+CD4+ T cells was significantly higher in patients with chronic HBV infection than in the HC group (p < 0.05). To further characterize the frequency of CXCR5+CD4+ T cells in patients with chronic HBV infection, it was necessary to determine whether differences existed between the chronic HBV infection subgroup and the HC group. Interestingly, the percentages of CXCR5+CD4+ T cells were greater in the HBeAg - positive chronic hepatitis B group than in the HC group (p < 0.05) (Figure 1D). In contrast, the frequency of CXCR5+CD4+ T cells in IT, IC or HBeAg- CHB patients was not significantly different from that observed in the healthy controls (p > 0.05) (Figure 1D). Moreover, no significant differences in the proportions of CXCR5+CD4+ T cells were observed among the chronic HBV infection subgroups (data not shown).
Fluorescence-activated cell sorter (FACS) analysis of the frequency of peripheral blood CXCR5+CD4+T cells in patients with chronic HBV infection patients. (A) Gating strategy. (B) The percentage of circulating CXCR5+CD4+ T cells was compared between the two groups. (C) The percentage of CXCR5+CD4+ T cells was significantly higher in patients with chronic HBV infection than in healthy controls (P < 0.05). (D) Comparison of the frequency of CXCR5+CD4+ T cells in the IT, IC, CHB(HBeAg+), CHB(HBeAg-) and HC groups. HC, healthy controls; HBV, patients with chronic HBV infection; IT, immune tolerant carrier; IC, inactive carrier; CHB1, HBeAg-negative chronic hepatitis B; CHB2, HBeAg-positive chronic hepatitis B; PI, propidium iodide. The horizontal lines represent the median values (±SEM).
Increased expression of ICOS, PD-1, CD40L and IL-21R in CXCR5+CD4+ T cells in patients with chronic HBV infection
A significantly higher frequency of CXCR5+CD4+ T cells was observed in the chronic HBV infection group than in the HC group. Thus, it was important to determine whether the expression of markers that are typically associated with TFH cells were altered. TFH cells are distinguished from other cell types by the expression of ICOS, PD-1, CD40L, IL-21R, CXCR5, and IL-21. The phenotype of TFH cells was assessed in this study (Figure 2A). Notably, the expression of ICOS was increased in CXCR5+CD4+ T cells in patients with chronic HBV infection compared to healthy controls (p < 0.05) (Figure 2B). More importantly, the percentages of ICOS+CXCR5+CD4+ T cells were significantly higher in the HBeAg + CHB, IT, IC and HBeAg- CHB groups compared to the HC group (p < 0.05) (Figure 2C). Likewise, differential expression of PD-1 was observed between the patients with chronic HBV infection and the healthy subjects (p < 0.01) (Figure 2D). In addition, the proportions of CD40L+CXCR5+CD4+ T cells and IL-21R+ CXCR5+CD4+ T cells were higher in patients with chronic HBV infection than in the healthy controls (p < 0.01) (Figure 2F, H). Remarkably, significantly higher levels of PD-1+CXCR5+CD4+ T cells, CD40L+CXCR5+CD4+ T cells, and IL-21R+ CXCR5+CD4+ T cells were observed in the IT, IC and HBeAg- CHB groups than in the HC group (p < 0.05) (Figure 2E, G, I). However, no significant difference in the proportions of PD-1+CXCR5+CD4+ T cells, CD40L+CXCR5+CD4+ T cells, and IL-21R+ CXCR5+CD4+ T cells were observed between the HBeAg + CHB group and the HC group (p > 0.05) (Figure 2E, G, I). Further analysis of the chronic HBV infection subgroups revealed no differences between the subgroups (data not shown).
The phenotype of circulating TFH cells was assessed in patients with chronic HBV infection and in HC. (A) The expression of ICOS, PD-1, CD40L and IL-21R by CXCR5+CD4+ T cells were detected by flow cytometry. At least 50,000 events were analyzed for each sample, and the data represent different groups of samples from at least two independent experiments. (B), (D), (F) and (H) Comparison of the percentages of ICOS+CXCR5+CD4+ T cells, PD-1+CXCR5+CD4+ T cells, CD40L+CXCR5+CD4+ T cells, and IL-21R+CXCR5+CD4+ T cells in the chronic HBV infection and HC groups. (C), (E), (G) and (I) Comparison of the percentages of ICOS+CXCR5+CD4+ T cells, PD-1+CXCR5+CD4+ T cells, CD40L+CXCR5+CD4+ T cells, and IL-21R+CXCR5+CD4+ T cells between the IT, IC, CHB(HBeAg+), CHB(HBeAg-) and HC groups. CHB1, HBeAg-negative chronic hepatitis B; CHB2, HBeAg-positive chronic hepatitis B. Each data point represents an individual subject. *, p < 0.05; **, p < 0.01.
Patients with chronic HBV infection exhibited overexpression of BCL-6, CXCR5, IL-6R, IL-4, and IL-21 mRNA in CXCR5+CD4+ T cells
As previously discussed, the two groups exhibited differential expression of ICOS, PD-1, CD40L, and IL-21R. Elucidating the transcription factors, cytokines and additional markers that are associated with TFH cells is critical for an improved understanding of the role of TFH cells. TFH cells rely on the expression of the master regulator transcription factor Bcl-6. CXCR5+CD4+ T cells in patients with chronic HBV infection significantly up-regulated expression of Bcl-6 mRNA compared to healthy controls (p < 0.01). IL-21 is a typical cytokine for TFH cells; as expected, IL-21 expression was significantly different between the chronic HBV infection and HC groups (p < 0.05). Moreover, the mRNA expression of additional markers that are associated with TFH cells was analyzed using real-time PCR. The expression of IL-6R, IL-4 and CXCR5 mRNA in circulating CXCR5+CD4+ T cells was higher in patients with chronic HBV infection than in healthy controls (p < 0.05) (Figure 3).
mRNA expression levels were determined by real-time PCR. Increased expression of BCL-6, CXCR5, IL-6R, IL-4, and IL-21 mRNA in CXCR5+CD4+ T cells in patients with chronic HBV infection (n = 16) compared to healthy controls (n = 16). Data are presented as the mean ± SD. *,p < 0.05; **, p < 0.01.
Correlation of CXCR5+CD4+ T cells with clinical parameters in patients with chronic HBV infection
Because of the high frequency of TFH cells and the upregulation of a number of molecules associated with TFH cells in patients with chronic HBV infection, we evaluated whether TFH cells were linked to clinical parameters. ALT is a commonly used clinical parameter that is associated with the inflammatory response in patients with chronic HBV infection, and AST is screened to determine the grade of liver injury. The percentage of CXCR5+CD4+ T cells positively correlated with the levels of serum ALT and AST in patients with chronic HBV infection (r = 0.485, p < 0.01 and r = 0.515, p < 0.01, respectively) (Figure 4A, B). However, no significant correlation was found between the percentages of ICOS+CXCR5+CD4+ T cells, PD-1+CXCR5+CD4+ T cells, CD40 L+CXCR5+CD4+ T cells, or IL-21R+CXCR5+CD4+ T cells and the levels of serum ALT and AST (data not shown). Additionally, the frequencies of CXCR5+CD4+ T cells, ICOS+CXCR5+CD4+ T cells, PD-1+CXCR5+CD4+ T cells, CD40L+CXCR5+CD4+ T cells, and IL-21R+CXCR5+CD4+ T cells were not correlated with HBV DNA loads (data not shown). Surprisingly, the percentage of CXCR5+CD4+ T cells in HBeAg + CHB patients was positively correlated with AST (r = 0.542, p < 0.05) (Figure 5A) but not with ALT or HBV DNA levels (data not shown). Moreover, the frequencies of ICOS+CXCR5+CD4+ T cells and PD-1+CXCR5+CD4+ T cells in HBeAg + CHB patients were negatively correlated with HBV DNA loads (r = -0.543, p < 0.05 and r = -0.543, p < 0.05, respectively (Figure 5B, C). Further, the percentage of CXCR5+CD4+ T cells in IC patients was not correlated with ALT, AST or HBV DNA loads (data not shown). In contrast, the proportions of ICOS+CXCR5+CD4+ T cells, PD-1+CXCR5+CD4+ T cells, and CD40L+CXCR5+CD4+ T cells in IC patients were positively correlated with AST (r = 0.698, p < 0.05; r = 0.858, p < 0.01; and r = 0.801, p < 0.01, respectively) (Figure 6A, B, C).
The correlation between CXCR5+CD4+T cells and clinical parameters in patients with chronic HBV infection. (A) The correlation between the percentage of CXCR5+CD4+ T cells and serum levels of ALT. (B) The correlation between the percentage of CXCR5+CD4+ T cells and serum levels of AST. (C) The correlation between the percentage of CXCR5+CD4+ T cells and HBV DNA loads. Data were expressed as the mean values of individual patients (n = 38) from three separate experiments.
The correlation between CXCR5+CD4+T cells and clinical parameters in HBeAg-positive chronic hepatitis B patients. (A) The correlation between the percentage of CXCR5+CD4+ T cells and serum levels of AST. (B) The correlation between the percentage of ICOS+CXCR5+CD4+ T cells and HBV DNA loads. (C) The correlation between the percentage of PD-1+CXCR5+CD4+ T cells and HBV DNA loads. Data were expressed as the mean values of individual patients (n = 14) from three separate experiments.
The correlation between CXCR5+CD4+T cells and clinical parameters in inactive carriers. (A) The correlation between the percentage of ICOS+CXCR5+CD4+ T cells and AST. (B) The correlation between the percentage of PD-1+CXCR5+CD4+ T cells and AST. (C) The correlation between the percentage of CD40L+CXCR5+CD4+ T cells and AST. Data were expressed as the mean values of individual patients (n = 10) from three separate experiments.
The role of TFH cells in infectious and autoimmune diseases has attracted recent attention. The mechanisms by which TFH cells develop and the mechanisms by which TFH cells or their associated molecules regulate antibody responses in humans remain largely unknown. Several studies demonstrated that the frequency of CXCR5+CD4+ T cells was not significantly increased in patients with autoimmune diseases, such as SLE [13], autoimmune thyroid disease [19], and juvenile dermatomyositis [14], compared to healthy controls. In contrast, conflicting results have been obtained concerning the existence of a significantly higher frequency of CXCR5+CD4+ T cells in patients with chronic HBV infection than in the HC group [20]. Consistent with previous studies, our findings demonstrated that the percentages of CXCR5+CD4+ T cells were increased in patients with chronic HBV infection compared to healthy controls. The data obtained in this study suggest that chronic HBV infection drives CXCR5+CD4+ T cell differentiation because in addition to the increased frequency of these cells, the phenotype of CXCR5+CD4+ T cells is altered.
The function of TFH cells is closely related to a combination of markers. In this study, the expression of ICOS was increased in CXCR5+CD4+ T cells in patients with chronic HBV infection compared to healthy controls. ICOS is not expressed by resting T cells and is rapidly upregulated after TCR stimulation. Previous studies demonstrated that ICOS was required for Bcl6 upregulation and for the initiation of the TFH cell differentiation program [21]. Reduced numbers of TFH cells were observed in the absence of ICOS signals [22]. ICOS delivers costimulatory signals by binding to ICOS ligand (ICOS-L) expressed on antigen presenting cells. In both mice and humans, the interruption of the ICOS-ICOS-L interaction leads to impaired GC reactions, Ab class switching, and affinity maturation [22, 23]. Differential expression of PD-1 was also observed between the two groups. PD-1 signaling plays a major role in inhibiting T cell responses. Previous studies demonstrated that PD-1 was elevated during a viral infection to inhibit chronically activated T cells from causing immunopathology or becoming autoreactive [24]. Accumulating evidence indicates that PD-L1- and/or PD-L2-expressing B cells interacted with PD-1+ TFH cells to regulate germinal center B cell survival and the formation and affinity of long-lived plasma cells [25]. We also found that the proportions of CD40L+CD4+CXCR5+ and IL-21R+CD4+CXCR5+ cells were higher in patients with chronic HBV infection than in healthy controls. The CD40L/CD40 interaction promotes germinal center formation, immunoglobulin isotype switching, and somatic hypermutation of the Ig to enhance affinity for antigens, as well as the subsequent formation of long-lived plasma cells and memory B cells [26].
BCL-6 was recently identified as a master regulator of TFH differentiation. Constitutive expression of Bcl-6 drives TFH differentiation in vivo [27]. Previous work demonstrated that GC TFH cells expressed a high level of Bcl-6, while blood CXCR5+CD4+ T cells failed to express elevated levels of the Bcl-6 protein [28]. In contrast to previous studies, blood CXCR5+CD4+ T cells in patients with chronic HBV infection exhibited significantly up-regulated levels of Bcl-6 mRNA compared to healthy controls. IL-21 has been reported to play a role in TFH cell formation and in B cell growth, survival, and isotype switching [29–32]. Our data demonstrated that IL-21 mRNA was highly expressed in circulating TFH cells in patients with chronic HBV infection. This finding suggests that circulating TFH cells can help naïve B cells to produce antibody via IL-21 in patients with chronic HBV infection. The observation that TFH cells produce IL-4 after parasite infection was confirmed by several studies [33, 34]. IL-4 expression by GC TFH cells that lack other Th2 characteristics is important for murine B cell IgG1 class switching.
