The bone morphogenetic protein (BMP) pathway is a major conserved signalling pathway with diverse roles in development and homeostasis. Given that cells exist in three-dimensional environments, one important area is to understand how the BMP pathway operates within such complex cellular environments. The extracellular matrix contains information regarding tissue architecture and its mechanical properties that is transmitted to the cell via integrin receptors. In this review, I describe various examples of modulation of the BMP pathway by integrins. In the case of the Drosophila embryo and some cell line-based studies, integrins have been found to enhance BMP responses through different mechanisms, such as enhancement of BMP ligand–receptor binding and effects on Smad phosphorylation or stability. In these contexts, BMP-dependent activation of integrins is a common theme. However, I also discuss examples where integrins inhibit the BMP pathway, highlighting the context-dependent nature of integrin–BMP cross-talk.
Within a tissue environment, a cell will typically be receiving and responding to different types of signalling molecules, while at the same time processing information relating to tissue architecture via integrin receptors. Integrins are obligate αβ heterodimers that mediate adhesion to extracellular matrix proteins, such as fibronectin and collagen IV, and can recruit different cytoplasmic signalling proteins, triggered by integrin intracellular domain clustering, to illicit diverse cellular responses . Given this mixture of signals received simultaneously by a cell, there are multiple opportunities for cross-regulation during their transduction. Modulation of bone morphogenetic protein (BMP) outputs by the components of other signalling pathways, such as the epidermal growth factor/mitogen-activated protein kinase (MAPK), Wnt and Hippo pathways, has been well documented [2–6]. However, regulation of BMP signalling by integrins has received less attention, despite extensive literature documenting cross-talk between integrins and other classes of signal, particularly MAPK signalling . In this review, I summarize data describing how integrins can influence the BMP pathway output and high-light common themes that are emerging from these studies.
Figure 1. Integrins are required for peak BMP signalling in the Drosophila embryo.
(A) Schematic of the BMP pathway. For simplicity, only the vertebrate and fly BMP receptors discussed here are listed. (B) Cartoon showing BMP (Dpp-Scw) distribution (green) in the dorsal ectoderm of the embryo, as a lateral/side view (top embryo) or rotated 90° to show the dorsal/top view (bottom embryo). There is a peak of BMP protein (dark green) at the dorsal-most region that will specify amnioserosa cell fate, whereas dorsal epidermis forms in response to lower BMP levels. (C) Wild-type and mysXG43 null mutant (lacking maternal and zygotic mys) embryos showing expression of Race, a marker of presumptive amnioserosa, as detected by RNA in situ hybridization. pMad protein is also visualized by immunostaining. Embryos are stage 6, dorsal views. Reproduced from ref. .
To distinguish between an adhesion versus signalling role for integrins, a chimeric TorD-βPScyt protein was used that has the βPS integrin cytoplasmic tail fused to the extracellular and transmembrane domains of a gain-of-function Torso receptor and clusters in the absence of ligand  (Figure 2A). This signalling-activated form of integrin had previously been shown to rescue the integrin loss-of-function phenotype in the Drosophila midgut . Expression of this TorD-βPScyt fusion protein in mys mutant embryos rescued the BMP signalling defect (Figure 2B), indicating that integrin signalling rather than adhesion mediates enhancement of BMP responses .
Figure 2. Integrin signalling enhances BMP responses.
(A) Cartoon showing ligand-dependent clustering of αβ integrin dimers, which can be mimicked by the TorD-βPScyt fusion protein. (B) RNA in situ hybridization showing loss of Race expression in the presumptive amnioserosa in a mysXG43 mutant embryo (top) that is rescued by expression of the TorD-βPScyt transgene (bottom). Embryos are stage 6, dorsal views. (C) Cartoon depicting that integrin signalling enhances BMP pathway activation (left). A loss of integrin signalling may contribute to the reduced BMP signalling observed in collagen IV mutants (middle) and be rescued by TorD-βPScyt-mediated integrin signalling (right, red arrow). (D) As in (C) except the embryos are from vkgk00236/+ females. Reproduced from ref. .
A Drosophila tissue culture model that mimics the in vivo situation was also established, in which integrins increased pMad levels in response to pathway activation by either BMPs or an activated form of the Thickveins (Tkv) type I BMP receptor, TkvQD . The ability of integrins to enhance TkvQD-activated pMad levels supports a role for integrins in enhancing the BMP pathway downstream of receptor activation. Moreover, the TorD-βPScyt fusion protein enhanced signalling activated by TkvQD, with this activity requiring the NPXY motifs in the βPS tail  that recruit various integrin binding proteins [11,12]. Co-immunoprecipitation studies revealed an association between Tkv and βPS and two α-integrins, αPS1 and αPS3, which, in the case of βPS, is dependent on sequences within its intracellular tail . We focused on αPS1 and αPS3, as although three α-integrins are expressed in the early embryo, only two — multiple edematous wings (mew) and scab (scb) encoding αPS1 and αPS3, respectively — have expression domains that overlap with the dorsal region of the embryo, where BMP signalling is active. In the tissue culture model, knock-down of both mew and scb together is necessary to reduce the pMad level similar to that observed upon βPS knock-down.
These observations suggest a redundant function of αPS1βPS and αPS3βPS receptors in mediating pMad enhancement through integrin signalling in cells. Analysis of mutant embryos revealed that although mutations in either mew or scb result in a loss of Race expression, these single mutants show different phenotypes with respect to the expression patterns of other BMP target genes. In particular, loss of mew, but not scb, gives rise to phenotypes similar to that of a short gastrulation (sog) mutant, albeit at low penetrance . Sog, the Drosophila ortholog of vertebrate Chordin, is an extracellular BMP-binding protein with a key role in BMP gradient formation . Sog distribution was previously shown to be modulated by αPS1βPS in both the pupal wing and ovarian follicle cells [13–15], likely through an interaction between αPS1 and full-length Sog or its cleavage fragments [13,14]. Therefore, we suggest that while both αPS1βPS and αPS3βPS can enhance pMad levels via intracellular signalling, αPS1 plays an additional role in BMP gradient formation through the regulation of Sog distribution or activity .
In terms of identifying the ECM protein that activates integrin receptor signalling in the Drosophila embryo, collagen IV functions as an integrin ligand in vertebrates. While the major collagen IV-binding integrins in vertebrates are α1β1 and α2β1, flies lack an ortholog of the vertebrate α1 and α2 integrins . However, there is evidence for a binding site for α3β1 integrin in the collagenous domain of collagen IV , with Drosophila αPS1 most closely related to vertebrate α3, α6 and α7 integrins . In addition, both α3β1 and α6β1 integrins, amongst others, can bind the collagen IV C-terminal NC1 domain, which is released during matrix turnover . Analysis of embryos with reduced levels of either of the two collagen IV proteins, called Viking (Vkg) and Cg25C, has shown that collagen IV augments BMP signalling by playing a key role in BMP gradient formation in Drosophila [19,20]. We hypothesized that another contributor to the reduced BMP signalling phenotype in collagen IV mutant embryos could be a failure to activate integrin signalling  (Figure 2C). In support of this hypothesis, the TorD-βPScyt signalling-activated integrin fusion protein, but not wild-type βPS, rescued the BMP phenotype in around half of the vkg mutant embryos (Figure 2D). Additional supporting data were obtained from tissue culture cells, in which integrins enhanced pMad levels when cells were plated on collagen IV but not plastic, whereas the TorD-βPScyt protein does increase pMad levels when cells are plated on plastic, consistent with it being constitutively active.
There is also evidence that collagen IV acts as an αPS1βPS integrin ligand in Drosophila during rotation of the egg chambers of ovarian follicles around their anterior–posterior axis that elongates the egg . This includes a critical requirement for both collagen IV fibres and regulation of αPS1βPS levels and adhesion in follicle cells for the cell migration, and the similarity in the vkg and mys phenotypes with both mutations giving round eggs [21,22]. Although our data support collagen IV as an integrin ligand, other data support laminin activating αPS1βPS integrins in Drosophila , which fits with the specificity of orthologous vertebrate integrins [16,24]. Similarly, evidence exists for laminin also activating αPS3βPS, including common mutant phenotypes, genetic interactions, and the ability of αPS3βPS-expressing tissue culture cells to spread on a laminin fragment [25,26]. Collectively, these findings suggest that the Drosophila αPS1βPS and αPS3βPS integrins can be activated by both laminin and collagen IV. A precedent for this exists for some of the vertebrate integrins, including α1β1, α2β1 and α3β1, with data supporting their activation by both laminin and collagen IV [17,27,28].
Analysis of embryos carrying a mutation in the β-laminin subunit revealed an increase in the expression of BMP target genes, including the peak target, Race . If, as discussed, αPS1βPS and αPS3βPS can be activated by laminin and collagen IV, this raises the possibility that these ligands compete for integrins in the early embryo, with only collagen IV-activated integrin signalling capable of augmenting the BMP pathway. In support of such competition, we found that adding laminin to BMP-treated tissue culture cells decreased pMad levels when cells are plated on collagen IV, an effect that can be rescued by mys overexpression. In contrast, no reduction in pMad levels was observed upon the addition of laminin to BMP-treated cells plated on plastic. Further experiments are required to fully address a role for ligand competition in vivo but, if true, this would suggest that it is the intricate balance of matrix protein abundance, rather than absolute levels, which determines BMP pathway activity.
Other examples of integrin–BMP synergy have been described through a range of different mechanisms (Table 1). For example, in human osteoblasts or osteosarcoma cells, type I and II BMP receptors associate with αv- (αvβ) and -β1 containing integrins . Blocking αvβ, α1β1 α2β1 integrin function reduced BMP responses and Smad-responsive transcription [29–31], without affecting BMP receptor-binding or BMP receptor–integrin co-localization . Attenuation of BMP responses was also observed when the BMP pathway was stimulated by a constitutively active BMP receptor, indicating that, as described for the Drosophila embryo , these integrins enhance BMP responses in osteoblasts downstream of BMP receptor activation.
In C2C12 cells, β3 integrins increase signalling by matrix-bound BMP-2 on soft substrate by inhibiting GSK3, which phosphorylates Smad1 leading to its proteasomal degradation . This mechanism requires the Src proto-oncogene tyrosine kinase and focal adhesion kinase (FAK), integrin-linked kinase (ILK) and the Rho GTPase Cdc42 , with ILK previously shown to negatively regulate glycogen synthase kinase 3 (GSK3) by phosphorylation . In addition, β3 integrins also increase pSmad1/5/8 levels by an unknown mechanism that is upstream of the integrin-dependent inhibition of GSK3-induced Smad degradation .
