The Hindenburg Line was a German defensive position built during the winter of 1916–1917 on the Western Front during the First World War. The line ran from Arras near Soissons on the Aisne. In 1916, the Battle of Verdun and the Battle of the Somme left the German western armies exhausted and on the Eastern Front, the Brusilov Offensive had inflicted huge losses on the Austro-Hungarian armies and forced the Germans to take over more of the front; the declaration of war by Romania had placed additional strain on the German war economy. The Hindenburg Line, built behind the Noyon Salient, was built to replace the old front line as a contingency. By wasting the intervening ground, the Germans could delay an expected spring offensive in 1917. A shortened front could be held with fewer troops and with troop dispersal, reverse-slope positions, defence in depth and camouflage, German infantry could be conserved. Unrestricted submarine warfare and strategic bombing would weaken the Anglo-French as the German armies in the west recuperated.
On 25 January 1917, the Germans had 133 divisions on the Western Front but this was insufficient to contemplate an offensive. Greater output of explosives and weapons by German industry against the Allied Materialschlacht was attempted in the Hindenburg Programme of August 1916. Production did not sufficiently increase over the winter, with only 60 percent of the programme expected to be fulfilled by the summer of 1917; the German Friedensangebot of December 1916 had been rejected by the Entente and the Auxiliary Service Law of December 1916, intended to further mobilise the civilian economy, had failed to supply the expected additional labour for war production. The retirement to the Hindenburg Line took place from February to March 1917. News of the demolitions and the deplorable condition of French civilians left by the Germans were serious blows to German prestige in neutral countries. Labour was transferred south in February 1917 to work on the Hundingstellung from La Fère to Rethel and on the forward positions on the Aisne front, which the Germans knew were due to be attacked by the French.
Divisions released by the retirement and other reinforcements increased the number of divisions on the Aisne front to 38 by early April. The Hindenburg Line was attacked several times in 1917, notably at St Quentin, the Aisne and Cambrai and was broken in September 1918 during the Hundred Days Offensive. In August 1916 the German armies on the Somme had been subjected to great strain. Ten fresh divisions had been brought into the Somme front and an extra division had been put into the line opposite the British. Movement behind the German front was made difficult by constant Anglo-French artillery harassing-fire, which added to equipment shortages by delaying deliveries by rail and interrupting road maintenance. Destruction, damage and defective ammunition had caused 1,068 of 1,208 field guns and 371 of 820 heavy guns to be out of action by the end of August; the artillery deficit was only improved by the plan of General Max von Gallwitz, to centralise the command of the remaining artillery for counter-battery fire and to use reinforcements of aircraft to increase the amount of observed artillery fire, which had little effect on Allied air superiority but did increase the accuracy and efficiency of German bombardments.
The 2nd Army had been starved of reinforcements in mid-August to replace exhausted divisions in the 1st Army and plans for a counter-stroke had been abandoned for lack of troops. The emergency in Russia caused by the Brusilov Offensive, the entry of Romania into the war and the French counter offensive at Verdun had overstretched the German army. General Erich von Falkenhayn the German Chief of the General Staff was dismissed on 29 August 1916 and replaced by Field Marshal Paul von Hindenburg, with First Generalquartiermeister General Erich Ludendorff as his deputy. Oberste Heeresleitung ordered an end to attacks at Verdun and the dispatch of troops from there to Romania and the Somme front. On 5 September, proposals for a new shorter defensive position to be built in France were requested from the commanders of the western armies, who met Hindenburg and Ludendorff at Cambrai on 8 September; the western front commanders were told that no reserves were available for offensive operations, except those planned for Romania.
Generalleutnant Georg Fuchs, one of the corps commanders, recommended that a defensive line be built from Arras to west of Laon, shortening the front by 25 mi and releasing ten divisions which, with other troops, could be used for an offensive in Alsace or Lorraine. Ludendorff criticised the practice of holding ground regardless of its tactical value and advocated holding front-line positions with a minimum of troops and the recapture of lost positions by counter-attacks, a practice, forced on the German armies on the Somme. On 15 September Generalfeldmarschall Crown Prince Rupprecht, commander of the northern group of armies, was ordered to prepare a rear defensive line and on 23 September work on the new Siegfriedstellung began. On 21 September, after the battle of Flers–Courcelette, Hindenburg ordered that the Somme front would have priority in the west for troops and supplies. By the end of the Battle of Morval Rupprecht had no reserves left on the Somme. During September, the Germans sent another thirteen fresh divisions to the British sector and scraped up troops wherever they c
Pune Pride is an annual LGBT pride parade, first held in Pune, Maharashtra on 11 December 2011. It is the second Pride parade to be organized in the state of Maharashtra, after the Queer Azaadi Mumbai Pride March; the city saw its first pride march known as the "Gay Pride & HIV awareness march" in the old city area of Pune on 11 December 2011 where around 50 people from the LGBT community and equal number of supporters participated. It was organised by Samapathik Trust, a men’s sexual health organization. Participants were requested to not wear masks or paint their faces and to not engage in "skin show"; the 11 December 2011 parade was the first open pride parade event in Pune's history, was organized by SAMAPATHIK TRUST, PUNE. Samapathik Trust Staff had requested participants, who numbered around 50-60 according to Daily News and Analysis, to not wear masks and to wear professional clothing in order to reflect the culturally-conservative "ethos" of the city. Participants who came from Mumbai noted the comparatively subdued atmosphere of the parade in comparison to the more-flamboyant atmosphere of Pride events in Mumbai.
