设计简答题问题

评估目标与认知层级
- 学习目标：考查学生能基于受体酪氨酸激酶（RTK）-Ras-MAPK 信号级联的关键节点，进行因果推断与机制性解释（分析/应用层级）。
- 适用对象：细胞生物学/分子生物学本科高年级或研究生课程之阶段性测验。

简答题（含情境）
某成纤维细胞系经血清饥饿后接受 EGF 10 ng/mL 刺激。对照组中，p-ERK1/2 于约 5 min 达峰，c-FOS mRNA 于约 30 min 明显上调。请在下列条件下，分别预测相对于对照的 ERK1/2 磷酸化水平（↑/↓/≈；是否仍出现短暂峰值）及 c-FOS mRNA 表达（↑/↓/≈），并用不超过 80 字解释机制。
a) EGFR 的 Y1068/Y1086→F 突变，其他位点正常；
b) 细胞表达 KRASG12V（构成性活化），未加配体；
c) 给予 MEK1/2 抑制剂 U0126 后再加 EGF。

参考答案要点（用于评分）
- a) 预期：p-ERK↓（峰消失或显著减弱）；c-FOS mRNA↓或不显著上调。机制要点：Y1068/Y1086 为 GRB2 对接位点，突变削弱 GRB2–SOS 招募，Ras 未有效换成 GTP，RAF–MEK–ERK 级联受阻[1–3]。
- b) 预期：p-ERK↑（可呈持续性且不依赖 EGF）；c-FOS mRNA↑。机制要点：KRASG12V 持续激活 RAF–MEK–ERK，旁路 RTK 上游；但下游仍依赖 MEK→ERK 驱动即刻早期基因表达[2,4,5]。
- c) 预期：p-ERK↓至接近背景（峰消失）；c-FOS mRNA 不上调。机制要点：MEK 被抑制，ERK 不能被磷酸化，ELK-1/SRF 等转录程序不被激活，IEG 表达受阻[5,6]。

评分细则（共 9 分）
- 每小问 3 分：
  - 方向性判断（p-ERK）：1 分；
  - 方向性判断（c-FOS）：1 分；
  - 机制解释（点到关键分子与因果链，如 GRB2–SOS→Ras、RAF–MEK–ERK、MEK 抑制对 ERK 与 IEG 的影响）：1 分。
- 可给部分分：若仅说明“经由 Ras-MAPK 受阻/增强”而未点明关键对接/抑制环节，记 0.5 分。
- 可接受等价表述：a 中提及“GRB2 对接减少/SH2 结合位点缺失”；b 中强调“旁路受体”与“仍依赖 MEK”；c 中指出“下游转录因子（ELK-1）不被 ERK 激活”均可酌情给分。
- 常见错误扣分：将 KRASG12V 判定为对 MEK 抑制不敏感；或将 EGFR Y→F 误判为不影响 GRB2 结合。

设计与依据（简述）
- 本题通过“上游对接位点突变、Ras 构成性活化、MEK 药理抑制”的正反向扰动，考查学生对级联传递、旁路激活与药物靶点的因果推断能力；以 p-ERK 与 c-FOS 作为可操作、可观测的分子 readout，具有良好的区分度与可评分性[1–6]。

参考文献（Vancouver 格式）
1. Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010;141(7):1117-1134.
2. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 7th ed. New York: W. W. Norton; 2022. Chapter on Cell Signaling.
3. Batzer AG, Rotin D, Ureña JM, Skolnik EY, Schlessinger J. Hierarchy of binding sites for Grb2 and Shc on the epidermal growth factor receptor. Mol Cell Biol. 1994;14(8):5192-5201.
4. Stephen AG, Esposito D, Bagni RK, McCormick F. Dragging ras back in the ring. Nat Rev Cancer. 2014;14(9):535-548.
5. Murphy LO, Blenis J. MAPK signal specificity: the right place at the right time. Trends Biochem Sci. 2006;31(5):268-275.
6. Favata MF, Horiuchi KY, Manos EJ, et al. Identification of a novel inhibitor of the mitogen-activated protein kinase kinase. J Biol Chem. 1998;273(29):18623-18632.

