Now when all were come upon the shore, the king gan ask: "Who will show us the right roads through this land, that we go not astray?"
"Now hold," quoth Hagen, "both knight and squire. Certes, me- thinketh right that we should heed our friends. With full monstrous tales I'll make you acquaint: we shall never come again to the Burgundian land. Two mermaids told me early in the morning that we should not come back again. I will now counsel you what ye do: ye must arm you, ye heroes, for we have mighty foes. Ye must guard you well and ride in warlike guise. I thought to catch these mermaids in a lie. They swore that none of us would come home safe and sound, save the chaplain alone. Therefore would I fain have drowned him to-day."
These tidings flew from band to band and valiant heroes grew pale from woe, as they began to fear a grewsome death on this journey to Etzel's court. Forsooth they had great need. When they had crossed at Moering, (2) where Else's ferryman had lost his life, Hagen spake again: "Sith I have gained me foes upon the way, we shall surely be encountered. I slew this same ferryman early on the morn to-day. Well they wot the tale. Now lay on boldly, so that it may go hard with Gelfrat and Else, should they match our fellowship here to-day. I know them to be so bold that 'twill not be left undone. Let the steeds jog on more gently, that none ween we be a-fleeing on the road."
"This counsel I will gladly follow," quoth Giselher, the knight; "but who shall guide the fellowship across the land?"
Ere the wish was fully spoken, men saw the doughty fiddler standing there well armed. On his head he bound his helmet, of lordly color was his fighting gear. On his spear shaft he tied a token, the which was red. Later with the kings he fell into direst need.
Trustworthy tidings of the ferryman's death were now come to Gelfrat's ears. The mighty Else had also heard the tale. Loth it was to both; they sent to fetch their heroes, who soon stood ready. In a passing short time, as I'll let you hear, one saw riding towards them those who had wrought scathe and monstrous wounds in mighty battles. Full seven hundred or more were come to Gelfret. When they began to ride after their savage foes, their lords did lead them, of a truth. A deal too strong they hasted after the valiant strangers; they would avenge their wrath. Therefore many of the lordings' friends were later lost.
Hagen of Troneg had well planned it (how might a hero ever guard his kinsmen better), that he had in charge the rear guard, with his liegemen and his brother Dankwart. This was wisely done.
The day had passed away; the night was come. For his friends he feared both harm and woe, as beneath their shields they rode through the Bavarian land. A short time thereafter the heroes were assailed. On either side of the highway and in the rear hard by they heard the beat of hoofs. Their foes pressed on too hard. Then spake hold Dankwart: "They purpose to attack us here, so hind on your helmets, for that be well to do."
They stayed their journey, as though it must needs he; in the gloom they spied the gleam of shining shields. Hagen would no longer keep his peace; he called: "Who chaseth us upon the highway?"
To this Gelfrat must needs give answer. Quoth the margrave of Bavaria: "We seek our foes and have galloped on behind you. I know not who slew my ferryman to-day, but it doth rue me enow, for he was a hero of his hands."
Then spake Hagen of Troneg: "And was then the ferryman thine? The fault was mine, he would not ferry us over, so I slew the knight. Forsooth I had great need, for I had sheer gained at his hands my death. As meed I offered him gold and trappings, that he ferry me across to thy land, Sir Knight. This angered him so greatly that he smote me with a mighty oar. At this I waxed grim enow. I seized my sword and fended him his anger with a grievous wound. Thus the hero met his death. I'll make amends, as doth think thee best."
"Well I wist," spake Gelfrat, "when Gunther and his fellowship rode hither, that Hagen of Troneg would do us harm. Now he shall not live; the knight must stand for the ferryman's life."
Over the bucklers Gelfrat and Hagen couched their spears for the thrust; each would charge the other. Else and Dankwart rode full gloriously; they tested who they were, fierce was the fight. How might heroes ever prove each other better? From a mighty thrust Hagen was unhorsed by Gelfrat's hand. His martingale snapped, he learnt what it was to fall. The crash of shafts resounded from their fellowship. Hagen, who from the thrust afore had come to earth, down on the grass, sprang up again. I trow, he was not gentle of mood towards Gelfrat then. Who held their steeds, I know not; both Hagen and Gelfrat had alighted on the sand and rushed together. Their fellowship helped thereby and became acquaint with strife. Albeit Hagen sprang at Gelfrat fiercely, the noble margrave smote from his shield a mickle piece, so that the sparks flew wide. Full nigh did Gunther's liegeman die therefrom. He began to call to Dankwart: "O help, dear brother! Certes, a hero of his hands hath matched me, he will not spare my life."