In murine embryonic endothelial cells, transforming growth factor β1 (TGF-β1) and BMP-9 signalling through the activin A receptor-like type 1 (ACVRL1, also called ALK1) receptor and endoglin co-receptor leads to Smad1/5/8 phosphorylation, which is increased by fibronectin activation of α5β1 integrin . α5 integrin associates with both endoglin, via its extracellular domain, and ACVRL1. Thereby, fibronectin-dependent clustering of α5β1 integrin can increase endoglin interaction with ACVRL1, which enhances Smad phosphorylation, potentially by increasing BMP binding to the clustered endoglin-ACVRL1 receptors. Co-internalization of endoglin and α5β1 integrin via a clathrin-dependent pathway was also observed. This internalization was required for activation of integrin signalling, but had no detectable effect on pSmad levels, suggesting that this is not part of the mechanism by which α5β1 integrin enhances Smad signalling.
Finally, oscillatory shear stress (OSS) in vascular endothelial cells has been proposed to promote Smad1/5 activation via a mechanism that involves αvβ3 integrin . OSS induces sustained association of BMP receptor type 1B (BMPR1B, also called ALK6) with αvβ3 integrin, which is dependent on the BMP receptor type 2 (BMPR2) intracellular kinase domain, leading to activation of a Shc–FAK–extracellular signal-regulated kinase (ERK) cascade and phosphorylation of Smad1/5. Smad1/5 associates with runt-related transcription factor-2 (Runx2), resulting in activation of Runx2, mammalian target of rapamycin and p70S6 kinase signalling that drives endothelial cell proliferation. Treatment with the BMP antagonist Noggin did not inhibit endothelial cell proliferation, suggesting that either the effect is ligand independent  or a Noggin-insensitive BMP, such as BMP-9 , may be involved.
In contrast with the enhancement of BMP signalling by integrins described thus far, other reports highlight how integrins can repress BMP signalling (Table 1). Ependymal zone stem cells (EZCs) can differentiate into astrocytes following spinal cord injury, with signalling through BMPR1B detrimental to recovery as it leads to the formation of a glial scar that inhibits axonal regeneration . However, EZCs up-regulate β1 integrin in response to injury, which inhibits canonical and non-canonical BMP signalling mediated by Smad1/5/8 phosphorylation and p38 MAPK activation, respectively. A similar negative effect of β1 integrin on BMP signalling is also observed in neural stem cells (NSCs), where BMP signalling can promote astrocytic differentiation. Loss of β1 integrin increases NSC differentiation. β1 integrin associates with BMP receptor type 1A (BMPR1A, also called ALK3) and BMPR1B in NSCs, but not with BMPR2, suggesting that the effect of β1 integrin on BMP signalling is mediated at the level of BMP receptors or downstream. Moreover, in the presence of β1 integrin, there is reduced partitioning of BMPR1B into lipid rafts, with BMPR1B localization in lipid rafts favouring signalling in NSCs. Together, these data suggest that β1 integrin limits the deleterious effect of BMP signalling in EZCs by preventing the movement of BMPR1B into lipid rafts that is necessary for signalling.
A study of bone marrow mesenchymal stem cells (BMMSCs) also provides evidence for integrin regulation of BMP receptor trafficking . On a soft versus stiff substrate, there is higher β1 integrin activation in these cells, but lower levels of cell surface β1 integrin due to enhanced internalization via caveolae. This β1 integrin internalization is necessary for neural fate specification on soft substrate. β1 integrin promotes caveolae-mediated internalization of BMPRIA, with co-localization of BMPRIA and β1 integrin in vesicles observed, which leads to reduced pSmad1/5/8 levels on soft substrate, allowing differentiation into a neural fate.
In contrast with the data described in the previous section, which support α1β1 integrin-mediated enhancement of BMP responses downstream of receptor activation , a negative role for α1β1 integrin through inhibition of BMP interaction with its receptor has also been proposed . Mutagenesis identified residues 85–89 in BMPR1A as important for the α1β1 integrin interaction in co-immunoprecipitation assays. As these BMPR1A residues have previously been shown to be required for BMP-2 interaction, this suggested that α1β1 integrin interaction with BMPR1A prevents BMP-2 binding. Consistent with this, α1 integrin knock-down in BMMSCs increases pSmad levels, although as yet it has not been directly shown that the presence of α1β1 integrin disrupts BMP receptor binding.
Positive regulation of integrins by BMP signalling has been reported in a range of contexts, with many of the studies described above showing increases in the expression levels or surface expression of integrins in response to BMP signalling. These include αvβ3, αvβ5, αvβ6, αvβ8 and α1β1 in osteoblasts [29,30] and β1 integrin in NSCs . Similarly, in endothelial cells, TGF-β1 increases α5β1 integrin levels by preventing lysosomal degradation, in addition to increasing α5β1 integrin activity by phosphorylation in an endoglin-dependent manner . In the Drosophila embryo, scb expression is transcriptionally activated by BMP signalling . While mew is expressed in the dorsal and neural ectoderm, scb has a restricted expression pattern in the dorsal ectoderm. Such restricted expression is the hallmark of a BMP target gene and we showed that increasing the copies of dpp or overexpression of TkvQD resulted in an expansion of scb, whereas its expression is lost in dpp mutant embryos. In addition to increasing integrin levels, BMPs can also promote integrin activation. In C2C12 cells, matrix-bound, but not soluble, BMP-2 induces cell spreading on soft matrix, by inducing clustering of fibronectin-activated β3 integrins, including αvβ3, which increases cell adhesion dynamics and leads to reorganization of the cytoskeleton and filopodia formation .
This stimulation of integrin levels by BMP signalling occurs in diverse contexts associated with integrins enhancing BMP responses. Such positive feedback may serve to amplify the BMP signal, generate a switch-like or bi-stable response from a graded input BMP signal and/or provide robustness to the cellular response [40,41]. It will be interesting to determine whether integrins are also BMP targets in the context of inhibitory cross-talk. If this is the case, such negative feedback could limit the duration of a signal, maintain homoeostasis by stabilising fluctuations in signalling or allow an adaptive or transient response to a constant BMP signal [40,41]. Finally, given that integrins are BMP targets in many of the synergistic contexts, it will also be useful to evaluate any BMP signalling regulatory roles for integrins in other situations, where BMPs are known to stimulate integrin levels. These include αPS2 integrin in the Drosophila eye disc , β1 integrin in rat pheochromocytoma-derived PC12 cells , αv integrin during hypertrophic differentiation of mouse chondrocytes  and αvβ3 in human chondrosarcoma cells .
It is clear that integrins regulate BMP signalling in a range of different cell types, with the resulting effect very context-dependent, much like the output of the BMP signalling pathway itself. One theme that has emerged though is that BMP receptor–integrin association — likely direct, although this has yet to be demonstrated — is central to the regulation [8,29,34,35,37,39]. In terms of the collagen IV–integrin–BMP synergy identified in the Drosophila embryo, this core mechanism may be relevant to angiogenesis, kidney development and stem cell fate decisions, as these are all contexts where collagen IV, integrin and BMP function have separately been implicated [46–51].
It is also possible that disruption of BMP–integrin cross-talk contributes to different disease phenotypes. For example, pulmonary arterial hypertension (PAH) is associated with disrupted BMP signalling, most commonly due to BMPR2 mutations. PAH arises from abnormal remodelling of small vessels in the lung, due to altered proliferation, survival and migration of vascular smooth muscle cells and endothelial cells with reduced BMP signalling [52,53]. As described above, BMPR1B and αvβ3 integrin associate in vascular endothelial cells, with integrins required for the Smad-dependent endothelial cell proliferation in response to OSS . Both BMP-9 and laminin-activated α3β1 integrin signalling protect pulmonary arterial endothelial cells from apoptosis [54,55], raising the possibility that BMP and integrin signalling also converge to promote cell survival. In these pulmonary arterial endothelial cells, laminin-activated α3-integrin recruits the adenomatous polyposis coli (APC) tumour suppressor protein, leading to activation of ILK1, phosphorylation of the serine/threonine kinase proto-oncogene Akt and cell survival. Reduced APC levels are detected in PAH patients' pulmonary arterial endothelial cells and it has been suggested that low APC activity may lead to a higher risk of PAH in combination with BMPR2 mutations . In pulmonary arterial smooth muscle cells, α4β1 integrin is required for BMP-2 induced cell migration, through effects on ILK-1 activation and both the canonical and planar cell polarity Wnt pathways , although how this mechanism is disrupted leading to the abnormal migration of smooth muscle cells in PAH is currently unclear.
Disruption of BMP–integrin synergy may also contribute to the anti-angiogenic properties of fragments of collagen IV that can suppress tumour growth in vivo . The effect of these collagen IV fragments is integrin-dependent, via an altered integrin signalling response . As BMPs can promote angiogenesis , it is possible that the soluble collagen IV fragments function, at least in part, by reducing BMP signalling. One option is that while the collagen IV network could activate integrins leading to a response that potentiates BMP signalling, the collagen IV fragments would outcompete the endogenous collagen IV network for binding to integrins, resulting in a distinct response that fails to enhance BMP responses. In this way, the collagen IV fragments would dampen the BMP pro-angiogenic response.
Finally, as BMPs are widely used to influence the fates of different stem cell types in vitro [46,58], manipulation of integrin signalling, potentially by plating cells on a particular substrate, may provide an opportunity to maximize, for example, the cellular response to BMP signalling. Consistent with this, addition of an RGD peptide with BMP-2 has been found to act synergistically to enhance the osteogenic commitment of human BMMSCs .
ACVRL1, activin A receptor-like type 1; APC, adenomatous polyposis coli; BMMSC, bone marrow mesenchymal stem cell; BMP, bone morphogenetic protein; BMPR1A, BMP receptor type 1A; BMPR1B, BMP receptor type 1B; BMPR2, BMP receptor type 2; CHO, Chinese Hamster Ovary; Dpp, Decapentaplegic; ERK, extracellular signal-regulated kinase; EZCs, ependymal zone stem cells; FAK, focal adhesion kinase; GSK3, glycogen synthase kinase 3; ILK, integrin-linked kinase; Mad, mothers against Dpp; MAPK, mitogen-activated protein kinase; mew, multiple edematous wings; mys, myospheroid; NSCs, neural stem cells; OSS, oscillatory shear stress; PAH, pulmonary arterial hypertension; pMad, phosphorylated Mad; RGD, Arg-Gly-Asp; Runx2, runt-related transcription factor-2; scb, scab; sog, short gastrulation; TGF-β1, transforming growth factor β1; Tkv, Thickveins; Vkg, Viking.
The Ashe lab research described in this review was supported by the Wellcome Trust (grant number [092005/Z/10/A]).
I thank Annick Sawala and Margherita Scarcia for helpful comments.


