14 Matching Annotations
  1. Oct 2021
  2. Mar 2021
    1. Results for individual PALB2 variants were normalized relative to WT-PALB2 and the p.Tyr551ter (p.Y551X) truncating variant on a 1:5 scale with the fold change in GFP-positive cells for WT set at 5.0 and fold change GFP-positive cells for p.Y551X set at 1.0. The p.L24S (c.71T>C), p.L35P (c.104T>C), p.I944N (c.2831T>A), and p.L1070P (c.3209T>C) variants and all protein-truncating frame-shift and deletion variants tested were deficient in HDR activity, with normalized fold change <2.0 (approximately 40% activity) (Fig. 1a).

      AssayResult: 5.8

      AssayResultAssertion: Normal

      StandardErrorMean: 1.15

    2. A total of 84 PALB2 patient-derived missense variants reported in ClinVar, COSMIC, and the PALB2 LOVD database were selected

      HGVS: NM_024675.3:c.925A>G p.(Ile309Val)

  3. Sep 2018
    1. Everything is not provided for, because a great deal is trusted lo the common sense of the people. I think it is quite fair and safe to assert that there is not the slightest danger that the Federal Parliament will perpetrate any injustice upon the local legislatures, because it would cause such a reaction as to compass the destruction of the power thus unjustly exercised. The veto power is necessary in order that the General Government may have a control over the proceedings of the local legislatures to a certain extent. The want of this power was the great source of weakness in the United States, and it is a want that will be remedied by an amendment in their Constitution very soon. So long as each state considered itself sovereign, whose acts and laws could not be called in question, it was quite clear that the central authority was destitute of power to compel obedience to general laws. If each province were able to enact such laws as it pleased, everybody would be at the mercy of the local legislatures, and the General Legislature would become of little importance. It is contended that the power of the General Legislature should be held in check by a veto power with reference to its own territory, resident in the local legislatures, respecting the application of general laws to their jurisdiction. All power, they say, comes from the people and ascends through them to their representatives, and through the representatives to the Crown. But it would never do to set the Local above the General, Government. The Central Parliament and Government must, of necessity, exercise the supreme power, and the local governments will have the exercise of power corresponding to the duties they have to perform. The system is a new and untried one, and may not work so harmoniously as we now anticipate, but there will always but p ¡war in the British Parliament and our own to remedy any defects that may be discovered after the system is in operation. Altogether, I regard the scheme as a magnificent one, and I look forward to the future with anticipate- tins of seeing a country and a government possessing great power and respectability, and of being, before I die, a citizen of an immense empire built up on our part of the North American continent, where the folds of the British flag will float in triumph over a people possessing freedom, happiness and prosperity equal to the people of any other nation on the earth.

      §.90 of the Constitution Act, 1867.

    1. any law it might pass to this effect and set it at nought. HON. MR. HOLTON—Would you advise it? HON. ATTY. GEN. CARTIER—Yes, I would recommend it myself in case of injustice. (Hear, hear.) HON. MR. ROSE—I am quite sure my hon. friend would do it rather than have an injustice perpetrated. There is another pout upon which I would like to have from the Attorney General East an explicit statement of the views of the Government. I refer to the provision in the 23rd resolution which I have just read ; what I wish to know is whether the Legislature therein spoken of means the Legislature of the province of Canada as it is now constituted, and whether it is contemplated to have any change in the boundaries of the electoral districts for representation in the first session of the Federal Legislature ? HON. ATTY. GEN. CARTIER—With regard to Lower Canada, it is not the intention to make any alteration in the electoral districts, because there will be no change in the number of representatives sent to the General Parliament. But with regard to Upper Canada, there will be a change in the electoral districts, because there will be an increase of members from that section. HON. MR. ROSE—So that I clearly understand from the statement of the hon. gentleman that in Lower Canada the constituencies, for the purposes of the first ejection to the Federal Legislature, will remain as they are now ? HON. ATTY. GEN. CARTIER—Yes, as they are now. HON. MR. ROSE—And that as regards the representation in the Local Legislature, the apportionment of the electoral districts by it will be subject to veto by the General Government. HON. ATTY. GEN. CARTIER—Yes, in case of injustice being done. (Hear, hear.)

      §§.40 and 90 of the Constitution Act, 1867.