Our study reveals that circulating TFH cells may be involved in HBV-related immune responses via transcription factors in combination with induction signals and secreted cytokines. We further clarify the relationship between circulating TFH cells and clinical parameters in patients with chronic HBV infection. The percentage of CXCR5+CD4+ T cells was positively correlated with serum levels of ALT and AST. However, the frequency of CXCR5+CD4+ T cells was not correlated with HBV DNA loads. These findings indicate that blood CXCR5+CD4+ T cells are associated with HBV-related liver damage. TFH cells may participate in the inflammatory response, but these cells have no relationship with HBV DNA load. Moreover, no significant correlations were observed between the percentage of ICOS+CXCR5+CD4+, PD-1+CXCR5+CD4+, CD40L+CXCR5+CD4+, or IL-21R+CXCR5+CD4+ T cells and serum levels of ALT, AST or HBV DNA loads. The frequency of CXCR5+CD4+ T cells was positively correlated with serum levels of ALT and AST, but no significant correlation was found between phenotype and serum levels of ALT and AST. Further studies are needed to determine whether the expression of CXCR5+CD4+ T cells varies at different stages of the chronic HBV infection process. In this study, the frequency of CXCR5+CD4+ T cells and ICOS+CXCR5+CD4+ T cells was significantly higher in HBeAg + CHB patients than in HC, and the percentage of CXCR5+CD4+ T cells in HBeAg + CHB patients was positively correlated with AST. In addition, the proportion of ICOS+CXCR5+CD4+ T cells in HBeAg + CHB patients was negatively correlated with HBV DNA loads. Further, the frequency of ICOS+CXCR5+CD4+ T cells, PD-1+CXCR5+CD4+ T cells, and CD40L+CXCR5+CD4+ T cells in IC patients was positively correlated with AST. Our findings reveal that TFH cells may reflect active immune responses because TFH cells are specialized providers of B cell help and promote humoral responses against viral infection. This positive correlation also suggests that the frequency and phenotype of CXCR5+CD4+ T cells is associated with HBV-related liver damage.
Our results demonstrated that the levels of CXCR5+CD4+ T cells and the expression of ICOS, PD-1, CD40L, and IL-21R in CXCR5+CD4+ T cells were increased in patients with chronic HBV infection compared to healthy controls. Moreover, CXCR5+CD4+ T cells were positively correlated with serum levels of ALT and AST in patients with chronic HBV infection, indicating that circulating counterparts of TFH cells may be involved in HBV-related immune responses. Further functional investigations of these cells may elucidate the pathogenesis of chronic HBV infection.
A total of 38 patients with chronic HBV infection were recruited from the outpatient service of the Second Affiliated Hospital of Chongqing Medical University from July to November 2012, and 25 healthy volunteers were selected as controls. Individual subjects with HBV infection were confirmed to be positive for both HBsAg and detectable HBV virions for more than 6 months. Subjects infected with the hepatitis A, C, D, or E viruses or the human immunodeficiency virus and patients with a history and clinical features of drug-induced liver injury, alcoholic hepatitis, autoimmune diseases and steatohepatitis were excluded. All of the included patients were naïve and had not been previously treated with nucleoside/nucleotide analog antiviral or immunomodulatory drugs. This study conformed to the ethical guidelines of the Declaration of Helsinki and was approved by the Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University. All subjects provided written informed consent.
Peripheral blood samples were obtained from individual subjects with written informed consent. Levels of HBV DNA were detected using a fully automated real-time PCR machine and the luciferase quantitation detection kit, with a detection limit of 300 copies/mL (Roche Amplicor, Basel, Switzerland). Serum markers of HBV, anti-HAV, anti-HCV and anti-HEV were determined via the Roche electrochemical luminescence method using an Architect i2000 system (Abbott Laboratories, Abbott Park, IL, USA). Serum anti-HDV was analyzed by ELISA according to the manufacturer's instructions (Kehua Bio-Engineering Co, Ltd, Shanghai, China). Serum levels of AST and ALT were detected using the Automatic Biochemistry Analyzer (Beckman LX-20, Beckman, USA).
Flow cytometry analysis
Five milliliters of heparinized peripheral venous blood was obtained from either healthy volunteers or patients with chronic HBV infection. After removing plasma, the red blood cells were lysed using an NH4Cl lysis solution. Flow cytometry analysis was performed on 106 cells per tube using the following fluorochrome-conjugated antibodies: anti-CD3–phycoerythrin (PE)–cyanine (CY) 7 (eBioscience, San Diego, CA, USA), anti- CD4–fluorescein isothiocyanate (FITC) (BD Company, San Jose, CA, USA), anti- CXCR5–allophycocyanin (APC) (BD Company, San Jose, CA, USA), anti-ICOS–PE (BD Company, San Jose, CA, USA), anti-PD1-PE (BD Company, San Jose, CA, USA), anti-CD40L–PE (eBioscience, San Diego, CA, USA), and anti-IL-21R-PE (BD Company, San Jose, CA, USA). Isotype-matched control antibodies (Beckton Dickinson, San Jose, USA) were used to correct nonspecific binding. After staining for 30 min at 4°C, the cells were washed twice with PBS containing 0.5% bovine serum albumin and subsequently analyzed using a FACS Canto II cytometer and FACSDiva software, version 4.1 (Becton Dickinson).
MACS cell separation
CXCR5+CD4+ T cells were isolated from PBMCs using an autoMACS to achieve >95% purity, as previously described. The employed MACS Cell Separation Reagents contained a CD4+ T cell biotin–antibody cocktail, a CXCR5-biotin-antibody, and micro-beads. CD4+ T cells were negatively selected using a CD4+ T cell isolation kit (Miltenyi Biotec, Germany), yielding populations of CD4+ cells with 96–99% purity. Next, CXCR5+ T cells were separated from CD4+ T cells on the AutoMACS via repetitive separation steps using a positive selection kit (Miltenyi Biotec).
Total RNA was extracted from blood TFH cells using Trizol (Invitrogen) according to the manufacturer's instructions. The concentration and the purity of the RNA were determined by absorbance at 260/280 nm, and cDNA was synthesized using the PrimeScript RT reagent Kit (TaKaRa, Japan). Relative levels of gene expression were measured by real-time PCR using the SYBRGreen master mix reagent in an ABI PRISM 7300 sequence detection system. The following primers were used: GAPDH (NSO_1236141_039, NSO_1236141_040, Invitrogen), BCL-6 (HP 205513, Origene), CXCR5 (HP205521, Origene), IL-6R (HP200535, Origene), IL-4 (HP200556, Origene), and IL-21 (HP214222, Origene). Amplification began with an initial denaturation for 30 seconds at 95°C followed by 40 cycles of denaturation at 95°C for 5 seconds and annealing and extension at 60°C for 31 seconds. The plate was subsequently read. Each sample was tested in triplicate, and the average values were used for subsequent calculations. The expression of each gene was normalized to the housekeeping gene GAPDH, and expressed values relative to control were calculated using the △△CT method. Amplified products were visualized using a UV transilluminator in combination with 1.2% agarose gel electrophoresis and ethidium bromide staining.
All statistical tests were performed using SPSS software, version 17.0 (SPSS Inc., Chicago, IL, USA). Data were presented as the mean ± SD. The t-test was used to compare two independent variables. Correlations between variables were evaluated using the Pearson correlation test. A two-tailed P < 0.05 was considered statistically significant.
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Yu D, Batten M, Mackay CR, King C: Lineage specification and heterogeneity of T follicular helper cells. Curr Opin Immunol 2009, 21: 619-625. 10.1016/j.coi.2009.09.013
King C, Tangye SG, Mackay CR: T follicular helper (TFH) cells in normal and dysregulated immune responses. Annu Rev Immunol 2008, 26: 741-766. 10.1146/annurev.immunol.26.021607.090344
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Fazilleau N, Mark L, McHeyzer-Williams LJ, McHeyzer-Williams MG: Follicular helper T cells: lineage and location. Immunity 2009, 30: 324-335. 10.1016/j.immuni.2009.03.003
Simpson N, Gatenby PA, Wilson A, Malik S, Fulcher DA, Tangye SG, Manku H, Vyse TJ, Roncador G, Huttley GA, Goodnow CC, Vinuesa CG, Cook MC: Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus. Arthritis Rheum 2010, 62: 234-244. 10.1002/art.25032
Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, Foucat E, Dullaers M, Oh S, Sabzghabaei N, Lavecchio EM, Punaro M, Pascual V, Banchereau J, Ueno H: Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity 2011, 34: 108-121. 10.1016/j.immuni.2010.12.012
Linterman MA, Vinuesa CG: Signals that influence T follicular helper cell differentiation and function. Semin Immunopathol 2010, 32: 183-196. 10.1007/s00281-009-0194-z
Chevalier N, Jarrossay D, Ho E, Avery DT, Ma CS, Yu D, Sallusto F, Tangye SG, Mackay CR: CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses. J Immunol 2011, 186: 5556-5568. 10.4049/jimmunol.1002828
Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B: CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med 2000, 192: 1553-1562. 10.1084/jem.192.11.1553
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Zhu C, Ma J, Liu Y, Tong J, Tian J, Chen J, Tang X, Xu H, Lu L, Wang S: Increased frequency of follicular helper T cells in patients with autoimmune thyroid disease. J Clin Endocrinol Metab 2012, 97: 943-950. 10.1210/jc.2011-2003
Li Y, Ma S, Tang L, Wang W, Huang X, Lai Q, Zhang M, Sun J, Li CK, Abbott WG, Naoumov NV, Zhang Y, Hou J: Circulating CXCR5 CD4 T cells benefit hepatitis B e antigen seroconversion through IL-21 in patients with chronic HBV infection. Hepatology 2013, 58: 1277-1286. 10.1002/hep.26489
Choi YS, Kageyama R, Eto D, Escobar TC, Johnston RJ, Monticelli L, Lao C, Crotty S: ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6. Immunity 2011, 34: 932-946. 10.1016/j.immuni.2011.03.023
Gigoux M, Shang J, Pak Y, Xu M, Choe J, Mak TW, Suh WK: Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase. Proc Natl Acad Sci USA 2009, 106: 20371-20376. 10.1073/pnas.0911573106
Baumjohann D, Preite S, Reboldi A, Ronchi F, Ansel KM, Lanzavecchia A, Sallusto F: Persistent antigen and germinal center B cells sustain T follicular helper cell responses and phenotype. Immunity 2013, 38: 596-605. 10.1016/j.immuni.2012.11.020
Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ: The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol 2007, 8: 239-245. 10.1038/ni1443
Good-Jacobson KL, Szumilas CG, Chen L, Sharpe AH, Tomayko MM, Shlomchik MJ: PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat Immunol 2010, 11: 535-542. 10.1038/ni.1877
Elgueta R, Benson MJ, de VVC, Wasiuk A, Guo Y, Noelle RJ: Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev 2009, 229: 152-172. 10.1111/j.1600-065X.2009.00782.x
Crotty S: Follicular helper CD4 T cells (TFH). Annu Rev Immunol 2011, 29: 621-663. 10.1146/annurev-immunol-031210-101400
Crotty S, Johnston RJ, Schoenberger SP: Effectors and memories: Bcl-6 and Blimp-1 in T and B lymphocyte differentiation. Nat Immunol 2010, 11: 114-120. 10.1038/ni.1837
Ettinger R, Sims GP, Fairhurst AM, Robbins R, da SYS, Spolski R, Leonard WJ, Lipsky PE: IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells. J Immunol 2005, 175: 7867-7879.
Abdulahad WH, Lepse N, Stegeman CA, Huitema MG, Doornbos-van der Meer B, Tadema HH, Rutgers A, Limburg PC, Kallenberg CG, Heeringa P: Increased frequency of circulating IL-21 producing Th-cells in patients with granulomatosis with polyangiitis. Arthritis Res Ther 2013, 15: R70. 10.1186/ar4247
Linterman MA, Beaton L, Yu D, Ramiscal RR, Srivastava M, Hogan JJ, Verma NK, Smyth MJ, Rigby RJ, Vinuesa CG: IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. J Exp Med 2010, 207: 353-363. 10.1084/jem.20091738
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King IL, Mohrs M: IL-4-producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells. J Exp Med 2009, 206: 1001-1007. 10.1084/jem.20090313
Glatman Zaretsky A, Taylor JJ, King IL, Marshall FA, Mohrs M, Pearce EJ: T follicular helper cells differentiate from Th2 cells in response to helminth antigens. J Exp Med 2009, 206: 991-999. 10.1084/jem.20090303
This research was supported by the National Natural Science Foundation of China (30930082, 81171561, and 30972584), the National Science and Technology Major Project of China (2008ZX10002-006, 2012ZX1002007001, 2011ZX09302005, 2012ZX09303001-001, and 2012ZX10002003), and The National High Technology Research and Development Program of China (2011AA020111).
Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400010, China
Ting-Ting Hu, Xiao-Fei Song, Yu Lei, Huai-Dong Hu, Hong Ren & Peng Hu
Ting-Ting Hu
Xiao-Fei Song
Yu Lei
Huai-Dong Hu
Correspondence to Peng Hu.
TTH and XFS performed all experiments and data analysis. TTH created the first draft of the manuscript. YL participated in the design of the study. HDH and HR provided assistance with experimental concepts. PH conceived and designed the study and finished the final manuscript. All authors read and approved the final manuscript.
Ting-Ting Hu, Xiao-Fei Song contributed equally to this work.
Authors' original file for figure 10
Hu, TT., Song, XF., Lei, Y. et al. Expansion of circulating TFH cells and their associated molecules: involvement in the immune landscape in patients with chronic HBV infection. Virol J 11, 54 (2014). https://doi.org/10.1186/1743-422X-11-54
T follicular helper cells
Interleukin 21
Inducible costimulator


