In 1939, the first director of the Princeton Institute for Advanced Study Abraham Flexner wrote an article in Harper’s Magazine entitled “The Usefulness of Useless Knowledge.” In this article he questioned “whether our conception of what is useful may not have become too narrow to be adequate to the roaming and capricious possibilities of the human spirit,” and he argued that real discoveries are made when scientists are allowed to explore the world without recourse to usefulness. Several Nobel prizes have been given for discoveries tangential to what was initially studied. I will argue that “useless knowledge” is needed as much today as in the past to improve human well-being and health. I will also suggest ways that we can encourage the finding of the unexpected, the discoveries that will enable future scientific revolutions.

1939年，普林斯頓高等研究學院的首任院長亞伯拉罕·弗萊克斯納（Abraham Flexner）在《哈潑雜誌》上發表了一篇名為《無用知識的用處》的文章。在這篇文章中，他質疑我們對於「有用」的理解是否已經變得太狹隘，無法滿足人類精神的漫遊和反復無常的可能性，他認為真正的發現，是在科學家們被允許在不顧及有用性的情況下，探索世界時才能做出的。有好幾位諾貝爾獎得主的獲獎發現，脫出了他們起始設定的研究。我認為「無用的知識」在當今與過去一樣的需要，藉以改善人類的福祉和健康。我還將提出一些方法，讓我們可用以鼓勵意想之外的發現，這些發現將推動未來的科學革命。

Yogi Berra once said, “You can observe a lot by watching.” Unfortunately, before the early 1990s observations in the biological sciences were usually done on dead specimens that were specially prepared to allow entry of reagents that stained cell components. These methods allowed a glimpse of what cells were doing, but they gave a necessarily static view of life. GFP and other fluorescent proteins revolutionized the biological sciences because they allowed scientists to look at the inner workings of living cells. The story of the discovery and development of GFP also provides a very nice example of how scientific progress is often made: through accidental discoveries, the willingness to ignore previous assumptions, and the combined efforts of many people. The story of GFP also shows the importance of basic research on non-traditional organisms.

約基·貝拉曾經說過：「通過觀察你可以看到很多東西」。 不幸的是，在1990年代初之前，生物科學中的觀察通常是在已經死亡的標本上進行的，這些標本經過特殊處理，以允許試劑進入並染色細胞成分。這些方法允許人們窺視細胞的活動，但它們給出了一個只是靜態的生命視角。GFP (Green Fluorescent Protein，綠色螢光蛋白)和其他螢光蛋白的出現澈底改變了生物科學，因為它們使科學家能夠觀察活細胞的內部運作。GFP的發現和發展過程也提供了一個很好的例子，說明科學進步通常是通過偶然的發現、願意忽視以前的假設，以及許多人的共同努力所實現的。GFP的故事還顯示了對非傳統生物體進行基礎研究的重要性。

The 2023 Nobel Prize in physics was bestowed on Anne L’Huillier, Pierre Agosstini, and Ferenc Krausz for their contribution to creation and characterization of attosecond light pulses (<10-15 sec) that opens the window for studies of attosecond dynamics. We’ll review here how decades of laser technology advancement, hinged on simple ideas but hard experimental implementation, from Q-switched nanosecond pulses to mode-locked picosecond and femtosecond pulses, had finally led to the creation of attosecond pulses through high harmonic generation of femtosecond pulses. How such short pulses can be characterized is not obvious and will be briefly described. Applications of attosecond pulses to studies of ultrafast dynamics will be discussed.

2023年諾貝爾物理學獎頒給安妮·呂利耶、皮耶·亞谷斯蒂尼和費倫茨·克勞斯，以表彰他們對阿秒光脈衝（<10-15秒）的創造和特性分析的貢獻，這開啟了對阿秒動力學的研究視窗。我們將在此回顧幾十年來的雷射技術進步，這些進步是從簡單的想法展開，可是實驗的實施難度很大，從Q開關奈秒(10-9秒)脈衝到鎖模皮秒(10−12秒)和飛秒(10⁻¹⁵秒)脈衝，最終通過飛秒脈衝的高次諧波，產生了阿秒(10⁻¹⁸秒)脈衝。如何表徵這樣短的脈衝不是顯而易見的，我們將做簡要的描述。我們還將討論阿秒脈衝在超快動力學研究中的應用。

The invention of lasers more than 60 years ago has dramatically changed our modern life. Lasers have become indispensable in essentially all areas of science and technology. Close to 20 Nobel prizes have been awarded to breakthroughs in frontier science related to optics. Here, we reflect, in simple physics terms, on several selected milestones in the development of modern optics and discuss how they have opened new fields and impacted other disciplines.