    1. Well, I ask the House, what is wrong in those two clauses ? At present, what is our position when a bill has passed the two Houses of our Legislature ? It is this : the bill is submitted for the sanction of the Governor General, and in nearly all cases is sanctioned without being referred to the Imperial Government. But if, for instance, the bill relates to a divorce, or to any question which concerns the Imperial Government, or if again it is a measure affecting our relations with our neighbors or any other nation, it is then reserved for Her Majesty’s sanction. When a measure is thus reserved, does the honorable member for Hochelaga suppose that the members of the English Government meet to take it into consideration ? Not at all ; there is in the Colonial Office a second or a third class clerk whose particular business it is, and who makes his report to the minister. This report decides either the sanction or the disallowance of the measure in question. If the measure is highly interesting to the country and is disallowed, we cannot blame any one and must submit, as the English ministry are not responsible to us. Under the Confederation this danger and inconvenience will no longer exist. In a case wherein the Local Government of Lower Canada should pass a law which the Lieutenant-Governor might think fit to reserve for the sanction of the Central Government, if the latter refused their sanction, although it was demanded by the people of the section, and there were no reason for this refusal, we should have our sixty-five members in the Central Parliament to protest against it, and who would unite and make combinations to turn out the ministry who should act in that manner.

      §§.56 and 90 of the Constitution Act, 1867.

    1. the Lieutenant-Governor, who will enjoy the right of reserving the bills of the Local Parliament for the sanction of the Governor General, will be appointed by the Governor General in Council, that is to say, by the Federal Government, and, as a matter of course, it must be expected that he will act in conformity with the views of the Federal Government. Any bill reserved by him will require to be sanctioned by the Federal Government, which may refuse such sanction if they think proper, as they undoubtedly will as regards any bill the object of which might be to give responsible government to Lower Canada, whilst all the other provinces would only have governments which were not responsible. And the militia,—it will be exclusively under the control of the Federal Government. Have the honorable the French-Canadian members, to whom I more particularly address myself at this moment, reflected on the danger to us that is contained in this provision ?

      §§.90 and 92(1) of the Constitution Act, 1867.

    1. to impose export duties on these articles. This provision, it seems, was too favorable to Lower Canada ; for it would have allowed Lower Canada to impose an export duty upon Upper Canadian timber. HON. MR. HOLTON—AS New Brunswick does upon American. HON. MR. DORION—And by this means raise a sufficient revenue, at the expense of Upper Canada, to meet its local expenditure. This mistake seems to have been corrected, for, in this respect, the resolutions before the House have been changed, but hardly amended. HON. MR. HOLTON—Changed in a sense hostile to Lower Canada. (Hear.) HON. MR. DORION—The clause of the resolutions to which I refer now reads, that the General Parliament shall have power to make laws ” respecting the imposition or regulation of duties of customs on imports and exports—except on exports of timber, logs, masts, spars, deals and sawn lumber from New Brunswick, and of coal and other minerals from Nova Scotia.” That is, the General Government may impose a tax for its own benefit upon all timber and minerals exported from Upper or Lower Canada, but not from New Brunswick or Nova Scotia. (Hoar, hear.) Then, among the powers granted to local legislatures, we find the power to pass by-laws imposing direct taxation. (Hear, hear.) That is the first power they have, and I have no doubt that, before many months have passed after they are constituted, they will find it necessary to resort to it. But, in addition to this, I find that New Brunswick and Nova Scotia, which, no doubt, are the favored children of the Confederation, have powers not granted to the other provinces. New Brunswick, the resolution declares, shall have the power to impose an export duty on timber, logs, masts, spars, deals and sawn lumber, and Nova Scotia on coal and other minerals, for local, purposes ; so that while our timber and minerals exported from Upper and Lower Canada will be taxed by the General Government for general purposes, the timber and minerals of New Brunswick and Nova Scotia will be exempt, the revenue derived from them going to the benefit of the local governments, to be expended on local objects. (Hear, hear.) This is one of the results of the Conference in which, of course, New Brunswick counted as much as Upper and Lower Canada, and Nova Scotia and the other Lower Provinces had the balance of influence.

      §§.90 and 95 of the Constitution Act, 1867.

    2. Then sir, I find that in addition to all the other sums that are to be paid by the general to the local governments, there are provisions in favor of New Brunswick and Nova Scotia, which must strike the House as being of a rather extraordinary nature. In the document, which was sent by the Provincial Secretary to the members of this House marked “Private,” there appears to have been a mistake. It was therein stated that the General Government would have no right to impose an export duty on timber, logs, masts, spars, deals and sawn lumber ; but that the local governments would have the power

      §.90 of the Constitution Act, 1867.