Meet your business long-term financing needs with a revolving line of credit.
Long-term business loans can provide your business with financing that can be repaid over several years. Business owners usually use it to meet long-term financing needs such as construction, equipment financing or purchasing an existing business. Terms usually start at two years or more, although 10 to 20 years is more likely, with amounts from $25,000 to $200,000.
The benefits of long-term business loans typically include larger funding amounts and lower interest rates and payments, compared to short-term business loans. However, short-term business loans are usually paid back over much shorter periods of time, so they can have lower total costs than long term loans. As with any business lending, you should compare the costs and terms carefully and find the one that works for your business.
Lenders will examine your cash flow and operating expenses. Do you have a steady business income that will ensure timely payments? They'll also consider your business credit.
An established business with years of success will usually have an easier time obtaining long term business loans, whereas a relatively new startup can find it harder to obtain business funding.
Lenders will want to see that an owner is personally invested in a business before granting a business loan. A lender might ask whether the owners could invest their own money in the business rather than seeking a loan.
The lender will want to know what this money is used for and why it's needed, whether it's for purchasing equipment or expanding business space.
What are your goals for the business and how will you achieve them? Are your goals attainable? The lender may also want to know the owner's background and history, as well as that of any other key players involved in reaching these goals.
Just like with a home mortgage, lenders want to make sure a business is properly insured in case of fire, flood or similar losses.
A business line of credit is an arrangement between a lender and a customer that establishes a maximum credit limit the business can borrow from. The business can withdraw funds on the line of credit at any time, as long as they do not exceed the maximum limit.
SBA loans aren't actually given out by the U.S. Small Business Administration. They're loans issued either by a bank or another lending institution that is guaranteed by the SBA. The "guaranteed" aspect means the SBA will repay the lender, up to a certain amount, if the loan holder defaults on their payments. This means that while getting approved by the SBA can be a lengthy and challenging process, but if approved, the loan usually comes with favorable rates and terms.
Business credit cards are very similar to personal credit cards, in that the individual's personal credit will be checked as part of the credit approval process (in addition to the business's credit ranking). The differences lie in the features offered and how your credit is affected.
Invoice factoring allows a business to sell its invoices to a third party (called a factor) at a discount. The factor then provides an advance on payments for those outstanding invoices. This way, businesses can have the working capital to reinvest in operations and growth sooner than they could if they were waiting for their customers to pay them.