The hero then sprang nearer and with a sharp sword smote Gelfrat such a blow that he fell down dead. Else then would fain avenge the knight, but he and his fellowship parted from the fray with scathe. His brother had been slain, he himself was wounded; full eighty of his knights remained with grim death behind upon the field. Their lord must needs turn in flight from Gunther's men.
When those from the Bavarian land gave way and fled, one heard the savage blows resound behind them. Those of Troneg chased their foes; they were in passing haste, who had not weened to make amends. Then spake Dankwart, the knight, in their pursuit: "Let us turn soon on this road and let them ride, for they be wot with blood. Haste we to our friends, this I advise you of a truth."
When they were come again, where the scathe had happed, Hagen of Troneg spake: "Heroes, prove now what doth fail us here, or whom we have lost in the strife through Gelfrat's wrath."
Four they had lost whom they must needs bewail. But they had been paid for dearly; for them a hundred or better from the Bavarian land were slain. From their blood the shields of the men of Troneg were dimmed and wet. Through the clouds there partly broke the gleam of the shining moon, as Hagen spake again: "Let none make known to my dear lords what we have wrought here to-day. Let them rest without care until the morn."
When those who just had fought were now come again, the fellowship was full weary from the way. "How long must we still ride?" asked many a man.
The doughty Folker, who had charge of the fellowship, bade ask the marshal: "Where may we find a place to-night, where our steeds may rest and our dear lords as well?"
Bold Dankwart answered: "I cannot tell you that, we may not rest till it begin to dawn. Wherever then we find a chance, we'll lay us down upon the grass."
How loth it was to some when they heard this tale! They remained unmarked with their stains of warm red blood, until the sun shot his gleaming light against the morn across the hills. Then the king beheld that they had fought. Wrathfully the hero spake: "How now, friend Hagen? I ween, ye scorned to have me with you when your rings grew wet with blood? Who hath done this?"
Quoth he: "This Else did, who encountered us by night. We were attacked because of his ferryman. Then my brother's hand smote Gelfrat down. Else soon escaped us, constrained thereto by mickle need. A hundred of them and but four of ours lay dead in the strife."
We cannot tell you where they laid them down to rest. All of the folk of the land learned soon that the sons of the noble Uta rode to court. Later they were well received at Passau. The uncle of the noble king, the Bishop Pilgrim, was blithe of mood, as his nephews came to his land with so many knights. That he bare them good will, they learned full soon. Well were they greeted, too, by friends along the way, sith men could not lodge them all at Passau. They had to cross the stream to where they found a field on which they set up pavilions and costly tents. All one day they must needs stay there, and a full night too. What good cheer men gave them! After that they had to ride to Rudeger's land, to whom the tidings were brought full soon. When the way- worn warriors had rested them and came nearer to the Hunnish land, they found a man asleep upon the border, from whom Hagen of Troneg won a sturdy sword. The same good knight hight Eckewart (3) in truth; sad of mood he grew, that he lost his weapon through the journey of the knights. They found Rudeger's marches guarded ill.
"Woe is me of this shame," spake Eckewart. "Certes this journey of the Burgundians rueth me full sore. My joy hath fled, sith I lost Knight Siegfried. Alas, Sir Rudeger, how I have acted toward thee!"
When Hagen heard the noble warrior's plight, he gave him back his sword and six red arm bands. "These keep, Sir Knight, as a token that thou art my friend. A bold knight thou art, though thou standest alone upon the marches."
"God repay you for your arm bands," Eckewart replied. "Yet your journey to the Huns doth rue me sore. Because ye slew Siegfried, men hate you here. I counsel you in truth, that ye guard you well."
