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Hartshorne conjectured that a smooth, codimension c subvariety of n-dimensional projective space must be a complete intersection, whenever c is less than n/3. We prove this in the special case when n is much larger than the degree of the subvariety. Similar results were known in characteristic zero due to Hartshorne, Barth-Van de Ven, and others. Our proof is field independent and employs quite different methods from those previous results, as we connect Hartshorne's Conjecture with the circle of ideas initiated by Ananyan and Hochster in their proof of Stillman's Conjecture., Comment: 5 pages

Multiple sclerosis (MS) is a central nervous system (CNS) disorder, which is mediated by an abnormal immune response coordinated by T and B cells resulting in areas of inflammation, demyelination, and axonal loss. Disease-modifying treatments (DMTs) are available to dampen the inflammatory aggression but are ineffective in many patients. Autologous hematopoietic stem cell transplantation (HSCT) has been used as treatment in patients with a highly active disease, achieving a long-term clinical remission in most. The rationale of the intervention is to eradicate inflammatory autoreactive cells with lympho-ablative regimens and restore immune tolerance. Immunological studies have demonstrated that autologous HSCT induces a renewal of TCR repertoires, resurgence of immune regulatory cells, and depletion of proinflammatory T cell subsets, suggesting a “resetting” of immunological memory. Although our understanding of the clinical and immunological effects of autologous HSCT has progressed, further work is required to characterize the mechanisms that underlie treatment efficacy. Considering that memory B cells are disease-promoting and stem-like T cells are multipotent progenitors involved in self-regeneration of central and effector memory cells, investigating the reconstitution of B cell compartment and stem and effector subsets of immunological memory following autologous HSCT could elucidate those mechanisms. Since all subjects need to be optimally protected from vaccine-preventable diseases (including COVID-19), there is a need to ensure that vaccination in subjects undergoing HSCT is effective and safe. Additionally, the study of vaccination in HSCT-treated subjects as a means of evaluating immune responses could further distinguish broad immunosuppression from immune resetting.

Combining recent results on noetherianity of twisted commutative algebras by Draisma and the resolution of Stillman's conjecture by Ananyan-Hochster, we prove a broad generalization of Stillman's conjecture. Our theorem yields an array of boundedness results in commutative algebra that only depend on the degrees of the generators of an ideal, and not the number of variables in the ambient polynomial ring., Comment: 16 pages

Let [math] be a graded ring. We introduce a class of graded [math] -modules called Gröbner-coherent modules. Roughly, these are graded [math] -modules that are coherent as ungraded modules because they admit an adequate theory of Gröbner bases. The class of Gröbner-coherent modules is formally similar to the class of coherent modules: for instance, it is an abelian category closed under extension. However, Gröbner-coherent modules come with tools for effective computation that are not present for coherent modules.

Hilbert famously showed that polynomials in n variables are not too complicated, in various senses. For example, the Hilbert Syzygy Theorem shows that the process of resolving a module by free modules terminates in finitely many (in fact, at most n) steps, while the Hilbert Basis Theorem shows that the process of finding generators for an ideal also terminates in finitely many steps. These results laid the foundations for the modern algebraic study of polynomials. Hilbert's results are not uniform in n: unsurprisingly, polynomials in n variables will exhibit greater complexity as n increases. However, an array of recent work has shown that in a certain regime---namely, that where the number of polynomials and their degrees are fixed---the complexity of polynomials (in various senses) remains bounded even as the number of variables goes to infinity. We refer to this as Stillman uniformity, since Stillman's Conjecture provided the motivating example. The purpose of this paper is to give an exposition of Stillman uniformity, including: the circle of ideas initiated by Ananyan and Hochster in their proof of Stillman's Conjecture, the followup results that clarified and expanded on those ideas, and the implications for understanding polynomials in many variables., This expository paper was written in conjunction with Craig Huneke's talk on Stillman's Conjecture at the 2018 JMM Current Events Bulletin

This is the first in a series of papers in which we study representations of the Brauer category and its allies. We define a general notion of triangular category that abstracts key properties of the triangular decomposition of a semisimple complex Lie algebra, and develop a highest weight theory for them. We show that the Brauer category, the partition category, and a number of related diagram categories admit this structure., Comment: 53 pages

