The advances in technology over the last decade and the massive amount of data passing through the internet has intrigued and challenged computer scientists, as the old models of computation used before this era are now less relevant or too slow. New computational models have been suggested to tackle these technological advances. In the most basic sense, these modern models allow one to scan the input only once, possible with small auxiliary memory. Nevertheless, modern techniques have also been introduced such as sparse recovery which has proven to be a very useful tool for dealing with modern challenges, and the very popular notion of conditional lower bounds which has provided evidence of hardness for various algorithmic tasks based on very popular conjectures. Pattern matching plays a crucial role in many computing applications that can be seen in day to day life. However, its research community has only recently started gaining insight on what can be done in modern models, and is lagging behind in this respect. In particular, there are no algorithms for pattern matching problems that have utilized ideas from sparse recovery, and only recently has there been progress in proving conditional lower bounds for string problems. Furthermore, conditional lower bounds suffer from the lack of hardness conjectures which address time/space tradeoffs. This proposal will close this gap for many important pattern matching problems within the new models of computation, and will be the first to utilize modern algorithmic techniques, such as sparse recovery, and adapting them into the pattern matching world. Furthermore, this proposal will focus on developing a theory for proving conditional time/space lower bounds, based on new hardness conjectures. This will greatly influence not only the pattern matching sub-field, but the entire algorithmic field at large.

How do emotional styles develop in colonial settings? What are their roles in the construction of settler identities? Such processes happen both “from below”—in the daily and often casual behavior of ordinary men, women, and children; and “from above”—in discourses about the ideal and actual characteristics of a settler. As the early Zionists, looking to execute their national project in the colonial world, fully realized, a colony, regardless of its function, always provides an opportunity to produce “new people.” In the case of the Yishuv—the Jewish community that coalesced in Mandatory Palestine—the top-down direction of this process can be identified in the extensive Zionist literature about the desired “New Jew” as well as in the attempts to embed his or her traits using printed matter (such as parents’ manuals and children’s literature). Drawing on this feature of the Yishuv, the research analyzes both the Zionist project of top-down emotional transformation and the actual expression and experiences of emotions in the burgeoning settler society. By integrating these two levels, the research goes beyond the existing scholarship, which usually focuses on one or the other, and breaks new ground in understanding how emotions were mobilized and how new emotional styles emerged in a colonial context. The outgoing phase, which will last two years at Harvard University, under the supervision of Prof. Derek Penslar, has two aims: (i) to understand how the colonial context (within which early Zionism operated) impacted ideas about new emotional styles; and (ii) to survey the attempts to bring these ideas into the homes of (the mostly European) settlers at the time. The incoming phase, running one year at Bar-Ilan University, under the supervision of Prof. Hizky Shoham, will assess the impact—or lack thereof—of the emotional transformation studied in the outgoing phase on the everyday emotional practices of families in the mainstream urban sector of the Yishuv.

Microfluidic systems, in general, have proven important platforms for biomedical assays. These systems benefit from reduced requirements for expensive reagents, short analysis times, and portability. Although microfluidic systems are convenient platforms, their use in the life sciences is still limited mainly due to the high-level fabrication expertise required for construction. Integrated microfluidics is one of the most sophisticated three-dimensional (multi layer) solution. It requires soft lithography (PDMS based chips), for production of high complexity microfluidic systems (multiple serial or parallel processes). Integrated microfluidics in particular is almost non-existent in the industry due to the low yield and uncontrolled production process. My ERC project (MUDLOC-2012) is to develop a microfluidic platform for multidimensional protein array analysis. It uses complex multilayer microfluidic devices that consist of 2 PDMS layers and a glass microarray. The integrated microfluidics system contains thousands of micromechanical valves in micrometer dimensions, controlling thousands of parallel reactions. Our research demands production of hundreds of such devices. We, as all others who produce integrated microfluidics, suffered from frustrating low yield (15%). In order to improve fabrication yield and to fabricate devices with increased density, we designed and manufactured, a first of its kind, full production process sequence, semi automatic Microfluidic Device Assembly System (µDAS). This resulted in a direct increase of device complexity and yield (85%) over the last half year. The 2nd generation automated µDAS prototype will become a generic assembly tool for soft lithography. µDAS will enable a critical production standard and process control, which will pave the road for significant penetration of complex integrated microfluidics technology into both academia and industry.

During mammalian sex determination, the bipotential embryonic gonad adopts either testicular or ovarian cell fates. This process highly relies on precise expression of several pro-male versus pro-female factors, most of which are transcription factors (TFs) and signalling pathway components. Yet, we still do not understand the interplay and hierarchy among these factors, their direct target genes, the regulatory elements they bind to, nor do we have an in vitro system to address these questions. We recently explored the complex gene expression regulation of Sox9, a key pro-male factor, and identified several active testis-specific enhancers. Remarkably, deletion of one of these led to XY male-to-female sex reversal in mice. The presence of several functional enhancers highlights the complex gene expression regulation present during sex determination, which we aim to address here in a systematic manner. Furthermore, we recently developed a system to generate mouse and human gonadal progenitors from embryonic stem cells. Building on our exciting results, we seek to decipher the gene regulatory networks governing mammalian sex determination using in vivo and in vitro approaches. This proposal will pursue three complementary aims: (i) Identify target genes of the key factors controlling gonad formation; (ii) Map the regulatory elements bound by these factors; (iii) Develop an in vitro organoid system to model testis development. Using cutting edge techniques as CUT&RUN ChIP-Seq, ATAC-Seq, Promoter Capture Hi-C, CRISPR genome editing, organoid culture and 3D scaffolding development, we will address the complex gene expression regulation governing sex determination. Insights gained from this basic research will shed light on cell fate decisions in general, allow better diagnosis of many patients with Disorders of Sex Development, and offer an in vitro system to study gonad development and function with implications for understanding and treating infertility.