"Now may God protect us," answered Hagen. "These knights, the kings and their liegemen, have forsooth no other care, save for their lodgement, where we may find quarters in this land to-night. Our steeds be spent by the distant way and our food run out," quoth Hagen, the knight. "We find naught anywhere for sale, and have need of a host, who through his courtesie would give us of his bread to-night."
Then Eckewart made answer: "I'll show you a host so good that full seldom have ye been lodged so well in any land, as here may hap you, an' ye will seek out Rudeger, ye doughty knights. He dwelleth by the highway and is the best host that ever owned a house. His heart giveth birth to courtesie, as the sweet May doth to grass and flowers. He is aye merry of mood, when he can serve good knights."
At this King Gunther spake: "Will ye be my messenger and ask whether my dear friend Rudeger will for my sake keep us, my kinsmen and our men? I will repay thee this, as best I ever can."
"Gladly will I be the messenger," Eckewart replied. With a right good will he gat him on the road and told Rudeger the message he had heard, to whom none such pleasing news had come in many a day.
He weened the foes had done him scathe. Before the gate he went to meet the messenger, who ungirt his sword and laid it from his hand. The tales he brought were not hidden from the host and his friends, but were straightway told them. To the margrave he spake: "Gunther, the lord of the Burgundian land, and Giselher, his brother, and Gernot, too, have sent me hither to you. Each of the warriors tendered you his service. Hagen and Folker, too, eagerly did the same in truth. Still more I'll tell you, that the king's marshal sendeth you by me the message, that the good knights have passing need of your lodgement."
Rudeger answered with a smile: "Now well is me of these tales, that the high-born kings do reck of my service. It shall not be denied them. Merry and blithe will I be, an' they come unto my house."
"Dankwart, the marshal, bade let you know whom ye should lodge in your house with them: sixty doughty champions, a thousand good knights, and nine thousand men-at-arms."
Merry of mood grew Rudeger; he spake: "Now well is me of these guests, that these noble warriors be coming to my house, whom I have served as yet full seldom. Now ride ye forth for to meet them, my kinsmen and my men."
Knights and squires now hied them to their horses; it thought them right, which their lord did bid. All the more they hasted with their service. As yet Lady Gotelind wist it not, who sate within her bower.
1Department of Pathology and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah.
2Department of Cancer Biology and Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio.
The DNA dependent protein kinase (DNA-PK) is a validated target for cancer therapeutics that drives the DNA damage response (DDR) and plays a critical role as a primary sensor in the non-homologous end joining (NHEJ) DNA double strand break (DSB) repair pathway. Various anti-cancer therapeutic strategies mediate their cytotoxic effects by inducing DSBs, including ionizing radiation (IR), and clinical outcomes are directly related to the repair of DNA damage. Modulating the pathway responsible for repairing DSBs will have a profound impact on the efficacy of DNA damaging agents in the clinic. To date, development of inhibitors for DNA-PK has focused on targeting the active site with ATP mimetics. We have taken the novel and innovative approach to inhibiting DNA-PK via blocking the Ku 70/80 heterodimer interaction with DNA, a necessary step in DNA-PK activation. Exploiting this unique mechanism of kinase activation, we have identified a series of highly potent and specific DNA-PK inhibitors that impart their inhibitory activity via disruption of the binding of Ku protein to DNA ends. This novel approach affords significant advantages to current approaches in kinase inhibition. Novel derivatives of our initial hit inhibit DNA-PK catalytic activity at nanomolar concentrations and potentiate cellular sensitivity to DSB-inducing agents like etoposide and bleomycin. Data demonstrate that the cellular effects observed are a function of Ku inhibition and that this novel class of DNA-PK inhibitors can be further developed as anti-cancer therapeutics that can be used as an adjuvant to, or concomitant with radiotherapy and other cancer therapies that induce DNA damage.
You are going to email the following Abstract LB-A11: Targeting DNA-PK and the DNA damage response via small molecule Ku inhibitors
Abstract LB-A12: Results from the phase 3 study ARIEL3: mutations in non-BRCA homologous recombination repair genes confer sensitivity to maintenance treatment with the PARP inhibitor rucaparib in patients with recurrent platinum-sensitive high-grade ovarian carcinoma