We prove an analogue of Ananyan--Hochster's small subalgebra theorem in the context of sheaves on projective space, and deduce from this a version of Stillman's Conjecture for cohomology tables of sheaves. The main tools in the proof are Draisma's GL-noetherianity theorem and the BGG correspondence., 15 pages

We study representations of wreath product analogues of categories of finite sets. This includes the category of finite sets and injections (studied by Church, Ellenberg, and Farb) and the opposite of the category of finite sets and surjections (studied by the authors in previous work). We prove noetherian properties for the injective version when the group in question is polycyclic-by-finite and use it to deduce general twisted homological stability results for such wreath products and indicate some applications to representation stability. We introduce a new class of formal languages (quasi-ordered languages) and use them to deduce strong rationality properties of Hilbert series of representations for the surjective version when the group is finite., Comment: 27 pages, split off from arXiv:1409.1670v1; v2: added Section 5.2 on wreath product version of Murnaghan's stability theorem; v3: significant rewrite; v4: corrected some proofs

We show that $\bigoplus_{n \ge 0} {\mathrm H}^t({\bf GL}_n({\bf F}_q), {\bf F}_\ell)$ canonically admits the structure of a module over the $q$-divided power algebra (assuming $q$ is invertible in ${\bf F}_{\ell}$), and that, as such, it is free and (for $q \neq 2$) generated in degrees $\le t$. As a corollary, we show that the cohomology of a finitely generated ${\bf VI}$-module in non-describing characteristic is eventually periodic in $n$. We apply this to obtain a new result on the cohomology of unipotent Specht modules., Comment: 19 pages

We prove a conjecture of Stembridge concerning stability of Kronecker coefficients that vastly generalizes Murnaghan's theorem. The main idea is to identify the sequences of Kronecker coefficients in question with Hilbert functions of modules over finitely generated algebras. The proof only uses Schur-Weyl duality and the Borel-Weil theorem and does not rely on any existing work on Kronecker coefficients., Comment: 8 pages, v2: Added references, Remark 4.5, and Section 4.3 on stability result for plethysms

We study the representation theory of the increasing monoid. Our results provide a fairly comprehensive picture of the representation category: for example, we describe the Grothendieck group (including the effective cone), classify injective objects, establish properties of injective and projective resolutions, construct a derived auto-duality, and so on. Our work is motivated by numerous connections of this theory to other areas, such as representation stability, commutative algebra, simplicial theory, and shuffle algebras., Comment: 105 pages

The purpose of this paper is to prove that certain limits of polynomial rings are themselves polynomial rings, and show how this observation can be used to deduce some interesting results in commutative algebra. In particular, we give two new proofs of Stillman's conjecture. The first is similar to that of Ananyan-Hochster, though more streamlined; in particular, it establishes the existence of small subalgebras. The second proof is completely different, and relies on a recent noetherianity result of Draisma., Comment: 21 pages. v4: removes all hypotheses that we are working over an infinite ground field. v5: Fixes a gap in the proof of Lemma 5.11

We previously showed that the inverse limit of standard-graded polynomial rings with perfect coefficient field is a polynomial ring, in an uncountable number of variables. In this paper, we show that the same result holds with arbitrary coefficient field. We also prove an analogous result for ultraproducts of polynomial rings., Comment: 20 pages

Draisma recently proved that polynomial representations of $\mathbf{GL}_{\infty}$ are topologically noetherian. We generalize this result to algebraic representations of infinite rank classical groups., 8 pages

A famous theorem of Nakaoka asserts that the cohomology of the symmetric group stabilizes. The first author generalized this theorem to non-trivial coefficient systems, in the form of $\mathrm{FI}$-modules over a field, though one now obtains periodicity of the cohomology instead of stability. In this paper, we further refine these results. Our main theorem states that if $M$ is a finitely generated $\mathrm{FI}$-module over a noetherian ring $\mathbf{k}$ then $\bigoplus_{n \ge 0} \mathrm{H}^t(S_n, M_n)$ admits the structure of a $\mathbf{D}$-module, where $\mathbf{D}$ is the divided power algebra over $\mathbf{k}$ in a single variable, and moreover, this $\mathbf{D}$-module is "nearly" finitely presented. This immediately recovers the periodicity result when $\mathbf{k}$ is a field, but also shows, for example, how the torsion varies with $n$ when $\mathbf{k}=\mathbf{Z}$. Using the theory of connections on $\mathbf{D}$-modules, we establish sharp bounds on the period in the case where $\mathbf{k}$ is a field. We apply our theory to obtain results on the modular cohomology of Specht modules and the integral cohomology of unordered configuration spaces of manifolds., Fixed some minor mistakes and expanded the section on configuration spaces