The parade was preceded the previous day by a Queer Fest in the Kala Chhaya, organized by Open Space, Birds of a Feather, The Queer Chronicle, India's longest running LGBT monthly online magazine and Quintessence and hosted over 200 participants. Pune witnessed its 2nd queer pride parade organized by Samapathik Trust on 9 December 2012; the pride parade focused upon breaking the stereotypical image of Queer people in the films and TV serials and creating awareness about the same along with clearing the misconceptions about the Gay community. On 24 November 2013, The third edition of Pune pride saw more than 150 people from the LGBT community and allies walking the pride and showing their support towards the LGBTQ community; the parade started from Pune Sarvajanik Sabha at 11AM and it was led by the Sonal Giani and other members from Umang Trust in order to spread the sensitization about issues faced by Lesbian and Transmen from the Queer community. The highlight of the pride was the open support shown by Police department led by Inspector Bhanupratap Barge, whose team distributed Red Roses to the participants as a gesture of support and cooperation towards the rights of the community.
The fourth edition of the Pune LGBT Pride March will be held on Sunday, 9 November 2014, Organized by Samapathik Trust, Pune. The Theme of this year would be "Youngistan Zindabaad"; as the theme suggests, The focus was on addressing the issues faced by the youngsters because it is important for them to accept their sexuality and be aware of their rights. To incorporate more youths, the organizers have changed the route of the march, While earlier it used to be a walk through Laxmi Road and the Peth areas, this time around they will follow the JM Road and FC Road route. On 23 August 2015 the fifth edition of Pune pride was organized by Samapathik Trust; the march started at 11AM from Sambaji Park at JM Road with participants from various cities walking down the lanes with posters and banners, colorful clothes and rainbow umbrellas with them. The pride theme this year was "Addressing the Transgender rights", in order to focus the issues related with the discrimination and harassment faced by Hijra/Transgender community due to section 377.
There was a special bus being arranged by an organization called "Gay Bombay" to provide an easy conveyance for the participants from Mumbai willing to attend this Pride. The sixth edition of Pune pride was organized by Samapathik Trust founded by Mr. Bindumadhav Khire on Sunday, 7 August 2016; the parade started from Sambhaji Park and following Fergusson college road it ended at back to JM Road. The pride theme for this year was "Inclusivity at workplace" to address the discrimination and challenges faced by LGBTQ employees in the corporate environment. Despite of heavy Rains, the pride march received a rousing response from the Queer community, it was the first time when the representatives from the multinational corporations like IBM, Symantec and Thoughtworks showed their active participation by attending the pride carrying supporting banners and T-shirts. The Seventh edition of Pune Pride took place on 11 June 2017 with a huge number of 700 people walking the pride this time; this pride is organized every year since 2011 by Samapathik Trust founded by Mr. Bindumadhav Khire.
This year the Pride parade received an open support by many known corporates like IBM, ADP, Thoughtworks,Symantec, Accenture and The Bank of New York Mellon. The pride started at 10:30 AM from The Chhatrapati Sambhaji Garden, went down to Garware Chowk and ended at JM Road; the pride theme for this year was to express the gratitude towards parents and allies of LGBTQ people for their understanding and due support. This was the first time when the grand Marshalls for the pride were the parents, siblings and friends of LGBTQ people leading the pride and spreading the message of supporting the cause; the pride received opposition from the participants due to its stringent rules asking the people to wear decent clothes and not to use any placards or slogans which are against Supreme Court, political parties, leaders and caste. The Pune Pride march in 2018 was once again organised by the Samapathik Trust took place on 3 June and more than 800 community members and supporters were in attendance; the march was supported by prominent organisations including Humsafar Trust, Umang Organisation For Lesbian Bisexual and Transgender Women and Sweekar, the Rainbow Parents of India.