题目（简答题，统计推断）
背景与目标：评估学生对单样本均值的参数估计与假设检验的掌握，包括模型设定、统计量计算、结论解释与前提假设识别。

题干
某制造过程产出重量近似独立同分布。为评估该过程的平均重量μ，随机抽取 n = 35 个样本，得到样本均值 x̄ = 102.4 与样本标准差 s = 4.2。管理方宣称过程均值为 μ0 = 100。

请回答：
1) 在合理前提下，构造 μ 的95%置信区间，并给出数值结果与区间的情境化解释。
2) 以显著性水平 α = 0.05，检验 H0: μ = 100 与 H1: μ ≠ 100。报告检验统计量、p 值（或临界值判断）及结论。
3) 简述上述推断所依赖的关键统计前提，并说明若存在明显偏离（如强烈偏态或离群）对结论的潜在影响。

作答限制：写出主要公式与关键中间量（如标准误、t 分位数），数值可四舍五入至小数点后两位。

参考答案要点与评分细则（总分10分）
- 构念对齐：单样本 t 推断（未知总体方差），含估计与检验的解释性应用。

A. 95%置信区间（3分）
- 方法选择（1分）：识别采用单样本 t 区间，x̄ ± t0.975, df=34 × s/√n。
- 计算（1分）：SE = s/√n = 4.2/√35 ≈ 0.71；t0.975,34 ≈ 2.03；误差界 ≈ 2.03 × 0.71 ≈ 1.44。
- 区间与解释（1分）：CI ≈ (102.4 − 1.44, 102.4 + 1.44) = (100.96, 103.84)；解释为：在重复抽样的95%情形下，构造的区间将覆盖μ；本次区间不包含100，提示均值高于宣称值的证据。

B. 假设检验（3分）
- 设定与统计量（1分）：H0: μ = 100；H1: μ ≠ 100；t = (x̄ − μ0)/(s/√n) = (102.4 − 100)/0.71 ≈ 3.38，df = 34。
- p 值/临界值与结论（2分）：两侧 p 值 ≈ 0.002（允许 p < 0.01 的近似表述）；或 |t| > t0.975,34 ≈ 2.03，故在 α = 0.05 拒绝 H0；结论：数据表明该过程均值显著高于100。

C. 前提与稳健性（2分）
- 关键前提（1分）：独立同分布；样本来自近似正态总体或样本量足够大以依赖 t 程序的稳健性/中心极限定理；无严重离群与强烈偏态。
- 影响（1分）：强离群或重尾可夸大/缩小标准误并扭曲 t 分布近似，导致第一类/第二类错误率偏离标称水平；系统性依赖或非随机抽样会破坏结论的可推广性。

D. 表达与解释准确性（2分）
- 将置信区间与p值的含义表述为长期频率/反事实重复抽样框架，避免将“95%概率地包含μ”误解为针对固定 μ 的概率陈述（1分）。
- 论断与数据一致、无过度外推（1分）。

部分给分与容差
- t 分位数取 2.03 的近似可接受；SE 与边际误差的数值误差在±0.02 内不扣分。
- 仅给出正确区间或正确检验结论之一，可按相应小项计分。
- 若采用 z 程序但结论方向一致，且说明理由，可酌情给 0.5–1.0 分，但不得满分（因未知σ时 t 程序更合适）。

认知层次与难度
- 认知层次：应用—分析（计算+假设识别+情境化解释）。
- 难度：中等；预计作答时间 8–10 分钟。

测量学合理性说明（简述）
- 效度：题目直接取样本均值推断的核心证据（t 区间与双侧检验），与“统计推断”学习目标高度对齐；同时要求阐明前提与影响，减少“只会算不懂用”的构念无关方差（AERA, APA, & NCME, 2014；Wasserman, 2004）。
- 评分信度：采用分析型评分量表、明确数值容差与要点列举，可提升评分一致性（Brookhart, 2018；Lane, Raymond, & Haladyna, 2016）。
- 解释恰当性：同时要求报告区间与检验并进行情境化解释，有助于抑制对单一 p 值的过度依赖与误读（Wasserstein & Lazar, 2016）。

参考文献（APA 第七版）
- American Educational Research Association, American Psychological Association, & National Council on Measurement in Education. (2014). Standards for Educational and Psychological Testing. American Educational Research Association.
- Brookhart, S. M. (2018). How to create and use rubrics for formative assessment and grading. ASCD.
- Casella, G., & Berger, R. L. (2002). Statistical inference (2nd ed.). Duxbury.
- Lane, S., Raymond, M. R., & Haladyna, T. M. (Eds.). (2016). Handbook of test development (2nd ed.). Routledge.
- Wasserman, L. (2004). All of statistics: A concise course in statistical inference. Springer.
- Wasserstein, R. L., & Lazar, N. A. (2016). The ASA’s statement on p-values: Context, process, and purpose. The American Statistician, 70(2), 129–133.