text:
« The Nose (part 6) | Main | The Nose (part 4) »
Saturday, October 22, 2011 at 17:18
The fifth part of a story by this Russian writer. You can read the original here.
With a feeling of inexpressible fear he raced to the table and moved the mirror nearer to himself, so as to make sure that he wouldn't put the nose on crookedly. His hands were shaking. Carefully and warily he placed it back in its former spot. Oh, the horror! The nose was not sticking back on! He lowered it to his mouth, blew some hot air on it and again raised it to that smooth spot between his two cheeks. But the nose would not stay on at all.
"Come on! Come on now! Get on there, you fool!" he said to it. But the nose seemed almost wooden and fell on the table with such an odd sound, as if it were a cork. The major's face convulsed. "Will it really never grow back on?" he said in panic. Yet however many times he tried to put the nose back in place, each new attempt was as unsuccessful as the last.
He summoned Ivan and sent him for the doctor, who happened to occupy in the very same building the nicest apartment on the second floor. The doctor was in all appearances a manly sort, with handsome, resinous sideburns and a lovely, healthy-looking wife. In the mornings he would eat fresh apples and kept his mouth unusually clean and pure, rinsing for at least three-quarters of an hour every morning and polishing his teeth with five different types of brushes. The doctor appeared that very minute. Having asked how long ago the misfortune occurred, he seized Kovalev by the chin and pushed his thumb down so hard on the spot where the nose had been that Kovalev snapped his head back and knocked it against the wall. The physician said that this was nothing and advised Kovalev to move away from the wall a bit. He then ordered him to turn his head to the right and, having felt about the nose's former spot, said "hmmm!" Then he ordered him to turn his head to the left and, having felt about the nose's former spot, said "hmmm!" Finally he again pressed his thumb onto the smooth spot with such force that Kovalev yanked back his head like a horse being looked at in the mouth. His test now complete, the doctor shook his head and said:
"No, it's not going to work. You're better off staying the way you are, because you could make it worse. Of course, it can be reattached; perhaps I could even reattach it for you right now. Yet I am convinced that this would be worse for you."
"Well that's just swell! What I am supposed to do without a nose?" said Kovalev. "It can't get any worse than it is now. Who knows what the hell it is! Where could I possibly show myself with such an absurdity? I know a large circle of people; this evening, for example, I was supposed to attend events at two different homes. A great many people know me: the wife of the state councillor, Chekhtareva, Podtochina, the wife of the staff officer ... although after her most recent act I will no longer have any dealings with her apart from those conducted by the police. Be so good as to tell me," said Kovalev with a pleading tone, "is there really no way? Just stick it on; it doesn't matter how as long as it holds. I could even prop it up with my hand in dangerous situations. And I won't dance so as not to harm it by some careless movement. Please be assured that with regard to my gratitude for your visit, all that my resources permit will be put to use ..."
"Believe me," said the doctor in neither a quiet nor a loud voice, but in a voice both extraordinarily tender and magnetic, "I never treat patients for mercenary reasons. This is against my rules and my art. True, I do take payments for house calls, but that is only so that I do not feel bad if I fail. Of course, I would reattach your nose; and yet I tell you upon my honor – if you don't happen to take me on my word – that it will be much worse. Leave that to nature itself. Wash more often with cold water and I assure you that you without a nose will be just as healthy as if you still had a nose. And I advise you to place your nose in a jar with some alcohol or, even better, pour in there two spoonfuls of sharp table vodka and a bit of heated vinegar. And then you could get quite a pretty penny for it. I could even take it off your hands if you don't ask too high a price ..."
"No, no, I won't sell it for anything!" screamed the desperate Major Kovalev. "It would be better if it simply disappeared!"
"I beg your pardon!" said the doctor, taking his leave. "I only wanted to do you a favor ... but what can I do? At least you see that I made an attempt."
Having said this, the doctor left the room with a rather noble bearing about him. Kovalev did not even notice his face, and in his profound numbness only saw the pure, snow-white sleeves of the doctor's shirt sticking out from under his frock coat.
The next day he decided, before formally filing a complaint, to write to the wife of the staff officer as to whether she would agree, without a struggle, to return to him what she owed. The contents of the letter were as follows:
"Dear Aleksandra Grigorevna!
Madam, I am still at a loss to understand an act on your part that I found strange. Rest assured that you will gain nothing in taking such a measure; in no way will you oblige me to marry your daughter. You should know that the story regarding my nose is well-known to me, just as it is known to me that you, and no other, are the main instigator in that affair. This sudden departure from its habitual place, its flight and its masking in the guise of a functionary, and, ultimately, in its own guise, are nothing more than the consequences of sorcery performed by you or by those who practice those arts precious to you. For my part I feel it my duty to warn you that if the aforementioned nose is not back in its place by today, I will be forced to resort to the defense and protection afforded me by the law.
Nevertheless, I have the great honor of remaining –
Your most humble servant,
Platon Kovalev."
"Dear Platon Kuzmich!
Sir, I was extraordinarily surprised by your last letter. I admit to you in all sincerity that I did not expect such a letter, and even less so the unjustified reproaches that you directed towards me. I will have you know that I never accepted into my home the functionary whom you mention, neither masked nor in his real identity. It is true that Filipp Ivanovich Potachnikov was at my house. And although he sought the hand of my daughter and is of good, sober manners and the highest personal integrity, I never allowed him any hope. You also mention the nose. If by this you mean that I wish to put your nose out of joint, that is, give you a formal refusal, then I am surprised that you are even talking about this since I, as far as you know, was of the contrary opinion. And if you now were to propose to her in accordance with the law, I would be prepared at this very minute to satisfy your request: for this has always comprised the subject of my most vivid desire, in the hope of which I remain
Most sincerely yours,
Aleksandra Podtochina."
"No," said Kovalev over and over again, having read the letter, "she is not guilty at all. It cannot be! The letter is written as no letter could possibly be written by someone guilty of a crime." The collegiate assessor was well-versed in such matters because he had been sent out several times on investigations in the Caucasus region. "How then, by what stroke of fate did this occur? May the Devil take it all!" he said at length, dropping his arms.
Meanwhile rumors about this unusual occurrence spread to all corners of the capital, and, as is almost always the case, not without a few additions. At that time everyone was in the mood for the extraordinary, and just recently had the effects of magnetism engrossed the public. Moreover, the story of the dancing chairs in Konyushennaya street was still fresh in everyone's mind, so it was hardly surprising that people began talking as if the nose of collegiate assessor Kovalev was strolling along Nevsky avenue at precisely three in the afternoon. Everyday a multitude of curious onlookers gathered. Someone had said that the nose was purportedly in Junker's store – and so a crowd assembled by Junker's and became such a throng that the police had to intervene. One whiskered spectator of very respectable appearance, having sold a number of dry baked goods at the entryway to the theater, intentionally set up some beautiful solid wood benches and offered a seat to curious onlookers for eighty kopecks. One very distinguished colonel intentionally left his home early and, with no small effort, made his way through the crowd. To his great chagrin, however, instead of a nose he espied in the shop window a run-of-the-mill woolen jersey, as well as a lithograph with the image of a girl mending a stocking and a young man with an open vest and burgeoning beard staring at her from behind a tree – a picture that had been hanging in the very same place for at least ten years. Walking away, he said in disappointment: "How can people get so worked up about such idiotic and absurd rumors?"
Then the rumor spread that the nose of Major Kovalev was not out strolling on Nevsky avenue, but in the Tauride garden, and it seemed as if it had been there for a long time already; even that Khosrow Mirza was still living there and that he was very surprised at this odd whim of nature. Several students from the surgeon's academy made their way there. One prominent, honorable lady in a particular letter asked the caretaker of the garden whether he couldn't show this rare phenomenon to her children and, if possible, with a didactic and edifying explanation for youths their age.
All these events were especially pleasing to those worldly, unnecessary attendees of balls, those who loved to make ladies laugh and whose reserve of wit had been exhausted by that point. A small group of honorable and well-intentioned people were extraordinarily unhappy. One gentleman said with no small indignation that he did not understand how in our enlightened age such silly inventions could possibly gain any currency, and he was just as astonished that this had not garnered the attention of the government. Obviously this fellow belonged to that rank of gentlemen who wanted to have the government interfere in everything, even in their daily quarrels with their wives. As a result ... and yet again the whole event is shrouded in fog, and what happened next is decidedly unknown.
tagged Gogol in Russian literature and film, Translation