text:
Tag: renewable energy stocks
Which state is the least energy efficient?
The state of Indiana has been ranked as the least efficient in the Midwest for the second straight year, according to data released by the U.S. Energy Information Administration.
The Indiana Energy Information Agency (EEI) ranks states based on how energy-efficient they are, based on energy efficiency measures like efficiency and efficiency improvement.
Indiana's ranking is the lowest in the country.
The U.N. Framework Convention on Climate Change has made it clear that states must be energy efficient.
The state ranked at 20th in the nation for energy efficiency last year, which means that Indiana ranked below the average for its regions.
The United States is also ranked 19th for the efficiency of its transportation systems, according the U,S.
But Indiana's energy efficiency has declined in recent years, with Indiana ranking 26th in 2015, according EnergyWire.
The data comes after Indiana was ranked as one of the top states for renewable energy in a 2016 report from the National Renewable Energy Laboratory (NREL).
Indiana is a leader in wind, solar and geothermal energy, but the state also has a lot of natural gas and oil and gas production.
It has also invested heavily in natural gas pipelines, which can carry more gas and liquefied natural gas than oil or coal pipelines.
A study from the U of H Energy Institute in 2015 found that Indiana has the third-highest energy cost in the U., with the average monthly electricity bill for consumers at $1,049 per month.
Indiana ranked No. 1 for average monthly energy costs in the state in 2015.