The pride saw the support of the local police force as well as corp
The norepinephrine transporter known as noradrenaline transporter and solute carrier family 6 member 2, is a protein that in humans is encoded by the SLC6A2 gene. NET is a monoamine transporter and is responsible for the sodium-chloride -dependent reuptake of extracellular norepinephrine, known as noradrenaline. NET can reuptake extracellular dopamine; the reuptake of these two neurotransmitters is essential in regulating concentrations in the synaptic cleft. NETs, along with the other monoamine transporters, are the targets of many antidepressants and recreational drugs. In addition, an overabundance of NET is associated with ADHD. There is evidence that single-nucleotide polymorphisms in the NET gene may be an underlying factor in some of these disorders; the norepinephrine transporter gene, SLC6A2 is located on human chromosome 16 locus 16q12.2. This gene is encoded by 14 exons. Based on the nucleotide and amino acid sequence, the NET transporter consists of 617 amino acids with 12 membrane-spanning domains.
The structural organization of NET is homologous to other members of a sodium/chloride-dependent family of neurotransmitter transporters, including dopamine, serotonin and GABA transporters. A single-nucleotide polymorphism is a genetic variation in which a genome sequence is altered by a single nucleotide. NET proteins with an altered amino acid sequence could be associated with various diseases that involve abnormally high or low plasma levels of norepinephrine due to altered NET function. NET SNPs and possible associations with various diseases are an area of focus for many research projects. There is evidence suggesting a relationship between NET SNPs and various disorders such as ADHD psychiatric disorders, postural tachycardia and orthostatic intolerance; the SNPs rs3785143 and rs11568324 have been related to attention-deficit hyperactivity disorder. Thus far, the only confirmed direct association between a SNP and a clinical condition is that of the SNP, Ala457Pro, orthostatic intolerance.
Thirteen NET missense mutations have been discovered so far. An epigenetic mechanism that results in reduced expression of the noradrenaline transporter and a phenotype of impaired neuronal reuptake of norepinephrine has been implicated in both postural orthostatic tachycardia syndrome and panic disorder; the norepinephrine transporter is composed of 12 transmembrane domains. The intracellular portion contains carboxyl group. In addition, there is a large extracellular loop located between TMD 3 and 4; the protein is composed of 617 amino acids. NET functions to transport synaptically released norepinephrine back into the presynaptic neuron; as much as 90% of the norepinephrine released will be taken back up in the cell by NET. NET functions by coupling the influx of sodium and chloride with the transport of norepinephrine; this occurs at a fixed ratio of 1:1:1. Both the NET and the dopamine transporter can transport dopamine; the reuptake of norepinephrine and dopamine is essential in regulating the concentration of monoamine neurotransmitters in the synaptic cleft.
The transporter helps maintain homeostatic balances of the presynaptic neuron. Norepinephrine is released from noradrenergic neurons that innervate both the CNS and PNS. NE known as noradrenaline, has an important role in controlling mood, memory and pain perception. NE is a part of the sympathetic nervous system. Dysregulation of the removal of norepinephrine by NET is associated with many neuropsychiatric diseases, discussed below. In addition, many antidepressants and recreational drugs compete for the binding of NET with NE; the transport of norepinephrine back into presynaptic cell is made possible by the cotransport with Na+ and Cl−. The sequential binding of the ions results in the eventual reuptake of norepinephrine; the ion gradients of Na+ and Cl− make this reuptake energetically favorable. The gradient is generated by the Na+/K+-ATPase which transports three sodium ions out and two potassium ions into the cell. NETs have conductances similar to those of ligand-gated ion channels; the expression of NET results in a leak-channel activity.
NETs are restricted to noradrenergic neurons and are not present on neurons that release dopamine or epinephrine. The transporters can be found along the cell body and dendrites of the neuron. NETs are located away from the synapse, they are found closer to the plasma membrane of the cell. This requires norepinephrine to diffuse from the site it is released to the transporter for reuptake. Norepinephrine transporters are confined to the neurons of the sympathetic system, those innervating the adrenal medulla and placenta. Regulation of NET function is a focus of current research. NETs are regulated at both the molecular level post-translation; the most understood mechanisms include phosphorylation by the second messenger protein kinase C. PKC has been shown to inhibit NET function by sequestration of the transporter from the plasma membrane; the amino acid sequence of NET has shown multiple sites related to protein kinase phosphorylation. Post-translational modifications can have a wide range of effects on the function of the NET, including the rate of fusion of NET-containing vesicles with the plasma membrane, transporter turnover.
Orthostatic intolerance is a disorder of the autonomic nervous system characterized by the onset of symptoms upon standing. Symptoms include fat