redpajama_set_name: RedPajamaCommonCrawl


My new #1 goal from side mount has become to scoop the near-side arm with my head-side knee, and trap it up in the air. Given the transformation to a tighter game I'm willing myself through, it is really an ideal set-up for everything you could want to do from there (mount, or attack arms or neck).
This is not news to most practitioners, but it is different than my previous, light floating, fast-spinning top-side game.
I've known about, and occasionally used, this approach of getting under the arm, but with no real strategy preceding it, besides capitalizing on opponents' mistake of practically sending a singing telegram asking me to scoop it.
Recently, among the videos I habitually peruse before sleep, I came across the one posted here. I think Brad Wolfson might have recommended this guy's videos to me before. Anyway, upon seeing this particular tutorial, my interest level might have peaked at about "Neat." The true impact of the power of this little detail came later, when I was rolling and remembered to try it.
The efficacy and simplicity of this really wowed me.
As you can see in the video, with the opponent's hips twisted to face away from you, the options for that trailing elbow are to remain glued to the side of the body (and come off the mat, where it can be attacked), or stay on the mat, leaving a triangle of open space, more than large enough for that knee to scoop.
Getting the opponent to face away is a matter of tipping their knees away, either by rotating around the body "through" them, or threading over the near leg to hold the far one, as Dan shows in the video, or going low-tech, and just pushin' 'em over, which I've been doing with reasonably high success, having missed other subtleties in the video until reviewing it now.
Would love to hear if this helps anyone else, or if anyone else has different entry point ideas. Comment away if so. Hope this helps your game!