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Take the dog for a walk	100%	Yes

Waste half the day on Twitter	20%	No

Feel inferior after viewing Dribble	80%	No

Wince at "to do" list	100%	Yes

Vow to complete personal project	23%	yes

Procrastinate	80%	No

Hyperlink Example	80%	Another

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Based in Simple Little Table by Orman Clark

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Tine kan hentyde til flere artikler:
 Tine (pigenavn)
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 Tine (film) – en filmatisering af ovennævnte roman fra 1964.

 TINE - Norsk virksomhed der fremstiller mejeriprodukter

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European Luxury River Cruises
RIVIERA TRAVEL – The Elbe, Berlin, Dresden & Prague – 8 days
Call River Cruise Tours free to book 0800 612 5677 and receive a free case of wine. PLUS we have no credit card fees!
The delightful and historic Elbe, once the border of the Holy Roman Empire is one of Europe's most undiscovered rivers and yet its hinterland has some world-class cities and places of interest!
You fly to Berlin where a coach will take you to the ship. The dedicated crew will welcome you aboard ensuring you settle into your comfortable and extremely well-appointed cabin, and familiarise yourself with the ship: your first class floating hotel.
Day 2 – Berlin
Relax over your first superb breakfast then join our sightseeing tour of Berlin, one of Europe's truly great cities. Having attained capital status only in 1871, Berlin exudes contrasts – famed for its role as a cultural capital, its heady days at the decadent heart of 1920's Europe then the wartime years and the turmoil of the Wall uniquely dividing the city. Berlin is thriving once more following its remarkable re-unification now amazingly over 20 years ago, with vast sums having been spent on its superb restoration. If you have visited the city before, you are really in for a shock at the stunning changes which have and continue to take place. Your tour takes in all the iconic locations; – the last remains of the Wall – ironically now a protected 'historic' monument!; the famous Checkpoint Charlie where apprehended spies were 'exchanged' during the cold war; the wonderfully restored Reichstag; the towering Brandenburg Gate standing sentinel over the magnificent avenue, Unter Den Linden, striding the heart of the city.
This afternoon is free for you to explore as you wish, but it is wrong to assume Berlin is all about politics; its ambience is really vibrant and its museums display some of world's finest collections from the ancient world especially Turkey and Greece, plus fine art by Monet, Degas, Van Gogh to name but a few. Visit the parks to see Berliners at play – more than a third of the city is green – or sample that Berlin institution, taking coffee at a pavement café. For something different visit the DDR museum, depicting the fascinating everyday life inside the former East Germany. Later the ship slips away from the quayside navigating the pleasant network of lakes along the river Spree. As the city's twinkling lights fade, you'll enjoy your first splendid dinner in the excellent restaurant before perhaps heading for the lounge and a chance to discuss impressions of Berlin with your fellow passengers over an after-dinner drink. Immersed in unfamiliar surroundings full of fascinating sights, stories and experiences, you will already feel a long way from home.
Day 3 – Potsdam
Overnight we have berthed in Potsdam, city of Prussian kings and German Kaisers, and this morning we visit Sanssouci Park and tour one of their magnificent 17th century residence, a frenzy of Rococo style, full of fine art and exquisite antiques. Its extensive temples and sculptures studded throughout the surrounding park are redolent of Versailles, which indeed was Sanssoucci's inspiration so its creator, Frederick the Great could escape the duty of Berlin's royal court, hence it's name Sanssouci – "without troubles". Returning to the ship you will be enthralled as the Captain skillfully navigates the fascinating series of locks taking us onto the mighty River Elbe itself.
After dinner you can witness a marine highlight of the cruise, the crossing of the momentous 918 metre Magdeburg Water Bridge, the world's longest navigable aqueduct soaring high above the surrounding countryside and a fitting monument to German engineering. We moor in Magdeburg this evening.
Day 4 – Dessau & Wittenberg
As you awake, the ship will be serenely cruising along the picturesque River Elbe, once the eastern border of Charlemagne's huge Holy Roman Empire. You really can absorb the peaceful atmosphere of one of Europe's less famous rivers and here, the Middle Elbe, has been declared a nature reserve, noted for its wildfowl thriving along its hilly, wooded banks. Riverside life is delightful as we pass numerous half-timbered villages, with couples strolling arm-in-arm along the river and after another superb lunch, we berth in Dessau visiting the stunning Wörlitzer Park, perhaps the finest example of an English-style landscape garden in Germany. Next we have a short visit to beautiful Wittenberg, a delightful town where Martin Luther nailed his 95 theses to the church door in 1517 initiating the Reformation thus changing Europe forever.
Day 5 – Meissen
This morning we pass Torgau, where Soviet and US forces met in 1945, and partly due to the lack of development in the communist East, the Elbe here retained superb biodiversity which continues due to present day environmental concern. The Floodplain forests are Germany's most extensive with over 1000 different plants, 40 mammal species and a plethora of invertebrates – with 500 species of butterflies native to the region being particularly impressive.
The countryside becomes ever more rolling with the occasional vineyard visible and this afternoon we visit Meissen, famous of course for its exquisite porcelain, the first to be made outside China. The rarity and cost of the factory's products ensured it was the preserve of the rich and famous with Europe's wealthy amassing vast collections – many of which now grace the world's great museums. We have a fascinating tour discovering how highly skilled artisans create these stunning works of art many of which take weeks, sometimes months to finish. Quite often referred to as Dresden porcelain, this is the only factory in Europe in which all the processes are completed by hand and we see the complete cycle from clay to finished article, after which there is a stunning museum displaying pieces from throughout the company's existence. We berth in Meissen, so after dinner why not take a stroll through the old town.
Day 6 – Dresden
This morning offers a real highlight – cruising into the heart of historic and truly majestic Dresden, one of central Europe's most beautiful cities with a classic waterfront. During our walking tour you will fall in love with this baroque and rococo icon controversially brought to its knees by massive bombing in 1945, it has been wonderfully restored, returning it to its dramatic former glory in probably the world's most remarkable such project ever. Saxony's capital, Dresden attracted many of Europe's best musicians, architects and artists, becoming an epicentre of European culture. Canaletto captured much of it during his many visits and during our morning tour you will be amazed at the magnificent buildings at the city's cultural core, including: the majestic Frauenkirche with its iconic domed roof; the remarkable 100m long Meissen tile mural depicting Saxony's monarchs; the Semper Opera where many of Wagner's works were first performed and the Royal Palace, with its splendid museums and galleries.
To cap it all are the unbelievable masterpieces in the incredible Zwinger Palace, home to the world's twelfth largest art collection including works by Rubens, Rembrandt, Van Dyke, El Greco, Canaletto and many more, plus a renowned collection of modern art and astonishing array of medieval armour and weapons. The river bisects Dresden's heart so after lunch it's easy to take a stroll exploring as you wish. There is a delightful ambience here and you'll revel in its tasteful shops, cobbled streets and occasional rather talented street musicians maintaining Dresden's musical heritage and giving the city its soul.
During afternoon tea the ship slips her moorings for a delightful evening cruise no doubt encountering the original paddle steamers which have plied these waters for over 130 years. The haunting tones of their chime whistles, the watery splashes of the paddles and the rhythmic chugging of the steam engines really are the sound of yesteryear. The scenery changes dramatically as we follow the river's amazingly sinuous course through the dense forests, contorted sandstone crags and deep valleys of "Saxon Switzerland" an area of outstanding natural beauty, berthing in the spa town of Bad Schandau on the Czech border.
Day 7 – Prague
After breakfast a coach will take us to the golden city of Prague. Centuries of royal patronage have created the masterpiece that you see today and our guided tour showcases the very best Prague can offer, the sheer beauty of which is beyond words! Walk through long stone palaces, cross the classic Charles Bridge or explore the cathedral, we defy you to suggest a more attractive city. You will see the principal monuments such as Tyn Church, the Powder Tower, Wenceslas Square, the unpronounceable Staromestske Namesti – the city's showpiece 11th century square complete with its amazing astronomical clock.
This afternoon you could visit Hradcany, the spectacular Prague Castle and Cathedral, the centre of political power for a thousand years and perched high on a clifftop with superb views over the River Vistula, an amazing display of historic rooftops and the countless churches giving the city its sobriquet 'City of a Hundred Spires'. Explore the remarkably preserved medieval Jewish Quarter together with its synagogue or the Gothic Tyn Church, famous for its irregular twin towers, dominating the central square and bristling with baubles. This has been the market place since Prague's foundation, lined with tall, tastefully restored, pastelcoloured houses, many of which are pavement cafés where you can watch the world go by in a city which genuinely can be called beautiful!
We return to the ship for the Captains Dinner serving specialities of the regions we have discovered, whilst returning to Dresden. You will have had a thought-provoking week, with echoes of Bach, Mendelssohn, Schumann and Wagner, witnessed the very cradle of the Reformation in Luther's Wittenberg, experienced the longest navigable aqueduct in Europe and explored some of Europe's most beautiful and historic cities on a trip that will live long in the memory.
After a final hearty breakfast, it's time to say a fond farewell to the friendly crew of the ship, returning to Berlin for your flight.
Prices are based on twin share departing from London Heathrow Airport. Other regional airports are available – please call us for details.
Depart UK
Arrive UK
14 Aug 2015 £1,619 MS Swiss Ruby 14:35info 18:30
18 Sep 2015 £1,719 MS Swiss Ruby 09:10info 13:50
17 Jun 2016 £1,719 MS Swiss Ruby 14:35info 13:50
15 Jul 2016 £1,619 MS Swiss Ruby 14:35info 13:50
Guided tour of Berlin, one of the world's most rapidly evolving and fascinating cities
Walking tour of Dresden, 'Florence of the Elbe', home of the world's twelfth largest art collection and former capital of the Kings of Saxony
Tour of Prague, central Europe's jewel and one of the world's most beautiful capitals
Visit to Potsdam and Sanssouci Park, home of Frederick the Great
Visit and tour of the Meissen porcelain studio
Visit Wittenberg, where Martin Luther challenged the established church, initiating the Reformation
Price includes full-board from dinner on your arrival day until breakfast on your final day
Prices are per person, based on two people sharing a twin cabin with a limited number of single cabins available on the all decks, at the relevant supplement. The price includes full board from dinner on your day of arrival until breakfast on your final day; if you choose to travel with us on any of the full day excursions by coach, a packed lunch will be provided. Anyone choosing to stay on the ship may of course have lunch in the restaurant; morning/afternoon tea and coffee; all visits and excursions as mentioned in the brochure, airport/station transfers, coach travel as mentioned, travel to and from port of embarkation and the services of a Riviera Travel Tour Manager.
© River Cruise Tours 2013