The theory of Schur functors provides a powerful and elegant approach to the representation theory of GL_n - at least to the so-called polynomial representations - especially to questions about how the theory varies with n. We develop parallel theories that apply to other classical groups and to non-polynomial representations of GL_n. These theories can also be viewed as linear analogs of the theory of FI-modules., Comment: 13 pages

Let A be the twisted commutative algebra freely generated by d indeterminates of degree 1. We show that the regularity of an A-module can be bounded from the first floor(d^2/4) + 2 terms of its minimal free resolution. This extends results of Church and Ellenberg from the d=1 case., Comment: 16 pages

Let $P_3(\mathbf{C}^{\infty})$ be the space of complex cubic polynomials in infinitely many variables. We show that this space is $\mathbf{GL}_{\infty}$-noetherian, meaning that any $\mathbf{GL}_{\infty}$-stable Zariski closed subset is cut out by finitely many orbits of equations. Our method relies on a careful analysis of an invariant of cubics introduced here called q-rank. This result is motivated by recent work in representation stability, especially the theory of twisted commutative algebras. It is also connected to certain stability problems in commutative algebra, such as Stillman's conjecture., 13 pages

We study modules for the divided power algebra $D$ in a single variable over a commutative noetherian ring $k$. Our first result states that $D$ is a coherent ring. In fact, we show that there is a theory of Gr\"obner bases for finitely generated ideals, and so computations with finitely presented $D$-modules are in principle algorithmic. We go on to determine much about the structure of finitely presented $D$-modules, such as: existence of certain nice resolutions, computation of the Grothendieck group, results about injective dimension, and how they interact with torsion modules. Our results apply not just to the classical divided power algebra, but to its $q$-variant as well, and even to a much broader class of algebras we introduce called "generalized divided power algebras." On the other hand, we show that the divided power algebra in two variables over $\mathbf{Z}_p$ is not coherent., Comment: 55 pages

Suppose that for each n >= 0 we have a representation $M_n$ of the symmetric group S_n. Such sequences arise in a wide variety of contexts, and often exhibit uniformity in some way. We prove a number of general results along these lines in this paper: our prototypical theorem states that if $M_n$ can be given a suitable module structure over a twisted commutative algebra then the sequence $M_n$ follows a predictable pattern. We phrase these results precisely in the language of Hilbert series (or Poincar�� series, or formal characters) of modules over tca's., 28 pages

Let $R$ be a (not necessarily commutative) ring whose additive group is finitely generated and let $U_n(R) \subset GL_n(R)$ be the group of upper-triangular unipotent matrices over $R$. We study how the homology groups of $U_n(R)$ vary with $n$ from the point of view of representation stability. Our main theorem asserts that if for each $n$ we have representations $M_n$ of $U_n(R)$ over a ring $\mathbf{k}$ that are appropriately compatible and satisfy suitable finiteness hypotheses, then the rule $[n] \mapsto \widetilde{H}_i(U_n(R),M_n)$ defines a finitely generated OI-module. As a consequence, if $\mathbf{k}$ is a field then $dim \widetilde{H}_i(U_n(R),\mathbf{k})$ is eventually equal to a polynomial in $n$. We also prove similar results for the Iwahori subgroups of $GL_n(\mathcal{O})$ for number rings $\mathcal{O}$., Comment: 33 pages; minor update; to appear in Algebra & Number Theory

Given a non-isotrivial elliptic curve over an arithmetic surface, one obtains a lisse $\ell$-adic sheaf of rank two over the surface. This lisse sheaf has a number of straightforward properties: cyclotomic determinant, finite ramification, rational traces of Frobenius, and somewhere not potentially good reduction. We prove that any lisse sheaf of rank two possessing these properties comes from an elliptic curve., Comment: 9 pages