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Can Monster Hunter: World Fans Enjoy God Eater 3?
It isn't really controversial to compare Monster Hunter to God Eater. The two series have been running alongside each other for several years now, with other competitors, such as Koei Tecmo's Toukiden, stepping up to the plate as well. But God Eater has maintained its solid number two spot, and with God Eater 3 debuting as a high quality console exclusive, that doesn't seem to be changing anytime soon. However, what has changed in all this time is where Monster Hunter stands. It isn't just the number one game in its genre, it's the number one game at Capcom full stop. So what does that mean for God Eater 3?
With Monster Hunter, by "change" I refer to the arrival of Monster Hunter: World. While that game is still thoroughly Monster Hunter, it managed to flip the script in how that series is perceived by the general gaming audience. The way it presents itself, and the way the formula is tweaked to make it seem more "casual" on the surface, led to an explosion to the tun of 11 million copies sold. Despite Monster Hunter: World still being much more complicated and unfriendly compared to the average, online AAA game, people were suddenly willing to engage with that complexity, thanks to some quality of life features, smart marketing, and perfect timing.
But by now, Monster Hunter: World has more or less run its course. The content stream is pretty much over for the main game, though Capcom does have a full expansion on the way. But that expansion won't be landing until later in 2019, so the fans had to find something else to do while they wait. Enter God Eater 3.
While Bandai Namco titles always come with that "niche" branding practically on the box, there's no denying the company has grown in prestige over the course of the PlayStation 4. This has resulted in more visibility for its library overall. Curiosity and hunger for more Monster Hunter-like experience could make this God Eater's chance to shine.
Why bother? Naturally, I would argue that God Eater 3 isn't just more of the same. Otherwise, this article probably wouldn't need to exist. Nearly every aspect of Monster Hunter: World one can think of has a parallel of sorts in God Eater 3, for better or worse. This is not just a derivative copycat, it's a take on the genre or style, an interpretation of it that seeks to stand out by doing things differently. While being different is something you'd expect from a derivative work, God Eater 3 is often different in that it flies off in the opposite direction, slamming on the proverbial gas pedal.
As a fan of "character action" games, God Eater 3 speaks to me in my own language. This is a huge, fundamental difference from a Monster Hunter of any subtitle, as those games are more about being careful, picking your shots, and scrambling to survive. In God Eater, the player is the feral creature backed into the corner, and the game provides the tools to properly lash out at the otherwordly forces threatening extinction.
In Monster Hunter: World, you have a relatively simple moveset. There are only so many outcomes to pressing buttons, and the real strategy comes from knowing when and where to press those buttons. It takes ten years to swing a weapon once, and you need to make sure that swing counts. Even when you score a knockdown and you get to wail on a giant dinosaur for a few seconds, you aren't exactly dialing in combo strings. Monster Hunter wants the players to feel like they're actually trying to take down a real, massive, force of nature.
Meanwhile, God Eater is Anime. Nothing about the world or its characters is grounded in reality in a gameplay sense. To that end, most of the gameplay is capitalizing on openings, and knocking an Aragami down is more of a bonus than a goal. You can fight on the ground, you can fight in the air, you can literally have your weapon produce a mouth and take a bite out of a monster (and get some wild bonuses as a result). This is a combat game, through and through. If you want to play fast and furious instead of cool and meticulous, you want to give God Eater 3 a whirl just for that reason.
To that end, unlike Monster Hunter: World, in God Eater 3 you have options. There are verbs in there that you have to not only manage, but study and learn so you can yank them out of your bag of tricks at a moment's notice. This includes building up to Burst state, in which "eating" your enemies fills up a meter that gives you even more options. In Burst, you can double-jump, use multi-context special attacks, swap to your gun and use special shots, and more. This is in addition to a dashing move that may as well be short-distance flight, your regular combo potential and dodging, and chances to literally change the physical properties of your weapon.
God Eater isn't just "Anime" because you're aggressively darting around impossible monsters and racking up combos with living weapons. It's also full of high concept narrative ambition that assaults the player with made-up words and loud, over the top dialogue spouted by characters bonding over their existential suffering. While Monster Hunter is more concerned with drawn-out brawls against enemies that can take upwards of thirty minutes or more, God Eater 3 has you in and out of missions in half the time or less. All that extra time is taken with consistent exposition delivered through cutscenes, something Monster Hunter: World doesn't do until deemed absolutely necessary.
That leaves me looking at two core differences between God Eater 3 and Monster Hunter: World, and these differences are significant enough to appeal to different kinds of tastes. Monster Hunter: World is more of a grand, epic experience that wants you to soak it all in take your time figuring it out, collaborating, and learning granular details. Meanwhile, God Eater 3 wants to tell you a story and feed that story with more arcade or character action-style combat. You're in and out of missions super quick, and spend more time smashing buttons than planning your approach. You have friends with you, but it's more of a brawl than a war.
Both entries are probably the most accessible in their respective series, with God Eater 3 literally scorching its narrative earth right away, and Monster Hunter: World changing many of its fundamentals to appeal to a wider audience.


Prof. Dr. H.G. (Han) van Dissel is currently executive dean of the Faculty of Economics and Business of the University of Amsterdam. The dean gives direction and guidance to the faculty and is responsible for education and research.
From 1985 until 2007, van Dissel held various positions at the Rotterdam School of Management (RSM), where he was the dean from 2002 until 2007. From 2007 until 2011, van Dissel was general director of the Centre Européen d'Education Permanente (Cedep) in Fontainebleau, Paris. Further, van Dissel was active in the Community of European Management School, chairman of the supervisory board of the Wereldmuseum in Rotterdam and he still is member of the international board of advice of the ESC Rennes School of Business in France.


The Texanist: Are Bring Your Own Meat Meals Acceptable?
The Texanist addresses contentious BYOMeat gatherings.
Q: In our neighborhood, there are two families my wife and I are very close with. About ten years ago one of our neighbors invited us for dinner, a "bring your own meat" meal. Have you ever heard of such a thing? I sure hadn't. Anyway, I bought two beautiful inch-and-a-half New York strips for us to bring. I worked late at the office and by the time I arrived there was one scrawny cooked-to-death half-inch sirloin left, so I just made a plate of sides and sat down at the table. Then I noticed the others were eating my strips. My wife did manage to snag half of a strip and offered me part of hers, but I declined. My mind wasn't right. In the years since, both families have continued hosting these types of dinners and now it has evolved into "bring your own meat and a side." I will say, I am always on time and never let my meat out of my sight. I have refused to host a such a dinner myself. I figure if I invite someone over, then I'm responsible for preparing the full dinner. Am I wrong or should I acquiesce and have a "bring your own damn meat and a damn side" dinner?
A: The Texanist senses a festering irritation in your letter. And you are not wrong to be somewhat chapped at the way things have unfolded there in your neighborhood. The Texanist, as has been observed, is both a social butterfly and a voracious eater. As such, he's always happy to be invited over to friends' houses for convivial fellowship and a free meal. Unless it's those new people down at the end of the block. They're not very good cooks. And their house smells funny. And they have that overly amorous bullmastiff that always seems to make the Texanist the sole focus of his aggressively libidinous desires. No, thank you. But if it's anybody else, yes, please count the Texanist in.
In the Texanist's experience, such meals are typically one-off deals—or seasonal affairs, or, at least, few and far between—with guest lists that vary. Pete and Terry, Rich and his new girlfriend, Jim from the office, and the Millers. Properly executed, they're not a bad way to defer costs. But what you've got going with the two families in your hood seems to be a more regular occurrence—and an increasingly unwelcome one. This potluck of sorts has gone to pot. No man should have to worry about sitting idly by and watching another man enjoy the juicy beef cuts he intended for himself and his mate.
It's the Texanist's opinion that the time has come for you to do something daring. It's time for you to hold your own dinner party and set a higher standard for everyone involved by, as you suggest, preparing the full dinner yourself. This means appetizers, entrees, side dishes, desserts, drinks, a solid playlist, and general good times for all.
Let's start with some prosciutto-wrapped grilled asparagus. Then we can sit down with Mrs. Name Withheld's famous mixed-greens salad with the walnuts, strawberries, gorgonzola crumbles, and that delicious homemade dressing of hers. And let's do those big strips you like. Remember, Mrs. Soandso likes hers a little on the done side. We can side them with those garlic mashers and a medley of steamed veggies. Don't forget the warm sourdough dinner rolls and the herbed butter. And for dessert? An assortment of hand-cranked ice cream. The Texanist likes peach.
If you pull this off with the sort of panache that you seem to regard as every host's obligation, your cheapskate friends will be shamed into following suit. And soon enough all will be right in the neighborhood.
Send your own questions to [email protected] and don't forget to tell him where you're from.
I agree with the Texanist. One way we overcame the meat problem was by having the sides (beans and potatoes) already prepared and kept warm. If the BYOM was set to begin at 7:00 PM I had the BBQ pit(s) ready to cook on when the guests arrived. By having 2 pits ready the 1 guy who wanted his steak well done could start it immediately upon arrival. As we enjoyed cold beers, the other guest could time their meat to come off approximately at the same time as the well done one. We all cooked our own steaks the way we wanted them and, as the guests were responsible for their own meat, there were no complaints.
My kids gave me a small branding iron with my nickname on it. Might be what the guy needs. Or of course he can let everyone watch him spit on his steak.
I don't agree. I think that the OP would find out that his neighbors are some of the most selfish people on the planet and will always take advantage of him and his wife. That comes from experience.