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Beyrie-en-Béarn (okzitanisch: Veiria) ist eine französische Gemeinde des Départements Pyrénées-Atlantiques mit  Einwohnern (Stand: ) in der Region Nouvelle-Aquitaine (vor 2016: Aquitanien). Administrativ ist sie dem Kanton Artix et Pays de Soubestre (bis 2015: Kanton Lescar) und dem Arrondissement Pau zugeteilt. Die Einwohner werden Beyriens genannt.

Geografie
Beyrie-en-Béarn liegt etwa elf Kilometer nordwestlich von Pau. Umgeben wird Beyrie-en-Béarn von den Nachbargemeinden Bougarber im Norden und Osten, Poey-de-Lescar im Süden, Aussevielle im Südwesten sowie Denguin im Westen.

Bevölkerungsentwicklung

Sehenswürdigkeiten
 Kirche Notre-Dame aus dem Jahre 1896

Weblinks

Ort in Nouvelle-Aquitaine


We're delighted to announce our investment in Gameye, the API that provides game studios and esports platforms with cost-effective and scalable solutions required to operate live multiplayer sessions, as part of their $1.6m seed round alongside Makers Fund and Niccolo Maisto, CEO of competitive gaming platform FACEIT.
Gameye has also attracted the interest of Craig Fletcher, founder of Global Service Provider and esports event organizer Multiplay, which was sold to UK retailer GAME in 2015 for £20m, who joins as an advisor.
Established in 2017 by Founder Sebastiaan Heijne and Co-founders Elmer Bulthuis, Ralph Heersink and Denise Helderop, Gameye created an API tailored to esports matchmaking platforms and quickly recognized a wider problem faced by many game studios looking to create a stable infrastructure required for multiplayer sessions. Studios were spending significant resources to ensure their games could handle spikes in play as well as deployment systems. Gameye's technology means studios can focus on developing great games with multiplayer functionality without the pressure of developing systems needed for multiplayer sessions internally thus enabling their games to ship sooner. For platform holders who traditionally require players to provide their own match servers, Gameye negates this need and makes entry to play easier for gamers.


Alexander: The Man Who Knows by David Charvet and John Pomeroy, very good. Throughout this book, two very different stories unfold. First there is the account of Claude Alexander Conlin, the man who became perhaps the highest paid entertainer in the field of magic.
Starting out as a stage illusionist, Alexander eventually discarded the large props and relied on his tremendous skills as a showman to put over an act of mentalism and psychic readings. As the turbaned Man Who Knows, Alexander earned four million dollars over the course of a relatively short career during the 1920s. The second story that runs concurrently with Alexander's theatrical career includes details on his seven marriages (sometimes to more than one woman at once), time spent in local jails and federal prison, his trial for attempting to extort an oilman millionaire, his failed attempt to out run the authorities in a high powered speed-boat loaded with bootlegged liquor, and the four men that he admitted killing.
It is not the kind of story in which you expect to find names like Harry Kellar, Dr. Wilson, Harry Houdini, Servais Le Roy, Howard Thurston, Floyd Thayer, Joe Dunninger and Harry Blackstone but here they are, both friend and foe alike. Mike Caveney's Magic Words 2004, illustrated, dust jacket. The item "Alexander The Man Who Knows by David Charvet and John Pomeroy, very good" is in sale since Tuesday, October 2, 2018. This item is in the category "Collectibles\Fantasy, Mythical & Magic\Magic\Books, Lecture Notes".
The seller is "szaut_szaut" and is located in Albuquerque, New Mexico. This item can be shipped to United States.


DataRobot is focused on automated machine learning and on helping customers build an AI driven business, especially by focusing on decisions that can be automated using machine learning and other AI technologies. DataRobot was founded in 2012 and currently has nearly 300 staff including 150+ data scientists. Since it was founded, well over 200M models have been built on the DataRobot cloud.
DataRobot's core value proposition is that they can speed the time to build and deploy custom machine learning models, deliver great accuracy "out of the box" and provide a simple UI for business analysts so they can leverage machine learning without being a data scientist. The technology can be used to make data scientists more productive as well as to increase the range of people who can solve data science problems.
DataRobot runs either on AWS or on a customer's hardware. Modeling-ready datasets can be loaded from ODBC databases, Hadoop, URLs or local files – partnerships with companies like Alteryx support data preparation, blending etc. The software then automatically performs the kind of data transformations needed to make machine learning work – data cleansing, feature engineering needed for the various machine learning algorithms such as scaling and converting data to match the algorithms. It does not currently generate domain-specific potential features/characteristics from raw data, instead making it easy for data and business analysts to create them and feed them into the modeling environment. Once data is loaded, some basic descriptive statistics are loaded and the tool recommends a measurement approach (to select between algorithms) based on the kind of data/target.
DataRobot can apply a wide variety of machine learning algorithms to these datasets, for now almost exclusively supervised learning techniques where a specific target is selected by the user. Multiple algorithms are run and DataRobot partitions data automatically to keep holdout data for validation (to prevent overfitting), applies smart downsampling to improve the accuracy of algorithms and allows some other advanced parameters to be configured for specific kinds of data. Once started, DataRobot looks at target variable, dataset, characteristics, combinations of characteristics and selects a set of machine learning algorithms/configurations (blueprints) to run. These then get trained and more "workers" can be configured to speed the time to complete, essentially spinning up more capacity for a specific job.
As the algorithms complete, the results are displayed on a leader board based on the measurement approach selected. DataRobot speeds this process by running the blueprints initially only against a subset of the data and then running the top ones against the full dataset. Users who are data scientists can investigate the blueprints, see exactly the approach taken for the blueprint in terms of algorithm configuration, data transformations etc. Key drivers- the features that make the most difference – are identified and a set of reason codes generated for each entry in the dataset. Several other descriptive elements, such as word clouds for text analytics, are also generated to allow models to be investigated.
The tool also has a UI for non-technical users. This skips the display of the leader board and internal status information and displays just a summary of the best model with its confusion matrix, lift and key drivers. A word cloud for text fields and a point and click deployment of a scoring UI (for batch scoring of a data file or scoring a single hand-entered record) complete the process. More advanced users can interact with the same projects, allowing the full range of deployment and reuse of projects created this way.
Once a model is done, the best way to deploy them is to use the DataRobot API. A REST API end point is generated for each model and can be used to score a record. All the fields used in the sample are used to create the REST API and the results come back with the reason codes generated. Everything to do with modeling is also available through an API, allowing customers to build applications that re-build and monitor models. Users can also generate code for models but this is discouraged.