Let V be a symplectic vector space of dimension 2n. Given a partition \lambda with at most n parts, there is an associated irreducible representation S_{[\lambda]}(V) of Sp(V). This representation admits a resolution by a natural complex L^\lambda, which we call the Littlewood complex, whose terms are restrictions of representations of GL(V). When \lambda has more than n parts, the representation S_{[\lambda]}(V) is not defined, but the Littlewood complex L^\lambda still makes sense. The purpose of this paper is to compute its homology. We find that either L^\lambda is acyclic or that it has a unique non-zero homology group, which forms an irreducible representation of Sp(V). The non-zero homology group, if it exists, can be computed by a rule reminiscent of that occurring in the Borel-Weil-Bott theorem. This result can be interpreted as the computation of the "derived specialization" of irreducible representations of Sp(\infty), and as such categorifies earlier results of Koike-Terada on universal character rings. We prove analogous results for orthogonal and general linear groups. Along the way, we will see two topics from commutative algebra: the minimal free resolutions of determinantal ideals and Koszul homology., Comment: 32 pages; v2: corrected minor typos and changed theorem/equation numbering

We show that if $\{\rho_{\ell}\}$ is a compatible system of absolutely irreducible Galois representations of a number field then the residual representation $\overline{\rho}_{\ell}$ is absolutely irreducible for $\ell$ in a density 1 set of primes. The key technical result is the following theorem: the image of $\rho_{\ell}$ is an open subgroup of a hyperspecial maximal compact subgroup of its Zariski closure with bounded index (as $\ell$ varies). This result combines a theorem of Larsen on the semi-simple part of the image with an analogous result for the central torus that was recently proved by Barnet-Lamb, Gee, Geraghty, and Taylor, and for which we give a new proof., Comment: 11 pages

Consider the projective coordinate ring of the GIT quotient (P 1 ) n //SL(2), with the usual lin- earization, where n is even. In 1894, Kempe proved that this ring is generated in degree one. In (HMSV2) we showed that, over Q, the relations between degree one invariants are generated by a class of quadratic relations — the simplest binomial relations — with the exception of n = 6, where there is a single cubic relation. The purpose of this paper is to show that these results hold over Z( 1 12! ), and to suggest why they may be true over Z( 1 ).

IgG1 antibodies produced in Chinese hamster ovary (CHO) cells are heavily alpha1,6-fucosylated, a modification that reduces antibody-dependent cellular cytotoxicity (ADCC) and can inhibit therapeutic antibody function in vivo. Addition of fucose is catalyzed by Fut8, a alpha1,6-fucosyltransferase. FUT8(-/-) CHO cell lines produce completely nonfucosylated antibodies, but the difficulty of recapitulating the knockout in protein-production cell lines has prevented the widespread adoption of FUT8(-/-) cells as hosts for antibody production. We have created zinc-finger nucleases (ZFNs) that cleave the FUT8 gene in a region encoding the catalytic core of the enzyme, allowing the functional disruption of FUT8 in any CHO cell line. These reagents produce FUT8(-/-) CHO cells in 3 weeks at a frequency of 5% in the absence of any selection. Alternately, populations of ZFN-treated cells can be directly selected to give FUT8(-/-) cell pools in as few as 3 days. To demonstrate the utility of this method in bioprocess, FUT8 was disrupted in a CHO cell line used for stable protein production. ZFN-derived FUT8(-/-) cell lines were as transfectable as wild-type, had similar or better growth profiles, and produced equivalent amounts of antibody during transient transfection. Antibodies made in these lines completely lacked core fucosylation but had an otherwise normal glycosylation pattern. Cell lines stably expressing a model antibody were made from wild-type and ZFN-generated FUT8(-/-) cells. Clones from both lines had equivalent titer, specific productivity distributions, and integrated viable cell counts. Antibody titer in the best ZFN-generated FUT8(-/-) cell lines was fourfold higher than in the best-producing clones of FUT8(-/-) cells made by standard homologous recombination in a different CHO subtype. These data demonstrate the straightforward, ZFN-mediated transfer of the Fut8- phenotype to a production CHO cell line without adverse phenotypic effects. This process will speed the production of highly active, completely nonfucosylated therapeutic antibodies.