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Below are highlights of What's On at the Precinct this week. We have lots of Trade Schools for you to enjoy!
Join three artists for a gentle walk along the Thames path. During the walk you will have an opportunity to take photos or sketch. No need to book; just show up at the Community Hub at 10.50am.


text:
Q: UWP ListView Drag and Drop I am going to drag an item from a ListView to drop a box to process something.
In this case, I am not able to get selected ListView item. Selected Index/Items always returns -1/null.
Note: I am able to get selected listview item when using SelectionChanged.
But not able to get drop event. Please advise.
The XAML source:
<ListView x:Name="lvMaster" CanDragItems="True" SelectionChanged="lvMaster_SelectionChanged" />

<Grid AllowDrop="True" Drop="Drop_Event" DragOver="DragOver_Event">
</Grid>

The C# source:
private void Drop_Event(object sender, DragEventArgs e)
{
    lvObj = new ListView();
    ListView)sender;
}

private void DragOver_Event(object sender, DragEventArgs e)
{
    AcceptedOperation = DataPackageOperation.Copy;
    DragUIOverride.IsCaptionVisible = true;
    DragUIOverride.IsContentVisible = true;
}

A: You can register DragItemsStarting event or DragItemsCompleted event for your listview, then in its handler method, you could get all items you dragged.
private void SourceListView_DragItemsCompleted(ListViewBase sender, DragItemsCompletedEventArgs args)
{
    var cc = args.Items;
}

Please refer to the official Drag and Drop sample for more details.
Please

redpajama_set_name: RedPajamaStackExchange


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Speaker Spotlight: Q&A With TU Wien's Allan Hanbury – Data Natives Berlin 2016
Juan Salazar · August 22, 2016
Juan Salazar 2016-08-22
Data Natives Berlin speaker Allan Hanbury is Senior Researcher and Privatdozent at the TU Wien, Austria. Since 2010, he has coordinated EU-funded research and development projects on analysis and search of medical text and image data. This led to the recent founding of a start-up, ContextFlow, which is bringing the developed radiology image search technology to the market. His team at the TU Wien also works on the analysis and search of unstructured data in technical documents (patents, scientific publications), financial documents (bank and company annual reports), and enterprise social networks. He also leads a project to develop the fundamentals of a Data-Services Ecosystem in Austria.
Go to datanatives.io and get instant access to speaker and ticket discount information on Data Natives Berlin 2016
Tell us a few words about yourself
My name is Allan Hanbury, and I am Senior Researcher at Technische Universität Wien (Vienna University of Technology). I work with the Institute of Software Technology and Interactive Systems, and will be speaking at Data Natives Berlin 2016.
What topic will you be discussing during Data Natives Berlin?
My talk focuses on analyzing and searching unstructured medical data
How did you get involved with medical data analysis?
I started off with a degree in physics, but I discovered that I had a lot more fun analyzing the data than actually setting up and doing the experiments to collect it, so I ended up in computer science. Here I have been concentrating on the analysis of unstructured data, which is the most challenging data to work on.
I got involved in working on analysis of data in the medical area after identifying an unmet technology need for analysis of multilingual medical text and medical images by discussing with people working in medicine and related areas. With this information, I wrote a proposal for an EU-funded project that was granted.
How is data being applied to change the medical field?
The most visible case in the medical field has been the discovery of major drug side effects by mining medical records. If a correlation between a drug and a specific side effect is discovered by mining the information in a huge number of anonymised patient records (i.e. a certain drug and a certain side effect happen to be mentioned together in many medical records), then this provides evidence for an investigation of whether the drug is actually causing the side effect. This has led to at least one drug being taken off the market, as it had heart attacks as a side effect.
There is a huge amount of data that is collected during routine medical care that is simply archived and never analyzed. There is a huge potential to access the implicit information in this data by mining it (in an anonymised form).
What do you hope to gain or learn during Data Natives Berlin?
I hope to meet many interesting people, and learn more about what is currently happening in data analytics in medicine and other areas.
What data-driven technologies are of particular interest to you and why?
I am interested in technologies that allow analysis and search of unstructured data, such as text, and which can find the relations between unstructured and structured data. For example, other work in my team is looking at predicting the evolution of financial indicators, based on the analysis of company and bank annual reports. At present, Word Embedding technologies are proving to be very powerful in text analysis, but they are basically mathematical tools that allow a text representation to be transformed in a way that is potentially useful – there is still plenty of investigation to be done on their limits and capabilities in practice.
Do you believe that Germany is a strategic market for showcasing data-driven technologies? If so, why?
Yes. Germany is a huge market that has a history of being innovative.
How is your field of interest driving the data revolution?
There is plenty of unstructured data stored everywhere, simply because it is easier to create unstructured data than structured data. It is easier to type text into a report, than going through the process of defining and using a data structure. Reading text is also easier for people, but of course it is challenging for automated analysis. The need to analyze the text out there is leading to really interesting technological approaches, but there are still many challenges.
Can you offer advice for other Data Natives wanting to get involved in this particular field?
It's not necessary to get a first degree in computer science. Any field that involves data analysis could be a starting point (such as physics, mathematics, statistics…) People coming from other fields into Data Science often bring useful skills and unexpected insights into the problems that need to be solved.
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Juan has experience working in communications and marketing, mainly with Berlin-based tech startups, and holds a B.A. from Humboldt University, Berlin. When he's not spending hours looking through data for good stories, he loves to read and write about the internet and the future of tech
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text:
What States Allow Late Term Abortion 2023
Abortion is the removal or expulsion of an embryo or fetus to end a pregnancy. Generally, there are two ways to end a pregnancy via abortion: an in-clinic procedure or the abortion pill. For many moral, ethical, religious, and political reasons, abortion is controversial in many countries.
Abortion is a relatively common procedure in the United States. According to the Guttmacher Institute, there were about 862,000 abortions in the U.S. in 2017. This is a 19% decline from 2011 when 1,058,000 were performed. Analyses have shown that abortion restriction, while harmful at an individual level, were not the main reason for the decline in abortions between 2011 and 2017. The decline in abortions seems to be part of a broader decline in pregnancies, evident in fewer births during the same period. The states with the highest abortion rates are the District of Columbia, New York, New Jersey, Maryland, and Florida.
Abortion Laws in the United States
Abortion laws permit, prohibit, restrict, or regulate the availability of abortion.
The Supreme Court decision of Roe v. Wade states that governments cannot regulate a woman's decision to have an abortion before the viability of the fetus. Viability is defined by the Supreme Court as the "the capacity of meaningful life outside the womb, albeit with artificial aid" and not just "momentary survival."
After viability, which is around 24-28 weeks, no government can impose a regulation that favors a fetus's life over a mother's. Despite this decision made by the Supreme court, the nation has divided into passion pro-life and pro-choice camps.
In recent years, some states have been proposing legislation to further restrict abortion earlier than fetus viability. States have recently introduced the "heartbeat" bill, which prohibits abortions after six weeks of pregnancy or when a fetal heartbeat can be detected.
In many cases, in the United States and around the world, restrictive abortion regulations do not always lead to lower abortion numbers. In some cases, abortion rates may actually be higher; however, restrictions could mean that more unsafe, illegal abortions are being performed. This causes complications and higher risks, such as death, for the mother.
States that Allow Late-term Abortions
A late-term abortion, also called a late-termination of pregnancy, refers to the termination of pregnancy by induced abortion during a late stage of gestation. "Late" is not precisely defined and medical publications have stated different thresholds, typically ranging from 20 to 28 weeks or around the fetus reaches viability.
Currently, 43 states prohibit some abortions after a certain point in pregnancy. Several states, such as California, Arizona, and New York, use fetus viability as the cutoff, while some other states use the third trimester (around 28 weeks). Other states use a specified number of weeks post-fertilization, after a women's last menstrual cycle, or after gestation. These weeks range anywhere from six to 20 weeks.
According to the Kaiser Family Foundation, as of August 1, 2020, 24 states prohibit some abortions at a specific gestational age.
States that allow for late-term abortions with no state-imposed thresholds are Alaska, Colorado, District of Columbia, New Hampshire, New Jersey, New Mexico, Oregon, and Vermont.
While other states have threshold restrictions for late-term abortions, all states have exceptions and allow late-term abortions when pregnancy threatens a woman's health, physical health, and/or life. The exception of "physical health" permits abortion when the woman suffers from a "substantial and irreversible impairment of a major bodily function." In the following states, the pregnancy must threaten the mother's life to permit a late-term abortion: Idaho, Michigan,and Rhode Island. In the following states, the pregnancy must either threaten the mother's life or health to permit a late-term abortion: Arizona, California, Connecticut, Delaware, Hawaii, Illinois, Maine, Maryland, Massachusetts, Minnesota, Nevada, New York, Virginia, and Washington.
In the following states, the pregnancy must either threaten the mother's life or physical health to permit a late-term abortion: Alabama, Arkansas, Florida, Georgia, Indiana, Iowa, Kansas, Kentucky, Louisiana, Mississippi, Missouri, Montana, Nebraska, North Carolina, North Dakota, Ohio, Oklahoma, Pennsylvania, South Carolina, South Dakota, Tennessee, Texas, Utah, West Virginia, Wisconsin, and Wyoming.
In Arkansas and Utah, late-term abortions are permitted in cases of rape or incest. Late-term abortions are almost permitted in case of fetal abnormality. In Delaware, Georgia, Louisiana, Mississippi, South Carolina, Texas, Utah, and West Virginia the law applies to a lethal abnormality.