We shall describe how lasers can be used to detect single atoms and molecules, how precision laser spectroscopy leads to an atomic clock with <10-17 accuracy in time, how laser cooling can lower the temperature of a system to a few nano-Kelvin, how laser super-resolution imaging can beat diffraction limit, how laser pulses from a table-top laser can have a peak field higher than 1011 V/cm, how laser implosion can create a material density 100 times higher than a typical solid, and how laser fusion can generate more energy in the output than in the input, and a few others. We shall discuss how research on quantum optics has led to the second quantum revolution in physics and created the current blooming activities in the fields of quantum cryptography, quantum data processing, and quantum computation.

60多年前，雷射的發明澈底改變了我們的現代生活。在幾乎所有的科學技術領域中，雷射已經成為不可或缺的工具。有近20座諾貝爾獎的頒發是表彰與光學相關的前沿科學的突破性貢獻。在這裡，我們以簡單的物理術語來回顧現代光學發展中的幾個里程碑，並討論它們如何開拓了新領域，並影響了其他學門。

我們將描述雷射如何用於檢測單個原子和分子，精密雷射光譜學如何達成時間精度小於10-17的原子鐘；雷射冷卻如何將系統溫度降低到幾個奈克耳文(10-9K)；雷射超解析度成像如何超越繞射極限；桌面雷射脈衝如何具有大於1011 V/cm的峰值電場強度；雷射內爆如何產生比典型固體密度高100倍的材料；以及雷射聚變如何產生輸出大於輸入的能量，等等。我們將討論量子光學研究如何引發了物理學中的第二次量子革命，並在量子密碼學、量子資料處理和量子計算等領域，引發了當前蓬勃發展的研究活動。

In every human cell, two meters of DNA is packed into a ~10 micron nucleus. The genome is extensively compacted, except for the active regulatory DNA elements that remain accessible. We have developed an Assay of Transpose Accessible Chromatin by sequencing (ATAC-seq) as a facile and sensitive method to map the landscape of gene regulation. The landscape of accessible chromatin from primary cells and tissues is unique informative for cell types, cell states, and the molecular basis of genetic variants associated with human diseases. Single cell chromatin accessibility reveals DNA elements and trans-acting factors that mediate cell-to-cell variation, which directly impacts cancer heterogeneity. Real time monitoring of gene regulation landscape in patients can provide prognostic prediction for response to cancer therapy. New technologies that integrate single cell multi-omics, receptor-ligand specificity, and spatial genomics, provide new levels of precision and insights into human diseases. The large corpus of data provide a starting point for machine learning approaches to refine experimental validation of biological insights.

The discovery of extensive transcription of long noncoding RNAs (lncRNAs) provide an important new perspective on the centrality of RNA in gene regulation. I will discuss genome-scale strategies to discover and characterize lncRNAs, notably the impact of lncRNAs on gene memory over time. LncRNAs form extensive networks of ribonucleoprotein (RNP) complexes with numerous chromatin regulators, and target these enzymatic activities to appropriate locations in the genome. Consistent with this notion, long noncoding RNAs can function as modular scaffolds to specify higher order organization in RNP complexes and in chromatin states. An emerging theme is the intersection between lncRNA biology and immunity. Self vs. foreign identity of lncRNA impacts innate and adaptive immunity. The importance of these modes of regulation is underscored by the newly recognized roles of long RNAs in human diseases.