We develop a functorial theory of spinor and oscillator representations parallel to the theory of Schur functors for general linear groups. This continues our work on developing orthogonal and symplectic analogues of Schur functors. As such, there are a few main points in common. We define a category of representations of what might be thought of as the infinite rank pin and metaplectic groups, and give three models of this category in terms of: multilinear algebra, diagram categories, and twisted Lie algebras. We also define specialization functors to the finite rank groups and calculate the derived functors., Comment: 31 pages; v2: corrections and expanded some proofs

A major open problem in the theory of twisted commutative algebras (tca's) is proving noetherianity of finitely generated tca's. For bounded tca's this is easy, in the unbounded case, noetherianity is only known for Sym(Sym^2(C^\infty)) and Sym(\wedge^2(C^\infty)). In this paper, we establish noetherianity for the skew-commutative versions of these two algebras, namely \wedge(Sym^2(C^\infty)) and \wedge(\wedge^2(C^\infty)). The result depends on work of Serganova on the representation theory of the infinite periplectic Lie superalgebra, and has found application in the work of Miller-Wilson on "secondary representation stability" in the cohomology of configuration spaces., Comment: 22 pages

Let $R$ be the polynomial ring $K[x_{i,j}]$ where $1 \le i \le r$ and $j \in \mathbb{N}$, and let $I$ be an ideal of $R$ stable under the natural action of the infinite symmetric group $S_{\infty}$. Nagel--R\"omer recently defined a Hilbert series $H_I(s,t)$ of $I$ and proved that it is rational. We give a much shorter proof of this theorem using tools from the theory of formal languages and a simple algorithm that computes the series., Comment: 8 pages, no figures

Clozel, Harris and Taylor have recently proved a modularity lifting theorem of the following general form: if \(\rho \) is an \(\ell \)-adic representation of the absolute Galois group of a number field for which the residual representation \(\overline{\rho }\) comes from a modular form then so does \(\rho \). This theorem has numerous hypotheses; a crucial one is that the image of \(\overline{\rho }\) must be “big,” a technical condition on subgroups of \(\mathrm {GL}_n\). In this paper we investigate this condition in compatible systems. Our main result is that in a sufficiently irreducible compatible system the residual images are big at a density one set of primes. This result should make some of the work of Clozel, Harris and Taylor easier to apply in the setting of compatible systems.

In recent years, researchers have discovered various large algebraic structures that have surprising finiteness properties, such as FI-modules and Delta-modules. In this paper, we add another example to the growing list: we show that certain degree two twisted commutative algebras are noetherian. This example appears to have some fundamental differences from previous examples, and is therefore especially interesting. Reflective of this, our proof introduces new methods for establishing noetherianity that are likely to be applicable in other situations. The algebras considered in this paper are closely related to the stable representation theory of classical groups, which is one source of motivation for their study., Comment: 21 pages; v2: small corrections and added Example 1.4

Given a category C of a combinatorial nature, we study the following fundamental question: how does the combinatorial behavior of C affect the algebraic behavior of representations of C? We prove two general results. The first gives a combinatorial criterion for representations of C to admit a theory of Gr\"obner bases. From this, we obtain a criterion for noetherianity of representations. The second gives a combinatorial criterion for a general "rationality" result for Hilbert series of representations of C. This criterion connects to the theory of formal languages, and makes essential use of results on the generating functions of languages, such as the transfer-matrix method and the Chomsky-Sch\"utzenberger theorem. Our work is motivated by recent work in the literature on representations of various specific categories. Our general criteria recover many of the results on these categories that had been proved by ad hoc means, and often yield cleaner proofs and stronger statements. For example: we give a new, more robust, proof that FI-modules (originally introduced by Church-Ellenberg-Farb), and a family of natural generalizations, are noetherian; we give an easy proof of a generalization of the Lannes-Schwartz artinian conjecture from the study of generic representation theory of finite fields; we significantly improve the theory of $\Delta$-modules, introduced by Snowden in connection to syzygies of Segre embeddings; and we establish fundamental properties of twisted commutative algebras in positive characteristic., Comment: 41 pages; v2: Moved old Sections 3.4, 10, 11, 13.2 and connected text to arxiv:1410.6054v1, Section 13.1 removed and will appear elsewhere; v3: substantial revision and reorganization of sections

Let V be a complex representation of a finite group G of order g. Derksen conjectured that the pth syzygies of the invariant ring Sym(V)^G are generated in degrees at most (p+1)g. We point out that a simple application of the theory of twisted commutative algebras -- using an idea due to Weyl -- gives the bound pg^3., Comment: 2 pages