Short-answer item (customer complaint handling)

Assessment objective: Evaluate the examinee’s ability to design a timely, principled, and feasible response to a customer complaint that aligns with recognized standards and justice-based service recovery.

Prompt: You are the customer service supervisor at a mid-sized e-commerce firm. A five-year loyal customer reports receiving a defective product, waited 25 minutes on hold before the call dropped, and has posted a negative public review threatening to switch suppliers. Replacement stock is limited; policy allows refund or replacement within 30 days; carrier damage is suspected. Within the next 24 hours, what actions will you take to address the complaint and stabilize the relationship? In 180–220 words, explicitly address: (a) acknowledgement/apology and ownership; (b) information gathering and documentation; (c) remedy selection under operational constraints and its rationale; (d) communication channel(s) and message content; and (e) follow-up and prevention. Briefly justify your choices using distributive, procedural, and interactional justice.

Scoring rubric (analytic; 10 points total)
- Acknowledgement/apology and ownership (2): Provides an immediate, sincere apology; accepts organizational responsibility; specifies timely outreach within 24 hours. Partial credit if apology lacks ownership or timeliness.
- Information gathering and documentation (2): Verifies order/defect facts; records the complaint and actions in a case log; captures root-cause hypothesis; aligns with a documented complaints process (e.g., ISO 10002). Partial if ad hoc or lacks documentation.
- Remedy selection and rationale (3): Chooses a feasible remedy (e.g., expedited replacement/backorder with clear timeline, refund, goodwill credit) that fits policy and loss incurred; explicitly justifies via distributive and procedural justice under stock constraints and addresses the public review. Partial if remedy is generic or ignores constraints/justice rationale.
- Communication strategy (2): Selects channel(s) (e.g., phone for immediacy plus written confirmation); specifies respectful, transparent messaging, offers choice, and explains steps; ties to interactional justice. Partial if “contact customer” is stated without content/channel rationale.
- Follow-up and prevention (1): Commits to confirm satisfaction, invite revision of the public review without pressure, and trigger internal corrective action (e.g., carrier QA, queue-time audit). Partial if follow-up is mentioned but lacks prevention.

Validity and reliability notes (for assessors): The item targets applied decision-making and justification using established complaint-handling standards (ISO 10002:2018) and the three justice dimensions shown to predict post-complaint satisfaction and loyalty (Tax, Brown, & Chandrashekaran, 1998; Colquitt, 2001). An analytic rubric supports inter-rater reliability and construct coverage (Jonsson & Svingby, 2007) and aligns evidence with the intended inference about competency (Messick, 1995). The constrained word limit promotes focus and comparability.

References (APA 7th)
- Colquitt, J. A. (2001). On the dimensionality of organizational justice: A construct validation of a measure. Journal of Applied Psychology, 86(3), 386–400. https://doi.org/10.1037/0021-9010.86.3.386
- International Organization for Standardization. (2018). ISO 10002:2018 Quality management—Customer satisfaction—Guidelines for complaints handling. ISO.
- Jonsson, A., & Svingby, G. (2007). The use of scoring rubrics: Reliability, validity and educational consequences. Educational Research Review, 2(2), 130–144. https://doi.org/10.1016/j.edurev.2007.05.002
- Messick, S. (1995). Validity of psychological assessment: Validation of inferences from persons’ responses and performances as scientific inquiry. American Psychologist, 50(9), 741–749. https://doi.org/10.1037/0003-066X.50.9.741
- Tax, S. S., Brown, S. W., & Chandrashekaran, M. (1998). Customer evaluations of service complaint experiences: Implications for relationship marketing. Journal of Marketing, 62(2), 60–76. https://doi.org/10.2307/1252161
- Davidow, M. (2003). Organizational responses to customer complaints: What works and what doesn’t. Journal of Service Research, 5(3), 225–250. https://doi.org/10.1177/1094670502238917