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Q: Splitting primes and quadratic reciprocity. I'm reading through Marcus's wonderful book Number Fields, and I had two questions on his proof of quadratic reciprocity in chapter $4$.
Marcus states first that if $p$ is an odd prime, and $q$ is any prime, that in the field $\mathbb{Q}[\omega]$ where $\omega = e^{2\pi i /p}$ that $q$ will split into $r$ primes, where $r = (p-1)/f$ and $f$ is the multiplicative order of $q \mod p$. He says this like it's obvious, so maybe I'm missing something simple, but I do not understand this line.
My second question is that Marcus also claims that the following are equivalent
$1)$ $q$ is a $d^{th}$ power $\mod p$
$2)$ $f|(p-1)/d$
$3)$ $d|r$
$4)$ $F_d \subset F_r$
Where $F_d$ is the unique subfield of $\mathbb{Q}[\omega]$ of degree $d$ over $\mathbb{Q}$ guaranteed by the fact that the Galois group of $\mathbb{Q}[\omega]/\mathbb{Q}$ is cyclic.
I think $1\implies 2\implies 3 \implies 4$ are pretty trivial, as well as $4\implies 3 \implies 2$, but I can't quite see the equivalence of $1$ with the rest of these statements.

A: Your first question has its answer in the Corollary of Theorem 26. Observe that as $q$ does not divide $p$, so it should split into exactly $\frac{p-1}{f}$ factors, which he has denoted by $r$, and where $f$ is the multiplicative order of $q$ modulo $p$. So, $r = \frac{p-1}{f}$.
In your second question, understanding the equivalence between two statements just as you have already mentioned will suffice to make sure that all are equivalent.


Appomattox Court House NHP is the village where Confederate General Robert E.Lee surrendered to Union General Ulysses S. Grant beginning the end of the US Civil War. Visit the site of Lee's surrender and experience a Civil War weekend where history comes to life.
Visiting Appomattox Court House NHP is largely a self-guided experience.
Start your tour at the visitor center, in the reconstructed courthouse building, and get a map of the Park.
The Junior Ranger Program helps kids (ages 6-13) have a meaningful interaction with our nation's history. Kids can get a workbook to complete as they tour the Park. Once completed, they receive a parole pass, a set of Appomattox trading cards and a Jr. Ranger badge.
Living History talks are presented, often at 50 minutes after the hour. These programs are presented by actors who portray people who were here in 1865, and who speak as though it is still 1865. These programs continue through the fall when possible.
Ranger Programs are also offered throughout the year.


Shark Rock just to the east of Tharal Point is named because of its form, not for your chances to see these magical creatures.
The Westward side of the harbour mouth is called on the charts "Tharal Point", but unmarked just to the East of the point is a rock which breaks at low water known as "Shark Rock". Care must be taken if boating in this area during high tide as it is very easy to hit this rock.
Shark Rock provides a variety of topography from reef walls to narrow gullies. If the weather allows, the best entry point is between the rock and the headland just inside of the harbour. At a depth of 8m the diver will find a kelp covered reef which falls onto a rocky bottom with sand patches at 18m. Keeping the reef wall to the right proceed at 15m until the start of a gully. A little further in, the gully divides into two paths, on the right a narrow, long, cave-like gully which leads to the outside of Tharal Point and on the left a gully which leads to the seaward side of Shark Rock. Choose either of these gullies and you will find jewel anemones, sponges and soft corals covering the walls like a brightly coloured carpet. The water normally has 20-30m visibility and overhead, shoals of pollack and occasional herring can be found passing into Donegal Bay. Amongst the other unusual sights on this dive is an abundance of Rainbow wrasse.
Heading South out of the gullies will lead the diver into deep water in excess of 34m. Here the bottom consists of large boulders with much fish life but few sponges or corals. To avoid deep water turn east after leaving the gully and you will come to a further series of gullies. After about 70m change North and this should bring you to the outside of Shark Rock. Beware that the sea breaks heavily at low tide and care should be taken when surfacing to avoid ascending through the surf caused by the rock.


So Jukka's groups result is that reversible MCMC is not necessary. As long as the usual Metropolis-Hastings acceptance condition applies, the MCMC process converges in the long term.
Anyway, I can now build split-merge operators using MCMC without requiring crazy reversability!


Description: While on vacation, Emmanuelle is pressed into service to help her friend. While traveling by train from Santa Barbara on the California coast to Aspen, Emmanuelle helps with the search for the kidnapped sister of the Count Eric Xavier. Neither Emmanuelle nor Eric are prepared for what awaits them as they travel into a concluding avalanche.