We develop a comprehensive theory of the stable representation categories of several sequences of groups, including the classical and symmetric groups, and their relation to the unstable categories. An important component of this theory is an array of equivalences between the stable representation category and various other categories, each of which has its own flavor (representation theoretic, combinatorial, commutative algebraic, or categorical) and offers a distinct perspective on the stable category. We use this theory to produce a host of specific results, e.g., the construction of injective resolutions of simple objects, duality between the orthogonal and symplectic theories, a canonical derived auto-equivalence of the general linear theory, etc., 79 pages; v2: increased font size, added 1.4.7, 3.3.8, Remark 6.2.6, and references

Mazur's theorem states that there are exactly 15 possibilities for the torsion subgroup of an elliptic curve over the rational numbers. We determine how often each of these groups actually occurs. Precisely, if $G$ is one of these 15 groups, we show that the number of elliptic curves up to height $X$ whose torsion subgroup is isomorphic to $G$ is on the order of $X^{1/d}$, for some number $d=d(G)$ which we compute., Comment: 16 pages. Comments welcome!

The demographic time bomb is alive and ticking some 10 years after the initial warnings of its presence began to be sounded. So what have we done about it and how can we reconcile the needs of the emerging society with the environmental challenges that threaten our very existence over the long term? This article explores the issues and challenges the packaging industry to take up the gauntlet. Copyright © 2003 John Wiley & Sons, Ltd.

Cell death due to apoptosis is frequently observed in large-scale manufacturing of therapeutic proteins, and can reduce product accumulation in bioreactors. Several different strategies that involve overexpression of antiapoptotic or downregulation of proapoptotic proteins have been designed in attempt to curb this problem in Chinese hamster ovary (CHO) cell culture. However, each of these designs has their own shortcomings and limits, rendering them ineffective for large-scale protein production. Recently, we have reported generation of a Bax and Bak deficient dhfr(-/-) CHO cell line using zinc-finger nucleases. Here we demonstrate that puromycin, but not methotrexate, selection can be used to generate antibody-expressing Bax and Bak deficient clones that are not only resistant to apoptosis, but that can also achieve higher titers relative to parental CHO cells due to higher cell density. Additionally, we show that Bax and Bak deficient cells have more mitochondria with healthy membrane potential, an attribute that perhaps contributes to their more potent growth compared to parental cells. Bax and Bak deficient cells do not readily apoptose, as shown by the ability to withstand high concentrations of apoptosis inducing agents, such as sodium butyrate, without a reduction in viability, growth, or titer. These traits render Bax and Bak deficient cells a potentially attractive host for production of therapeutic proteins at industrial scale.

Consider the polynomial ring in countably infinitely many variables over a field of characteristic zero, together with its natural action of the infinite general linear group G. We study the algebraic and homological properties of finitely generated modules over this ring that are equipped with a compatible G-action. We define and prove finiteness properties for analogues of Hilbert series, systems of parameters, depth, local cohomology, Koszul duality, and regularity. We also show that this category is built out of a simpler, more combinatorial, quiver category which we describe explicitly. Our work is motivated by recent papers in the literature which study finiteness properties of infinite polynomial rings equipped with group actions. (For example, the paper by Church, Ellenberg and Farb on the category of FI-modules, which is equivalent to our category.) Along the way, we see several connections with the character polynomials from the representation theory of the symmetric groups. Several examples are given to illustrate that the invariants we introduce are explicit and computable., 59 pages, uses ytableau.sty; v2: expanded details in many proofs especially in Sections 2 and 4, Section 6 substantially expanded, added references; v3: corrected typos and Remark 4.3.3 from published version

Given a finite field k of characteristic at least 5, we show that the Tate conjecture holds for K3 surfaces defined over the algebraic closure of k if and only if there are only finitely many K3 surfaces over each finite extension of k., Final version