A beta reader is one of the most important people you can have on deck during the revision and editing process. Beta readers are essential to the writing process for many authors, and yet not everyone knows what they are and what they do. If you're curious about beta readers and want to learn more about working with them, keep reading.
A beta reader is a person who reads and provides feedback on your manuscript before publishing.
You've self-edited your manuscript. You've inspected it for typos, grammatical errors, and structural integrity. Your manuscript looks perfect. No, scratch that. It is perfect. Is it really necessary to hand over a perfect manuscript to a beta reader who's only going to rip it apart?
Here's the thing: While your work may be perfect technically, it may not offer a compelling story or a riveting read. Your manuscript may suffer from plot-hole-itis or another common ailment known as changing-point-of-view-osis.
Beta readers help you see your story from another set of eyeballs.
Let's face it: You don't have the necessary emotional distance to read your own work objectively. For the same reason that you need an editor, you also need a beta reader to give you unbiased feedback on your manuscript.
Here's a list of questions to ask your beta readers.
There isn't a one-size-fits-all answer here. You may have five or six beta readers, or you may have several dozen.
Human nature predicts that some of the beta readers who commit to reading your manuscript won't actually complete it. To ensure that you don't waste time with non-starters or non-completers, you need a variety of beta readers.
Another reason to go for more than one beta reader? A more accurate sampling of your ideal audience. If you're only relying on the feedback of one reader, it'll be difficult to decide what's personal opinion and what's general consensus. However, if you have 11 different readers, and nine of them return with the same feedback, you minimize the guesswork.
Speaking of numbers, some writers prefer to have an odd number of readers. Theoretically, it's possible to have 10 beta readers with five saying, "Do this," and the other five saying, "Do that." To avoid a tie from happening, choose an odd number. Of course, this doesn't mean that you'll end up with an odd number (because, human nature), but at least you tried.
Do Beta Readers Replace Editors?
It's important to note that not all authors take this same path. Some authors work with beta readers earlier in the process. For example, you may work with a beta reader during step 2 while still writing your second draft. In this example, you'd share your book chapter by chapter, or section by section, with the beta readers. This allows for real-time feedback. You won't have to wait to make necessary corrections.
The drawback of this method is that your beta readers won't have the luxury of seeing the whole story before providing feedback, so their feedback may be resolved and therefore unnecessary.
Although beta readers are part of the editing stage, they don't replace professional editors. Professional editors are paid to comb through your entire manuscript and check for discrepancies, pacing, plot holes, and more.
Most professional editors (like the ones you'll work with here at NY Book Editors) have years of editing experience. Some of our editors have also worked as literary agents, too. When working with a professional editor, you'll have access to an industry professional who has an eye for detail and knows exactly what to look for in a manuscript.
Let's start out by saying that beta readers are most likely not your friends and family. Your loved ones love you. Unfortunately, that's a disqualifier.
So, where do the perfect beta readers hang out?
Are you a part of a writing community? If so, you have a candy store full of beta readers to choose from. Most writers, especially those within a supportive community, are willing beta readers– but remember that not all beta readers are writers. Here's a list of 11 top writing communities you should join and why.
Do you have a website? Do you receive traffic on your website? If you don't have a website, what about a social media presence? Do you have fans/ followers on your social media pages?
If you've already built a fan base, you can invite them to become beta readers of your work in progress.
Ideally, your beta reader should be well-read and familiar with the genre of your manuscript. You don't want to court a beta reader who enjoys romance for your sci-fi novel. It's not the end of the world, but probably won't give you the most insight with your target audience.
This is the reason you can't go with friends and family. Try as they may, they can't be completely honest with you about your work for fear of hurting your feelings and damaging your relationship. You need readers who don't have a reason to hold back and are willing to be brutally honest. When reaching out to potential readers, make this one of the first questions that you ask: Are you able to be brutally honest?
Do You Pay Beta Readers?
Most beta readers are not paid for their services. However, you should send your beta readers a free copy of your finished book, whether in the form of a hardcover or an eBook. It's also a nice gesture to autograph the copy. If you want to proclaim your never-ending gratitude, you can also list their names (not necessarily the role that they played) in the "Acknowledgement" section of your book.
When Should You Not Work With Beta Readers?
Beta readers almost always provide a benefit to authors. However, if you're writing certain genres, a beta reader may be limited in their helpfulness. For example, if you're writing a sci-fi novel that deals with quantum physics, you may need help from a subject matter expert, not your average beta reader.
Or, if you're writing a nonfiction book, it may be better to opt for a fact-checker instead of a beta reader. Because of the sensitive and laborious work involved, fact-checkers are usually professional editors who are paid for their efforts.
Another reason to forego beta readers is if you're in a time crunch and want to get your book published as soon as possible. In this case, consider only working with a professional editor who can provide both developmental and comprehensive edit within an agreed upon time frame.
Let's go over the best practices of working with beta readers.
You're going to need tough skin as a writer anyway. But if you haven't yet, now's the time to adopt a steely mindset. You're not looking for ego boosters, but people who can help you shape up your manuscript.
That said, it's not easy to let someone dismantle your work right in front of you. Just remember that they're critiquing your work and not your self-worth (and they're not always right). Also, remember that sharing your art with others requires bravery.
Not sure if something's working? Are you on the fence about a character or a plot element? Ask your beta readers what they think. It's almost like crowdsourcing your novel. Instead of waiting for the reviews to figure out what your readers really think, you can ask them during the beta process. These are real readers, and you've given them permission to share their real thoughts with you.
Remember to be as specific as possible with these questions. Don't say "whatever you can offer is fine". Instead, include a questionnaire with your manuscript that defines what you most help with (for example, What did you think about the character reveal in chapter 4? Did you get a sense of the world, or should I include more of the setting into the story?). Specific answers are much more valuable for you. Beta readers will also appreciate the guidance.
You've waited weeks for the feedback from these beta readers. You're ready to get cracking– but don't. At least, not yet. Read the feedback and let it wash over you. Think about how this feedback impacts your story and the characters within it. After a few days of thinking about it, you may decide to incorporate it or scrap it altogether.
While many (if not most) beta readers will prefer an ebook version of your manuscript, some beta readers actually want it printed on copy paper. Be flexible. Keep in mind that your beta readers are providing you with an invaluable service (and you're not paying them for it).
Give your beta readers a specific deadline for finishing your book. Be realistic. A good time to set for beta readers is one month.
Don't forget to download your free list of questions to ask your beta readers!
I don't trust beta readers for they might not critique your story in fear of hurting your feelings. So my question is, do I really need it? Will it prevent my novel from being published if I don't send it to a beta reader? I'm new to this field of publishing.
Where do I find beta readers, and do I have to pay for them?
You are making it look like these "beta readers" are something that should be part of a professional's process as well as beginners. This article will give new writers the impression that their books don't really have to be perfect due to their efforts. Their work can be substandard. The beta will fix it. Yawn. This beta think is just a handy and "legitimate" crutch for the wannabe hordes. Yawn.
Since many professional authors I've spoken to or heard speak use and appreciate beta readers, yes, it can be part of a professional's process. The point of a book is to be read by readers. Having someone read it before publication allows you to test whether you have succeeded in writing a readable book. They don't fix your book, they tell you if it is broken.
And 'Yawn'? Could you be any more condescending?
My novel: What happens when a middle-aged woman admits to wasting her life making do with a miserable marriage; but being stuck in a cult, is unable to make decisions and take control of her destiny.
I need honest readers. Soon. I'm twenty years older than when I began. Sigh.
Here's a list of questions to hand out to your beta readers. Subscribe to receive this extra resource.