在每一個人類細胞中，約兩米長的DNA被壓縮封入一個大小約10微米的細胞核。除了一些活躍的DNA調控元件保持開放、可被觸及之外，整個基因組都處於被高度緊密而不可及的狀態。我們發展出一種使用定序轉座酶可觸及的染色質分析技術（ATAC-seq），作為一種簡便靈敏的方法來繪製基因調控的景觀圖。解析初代細胞和組織的可觸及染色質景觀圖，對於細胞類型、細胞狀態和與人類疾病相關的遺傳變異的分子基礎，具有獨特的訊息意義。舉例來說，單細胞染色質的可觸及性，揭示了介導細胞間變異的DNA元件和反式作用因子，可直接影響癌症的異質性。此外，即時監測病人基因調控景觀圖，可以為癌症治療的反應提供預後預測。整合單細胞多組體學、受體-配體特異性、和空間基因組的新技術，可以為人類疾病研究提供新的精準度和見解。大量的資料也為機器學習方法提供了一個起點，增益對相關生物意義的驗證和見解。

對長鏈非編碼RNA (lncRNA)廣泛轉錄的發現，為RNA在基因調控中的核心地位提供了重要的新視角。我將討論用於發現和驗證lncRNA的基因組規模策略，特別是lncRNA隨時間推移對基因記憶的影響。lncRNA與眾多染色質調控因子互動，形成廣泛的核糖核蛋白（RNP）複合物網路，並將這些酶活動定位到基因組中的適當位置。與此概念一致的是，lncRNA可作為模組化支架，去指定RNP複合物和染色質狀態的更高層次組織。相關研究領域中一個新興的主題，是lncRNA生物學與免疫學的交集。lncRNA的自源與外源識別，可影響先天性免疫和後天性免疫。這些新發現的調控方式，凸顯lncRNA在人體疾病中的重要性。

RNA has become a household word. We are now see RNA mentioned in the news, discussed by political leaders, physicians, and entrepreneurs. But this is a recent transformation that underlies a six decades long journey from basic discoveries in RNA science to the widespread adoption of RNA medicines. I will discuss the challenges and ongoing efforts to engineer a new type of RNA called circular RNA for human therapies. I will further discuss the opportunities for massively increasing the scale of information about RNA. A revolution in genomics and internet scale data collection can empower new educational opportunities to connect students and scientists to fuse human intelligence and machine intelligence.

Please download and play Eterna at: https://eternagame.org/

RNA (Ribonucleic Acid，核糖核酸)已經成為家喻戶曉的詞語。我們現在經常在新聞中看到RNA被提及，政治領導人、醫生和企業家也在討論RNA。但這近期才展開的蛻轉，蓄勢已久，從RNA科學的基礎發現到RNA藥物的廣泛應用，經歷了長達六十年的積累。我將討論如何構建改造一種名為環狀RNA的新型RNA，以用於疾病治療所面臨的挑戰，和正在進行的努力。我還將進一步討論可如何大量增加對RNA理解的機遇。基因組學的革命，和互聯網規模的資料收集，賦予新的教育機會將學生和科學家連接起來，促進人類智慧和機器智慧的融合。

請下載並玩「Eterna」遊戲：https://eternagame.org/

Black holes are spectacular end products of the fatal attraction of gravity. “Small” black holes are graveyards of massive stars. Big black holes reside at the centers of galaxies and have masses reaching many billion suns. Moreover, both singlet and twin black holes have been sighted. I will highlight some recent exciting discoveries in black hole research and describe our effort in uncovering a new population of ultra-massive black holes.

黑洞是重力致命吸引的壯觀終極產物。「小型」黑洞是巨大恆星的墳墓。「大型」黑洞位於星系中心，質量達到數十億個太陽的質量。此外，獨生的和雙生的黑洞都已被觀測到。我將重點介紹一些最近在黑洞研究中的令人興奮的發現，並描述我們在揭示一種新的超大質量黑洞群體方面所做的努力。

Science and art are taught as separate subjects in classrooms, but both are human’s inquiries about the nature of the world. Einstein once said the greatest scientists are artists as well. I will give some examples of where science and art meet. Aspiring scientists can enrich their worldviews by contemplating the art of science and the science of art.

科學和藝術是作為分開的學科在課堂上講授，但兩者都是人類對世界本質的探究。愛因斯坦曾說過：最偉大的科學家也是藝術家。我將提供一些科學與藝術相遇的例子。有抱負的科學家可以通過思考「科學的藝術」和「藝術的科學」來豐富他們的世界觀。