This paper deals with the geometry of the space (GIT quotient) M_8 of 8 points in P^1, and the Gale-quotient N'_8 of the GIT quotient of 8 points in P^3. The space M_8 comes with a natural embedding in P^{13}, or more precisely, the projectivization of the S_8-representation V_{4,4}. There is a single S_8-skew cubic C in P^{13}. The fact that M_8 lies on the skew cubic C is a consequence of Thomae's formula for hyperelliptic curves, but more is true: M_8 is the singular locus of C. These constructions yield the free resolution of M_8, and are used in the determination of the "single" equation cutting out the GIT quotient of n points in P^1 in general. The space N'_8 comes with a natural embedding in P^{13}, or more precisely, PV_{2,2,2,2}. There is a single skew quintic Q containing N'_8, and N'_8 is the singular locus of the skew quintic Q. The skew cubic C and skew quintic Q are projectively dual. (In particular, they are surprisingly singular, in the sense of having a dual of remarkably low degree.) The divisor on the skew cubic blown down by the dual map is the secant variety Sec(M_8), and the contraction Sec(M_8) - - > N'_8 factors through N_8 via the space of 8 points on a quadric surface. We conjecture that the divisor on the skew quintic blown down by the dual map is the quadrisecant variety of N'_8 (the closure of the union of quadrisecant *lines*), and that the quintic Q is the trisecant variety. The resulting picture extends the classical duality in the 6-point case between the Segre cubic threefold and the Igusa quartic threefold. We note that there are a number of geometrically natural varieties that are (related to) the singular loci of remarkably singular cubic hypersurfaces. Some of the content of this paper appeared in arXiv/0809.1233., 31 pages, 4 figures

Let R^univ be the universal deformation ring of a residual representation of a local Galois group. Kisin showed that many loci in MaxSpec(R^univ[1/p]) of interest are Zariski closed, and gave a way to study the generic fiber of the corresponding quotient of R^univ. However, his method gives little information about the quotient ring before inverting p. We give a method for studying this quotient in certain cases, and carry it out in the simplest non-trivial case. Precisely, suppose that V_0 is the trivial two dimensional representation and let R be the unique Z_p-flat and reduced quotient of R^univ such that MaxSpec(R[1/p]) consists of ordinary representations with Hodge--Tate weights 0 and 1. We describe the functor of points of (a slightly modified version of) R and show that the irreducile components of Spec(R) are normal, Cohen--Macaulay and not Gorenstein. This has two well-known applications to global deformation rings: first, a global deformation ring employing these local conditions is torsion-free; and second, Kisin's R[1/p]=T[1/p] theorem can be upgraded in this setting to an R=T theorem., Comment: 20 pages

We study syzygies of the Segre embedding of P(V_1) x ... x P(V_n), and prove two finiteness results. First, for fixed p but varying n and V_i, there is a finite list of "master p-syzygies" from which all other p-syzygies can be derived by simple substitutions. Second, we define a power series f_p with coefficients in something like the Schur algebra, which contains essentially all the information of p-syzygies of Segre embeddings (for all n and V_i), and show that it is a rational function. The list of master p-syzygies and the numerator and denominator of f_p can be computed algorithmically (in theory). The central observation of this paper is that by considering all Segre embeddings at once (i.e., letting n and the V_i vary) certain structure on the space of p-syzygies emerges. We formalize this structure in the concept of a Delta-module. Many of our results on syzygies are specializations of general results on Delta-modules that we establish. Our theory also applies to certain other families of varieties, such as tangent and secant varieties of Segre embeddings., Comment: 34 pages

Anoxic and metabolic stresses in large-scale cell culture during biopharmaceutical production can induce apoptosis. Strategies designed to ameliorate the problem of apoptosis in cell culture have focused on mRNA knockdown of pro-apoptotic proteins and over-expression of anti-apoptotic ones. Apoptosis in cell culture involves mitochondrial permeabilization by the pro-apoptotic Bak and Bax proteins; activity of either protein is sufficient to permit apoptosis. We demonstrate here the complete and permanent elimination of both the Bak and Bax proteins in combination in Chinese hamster ovary (CHO) cells using zinc-finger nuclease-mediated gene disruption. Zinc-finger nuclease cleavage of BAX and BAK followed by inaccurate DNA repair resulted in knockout of both genes. Cells lacking Bax and Bak grow normally but fail to activate caspases in response to apoptotic stimuli. When grown using scale-down systems under conditions that mimic growth in large-scale bioreactors they are significantly more resistant to apoptosis induced by starvation, staurosporine, and sodium butyrate. When grown under starvation conditions, BAX- and BAK-deleted cells produce two- to fivefold more IgG than wild-type CHO cells. Under normal growth conditions in suspension culture in shake flasks, double-knockout cultures achieve equal or higher cell densities than unmodified wild-type cultures and reach viable cell densities relevant for large-scale industrial protein production.