    3. Now, knowing that the General Government will be party in its character, may it not for party purposes reject laws passed by the local legislatures and demanded by a majority of the people of that locality. This power conferred upon the General Government has been compared to the veto power that exists in England in respect to our legislation ; but we know that the statesmen of England are not actuated by the local feelings and prejudices, and do not partake of the local jealousies, that prevail in the colonies. The local governments have therefore confidence in them, and respect for their decisions; and generally, when a law adopted by a colonial legislature is sent to them, if it does not clash with the policy of the Empire at large, it is not disallowed, and more especially of late has it been the policy of the Imperial Government to do whatever the colonies desire in this respect, when their wishes are constitutionally expressed. The axiom on which they seem to act is that the less they hear of the colonies the better. (Hear, hear.) But how different will be the result in this case, when the General Government exercises the veto power over the acts of local legislatures. Do you not see that it is quite possible for a majority in a local government to be opposed to the General Government; and in such a case the minority would call upon the General Government to disallow the laws enacted by the majority ? The men who shall compose the General Government will be dependent for their support upon their political friends in the local legislatures, and it may so happen that, in order to secure this support, or in order to serve their own purposes or that of their supporters, they will veto laws which the majority of a local legislature find necessary and good.

      §.90 of the Constitution Act, 1867.

    1. HON. MR. MOORE—It will be conceded that the question of the veto power was very ably discussed, at one time, in the United States Congress, and that discussion led to a qualification of the veto power in the Constitution of the United States, so that now any bill passed by both Houses may be vetoed by the President within ten days thereafter, by assigning reasons for doing so. Both Houses may then, however, again take up the measure, and if they pass it by a two-third vote, it becomes the law of the land, independent of the President’s will. Now, I would have the veto power applied in a similar way in our new Constitution. Exercising it in an arbitrary manner, as the Federal power is privileged to do, it must, from the very nature of things, create dissatisfaction and difficulty between the two governments.

      §.90 of the Constitution Act, 1867.

    2. I think that the engrafting of this system of government upon the British Constitution has a tendency to at least introduce the republican system. It is republican so far as it goes, and that is another reason why I do not approve of it. If we commence to adopt the republican system, we shall perhaps get the idea of continuing the system until we go too far. I t is also said that we are to have a new nationality. I do not understand that term, honorable gentlemen. If we were going to have an independent sovereignty in this country, then I could understand it. I believe honorable gentlemen will agree with me, that after this scheme is fully carried into operation, we shall still be colonies. HON. SIR E. P. TACHÉ—Of course. HON. MR. MOORE—NOW, that being the case, I think our Local Government will be placed in a lower position than in the Government we have now. Every measure resolved upon in the Local Government will be subject to the veto of the Federal Government—that is, any measure or bill passing the Local Legislature may be disallowed within one year by the Federal Government. HON. SIR E. P. TACHÉ—That is the case at present as between Canada and the Imperial Government. HON. MR. MOORE—I beg to differ slightly with the honorable gentleman. Any measure passed by this province may be disallowed within two years thereafter by the Imperial Government. But the local governments, under Confederation, are to be subjected to having their measures vetoed within one year by the Federal Government, and then the Imperial Government has the privilege of vetoing anything the Federal Government may do, within two years. The veto power thus placed in the hands of the Federal Government, if exercised frequently, would be almost certain to cause difficulty between the local and general governments. I observe that my honorable friend, Sir ETIENNE P. TACHÉ, does not approbate that remark. HON. SIR E. P. TACHÉ—You understand me correctly.

      Preamble and §.90 of the Constitution Act, 1867.

    1. The Federal Government will have the right of imposing taxes on the provinces without the concurrence of the local governments. Under article five of the 29th resolution, the Federal Government may raise moneys by all modes or systems of taxation, and I look upon this power as most excessive. Thus, in case it should happen, as I said a moment ago, that the Lower Canada Government refused to undertake the payment of the debt contracted for the redemption of the Seigniorial Tenure, the Federal Government would have two methods of compelling it to do so. First, by retaining the amount out of the eighty cents per head indemnity to be accorded to the Local Government, and secondly, by imposing a local and direct tax. The Lieutenant Governor of the Local Government will be appointed by the Federal Government, and will be guided by its instructions. We are not told whether the Local Government will be responsible to the Local Legislature; whether there will be only one or two branches of the Legislature, nor how the Legislative Council will be composed, if there is to be one ; we are refused any information whatsoever on these points, which are nevertheless of some importance.

      Preamble, Part V, §§.90 and 91(3).

  4. Aug 2018
    1. but I can tell him that the Protestant minority of Lower Canada have nothing to fear from the Catholic majority of that province : their religion is guaranteed by treaty, and their schools and the rights which may be connected with them, are to be settled by legislation to take place hereafter, and when that legislation is laid before the Houses, those members who so greatly tremble now for the rights of the Protestant minority will have an opportunity of protecting that minority ; they may then urge their reasons, and insist that the Protestants shall not be placed in a position of the slightest danger. But even granting that the Protestants were wronged by the Local Legislature of Lower Canada, could they not avail themselves of the protection of the Federal Legislature ? And would not the Federal Government exercise strict surveillance over the action of the local legislatures in these matters ? Why should it be sought to give existence to imaginary fears in Lower Canada ?

      §§.90 and 93 of the Constitution Act, 1867.