text:
LNG INVOKES DEBATE IN THE BAY
A highly debated topic sparked a visit from a United States senator, Ron Wyden, to an appearance at the town hall meeting this past Sunday. The discussion of the Jordan Cove Energy Project was the primary cause of the senator's visit. This project would allow a liquefied natural gas export site to be built on the North Spit of Coos Bay.
"We have natural gas here that the world wants. It could economically put Coos Bay back on the map," Wyden Said.
Economic incentives have created an interest in the project by many, as an estimated 300 temporary construction jobs and 100 permanent family-wage jobs would be generated. However, an opposition to the project also was stated, as pollutants come along with natural gas.
"The big threat to natural gas is the methane that is emitted." Wyden said.
Residents representing both sides showed up to the town hall meeting, which was so large it had to be moved to the Hales Center Auditorium at Southwestern Oregon Community College. Wyden welcomed both sides of the debate, and wishes for it to continue.
"What we try to do in Oregon is reject the D.C. approach where you shoot down every belief," Wyden said.
pjs doudoune homme • Dec 8, 2013 at 5:25 pm
I really like it when folks come together and share ideas.
https://themarshfieldtimes.com/918/news/2537/#comment-24


Yo, check the acknowledgements... *flails and points at my name*Wish I had a brother like Michael. Well, a brother full stop... but to be like Michael. Yep. I was completely surprised, yo, at one of the turning points of Spirit. Just didn't expect it. Full review to come.


text:
Q: javascript dynamic form generation based on select option I have a small javascript problem ( i don't really know javascript, I just started to learn a little).
So it goes something like this:

*

*I have a form which should load a specific set of fields according to a selected option inside a html select tag so it should have three options in the select.

*

*choose option

*offer

*email

Someone I know told me to do something using switch/case but I honestly have no idea where to start from.
I've tried to do something with those hide/block thingies in css in order to hide /show a specific form div according to the selected option, but it doesn't work for me giving me the following issues:

*

*when i use the form submit button the whole form disappears so that should not happen

*the second thing i have a text field that has the same name in both divs called -url- and because the inputs are hidden yet still present on the page
if I write an url in the -offer- part it will set it to blank because the -url- field (hidden at the moment and under the offer part) in the e-mail part of the form is blank.
I hope it's clear, if you have any questions please ask me !
Here's the code :

 <form action="#" method="post" id="add" enctype="multipart/form-data" class="form-signin">
     <input type="hidden" name="id" value="{- $item.id -}" />
     <input type="hidden" name="save" value="1" />
     <input type="hidden" name="store" value="1" />
        <select name="is_type">
            <option value="choose">Choose option</option>
            <option value="offer">Offer</option>
            <option value="email">E-mail</option>
        </select>

choose your option

      {- "Url"|translate -} :

        <input type="text" class="form-control" id="url" name="url" value="{- $item.url|escape -}" size="50" />
        {-if $error.url-}
{-"The url is mandatory"|translate-}
{-/if-}

      {- "Name"|translate -} :

        <input type="text" class="form-control" id="name" name="name" value="{- $item.name|escape -}" size="50" />
        {-if $error.name-}
{-"The name is mandatory"|translate-}
{-/if-}

      {- "E-mail list:"|translate -} :

          <textarea name="list" rows="10" style="width:100%">{- $item.data|escape -}</textarea>
        {-if $error.list-}
{-"Insert at least one e-mail address"|translate-}
{-/if-}

      {- "E-mail"|translate -} :

        <input type="text" class="form-control" id="url" name="email" value="{- $item.url|escape -}" size="50" />
        {-if $error.url-}
{-"The E-mail is mandatory"|translate-}
{-/if-}

      {- "Url"|translate -} :

        <input type="text" class="form-control" id="url" name="url1" value="{- $item.url|escape -}" size="50" />
        {-if $error.url-}
{-"The url is mandatory"|translate-}
{-/if-}

     {- if $item.id -}
  <button class="btn btn-default"  type="submit">{- "Modify"|translate -}</button>
  {- else -}
  <button class="btn btn-default"  type="submit">{- "Add"|translate -}</button>
  {- /if -}

  {- "Cancel"|translate -}

</form>

Now don't worry about the curly braces in the form as it uses some weird smarty adaptation(made by some guy i know).

I guess it'a long read for a question along the lines : how do i generate the inputs based on a selected option in html select tag in javascript.
Thanks for taking the time to actually go through all of this mess, and again if you have questions please ask them, I really have to get this done.
edit someone asked something: where does this form go?
it gows to a controller called links_edit.php which processes the information , I know there is no action specified but it defaults to that controller, so it does the database query and form validations.
Additional code from the controller part(this is how i get the data from the form in the controller:
<?php
    $id       = $dbt->varGetFromInput('id');
    $store    = $dbt->varGetFromInput('store');
    $save     = $dbt->varGetFromInput('save');
    $is_type  = $dbt->varGetFromInput('is_type');
    ?>

from here on end I can do whatever to it

A: Try to follow my example:

jQuery(document).ready(SwitchFormCtrl);

function SwitchFormCtrl($) {
  var self = this;

  var select = $('select[name="is_type"]');
  var offerFieldset = $('.choose.offer');
  var emailFieldset = $('.choose.email');

  self.showEmailFieldset = function() {
    return offerFieldset
      .fadeOut()
      .promise()
      .then(function() {
        return emailFieldset
          .fadeIn()
          .promise()
        ;
      })
    ;
  };

  self.showOfferFieldset = function() {
    return emailFieldset
      .fadeOut()
      .promise()
      .then(function() {
        return offerFieldset
          .fadeIn()
          .promise()
        ;
      })
    ;
  };

  select.change(function() {

    switch((this.value || '').toLowerCase()) {
      case "offer":
        self.showOfferFieldset();
        break;

      case "email":
        self.showEmailFieldset();
        break;
    }

  });
}
.choose { margin: 5px; border: 1px solid green; padding: 5px; }
.choose.email { background: yellow; }
.choose.offer { background: cyan; }

/** hide both email and offer fieldset **/
.choose.offer,
.choose.email { display: none; }

<form action="#" method="post" id="add" enctype="multipart/form-data" class="form-signin">
     <input type="hidden" name="id" value="{- $item.id -}" />
     <input type="hidden" name="save" value="1" />
     <input type="hidden" name="store" value="1" />
        <select name="is_type">
            <option value="choose">Choose option</option>
            <option value="offer">Offer</option>
            <option value="email">E-mail</option>
        </select>

choose your option

      {- "Url"|translate -} :

        <input type="text" class="form-control" id="url" name="url" value="{- $item.url|escape -}" size="50" />
        {-if $error.url-}
{-"The url is mandatory"|translate-}
{-/if-}

      {- "Name"|translate -} :

        <input type="text" class="form-control" id="name" name="name" value="{- $item.name|escape -}" size="50" />
        {-if $error.name-}
{-"The name is mandatory"|translate-}
{-/if-}

      {- "E-mail list:"|translate -} :

          <textarea name="list" rows="10" style="width:100%">{- $item.data|escape -}</textarea>
        {-if $error.list-}
{-"Insert at least one e-mail address"|translate-}
{-/if-}

      {- "E-mail"|translate -} :

        <input type="text" class="form-control" id="url" name="email" value="{- $item.url|escape -}" size="50" />
        {-if $error.url-}
{-"The E-mail is mandatory"|translate-}
{-/if-}

      {- "Url"|translate -} :

        <input type="text" class="form-control" id="url" name="url1" value="{- $item.url|escape -}" size="50" />
        {-if $error.url-}
{-"The url is mandatory"|translate-}
{-/if-}

     {- if $item.id -}
  <button class="btn btn-default"  type="submit">{- "Modify"|translate -}</button>
  {- else -}
  <button class="btn btn-default"  type="submit">{- "Add"|translate -}</button>
  {- /if -}

  {- "Cancel"|translate -}

</form>


I have two forms: adding Item and invalidating Item I have ItemAddEditCommand that references Item and some other data.
Adding Item works great but I have problem with invalidating Item. In general it is an edit form that contains two form fields - expirationDate and comment.
When user inserts expireDate and comment and submits the form then all other fields except expiresDate and comment are nulled.
Btw. Maybe anyone can give me pointers how to get rid of DefaultBindInitializer.initBinder(binder); that initializes some property editors that should be ALWAYS used. Maybe some bean to make it default so I wouldn't have to call this method all the time.
How to bind Java Spring time attribute to a Thymeleaf field?