text:
What did Dudley hear when attacked by the Dementors?
I've been re-reading the Harry Potter books over the last month, and this particular question occurred to me when reading the start of Order of the Phoenix. The following quote sums it up rather nicely:
Dudley seemed incapable of saying. He shuddered again and shook his large blond head, and despite the sense of numb dread that had settled on Harry since the arrival of the first owl, he felt a certain curiosity. Dementors caused a person to relive the worst moments of their life. What would spoiled, pampered, bullying Dudley have been forced to hear?
Chapter Two - A Peck of Owls, Order of the Phoenix
All I managed to find at the time was this quote from JKR:
Amy: What did Dudley see when he faced the Dementors in book five?
JK Rowling replies -> Ah, good question. You'll find out!
So, thinking that perhaps there was something in one of the final two books that answered the question, I carried on reading. However, I'm now about a third of the way through the last book and this hasn't been answered; I don't recall there being any scenes with the Dursleys (other than a young Petunia) in the remainder of Deathly Hallows so I'm expecting to finish reading without an answer.
Is there any canon information (JKR writings, interviews or a book quote that I've missed or yet to read) that states what Dudley heard when he and Harry were attacked by the Dementors?
harry-potter dementors
Anthony GristAnthony Grist
There's no book quote - the only other conversation it might have come out would have been in book 7 before the Dursleys left Privet Drive (when Dudley acted like Harry was a real person for the first time), and there was nothing there about what Dudley saw or heard. – Adam V Aug 26 '13 at 14:17
@AdamV Yes, I didn't have much hope that there was one; all Dudley really says in book seven is "Thanks for saving my life." It's a bit annoying that JKR raised the question herself in the book, said in an interview that we'd find out, then seemingly never addressed it. – Anthony Grist Aug 26 '13 at 14:28
Totally agree! Now that I see the question, I want to know as well. Hopefully someone finds an interview where she answers it! It's quite possible she intended to have it in the book (just as she had intended for 'scar' to be the last word in the series), and it got cut for one reason or another. – Adam V Aug 26 '13 at 14:32
There's a circular link between the two questions: this one and scifi.stackexchange.com/questions/55584/…. What are the chances of that! – cst1992 Dec 5 '16 at 10:42
Not exactly an answer to what he heard, but here it goes anyway:
As far as I remember it's never mentioned again in the books. I did find this, but not sure how credible it is
And here's the quote:
"People usually ask me, what is it that Dudley saw during the Dementor attack?" Rowling said. "My feeling is that he saw himself, exactly for what he was, and for a boy that spoiled, it would be terrifying. So he was jolted out of it. Dementor attacks aren't usually good for people, but this one was."
Odd, now that you've posted it I feel like I've read that quote before. – Anthony Grist Aug 26 '13 at 16:07
I was also sure I had seen this question before as well, here on stackexchange, but couldn't find it – user13267 Aug 26 '13 at 16:08
@user13267, it's here: scifi.stackexchange.com/questions/55584/… – PointlessSpike Feb 9 '15 at 13:38
The transcript of the 2007 question and answer session that this article refers to accio-quote.org/articles/2007/0730-bloomsbury-chat.html contains a similar quote: "I think that when Dudley was attacked by the Dementors he saw himself, for the first time, as he really was. This was an extremely painful, but ultimately salutory lesson, and began the transformation in him." – b_jonas Jan 13 '16 at 14:50
I think he saw the times such as when Hagrid gave him a pig's tail (and the surgery he had to go through to get it removed), as well as the time Harry blew up his aunt or when his tongue grew 4 feet long. I think he would be scared of something like magic because it is the one thing he can't control.
HannahHannah
While this certainly seems plausible, the accepted answer says something different. Is there any evidence (in the books or elsewhere) that this is what he saw? – Adamant Oct 16 '16 at 1:46
Welcome to the site :) Some of these suggestions seem more plausible than others to me, but it's not too important. What is important is to try and provide supporting evidence rather than reckons -- even more so to very old questions with multiply-upvoted accepted answers. Please don't be discouraged, you're absolutely not the first to run afoul of stackexchange, but we aren't a forum or chat room here and we tend to ask for and expect quite high standards, rather than people's two cents – Au101 Oct 16 '16 at 1:52
Do you have any evidence for this, or is it just speculation? – Blackwood Aug 29 '17 at 20:58
Not the answer you're looking for? Browse other questions tagged harry-potter dementors or ask your own question.
Why did Dumbledore say that Dudley had been mistreated by the Dursleys?
Did any Muggles actively fight against Voldemort?
Why did the two dementors have a much greater effect on Dudley than what Prisoner of Azkaban would have us expect?
What was in the letter to the Dursleys Dumbledore left with baby Harry?
Was Harry Potter being a Horcrux making the Dursleys act mean?
Can Squibs see Dementors?
Who was "that awful boy" that Petunia refers to?
How did Uncle Vernon forget that magical events appear on the Muggle news?
What exactly about Aunt Petunia is "More than meets the eye"?
How did Petunia recognise Dumbledore's voice?
HP fan-fiction where an Imperiused Dudley jumps off a building
How did Dudley Dursley recover from the dementor attack?


You want your kids to see the world (or at least your little part of it) but the idea of travelling with one or more children can seem daunting. There's packing, mode or method of travel, and keeping the kids occupied, not to mention finding a kid-friendly destination. Here are five ways to make holiday travel with children a little easier.
Create a packing list. Write down everything you think you'll need for the trip, and cross it off the list when you've packed it. You'll feel reassured that you've covered all your bases, and if you bring it with you on your trip you're less likely to forget something and leave it behind.
Have the kids share a suitcase. Children don't have as many extra packing "skincare essentials" as adults do and their clothes take up less room. Save on the cost of luggage or make more room in the car by packing all of the kids' clothes into one bag or by spreading them out between suitcases.
Be armed and ready for the journey. Long flight or car ride? You can survive it if you prepare for it! Pack (sugar-free) snacks in your bag separate from whatever you've stashed in the kids' bags so you can bring them out at intervals throughout the trip, as a distraction or bribery. Have something on hand to entertain them – a colouring book, activity set, or stickers (Orchard Games toys from Squires Garden Centre in Woking are the perfect size for packing away and robust enough for the journey). Gel window clings work for car rides as well as window seats on planes, or you can pack some books like 100 Things For Kids To Do On A Journey and/or Axel Sheffler's Flip Flap books stocked by Calliope Gifts in Dorking. And if all else fails, there's always the electronics you've been hiding.
Do your research before the trip. This awesome guide by Lonely Planet is packed with helpful info for travel with kids. Know if the city is going to be hilly or full of steps (in other words not pram friendly), where the good family restaurants are, and what activities you can plan in advance (and maybe get the kids in for free). Interactive museums, aquariums, and zoos are all great destinations for keeping kids entertained.
Find kid-friendly locations. Not only are you looking for places with a kiddie pool, but some resorts have activity centres for kids where they can learn to surf, or go on nature walks, or just make new friends. Having a quiet afternoon to yourself while your kid learns to make friendship bracelets or joins in a talent show is a win-win situation. Honest Mum blogger shares top tips in her latest article and you can also win a holiday to beautiful Bahia, Spain.
Do you have any hacks to share? What do you do to keep your children happy while you travel?


text:
var fs = require('fs');
var Steam = require('steam');
var SteamTrade = require('steam-trade');
var Coinbase = require('coinbase');
//var doge = require('../node_modules/dogeapi.js/src/index.js') // I know this is dumb, but the DogeAPI.js module is awful and this appears to be the only way to import it
//var config = require('../config')
var http = require('http');
var https = require('https');
var url = require('url');
var util = require('util');
var redis = require('redis');

//Redis Test
console.log("Connecting to Redis...");
rclient = redis.createClient();


text:
Ukrainian composer Heinali shares 'Kyiv Eternal', a tribute to his home city
Home / Music / Ukrainian composer Heinali...
Kyiv-based composer Heinali has revealed details of his new album Kyiv Eternal, which pays homage to his home city.
The first track to be shared from the release is the title track which is awash with moving chords and a strong, powerful sense of hope. In its entirety the album features fragments of field recordings taken from different locations around the city and matched with ambient soundscapes from his archives.
Having spent 37 years living in the city, Heinali sees it as an 'inseparable part' of his identity, and he wanted to give something back to it after it had given so much to him.
Heinali expands on this point: "After the Battle of Kyiv was over, many Kyivites noticed this strange feeling, it was as if the city was alive, breathing. We wanted to hug it, to protect every inch of it from harm. I didn't know how to do it back then. It took time and distance to figure it out, but Kyiv Eternal is my hug."
Heinali is composer and sound designer Oleh Shpudeiko. He has a longstanding relationship with Sine Buyuka's Injazero Records, and has released three albums for the imprint. Over the years, as a solo artist, he's also released multiple offerings on Paradigm Recordings, NEN and Fluttery, while his work also takes in interdisciplinary, multi-media art projects and soundtracks.
Listen to Eternal Kyiv.
Kyiv Eternal will be released on 24th February.
Heinali Ukraine
Anklav announce their first release to raise money for Ukraine war relief
Reel Long Overdub call on friends and family for Ukraine fundraiser compilation
Russian artists come together for Ukraine fundraiser compilation


their own two cents in to other people's business.
like some one just foaming from the mouth.
Just word vomit, spilling out all over the floor.
Letting words of opinionated unknown knowledge seep from their mouths & lips.
Is it because they are so boring or bored of their life that they start to begin to be curious in other's?
Try to control and live through out some one else's?
I just don't get it & I am over it today.
So what if I wear colors in my hair.
So what if I want another tatoo.
So what if I want a dog.
It's MY choice, choices & decisions.
Get a life & get frak out of mine. the end.
insert in le ear holes s.a.p.